@article{D'EliaTruuLahtietal.2023, author = {D'Elia, Domenica and Truu, Jaak and Lahti, Leo and Berland, Magali and Papoutsoglou, Georgios and Ceci, Michelangelo and Zomer, Aldert and Lopes, Marta B. and Ibrahimi, Eliana and Gruca, Aleksandra and Nechyporenko, Alina and Frohme, Marcus and Klammsteiner, Thomas and Carrillo de Santa Pau, Enrique and Marcos-Zambrano, Laura Judith and Hron, Karel and Pio, Gianvito and Simeon, Andrea and Suharoschi, Ramona and Moreno-Indias, Isabel and Temko, Andriy and Nedyalkova, Miroslava and Apostol, Elena-Simona and Truică, Ciprian-Octavian and Shigdel, Rajesh and Telalović, Jasminka Hasić and Bongcam-Rudloff, Erik and Przymus, Piotr and Jordamović, Naida Babić and Falquet, Laurent and Tarazona, Sonia and Sampri, Alexia and Isola, Gaetano and P{\´e}rez-Serrano, David and Trajkovik, Vladimir and Klucar, Lubos and Loncar-Turukalo, Tatjana and Havulinna, Aki S. and Jansen, Christian and Bertelsen, Randi J. and Claesson, Marcus Joakim}, title = {Advancing microbiome research with machine learning: key findings from the ML4Microbiome COST action}, series = {Frontiers in Microbiology}, volume = {14}, journal = {Frontiers in Microbiology}, publisher = {Frontiers}, issn = {1664-302X}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-18004}, year = {2023}, abstract = {The rapid development of machine learning (ML) techniques has opened up the data-dense field of microbiome research for novel therapeutic, diagnostic, and prognostic applications targeting a wide range of disorders, which could substantially improve healthcare practices in the era of precision medicine. However, several challenges must be addressed to exploit the benefits of ML in this field fully. In particular, there is a need to establish "gold standard" protocols for conducting ML analysis experiments and improve interactions between microbiome researchers and ML experts. The Machine Learning Techniques in Human Microbiome Studies (ML4Microbiome) COST Action CA18131 is a European network established in 2019 to promote collaboration between discovery-oriented microbiome researchers and data-driven ML experts to optimize and standardize ML approaches for microbiome analysis. This perspective paper presents the key achievements of ML4Microbiome, which include identifying predictive and discriminatory 'omics' features, improving repeatability and comparability, developing automation procedures, and defining priority areas for the novel development of ML methods targeting the microbiome. The insights gained from ML4Microbiome will help to maximize the potential of ML in microbiome research and pave the way for new and improved healthcare practices.}, language = {en} } @article{BeisserGrohmeKopkaetal.2012, author = {Beisser, Daniela and Grohme, Markus and Kopka, Joachim and Frohme, Marcus and Schill, Ralph O. and Hengherr, Steffen and Dandekar, Thomas and Klau, Gunnar W. and Dittrich, Marcus and M{\"u}ller, Tobias}, title = {Integrated pathway modules using time-course metabolic profiles and EST data from Milnesium tardigradum}, series = {BMC Systems Biology}, volume = {6}, journal = {BMC Systems Biology}, number = {72}, issn = {1752-0509}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-6146}, pages = {13}, year = {2012}, abstract = {Tardigrades are multicellular organisms, resistant to extreme environmental changes such as heat, drought, radiation and freezing. They outlast these conditions in an inactive form (tun) to escape damage to cellular structures and cell death. Tardigrades are apparently able to prevent or repair such damage and are therefore a crucial model organism for stress tolerance. Cultures of the tardigrade Milnesium tardigradum were dehydrated by removing the surrounding water to induce tun formation. During this process and the subsequent rehydration, metabolites were measured in a time series by GC-MS. Additionally expressed sequence tags are available, especially libraries generated from the active and inactive state. The aim of this integrated analysis is to trace changes in tardigrade metabolism and identify pathways responsible for their extreme resistance against physical stress.}, language = {en} } @article{MarcosZambranoLopezMolinaBakirGungoretal.2023, author = {Marcos-Zambrano, Laura Judith and L{\´o}pez-Molina, V{\´i}ctor Manuel and Bakir-Gungor, Burcu and Frohme, Marcus and Karaduzovic-Hadziabdic, Kanita and Klammsteiner, Thomas and Ibrahimi, Eliana and Lahti, Leo and Loncar-Turukalo, Tatjana and Dhamo, Xhilda and Simeon, Andrea and Nechyporenko, Alina and Pio, Gianvito and Przymus, Piotr and Sampri, Alexia and Trajkovik, Vladimir and Lacruz-Pleguezuelos, Blanca and Aasmets, Oliver and Araujo, Ricardo and Anagnostopoulos, Ioannis and Aydemir, {\"O}nder and Berland, Magali and Calle, M. Luz and Ceci, Michelangelo and Duman, Hatice and G{\"u}ndoğdu, Aycan and Havulinna, Aki S. and Kaka Bra, Kardokh Hama Najib and Kalluci, Eglantina and Karav, Sercan and Lode, Daniel and Lopes, Marta B. and May, Patrick and Nap, Bram and Nedyalkova, Miroslava and Paci{\^e}ncia, In{\^e}s and Pasic, Lejla and Pujolassos, Meritxell and Shigdel, Rajesh and Sus{\´i}n, Antonio and Thiele, Ines and Truică, Ciprian-Octavian and Wilmes, Paul and Yilmaz, Ercument and Yousef, Malik and Claesson, Marcus Joakim and Truu, Jaak and Carrillo de Santa Pau, Enrique}, title = {A toolbox of machine learning software to support microbiome analysis}, series = {Frontiers in Microbiology}, volume = {14}, journal = {Frontiers in Microbiology}, publisher = {Frontiers}, issn = {1664-302X}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-18271}, year = {2023}, abstract = {The human microbiome has become an area of intense research due to its potential impact on human health. However, the analysis and interpretation of this data have proven to be challenging due to its complexity and high dimensionality. Machine learning (ML) algorithms can process vast amounts of data to uncover informative patterns and relationships within the data, even with limited prior knowledge. Therefore, there has been a rapid growth in the development of software specifically designed for the analysis and interpretation of microbiome data using ML techniques. These software incorporate a wide range of ML algorithms for clustering, classification, regression, or feature selection, to identify microbial patterns and relationships within the data and generate predictive models. This rapid development with a constant need for new developments and integration of new features require efforts into compile, catalog and classify these tools to create infrastructures and services with easy, transparent, and trustable standards. Here we review the state-of-the-art for ML tools applied in human microbiome studies, performed as part of the COST Action ML4Microbiome activities. This scoping review focuses on ML based software and framework resources currently available for the analysis of microbiome data in humans. The aim is to support microbiologists and biomedical scientists to go deeper into specialized resources that integrate ML techniques and facilitate future benchmarking to create standards for the analysis of microbiome data. The software resources are organized based on the type of analysis they were developed for and the ML techniques they implement. A description of each software with examples of usage is provided including comments about pitfalls and lacks in the usage of software based on ML methods in relation to microbiome data that need to be considered by developers and users. This review represents an extensive compilation to date, offering valuable insights and guidance for researchers interested in leveraging ML approaches for microbiome analysis.}, language = {en} } @article{GrebinykPrylutskaChepurnaetal.2019, author = {Grebinyk, Anna and Prylutska, Svitlana and Chepurna, Oksana and Grebinyk, Sergii and Prylutskyy, Yuriy and Ritter, Uwe and Ohulchanskyy, Tymish Y. and Matyshevska, Olga and Dandekar, Thomas and Frohme, Marcus}, title = {Synergy of Chemo- and Photodynamic Therapies with C60 Fullerene-Doxorubicin Nanocomplex}, series = {Nanomaterials}, volume = {9}, journal = {Nanomaterials}, number = {11}, publisher = {MDPI}, issn = {2079-4991}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-12940}, year = {2019}, abstract = {A nanosized drug complex was explored to improve the efficiency of cancer chemotherapy, complementing it with nanodelivery and photodynamic therapy. For this, nanomolar amounts of a non-covalent nanocomplex of Doxorubicin (Dox) with carbon nanoparticle C60 fullerene (C60) were applied in 1:1 and 2:1 molar ratio, exploiting C60 both as a drug-carrier and as a photosensitizer. The fluorescence microscopy analysis of human leukemic CCRF-CEM cells, in vitro cancer model, treated with nanocomplexes showed Dox's nuclear and C60's extranuclear localization. It gave an opportunity to realize a double hit strategy against cancer cells based on Dox's antiproliferative activity and C60's photoinduced pro-oxidant activity. When cells were treated with 2:1 C60-Dox and irradiated at 405 nm the high cytotoxicity of photo-irradiated C60-Dox enabled a nanomolar concentration of Dox and C60 to efficiently kill cancer cells in vitro. The high pro-oxidant and pro-apoptotic efficiency decreased IC50 16, 9 and 7 × 103-fold, if compared with the action of Dox, non-irradiated nanocomplex, and C60's photodynamic effect, correspondingly. Hereafter, a strong synergy of therapy arising from the combination of C60-mediated Dox delivery and C60 photoexcitation was revealed. Our data indicate that a combination of chemo- and photodynamic therapies with C60-Dox nanoformulation provides a promising synergetic approach for cancer treatment.}, language = {en} } @article{KoberHollertFrohme2019, author = {Kober, Liane and Hollert, Henner and Frohme, Marcus}, title = {Quantification of nitroaromatic explosives in contaminated soil using MALDI-TOF mass spectrometry}, series = {Analytical and Bioanalytical Chemistry}, volume = {411}, journal = {Analytical and Bioanalytical Chemistry}, number = {23}, issn = {1618-2650}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-12388}, pages = {5993 -- 6003}, year = {2019}, abstract = {Contamination from various sources is a global environmental and health threat, with mining and military activities in particular having spread nitroaromatic compounds, such as 2,4,6-trinitrotoluene and its degradation products and by-products, to the soil. The investigation and monitoring of large contaminated areas requires new detection methods since the established ones are expensive and time-consuming. Hence, we established a matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI--TOF MS) method using 1,5-diaminonaphthalene as the matrix substance and an internal standard for quantification. Analyzing standard substances, we found specific signals for radical and fragment ions of different nitrotoluenes and nitrobenzenes with good reproducibility and detection limits down to 0.25 ng/μL. The analysis of soil sample extracts from a former production site showed clear signals for 2,4,6-trinitrotoluene and the primary degradation products aminodinitrotoluenes. Furthermore, quantification gave results comparable to those obtained by conventional liquid chromatography--tandem mass spectrometry analysis. The MALDI-TOF MS method has a comparatively lower reproducibility, with relative standard deviations of 6\% to 20\% for multiple measurements of standard solutions and soil sample extracts. Nevertheless, a comparison of both methods revealed the advantages of MALDI-TOF MS analysis of explosive-contaminated areas with regard to costs, time, and handling. Finally, our MALDI-TOF MS method fulfills all the needs for high sample throughput and can therefore be a valuable screening tool for explosive-contaminated areas.}, language = {en} } @article{GrebinykPrylutskaGrebinyketal.2019, author = {Grebinyk, Anna and Prylutska, Svitlana and Grebinyk, Sergii and Prylutskyy, Yuriy and Ritter, Uwe and Matyshevska, Olga and Dandekar, Thomas and Frohme, Marcus}, title = {Complexation with C60 Fullerene Increases Doxorubicin Efficiency against Leukemic Cells In Vitro}, series = {Nanoscale Research Letters}, volume = {14}, journal = {Nanoscale Research Letters}, issn = {1556-276X}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-10966}, year = {2019}, abstract = {Conventional anticancer chemotherapy is limited because of severe side effects as well as a quickly evolving multidrug resistance of the tumor cells. To address this problem, we have explored a C60 fullerene-based nanosized system as a carrier for anticancer drugs for an optimized drug delivery to leukemic cells. Here, we studied the physicochemical properties and anticancer activity of C60 fullerene noncovalent complexes with the commonly used anticancer drug doxorubicin. C60-Doxorubicin complexes in a ratio 1:1 and 2:1 were characterized with UV/Vis spectrometry, dynamic light scattering, and high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The obtained analytical data indicated that the 140-nm complexes were stable and could be used for biological applications. In leukemic cell lines (CCRF-CEM, Jurkat, THP1 and Molt-16), the nanocomplexes revealed ≤ 3.5 higher cytotoxic potential in comparison with the free drug in a range of nanomolar concentrations. Also, the intracellular drug's level evidenced C60 fullerene considerable nanocarrier function. The results of this study indicated that C60 fullerene-based delivery nanocomplexes had a potential value for optimization of doxorubicin efficiency against leukemic cells.}, language = {en} } @article{GrebinykPrylutskaGrebinyketal.2019, author = {Grebinyk, Anna and Prylutska, Svitlana and Grebinyk, Sergii and Prylutskyy, Yuriy and Ritter, Uwe and Matyshevska, Olga and Dandekar, Thomas and Frohme, Marcus}, title = {Complexation with C60 Fullerene Increases Doxorubicin Efficiency against Leukemic Cells In Vitro}, series = {Nanoscale Research Letters}, volume = {14}, journal = {Nanoscale Research Letters}, issn = {1556-276X}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-11415}, year = {2019}, abstract = {Conventional anticancer chemotherapy is limited because of severe side effects as well as a quickly evolving multidrug resistance of the tumor cells. To address this problem, we have explored a C60 fullerene-based nanosized system as a carrier for anticancer drugs for an optimized drug delivery to leukemic cells. Here, we studied the physicochemical properties and anticancer activity of C60 fullerene noncovalent complexes with the commonly used anticancer drug doxorubicin. C60-Doxorubicin complexes in a ratio 1:1 and 2:1 were characterized with UV/Vis spectrometry, dynamic light scattering, and high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The obtained analytical data indicated that the 140-nm complexes were stable and could be used for biological applications. In leukemic cell lines (CCRF-CEM, Jurkat, THP1 and Molt-16), the nanocomplexes revealed ≤ 3.5 higher cytotoxic potential in comparison with the free drug in a range of nanomolar concentrations. Also, the intracellular drug's level evidenced C60 fullerene considerable nanocarrier function. The results of this study indicated that C60 fullerene-based delivery nanocomplexes had a potential value for optimization of doxorubicin efficiency against leukemic cells.}, language = {en} } @article{HornemannSinningCortesetal.2017, author = {Hornemann, Andrea and Sinning, Denise and Cortes, Sofia and Campino, Lenea and Emmer, Peggy and Kuhls, Katrin and Ulm, Gerhard and Frohme, Marcus and Beckhoff, Burkhard}, title = {A pilot study on fingerprinting Leishmania species from the Old World using Fourier transform infrared spectroscopy}, series = {Analytical and Bioanalytical Chemistry}, journal = {Analytical and Bioanalytical Chemistry}, issn = {1432-1130}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-10080}, year = {2017}, abstract = {Leishmania species are protozoan parasites and the causative agents of leishmaniasis, a vector borne disease that imposes a large health burden on individuals living mainly in tropical and subtropical regions. Different Leishmania species are responsible for the distinct clinical patterns, such as cutaneous, mucocutaneous, and visceral leishmaniasis, with the latter being potentially fatal if left untreated. For this reason, it is important to perform correct species identification and differentiation. Fourier transform infrared spectroscopy (FTIR) is an analytical spectroscopic technique increasingly being used as a potential tool for identification of microorganisms for diagnostic purposes. By employing mid-infrared (MIR) spectral data, it is not only possible to assess the chemical structures but also to achieve differentiation supported by multivariate statistic analysis. This work comprises a pilot study on differentiation of Leishmania species of the Old World (L. major, L. tropica, L. infantum, and L. donovani) as well as hybrids of distinct species by using vibrational spectroscopic fingerprints. Films of intact Leishmania parasites and their deoxyribonucleic acid (DNA) were characterized comparatively with respect to their biochemical nature and MIR spectral patterns. The strains' hyperspectral datasets were multivariately examined by means of variance-based principal components analysis (PCA) and distance-based hierarchical cluster analysis (HCA). With the implementation of MIR spectral datasets we show that a phenotypic differentiation of Leishmania at species and intra-species level is feasible. Thus, FTIR spectroscopy can be further exploited for building up spectral databases of Leishmania parasites in view of high-throughput analysis of clinical specimens.}, language = {en} } @article{GrebinykGrebinykPrylutskaetal.2018, author = {Grebinyk, Anna and Grebinyk, Sergii and Prylutska, Svitlana and Ritter, Uwe and Matyshevska, Olga and Dandekar, Thomas and Frohme, Marcus}, title = {HPLC-ESI-MS method for C60 fullerene mitochondrial content quantification}, series = {Data in Brief}, volume = {19}, journal = {Data in Brief}, issn = {2352-3409}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-10368}, pages = {2047 -- 2052}, year = {2018}, abstract = {The presented dataset describes the quantification of carbon nanoparticle C60 fullerene accumulated in mitochondria of human leukemic cells treated with nanostructure. Firstly, the high performance liquid chromatography-electro spray ionization-mass spectrometry (HPLC-ESI-MS) method was developed for quantitative analysis of pristine C60 fullerene. Then, human leukemic cells were incubated with C60 fullerene, homogenized and subjected to the differential centrifugation to retrieve mitochondrial fraction. The C60 fullerene content was quantified by HPLC-ESI-MS in extracts of cellular fractions. This data article refers to the research article "C60 Fullerene Accumulation in Human Leukemic Cells and Perspectives of LED-mediated Photodynamic Therapy" by Grebinyk et al.}, language = {en} } @article{FischbachFrohmeGloekler2017, author = {Fischbach, Jens and Frohme, Marcus and Gl{\"o}kler, J{\"o}rn}, title = {Hinge-initiated Primer-dependent Amplification of Nucleic Acids (HIP) - A New Versatile Isothermal Amplification Method}, series = {Scientific Reports}, volume = {7}, journal = {Scientific Reports}, issn = {2045-2322}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-9824}, year = {2017}, abstract = {The growing demand for cost-effective nucleic acid detection assays leads to an increasing number of different isothermal amplification reaction methods. However, all of the most efficient methods suffer from highly complex assay conditions due to the use of complicated primer sets and/or auxiliary enzymes. The present study describes the application of a new linker moiety that can be incorporated between a primer and a secondary target binding site which can act both as a block to polymerase extension as well as a hinge for refolding. This novel "hinge-primer" approach results in an efficient regeneration of the primer binding site and thus improves the strand-displacement and amplification process under isothermal conditions. Our investigations revealed that the reaction with forward and reverse hinge-primer including an abasic site is very efficient. The assay complexity can be reduced by combining the hinge-primer with a corresponding linear primer. Furthermore, the reaction speed can be increased by reducing the length of the amplified target sequence. We tested the sensitivity down to 104 copies and found a linear correlation between reaction time and input copy number. Our approach overcomes the usually cumbersome primer-design and extends the range of isothermal amplification methods using a polymerase with strand-displacement activity.}, language = {en} } @article{PfeilFrohmeSchulze2018, author = {Pfeil, Juliane and Frohme, Marcus and Schulze, Katja}, title = {Mobile microscopy for the examination of blood samples}, series = {EMBnet.journal}, volume = {23}, journal = {EMBnet.journal}, issn = {2226-6089}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-10509}, pages = {e904}, year = {2018}, abstract = {The analysis of blood is one of the best possibilities to diagnose and control diseases and deficiency symptoms. Common blood tests that are performed in medical laboratories are time-consuming and work-intensive. In under-developed areas, there is often also a lack of specialised staff and facilities. The development of a mobile microscopic system that contains an automated image analysis and that can be used via a smartphone, could represent a valuable help to improve the diagnostic care, especially in those areas. it aims to enable a very fast, cheap, location- and knowledge-independent application for many use cases.}, language = {en} } @article{GrebinykGrebinykPrylutskaetal.2018, author = {Grebinyk, Anna and Grebinyk, Sergii and Prylutska, Svitlana and Ritter, Uwe and Matyshevska, Olga and Dandekar, Thomas and Frohme, Marcus}, title = {C60 fullerene accumulation in human leukemic cells and perspectives of LED-mediated photodynamic therapy}, series = {Free Radical Biology and Medicine}, volume = {124}, journal = {Free Radical Biology and Medicine}, issn = {1873-4596}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-10588}, pages = {319 -- 327}, year = {2018}, abstract = {Recent progress in nanobiotechnology has attracted interest to a biomedical application of the carbon nanostructure C60 fullerene since it possesses a unique structure and versatile biological activity. C60 fullerene potential application in the frame of cancer photodynamic therapy (PDT) relies on rapid development of new light sources as well as on better understanding of the fullerene interaction with cells. The aim of this study was to analyze C60 fullerene effects on human leukemic cells (CCRF-CEM) in combination with high power single chip light-emitting diodes (LEDs) light irradiation of different wavelengths: ultraviolet (UV, 365 nm), violet (405 nm), green (515 nm) and red (632 nm). The time-dependent accumulation of fullerene C60 in CCRF-CEM cells up to 250 ng/106 cells at 24 h with predominant localization within mitochondria was demonstrated with immunocytochemical staining and liquid chromatography mass spectrometry. In a cell viability assay we studied photoexcitation of the accumulated C60 nanostructures with ultraviolet or violet LEDs and could prove that significant phototoxic effects did arise. A less pronounced C60 fullerene phototoxic effect was observed after irradiation with green, and no effect was detected with red light. A C60 fullerene photoactivation with violet light induced substantial ROS generation and apoptotic cell death, confirmed by caspase3/7 activation and plasma membrane phosphatidylserine externalization. Our work proved C60 fullerene ability to induce apoptosis of leukemic cells after photoexcitation with high power single chip 405 nm LED as a light source. This underlined the potential for application of C60 nanostructure as a photosensitizer for anticancer therapy.}, language = {en} } @article{KinuthiaFrohmeBroedeletal.2017, author = {Kinuthia, Chuaga and Frohme, Marcus and Br{\"o}del, Oliver and Mugendi, Beatrice}, title = {LCMS Analysis of Biochemical Composition in Different Kenyan Coffee Classifications}, series = {Food Science and Quality Management}, volume = {69}, journal = {Food Science and Quality Management}, issn = {2225-0557}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-10185}, pages = {44 -- 52}, year = {2017}, abstract = {Kenyan coffee is classified by defects after grading by the 'Devonshire method.' The method involves classification of the coffee beans into different classes based on the raw and roasted coffees and cup quality, with class one being the best and ten the poorest. In this study, the relationship between classification of the coffee and the content of sucrose, trigonelline, caffeine and chlorogenic acids was determined by simultaneous LC-MS analysis. By using the sensory variables the class 3 coffee portrayed the best quality, followed by class 4 and 5 which were placed further distinctively from the other classes (6, 7, 8 and 9). The class 3 coffee had a high percent of non-defective beans with 94.31\% and class 9 had a high defect count at 79.53\% hence the defective beans increased with decrease in coffee class. The caffeine concentration in green coffee for class 3 coffee was significantly different from the rest of the coffees at 1.23 ± 0.00g/100g. A higher content of trigonelline levels was observed as the quality of the green coffee decreased in classes 6, 7 and 8. The highest level of sucrose in green coffee beans was observed in class 3 coffee and the lowest in the class 9. Lower content of chlorogenic acids were observed among the high quality coffees i.e. class 3, 4 and 5 with class 3 having the lowest while a higher content was observed among the lower quality coffees i.e. classes 6, 7 and 9 with class 6 having a higher content was it significantly different in class 6 compared to 7 and 9?. Quantities of different chemical components among the classes are clear indicators that the classification method used on the Kenyan coffees brings out the differences in coffee quality based on the analysis of the green and the roasted coffees.}, language = {en} } @article{GrebinykPrylutskaGrebinyketal.2021, author = {Grebinyk, Anna and Prylutska, Svitlana and Grebinyk, Sergii and Evstigneev, Maxim and Krysiuk, Iryna and Skaterna, Tetiana and Horak, Iryna and Sun, Yanfang and Drobot, Liudmyla and Matyshevska, Olga and Prylutskyy, Yuriy and Ritter, Uwe and Frohme, Marcus}, title = {Antitumor efficiency of the natural alkaloid berberine complexed with C60 fullerene in Lewis lung carcinoma in vitro and in vivo}, series = {Cancer Nanotechnology}, volume = {12}, journal = {Cancer Nanotechnology}, publisher = {BioMed Central}, issn = {1868-6966}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-14749}, pages = {24}, year = {2021}, abstract = {Background Berberine (Ber) is a herbal alkaloid with pharmacological activity in general and a high anticancer potency in particular. However, due to its low bioavailability, the difficulty in reaching a target and choosing the right dose, there is a need to improve approaches of Ber use in anticancer therapy. In this study, Ber, noncovalently bound to a carbon nanostructure C60 fullerene (C60) at various molar ratios of the components, was explored against Lewis lung carcinoma (LLC). Methods C60-Ber noncovalent nanocomplexes were synthesized in 1:2, 1:1 and 2:1 molar ratios. Ber release from the nanocomplexes was studied after prolonged incubation at different pH with the liquid chromatography-mass spectrometry analysis of free Ber content. Biological effects of the free and C60-complaxated Ber were studied in vitro towards LLC cells with phase-contrast and fluorescence microscopy, flow cytometry, MTT reduction, caspase activity and wound closure assays. The treatment with C60-Ber nanocomplex was evaluated in vivo with the LLC-tumored C57Bl mice. The mice body weight, tumor size, tumor weight and tumor weight index were assessed for four groups, treated with saline, 15 mg C60/kg, 7.5 mg Ber/kg or 2:1 C60-Ber nanocomplex (15 mg C60/kg, 7.5 mg Ber/kg). Results Ber release from C60-Ber nanocomplexes was promoted with medium acidification. LLC cells treatment with C60-Ber nanocomplexes was followed by enhanced Ber intracellular uptake as compared to free Ber. The cytotoxicity of the studied agents followed the order: free Ber < 1:2 < 1:1 < 2:1 C60-Ber nanocomplex. The potency of cytotoxic effect of 2:1 C60-Ber nanocomplex was confirmed by 21.3-fold decrease of IC50 value (0.8 ± 0.3 µM) compared to IC50 for free Ber (17 ± 2 µM). C60-Ber nanocomplexes induced caspase 3/7 activation and suppressed the migration activity of LLC cells. The therapeutic potency of 2:1 C60-Ber nanocomplex was confirmed in a mouse model of LLC. The tumor growth in the group treated with 2:1 C60-Ber nanocomplex is suppressed by approximately 50\% at the end of experiment, while in the tumor-bearing group treated with free Ber no therapeutic effect was detected. Conclusions This study indicates that complexation of natural alkaloid Ber with C60 may be a novel therapeutic strategy against lung carcinoma.}, language = {en} } @article{PajčinVlajkovFrohmeetal.2020, author = {Pajčin, Ivana and Vlajkov, Vanja and Frohme, Marcus and Grebinyk, Sergii and Grahovac, Mila and Mojićević, Marija and Grahovac, Jovana}, title = {Pepper Bacterial Spot Control by Bacillus velezensis: Bioprocess Solution}, series = {Microorganisms}, volume = {8}, journal = {Microorganisms}, number = {10}, publisher = {MDPI}, issn = {2076-2607}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-13510}, year = {2020}, abstract = {Pepper bacterial spot is one of the most severe plant diseases in terms of infection persistence and economic losses when it comes to fresh pepper fruits used in nutrition and industrial processing. In this study, Bacillus velezensis IP22 isolated from fresh cheese was used as a biocontrol agent of pepper bacterial spot, whose main causal agent is the cosmopolitan pathogen Xanthomonas euvesicatoria. After optimization of the cultivation medium composition aimed at maximizing of the antimicrobial activity against X. euvesicatoria and validation of the optimized medium at the scale of a laboratory bioreactor, in planta tests were performed. The results have showed significant suppression of bacterial spot symptoms in pepper plants by the produced biocontrol agent, as well as reduction of disease spreading on the healthy (uninoculated) pepper leaves. Furthermore, HPLC-MS (high pressure liquid chromatography-mass spectrometry) analysis was employed to examine antimicrobial metabolites produced by B. velezensis IP22, where lipopeptides were found with similar m/z values compared to lipopeptides from fengycin and locillomycin families. The bioprocess solution developed at the laboratory scale investigated in this study represents a promising strategy for production of pepper bacterial spot biocontrol agent based on B. velezensis IP22, a food isolate with a great perspective for application in plant protection.}, language = {en} } @misc{SchulzeGloeklerKadolskyetal.2011, author = {Schulze, Katja and Gl{\"o}kler, J{\"o}rn and Kadolsky, Marianne and Frohme, Marcus}, title = {Detektion des Kartoffelspindelknollen Viroids mit Hilfe der Loop Mediated Isothermal Amplification}, series = {Wissenschaftliche Beitr{\"a}ge 2011}, volume = {15}, journal = {Wissenschaftliche Beitr{\"a}ge 2011}, issn = {0949-8214}, doi = {10.15771/0949-8214_2011_1_1}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus-1025}, pages = {7 -- 12}, year = {2011}, abstract = {PSTV ist ein hoch infekti{\"o}ses Viroid, das in Kartoffeln verkleinerte und spindel{\"a}hnliche Knollen verursacht. Um Ernteverlusten vorzubeugen, ist eine Detektion in fr{\"u}hen Infektionsstadien von großer Bedeutung. Aufgrund ihrer hohen Sensitivit{\"a}t und Spezifit{\"a}t wird die PCR als Standardnachweisverfahren f{\"u}r PSTV verwendet. Nachteilig an dieser Methode sind der apparative Aufwand und die zeitaufw{\"a}ndige Durchf{\"u}hrung. Als viel versprechende Alternative konnte der Nachweis von PSTV mit Hilfe der Reverse Transcription Loop Mediated Isothermal Amplification (RT-LAMP) gezeigt werden. Hierbei handelt es sich um eine einfache und schnelle Methode, f{\"u}r die wenig aufw{\"a}ndige Laborausr{\"u}stung ben{\"o}tigt wird. Dabei erm{\"o}glichte eine an den Amplifikationsprozess gekoppelte Fluoreszenzreaktion die Detektion von Produkten direkt nach der Nachweisreaktion mit dem bloßen Auge (bzw. unter UV-Licht). Die Ergebnisse konnten mit Hilfe einer Real Time Detektion des auftretenden Fluoreszenzsignals best{\"a}tigt werden.}, language = {de} } @article{KoberMeyerAlertGrienitzetal.2015, author = {Kober, Liane and Meyer-Alert, Henriette and Grienitz, Desir{\´e}e and Hollert, Henner and Frohme, Marcus}, title = {Intact cell mass spectrometry as a rapid and specific tool for the differentiation of toxic effects in cell-based ecotoxicological test systems}, series = {Analytical and Bioanalytical Chemistry}, volume = {407}, journal = {Analytical and Bioanalytical Chemistry}, number = {25}, issn = {1618-2650}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-5900}, pages = {7721 -- 7731}, year = {2015}, abstract = {In the last few decades, MALDI-TOF MS has become a useful technique not only in proteomics, but also as a fast and specific tool for whole cell analysis through intact cell mass spectrometry (IC-MS). The present study evaluated IC-MS as a novel tool for the detection of distinct patterns that can be observed after exposure to a certain toxin or concentration by utilizing the eukaryotic fish cell line RTL-W1. Two different viability assays were performed to define the range for IC-MS investigations, each of which employing copper sulfate, acridine, and β-naphthoflavone (BNF) as model compounds for several classes of environmental toxins. The IC-MS of RTL-W1 cells revealed not only specific spectral patterns for the various toxins, but also that the concentration used had an effect on RTL-W1 profiles. After the exposure with copper sulfate and acridine, the spectra of RTL-W1 showed a significant increase of certain peaks in the higher mass range (m/z >7000), which is probably attributed to the apoptosis of RTL-W1. On the contrary, exposure to BNF showed a distinct change of ion abundances only in the lower mass range (m/z <7000). Furthermore, a set of mass peaks could be identified as a specific biomarker for a single toxin treatment, so IC-MS demonstrates a new method for the distinction of toxic effects in fish cells. Due to fast sample preparation and high throughput, IC-MS offers great potential for ecotoxicological studies to investigate cellular effects of different substances and complex environmental samples.}, language = {en} } @article{SchulzeLangEnkeetal.2015, author = {Schulze, Katja and Lang, Imke and Enke, Heike and Grohme, Diana and Frohme, Marcus}, title = {The use of fluorescence microscopy and image analysis for rapid detection of non-producing revertant cells of Synechocystis sp. PCC6803 and Synechococcus sp. PCC7002}, series = {BMC Research Notes}, volume = {8}, journal = {BMC Research Notes}, number = {160}, issn = {1756-0500}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-5911}, pages = {11}, year = {2015}, abstract = {Ethanol production via genetically engineered cyanobacteria is a promising solution for the production of biofuels. Through the introduction of a pyruvate decarboxylase and alcohol dehydrogenase direct ethanol production becomes possible within the cells. However, during cultivation genetic instability can lead to mutations and thus loss of ethanol production. Cells then revert back to the wild type phenotype. A method for a rapid and simple detection of these non-producing revertant cells in an ethanol producing cell population is an important quality control measure in order to predict genetic stability and the longevity of a producing culture. Several comparable cultivation experiments revealed a difference in the pigmentation for non-producing and producing cells: the accessory pigment phycocyanin (PC) is reduced in case of the ethanol producer, resulting in a yellowish appearance of the culture. Microarray and western blot studies of Synechocystis sp. PCC6803 and Synechococcus sp. PCC7002 confirmed this PC reduction on the level of RNA and protein.}, language = {en} } @article{BilousMalkoFrohmeetal.2024, author = {Bilous, Nataliya and Malko, Vladyslav and Frohme, Marcus and Nechyporenko, Alina}, title = {Comparison of CNN-Based Architectures for Detection of Different Object Classes}, series = {AI}, volume = {5}, journal = {AI}, number = {4}, publisher = {MDPI}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-19634}, pages = {2300 -- 2320}, year = {2024}, abstract = {(1) Background: Detecting people and technical objects in various situations, such as natural disasters and warfare, is critical to search and rescue operations and the safety of civilians. A fast and accurate detection of people and equipment can significantly increase the effectiveness of search and rescue missions and provide timely assistance to people. Computer vision and deep learning technologies play a key role in detecting the required objects due to their ability to analyze big volumes of visual data in real-time. (2) Methods: The performance of the neural networks such as You Only Look Once (YOLO) v4-v8, Faster R-CNN, Single Shot MultiBox Detector (SSD), and EfficientDet has been analyzed using COCO2017, SARD, SeaDronesSee, and VisDrone2019 datasets. The main metrics for comparison were mAP, Precision, Recall, F1-Score, and the ability of the neural network to work in real-time. (3) Results: The most important metrics for evaluating the efficiency and performance of models for a given task are accuracy (mAP), F1-Score, and processing speed (FPS). These metrics allow us to evaluate both the accuracy of object recognition and the ability to use the models in real-world environments where high processing speed is important. (4) Conclusion: Although different neural networks perform better on certain types of metrics, YOLO outperforms them on all metrics, showing the best results of mAP-0.88, F1-0.88, and FPS-48, so the focus was on these models.}, language = {en} } @article{PrzymusRykaczewskiMartinSeguraetal.2025, author = {Przymus, Piotr and Rykaczewski, Krzysztof and Mart{\´i}n-Segura, Adri{\´a}n and Truu, Jaak and De Santa Pau, Enrique Carrillo and Kolev, Mikhail and Naskinova, Irina and Gruca, Aleksandra and Sampri, Alexia and Frohme, Marcus and Nechyporenko, Alina}, title = {Deep Learning in Microbiome Analysis: A Comprehensive Review of Neural Network Models}, series = {Frontiers in Microbiology}, volume = {15}, journal = {Frontiers in Microbiology}, publisher = {Frontiers}, issn = {1664-302X}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-19889}, year = {2025}, abstract = {Microbiome research, the study of microbial communities in diverse environments, has seen significant advances due to the integration of deep learning (DL) methods. These computational techniques have become essential for addressing the inherent complexity and high-dimensionality of microbiome data, which consist of different types of omics datasets. Deep learning algorithms have shown remarkable capabilities in pattern recognition, feature extraction, and predictive modeling, enabling researchers to uncover hidden relationships within microbial ecosystems. By automating the detection of functional genes, microbial interactions, and host-microbiome dynamics, DL methods offer unprecedented precision in understanding microbiome composition and its impact on health, disease, and the environment. However, despite their potential, deep learning approaches face significant challenges in microbiome research. Additionally, the biological variability in microbiome datasets requires tailored approaches to ensure robust and generalizable outcomes. As microbiome research continues to generate vast and complex datasets, addressing these challenges will be crucial for advancing microbiological insights and translating them into practical applications with DL. This review provides an overview of different deep learning models in microbiome research, discussing their strengths, practical uses, and implications for future studies. We examine how these models are being applied to solve key problems and highlight potential pathways to overcome current limitations, emphasizing the transformative impact DL could have on the field moving forward.}, language = {en} } @article{NarvekarBerrielDiazKronesHerzigetal.2009, author = {Narvekar, Prachiti and Berriel Diaz, Mauricio and Krones-Herzig, Anja and Hardeland, Ulrike and Strzoda, Daniela and St{\"o}hr, Sigrid and Frohme, Marcus and Herzig, Stephan}, title = {Liver-specific loss of lipolysis-stimulated lipoprotein receptor triggers systemic hyperlipidemia in mice}, series = {Diabetes}, volume = {58}, journal = {Diabetes}, number = {5}, publisher = {American Diabetes Association}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-19954}, pages = {1040 -- 1049}, year = {2009}, abstract = {In mammals, proper storage and distribution of lipids in and between tissues is essential for the maintenance of energy homeostasis. In contrast, aberrantly high levels of triglycerides in the blood ("hypertriglyceridemia") represent a hallmark of the metabolic syndrome and type 2 diabetes. As hypertriglyceridemia has been identified as an important risk factor for cardiovascular complications, in this study we aimed to identify molecular mechanisms in aberrant triglyceride elevation under these conditions. To determine the importance of hepatic lipid handling for systemic dyslipidemia, we profiled the expression patterns of various hepatic lipid transporters and receptors under healthy and type 2 diabetic conditions. A differentially expressed lipoprotein receptor was functionally characterized by generating acute, liver-specific loss- and gain-of-function animal models. We show that the hepatic expression of lipid transporter lipolysis-stimulated lipoprotein receptor (LSR) is specifically impaired in mouse models of obesity and type 2 diabetes and can be restored by leptin replacement. Experimental imitation of this pathophysiological situation by liver-specific knockdown of LSR promotes hypertriglyceridemia and elevated apolipoprotein (Apo)B and E serum levels in lean wild-type and ApoE knockout mice. In contrast, genetic restoration of LSR expression in obese animals to wild-type levels improves serum triglyceride levels and serum profiles in these mice. The dysregulation of hepatic LSR under obese and diabetic conditions may provide a molecular rationale for systemic dyslipidemia in type 2 diabetes and the metabolic syndrome and represent a novel target for alternative treatment strategies in these patients.}, language = {en} } @article{ReunerHengherrMalietal.2010, author = {Reuner, Andy and Hengherr, Steffen and Mali, Brahim and F{\"o}rster, Frank and Arndt, Detlev and Reinhardt, Richard and Dandekar, Thomas and Frohme, Marcus and Br{\"u}mmer, Franz and Schill, Ralph O.}, title = {Stress response in tardigrades: differential gene expression of molecular chaperones}, series = {Cell Stress and Chaperones}, volume = {15}, journal = {Cell Stress and Chaperones}, number = {4}, publisher = {Springer}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-19994}, pages = {423 -- 430}, year = {2010}, abstract = {Semi-terrestrial tardigrades exhibit a remarkable tolerance to desiccation by entering a state called anhydrobiosis. In this state, they show a strong resistance against several kinds of physical extremes. Because of the probable importance of stress proteins during the phases of dehydration and rehydration, the relative abundance of transcripts coding for two α-crystallin heat-shock proteins (Mt-sHsp17.2 and Mt-sHsp19.5), as well for the heat-shock proteins Mt-sHsp10, Mt-Hsp60, Mt-Hsp70 and Mt-Hsp90, were analysed in active and anhydrobiotic tardigrades of the species Milnesium tardigradum. They were also analysed in the transitional stage (I) of dehydration, the transitional stage (II) of rehydration and in heat-shocked specimens. A variable pattern of expression was detected, with most candidates being downregulated. Gene transcripts of one Mt-hsp70 isoform in the transitional stage I and Mt-hsp90 in the anhydrobiotic stage were significantly upregulated. A high gene expression (778.6-fold) was found for the small α-crystallin heat-shock protein gene Mt-sHsp17.2 after heat shock. We discuss the limited role of the stress-gene expression in the transitional stages between the active and anhydrobiotic tardigrades and other mechanisms which allow tardigrades to survive desiccation.}, language = {en} } @article{TillichLehmannSchulzeetal.2012, author = {Tillich, Ulrich M. and Lehmann, Sandra and Schulze, Katja and D{\"u}hring, Ulf and Frohme, Marcus}, title = {The Optimal Mutagen Dosage to Induce Point-Mutations in Synechocystis sp. PCC6803 and Its Application to Promote Temperature Tolerance}, series = {PLoS ONE}, volume = {7}, journal = {PLoS ONE}, number = {11}, issn = {1932-6203}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-6186}, pages = {8}, year = {2012}, abstract = {Random mutagenesis is a useful tool to genetically modify organisms for various purposes, such as adaptation to cultivation conditions, the induction of tolerances, or increased yield of valuable substances. This is especially attractive for systems where it is not obvious which genes require modifications. Random mutagenesis has been extensively used to modify crop plants, but even with the renewed interest in microalgae and cyanobacteria for biofuel applications, there is relatively limited current research available on the application of random mutagenesis for these organisms, especially for cyanobacteria. In the presented work we characterized the lethality and rate of non-lethal point mutations for ultraviolet radiation and methyl methanesulphonate on the model cyanobacteria Synechocystis sp. PCC6803. Based on these results an optimal dosage of 10-50 J/m2 for UV and either 0.1 or 1 v\% for MMS was determined. A Synechocystis wildtype culture was then mutagenized and selected for increased temperature tolerance in vivo. During the second round of mutagenesis the viability of the culture was monitored on a cell by cell level from the treatment of the cells up to the growth at an increased temperature. After four distinct rounds of treatment (two with each mutagen) the temperature tolerance of the strain was effectively raised by about 2°C. Coupled with an appropriate in vivo screening, the described methods should be applicable to induce a variety of desirable characteristics in various strains. Coupling random mutagenesis with high-throughput screening methods would additionally allow to select for important characteristics for biofuel production, which do not yield a higher fitness and can not be selected for in vivo, such as fatty acid concentration. In a combined approach with full genome sequencing random mutagenesis could be used to determine suitable target-genes for more focused methods.}, language = {en} } @article{SchulzeLopezTillichetal.2011, author = {Schulze, Katja and L{\´o}pez, Diana A. and Tillich, Ulrich M. and Frohme, Marcus}, title = {A simple viability analysis for unicellular cyanobacteria using a new autofluorescence assay, automated microscopy, and ImageJ}, series = {BMC Biotechnology}, volume = {11}, journal = {BMC Biotechnology}, number = {118}, issn = {1472-6750}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-6192}, pages = {8}, year = {2011}, abstract = {Currently established methods to identify viable and non-viable cells of cyanobacteria are either time-consuming (eg. plating) or preparation-intensive (eg. fluorescent staining). In this paper we present a new and fast viability assay for unicellular cyanobacteria, which uses red chlorophyll fluorescence and an unspecific green autofluorescence for the differentiation of viable and non-viable cells without the need of sample preparation.}, language = {en} } @article{SchulzeTillichDandekaretal.2013, author = {Schulze, Katja and Tillich, Ulrich M. and Dandekar, Thomas and Frohme, Marcus}, title = {PlanktoVision - an automated analysis system for the identification of phytoplankton}, series = {BMC Bioinformatics}, volume = {14}, journal = {BMC Bioinformatics}, number = {115}, issn = {1471-2105}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-6364}, pages = {10}, year = {2013}, abstract = {Phytoplankton communities are often used as a marker for the determination of fresh water quality. The routine analysis, however, is very time consuming and expensive as it is carried out manually by trained personnel. The goal of this work is to develop a system for an automated analysis.}, language = {en} } @article{TillichWolterSchulzeetal.2014, author = {Tillich, Ulrich M. and Wolter, Nick and Schulze, Katja and Kramer, Dan and Br{\"o}del, Oliver and Frohme, Marcus}, title = {High-throughput cultivation and screening platform for unicellular phototrophs}, series = {BMC Microbiology}, volume = {14}, journal = {BMC Microbiology}, number = {239}, issn = {1471-2180}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-6007}, pages = {13}, year = {2014}, abstract = {In this work we describe and test high-throughput methods with the model organism Synechocystis sp. PCC6803. The required technical automation for these processes was achieved with a Tecan Freedom Evo 200 pipetting robot. The cultivation was performed in 2.2 ml deepwell microtiter plates within a cultivation chamber outfitted with programmable shaking conditions, variable illumination, variable temperature, and an adjustable CO2 atmosphere. Each microtiter-well within the chamber functions as a separate cultivation vessel with reproducible conditions. The automated measurement of various parameters such as growth, full absorption spectrum, chlorophyll concentration, MALDI-TOF-MS, as well as a novel vitality measurement protocol, have already been established and can be monitored during cultivation. Measurement of growth parameters can be used as inputs for the system to allow for periodic automatic dilutions and therefore a semi-continuous cultivation of hundreds of cultures in parallel. The system also allows the automatic generation of mid and long term backups of cultures to repeat experiments or to retrieve strains of interest.}, language = {en} } @article{TillichWolterFrankeetal.2014, author = {Tillich, Ulrich M. and Wolter, Nick and Franke, Philipp and D{\"u}hring, Ulf and Frohme, Marcus}, title = {Screening and genetic characterization of thermo-tolerant Synechocystis sp. PCC6803 strains created by adaptive evolution}, series = {BMC Biotechnology}, volume = {14}, journal = {BMC Biotechnology}, number = {66}, issn = {1472-6750}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-6014}, pages = {15}, year = {2014}, abstract = {Temperature tolerance is an important aspect for commercial scale outdoor cultivation of microalgae and cyanobacteria. While various genes are known to be related to Synechocystis sp. PCC6803's heat shock response, there is very limited published data concerning the specific genes involved in long term thermal tolerance. We have previously used random mutagenesis and adaptive evolution to generate a mixture of strains of Synechocystis sp. PCC6803 with significantly increased thermal tolerance. The genetic modifications leading to the phenotypes of the newly generated strains are the focus of this work.}, language = {en} } @article{KipkorirMuhohoMuliroetal.2015, author = {Kipkorir, R. and Muhoho, S. and Muliro, P. and Mugendi, Beatrice and Frohme, Marcus and Br{\"o}del, Oliver}, title = {Effects of Coffee Processing Technologies on Aroma Profiles and Sensory Quality of Ruiru 11 and SL 28 Kenyan Coffee Varieties}, series = {Asian Journal of Agriculture and Food Sciences}, volume = {3}, journal = {Asian Journal of Agriculture and Food Sciences}, number = {2}, issn = {2321-1571}, doi = {10.15771/2321-1571_2015_1}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-6482}, pages = {178 -- 188}, year = {2015}, abstract = {The study aimed at comparing the effects of three coffee processing methods on aroma profiles and sensory quality of Ruiru 11 and SL 28 coffee varieties. The processing methods varied on stages of processing and method of mucilage removal. The green coffee beans obtained from the three processing methods were graded and roasted, ground and analyzed for the aroma profiles and sensory quality. Headspace Solid phase Microextraction fibre (SPME) technique were used for the extraction of aroma compounds from coffee samples and characterization of the compounds with use of gas chromatography mass spectrometry (GC-MS). Sensory quality were analyzed by an expert panelist. Various volatile aroma compounds were identified in roasted coffee and classified into their chemical classes involving furans, ketones, pyrazines ketones pyridines, pyrroles and acids. The intensity of aroma compounds were compared in terms of their peak areas and variations were noted between the processing methods with the ecopulper showing higher levels of pyrazines such as 2-methylpyrazine, 2-ethyl-6-methylpyrazine, and wet pulper showing higher levels of furans such as furfuryl formate and furfuryl alcohol, acetate. The hand pulper was high in the level of acids and esters such as acetic acid and propanoic acid, ethyl ester. Similar aroma compounds were identified in headspace of Ruiru 11 and SL 28 and there were variations in the intensities of aroma groups such as pyrroles and pyridines. It was concluded that the eco-pulper and hand pulper methods gives better aroma quality than the wet pulper while SL 28 variety gives higher sensory quality than Ruiru 11.}, language = {en} } @article{PraiaHerkenhoffBroedeletal.2022, author = {Praia, Ana Beatriz and Herkenhoff, Marcos Edgar and Br{\"o}del, Oliver and Frohme, Marcus and Saad, Susana Marta Isay}, title = {Sour Beer with Lacticaseibacillus paracasei subsp. paracasei F19: Feasibility and Influence of Supplementation with Spondias mombin L. Juice and/or By-Product}, series = {Foods}, volume = {11}, journal = {Foods}, number = {24}, publisher = {MDPI}, issn = {2304-8158}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-16852}, year = {2022}, abstract = {This study aimed to evaluate the probiotic strain Lacticaseibacillus (L.) paracasei subsp. paracasei F19 (F19) with the yeast Saccharomyces cerevisiae US-05 (US-05), using Spondias mombin L. ('tapereb{\´a}' or 'caj{\´a}') juice and by-product, in four sour-type beer formulations: control, with bagasse, juice, and juice and bagasse. The viability of F19 was evaluated by pour-plating and PMA-qPCR. Fermentability, in addition to physicochemical and sensory parameters, and aroma and flavor, were evaluated during brewery by using Headspace Solid-Phase Microextraction (HS-SPME) coupled with gas chromatography-mass spectrometry (GC-MS). F19 was successful in fermenting bagasse in a MRS medium (9.28 log CFU/mL in 24 h) but had a low viability in hopped wort, growing better in formulations without bagasse or juice. No difference between formulations was observed regarding sensory acceptability, and the HS-SPME/GC-MS revealed different flavors and aroma compounds. In conclusion, the production of a potential probiotic sour beer with F19 and US-05 is feasible regarding probiotic viability. However, S. mombin, as juice or bagasse, threatened probiotic survival. Different flavors and aroma compounds were detected, whereas no difference between formulations was found regarding sensory acceptability. The moderate alcohol content achieved is important for bacterial survival and for the development of a probiotic beer with health claims.}, language = {en} } @article{RadivoievychKolpGrebinyketal.2023, author = {Radivoievych, Aleksandar and Kolp, Benjamin and Grebinyk, Sergii and Prylutska, Svitlana and Ritter, Uwe and Zolk, Oliver and Gl{\"o}kler, J{\"o}rn and Frohme, Marcus and Grebinyk, Anna}, title = {Silent Death by Sound: C60 Fullerene Sonodynamic Treatment of Cancer Cells}, series = {International Journal of Molecular Sciences}, volume = {24}, journal = {International Journal of Molecular Sciences}, number = {2}, publisher = {MDPI}, issn = {1422-0067}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-16877}, year = {2023}, abstract = {The acoustic pressure waves of ultrasound (US) not only penetrate biological tissues deeper than light, but they also generate light emission, termed sonoluminescence. This promoted the idea of its use as an alternative energy source for photosensitizer excitation. Pristine C60 fullerene (C60), an excellent photosensitizer, was explored in the frame of cancer sonodynamic therapy (SDT). For that purpose, we analyzed C60 effects on human cervix carcinoma HeLa cells in combination with a low-intensity US treatment. The time-dependent accumulation of C60 in HeLa cells reached its maximum at 24 h (800 ± 66 ng/106 cells). Half of extranuclear C60 is localized within mitochondria. The efficiency of the C60 nanostructure's sonoexcitation with 1 MHz US was tested with cell-based assays. A significant proapoptotic sonotoxic effect of C60 was found for HeLa cells. C60′s ability to induce apoptosis of carcinoma cells after sonoexcitation with US provides a promising novel approach for cancer treatment.}, language = {en} } @article{AlekseevaNechyporenkoFrohmeetal.2023, author = {Alekseeva, Victoriia and Nechyporenko, Alina and Frohme, Marcus and Gargin, Vitaliy and Meniailov, Ievgen and Chumachenko, Dmytro}, title = {Intelligent Decision Support System for Differential Diagnosis of Chronic Odontogenic Rhinosinusitis Based on U-Net Segmentation}, series = {Electronics}, volume = {12}, journal = {Electronics}, number = {5}, publisher = {MDPI}, issn = {2079-9292}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-17088}, year = {2023}, abstract = {The share of chronic odontogenic rhinosinusitis is 40\% among all chronic rhinosinusitis. Using automated information systems for differential diagnosis will improve the efficiency of decision-making by doctors in diagnosing chronic odontogenic rhinosinusitis. Therefore, this study aimed to develop an intelligent decision support system for the differential diagnosis of chronic odontogenic rhinosinusitis based on computer vision methods. A dataset was collected and processed, including 162 MSCT images. A deep learning model for image segmentation was developed. A 23 convolutional layer U-Net network architecture has been used for the segmentation of multi-spiral computed tomography (MSCT) data with odontogenic maxillary sinusitis. The proposed model is implemented in such a way that each pair of repeated 3 × 3 convolutions layers is followed by an Exponential Linear Unit instead of a Rectified Linear Unit as an activation function. The model showed an accuracy of 90.09\%. To develop a decision support system, an intelligent chatbot allows the user to conduct an automated patient survey and collect patient examination data from several doctors of various profiles. The intelligent information system proposed in this study made it possible to combine an image processing model with a patient interview and examination data, improving physician decision-making efficiency in the differential diagnosis of Chronic Odontogenic Rhinosinusitis. The proposed solution is the first comprehensive solution in this area.}, language = {en} } @article{ChumachenkoButkevychLodeetal.2022, author = {Chumachenko, Dmytro and Butkevych, Mykola and Lode, Daniel and Frohme, Marcus and Schmailzl, Kurt J. G. and Nechyporenko, Alina}, title = {Machine Learning Methods in Predicting Patients with Suspected Myocardial Infarction Based on Short-Time HRV Data}, series = {Sensors}, volume = {22}, journal = {Sensors}, number = {18}, publisher = {MDPI}, issn = {1424-8220}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-16521}, year = {2022}, abstract = {Diagnosis of cardiovascular diseases is an urgent task because they are the main cause of death for 32\% of the world's population. Particularly relevant are automated diagnostics using machine learning methods in the digitalization of healthcare and introduction of personalized medicine in healthcare institutions, including at the individual level when designing smart houses. Therefore, this study aims to analyze short 10-s electrocardiogram measurements taken from 12 leads. In addition, the task is to classify patients with suspected myocardial infarction using machine learning methods. We have developed four models based on the k-nearest neighbor classifier, radial basis function, decision tree, and random forest to do this. An analysis of time parameters showed that the most significant parameters for diagnosing myocardial infraction are SDNN, BPM, and IBI. An experimental investigation was conducted on the data of the open PTB-XL dataset for patients with suspected myocardial infarction. The results showed that, according to the parameters of the short ECG, it is possible to classify patients with a suspected myocardial infraction as sick and healthy with high accuracy. The optimized Random Forest model showed the best performance with an accuracy of 99.63\%, and a root mean absolute error is less than 0.004. The proposed novel approach can be used for patients who do not have other indicators of heart attacks.}, language = {en} } @article{GrebinykPrylutskaGrebinyketal.2022, author = {Grebinyk, Anna and Prylutska, Svitlana and Grebinyk, Sergii and Ponomarenko, Stanislav and Virych, Pavlo and Chumachenko, Vasyl and Kutsevol, Nataliya and Prylutskyy, Yuriy and Ritter, Uwe and Frohme, Marcus}, title = {Drug delivery with a pH-sensitive star-like dextran-graft polyacrylamide copolymer}, series = {Nanoscale Advances}, volume = {4}, journal = {Nanoscale Advances}, number = {23}, publisher = {Royal Society of Chemistry (RSC)}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-16749}, pages = {5077 -- 5088}, year = {2022}, abstract = {The development of precision cancer medicine relies on novel formulation strategies for targeted drug delivery to increase the therapeutic outcome. Biocompatible polymer nanoparticles, namely dextran-graft-polyacrylamide (D-g-PAA) copolymers, represent one of the innovative non-invasive approaches for drug delivery applications in cancer therapy. In this study, the star-like D-g-PAA copolymer in anionic form (D-g-PAAan) was developed for pH-triggered targeted drug delivery of the common chemotherapeutic drugs - doxorubicin (Dox) and cisplatin (Cis). The initial D-g-PAA copolymer was synthesized by the radical graft polymerization method, and then alkaline-hydrolyzed to get this polymer in anionic form for further use for drug encapsulation. The acidification of the buffer promoted the release of loaded drugs. D-g-PAAan nanoparticles increased the toxic potential of the drugs against human and mouse lung carcinoma cells (A549 and LLC), but not against normal human lung cells (HEL299). The drug-loaded D-g-PAAan-nanoparticles promoted further oxidative stress and apoptosis induction in LLC cells. D-g-PAAan-nanoparticles improved Dox accumulation and drugs' toxicity in a 3D LLC multi-cellular spheroid model. The data obtained indicate that the strategy of chemotherapeutic drug encapsulation within the branched D-g-PAAan nanoparticle allows not only to realize pH-triggered drug release but also to potentiate its cytotoxic, prooxidant and proapoptotic effects against lung carcinoma cells.}, language = {en} } @article{KoberSchaeferHollertetal.2023, author = {Kober, Liane and Schaefer, Paul and Hollert, Henner and Frohme, Marcus}, title = {A novel strategy for high-throughput sample collection, analysis and visualization of explosives' concentrations for contaminated areas}, series = {International Journal of Environmental Science and Technology}, volume = {20}, journal = {International Journal of Environmental Science and Technology}, number = {2}, publisher = {Springer Nature}, issn = {1735-2630}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-15981}, pages = {1399 -- 1410}, year = {2023}, abstract = {The use of explosives has led to a widespread distribution of 2,4,6-trinitrotoluene (TNT) and its by- and degradation products in the soil on former production and testing sites. The investigation of those large contaminated sites is so far based on a few selected soil samples, due to high costs of conventional HPLC and GC analysis, although huge differences in concentrations can already be found in small areas and different collection depths. We introduce a novel high-throughput screening system for those areas, which combines a smartphone-based collection of GPS data and soil characteristics with a fast MALDI-TOF MS quantification of explosives in soil sample extracts and finally a heatmap visualization of the explosives' spread in soil and an analysis of correlation between concentrations and soil characteristics. The analysis of a 400 m2 area presented an extensive contamination with TNT and lower concentrations of the degradation and by-products aminodinitrotoluenes (ADNT) and dinitrotoluenes (DNT) next to a former production facility for TNT. The contamination decreased in deeper soil levels and depended on the soil type. Pure humus samples showed significantly lower contaminations compared to sand and humus/sand mixtures, which is likely to be caused by an increased binding potential of the humic material. No correlation was found between the vegetation and the concentration of explosives. Since the results were obtained and visualized within several hours, the MALDI-TOF MS based comprehensive screening and heatmap analysis might be valuable for a fast and high-throughput characterization of contaminated areas.}, language = {en} } @article{PfeilNechyporenkoFrohmeetal.2022, author = {Pfeil, Juliane and Nechyporenko, Alina and Frohme, Marcus and Hufert, Frank T. and Schulze, Katja}, title = {Examination of blood samples using deep learning and mobile microscopy}, series = {BMC Bioinformatics}, volume = {23}, journal = {BMC Bioinformatics}, publisher = {BioMed Central}, issn = {1471-2105}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-15802}, year = {2022}, abstract = {Microscopic examination of human blood samples is an excellent opportunity to assess general health status and diagnose diseases. Conventional blood tests are performed in medical laboratories by specialized professionals and are time and labor intensive. The development of a point-of-care system based on a mobile microscope and powerful algorithms would be beneficial for providing care directly at the patient's bedside. For this purpose human blood samples were visualized using a low-cost mobile microscope, an ocular camera and a smartphone. Training and optimisation of different deep learning methods for instance segmentation are used to detect and count the different blood cells. The accuracy of the results is assessed using quantitative and qualitative evaluation standards.}, language = {en} } @article{HerkenhoffBovolentaBroedeletal.2021, author = {Herkenhoff, Marcos Edgar and Bovolenta, Luiz A. and Br{\"o}del, Oliver and dos Santos, Lucilene Delazari and de Oliveira, Arthur C. and Chuffa, Luiz G.A. and Ribeiro, Amanda O. and Lupi, Luiz A. and Dias, Marco A.D. and Hilsdorf, Alexandre W.S. and Frohme, Marcus and Pinhal, Danillo}, title = {Variant expression signatures of microRNAs and protein related to growth in a crossbreed between two strains of Nile tilapia (Oreochromis niloticus)}, series = {Genomics}, volume = {113}, journal = {Genomics}, number = {6}, publisher = {Elsevier}, issn = {0888-7543}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-15571}, pages = {4303 -- 4312}, year = {2021}, abstract = {Nile tilapia (Oreochromis niloticus) is a species of worldwide importance for aquaculture. A crossbred lineage was developed through introgressive backcross breeding techniques and combines the high growth performance of the Chitralada (CHIT) lwith attractive reddish color of the Red Stirling (REDS) strains. Since the crossbreed has an unknown genetically improved background, the objective of this work was to characterize expression signatures that portray the advantageous phenotype of the crossbreeds. We characterized the microRNA transcriptome by high throughput sequencing (RNA-seq) and the proteome through mass spectrometry (ESI-Q-TOF-MS) and applied bioinformatics for the comparative analysis of such molecular data on the three strains. Crossbreed expressed a distinct set of miRNAs and proteins compared to the parents. They comprised several microRNAs regulate traits of economic interest. Proteomic profiles revealed differences between parental and crossbreed in expression of proteins associated with glycolisis. Distinctive miRNA and protein signatures contribute to the phenotype of crossbreed.}, language = {en} } @article{GloeklerLimIdaetal.2021, author = {Gl{\"o}kler, J{\"o}rn and Lim, Theam Soon and Ida, Jeunice and Frohme, Marcus}, title = {Isothermal amplifications - a comprehensive review on current methods}, series = {Critical Reviews in Biochemistry and Molecular Biology}, journal = {Critical Reviews in Biochemistry and Molecular Biology}, publisher = {Taylor \& Francis}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-15154}, pages = {1 -- 44}, year = {2021}, abstract = {AbstractThe introduction of nucleic acid amplification techniques has revolutionized the field of medical diagnostics in the last decade. The advent of PCR catalyzed the increasing application of DNA, not just for molecular cloning but also for molecular based diagnostics. Since the introduction of PCR, a deeper understanding of molecular mechanisms and enzymes involved in DNA/RNA replication has spurred the development of novel methods devoid of temperature cycling. Isothermal amplification methods have since been introduced utilizing different mechanisms, enzymes, and conditions. The ease with which isothermal amplification methods have allowed nucleic acid amplification to be carried out has had a profound impact on the way molecular diagnostics are being designed after the turn of the millennium. With all the advantages isothermal amplification brings, the issues or complications surrounding each method are heterogeneous making it difficult to identify the best approach for an end-user. This review pays special attention to the various isothermal amplification methods by classifying them based on the mechanistic characteristics which include reaction formats, amplification information, promoter, strand break, and refolding mechanisms. We would also compare the efficiencies and usefulness of each method while highlighting the potential applications and detection methods involved. This review will serve as an overall outlook on the journey and development of isothermal amplification methods as a whole.}, language = {en} } @article{RadivoievychPrylutskaZolketal.2023, author = {Radivoievych, Aleksandar and Prylutska, Svitlana and Zolk, Oliver and Ritter, Uwe and Frohme, Marcus and Grebinyk, Anna}, title = {Comparison of Sonodynamic Treatment Set-Ups for Cancer Cells with Organic Sonosensitizers and Nanosonosensitizers}, series = {Pharmaceutics}, volume = {15}, journal = {Pharmaceutics}, number = {11}, publisher = {MDPI}, issn = {1999-4923}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-18223}, year = {2023}, abstract = {Cancer sonodynamic therapy (SDT) is the therapeutic strategy of a high-frequency ultrasound (US) combined with a special sonosensitizer that becomes cytotoxic upon US exposure. The growing number of newly discovered sonosensitizers and custom US in vitro treatment solutions push the SDT field into a need for systemic studies and reproducible in vitro experimental set-ups. In the current research, we aimed to compare two of the most used and suitable SDT in vitro set-ups—"sealed well" and "transducer in well"—in one systematic study. We assessed US pressure, intensity, and temperature distribution in wells under US irradiation. Treatment efficacy was evaluated for both set-ups towards cancer cell lines of different origins, treated with two promising sonosensitizer candidates—carbon nanoparticle C60 fullerene (C60) and herbal alkaloid berberine. C60 was found to exhibit higher sonotoxicity toward cancer cells than berberine. The higher efficacy of sonodynamic treatment with a "transducer in well" set-up than a "sealed well" set-up underlined its promising application for SDT in vitro studies. The "transducer in well" set-up is recommended for in vitro US treatment investigations based on its US-field homogeneity and pronounced cellular effects. Moreover, SDT with C60 and berberine could be exploited as a promising combinative approach for cancer treatment.}, language = {en} } @article{ShchotkinaPalamarchukSkorokhodetal.2023, author = {Shchotkina, Nataliia and Palamarchuk, Y. and Skorokhod, Iryna and Dolinchuk, Liudmyla and Sokol, Anatoliy and Motronenko, Valentina and Besarab, A. and Gorchakova, N. and Frohme, Marcus and Herzog, Michael}, title = {Features of technological regulation for cardiac bioimplants}, series = {Cell and Organ Transplantology}, volume = {11}, journal = {Cell and Organ Transplantology}, number = {1}, publisher = {Institute of Cell Therapy}, address = {Kiev}, issn = {2311-021X}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-18248}, pages = {26 -- 33}, year = {2023}, abstract = {Patients with congenital heart defects and cardiovascular diseases are required new approaches to surgical intervention. The use of biological cardiac implants, which are made from the extracellular matrix, is a promising trend in modern regenerative medicine. These bioimplants can completely replace defective tissue or organs, and when manufactured with strict protocols and quality control measures, can be safe and effective for therapeutic applications. The process of manufacturing bioimplants involves various risks that need to be assessed and mitigated with ongoing monitoring and evaluation necessary to ensure the highest standards of quality. Overall, this study was successfully evaluated the requirements for introducing a new medical device into practice and created a technical file that meets all necessary documentation for certification.}, language = {en} } @article{PrylutskaGrebinykPonomarenkoetal.2024, author = {Prylutska, Svitlana and Grebinyk, Anna and Ponomarenko, Stanislav and G{\"o}vem, Defne and Chumachenko, Vasyl and Kutsevol, Nataliya and Petrovsky, Mykola and Ritter, Uwe and Frohme, Marcus and Piosik, Jacek and Prylutskyy, Yuriy}, title = {Toxicity of Water-Soluble D-g-PNIPAM Polymers in a Complex with Chemotherapy Drugs and Mechanism of Their Action In Vitro}, series = {International Journal of Molecular Sciences}, volume = {25}, journal = {International Journal of Molecular Sciences}, number = {5}, publisher = {MDPI}, issn = {1422-0067}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-18790}, year = {2024}, abstract = {The application of a biocompatible polymer nanocarrier can provide target delivery to tumor tissues, improved pharmacokinetics, controlled drug release, etc. Therefore, the proposed strategy was to use the water-soluble star-like copolymers with a Dextran core and Poly(N-isopropylacrylamide) grafts (D-g-PNIPAM) for conjugation with the widely used chemotherapy drugs in oncology-Cisplatin (Cis-Pt) and Doxorubicin (Dox). The molecular characteristics of the copolymer were received using size-exclusion chromatography. The physicochemical characterization of the D-g-PNIPAM-Cis-Pt (or Dox) nanosystem was conducted using dynamic light scattering and FTIR spectroscopy. Using traditional biochemical methods, a comparative analysis of the enhancement of the cytotoxic effect of free Cis-Pt and Dox in combination with D-g-PNIPAM copolymers was performed in cancer cells of the Lewis lung carcinoma line, which are both sensitive and resistant to Dox; in addition, the mechanism of their action in vitro was evaluated.}, language = {en} } @inproceedings{AlekseevaReshetnikFrohmeetal.2023, author = {Alekseeva, Victoriia and Reshetnik, Viktor and Frohme, Marcus and Kachailo, Irina and Murizyna, Irina and Nechyporenko, Alina}, title = {Investigation of the Impact of Insulin Resistance on the Bone Density of the Upper Wall of the Maxillary Sinus}, series = {Proceedings of the 3rd International Workshop of IT-professionals on Artificial Intelligence, ProfIT AI 2023, Waterloo, Canada, November 20-22, 2023}, volume = {3641}, booktitle = {Proceedings of the 3rd International Workshop of IT-professionals on Artificial Intelligence, ProfIT AI 2023, Waterloo, Canada, November 20-22, 2023}, editor = {Chumachenko, Dmytro and Kaur, Jasleen and Yakovlev, Sergiy and Morita, Plinio P.}, publisher = {CEUR-WS.org}, url = {http://nbn-resolving.de/urn:nbn:de:0074-3641-3}, pages = {216 -- 223}, year = {2023}, abstract = {The aim of our study was to investigate the impact of insulin resistance on the bone density of the upper wall of the maxillary sinus. Materials and Methods: The study included 100 female participants aged 18 to 44 years, divided into two groups. The first group consisted of individuals with insulin resistance, while the control group comprised individuals without signs of insulin resistance. In each group, we conducted an investigation of the radiological density of the upper wall of the maxillary sinus using uncertainty calculations. Results of the study suggest a potential influence of insulin resistance on the density of bone tissue around the nasal sinuses, specifically the upper wall of the maxillary sinus in our case. This parameter was found to be minimal in the group of individuals with insulin resistance. It is particularly noteworthy that both minimum and maximum bone density decreased in this group. Conclusions. The research focused on how insulin resistance affects the density of the upper wall of the maxillary sinus. By employing uncertainty calculations, the study revealed that insulin resistance is associated with a decrease in the minimum density of the upper wall of the maxillary sinus. This tendency may act as a catalyst for the emergence of significant inflammatory alterations in the nasal sinuses, serving as a foundation for the initiation of complications.}, language = {en} } @article{RadivoievychSchnepelPrylutskaetal.2024, author = {Radivoievych, Aleksandar and Schnepel, Sophia and Prylutska, Svitlana and Ritter, Uwe and Zolk, Oliver and Frohme, Marcus and Grebinyk, Anna}, title = {From 2D to 3D In Vitro World: Sonodynamically-Induced Prooxidant Proapoptotic Effects of C60-Berberine Nanocomplex on Cancer Cells}, series = {Cancers}, volume = {16}, journal = {Cancers}, number = {18}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-19438}, year = {2024}, abstract = {Recently, sonodynamic therapy (SDT) has emerged as a promising non-invasive approach for treating cancer by activating sensitizers with ultrasound (US). In this context, we investigated C60 fullerene (C60) as a nanocarrier for the promising drug Berberine (Ber)—both potential aromatic sonosensitizers. The preferential mitochondrial accumulation of C60 and the proapoptotic effects of Ber also make the C60-Berberine nanocomplex (C60-Ber) a good candidate for direct induction of the intrinsic apoptotic cell death under US action. The in vitro research on C60-Ber can provide insights into novel, non-invasive cancer treatments. These findings lead to the development of targeted therapies with reduced side effects, inspire interdisciplinary collaboration, and open new avenues for drug delivery and cancer therapy research.}, language = {en} } @article{NechyporenkoFrohmeStrelchuketal.2024, author = {Nechyporenko, Alina and Frohme, Marcus and Strelchuk, Yaroslav and Omelchenko, Vladyslav and Gargin, Vitaliy and Ishchenko, Liudmyla and Alekseeva, Victoriia}, title = {Galvanic Skin Response and Photoplethysmography for Stress Recognition Using Machine Learning and Wearable Sensors}, series = {Applied Sciences}, volume = {14}, journal = {Applied Sciences}, number = {24}, publisher = {MDPI}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-19803}, year = {2024}, abstract = {This study investigates stress recognition using galvanic skin response (GSR) and photoplethysmography (PPG) data and machine learning, with a new focus on air raid sirens as a stressor. It bridges laboratory and real-world conditions and highlights the reliability of wearable sensors in dynamic, high-stress environments such as war and conflict zones. The study involves 37 participants (20 men, 17 women), aged 20-30, who had not previously heard an air raid siren. A 70 dB "S-40 electric siren" (400-450 Hz) was delivered via headphones. The protocol included a 5 min resting period, followed by 3 min "no-stress" phase, followed by 3 min "stress" phase, and finally a 3 min recovery phase. GSR and PPG signals were recorded using Shimmer 3 GSR+ sensors on the fingers and earlobes. A single session was conducted to avoid sensitization. The workflow includes signal preprocessing to remove artifacts, feature extraction, feature selection, and application of different machine learning models to classify the "stress "and "no-stress" states. As a result, the best classification performance was shown by the k-Nearest Neighbors model, achieving 0.833 accuracy. This was achieved by using a particular combination of heart rate variability (HRV) and GSR features, which can be considered as new indicators of siren-induced stress.}, language = {en} } @article{HerkenhoffBroedelFrohme2024, author = {Herkenhoff, Marcos Edgar and Br{\"o}del, Oliver and Frohme, Marcus}, title = {Aroma component analysis by HS-SPME/GC-MS to characterize Lager, Ale, and sour beer styles}, series = {Food Research International}, volume = {194}, journal = {Food Research International}, publisher = {Elsevier}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-19830}, year = {2024}, abstract = {The world of beer is a rich tapestry woven with diverse styles, each with its unique character. Lager, known for its crispness, ferments at lower temperatures, while ale, at warmer ones, boasts a wide spectrum of aromas. Belgian beers dazzle with their complexity, from fruity Trappist ales to sour lambics. German wheat beers, like hefeweizens, charm with their effervescence and fruity undertones. India Pale Ales (IPAs) showcase a hoppy burst, while sour ales tantalize with their tanginess. Craftsmanship, history, and regional ingredients intertwine in this world of brewing, offering aficionados an array of delightful experiences. Research on craft beer aromas is limited, and molecular fingerprint could be crucial. To date, there have been no studies focused on characterizing compound profiles to differentiate beer styles. The Headspace Solid Phase Microextraction (HS-SPME) method provides a rapid and solvent-free approach to volatile compound. The present study aims to characterize the aroma profile of a wide range of beers by using HS-SPME/GC-MS technique combined with multivariate data processing. A total of 120 beer samples were collected and divided into five categories: Pilsen (n = 28); Lager (n = 23); Ale (n = 32); Sour (n = 24); and Belgian Ales (n = 13). Among the Pilsen beers, 18 unique compounds were found for beers with hop extract and hops, and 2 for beers with hop extract (Octyl acetate; and alpha-Terpineol). When comparing the remaining groups to each other, Belgian beers exhibited 5 unique compounds, and Lagers had one (nonanal). Sours and Ales did not have unique compounds but shared 2 distinct compounds with the Belgian group each. We concluded that Belgian beers are the most complex in terms of various aroma-related compounds, and that it is possible to distinguish beers that use pure hops from hop extract.}, language = {en} } @article{SuzukiHerkenhoffBroedeletal.2024, author = {Suzuki, Juliana Yumi and Herkenhoff, Marcos Edgar and Br{\"o}del, Oliver and Cucick, Ana Clara Candelaria and Frohme, Marcus and Saad, Susana Marta Isay}, title = {Exploring the potential of red pitaya pulp (Hylocererus sp.) as a plant-based matrix for probiotic delivery and effects on betacyanin content and flavoromics}, series = {Food Research International}, volume = {192}, journal = {Food Research International}, publisher = {Elsevier}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-19843}, year = {2024}, abstract = {This study evaluated the potential of red pitaya pulp fermented with Lacticaseibacillus paracasei subsp. paracasei F-19 (F-19) as a base for probiotic products. Physicochemical parameters, sugar, betacyanin, and phenolic contents, and antioxidant activity were analyzed over 28 days at 4 °C and compared to a non-fermented pulp, and to a pulp fermented with Bifidobacterium animalis subsp. lactis BB-12 (BB-12). Volatile compounds were identified using HS-SPME/GC-MS. Probiotic viability during storage and survival through in vitro-simulated gastrointestinal tract (GIT) stress were assessed. Red pitaya pulp, rich in moisture (85.83 g/100 g), carbohydrates (11.65 g/100 g), and fibers (2.49 g/100 g), supported fermentation by both strains. F-19 and BB-12 lowered pH, with F-19 showing stronger acidification, and maintained high viability (8.85-8.90 log CFU/mL). Fermentation altered sugar profiles and produced unique volatile compounds, enhancing aroma and sensory attributes. F-19 generated 2-phenylethanol, a unique flavor compound, absent in BB-12. Phenolic content initially increased but antioxidant activity decreased during storage. Betacyanin remained stable for up to 14 days. Red pitaya improved F-19 viability through the simulated GIT, while BB-12 populations significantly decreased (p < 0.05). These results suggest red pitaya pulp is a promising plant-based matrix for F-19, offering protection during digestion and highlighting its potential as a functional food with enhanced bioactive compound bioavailability and sensory attributes.}, language = {en} } @article{HerkenhoffBattistiniPraiaetal.2023, author = {Herkenhoff, Marcos Edgar and Battistini, Carolina and Praia, Ana Beatriz and Rossini, Bruno Cesar and dos Santos, Lucilene Delazari and Br{\"o}del, Oliver and Frohme, Marcus and Saad, Susana Marta Isay}, title = {The combination of omics strategies to evaluate starter and probiotic strains in the Catharina sour Brazilian-style beer}, series = {Food Research International}, volume = {167}, journal = {Food Research International}, publisher = {Elsevier}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-19858}, year = {2023}, abstract = {Catharina sour, the first internationally recognized Brazilian beer, is characterized by fermentation with lactic acid bacteria (LAB), which may have probiotic potential, and the addition of fruit juice. This study aimed to evaluate the use of the starter Streptococcus thermophilus TH-4 (TH-4) and the probiotics Lacticaseibacillus paracasei F19 and 431, associated with Saccharomyces cerevisiae US-05, in the absence (control)/presence of passion fruit or peach juices. Evaluation proceeded during fermentation and storage by enumeration using pour-plate and qPCR; gene expressions of hop resistance; proteome by Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS); and odor, flavor, and metabolome by Headspace Solid-Phase Microextraction (HS-SPME), coupled with the gas chromatography-mass spectrometry (GC-MS) analysis. We concluded that the strains studied are recommended for applications in sour beers, due to the presence of defense mechanisms like membrane adhesion and H+ pump. Furthermore, HS-SPME/GC-MS indicated that the strains may contribute to the beer flavor and odor.}, language = {en} } @article{FalckenhaynBoerjanRaddatzetal.2013, author = {Falckenhayn, Cassandra and Boerjan, Bart and Raddatz, G{\"u}nter and Frohme, Marcus and Schoofs, Liliane and Lyko, Frank}, title = {Characterization of genome methylation patterns in the desert locust Schistocerca gregaria}, series = {The Journal of Experimental Biology}, volume = {216}, journal = {The Journal of Experimental Biology}, issn = {0022-0949}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-6350}, pages = {1423 -- 1429}, year = {2013}, abstract = {DNA methylation is a widely conserved epigenetic modification. The analysis of genome-scale DNA methylation patterns in various organisms suggests that major features of animal methylomes are widely conserved. However, based on the variation of DNA methyltransferase genes in invertebrates, it has also been proposed that DNA methylation could provide a molecular mechanism for ecological adaptation. We have now analyzed the methylome of the desert locust, Schistocerca gregaria, which represents an organism with a high degree of phenotypic plasticity. Using genome-scale bisulfite sequencing, we show here that the S. gregaria methylome is characterized by CpG- and exon-specific methylation and thus shares two major features with other animal methylomes. In contrast to other invertebrates, however, overall methylation levels were substantially higher and a significant fraction of transposons was methylated. Additionally, genic sequences were densely methylated in a pronounced bimodal pattern, suggesting a role for DNA methylation in the regulation of locust gene expression. Our results thus uncover a unique pattern of genome methylation in locusts and provide an important foundation for investigating the role of DNA methylation in locust phase polyphenism.}, language = {en} } @inproceedings{NechyporenkoReshetnikFrohmeetal.2024, author = {Nechyporenko, Alina and Reshetnik, Viktor and Frohme, Marcus and Alekseeva, Victoriia and Lupyr, Andrii and Gargin, Vitaliy}, title = {Evaluation of Bone Radiodensity in Smokers}, series = {Proceedings of the 4th International Workshop of IT-professionals on Artificial Intelligence (ProfIT AI 2024) 2024, Cambridge, MA, USA, September 25-27, 2024}, booktitle = {Proceedings of the 4th International Workshop of IT-professionals on Artificial Intelligence (ProfIT AI 2024) 2024, Cambridge, MA, USA, September 25-27, 2024}, number = {3777}, editor = {Chumachenko, Dmytro and Golland, Polina and Yakovlev, Sergiy}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-19616}, pages = {238 -- 244}, year = {2024}, abstract = {One of the most prevalent harmful habits that affect people daily is smoking. The aim of our study was to investigate changes in the bone density of the human paranasal sinuses under the influence of smoking using uncertainty calculation. Material and Methods. The study involved 150 male and female individuals aged 20-40 years, which helps to exclude other factors that could influence the reduction in bone radiodensity (e.g., menopause in women, age-related changes, etc.). The participants were divided into three groups based on the duration of their smoking habits. Results. Smoking has almost no effect on the maximum bone density. All groups show nearly identical values. In the first group, consisting of individuals who smoked for up to 5 years, the maximum density is 75.22 ± 37.61 Hu. In the second group, those who smoked for up to 10 years have a density of 84.22 ± 42.11 Hu, while in the third control group, the density is 74.29 ± 37.15 Hu. On the other hand, smoking has a greater impact on the minimum radiological bone density of the upper wall of the maxillary sinus. The lowest values are found in the group of individuals who smoked for 10 or more years, with a minimum density of 23.86 ± 11.93 Hu. For those who smoked for up to 5 years, the radiological bone density was 52.65 ± 26.32 Hu. In the control group, the density values were slightly higher than those of individuals who smoked for up to 5 years, with the highest values being 58.12 ± 29.06 Hu. Conclusion. The study investigated changes in the bone density of the human paranasal sinuses under the influence of smoking, utilizing uncertainty calculation. It was found that the most sensitive indicator to nicotine exposure is the minimum radiological density, which can significantly increase the risk of developing complications. Specifically, the lowest radiological density was observed in the group of individuals who smoked for 10 years or more, with a value of 23.86 ± 11.93 Hu.}, language = {en} } @inproceedings{ReshetnikMuryzinaFrohmeetal.2024, author = {Reshetnik, Viktor and Muryzina, Irina and Frohme, Marcus and Alekseeva, Victoriia and Dzyza, Alla and Nechyporenko, Alina}, title = {Uncertainty Estimation Method for Determining Bone Density in Patients with Infiltrating Intraductal Carcinoma Undergoing Anti-Cancer Therapy}, series = {Proceedings of the 4th International Workshop of IT-professionals on Artificial Intelligence (ProfIT AI 2024) 2024, Cambridge, MA, USA, September 25-27, 2024}, booktitle = {Proceedings of the 4th International Workshop of IT-professionals on Artificial Intelligence (ProfIT AI 2024) 2024, Cambridge, MA, USA, September 25-27, 2024}, number = {3777}, editor = {Chumachenko, Dmytro and Golland, Polina and Yakovlev, Sergiy}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-19628}, pages = {222 -- 228}, year = {2024}, abstract = {Identification of a bone density is crucial in all branches of medicine. Assessing bone density is a labor-intensive process. Bone density is quite unstable and depends on many factors, both physiological (aging, hormonal balance) and pathological (medication use, various underlying conditions). The aim of our study is to determine bone density in patients with malignant breast tumors undergoing anti-cancer therapy. Material and Methods. The study included 50 women aged 60-70 years who were diagnosed with infiltrating intraductal carcinoma. According to established protocols, MSCT is recommended for this category of women at intervals of once every six months. The first MSCT scan was performed immediately after the diagnosis was made, before the start of treatment, and the second scan was conducted six months later. Results. The maximum radiological density was 75.8954±37.9477 Hu in the group of women who had been receiving treatment for six months, compared to 93.9388±46.9694 Hu in the group of patients who did not take the drug. Meanwhile, the minimum density showed a slight increase from 29.7295±14.8647 Hu to 38.6919±19.3460 Hu, which can be attributed to the compensatory mechanisms of the body. Conclusions. In the course of this study, bone density in patients with infiltrating intraductal carcinoma undergoing anti-cancer therapy was determined using uncertainty estimation. It was found that after six months, the first to respond to changes in density was the maximum bone density.}, language = {en} } @article{RadkeSandigLubitzetal.2017, author = {Radke, Lars and Sandig, Grit and Lubitz, Annika and Schließer, Ulrike and von Horsten, Hans Henning and Blanchard, V{\´e}ronique and Keil, Karolin and Sandig, Volker and Giese, Christoph and Hummel, Michael and Hinderlich, Stephan and Frohme, Marcus}, title = {In Vitro Evaluation of Glycoengineered RSV-F in the Human Artificial Lymph Node Reactor}, series = {Bioengineering}, volume = {4}, journal = {Bioengineering}, number = {3}, issn = {2306-5354}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-9831}, year = {2017}, abstract = {Subunit vaccines often require adjuvants to elicit sustained immune activity. Here, a method is described to evaluate the efficacy of single vaccine candidates in the preclinical stage based on cytokine and gene expression analysis. As a model, the recombinant human respiratory syncytial virus (RSV) fusion protein (RSV-F) was produced in CHO cells. For comparison, wild-type and glycoengineered, afucosylated RSV-F were established. Both glycoprotein vaccines were tested in a commercial Human Artificial Lymph Node in vitro model (HuALN®). The analysis of six key cytokines in cell culture supernatants showed well-balanced immune responses for the afucosylated RSV-F, while immune response of wild-type RSV-F was more Th1 accentuated. In particular, stronger and specific secretion of interleukin-4 after each round of re-stimulation underlined higher potency and efficacy of the afucosylated vaccine candidate. Comprehensive gene expression analysis by nCounter gene expression assay confirmed the stronger onset of the immunologic reaction in stimulation experiments with the afucosylated vaccine in comparison to wild-type RSV-F and particularly revealed prominent activation of Th17 related genes, innate immunity, and comprehensive activation of humoral immunity. We, therefore, show that our method is suited to distinguish the potency of two vaccine candidates with minor structural differences.}, language = {en} } @article{SandigvonHorstenRadkeetal.2017, author = {Sandig, Grit and von Horsten, Hans Henning and Radke, Lars and Blanchard, V{\´e}ronique and Frohme, Marcus and Giese, Christoph and Sandig, Volker and Hinderlich, Stephan}, title = {Engineering of CHO Cells for the Production of Recombinant Glycoprotein Vaccines with Xylosylated N-glycans}, series = {Bioengineering}, volume = {4}, journal = {Bioengineering}, number = {2}, issn = {2306-5354}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-9620}, year = {2017}, abstract = {Xylose is a general component of O-glycans in mammals. Core-xylosylation of N-glycans is only found in plants and helminth. Consequently, xylosylated N-glycans cause immunological response in humans. We have used the F-protein of the human respiratory syncytial virus (RSV), one of the main causes of respiratory tract infection in infants and elderly, as a model protein for vaccination. The RSV-F protein was expressed in CHO-DG44 cells, which were further modified by co-expression of β1,2-xylosyltransferase from Nicotiana tabacum. Xylosylation of RSV-F N-glycans was shown by monosaccharide analysis and MALDI-TOF mass spectrometry. In immunogenic studies with a human artificial lymph node model, the engineered RSV-F protein revealed improved vaccination efficacy.}, language = {en} } @misc{RadkeLubitzGieseetal.2012, author = {Radke, Lars and Lubitz, Annika and Giese, Christoph and Frohme, Marcus}, title = {Einfluss der Kryokonservierung auf die Immunantwort von Leukozyten}, series = {Wissenschaftliche Beitr{\"a}ge 2012}, volume = {16}, journal = {Wissenschaftliche Beitr{\"a}ge 2012}, issn = {0949-8214}, doi = {10.15771/0949-8214_2012_1_1}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus-1363}, pages = {9 -- 14}, year = {2012}, abstract = {Die Messung von Zytokinen in Stimulationsexperimenten zur Bestimmung von St{\"a}rke und Umfang einer Immunreaktion werden in der Praxis h{\"a}ufig an kryokonserviertem Zellmaterial durchgef{\"u}hrt. Bisherige Untersuchungen zum Einfluss der Kryokonservierung auf die Zytokinexpression sind widerspr{\"u}chlich. In den hier durchgef{\"u}hrten Experimenten wurden die Genexpression und/ oder Sekretion der Zytokine IL-2, IL-4, IL-5, IL-10, IL-12, IL-13, GM-CSF, IFN-γ und TNF-α in frisch isolierten und kryokonservierten Immunzellen aus Blut (PBMC) eines gesunden Spenders bestimmt. Diese wurden mit den Immunsystem-aktivierenden Stoffen OKT-3 und Concanavalin A (Con A) stimuliert und f{\"u}r 4 bzw. 24 h kultiviert. Ein Vergleich der frisch-isolierten und kryokonservierten PBMC in Stimulationsexperimenten zeigt, (1) dass die Messung der Genexpression genauere Einblicke zu Beginn der einsetzenden Immunreaktion verschafft, als die Messung der ausgesch{\"u}tteten Zytokine, (2) dass durch Einfrieren die Immunreaktion insbesondere zu diesem Zeitpunkt beeinflusst wird und (3) dass zu sp{\"a}teren Zeitpunkten die Konzentrationsbestimmung der Zytokine im Zellkultur{\"u}berstand das Mittel der Wahl ist.}, language = {de} } @misc{ReichFrohmeRantalaetal.2008, author = {Reich, Peggy and Frohme, Marcus and Rantala, Juha and Nees, Matthias}, title = {Implementation of a siRNA Screen for Prostate Tumour Cell Lines Using Living Cell Arrays}, series = {Wissenschaftliche Beitr{\"a}ge 2008}, volume = {13}, journal = {Wissenschaftliche Beitr{\"a}ge 2008}, issn = {0949-8214}, doi = {10.15771/0949-8214_2008_1_3}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus-635}, pages = {19 -- 24}, year = {2008}, abstract = {Prostate cancer is one of the most common causes of death in men. In this work a siRNA screen of around 1500 cancer-relevant genes was performed using 3 different cell lines (VCaP, LAPC-4, RWPE-1). A novel technique, the living cell array, was initiated in order to obtain information about the biology of Androgeninduced growth in prostate tumour cell lines. This technique is based on the principal of reverse transfection [1] and genes are knocked down by siRNAs. The cells on the living cell array were set under stress by reduction of the androgens in the media while the proliferation and apoptosis were quantified. The statistical analysis of the data implicates the success of the screen and shows that this method is suitable for large-scale experiments.}, language = {en} } @inproceedings{StrelchukNechyporenkoFrohmeetal.2024, author = {Strelchuk, Yaroslav and Nechyporenko, Alina and Frohme, Marcus and Gargin, Vitaliy and Lupyr, Andrii and Alekseeva, Victoriia}, title = {Detection of stress using photoplethysmography}, series = {Proceedings of the 7th International Conference on Informatics \& Data-Driven Medicine (IDDM 2024)}, volume = {3892}, booktitle = {Proceedings of the 7th International Conference on Informatics \& Data-Driven Medicine (IDDM 2024)}, editor = {Shakhovska, Nataliya and Jiao, Jianbo and Izonin, Ivan and Chretien, Stephane}, publisher = {RWTH Aachen}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-19896}, pages = {196 -- 202}, year = {2024}, abstract = {Stress is an important factor affecting human health, and its timely detection can significantly improve quality of life. This study addresses the current issue of identifying stress states using photoplethysmography signals obtained from the wearable Shimmer 3 sensor. The purpose of the study was to establish an effective approach for stress detection, specifically through the analysis of heart rate variability changes during different states: rest and stress. A distinctive feature of the research is the use of the air raid siren sound as a stress factor. The research methodology includes the collection and analysis of biosignals, allowing for the assessment of cardiovascular system functioning under the impact of stress factors. The results of the study demonstrated significant differences in heart rhythm indicators depending on the person's state, highlighting the potential of these metrics as a tool for health monitoring and stress detection. The paper proposes a new approach to using photoplethysmography for assessing stress responses, which may contribute to the development of personalized stress management methods.}, language = {en} } @inproceedings{NechyporenkoFrohmeOmelchenkoetal.2023, author = {Nechyporenko, Alina and Frohme, Marcus and Omelchenko, Vladyslav and Alekseeva, Victoriia and Lupyr, Andrii and Gargin, Vitaliy}, title = {Identification of Personality Based on the Sphenoid Sinus Structure Using Machine Learning}, series = {Proceedings of the 6th International Conference on Informatics \& Data-Driven Medicine, Bratislava, Slovakia, November 17-19, 2023}, volume = {3609}, booktitle = {Proceedings of the 6th International Conference on Informatics \& Data-Driven Medicine, Bratislava, Slovakia, November 17-19, 2023}, editor = {Shakhovska, Nataliya and Kov{\´a}c, Michal and Izonin, Ivan and Chr{\´e}tien, St{\´e}phane}, publisher = {CEUR-WS.org}, url = {http://nbn-resolving.de/urn:nbn:de:0074-3609-1}, pages = {167 -- 173}, year = {2023}, abstract = {The aim of our study is to develop a new, simple, and effective method for identification of personality based on the characteristics of the sphenoid sinus structure, using machine learning for subsequent implementation into routine medical practice in Ukraine. The study involved 200 multislice computed tomography (MSCT) scans of individuals of various genders and ages. During the study, we obtained results with an accuracy exceeding 70\%.}, language = {en} } @inproceedings{ChumachenkoNechyporenkoFrohme2022, author = {Chumachenko, Dmytro and Nechyporenko, Alina and Frohme, Marcus}, title = {Impact of Russian War on COVID-19 Dynamics in Germany: the Simulation Study by Statistical Machine Learning}, series = {Proceedings of the 5th International Conference on Informatics \& Data-Driven Medicine, Lyon, France, November 18 - 20, 2022}, volume = {3302}, booktitle = {Proceedings of the 5th International Conference on Informatics \& Data-Driven Medicine, Lyon, France, November 18 - 20, 2022}, editor = {Shakhovska, Nataliya and Chr{\´e}tien, St{\´e}phane and Izonin, Ivan and Campos, Jaime}, publisher = {RWTH Aachen}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-19074}, pages = {78 -- 85}, year = {2022}, abstract = {The new coronavirus COVID-19 has been spreading worldwide for almost three years. The global community has developed effective measures to contain and control the pandemic. However, new factors are emerging that are driving the dynamics of COVID-19. One of these factors was the escalation of Russia's war in Ukraine. This study aims to test the hypothesis of the influence of migration flows caused by the Russian war in Ukraine on the dynamics of the epidemic process in Germany. For this, a model of the COVID-19 epidemic process was built based on the polynomial regression method. The model's adequacy was tested 30 days before the start of the escalation of the Russian war in Ukraine. To assess the impact of the war on the dynamics of COVID-19, the model was used to calculate the forecast of cumulative new and fatal cases of COVID-19 in Germany in the first 30 days after the start of the escalation of the Russian war in Ukraine. Modeling showed that migration flows from Ukraine are not a critical factor in the growth of the dynamics of the incidence of COVID-19 in Germany, but they influenced the number of cases. The next stage of the study is the development of more complex models for a detailed analysis of population dynamics, identifying factors influencing the epidemic process in the context of the Russian war in Ukraine, and assessing their information content.}, language = {en} } @unpublished{HollmannKremerBaebleretal.2020, author = {Hollmann, Susanne and Kremer, Andreas and Baebler, Špela and Trefois, Christophe and Gruden, Kristina and Rudnicki, Witold R. and Tong, Weida and Gruca, Aleksandra and Bongcam-Rudloff, Erik and Evelo, Chris T. and Nechyporenko, Alina and Frohme, Marcus and Šafr{\´a}nek, David and Regierer, Babette and D'Elia, Domenica}, title = {The need for standardisation in life science research - an approach to excellence and trust. [version 1; peer review: 3 approved]}, series = {F1000Research}, volume = {9}, journal = {F1000Research}, issn = {2046-1402}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-13891}, year = {2020}, abstract = {Today, academic researchers benefit from the changes driven by digital technologies and the enormous growth of knowledge and data, on globalisation, enlargement of the scientific community, and the linkage between different scientific communities and the society. To fully benefit from this development, however, information needs to be shared openly and transparently. Digitalisation plays a major role here because it permeates all areas of business, science and society and is one of the key drivers for innovation and international cooperation. To address the resulting opportunities, the EU promotes the development and use of collaborative ways to produce and share knowledge and data as early as possible in the research process, but also to appropriately secure results with the European strategy for Open Science (OS). It is now widely recognised that making research results more accessible to all societal actors contributes to more effective and efficient science; it also serves as a boost for innovation in the public and private sectors. However for research data to be findable, accessible, interoperable and reusable the use of standards is essential. At the metadata level, considerable efforts in standardisation have already been made (e.g. Data Management Plan and FAIR Principle etc.), whereas in context with the raw data these fundamental efforts are still fragmented and in some cases completely missing. The CHARME consortium, funded by the European Cooperation in Science and Technology (COST) Agency, has identified needs and gaps in the field of standardisation in the life sciences and also discussed potential hurdles for implementation of standards in current practice. Here, the authors suggest four measures in response to current challenges to ensure a high quality of life science research data and their re-usability for research and innovation.}, language = {en} } @article{SukiasyanKeshishyanManukyanetal.2019, author = {Sukiasyan, Anna and Keshishyan, Ara and Manukyan, Dezdemonia and Melik-Andreasyan, Gayane and Atshemyan, Liana and Apresyan, Hripsime and Strelkova, Margarita V. and Frohme, Marcus and Cortes, Sofia and Kuhls, Katrin}, title = {Re-Emerging Foci of Visceral Leishmaniasis in Armenia - First Molecular Diagnosis of Clinical Samples}, series = {Parasitology}, journal = {Parasitology}, issn = {1469-8161}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-12018}, pages = {20}, year = {2019}, abstract = {Visceral leishmaniasis (VL) was firstly reported in Armenia in 1913. Following a considerable increase of the number of cases until the mid 1950s, the diseases disappeared after 1969 and re-emerged in 1999. Scientific literature about VL in Armenia is available only in Russian or Armenian. This paper presents a historical overview about leishmaniasis in Armenia based on this literature as well as an epidemiological update since the re-emergence of the disease. In 1999- 2016, 116 indigenous VL cases were recorded mainly in children in 8 of the 11 districts, however VL is underreported because of lack of trained medical personal and diagnostic facilities. The aim of this work was to apply for the first time molecular diagnosis of VL in Armenia. Out of 25 VL suspected patients, 22 were positive by microscopy and PCR. Genotyping using ITS1-PCR-RFLP and sequencing identified the causative agent of VL in Armenia as Leishmania infantum. The present work is an important step towards the inclusion of molecular techniques in the current diagnosis of VL in Armenia and the establishment of local molecular diagnostic facilities.}, language = {en} } @misc{MaliGrohmeWełniczetal.2008, author = {Mali, Brahim and Grohme, Markus and Wełnicz, Weronika and Dandekar, Thomas and Schn{\"o}lzer, Martina and Reuter, Dirk and Schill, Ralph O. and Frohme, Marcus}, title = {Genomic Analyses of Cryptobiotic Tardigrades}, series = {Wissenschaftliche Beitr{\"a}ge 2008}, volume = {13}, journal = {Wissenschaftliche Beitr{\"a}ge 2008}, issn = {0949-8214}, doi = {10.15771/0949-8214_2008_1_5}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus-672}, pages = {35 -- 39}, year = {2008}, abstract = {Genomics technologies, especially transcriptional profiling, allows comparisons of gene expression within and across different organisms. By the use of the model group Tardigrada, also known as water bear, we try to understand the phenomenon of cryptobiosis. The dry organisms can survive for years without water. When re-exposed to water, the animals rehydrate and come back to life. The expression of genes in response to dehydratation and rehydratation is being examined in our laboratory through the generation of expressed sequence tags (ESTs), representational difference analysis (RDA) and subsequent microarray analysis. Molecular dissection of this complex phenomenom, including gene regulation, will allow the development of techniques for preservation and stabilisation of biological materials in a dried state.}, language = {en} } @article{SchokraieHotzWagenblattWarnkenetal.2010, author = {Schokraie, Elham and Hotz-Wagenblatt, Agnes and Warnken, Uwe and Mali, Brahim and Frohme, Marcus and F{\"o}rster, Frank and Dandekar, Thomas and Hengherr, Steffen and Schill, Ralph O. and Schn{\"o}lzer, Martina}, title = {Proteomic Analysis of Tardigrades: Towards a Better Understanding of Molecular Mechanisms by Anhydrobiotic Organisms}, series = {PLoS ONE}, volume = {5}, journal = {PLoS ONE}, number = {3}, issn = {1932-6203}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-6214}, pages = {37}, year = {2010}, abstract = {Tardigrades are small, multicellular invertebrates which are able to survive times of unfavourable environmental conditions using their well-known capability to undergo cryptobiosis at any stage of their life cycle. Milnesium tardigradum has become a powerful model system for the analysis of cryptobiosis. While some genetic information is already available for Milnesium tardigradum the proteome is still to be discovered.}, language = {en} } @article{SchokraieWarnkenHotzWagenblattetal.2012, author = {Schokraie, Elham and Warnken, Uwe and Hotz-Wagenblatt, Agnes and Grohme, Markus and Hengherr, Steffen and F{\"o}rster, Frank and Schill, Ralph O. and Frohme, Marcus and Dandekar, Thomas and Schn{\"o}lzer, Martina}, title = {Comparative proteome analysis of Milnesium tardigradum in early embryonic state versus adults in active and anhydrobiotic state}, series = {PLoS ONE}, volume = {7}, journal = {PLoS ONE}, number = {9}, issn = {1932-6203}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-6392}, pages = {25}, year = {2012}, abstract = {Tardigrades have fascinated researchers for more than 300 years because of their extraordinary capability to undergo cryptobiosis and survive extreme environmental conditions. However, the survival mechanisms of tardigrades are still poorly understood mainly due to the absence of detailed knowledge about the proteome and genome of these organisms. Our study was intended to provide a basis for the functional characterization of expressed proteins in different states of tardigrades. High-throughput, high-accuracy proteomics in combination with a newly developed tardigrade specific protein database resulted in the identification of more than 3000 proteins in three different states: early embryonic state and adult animals in active and anhydrobiotic state. This comprehensive proteome resource includes protein families such as chaperones, antioxidants, ribosomal proteins, cytoskeletal proteins, transporters, protein channels, nutrient reservoirs, and developmental proteins. A comparative analysis of protein families in the different states was performed by calculating the exponentially modified protein abundance index which classifies proteins in major and minor components. This is the first step to analyzing the proteins involved in early embryonic development, and furthermore proteins which might play an important role in the transition into the anhydrobiotic state.}, language = {en} } @article{FoersterBeisserGrohmeetal.2012, author = {F{\"o}rster, Frank and Beisser, Daniela and Grohme, Markus and Liang, Chunguang and Mali, Brahim and Siegl, Alexander Matthias and Engelmann, Julia C. and Shkumatov, Alexander and Schokraie, Elham and M{\"u}ller, Tobias and Schn{\"o}lzer, Martina and Schill, Ralph O. and Frohme, Marcus and Dandekar, Thomas}, title = {Transcriptome Analysis in Tardigrade Species Reveals Specific Molecular Pathways for Stress Adaptations}, series = {Bioinformatics and Biology Insights}, volume = {2012}, journal = {Bioinformatics and Biology Insights}, number = {6}, issn = {1177-9322}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-6153}, pages = {69 -- 96}, year = {2012}, abstract = {Tardigrades have unique stress-adaptations that allow them to survive extremes of cold, heat, radiation and vacuum. To study this, encoded protein clusters and pathways from an ongoing transcriptome study on the tardigrade Milnesium tardigradum were analyzed using bioinformatics tools and compared to expressed sequence tags (ESTs) from Hypsibius dujardini, revealing major pathways involved in resistance against extreme environmental conditions. ESTs are available on the Tardigrade Workbench along with software and databank updates. Our analysis reveals that RNA stability motifs for M. tardigradum are different from typical motifs known from higher animals. M. tardigradum and H. dujardini protein clusters and conserved domains imply metabolic storage pathways for glycogen, glycolipids and specific secondary metabolism as well as stress response pathways (including heat shock proteins, bmh2, and specific repair pathways). Redox-, DNA-, stress- and protein protection pathways complement specific repair capabilities to achieve the strong robustness of M. tardigradum. These pathways are partly conserved in other animals and their manipulation could boost stress adaptation even in human cells. However, the unique combination of resistance and repair pathways make tardigrades and M. tardigradum in particular so highly stress resistant.}, language = {en} } @article{FoersterLiangShkumatovetal.2009, author = {F{\"o}rster, Frank and Liang, Chunguang and Shkumatov, Alexander and Beisser, Daniela and Engelmann, Julia C. and Schn{\"o}lzer, Martina and Frohme, Marcus and M{\"u}ller, Tobias and Schill, Ralph O. and Dandekar, Thomas}, title = {Tardigrade workbench: comparing stress-related proteins, sequence-similar and functional protein clusters as well as RNA elements in tardigrades}, series = {BMC Genomics}, volume = {10}, journal = {BMC Genomics}, number = {469}, issn = {1471-2164}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-6461}, pages = {10}, year = {2009}, abstract = {Background Tardigrades represent an animal phylum with extraordinary resistance to environmental stress. Results To gain insights into their stress-specific adaptation potential, major clusters of related and similar proteins are identified, as well as specific functional clusters delineated comparing all tardigrades and individual species (Milnesium tardigradum, Hypsibius dujardini, Echiniscus testudo, Tulinus stephaniae, Richtersius coronifer) and functional elements in tardigrade mRNAs are analysed. We find that 39.3\% of the total sequences clustered in 58 clusters of more than 20 proteins. Among these are ten tardigrade specific as well as a number of stress-specific protein clusters. Tardigrade-specific functional adaptations include strong protein, DNA- and redox protection, maintenance and protein recycling. Specific regulatory elements regulate tardigrade mRNA stability such as lox P DICE elements whereas 14 other RNA elements of higher eukaryotes are not found. Further features of tardigrade specific adaption are rapidly identified by sequence and/or pattern search on the web-tool tardigrade analyzer http://waterbear.bioapps.biozentrum.uni-wuerzburg.de. The work-bench offers nucleotide pattern analysis for promotor and regulatory element detection (tardigrade specific; nrdb) as well as rapid COG search for function assignments including species-specific repositories of all analysed data. Conclusion Different protein clusters and regulatory elements implicated in tardigrade stress adaptations are analysed including unpublished tardigrade sequences.}, language = {en} } @article{MaliGrohmeFoersteretal.2010, author = {Mali, Brahim and Grohme, Markus and F{\"o}rster, Frank and Dandekar, Thomas and Schn{\"o}lzer, Martina and Reuter, Dirk and Wełnicz, Weronika and Schill, Ralph O. and Frohme, Marcus}, title = {Transcriptome survey of the anhydrobiotic tardigrade Milnesium tardigradum in comparison with Hypsibius dujardini and Richtersius coronifer}, series = {BMC Genomics}, volume = {11}, journal = {BMC Genomics}, number = {168}, issn = {1471-2164}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-6207}, pages = {11}, year = {2010}, abstract = {The phenomenon of desiccation tolerance, also called anhydrobiosis, involves the ability of an organism to survive the loss of almost all cellular water without sustaining irreversible damage. Although there are several physiological, morphological and ecological studies on tardigrades, only limited DNA sequence information is available. Therefore, we explored the transcriptome in the active and anhydrobiotic state of the tardigrade Milnesium tardigradum which has extraordinary tolerance to desiccation and freezing. In this study, we present the first overview of the transcriptome of M. tardigradum and its response to desiccation and discuss potential parallels to stress responses in other organisms.}, language = {en} } @article{JanowskiGrossSauerGuerthetal.2016, author = {Janowski, Susann and Gross, Ina and Sauer-G{\"u}rth, Hedwig and Tietze, Dieter Thomas and Grohme, Markus and Frohme, Marcus and Becker, Peter and Wink, Michael}, title = {New Microsatellite Markers for the Common Tern (Sterna hirundo) Developed with 454 Shot-Gun Pyrosequencing}, series = {The Open Ornithology Journal}, volume = {9}, journal = {The Open Ornithology Journal}, issn = {1874-4532}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-6789}, pages = {50 -- 59}, year = {2016}, abstract = {Long term studies, focusing on population- and socio-biology research, require the unequivocal identification of individuals. DNA studies with Short Tandem Repeats (STR loci) became a widespread tool in population genetics. We used the next-generation sequencing (NGS) approach with 454 shot-gun pyrosequencing to identify 13 new polymorphic STR loci for the Common Tern, Sterna hirundo. To enlarge the marker set we added two more loci originally developed for Black-legged Kittiwake (Rissa tridactyla) and Red-billed Gull (Chroicocephalus scopulinus) and arranged these 15 loci into three multiplex PCR panels for high throughput genotyping. Loci characterization demonstrated that our marker set is of high quality. A PIC value of about 0.67 and a power of exclusion value of 0.99 were reached. Deviation from Hardy-Weinberg expectations of some loci and low frequencies for null alleles are interpreted as a result of inbreeding and founder effect in the investigated tern colony. We used a test data set of this well-studied breeding colony of Common Tern at Banter Lake, Wilhelmshaven, Germany, to perform a parentage test. Parent-chick relationships, known from the social pedigree of that colony, were compared with genetically calculated ones. In order to test our markers and the used parentage program COLONY, we conducted six competing data sets with varying completeness of included parental genotypes. By including fully sampled parent pairs of known family assignment, results were correct for nest mates, single parents and parent pairs. Our marker set provides a powerful tool to investigate life-time reproductive success and other issues of population and socio-biology for Common Terns, e.g. in the aforementioned colony monitored for decades.}, language = {en} } @article{WangGrohmeMalietal.2014, author = {Wang, Chong and Grohme, Markus and Mali, Brahim and Schill, Ralph O. and Frohme, Marcus}, title = {Towards Decrypting Cryptobiosis—Analyzing Anhydrobiosis in the Tardigrade Milnesium tardigradum Using Transcriptome Sequencing}, series = {PLoS ONE}, volume = {9}, journal = {PLoS ONE}, number = {3}, issn = {1932-6203}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-6029}, pages = {15}, year = {2014}, abstract = {Many tardigrade species are capable of anhydrobiosis; however, mechanisms underlying their extreme desiccation resistance remain elusive. This study attempts to quantify the anhydrobiotic transcriptome of the limno-terrestrial tardigrade Milnesium tardigradum.}, language = {en} } @article{GrohmeMaliWełniczetal.2013, author = {Grohme, Markus and Mali, Brahim and Wełnicz, Weronika and Michel, Stephanie and Schill, Ralph O. and Frohme, Marcus}, title = {The Aquaporin Channel Repertoire of the Tardigrade Milnesium tardigradum}, series = {Bioinformatics and Biology Insights}, volume = {2013}, journal = {Bioinformatics and Biology Insights}, number = {7}, issn = {1177-9322}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-6092}, pages = {153 -- 165}, year = {2013}, abstract = {Limno-terrestrial tardigrades are small invertebrates that are subjected to periodic drought of their micro-environment. They have evolved to cope with these unfavorable conditions by anhydrobiosis, an ametabolic state of low cellular water. During drying and rehydration, tardigrades go through drastic changes in cellular water content. By our transcriptome sequencing effort of the limno-terrestrial tardigrade Milnesium tardigradum and by a combination of cloning and targeted sequence assembly, we identified transcripts encoding eleven putative aquaporins. Analysis of these sequences proposed 2 classical aquaporins, 8 aquaglyceroporins and a single potentially intracellular unorthodox aquaporin. Using quantitative real-time PCR we analyzed aquaporin transcript expression in the anhydrobiotic context. We have identified additional unorthodox aquaporins in various insect genomes and have identified a novel common conserved structural feature in these proteins. Analysis of the genomic organization of insect aquaporin genes revealed several conserved gene clusters.}, language = {en} } @article{JanowskiGrohmeFrohmeetal.2014, author = {Janowski, Susann and Grohme, Markus and Frohme, Marcus and Wink, Michael}, title = {Development of New Microsatellite (STR) Markers for Montagu's Harrier (Circus pygargus) via 454 Shot-Gun Pyrosequencing}, series = {The Open Ornithology Journal}, volume = {7}, journal = {The Open Ornithology Journal}, issn = {1874-4532}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-5966}, pages = {11 -- 18}, year = {2014}, abstract = {During the last decades the ground-breeding Montagu's harrier ( Circus pygargus , Linnaeus, 1758) has changed its breeding habitats in Europe to agricultural areas in which many local populations would be close to extinction without a special nest protection regime. Although Montagu's harrier is a well-studied species in terms of ecology and breeding biology, its genetic structure and population genetics are almost unknown. As there is a lack of good genetic markers we developed a set of 19 microsatellite markers comprising 16 new STR markers which were identified by next-generation sequencing (NGS) using 454 shot-gun pyrosequencing of genomic DNA. The STR markers were arranged into three multiplex PCR sets for high throughput genotyping and characterised. The marker set provides a powerful tool for kinship analysis. The combined non-exclusion probability for parent pairs was 1.13* 10-11. Only three loci showed PIC values < 0.50. In total, 121 known family relationships were compared with genetically calculated ones to test the markers suitability for parentage analysis. In 97.5\% of all cases full-sibships were accurately determined and 97.6\% of all mothers were assigned correctly to their chicks. The present multiplex PCR panels can be used to investigate several hypotheses concerning breeding behaviour, kinship, exchange rates between populations and phylogeography.}, language = {en} } @misc{KeilRadkeTillichetal.2015, author = {Keil, Karolin and Radke, Lars and Tillich, Ulrich M. and Frohme, Marcus}, title = {Automatisierung des Bio-Plex Pro Analyseverfahrens}, series = {Wissenschaftliche Beitr{\"a}ge 2015}, volume = {19}, journal = {Wissenschaftliche Beitr{\"a}ge 2015}, issn = {0949-8214}, doi = {10.15771/0949-8214_2015_1_2}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-3524}, pages = {15 -- 19}, year = {2015}, abstract = {F{\"u}r den simultanen Nachweis mehrerer Analyten innerhalb einer Probe ist die Bead-basierte Multiplexanalytik ein h{\"a}ufig verwendetes Verfahren und wird beispielsweise zur Quantifizierung von Proteinen genutzt. Die aufwendige Durchf{\"u}hrung der Assays soll durch Automatisierung einerseits dem Anwender abgenommen werden, w{\"a}hrend andererseits die Genauigkeit und Reproduzierbarkeit der Analyse gesteigert wird. Die Automatisierung des Bio-Plex Pro™ Assays ist mit dem Pipettierroboter Tecan Freedom EVO 200 umgesetzt worden. Es ist ein Skript mit der Software Freedom EVOware® entwickelt worden, welches die Probenvorbereitung des Assays vollst{\"a}ndig {\"u}bernimmt. F{\"u}r einen Vergleich der manuellen und automatisierten Methode sind die humanen Zytokine IL-2, IL-4, IL-10, GM-CSF, IFN-γ und TNF-α in einer achtstufigen Standardverd{\"u}nnungsreihe und in unterschiedlich konzentrierten Proben gemessen worden. Die Berechnung der Streuungen (Standardabweichung und Variationskoeffizient) der einzelnen Standardverd{\"u}nnungsreihen sowie der Vergleich von gemessenen und erwarteten Konzentrationen der automatisierten und manuellen Methode zeigen, dass die Automatisierung neben der zeitlichen Optimierung auch die Genauigkeit und Reproduzierbarkeit der Analyse verbessert.}, language = {de} } @misc{MichelJorkRockmannetal.2013, author = {Michel, Stephanie and Jork, Nadine and Rockmann, Christian and Grohme, Markus and Franke, Philipp and Menzel, Detlef and Frohme, Marcus}, title = {Charakterisierung des mikrobiellen Symbioms von Blutegeln}, series = {Wissenschaftliche Beitr{\"a}ge 2013}, volume = {17}, journal = {Wissenschaftliche Beitr{\"a}ge 2013}, issn = {0949-8214}, doi = {10.15771/0949-8214_2013_1_1}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-3084}, pages = {8 -- 12}, year = {2013}, abstract = {Die medizinischen Blutegel, Hirudo medicinalis und Hirudo verbana, werden wegen ihrer kurativen Wirkung in der Humanmedizin angewandt. W{\"a}hrend des Blutsaugens injizieren sie {\"u}ber ihren Speichel eine Vielzahl bioaktiver, derzeit noch unbekannter Molek{\"u}le. Eine vollst{\"a}ndige Aufkl{\"a}rung aller Inhaltsstoffe mit Wirkmechanismen ist f{\"u}r die Entwicklung von neuen Pharmaka von großem Interesse. Vor diesem Hintergrund wurden verschiedene Organe beider Arten auf ihre Besiedlung durch symbiontische Bakterien untersucht. Dazu wurden die Bakterien zun{\"a}chst unter geeigneten Bedingungen kultiviert und mittels biochemischer Methoden charakterisiert. Die Identifizierung der Symbionten erfolgte durch Polymerasekettenreaktion (PCR) und Sequenzierung der 16S rDNA. Die biochemischen Tests ergaben, dass die kultivierbaren Bakterien Amylase positiv, Gram negativ und Ornithin Decarboxylase negativ sind. Mit Hilfe von datenbankgest{\"u}tzten Analysen der 16S rDNA-Sequenzen konnte Aeromonas veronii biovar sobria nachgewiesen werden. Hochdurchsatzsequenzierungen der gesamtgenomischen DNA des Bakteriums aus H. medicinalis zeigten deutliche Abweichungen zum Referenzgenom von Aeromonas veronii B565.}, language = {de} } @inproceedings{MessaoudiDasLangeetal.2014, author = {Messaoudi, Hamza and Das, Susanta Kumar and Lange, Janine and Heinrich, Friedhelm and Schrader, Sigurd and Frohme, Marcus and Grunwald, R{\"u}diger}, title = {Femtosecond laser induced nanostructuring for surface enhanced Raman spectroscopy}, publisher = {Society of Photo-Optical Instrumentation Engineers (SPIE)}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-15252}, pages = {61 -- 68}, year = {2014}, abstract = {The formation of periodical nanostructures with femtosecond laser pulses was used to create highly efficient substrates for surface-enhanced Raman spectroscopy (SERS). We report about the structuring of silver and copper substrates and their application to the SERS of DNA (herring sperm) and protein molecules (egg albumen). The maximum enhancement factors were found on Ag substrates processed with the second harmonic generation (SHG) of a 1-kHz Ti:sapphire laser and structure periods near the SHG wavelength. In the case of copper, however, the highest enhancement was obtained with long-period ripples induced with at fundamental wavelength. This is explained by an additional significant influence of nanoparticles on the surface. Nanostructured areas in the range of 1.25 mm2 were obtained in 10 s. The surfaces were characterized by scanning electron microscopy, Fast Fourier Transform and Raman spectroscopy. Moreover, the role of the chemical modification of the metal structures is addressed. Thin oxide layers resulting from working in atmosphere which improve the biocompatibility were indicated by vibration spectra. It is expected that the detailed study of the mechanisms of laser-induced nanostructure formation will stimulate further applications of functionalized surfaces like photocatalysis, selective chemistry and nano-biology.}, language = {en} } @misc{LangeMessaoudiDasetal.2014, author = {Lange, Janine and Messaoudi, Hamza and Das, Susanta Kumar and Grunwald, R{\"u}diger and Schrader, Sigurd and Frohme, Marcus and Heinrich, Friedhelm}, title = {Analyse komplexer biologischer Proben mittels oberfl{\"a}chenverst{\"a}rkter Ramanspektroskopie (SERS)}, series = {Wissenschaftliche Beitr{\"a}ge 2014}, volume = {18}, journal = {Wissenschaftliche Beitr{\"a}ge 2014}, issn = {0949-8214}, doi = {10.15771/0949-8214_2014_1_3}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-3300}, pages = {27 -- 32}, year = {2014}, abstract = {Diese Studie besch{\"a}ftigt sich mit dem Nachweis biologischer Proben mit Hilfe der Raman-Mikroskopie. Um ausreichende Signalintensit{\"a}ten auch bei niedrigen Konzentrationen zu erhalten, wurde insbesondere der Effekt der oberfl{\"a}chenverst{\"a}rkten Raman-Streuung (SERS) n{\"a}her untersucht. Als Proben dienten DNA aus Hering-Sperma und das Protein Albumin. Zur Verst{\"a}rkung des Raman-Spektrums wurden zwei unterschiedliche Methoden verwendet. Zum Einen wurden in einem chemischen Reduktionsprozess Nanosilberpartikel hergestellt und den biologischen Proben zugemischt. Zum Anderen wurden mit Hilfe laserangeregter periodischer Oberfl{\"a}chenstrukturierung (LIPSS) erzeugte nanostrukturierte Silberoberfl{\"a}chen als Substrate f{\"u}r die Proben verwendet. Diese Methode wurde bislang nicht f{\"u}r die SERS-Analyse biologischer Proben eingesetzt. Erste hier pr{\"a}sentierte Messungen zeigen, dass beide Verfahren signifikante SERS-Verst{\"a}rkungen liefern und potentiell leistungsstarke Methoden f{\"u}r die zerst{\"o}rungsfreie Analyse biologischer Proben darstellen.}, language = {de} } @misc{TillichGrueberFrohme2012, author = {Tillich, Ulrich M. and Gr{\"u}ber, Stefanie and Frohme, Marcus}, title = {Etablierung von Hochdurchsatz-Kultivierungs- und -Screeningmethoden f{\"u}r phototrophe Einzeller}, series = {Wissenschaftliche Beitr{\"a}ge 2012}, volume = {16}, journal = {Wissenschaftliche Beitr{\"a}ge 2012}, issn = {0949-8214}, doi = {10.15771/0949-8214_2012_1_4}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus-1335}, pages = {31 -- 36}, year = {2012}, abstract = {Mit Hochdurchsatz-Kultivierungs- und -Screeningmethoden k{\"o}nnen viele Proben parallel, miniaturisiert und kosteng{\"u}nstig bearbeitet werden. F{\"u}r phototrophe Organismen wie Mikroalgen und Cyanobakterien sind Hochdurchsatz-Kultivierungsverfahren jedoch bis heute kaum etabliert. Im Rahmen dieser Arbeit wurden diese Verfahren beispielhaft f{\"u}r das Cyanobakterium Synechocystis sp. PCC 6803 etabliert. Die ben{\"o}tigte technische Automatisierung wurde hierbei durch den Einsatz eines Tecan Genesis RSP 150 Pipettierroboters erreicht. Die Kultivierung erfolgte in Deepwell-Mikrotiterplatten innerhalb einer speziell angefertigten Kammer mit programmierbaren Sch{\"u}ttlern, einstellbarer Belichtung und CO2-Atmosph{\"a}re. Die in diesem System erreichten Wachstumsraten sind vergleichbar mit publizierten Kultivierungsmethoden. Das Hochdurchsatz-Screening wurde mit Hilfe eines in den Roboter integrierten Tecan Genios Plus Plattenreaders durchgef{\"u}hrt. Es wurden beispielhaft Methoden zur Bestimmung von optischer Dichte und Chlorophyllgehalt etabliert. Die hier vorgestellte Plattform kann vielseitig zur Analyse phototropher Organismen eingesetzt werden und ist durch entsprechende Assays leicht zur Messung anderer Parameter erweiterbar.}, language = {de} } @misc{RadkeLopezHemmerlingLubitzetal.2010, author = {Radke, Lars and L{\´o}pez-Hemmerling, Diana and Lubitz, Annika and Giese, Christoph and Wildenauer, Franz-Xaver and Frohme, Marcus}, title = {Etablierung verschiedener Bead-basierter Multiplexmethoden mit einem Suspensions Array-System f{\"u}r molekulardiagnostische Zwecke}, series = {Wissenschaftliche Beitr{\"a}ge 2009/2010}, volume = {14}, journal = {Wissenschaftliche Beitr{\"a}ge 2009/2010}, issn = {0949-8214}, doi = {10.15771/0949-8214_2010_1_1}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus-802}, pages = {6 -- 12}, year = {2010}, abstract = {Die simultane Bestimmung mehrerer Analyten und die Erstellung komplexer Parameterprofile erlangt immer gr{\"o}ßere Bedeutung in der heutigen Labordiagnostik. Die Bead-basierte Multiplexanalytik bietet hier eine flexible, schnelle und einfache Methode zur Erstellung individueller Analysen. Aufgrund der Vielzahl von Anwendungsm{\"o}glichkeiten, die diese moderne Nachweismethode im Bereich molekularbiologischer Fragestellungen bietet, ist die Etablierung der Beadbasierten Multiplexanalytik im Labor f{\"u}r Molekularbiologie und funktionelle Genomik der Technischen Hochschule Wildau von großem Nutzen. Zur Einarbeitung in das Testsystem wurden die Konzentrationen der Zytokine IL-2, IL-4, IFN-γ und TNF-α in Zellkultur{\"u}berst{\"a}nden mit kommerziellen Fertigsystemen gemessen und mit mRNA-Expressionsraten der gleichen Proben verglichen. Des Weiteren wurde ein Testsystem zum Nachweis von humanen Antik{\"o}rpern der Klassen IgG und IgM sowie deren antigen-spezifischer Anteil in Zellkultur{\"u}berst{\"a}nden entwickelt. Außerdem konnte durch die erfolgreiche Detektion von DNA-gekoppelten Beads mittels markierter Oligonukleotidsequenz die Kopplung und die Anwendbarkeit der Methode auf Bindungsexperimente mit Nukleotidsequenzen gezeigt werden.}, language = {de} } @misc{SinningKoehlerLitzkeetal.2014, author = {Sinning, Denise and K{\"o}hler, Kernt and Litzke, Lutz-Ferdinand and Sch{\"o}nian, Gabriele and Frohme, Marcus and Kuhls, Katrin}, title = {Leishmania siamensis als Erreger von autochthoner kutaner Leishmaniose bei Pferden in Deutschland - eine neue Infektionskrankheit in Mitteleuropa?}, series = {Wissenschaftliche Beitr{\"a}ge 2014}, volume = {18}, journal = {Wissenschaftliche Beitr{\"a}ge 2014}, issn = {0949-8214}, doi = {10.15771/0949-8214_2014_1_2}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-3295}, pages = {17 -- 25}, year = {2014}, abstract = {Aus mitteleurop{\"a}ischer Sicht ist die durch Parasiten verursachte und von Sandm{\"u}cken {\"u}bertragene Leishmaniose eine in L{\"a}ndern tropischer und subtropischer Regionen auftretende Infektionskrankheit. In zunehmendem Maße werden jedoch autochthone F{\"a}lle in Mitteleuropa, insbesondere in S{\"u}ddeutschland, verzeichnet. Dies ist vermutlich auf die globale Erw{\"a}rmung und die Ausdehnung des Verbreitungsgebietes der Sandm{\"u}cken nach Norden zur{\"u}ckzuf{\"u}hren. Die vorliegende Arbeit befasst sich mit der Identifizierung und phylogenetischen Charakterisierung der Erreger dieser F{\"a}lle. Dazu wurden verschiedene Marker im Leishmaniengenom sequenziert und mit bekannten Arten verglichen. Die untersuchte DNA stammte von autochthonen kutanen Leishmaniosen bei Pferden und einem Rind, die in den letzten zehn Jahren in Deutschland und der Schweiz auftraten. Aufgrund identischer Sequenzen konnten die Parasiten als L. siamensis identifiziert bzw. verifiziert werden, eine erst im Jahr 2008 neu beschriebene Art, die in Thailand humane viszerale Leishmaniose verursacht. Die phylogenetischen Analysen zeigten die {\"A}hnlichkeit von L. siamensis mit weiteren bisher nicht identifizierten St{\"a}mmen aus Martinique und Ghana, die kutane Leishmaniose bei Menschen verursachen. Um die Frage zu beantworten, ob sich die Leishmaniose zu einer in Mitteleuropa endemischen zoonotischen Krankheit entwickeln k{\"o}nnte, m{\"u}ssen weitere Studien {\"u}ber kompatible Vektoren, m{\"o}gliche Reservoire und zur Virulenz durchgef{\"u}hrt werden.}, language = {de} } @article{EndrullatGloeklerFrankeetal.2016, author = {Endrullat, Christoph and Gl{\"o}kler, J{\"o}rn and Franke, Philipp and Frohme, Marcus}, title = {Standardization and quality management in next-generation sequencing}, series = {Applied \& Translational Genomics}, volume = {10}, journal = {Applied \& Translational Genomics}, issn = {2212-0661}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-6637}, pages = {2 -- 9}, year = {2016}, abstract = {DNA sequencing continues to evolve quickly even after > 30 years. Many new platforms suddenly appeared and former established systems have vanished in almost the same manner. Since establishment of next-generation sequencing devices, this progress gains momentum due to the continually growing demand for higher throughput, lower costs and better quality of data. In consequence of this rapid development, standardized procedures and data formats as well as comprehensive quality management considerations are still scarce. Here, we listed and summarized current standardization efforts and quality management initiatives from companies, organizations and societies in form of published studies and ongoing projects. These comprise on the one hand quality documentation issues like technical notes, accreditation checklists and guidelines for validation of sequencing workflows. On the other hand, general standard proposals and quality metrics are developed and applied to the sequencing workflow steps with the main focus on upstream processes. Finally, certain standard developments for downstream pipeline data handling, processing and storage are discussed in brief. These standardization approaches represent a first basis for continuing work in order to prospectively implement next-generation sequencing in important areas such as clinical diagnostics, where reliable results and fast processing is crucial. Additionally, these efforts will exert a decisive influence on traceability and reproducibility of sequence data.}, language = {en} } @article{GrebinykPrylutskaGrynyuketal.2018, author = {Grebinyk, Anna and Prylutska, Svitlana and Grynyuk, I. and Kolp, Benjamin and Hurmach, V. and Sliva, T. and Amirkhanov, Volodymyr and Trush, V. and Matyshevska, Olga and Slobodyanik, M. and Prylutskyy, Yuriy and Frohme, Marcus and Ritter, Uwe}, title = {C60 Fullerene Effects on Diphenyl-N-(trichloroacetyl)-amidophosphate Interaction with DNA In Silico and Its Cytotoxic Activity Against Human Leukemic Cell Line In Vitro}, series = {Nanoscale Research Letters}, volume = {2018}, journal = {Nanoscale Research Letters}, issn = {1556-276X}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-10515}, pages = {1 -- 9}, year = {2018}, abstract = {New representative of carbacylamidophosphates - diphenyl-N-(trichloroacetyl)-amidophosphate (HL), which contains two phenoxy substituents near the phosphoryl group, was synthesized, identified by elemental analysis and IR and NMR spectroscopy, and tested as a cytotoxic agent itself and in combination with C60 fullerene. According to molecular simulation results, C60 fullerene and HL could interact with DNA and form a rigid complex stabilized by stacking interactions of HL phenyl groups with C60 fullerene and DNA G nucleotide, as well as by interactions of HL CCl3 group by ion-π bonds with C60 molecule and by electrostatic bonds with DNA G nucleotide. With the use of MTT test, the cytotoxic activity of HL against human leukemic CCRF-CM cells with IC50 value detected at 10 μM concentration at 72 h of cells treatment was shown. Under combined action of 16 μM C60 fullerene and HL, the value of IC50 was detected at lower 5 μM HL concentration and at earlier 48 h period of incubation, besides the cytotoxic effect of HL was observed at a low 2.5 μM concentration at which HL by itself had no influence on cell viability. Binding of C60 fullerene and HL with minor DNA groove with formation of a stable complex is assumed to be one of the possible reasons of their synergistic inhibition of CCRF-CЕM cells proliferation. Application of C60 fullerene in combination with 2.5 μM HL was shown to have no harmful effect on structural stability of blood erythrocytes membrane. Thus, combined action of C60 fullerene and HL in a low concentration potentiated HL cytotoxic effect against human leukemic cells and was not followed by hemolytic effect.}, language = {en} } @article{HollmannFrohmeEndrullatetal.2020, author = {Hollmann, Susanne and Frohme, Marcus and Endrullat, Christoph and Kremer, Andreas and D'Elia, Domenica and Regierer, Babette and Nechyporenko, Alina}, title = {Ten simple rules on how to write a standard operating procedure}, series = {PLoS Computational Biology}, volume = {16}, journal = {PLoS Computational Biology}, number = {9}, issn = {1553-7358}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-13598}, pages = {e1008095}, year = {2020}, abstract = {Research publications and data nowadays should be publicly available on the internet and, theoretically, usable for everyone to develop further research, products, or services. The long-term accessibility of research data is, therefore, fundamental in the economy of the research production process. However, the availability of data is not sufficient by itself, but also their quality must be verifiable. Measures to ensure reuse and reproducibility need to include the entire research life cycle, from the experimental design to the generation of data, quality control, statistical analysis, interpretation, and validation of the results. Hence, high-quality records, particularly for providing a string of documents for the verifiable origin of data, are essential elements that can act as a certificate for potential users (customers). These records also improve the traceability and transparency of data and processes, therefore, improving the reliability of results. Standards for data acquisition, analysis, and documentation have been fostered in the last decade driven by grassroot initiatives of researchers and organizations such as the Research Data Alliance (RDA). Nevertheless, what is still largely missing in the life science academic research are agreed procedures for complex routine research workflows. Here, well-crafted documentation like standard operating procedures (SOPs) offer clear direction and instructions specifically designed to avoid deviations as an absolute necessity for reproducibility. Therefore, this paper provides a standardized workflow that explains step by step how to write an SOP to be used as a starting point for appropriate research documentation.}, language = {en} } @article{PrylutskaGrynyukGrebinyketal.2017, author = {Prylutska, Svitlana and Grynyuk, I. and Grebinyk, Anna and Hurmach, V. and Shatrava, Iu. and Sliva, T. and Amirkhanov, Volodymyr and Prylutskyy, Yuriy and Matyshevska, Olga and Slobodyanik, M. and Frohme, Marcus and Ritter, Uwe}, title = {Cytotoxic Effects of Dimorfolido-N-Trichloroacetylphosphorylamide and Dimorfolido-N-Benzoylphosphorylamide in Combination with C60 Fullerene on Leukemic Cells and Docking Study of Their Interaction with DNA}, series = {Nanoscale Research Letters}, volume = {12}, journal = {Nanoscale Research Letters}, number = {124}, issn = {1556-276X}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-9273}, year = {2017}, abstract = {Dimorfolido-N-trichloroacetylphosphorylamide (HL1) and dimorfolido-N-benzoylphosphorylamide (HL2) as representatives of carbacylamidophosphates were synthesized and identified by the methods of IR, 1H, and 31P NMR spectroscopy. In vitro HL1 and HL2 at 1 mM concentration caused cell specific and time-dependent decrease of leukemic cell viability. Compounds caused the similar gradual decrease of Jurkat cells viability at 72 h (by 35\%). HL1 had earlier and more profound toxic effect as compared to HL2 regardless on leukemic cell line. Viability of Molt-16 and CCRF-CEM cells under the action of HL1 was decreased at 24 h (by 32 and 45\%, respectively) with no substantial further reducing up to 72 h. Toxic effect of HL2 was detected only at 72 h of incubation of Jurkat and Molt-16 cells (cell viability was decreased by 40 and 45\%, respectively). It was shown that C60 fullerene enhanced the toxic effect of HL2 on leukemic cells. Viability of Jurkat and CCRF-CEM cells at combined action of C60 fullerene and HL2 was decreased at 72 h (by 20 and 24\%, respectively) in comparison with the effect of HL2 taken separately. In silico study showed that HL1 and HL2 can interact with DNA and form complexes with DNA both separately and in combination with C60 fullerene. More stable complexes are formed when DNA interacts with HL1 or C60 + HL2 structure. Strong stacking interactions can be formed between HL2 and C60 fullerene. Differences in the types of identified bonds and ways of binding can determine distinction in cytotoxic effects of studied compounds.}, language = {en} } @article{AmroAlDwibeGashoutetal.2017, author = {Amro, Ahmad and Al-Dwibe, Hamida and Gashout, Aisha and Moskalenko, Olga and Galafin, Marlena and Hamarsheh, Omar and Frohme, Marcus and Jaeschke, Anja and Sch{\"o}nian, Gabriele and Kuhls, Katrin}, title = {Spatiotemporal and molecular epidemiology of cutaneous leishmaniasis in Libya}, series = {PLoS Neglected Tropical Diseases}, volume = {11}, journal = {PLoS Neglected Tropical Diseases}, number = {9}, issn = {1935-2735}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-10054}, year = {2017}, abstract = {Cutaneous leishmaniasis (CL) is a skin infection caused by a single-celled parasite that is transmitted by the bite of a phlebotomine sandfly. CL is the most common form of leishmaniasis characterized by localized lesions in the skin and mucous membranes. The disease is prevalent in all countries around the Mediterranean Basin. In this paper, we describe spatiotemporal and eco-epidemiological parameters of CL in Libya. Moreover, we explored current spatiotemporal distributions of CL cases and explored the future projection of the disease. Our study indicates the presence of higher risk of CL in the coastal regions of Libya. Future projection until 2060 showed a trend of increasing incidence of CL in the north-western part of Libya, a spread along the coastal region and a possible emergence of new endemics in the north-eastern districts of Libya. These scenarios should be considered by health authorities in order to develop appropriate intervention strategies and plan effective control programs.}, language = {en} } @article{KuhlsMoskalenkoSukiasyanetal.2021, author = {Kuhls, Katrin and Moskalenko, Olga and Sukiasyan, Anna and Manukyan, Dezdemonia and Melik-Andreasyan, Gayane and Atshemyan, Liana and Apresyan, Hripsime and Strelkova, Margarita V. and Jaeschke, Anja and Wieland, Ralf and Frohme, Marcus and Cortes, Sofia and Keshishyan, Ara}, title = {Microsatellite based molecular epidemiology of Leishmania infantum from re-emerging foci of visceral leishmaniasis in Armenia and pilot risk assessment by ecological niche modeling}, series = {PLoS Neglected Tropical Diseases}, volume = {15}, journal = {PLoS Neglected Tropical Diseases}, number = {4}, publisher = {Public Library of Science (PLoS)}, issn = {1935-2735}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-14004}, pages = {e0009288}, year = {2021}, abstract = {Leishmaniasis is a vector-borne disease caused by protozoan parasites of the genus Leishmania. In Armenia visceral leishmaniasis (VL) is re-emerging since 1999 after a long break of 30 years, with 167 cases recorded until 2019. Molecular diagnosis of VL was implemented only in 2016, and the causative agent was identified as L. infantum. In the present study we expanded the investigation of the causative agent to a characterization at strain level and the identification of its phylogenetic position among the L. infantum genotypes circulating worldwide. This is the first study addressing genetic diversity and population structure of L. infantum in Armenia and in Transcaucasia. Armenia is an extremely interesting region due to its bio-geographic specificities e.g. the high number of different climates in this small mountainous country and the observed high diversity of sand fly species, part of which occurring in very high altitudes. Ecological niche modeling based on registered VL cases and sand fly vectors collected in active VL foci revealed that the risk of further spread of VL is very high due to climate change. Studies of this region should be expanded to enable targeted control measures.}, language = {en} } @article{AmroMoskalenkoHamarshehetal.2022, author = {Amro, Ahmad and Moskalenko, Olga and Hamarsheh, Omar and Frohme, Marcus}, title = {Spatiotemporal analysis of cutaneous leishmaniasis in Palestine and foresight study by projections modelling until 2060 based on climate change prediction}, series = {PLoS ONE}, volume = {17}, journal = {PLoS ONE}, number = {6}, publisher = {Public Library of Science (PLoS)}, issn = {1932-6203}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-16166}, year = {2022}, abstract = {Background Cutaneous leishmaniasis (CL) is a vector-borne parasitic diseases of public health importance that is prevalent in the West Bank but not in the Gaza Strip. The disease caused by parasitic protozoans from the genus Leishmania and it is transmitted by infected phlebotomine sand flies. The aim of our study is to investigate the eco-epidemiological parameters and spatiotemporal projections of CL in Palestine over a 30-years period from 1990 through 2020 and to explore future projections until 2060. Methodology/Principal findings This long-term descriptive epidemiological study includes investigation of demographic characteristics of reported patients by the Palestinian Ministry of Health (PMoH). Moreover, we explored spatiotemporal distribution of CL including future projection based on climate change scenarios. The number of CL patients reported during this period was 5855 cases, and the average annual incidence rate (AAIR) was 18.5 cases/105 population. The male to female ratio was 1.25:1. Patients-age ranged from 2 months to 89 years (mean = 22.5, std 18.67, and the median was 18 years). More than 65\% of the cases came from three governates in the West Bank; Jenin 29\% (1617 cases), Jericho 25\% (1403), and Tubas 12\% (658) with no cases reported in the Gaza Strip. Seasonal occurrence of CL starts to increase in December and peaked during March and April of the following year. Current distribution of CL indicate that Jericho, Tubas, Jenin and Nablus have the most suitable climatic settings for the sandfly vectors. Future projections until 2060 suggest an increasing incidence from northwest of Jenin down to the southwest of Ramallah, disappearance of the foci in Jericho and Tubas throughout the Jordan Vally, and possible emergence of new foci in Gaza Strip. Conclusions/Significance The future projection of CL in Palestine until 2060 show a tendency of increasing incidence in the north western parts of the West Bank, disappearance from Jericho and Tubas throughout the Jordan Vally, and emergence of new CL endemic foci in the Gaza Strip. These results should be considered to implement effective control and surveillance systems to counteract spatial expansion of CL vectors.}, language = {en} } @article{KagelBierFrohmeetal.2019, author = {Kagel, Heike and Bier, Frank Fabian and Frohme, Marcus and Gl{\"o}kler, J{\"o}rn}, title = {A Novel Optical Method To Reversibly Control Enzymatic Activity Based On Photoacids}, series = {Scientific Reports}, volume = {9}, journal = {Scientific Reports}, issn = {2045-2322}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-12685}, year = {2019}, abstract = {Most biochemical reactions depend on the pH value of the aqueous environment and some are strongly favoured to occur in an acidic environment. A non-invasive control of pH to tightly regulate such reactions with defined start and end points is a highly desirable feature in certain applications, but has proven difficult to achieve so far. We report a novel optical approach to reversibly control a typical biochemical reaction by changing the pH and using acid phosphatase as a model enzyme. The reversible photoacid G-acid functions as a proton donor, changing the pH rapidly and reversibly by using high power UV LEDs as an illumination source in our experimental setup. The reaction can be tightly controlled by simply switching the light on and off and should be applicable to a wide range of other enzymatic reactions, thus enabling miniaturization and parallelization through non-invasive optical means.}, language = {en} } @article{KagelJacobsBieretal.2019, author = {Kagel, Heike and Jacobs, Hannes and Bier, Frank Fabian and Gl{\"o}kler, J{\"o}rn and Frohme, Marcus}, title = {A Novel Microtiter Plate Format High Power Open Source LED Array}, series = {Photonics}, volume = {6}, journal = {Photonics}, number = {1}, issn = {2304-6732}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-11307}, year = {2019}, abstract = {Many photochemical or photobiological applications require the use of high power ultraviolet light sources, such as high-pressure mercury arc lamps. In addition, many photo-induced chemical, biochemical and biological applications require either a combinatorial setting or a parallel assay of multiple samples under the same environmental conditions to ensure reproducibility. To achieve this, alternative, controllable light sources, such as ultraviolet light emitting diodes (UV LEDs) with high power and spatial control are required. Preferably, LEDs are arranged in a suitable standardized 96-well microtiter plate format. We designed such an array and established the methods required for heat management and enabling stable, controllable illumination over time.}, language = {en} } @inproceedings{HollmannRegiererD'Eliaetal.2018, author = {Hollmann, Susanne and Regierer, Babette and D'Elia, Domenica and Frohme, Marcus and Gruden, Kristina and Pfeil, Juliane and Baebler, Spela and Sezerman, Ugur and Evelo, Chris T. and Erhart, Friederike and Huppertz, Berthold and Bongcam-Rudloff, Erik and Trefois, Christophe and Gruca, Aleksandra and Duca, Deborah and Colotti, Gianni and Merino-Martinez, Roxana and Ouzounis, Christos and Hunewald, Oliver and He, Feng and Kremer, Andreas}, title = {Standardisation in life-science research - Making the case for harmonization to improve communication and sharing of data amongst researchers}, editor = {Kalajdziski, Slobodan and Ackovska, Nevena}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-20118}, pages = {11}, year = {2018}, abstract = {Modern, high-throughput methods for the analysis of genetic information, gene and metabolic products and their interactions offer new opportunities to gain comprehensive information on life processes. The data and knowledge generated open diverse application possibilities with enormous innovation potential. To unlock that potential skills in generating but also properly annotating the data for further data integration and analysis are needed. The data need to be made computer readable and interoperable to allow integration with existing knowledge leading to actionable biological insights. To achieve this, we need common standards and standard operating procedures as well as workflows that allow the combination of data across standards. Currently, there is a lack of experts who understand the principles and possess knowledge of the principles and relevant tools. This is a major barrier hindering the implementation of FAIR (findable, accessible, interoperable and reusable) data principles and the actual reusability of data. This is mainly due to insufficient and unequal education of the scientists and other stakeholders involved in producing and handling big data in life science that is inherently varied and complex in nature, and large in volume. Due to the interdisciplinary nature of life science research, education within this field faces numerous hurdles including institutional barriers, lack of local availability of all required expertise, as well as lack of appropriate teaching material and appropriate adaptation of curricula.}, language = {en} } @misc{WeinertWohlfahrtSchmidetal.2010, author = {Weinert, Stefan and Wohlfahrt, Ingolf and Schmid, Andrea and Frohme, Marcus}, title = {Einf{\"u}hrung eines Qualit{\"a}tsmanagement-Systems in einem molekularbiologischen Labor einer Hochschule}, series = {Wissenschaftliche Beitr{\"a}ge 2009/2010}, volume = {14}, journal = {Wissenschaftliche Beitr{\"a}ge 2009/2010}, issn = {0949-8214}, doi = {10.15771/0949-8214_2010_1_6}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus-859}, pages = {49 -- 56}, year = {2010}, abstract = {Zertifizierte Qualit{\"a}tsmanagementsysteme (QM-Systeme) sind in akademischen Forschungslaboren bisher kaum vertreten. Hier ist vor allem die Bedeutung eines zertifizierten Labors vor dem Hintergrund der Ver{\"o}ffentlichung wissenschaftlicher Publikationen scheinbar bedeutungslos. Im industriellen Bereich hingegen sind QM-Systeme weitaus h{\"a}ufiger eingef{\"u}hrt. Labore im akademischen Bereich stehen jedoch grunds{\"a}tzlich in der Verantwortung, schonend mit den Ressourcen des Staates umzugehen, und haben dar{\"u}ber hinaus das Bestreben, Forschungs-/Industrieauftr{\"a}ge einzuwerben. Mit dieser Publikation wird gezeigt, wie durch die Einrichtung eines QM-Systems und der Einhaltung der normativen Vorgabe ein verbesserter schonender Umgang mit staatlichen Ressourcen m{\"o}glich ist, die Ergebnissicherheit erh{\"o}ht, Betriebsabl{\"a}ufe optimiert, die Chancen f{\"u}r Studenten auf dem Arbeitsmarkt verbessert werden und mehr Forschungs-/Industrieauftr{\"a}ge akquiriert werden k{\"o}nnen. Es wird dargestellt, wie ein QM-System in einem Labor eingerichtet werden kann. Dabei wird erl{\"a}utert, welche QM-Regelwerke f{\"u}r ein Labor im Hochschulbereich in Betracht kommen. Zudem wird eine Methodik in Form eines Projektplans vorgestellt, mit dem die Anforderungen der Norm strukturiert umgesetzt werden k{\"o}nnen. Das QM-System wurde im Labor f{\"u}r Molekularbiologie und Funktionelle Genomik an der Technischen Hochschule Wildau [FH] eingef{\"u}hrt und im Rahmen der Zertifizierung der Hochschule in das Audit einbezogen.}, language = {de} } @article{FischbachLohBieretal.2017, author = {Fischbach, Jens and Loh, Qiuting and Bier, Frank Fabian and Lim, Theam Soon and Frohme, Marcus and Gl{\"o}kler, J{\"o}rn}, title = {Alizarin Red S for Online Pyrophosphate Detection Identified by a Rapid Screening Method}, series = {Scientific Reports}, volume = {7}, journal = {Scientific Reports}, issn = {2045-2322}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-9248}, year = {2017}, abstract = {We identified Alizarin Red S and other well known fluorescent dyes useful for the online detection of pyrophosphate in enzymatic assays, including the loop mediated isothermal amplification (LAMP) and polymerase chain reaction (PCR) assays. An iterative screening was used for a selected set of compounds to first secure enzyme compatibility, evaluate inorganic pyrophosphate sensitivity in the presence of manganese as quencher and optimize conditions for an online detection. Of the selected dyes, the inexpensive alizarin red S was found to selectively detect pyrophosphate under LAMP and PCR conditions and is superior with respect to its defined red-shifted spectrum, long shelf life and low toxicity. In addition, the newly identified properties may also be useful in other enzymatic assays which do not generate nucleic acids but are based on inorganic pyrophosphate. Finally, we propose that our screening method may provide a blueprint for rapid screening of compounds for detecting inorganic pyrophosphate.}, language = {en} } @article{GrebinykYashchukBashmakovaetal.2019, author = {Grebinyk, Anna and Yashchuk, Valeriy and Bashmakova, Nataliya and Gryn, Dmytro and Hagemann, Tobias and Naumenko, Antonina and Kutsevol, Nataliya and Dandekar, Thomas and Frohme, Marcus}, title = {A New Triple System DNA-Nanosilver-Berberine for Cancer Therapy}, series = {Applied Nanoscience}, journal = {Applied Nanoscience}, issn = {2190-5517}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-10628}, year = {2019}, abstract = {The isoquinoline quaternary alkaloid Berberine possesses a variety of pharmacological properties that suggests its promising application for an anticancer delivery system design utilizing its ability to intercalate DNA.In the current work we have investigated the effects of Berberine on the human T-cell leukemia cell line in vitro.Fluorescent microscopy of leukemic cells revealed Berberine nuclear localization. The results showed that Berberine inhibited leukemic cell growth in a time-and dose-dependent manner, that was associated with reactive oxygen species production intensification and caspase 3/7 activity increase with followed apoptosis induction.Berberine was used as a toxic and phototoxic agent for triple system synthesis along with DNA as a carrier and nanosilver as a plasmonic accelerator of Berberine electronic transitions and high energy emission absorbent centers.The proposed method allows to obtain the complex of DNA with Berberine molecules and silver nanopoarticles. The optical properties of free components as well as their various combinations, including the final triple system DNA-Nanosilver-Berberine, were investigated. Obtained results support the possibility to use the triple system DNA-Nanosilver-Berberine as an alternative therapeutic agent for cancer treatment.}, language = {en} } @article{HerkenhoffBroedelFrohme2024, author = {Herkenhoff, Marcos Edgar and Br{\"o}del, Oliver and Frohme, Marcus}, title = {Hops across Continents: Exploring How Terroir Transforms the Aromatic Profiles of Five Hop (Humulus lupulus) Varieties Grown in Their Countries of Origin and in Brazil}, series = {Plants}, volume = {13}, journal = {Plants}, number = {19}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-19470}, year = {2024}, abstract = {Humulus lupulus, or hops, is a vital ingredient in brewing, contributing bitterness, flavor, and aroma. The female plants produce strobiles rich in essential oils and acids, along with bioactive compounds like polyphenols, humulene, and myrcene, which offer health benefits. This study examined the aromatic profiles of five hop varieties grown in Brazil versus their countries of origin. Fifty grams of pelletized hops from each strain were collected and analyzed using HS-SPME/GC-MS to identify volatile compounds, followed by statistical analysis with PLS-DA and ANOVA. The study identified 330 volatile compounds and found significant aromatic differences among hops from different regions. For instance, H. Mittelfr{\"u}her grown in Brazil has a fruity and herbaceous profile, while the German-grown variety is more herbal and spicy. Similar variations were noted in the Magnum, Nugget, Saaz, and Sorachi Ace varieties. The findings underscore the impact of terroir on hop aromatic profiles, with Brazilian-grown hops displaying distinct profiles compared to their counterparts from their countries of origin, including variations in aromatic notes and α-acid content.}, language = {en} } @article{HerkenhoffBroedelDilarrietal.2026, author = {Herkenhoff, Marcos Edgar and Br{\"o}del, Oliver and Dilarri, Guilherme and Bajay, Miklos Maximiliano and Frohme, Marcus and Costamilan, Carlos Andr{\´e} da Veiga Lima Rosa}, title = {Characterization of Volatile Compounds in Amarillo, Ariana, Cascade, Centennial, and El Dorado Hops Using HS-SPME/GC-MS}, series = {Compounds}, volume = {6}, journal = {Compounds}, number = {1}, publisher = {MDPI}, issn = {2673-6918}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-21029}, year = {2026}, abstract = {Humulus lupulus L. (hops) is essential in brewing due to its contributions to bitterness, flavor, and aroma. This study compared the volatile profiles of five commercially important hop varieties—Amarillo, Ariana, Cascade, Centennial, and El Dorado—grown in their main regions of origin (United States for Amarillo, Cascade, and El Dorado; Germany for Ariana; and Brazil for Centennial). Headspace solid-phase microextraction coupled with gas chromatography-mass spectrometry (HS-SPME/GC-MS) enabled the identification of 312 volatile compounds, including monoterpenes (e.g., myrcene, linalool, geraniol), sesquiterpenes (e.g., humulene, caryophyllene), esters, alcohols, aldehydes, and ketones. Amarillo showed the highest myrcene content (22.61\% of the total volatile area), while Centennial was distinguished by elevated γ-muurolene (20.59\%), and El Dorado by the highest level of undecan-2-one (10.47\%), highlighting marked varietal differences in key aroma-active constituents. Multivariate, including principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA), clearly discriminated the five varieties: PC1 (41.04\% of the variance) separated samples enriched in fruity/floral monoterpenes and esters from those dominated by woody/resinous sesquiterpenes, whereas PC2 (25.93\% of the variance) reflected variation in medium-chain esters, ketones, and waxy compounds. These chemometric patterns demonstrate that both genetic background and growing region terroir strongly shape hop volatile composition and, consequently, aroma potential, providing brewers with objective criteria for selecting hop varieties to achieve specific sensory profiles in beer.}, language = {en} } @article{LiAmirkhanyanGrebinyketal.2025, author = {Li, Xiangkun and Amirkhanyan, Zohrab and Grebinyk, Anna and Gross, Matthias and Komar, Yuliia and Riemer, Felix and Asoyan, Aida and Boonpornprasert, Prach and Borchert, Paul and Davtyan, Hakob and Dmytriiev, Dmytro and Frohme, Marcus and Hoffmann, Andreas and Krasilnikov, Mikhail and Loisch, Gregor and Lotfi, Zahra and M{\"u}ller, Frieder and Schmitz, Michael and Obier, Frank and Oppelt, Anne and Philipp, Sebastian and Richard, Christopher and Vashchenko, Grygorii and Villani, Daniel and Worm, Steven and Stephan, Frank}, title = {Demonstration of ultra-high dose rate electron irradiation at FLASHlab@PITZ}, series = {Physics in Medicine \& Biology}, volume = {70}, journal = {Physics in Medicine \& Biology}, number = {5}, publisher = {Institute of Physics Publishing (IOP)}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-20092}, year = {2025}, abstract = {Objective. The photo injector test facility at DESY in Zeuthen (PITZ) is building up an R\&D platform, known as FLASHlab@PITZ, for systematically studying the FLASH effect in cancer treatment with its high-brightness electron beams, which can provide a uniquely large dose parameter range for radiation experiments. In this paper, we demonstrate the capabilities by experiments with a reduced parameter range on a startup beamline and study the potential performance of the full beamline by simulations. Approach. To measure the dose, Gafchromic films are installed both in front of and after the samples; Monte Carlo simulations are conducted to predict the dose distribution during beam preparation and help understand the dose distribution inside the sample. Plasmid DNA is irradiated under various doses at conventional and ultra-high dose rate (UHDR) to study the DNA damage by radiations. Start-to-end simulations are performed to verify the performance of the full beamline. Main results. On the startup beamline, reproducible irradiation has been established with optimized electron beams and the delivered dose distributions have been measured with Gafchromic films and compared to FLUKA simulations. The functionality of this setup has been further demonstrated in biochemical experiments at conventional dose rate of 0.05 Gy s-1 and UHDR of several 105 Gy s-1 and a varying dose up to 60 Gy, with the UHDR experiments finished within a single RF pulse (less than 1 millisecond); the observed conformation yields of the irradiated plasmid DNA revealed its dose-dependent radiation damage. The upgrade to the full FLASHlab@PITZ beamline is justified by simulations with homogeneous radiation fields generated by both pencil beam scanning and scattering beams. Significance. With the demonstration of UHDR irradiation and the simulated performance of the new beamline, FLASHlab@PITZ will serve as a powerful platform for studying the FLASH effects in cancer treatment.}, language = {en} } @inproceedings{LiAmirkhanyanAftabetal.2024, author = {Li, Xiangkun and Amirkhanyan, Zohrab and Aftab, Namra and Boonpornprasert, Prach and Dmytriiev, Dmytro and Frohme, Marcus and Georgiev, Georgi and Grebinyk, Anna and Gross, Matthias and Hoffmann, Andreas and Komar, Yuliia and Krasilnikov, Mikhail and Loisch, Gregor and Oppelt, Anne and Richard, Christopher and Riemer, F. and Philipp, Sebastian and Schmitz, Michael and M{\"u}ller, Frieder and Obier, Frank and Vashchenko, Grygorii and Worm, Steven and Stephan, Frank}, title = {Overview of FLASHlab@PITZ: the new R\&D platform for FLASH radiation therapy and radiation biology}, series = {Journal of Physics: Conference Series, Volume 2687, Applications of Accelerators, Technology Transfer and Industrial Relations and Outreach}, volume = {2687}, booktitle = {Journal of Physics: Conference Series, Volume 2687, Applications of Accelerators, Technology Transfer and Industrial Relations and Outreach}, publisher = {Institute of Physics Publishing (IOP)}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-18474}, year = {2024}, abstract = {An R\&D platform for electron FLASH radiation therapy and radiation biology is being prepared at the Photo Injector Test facility at DESY in Zeuthen (FLASHlab@PITZ). This platform is based on the unique beam parameters available at PITZ: ps scale electron bunches of up to 22 MeV with up to 5 nC bunch charge at MHz bunch repetition rate in bunch trains of up to 1 ms in length repeating at 1 to 10 Hz. It works together with the Technical University of Applied Sciences Wildau (TH Wildau) as partner in close vicinity for the biological resources. A startup beamline has been installed to allow dosimetry studies and irradiation experiments on chemical, biochemical and biological samples after a 60-degree dispersive arm. The measured dose and dose rates under different beam conditions and first experimental results will be reported in this paper. In addition, a dedicated beamline for FLASHlab@PITZhas been designed for better control of the high brightness electron beams. This includes a dogleg to translate the beam and a 2D kicker system to scan the tiny beam focused by quadrupoles across the samples within less than 1 ms. Simulation studies will be presented to demonstrate the extremely flexible dose parameters with various irradiation options for electron FLASH radiation therapy and radiation biology studies.}, language = {en} } @inproceedings{ChepurnaGrebinykPetrushkoetal.2019, author = {Chepurna, Oksana and Grebinyk, Anna and Petrushko, Yulia and Prylutska, Svitlana and Grebinyk, Sergii and Yashchuk, Valeriy and Matyshevska, Olga and Ritter, Uwe and Dandekar, Thomas and Frohme, Marcus and Qu, Junle and Ohulchanskyy, Tymish Y.}, title = {LED-based portable light source for photodynamic therapy}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-14778}, year = {2019}, abstract = {Photodynamic therapy (PDT) employs light activation of tissue-localized photosensitizer in an oxygen-dependent process which initiates oxidative stress, inflammation, and cell death. Laser systems, which are mostly used in PDT as light sources can be costly and oversized. light-emitting diodes (LEDs) equipment has a high potential to simplify technical part of phototriggered therapies and to reduce its costs. We develop the LED-based system that includes the control and irradiation units. The system provides the same power density at any irradiation point. Among the advantages of the device is a possibility to change the irradiation area and tune the irradiation dose. PDT experiments with cancer cells in vitro treated with two different photosensitizers demonstrated a possibility to use the developed LED-based system as a low-cost light source in PDT.}, language = {en} } @article{GrebinykPrylutskaBuchelnikovetal.2019, author = {Grebinyk, Anna and Prylutska, Svitlana and Buchelnikov, Anatoliy and Tverdokhleb, Nina and Grebinyk, Sergii and Evstigneev, Maxim and Matyshevska, Olga and Cherepanov, Vsevolod and Prylutskyy, Yuriy and Yashchuk, Valeriy and Naumovets, Anton and Ritter, Uwe and Dandekar, Thomas and Frohme, Marcus}, title = {C60 Fullerene as an Effective Nanoplatform of Alkaloid Berberine Delivery into Leukemic Cells}, series = {Pharmaceutics}, volume = {11}, journal = {Pharmaceutics}, number = {11}, publisher = {MDPI}, issn = {1999-4923}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-12932}, year = {2019}, abstract = {A herbal alkaloid Berberine (Ber), used for centuries in Ayurvedic, Chinese, Middle-Eastern, and native American folk medicines, is nowadays proved to function as a safe anticancer agent. Yet, its poor water solubility, stability, and bioavailability hinder clinical application. In this study, we have explored a nanosized carbon nanoparticle—C60 fullerene (C60)—for optimized Ber delivery into leukemic cells. Water dispersions of noncovalent C60-Ber nanocomplexes in the 1:2, 1:1, and 2:1 molar ratios were prepared. UV-Vis spectroscopy, dynamic light scattering (DLS), and atomic force microscopy (AFM) evidenced a complexation of the Ber cation with the negatively charged C60 molecule. The computer simulation showed that π-stacking dominates in Ber and C60 binding in an aqueous solution. Complexation with C60 was found to promote Ber intracellular uptake. By increasing C60 concentration, the C60-Ber nanocomplexes exhibited higher antiproliferative potential towards CCRF-CEM cells, in accordance with the following order: free Ber < 1:2 < 1:1 < 2:1 (the most toxic). The activation of caspase 3/7 and accumulation in the sub-G1 phase of CCRF-CEM cells treated with C60-Ber nanocomplexes evidenced apoptosis induction. Thus, this study indicates that the fast and easy noncovalent complexation of alkaloid Ber with C60 improved its in vitro efficiency against cancer cells.}, language = {en} } @article{GrebinykYashchukBashmakovaetal.2019, author = {Grebinyk, Anna and Yashchuk, Valeriy and Bashmakova, Nataliya and Gryn, Dmytro and Hagemann, Tobias and Naumenko, Antonina and Kutsevol, Nataliya and Dandekar, Thomas and Frohme, Marcus}, title = {A new triple system DNA-Nanosilver-Berberine for cancer therapy}, series = {Applied Nanoscience}, volume = {9}, journal = {Applied Nanoscience}, publisher = {Springer}, issn = {2190-5517}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-16105}, pages = {945 -- 956}, year = {2019}, abstract = {The isoquinoline quaternary alkaloid Berberine possesses a variety of pharmacological properties that suggests its promising application for an anticancer delivery system design utilizing its ability to intercalate DNA. In the current work, we have investigated the effects of Berberine on the human T cell leukemia cell line in vitro. Fluorescent microscopy of leukemic cells revealed Berberine nuclear localization. The results showed that Berberine inhibited leukemic cell growth in a time- and dose-dependent manner, that was associated with reactive oxygen species production intensification and caspase 3/7 activity increase with followed apoptosis induction. Berberine was used as a toxic and phototoxic agent for triple system synthesis along with DNA as a carrier and nanosilver as a plasmonic accelerator of Berberine electronic transitions and high energy emission absorbent centers. The proposed method allows to obtain the complex of DNA with Berberine molecules and silver nanoparticles. The optical properties of free components as well as their various combinations, including the final triple system DNA-Nanosilver-Berberine, were investigated. Obtained results support the possibility to use the triple system DNA-Nanosilver-Berberine as an alternative therapeutic agent for cancer treatment.}, language = {en} } @misc{GossingRadkeFrohmeetal.2016, author = {Gossing, Wilhelm and Radke, Lars and Frohme, Marcus and Biering, Henrik}, title = {ECS-Komplex - ein neuer Biomarker bei Wachstumshormonst{\"o}rungen?}, series = {Wissenschaftliche Beitr{\"a}ge 2016}, volume = {20}, journal = {Wissenschaftliche Beitr{\"a}ge 2016}, issn = {0949-8214}, doi = {10.15771/0949-8214_2016_1_3}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-5308}, pages = {23 -- 29}, year = {2016}, abstract = {St{\"o}rungen im Metabolismus des Wachstumshormons k{\"o}nnen sich als Wachstumshormonmangel oder -{\"u}berschuss (Akromegalie) {\"a}ußern. In beiden F{\"a}llen handelt es sich um seltene Krankheiten, die aufwendig behandelt werden m{\"u}ssen, da jeder Patient anders auf seine jeweilige Medikation anspricht. Zur Bestimmung des individuellen Ansprechverhaltens auf die medikament{\"o}se Behandlung wird Insulin-like Growth Factor 1 verwendet, das jedoch als unzuverl{\"a}ssig f{\"u}r die Therapiekontrolle gilt. Um die Diagnostik und Therapie von Wachstumshormonst{\"o}rungen zu verbessern, wurde in dieser Pilotstudie der Nutzen des neuen potenziellen Biomarkers Elongin B/C-Cullin5-Socs-box Komplex (ECS-Komplex) {\"u}berpr{\"u}ft. Die f{\"u}nf Proteine des Komplexes {\"u}ben zusammen einen negativen Feedback-Mechanismus auf den Wachstumshormonrezeptor aus und regulieren ihn in Abh{\"a}ngigkeit vom Wachstumshormonspiegel im Blut. F{\"u}r diese Pilotstudie wurden vier Patienten mit Wachstumshormondefizienz und 15 Patienten mit Akromegalie rekrutiert. Die Messung von Unterschieden in der Expression der Gene auf RNA-Ebene in Blutproben der Patienten erlaubt erste Aussagen {\"u}ber deren Eignung als therapeutische Marker f{\"u}r diese Krankheiten.}, language = {de} } @article{GossingFrohmeRadke2020, author = {Gossing, Wilhelm and Frohme, Marcus and Radke, Lars}, title = {Biomarkers for Liquid Biopsies of Pituitary Neuroendocrine Tumors}, series = {Biomedicines}, volume = {8}, journal = {Biomedicines}, number = {6}, issn = {2227-9059}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-13307}, year = {2020}, abstract = {Pituitary neuroendocrine tumors (PitNET) do not only belong to the most common intracranial neoplasms but seem to be generally more common than has been thought. Minimally invasive liquid biopsies have the potential to improve their early screening efficiency as well as monitor prognosis by facilitating the diagnostic procedures. This review aims to assess the potential of using liquid biopsies of different kinds of biomarker species that have only been obtained from solid pituitary tissues so far. Numerous molecules have been associated with the development of a PitNET, suggesting that it often develops from the cumulative effects of many smaller genetic or epigenetic changes. These minor changes eventually pile up to switch critical molecules into tumor-promoting states, which may be the key regulatory nodes representing the most potent marker substances for a diagnostic test. Drugs targeting these nodes may be superior for the therapeutic outcome and therefore the identification of such pituitary-specific cellular key nodes will help to accelerate their application in medicine. The ongoing genetic degeneration in pituitary adenomas suggests that repeated tumor profiling via liquid biopsies will be necessary for personalized and effective treatment solutions.}, language = {en} } @article{GossingRadkeBieringetal.2021, author = {Gossing, Wilhelm and Radke, Lars and Biering, Henrik and Diederich, Sven and Mai, Knut and Frohme, Marcus}, title = {The ElonginB/C-Cullin5-SOCS-Box-Complex Is a Potential Biomarker for Growth Hormone Disorders}, series = {Biomedicines}, volume = {9}, journal = {Biomedicines}, number = {2}, publisher = {MDPI}, issn = {2227-9059}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-13802}, year = {2021}, abstract = {Insulin-like growth factor 1 (IGF-1) is the standard biochemical marker for the diagnosis and treatment control of acromegaly and growth hormone deficiency (GHD). However, its limitations necessitate the screening for new specific and sensitive biomarkers. The elonginB/C-cullin5-SOCS-box-complex (ECS-complex) (an intracellular five-protein complex) is stimulated by circulating growth hormone (GH) and regulates GH receptor levels through a negative feedback loop. It mediates the cells' sensitivity for GH and therefore, represents a potent new biomarker for those diseases. In this study, individual ECS-complex proteins were measured in whole blood samples of patients with acromegaly (n = 32) or GHD (n = 12) via ELISA and compared to controls. Hierarchical clustering of the results revealed that by combining the three ECS-complex proteins suppressor of cytokine signaling 2 (SOCS2), cullin-5 and ring-box protein 2 (Rbx-2), 93\% of patient samples could be separated from controls, despite many patients having a normal IGF-1 or not receiving medical treatment. SOCS2 showed the best individual diagnostic performance with an overall accuracy of 0.93, while the combination of the three proteins correctly identified all patients and controls. This resulted in perfect sensitivity and specificity for all patient groups, which demonstrates potential benefits of the ECS-complex proteins as clinical biomarkers for the diagnostics of GH-related diseases and substantiates their important role in GH metabolism.}, language = {en} } @article{KagelFrohmeGloekler2019, author = {Kagel, Heike and Frohme, Marcus and Gl{\"o}kler, J{\"o}rn}, title = {Photoacids in biochemical applications}, series = {Journal of Cellular Biotechnology}, volume = {4}, journal = {Journal of Cellular Biotechnology}, number = {1-2}, publisher = {IOS Press}, issn = {2352-3697}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-16123}, pages = {23 -- 30}, year = {2019}, abstract = {BACKGROUND: After excitation with light photoacids can change the pH in a solution by release of a proton. They have been used mostly for excited state proton transfer studies. In this review the general functionality and mechanisms and the subdivision of photoacids is explained. STATE OF THE ART: Different uses of photoacids are described, covering a wide range of various biochemical topics, focusing on biochemical applications. Examples for the introduced subdivisions are covered. CONCLUSIONS AND OUTLOOK: The areas in which photoacids can be employed are diverse. Photoacids have a promising future in biotechnology and biochemistry and should be considered for upcoming applications, especially in non-invasive control of biochemical reactions.}, language = {en} } @article{SilbermannWernickePospisiletal.2013, author = {Silbermann, Jascha and Wernicke, Catrin and Pospisil, Heike and Frohme, Marcus}, title = {RefPrimeCouch—a reference gene primer CouchApp}, series = {Database: The Journal of Biological Databases and Curation}, volume = {2013}, journal = {Database: The Journal of Biological Databases and Curation}, issn = {1758-0463}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:526-opus4-6330}, pages = {8}, year = {2013}, abstract = {To support a quantitative real-time polymerase chain reaction standardization project, a new reference gene database application was required. The new database application was built with the explicit goal of simplifying not only the development process but also making the user interface more responsive and intuitive. To this end, CouchDB was used as the backend with a lightweight dynamic user interface implemented client-side as a one-page web application. Data entry and curation processes were streamlined using an OpenRefine-based workflow. The new RefPrimeCouch database application provides its data online under an Open Database License.}, language = {en} }