570 Biowissenschaften; Biologie
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Progress in the diagnosis of leishmaniases depends on the development of effective methods and the discovery of suitable biomarkers. We propose firstly an update classification of Leishmania species and their synonymies. We demonstrate a global map highlighting the geography of known endemic Leishmania species pathogenic to humans. We summarize a complete list of techniques currently in use and discuss their advantages and limitations. The available data highlights the benefits of molecular markers in terms of their sensitivity and specificity to quantify variation from the subgeneric level to species complexes, (sub) species within complexes, and individual populations and infection foci. Each DNA-based detection method is supplied with a comprehensive description of markers and primers and proposal for a classification based on the role of each target and primer in the detection, identification and quantification of leishmaniasis infection. We outline a genome-wide map of genes informative for diagnosis that have been used for Leishmania genotyping. Furthermore, we propose a classification method based on the suitability of well-studied molecular markers for typing the 21 known Leishmania species pathogenic to humans. This can be applied to newly discovered species and to hybrid strains originating from inter-species crosses. Developing more effective and sensitive diagnostic methods and biomarkers is vital for enhancing Leishmania infection control programs.
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.
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.
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.
In drug discovery, the characterisation of the precise modes of action (MoA) and of unwanted off-target effects of novel molecularly targeted compounds is of highest relevance. Recent approaches for identification of MoA have employed various techniques for modeling of well defined signaling pathways including structural information, changes in phenotypic behavior of cells and gene expression patterns after drug treatment. However, efficient approaches focusing on proteome wide data for the identification of MoA including interference with mutations are underrepresented. As mutations are key drivers of drug resistance in molecularly targeted tumor therapies, efficient analysis and modeling of downstream effects of mutations on drug MoA is a key to efficient development of improved targeted anti-cancer drugs. Here we present a combination of a global proteome analysis, reengineering of network models and integration of apoptosis data used to infer the mode-of-action of various tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML) cell lines expressing wild type as well as TKI resistance conferring mutants of BCR-ABL. The inferred network models provide a tool to predict the main MoA of drugs as well as to grouping of drugs with known similar kinase inhibitory activity patterns in comparison to drugs with an additional MoA. We believe that our direct network reconstruction approach, demonstrated on proteomics data, can provide a complementary method to the established network reconstruction approaches for the preclinical modeling of the MoA of various types of targeted drugs in cancer treatment. Hence it may contribute to the more precise prediction of clinically relevant on- and off-target effects of TKIs.
Visceral leishmaniasis (VL), caused by the members of the Leishmania donovani complex, has been responsible for devastating VL epidemics in the Sudan. Multilocus microsatellite and sequence typing studies can provide valuable insights into the molecular epidemiology of leishmaniasis, when applied at local scales. Here we present population genetic data for a large panel of strains and clones collected in endemic Sudan between 1993 and 2001.
Entwicklung eines impedimetrischen Biosensors für den Nachweis von Antigliadin Autoantikörpern
(2007)
In der vorliegenden Arbeit wurde ein Biosensor für den Nachweis von Antikörpern gegen Gliadin entwickelt. Gliadine sind Bestandteile der Getreideglutene und verantwortlich für die Manifestation der Zöliakie (Gluten-Unverträglichkeit). Der Biosensor basiert auf der Immobilisierung von Gliadin auf Goldelektroden, die zuvor mit Polystyrensulfonsäure beschichtet worden waren. Die erfolgreiche Immobilisierung wurde mit Hilfe der Quarzmikrowaage dokumentiert. Die Antigen-Antikörper-Bindung konnte durch die Inkubation mit einem Peroxidase-markierten Zweitantikörper und der enzymatischen Oxidation von 3-Amino-9- Ethylcarbazol (AEC) verstärkt werden. Die Zunahme in der Elektrodenisolierung durch die Bindungs- und Ablagerungsreaktion konnte durch elektrochemische Impedanzspektroskopie (EIS) in Anwesenheit des Hexacyanoferrat- Redoxsystems gemessen werden. Die Spektren wurden mit Hilfe eines Randles-Ersatzschaltbildes ausgewertet. Hierbei konnte eine Zunahme im Ladungstransferwiderstand festgestellt werden, die pro portional zur Antigliadin-Antikörperkonzentration, im Bereich von 10-8 M bis 10-6 M, war. Mit Hilfe dieses Sensors wurden schließlich humane Seren hinsichtlich ihrer Konzentration an Gliadinantikörpern, sowohl für Immunglobuline vom Typ IgG als auch IgA, untersucht.
Throughout the recent years, 454 pyrosequencing has emerged as an efficient alternative to traditional Sanger sequencing and is widely used in both de novo whole-genome sequencing and metagenomics. Especially the latter application is extremely sensitive to sequencing errors and artificially duplicated reads. Both are common in 454 pyrosequencing and can create a strong bias in the estimation of diversity and composition of a sample. To date, there are several tools that aim to remove both sequencing noise and duplicates. Nevertheless, duplicate removal is often based on nucleotide sequences rather than on the underlying flow values, which contain additional information.
G-quadruplex is a DNA secondary structure that has been shown to play an important role in biological systems. In a previous study, we identified 1998 G-quadruplex-forming sequences using a mouse CpG islands DNA microarray with a fluorescent-labeled G-quadruplex ligand. Among these putative G-quadruplex-forming sequences, G-quadruplex formation was verified for 10 randomly selected sequences by CD spectroscopy and DMS footprinting analysis. In this study, the biological function of the 10 G-quadruplex-forming sequences in the transcriptional regulation has been analyzed using a reporter assay.