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High Throughput Sequencing Identifies Misregulated Genes in the Drosophila Polypyrimidine Tract-Binding Protein (hephaestus) Mutant Defective in Sper…
2015
The Drosophila polypyrimidine tract-binding protein (dmPTB or hephaestus) plays an important role during spermatogenesis. The heph2 mutation in this gene results in a specific defect in spermatogenesis, causing aberrant spermatid individualization and male sterility. However, the array of molecular defects in the mutant remains uncharacterized. Using an unbiased high throughput sequencing approach, we have identified transcripts that are misregulated in this mutant. Aberrant transcripts show altered expression levels, exon skipping, and alternative 5' ends. We independently verified these findings by reverse-transcription and polymerase chain reaction (RT-PCR) analysis. Our analysis shows m…
From mammals back to birds: Host-switch of the acanthocephalan Corynosoma australe from pinnipeds to the Magellanic penguin Spheniscus magellanicus.
2017
Trophically-transmitted parasites are regularly exposed to potential new hosts through food web interactions. Successful colonization, or switching, to novel hosts, occur readily when ?donor? and ?target? hosts are phylogenetically related, whereas switching between distantly related hosts is rare and may result from stochastic factors (i.e. rare favourable mutations). This study investigates a host-switching event between a marine acanthocephalan specific to pinnipeds that is apparently able to reproduce in Magellanic penguins Spheniscus magellanicus from Brazil. Detailed analysis of morphological and morphometrical data from acanthocephalans from penguins indicates that they belong to Cor…
Repurposing a Library of Human Cathepsin L Ligands: Identification of Macrocyclic Lactams as Potent Rhodesain and Trypanosoma brucei Inhibitors.
2018
Rhodesain (RD) is a parasitic, human cathepsin L (hCatL) like cysteine protease produced by Trypanosoma brucei (T. b.) species and a potential drug target for the treatment of human African trypanosomiasis (HAT). A library of hCatL inhibitors was screened, and macrocyclic lactams were identified as potent RD inhibitors (Ki < 10 nM), preventing the cell-growth of Trypanosoma brucei rhodesiense (IC50 < 400 nM). SARs addressing the S2 and S3 pockets of RD were established. Three cocrystal structures with RD revealed a noncovalent binding mode of this ligand class due to oxidation of the catalytic Cys25 to a sulfenic acid (Cys–SOH) during crystallization. The P-glycoprotein efflux ratio was mea…
Novel DNA Methylation Sites Influence GPR15 Expression in Relation to Smoking
2018
Smoking is a major risk factor for cardiovascular diseases and has been implicated in the regulation of the G protein-coupled receptor 15 (GPR15) by affecting CpG methylation. The G protein-coupled receptor 15 is involved in angiogenesis and inflammation. An effect on GPR15 gene regulation has been shown for the CpG site CpG3.98251294. We aimed to analyze the effect of smoking on GPR15 expression and methylation sites spanning the GPR15 locus. DNA methylation of nine GPR15 CpG sites was measured in leukocytes from 1291 population-based individuals using the EpiTYPER. Monocytic GPR15 expression was measured by qPCR at baseline and five-years follow up. GPR15 gene expression was upregulated i…
Skin and gut microbiomes of a wild mammal respond to different environmental cues
2018
Background Animal skin and gut microbiomes are important components of host fitness. However, the processes that shape the microbiomes of wildlife are poorly understood, particularly with regard to exposure to environmental contaminants. We used 16S rRNA amplicon sequencing to quantify how exposure to radionuclides impacts the skin and gut microbiota of a small mammal, the bank vole Myodes glareolus, inhabiting areas within and outside the Chernobyl Exclusion Zone (CEZ), Ukraine. Results Skin microbiomes of male bank voles were more diverse than females. However, the most pronounced differences in skin microbiomes occurred at a larger spatial scale, with higher alpha diversity in the skin m…
Conf-VLKA: A structure-based revisitation of the Virtual Lock-and-key Approach
2016
In a previous work, we developed the in house Virtual Lock-and-Key Approach (VLKA) in order to evaluate target assignment starting from molecular descriptors calculated on known inhibitors used as an information source. This protocol was able to predict the correct biological target for the whole dataset with a good degree of reliability (80%), and proved experimentally, which was useful for the target fishing of unknown compounds. In this paper, we tried to remodel the previous in house developed VLKA in a more sophisticated one in order to evaluate the influence of 3D conformation of ligands on the accuracy of the prediction. We applied the same previous algorithm of scoring and ranking b…
Bi-layered polyurethane – Extracellular matrix cardiac patch improves ischemic ventricular wall remodeling in a rat model
2016
As an intervention to abrogate ischemic cardiomyopathy, the concept of applying a temporary, local patch to the surface of the recently infarcted ventricle has been explored from a number of design perspectives. Two important features considered for such a cardiac patch include the provision of appropriate mechanical support and the capacity to influence the remodeling pathway by providing cellular or biomolecule delivery. The objective of this report was to focus on these two features by first evaluating the incorporation of a cardiac extracellular matrix (ECM) component, and second by evaluating the impact of patch anisotropy on the pathological remodeling process initiated by myocardial …
Monocyte preseeding leads to an increased implant bed vascularization of biphasic calcium phosphate bone substitutes via vessel maturation
2016
The present study analyzes the influence of the addition of monocytes to a biphasic bone substitute with two granule sizes (400-700 μm and 500-1000 μm). The majority of the added monocytes was detectable as mononuclear cells, while also low amounts of (chimeric) multinucleated giant cells (MNGCs) were found. No increase in the total number of MNGCs was established, but a significantly increased percent vascularization. Altogether, the results show that the added monocytes become involved in the tissue response to a biomaterial without marked changes in the overall reaction. Monocyte addition enables an increased implant bed vascularization especially via induction of vessel maturation and, …
Effect of Low-Intensity Pulsed Ultrasound on Osteogenic Human Mesenchymal Stem Cells Commitment in a New Bone Scaffold
2017
Purpose Bone tissue engineering is helpful in finding alternatives to overcome surgery limitations. Bone growth and repair are under the control of biochemical and mechanical signals; therefore, in recent years several approaches to improve bone regeneration have been evaluated. Osteo-inductive biomaterials, stem cells, specific growth factors and biophysical stimuli are among those. The aim of the present study was to evaluate if low-intensity pulsed ultrasound stimulation (LIPUS) treatment would improve the colonization of an MgHA/Coll hybrid composite scaffold by human mesenchymal stem cells (hMSCs) and their osteogenic differentiation. LIPUS stimulation was applied to hMSCs cultured on …
Damage detection of a hybrid composite laminate aluminum/glass under quasi-static and fatigue loadings by acoustic emission technique
2019
Abstract This paper deals with the characterization by Acoustic Emission technique of damages occurring in a hybrid laminate aluminium/glass during quasi-static and fatigue tests. Indeed, hybrid laminates materials metal/composites are more and more considered in structure, automotive and aerospace designs because of their good mechanical performances and lightness. To understand their damages characteristics, several types of laminates (fiber orientations, number of folds, presence or not of an aluminium sheet) have been tested. The acoustic emission analysis has been realized using statistical multi-parameters methods of data clustering: combination of Principal Components Analysis (PCA) …