Presentations: from Kac-Moody groups to profinite and back

We go back and forth between, on the one hand, presentations of arithmetic and Kac-Moody groups and, on the other hand, presentations of profinite groups, deducing along the way new results on both

Features of the ancestral bilaterian inferred from Platynereis dumerilii ParaHox genes

Background The ParaHox gene cluster is the evolutionary sister to the Hox cluster. Whilst the role of the Hox cluster in patterning the anterior-posterior axis of bilaterian animals is well established, and the organisation of vertebrate Hox clusters is intimately linked to gene regulation, much less is known about the more recently discovered ParaHox cluster. ParaHox gene clustering, and its relationship to expression, has only been described in deuterostomes. Conventional protostome models (Drosophila melanogaster and Caenorhabditis elegans) are secondarily derived with respect to ParaHox genes, suffering gene loss and cluster break-up. Results We provide the first evidence for ParaHox gene clustering from a less-derived protostome animal, the annelid Platynereis dumerilii. Clustering of these genes is thus not a sole preserve of the deuterostome lineage within Bilateria. This protostome ParaHox cluster is not entirely intact however, with Pdu-Cdx being on the opposite end of the same chromosome arm from Pdu-Gsx and Pdu-Xlox. From the genomic sequence around the P. dumerilii ParaHox genes the neighbouring genes are identified, compared with other taxa, and the ancestral arrangement deduced. Conclusion We relate the organisation of the ParaHox genes to their expression, and from comparisons with other taxa hypothesise that a relatively complex pattern of ParaHox gene expression existed in the protostome-deuterostome ancestor, which was secondarily simplified along several invertebrate lineages. Detailed comparisons of the gene content around the ParaHox genes enables the reconstruction of the genome surrounding the ParaHox cluster of the protostome-deuterostome ancestor, which existed over 550 million years ago.Publisher PDFPeer reviewe

Promising New Inhibitors of Tyrosyl-DNA Phosphodiesterase I (Tdp 1) Combining 4-Arylcoumarin and Monoterpenoid Moieties as Components of Complex Antitumor Therapy

Tyrosyl-DNA phosphodiesterase 1 (Tdp1) is an important DNA repair enzyme in humans, and a current and promising inhibition target for the development of new chemosensitizing agents due to its ability to remove DNA damage caused by topoisomerase 1 (Top1) poisons such as topotecan and irinotecan. Herein, we report our work on the synthesis and characterization of new Tdp1 inhibitors that combine the arylcoumarin (neoflavonoid) and monoterpenoid moieties. Our results showed that they are potent Tdp1 inhibitors with IC50 values in the submicromolar range. In vivo experiments with mice revealed that compound 3ba (IC50 0.62 µM) induced a significant increase in the antitumor effect of topotecan on the Krebs-2 ascites tumor model. Our results further strengthen the argument that Tdp1 is a druggable target with the potential to be developed into a clinically-potent adjunct therapy in conjunction with Top1 poisons

Three deaf mice: mouse models for TECTA-based human hereditary deafness reveal domain-specific structural phenotypes in the tectorial membrane

Tecta is a modular, non-collagenous protein of the tectorial membrane, an extracellular matrix of the cochlea essential for normal hearing. Missense mutations in Tecta cause dominant forms of nonsyndromic deafness and a genotype-phenotype correlation has been reported in humans, with mutations in different Tecta domains causing mid- or high-frequency hearing impairments that are either stable or progressive. Three mutant mice were created as models for human Tecta mutations; the TectaL1820F, G1824D/+ mouse for zona pellucida (ZP) domain mutations causing stable mid-frequency hearing loss in a Belgian family, the TectaC1837G/+ mouse for a ZP-domain mutation underlying progressive mid-frequency hearing loss in a Spanish family, and the TectaC1619S/+ mouse for a zonadhesin-like (ZA) domain mutation responsible for progressive, high-frequency hearing loss in a French family. Mutations in the ZP and ZA domains generate distinctly different changes in the structure of the tectorial membrane. ABR thresholds in the 8-40 kHz range are elevated by 30-40 dB in the ZP-domain mutants, whilst those in the ZA-domain mutant are elevated by 20-30 dB. The phenotypes are stable and no evidence has been found for a progressive deterioration in tectorial membrane structure or auditory function. Despite elevated auditory thresholds, the Tecta mutant mice all exhibit an enhanced tendency to have audiogenic seizures in response to white noise stimuli at low sound pressure levels (≤84 dB SPL), revealing a previously unrecognised consequence of Tecta mutations. These results, together with those from previous studies, establish an allelic series for Tecta unequivocally demonstrating an association between genotype and phenotype

A Comparison of Depression and Anxiety among University Students in Nine Countries during the COVID-19 Pandemic.

The mental health of young adults, particularly students, is at high risk during the COVID-19 pandemic. The purpose of this studywas to examine differences inmental health between university students in nine countries during the pandemic. The study encompassed 2349 university students (69% female) from Colombia, the Czech Republic (Czechia), Germany, Israel, Poland, Russia, Slovenia, Turkey, and Ukraine. Participants underwent the following tests: Patient Health Questionnaire (PHQ-8), Generalized Anxiety Disorder (GAD-7), Exposure to COVID-19 (EC-19), Perceived Impact of Coronavirus (PIC) on students’ well-being, PhysicalActivity (PA), andGeneral Self-ReportedHealth (GSRH). The one-wayANOVAshowed significant differences between countries. The highest depression and anxiety risk occurred in Turkey, the lowest depression in the Czech Republic and the lowest anxiety in Germany. The 2 independence test showed that EC-19, PIC, and GSRHwere associatedwith anxiety and depression inmost of the countries, whereas PA was associated in less than half of the countries. Logistic regression showed distinct risk factors for each country. Gender and EC-19 were the most frequent predictors of depression and anxiety across the countries. The role of gender and PA for depression and anxiety is not universal and depends on cross-cultural differences. Students’mental health should be addressed froma cross-cultural perspective

Development of a regression model of dependence of territorial development of the Republic of Tatarstan on implementation of infrastructure projects

© 2019, Research Trend. All rights reserved. The article is devoted to development of a model of regression dependence of territorial development of Republic of Tatarstan on implementation of infrastructure projects. The relevance of the studied issues is due to a number of factors. The main ones are: satisfaction of infrastructure needs of the population in the form of a range of services and, as a result, improving the quality of life of the population. In addition, infrastructure projects in modern realities are tools for the implementation of strategic plans. As elements of federal and regional development programs, they are included in the group of priority national projects approved by the President of the Russian Federation. According to experts, infrastructure projects can become drivers of the socio-economic development of territories of various levels, bringing them to a new level of existence. Thus, the built-up regression model of dependence is aimed at identifying the role of infrastructure projects in the territorial development of the Republic of Tatarstan. On the way to achieving the goal, the stages of the development of the methodology are shown with a detailed description of the methods used, the rationale for their use in relation to the specifics of the Tatarstan region is presented, the difficulties encountered and the chosen ways to overcome them are described, and the conclusions are presented. The result of the study was a regression model with socio-economic indicators of the dependence of the gross territorial product of the municipal regions of the republic on the financing of infrastructure projects in them. Verification of the model showed its compliance with all Gauss-Markov conditions, which proves its applicability for predicting the process in the region