Image of Muslim women represented by means of modern English

The aim of the study is to show the image of Muslim women and to identify their position at the language leve

Treatment results of children at the age of 3-5 years with class iii malocclusion

Class III malocclusion is up to 16% among diseases of the maxillofacial region. Class III malocclusion comes amid significant morphological, functional and aesthetic disturbances even during the period of primary occlusion. Orthodontic treatment of 20 children at the age of 3-5 years with class III malocclusion and anterior cross-bite was carried out with the author's device. The analysis of the results of orthodontic treatment of children aged 3-5 years showed the elimination of class III malocclusion and anterior cross-bite in a short time, which creates conditions for the harmonious growth and development of the dentitionСреди заболеваний челюстно-лицевой области мезиальная окклюзия составляет до 16%. Мезиальная окклюзия сопровождается значительными морфологическими, функциональными и эстетическими нарушениями даже в период временной окклюзии. Проведено ортодонтическое лечение 20 детей 3-5 лет с мезиальной окклюзией и обратным резцовым перекрытием авторским аппаратом. Проведенный анализ результатов ортодонтического лечения детей 3-5 лет показал устранение мезиальной окклюзии и обратного резцового перекрытия в короткие сроки, что создает условия для гармоничного роста и развития зубочелюстной систем

Inhibition of Ubc13-mediated ubiquitination by GPS2 regulates multiple stages of B cell development

Non-proteolytic ubiquitin signaling mediated by Lys63 ubiquitin chains plays a critical role in multiple pathways that are key to the development and activation of immune cells. Our previous work indicates that GPS2 (G-protein Pathway Suppressor 2) is a multifunctional protein regulating TNF signaling and lipid metabolism in the adipose tissue through modulation of Lys63 ubiquitination events. However, the full extent of GPS2-mediated regulation of ubiquitination and the underlying molecular mechanisms are unknown. Here, we report that GPS2 is required for restricting the activation of TLR and BCR signaling pathways and the AKT/FOXO1 pathway in immune cells based on direct inhibition of Ubc13 enzymatic activity. Relevance of this regulatory strategy is confirmed in vivo by B cell-targeted deletion of GPS2, resulting in developmental defects at multiple stages of B cell differentiation. Together, these findings reveal that GPS2 genomic and non-genomic functions are critical for the development and cellular homeostasis of B cells

Fatty Acid Metabolites Combine with Reduced β Oxidation to Activate Th17 Inflammation in Human Type 2 Diabetes

Mechanisms that regulate metabolites and downstream energy generation are key determinants of T cell cytokine production, but the processes underlying the Th17 profile that predicts the metabolic status of people with obesity are untested. Th17 function requires fatty acid uptake, and our new data show that blockade of CPT1A inhibits Th17-associated cytokine production by cells from people with type 2 diabetes (T2D). A low CACT:CPT1A ratio in immune cells from T2D subjects indicates altered mitochondrial function and coincides with the preference of these cells to generate ATP through glycolysis rather than fatty acid oxidation. However, glycolysis was not critical for Th17 cytokines. Instead, β oxidation blockade or CACT knockdown in T cells from lean subjects to mimic characteristics of T2D causes cells to utilize 16C-fatty acylcarnitine to support Th17 cytokines. These data show long-chain acylcarnitine combines with compromised β oxidation to promote disease-predictive inflammation in human T2D. Although glycolysis generally fuels inflammation, Nicholas, Proctor, and Agrawal et al. report that PBMCs from subjects with type 2 diabetes use a different mechanism to support chronic inflammation largely independent of fuel utilization. Loss- and gain-of-function experiments in cells from healthy subjects show mitochondrial alterations combine with increases in fatty acid metabolites to drive chronic T2D-like inflammation

A Loss of Function Screen of Identified Genome-Wide Association Study Loci Reveals New Genes Controlling Hematopoiesis

The formation of mature cells by blood stem cells is very well understood at the cellular level and we know many of the key transcription factors that control fate decisions. However, many upstream signalling and downstream effector processes are only partially understood. Genome wide association studies (GWAS) have been particularly useful in providing new directions to dissect these pathways. A GWAS meta-analysis identified 68 genetic loci controlling platelet size and number. Only a quarter of those genes, however, are known regulators of hematopoiesis. To determine function of the remaining genes we performed a medium-throughput genetic screen in zebrafish using antisense morpholino oligonucleotides (MOs) to knock down protein expression, followed by histological analysis of selected genes using a wide panel of different hematopoietic markers. The information generated by the initial knockdown was used to profile phenotypes and to position candidate genes hierarchically in hematopoiesis. Further analysis of brd3a revealed its essential role in differentiation but not maintenance and survival of thrombocytes. Using the from-GWAS-to-function strategy we have not only identified a series of genes that represent novel regulators of thrombopoiesis and hematopoiesis, but this work also represents, to our knowledge, the first example of a functional genetic screening strategy that is a critical step toward obtaining biologically relevant functional data from GWA study for blood cell traits

Selective small molecule induced degradation of the BET bromodomain protein BRD4

The Bromo- and Extra-Terminal (BET) proteins BRD2, BRD3, and BRD4 play important roles in transcriptional regulation, epigenetics, and cancer and are the targets of pan-BET selective bromodomain inhibitor JQ1. However, the lack of intra-BET selectivity limits the scope of current inhibitors as probes for target validation and could lead to unwanted side effects or toxicity in a therapeutic setting. We designed Proteolysis Targeted Chimeras (PROTACs) that tether JQ1 to a ligand for the E3 ubiquitin ligase VHL, aimed at triggering the intracellular destruction of BET proteins. Compound MZ1 potently and rapidly induces reversible, long-lasting, and unexpectedly selective removal of BRD4 over BRD2 and BRD3. The activity of MZ1 is dependent on binding to VHL but is achieved at a sufficiently low concentration not to induce stabilization of HIF-1α. Gene expression profiles of selected cancer-related genes responsive to JQ1 reveal distinct and more limited transcriptional responses induced by MZ1, consistent with selective suppression of BRD4. Our discovery opens up new opportunities to elucidate the cellular phenotypes and therapeutic implications associated with selective targeting of BRD4

A glimpse of the ERM proteins

In all eukaryotes, the plasma membrane is critically important as it maintains the architectural integrity of the cell. Proper anchorage and interaction between the plasma membrane and the cytoskeleton is critical for normal cellular processes. The ERM (ezrin-radixin-moesin) proteins are a class of highly homologous proteins involved in linking the plasma membrane to the cortical actin cytoskeleton. This review takes a succinct look at the biology of the ERM proteins including their structure and function. Current reports on their regulation that leads to activation and deactivation was examined before taking a look at the different interacting partners. Finally, emerging roles of each of the ERM family members in cancer was highlighted

Клинико-эпидемиологическая характеристика гепатита А у детей в период подъема заболеваемости

Objective. Study of clinical and epidemiological characteristicsof hepatitis A in children.Materials and methods. The paper presents the epidemiological situation of this issue in the Krasnoyarsk Territory, as well as the results of clinical observations of 104 children with hepatitis A in age from 1 to 14 years.Results. It was found that at the present time is marked deterioration of the epidemiological situation of hepatitis A with involvement in the epidemiological process of young children. In this severe hepatitis A, often occurring with the phenomena of cholestasis, significantly more frequent among children aged 7–14 years. Despite the apparent beneficial for the infection at discharge on the part of school-age children has been a recovery with residual effects that require continued monitoring and corrective therapy appointment.Цель. Изучение клинико-эпидемиологической характеристики гепатита А (ГА) у детей.Материалы и методы. Представлена эпидемиологическая ситуация по данной проблеме в Красноярском крае, а также результаты клинического наблюдения за 104 детьми с ГА в возрасте от 1 до 14 лет.Результаты. Установлено, что в настоящее время отмечено ухудшение эпидемиологической ситуации по ГА с вовлечением в эпидемиологический процесс детей раннего возраста. При этом тяжелые формы ГА, зачастую протекающие с явлениями холестаза, достоверно чаще встречаются у детей 7–14 лет. Несмотря на кажущееся благоприятное течение данной инфекции, при выписке у части детей школьного возраста имело место выздоровление с остаточными явлениями, что требовало продолжения наблюдения и назначения корригирующей терапии