Современные клинико-эволютивные аспекты острой диареи у грудных детей осложненной токсико-инфекционной энцефалопатией

Department of Pediatrics, Pediatrics from Municipal Clinical Hospital of children No 1, Nicolae Testemitanu State Medical and Pharmaceutical University, Congresul III al Medicilor de Familie din Republica Moldova, 17–18 mai, 2012, Chişinău, Republica Moldova, Conferinţa Naţională „Maladii bronhoobstructive la copii”, consacrată profesorului universitar, doctor habilitat Victor Gheţeul, 27 aprilie, Chişinău, Republica MoldovaAcute diarrheal disease is ranked second after the morbidity and mortality place in early childhood by WHO. Toxic infectious encephalopathy complication has an incidence of 56.6% (in our survey it is 18.6%), prevalent in children with neurological compromise substrate and disturbance of background states with direct input from these indices. So it is a major health and social problem by high mortality and serious social impact.По данным Всемирной Организации Здравоохранения острые диареи занимают второе место в структуре заболеваемости и третье место в структуре смертности детей раннего возраста. Осложнение в виде токсико-инфекционной энцефалопатии встречается в 56,6% случаев (в нашем исследовании – 18,6%), у детей с патологическим преморбидным фоном, неврологической патологией, представляя собой серьезную медицинскую и социальную проблему из-за высокой смертности и тяжелых последствий

Клинико-иммунологическая характеристика острых респираторных заболеваний у детей в возрасте до 5 лет ассоциированные с герпес инфекцией

Department of Pediatrics, Municipal Clinical Hospital of Children No 1, Nicolae Testemitanu State Medical and Pharmaceutical University, Congresul III al Medicilor de Familie din Republica Moldova, 17–18 mai, 2012, Chişinău, Republica Moldova, Conferinţa Naţională „Maladii bronhoobstructive la copii”, consacrată profesorului universitar, doctor habilitat Victor Gheţeul, 27 aprilie, Chişinău, Republica MoldovaThe research group was 47 children under 5 years old with severe respiratory diseases, associated with Herpes-infection. Diagnosis of Herpes-infection was confirmed by PCR and IFM. Immunological disorders were observed in 2/3 cases (decreasing level of CD4, CD8, CD20 and serological fraction IgA and IgG). The presence of HSV and/or CMV in parents was confirmed (PCR – 79%, ELISA – 11%). Viral association (ARD, HSV, CMV) determines immunological disorder and severity of clinical manifestations.Группа исследования составила 47 детей в возрасте до 5 лет с тяжелыми респираторными заболеваниями, сочетанные с герпес инфекцией. Диагноз герпетической инфекции подтвержден методами ПЦР и ИФМ. Иммунологический дисбаланс отмечен у 2\3 случаев (снижение уровня СД8, СД4, СД20 и сывороточных фракций IgA и IgG). Подтверждено наличие HSV и\или CMV у родителей (методом ПЦР – 79% и ИФА – 11%). Вирусная ассоциация (ОРЗ, HSV, CMV) определяет иммунный дисбаланс и тяжесть клинического течения

A Conserved Noncoding Locus Regulates Random Monoallelic Xist Expression across a Topological Boundary

cis-Regulatory communication is crucial in mammalian development and is thought to be restricted by the spatial partitioning of the genome in topologically associating domains (TADs). Here, we discovered that the Xist locus is regulated by sequences in the neighboring TAD. In particular, the promoter of the noncoding RNA Linx (LinxP) acts as a long-range silencer and influences the choice of X chromosome to be inactivated. This is independent of Linx transcription and independent of any effect on Tsix, the antisense regulator of Xist that shares the same TAD as Linx. Unlike Tsix, LinxP is well conserved across mammals, suggesting an ancestral mechanism for random monoallelic Xist regulation. When introduced in the same TAD as Xist, LinxP switches from a silencer to an enhancer. Our study uncovers an unsuspected regulatory axis for X chromosome inactivation and a class of cis-regulatory effects that may exploit TAD partitioning to modulate developmental decisions.Galupa et al. uncover elements important for Xist regulation in its neighboring TAD and reveal that these elements can influence gene regulation both within and between topological domains. These findings, in a context where dynamic, developmental expression is necessary, challenge current models for TAD-based gene-regulatory landscapes

Psip1/p52 regulates posterior Hoxa genes through activation of lncRNA Hottip

Long noncoding RNAs (lncRNAs) have been implicated in various biological functions including the regulation of gene expression, however, the functionality of lncRNAs is not clearly understood and conflicting conclusions have often been reached when comparing different methods to investigate them. Moreover, little is known about the upstream regulation of lncRNAs. Here we show that the short isoform (p52) of a transcriptional co-activator—PC4 and SF2 interacting protein (Psip1), which is known to be involved in linking transcription to RNA processing, specifically regulates the expression of the lncRNA Hottip–located at the 5’ end of the Hoxa locus. Using both knockdown and knockout approaches we show that Hottip expression is required for activation of the 5’ Hoxa genes (Hoxa13 and Hoxa10/11) and for retaining Mll1 at the 5’ end of Hoxa. Moreover, we demonstrate that artificially inducing Hottip expression is sufficient to activate the 5’ Hoxa genes and that Hottip RNA binds to the 5’ end of Hoxa. By engineering premature transcription termination, we show that it is the Hottip lncRNA molecule itself, not just Hottip transcription that is required to maintains active expression of posterior Hox genes. Our data show a direct role for a lncRNA molecule in regulating the expression of developmentally-regulated mRNA genes in cis

Long non-coding RNAs: spatial amplifiers that control nuclear structure and gene expression

Over the past decade, it has become clear that mammalian genomes encode thousands of long non-coding RNAs (lncRNAs), many of which are now implicated in diverse biological processes. Recent work studying the molecular mechanisms of several key examples — including Xist, which orchestrates X chromosome inactivation — has provided new insights into how lncRNAs can control cellular functions by acting in the nucleus. Here we discuss emerging mechanistic insights into how lncRNAs can regulate gene expression by coordinating regulatory proteins, localizing to target loci and shaping three-dimensional (3D) nuclear organization. We explore these principles to highlight biological challenges in gene regulation, in which lncRNAs are well-suited to perform roles that cannot be carried out by DNA elements or protein regulators alone, such as acting as spatial amplifiers of regulatory signals in the nucleus

The bipartite TAD organization of the X-inactivation center ensures opposing developmental regulation of Tsix and Xist

The mouse X-inactivation center (Xic) locus represents a powerful model for understanding the links between genome architecture and gene regulation, with the non-coding genes Xist and Tsix showing opposite developmental expression patterns while being organized as an overlapping sense/antisense unit. The Xic is organized into two topologically associating domains (TADs) but the role of this architecture in orchestrating cis-regulatory information remains elusive. To explore this, we generated genomic inversions that swap the Xist/Tsix transcriptional unit and place their promoters in each other's TAD. We found that this led to a switch in their expression dynamics: Xist became precociously and ectopically upregulated, both in male and female pluripotent cells, while Tsix expression aberrantly persisted during differentiation. The topological partitioning of the Xic is thus critical to ensure proper developmental timing of X inactivation. Our study illustrates how the genomic architecture of cis-regulatory landscapes can affect the regulation of mammalian developmental processes

The bipartite TAD organization of the X-inactivation center ensures opposing developmental regulation of Tsix and Xist

The mouse X-inactivation center (Xic) locus represents a powerful model for understanding the links between genome architecture and gene regulation, with the non-coding genes Xist and Tsix showing opposite developmental expression patterns while being organized as an overlapping sense/antisense unit. The Xic is organized into two topologically associating domains (TADs) but the role of this architecture in orchestrating cis-regulatory information remains elusive. To explore this, we generated genomic inversions that swap the Xist/Tsix transcriptional unit and place their promoters in each other's TAD. We found that this led to a switch in their expression dynamics: Xist became precociously and ectopically upregulated, both in male and female pluripotent cells, while Tsix expression aberrantly persisted during differentiation. The topological partitioning of the Xic is thus critical to ensure proper developmental timing of X inactivation. Our study illustrates how the genomic architecture of cis-regulatory landscapes can affect the regulation of mammalian developmental processes