The influence of heat and cold waves on mortality in Russian subarctic cities with varying climates.

Publications on ambient temperature-related mortality among Arctic or subarctic populations are extremely rare. While circumpolar areas cover large portions of several European countries, Canada, and the USA, the population of these territories is relatively small, and the data needed for statistical analysis of the health impacts of extreme temperature events are frequently insufficient. This study utilizes standard time series regression techniques to estimate relative increases in cause- and age-specific daily mortality rates during heat waves and cold spells in four Russian cities with a subarctic climate.

Chromatin-Associated Membraneless Organelles in Regulation of Cellular Differentiation.

Membrane-free intracellular biocondensates are enclosures of proteins and nucleic acids that form by phase separation. Extensive ensembles of nuclear "membraneless organelles" indicate their involvement in genome regulation. Indeed, nuclear bodies have been linked to regulation of gene expression by formation of condensates made of chromatin and RNA processing factors.

BART-Seq: cost-effective massively parallelized targeted sequencing for genomics, transcriptomics, and single-cell analysis.

We describe a highly sensitive, quantitative, and inexpensive technique for targeted sequencing of transcript cohorts or genomic regions from thousands of bulk samples or single cells in parallel. Multiplexing is based on a simple method that produces extensive matrices of diverse DNA barcodes attached to invariant primer sets, which are all pre-selected and optimized in silico. By applying the matrices in a novel workflow named Barcode Assembly foR Targeted Sequencing (BART-Seq), we analyze developmental states of thousands of single human pluripotent stem cells, either in different maintenance media or upon Wnt/β-catenin pathway activation, which identifies the mechanisms of differentiation induction.

Cross-Regulation between TDP-43 and Paraspeckles Promotes Pluripotency-Differentiation Transition.

RNA-binding proteins (RBPs) and long non-coding RNAs (lncRNAs) are key regulators of gene expression, but their joint functions in coordinating cell fate decisions are poorly understood. Here we show that the expression and activity of the RBP TDP-43 and the long isoform of the lncRNA Neat1, the scaffold of the nuclear compartment "paraspeckles," are reciprocal in pluripotent and differentiated cells because of their cross-regulation. In pluripotent cells, TDP-43 represses the formation of paraspeckles by enhancing the polyadenylated short isoform of Neat1.

Сardiovascular mortality during heat waves in temperate climate: an association with bioclimatic indices.

The authors studied the relative predictive powers of several bioclimatic indices as predictors of population mortality during heat waves. Daily mean and maximum values of air temperature, Humidex, apparent, and physiological equivalent temperatures (PETs) were examined. The numbers of daily deaths and daily meteorological data in Rostov-on-Don (southern Russia) were used.

GATA2/3-TFAP2A/C transcription factor network couples human pluripotent stem cell differentiation to trophectoderm with repression of pluripotency.

To elucidate the molecular basis of BMP4-induced differentiation of human pluripotent stem cells (PSCs) toward progeny with trophectoderm characteristics, we produced transcriptome, epigenome H3K4me3, H3K27me3, and CpG methylation maps of trophoblast progenitors, purified using the surface marker APA. We combined them with the temporally resolved transcriptome of the preprogenitor phase and of single APA+ cells. This revealed a circuit of bivalent TFAP2A, TFAP2C, GATA2, and GATA3 transcription factors, coined collectively the "trophectoderm four" (TEtra), which are also present in human trophectoderm in vivo.

Scanpaths of Complex Image Viewing: Insights From Experimental and Modeling Studies.

From the first works of Buswell, Yarbus, and Noton and Stark, the scan path for viewing complex images has been considered as a possible key to objective estimation of cognitive processes and their dynamics. However, evidences both pro and con were revealed in the modern research. In this article, the results supporting the Yarbus-Stark concept are presented.

Mortality related to air pollution with the moscow heat wave and wildfire of 2010.

Background: Prolonged high temperatures and air pollution from wildfires often occur together, and the two may interact in their effects on mortality. However, there are few data on such possible interactions.

Methods: We analyzed day-to-day variations in the number of deaths in Moscow, Russia, in relation to air pollution levels and temperature during the disastrous heat wave and wildfire of 2010.

The influence of meteorological and geomagnetic factors on acute myocardial infarction and brain stroke in Moscow, Russia.

Evidence of the impact of air temperature and pressure on cardiovascular morbidity is still quite limited and controversial, and even less is known about the potential influence of geomagnetic activity. The objective of this study was to assess impacts of air temperature, barometric pressure and geomagnetic activity on hospitalizations with myocardial infarctions and brain strokes. We studied 2,833 myocardial infarctions and 1,096 brain strokes registered in two Moscow hospitals between 1992 and 2005.

Myocardin related transcription factors are required for coordinated cell cycle progression.

Myocardin related transcription factors A and B (MRTFs) activate serum response factor-driven transcription in response to Rho signaling and changes in actin dynamics. Myocardin and MRTFs have been implicated in anti-proliferative effects on a range of cell types. The precise mechanisms, however, remained elusive.

The OPCML tumor suppressor functions as a cell surface repressor-adaptor, negatively regulating receptor tyrosine kinases in epithelial ovarian cancer.

Unlabelled: Epithelial ovarian cancer is the leading cause of death from gynecologic malignancy, and its molecular basis is poorly understood. We previously demonstrated that opioid binding protein cell adhesion molecule (OPCML) was frequently epigenetically inactivated in epithelial ovarian cancers, with tumor suppressor function in vitro and in vivo. Here, we further show the clinical relevance of OPCML and demonstrate that OPCML functions by a novel mechanism in epithelial ovarian cancer cell lines and normal ovarian surface epithelial cells by regulating a specific repertoire of receptor tyrosine kinases: EPHA2, FGFR1, FGFR3, HER2, and HER4.

MAL/MRTF-A controls migration of non-invasive cells by upregulation of cytoskeleton-associated proteins.

Monomeric actin regulates gene expression through serum response factor (SRF) by inhibiting its transcriptional coactivator myocardin-related transcription factor (MAL/MRTF). Many affected genes encode cytoskeletal components. We have analysed the migratory effects of actin-MAL signalling and of new target genes in non-invasive highly adherent cells.

Myocardin-related transcription factor A regulates expression of Bok and Noxa and is involved in apoptotic signalling.

The myocardin-related transcription factor MAL/MRTF-A relates changes in G-actin to SRF-mediated gene expression. The set of G-actin-controlled SRF target genes includes components of the cytoskeleton and cell migration machinery as well as various signal transducers. Our previous screen for G-actin regulated genes identified a number of targets with well-established anti-proliferative and proapoptotic functions.

Extreme temperature episodes and mortality in Yakutsk, East Siberia.

Introduction: Although the health impacts of heat waves and, to a lesser extent, cold spells in big cities in moderate climates have been well documented, little is known about the same impacts in the circumpolar region. An epidemiological study in an Arctic town presents considerable difficulties for the statistician because of small population sizes. When daily mortality counts are mostly 0, 1 or 2, they are not normally distributed and do not fit the independence assumption.

Epithelial Protein Lost in Neoplasm alpha (Eplin-alpha) is transcriptionally regulated by G-actin and MAL/MRTF coactivators.

Epithelial Protein Lost in Neoplasm alpha is a novel cytoskeleton-associated tumor suppressor whose expression inversely correlates with cell growth, motility, invasion and cancer mortality. Here we show that Eplin-alpha transcription is regulated by actin-MAL-SRF signalling. Upon signal induction, the coactivator MAL/MRTF is released from a repressive complex with monomeric actin, binds the transcription factor SRF and activates target gene expression.

Temporal dynamics of fixation duration, saccade amplitude, and viewing trajectory.

The prospective goal of our study is a quantitative estimation of the contribution of various factors and mechanisms during image viewing. In this paper, experimental data about temporal dynamics of eye movement parameters and viewing trajectory are considered. Three images were presented to each subject (n = 12) under two experimental conditions: "free viewing of initial images" and "search for modified regions in previously presented images".

Negative regulation of the EGFR-MAPK cascade by actin-MAL-mediated Mig6/Errfi-1 induction.

We analyzed the G-actin-regulated transcriptome by gene expression analysis using previously characterized actin-binding drugs. We found many known MAL/MRTF-dependent target genes of serum response factor (SRF), as well as additional directly regulated genes. Surprisingly, several putative antiproliferative target genes were identified, including mig6/errfi-1, a negative regulator of the EGFR family.