Effect of promoter architecture on the cell-to-cell variability in gene expression

According to recent experimental evidence, the architecture of a promoter, defined as the number, strength and regulatory role of the operators that control the promoter, plays a major role in determining the level of cell-to-cell variability in gene expression. These quantitative experiments call for a corresponding modeling effort that addresses the question of how changes in promoter architecture affect noise in gene expression in a systematic rather than case-by-case fashion. In this article, we make such a systematic investigation, based on a simple microscopic model of gene regulation that incorporates stochastic effects. In particular, we show how operator strength and operator multiplicity affect this variability. We examine different modes of transcription factor binding to complex promoters (cooperative, independent, simultaneous) and how each of these affects the level of variability in transcription product from cell-to-cell. We propose that direct comparison between in vivo single-cell experiments and theoretical predictions for the moments of the probability distribution of mRNA number per cell can discriminate between different kinetic models of gene regulation.Comment: 35 pages, 6 figures, Submitte

Search for gravitational waves from Scorpius X-1 in the second Advanced LIGO observing run with an improved hidden Markov model

We present results from a semicoherent search for continuous gravitational waves from the low-mass X-ray binary Scorpius X-1, using a hidden Markov model (HMM) to track spin wandering. This search improves on previous HMM-based searches of LIGO data by using an improved frequency domain matched filter, the $\mathcal{J}$-statistic, and by analysing data from Advanced LIGO's second observing run. In the frequency range searched, from $60$ to $650\,\mathrm{Hz}$, we find no evidence of gravitational radiation. At $194.6\,\mathrm{Hz}$, the most sensitive search frequency, we report an upper limit on gravitational wave strain (at 95\% confidence) of $h_0^{95\%} = 3.47 \times 10^{-25}$ when marginalising over source inclination angle. This is the most sensitive search for Scorpius X-1, to date, that is specifically designed to be robust in the presence of spin wandering

Polymorphic Allele of Human IRGM1 Is Associated with Susceptibility to Tuberculosis in African Americans

An ancestral polymorphic allele of the human autophagy-related gene IRGM1 is associated with altered gene expression and a genetic risk for Crohn's Disease (CD). We used the single nucleotide polymorphism rs10065172C/T as a marker of this polymorphic allele and genotyped 370 African American and 177 Caucasian tuberculosis (TB) cases and 180 African American and 110 Caucasian controls. Among African Americans, the TB cases were more likely to carry the CD-related T allele of rs10065172 (odds ratio of 1.54; 95% confidence interval, 1.17–2.02; P<0.01) compared to controls. Our finding suggests that this CD-related IRGM1 polymorphic allele is also associated with human susceptibility to TB disease among African Americans

Role of mitochondrial raft-like microdomains in the regulation of cell apoptosis

Lipid rafts are envisaged as lateral assemblies of specific lipids and proteins that dissociate and associate rapidly and form functional clusters in cell membranes. These structural platforms are not confined to the plasma membrane; indeed lipid microdomains are similarly formed at subcellular organelles, which include endoplasmic reticulum, Golgi and mitochondria, named raft-like microdomains. In addition, some components of raft-like microdomains are present within ER-mitochondria associated membranes. This review is focused on the role of mitochondrial raft-like microdomains in the regulation of cell apoptosis, since these microdomains may represent preferential sites where key reactions take place, regulating mitochondria hyperpolarization, fission-associated changes, megapore formation and release of apoptogenic factors. These structural platforms appear to modulate cytoplasmic pathways switching cell fate towards cell survival or death. Main insights on this issue derive from some pathological conditions in which alterations of microdomains structure or function can lead to severe alterations of cell activity and life span. In the light of the role played by raft-like microdomains to integrate apoptotic signals and in regulating mitochondrial dynamics, it is conceivable that these membrane structures may play a role in the mitochondrial alterations observed in some of the most common human neurodegenerative diseases, such as Amyotrophic lateral sclerosis, Huntington's chorea and prion-related diseases. These findings introduce an additional task for identifying new molecular target(s) of pharmacological agents in these pathologies

Prevalence and associated factors of depressive and anxiety symptoms during pregnancy: A population based study in rural Bangladesh

<p>Abstract</p> <p>Background</p> <p>Few studies have examined the associated factors of antepartum depressive and anxiety symptoms (ADS and AAS) in low-income countries, yet the World Health Organization identifies depressive disorders as the second leading cause of global disease burden by 2020. There is a paucity of research on mental disorders and their predictors among pregnant women in Bangladesh. This study aims to estimate the prevalence of depressive and anxiety symptoms and explore the associated factors in a cross-section of rural Bangladeshi pregnant women.</p> <p>Methods</p> <p>The study used cross-sectional data originating from a rural community-based prospective cohort study of 720 randomly selected women in their third trimester of pregnancy from a district of Bangladesh. The validated Bangla version of the Edinburgh Postnatal Depression Scale was used to measure ADS, and a trait anxiety inventory to assess general anxiety symptoms. Background information was collected using a structured questionnaire at the respondents' homes.</p> <p>Results</p> <p>Prevalence of ADS was 18% and AAS 29%. Women's literacy (OR 0.59, 95% CI 0.37-0.95), poor partner relationship (OR 2.23, 95% CI 3.37-3.62), forced sex (OR 1.95, 95% CI 1.01-3.75), physical violence by spouse (OR 1.69, 95% CI 1.02-2.80), and previous depression (OR 4.62 95% CI 2.72-7.85) were found to be associated with ADS. The associated factors of AAS were illiteracy, poor household economy, lack of practical support, physical partner violence, violence during pregnancy, and interaction between poor household economy and poor partner relationship.</p> <p>Conclusion</p> <p>Depressive and anxiety symptoms are found to occur commonly during pregnancy in Bangladesh, drawing attention to a need to screen for depression and anxiety during antenatal care. Policies aimed at encouraging practical support during pregnancy, reducing gender-based violence, supporting women with poor partner relationships, and identifying previous depression may ameliorate the potentially harmful consequences of antepartum depression and anxiety for the women and their family, particularly children.</p

Tunable Frohlich Polarons in Organic Single-Crystal Transistors

In organic field effect transistors (FETs), charges move near the surface of an organic semiconductor, at the interface with a dielectric. In the past, the nature of the microscopic motion of charge carriers -that determines the device performance- has been related to the quality of the organic semiconductor. Recently, it has been appreciated that also the nearby dielectric has an unexpectedly strong influence. The mechanisms responsible for this influence are not understood. To investigate these mechanisms we have studied transport through organic single crystal FETs with different gate insulators. We find that the temperature dependence of the mobility evolves from metallic-like to insulating-like with increasing the dielectric constant of the insulator. The phenomenon is accounted for by a two-dimensional Frohlich polaron model that quantitatively describes our observations and shows that increasing the dielectric polarizability results in a crossover from the weak to the strong polaronic coupling regime