A Genetic Locus Regulates the Expression of Tissue-Specific mRNAs from Multiple Transcription Units

129 GIX- mice, unlike animals of the congeneic partner strain GIX+, do not express significant amounts of the retroviral antigens gp70 and p30. Evidence is presented indicating that the GIX phenotype is specified by a distinct regulatory gene acting on multiple transcription units to control the levels of accumulation of specific mRNA species. The steady-state levels of retroviral-homologous mRNA from the tissues of GIX+ and GIX- mice were examined by blot hybridization using as probes DNA fragments from cloned murine leukemia viruses. RNA potentially encoding viral antigens was reduced or absent in GIX- mice, even though no differences in integrated viral genomes were detected between these congeneic strains by DNA blotting. Tissue-specific patterns of accumulation of these RNA species were detected in brain, epididymis, liver, spleen, and thymus, and several distinct RNA species were found to be coordinately regulated with the GIX phenotype. Measurements of RNA synthesis suggest a major role for transcriptional control in the regulation of some retroviral messages

ATRX regulates H3.3 incorporation and gene expression at G-rich ancestral pseudoautosomal genes

Mutations in the ATRX gene cause alpha thalassaemia mental retardation, X linked, or can enable cancer progression. ATRX encodes a Swi2/Snf2 chromatin remodeling protein involved in deposition of the histone variant H3.3 at telomeres and pericentromeric heterochromatin. The aim of this study was to determine the role of ATRX in the regulation of gene expression. I identified the ancestral pseudoautosomal region (aPAR) genes as some of the most downregulated genes throughout forebrain development. The PARs are homologous regions located at the ends of the X and Y chromosomes, and are rich in repetitive sequences and GC content. However, mouse PAR homologs have translocated to autosomes and are called aPAR genes. The mouse aPAR genes regulated by ATRX are all located near telomeres. To determine how ATRX promotes aPAR gene expression, we focused on Dhrsx. I found that ATRX and H3.3 occupy the Dhrsx gene body in a guanine-rich segment predicted to form secondary structures called G-quadruplexes. In the absence of ATRX, I observed a decrease in H3.3 at Dhrsx and at other downregulated aPAR genes. Several other epigenetic marks are not altered in and around Dhrsx in the ATRX-null forebrain, and thus cannot provide an explanation for transcriptional dysregulation. However, increased RNA PolII occupancy at the ATRX/H3.3/G-rich region of Dhrsx indicates PolII stalling in the absence of ATRX, and suggests that ATRX promotes transcriptional elongation. I conclude that ATRX facilitates passage of the transcription machinery at G-quadruplex forming regions of a gene in a process that involves incorporation of H3.3

Pregnancy, prison and perinatal outcomes in New South Wales, Australia: a retrospective cohort study using linked health data

BACKGROUND Studies from the United States and the United Kingdom have found that imprisoned women are less likely to experience poorer maternal and perinatal outcomes than other disadvantaged women. This population-based study used both community controls and women with a history of incarceration as a control group, to investigate whether imprisoned pregnant women in New South Wales, Australia, have improved maternal and perinatal outcomes. METHODS Retrospective cohort study using probabilistic record linkage of routinely collected data from health and corrective services in New South Wales, Australia. Comparison of the maternal and perinatal outcomes of imprisoned pregnant women aged 18-44 years who gave birth between 2000-2006 with women who were (i) imprisoned at a time other than pregnancy, and (ii) community controls. OUTCOMES OF INTEREST onset of labour, method of birth, pre-term birth, low birthweight, Apgar score, resuscitation, neonatal hospital admission, perinatal death. RESULTS Babies born to women who were imprisoned during pregnancy were significantly more likely to be born pre-term, have low birthweight, and be admitted to hospital, compared with community controls. Pregnant prisoners did not have significantly better outcomes than other similarly disadvantaged women (those with a history of imprisonment who were not imprisoned during pregnancy). CONCLUSIONS In contrast to the published literature, we found no evidence that contact with prison health services during pregnancy was a "therapunitive" intervention. We found no association between imprisonment during pregnancy and improved perinatal outcomes for imprisoned women or their neonates. A history of imprisonment remained the strongest predictor of poor perinatal outcomes, reflecting the relative health disadvantage experienced by this population of women.This work was undertaken with funding from the National Health and Medical Research Council of Australia. Project Grant ID 457515

Reach of Supplemental Nutrition Assistance Program-Education (SNAP-Ed) interventions and nutrition and physical activity-related outcomes, California, 2011-2012.

IntroductionThis study combined information on the interventions of the US Department of Agriculture's Supplemental Nutrition Assistance Program-Education with 5,927 interview responses from the California Health Interview Survey to investigate associations between levels of intervention reach in low-income census tracts in California and self-reported physical activity and consumption of fruits and vegetables, fast food, and sugar-sweetened beverages.MethodsWe determined 4 levels of intervention reach (low reach, moderate reach, high reach, and no intervention) across 1,273 program-eligible census tracts from data on actual and eligible number of intervention participants. The locations of California Health Interview Survey respondents were geocoded and linked with program data. Regression analyses included measures for sex, age, race/ethnicity, and education.ResultsAdults and children from high-reach census tracts reported eating more fruits and vegetables than adults and children from no-intervention census tracts. Adults from census tracts with low, moderate, or high levels of reach reported eating fast food less often than adults from no-intervention census tracts. Teenagers from low-reach census tracts reported more physical activity than teenagers in no-intervention census tracts.ConclusionThe greatest concentration of Supplemental Nutrition Assistance Program-Education interventions was associated with adults and children eating more fruits and vegetables and adults eating fast food less frequently. These findings demonstrate the potential impact of such interventions as implemented by numerous organizations with diverse populations; these interventions can play an important role in addressing the obesity epidemic in the United States. Limitations of this study include the absence of measures of exposure to the intervention at the individual level and low statistical power for the teenager sample

Recurrent sublethal warming reduces embryonic survival, inhibits juvenile growth, and alters species distribution projections under climate change

The capacity to tolerate climate change often varies across ontogeny in organisms with complex life cycles. Recently developed species distribution models incorporate traits across life stages; however, these life-cycle models primarily evaluate effects of lethal change. Here, we examine impacts of recurrent sublethal warming on development and survival in ecological projections of climate change. We reared lizard embryos in the laboratory under temperature cycles that simulated contemporary conditions and warming scenarios. We also artificially warmed natural nests to mimic laboratory treatments. In both cases, recurrent sublethal warming decreased embryonic survival and hatchling sizes. Incorporating survivorship results into a mechanistic species distribution model reduced annual survival by up to 24% compared to models that did not incorporate sublethal warming. Contrary to models without sublethal effects, our model suggests that modest increases in developmental temperatures influence species ranges due to effects on survivorship

Two Photon Absorption in Chromophore Doped Solid Matrices

Over the past decades organic materials have shown an important potential for applications in the field of nonlinear optics. Two-photon absorbing materials can be optically addressed in three dimensions of space, which make them unique for many new applications, including 3D displays, optical memories, bio-sensors, etc. Fluorescent organic chromophores can be synthesized with structures especially optimized for this nonlinear optical property. Yet, for some applications, they have to be incorporated in solid state matrices. We especially investigate hybrid organic/inorganic doped matrices synthesized by solgel process. However , the linear transmission for such molecules is often significantly less than unity. Two-photon absorption (TPA) offers the advantage of very high transmission at low incident intensity, while being sensitive to high intensity laser pulses. Our aim is to record a 3D layered pattern of optical memory inside the sample by the use of the picosecond pulsed ND3+:YAG laser at 532nm, or 1064nm

ATRX promotes gene expression by facilitating transcriptional elongation through guanine-rich coding regions

ATRX is a chromatin remodeling protein involved in deposition of the histone variant H3.3 at telomeres and pericentromeric heterochromatin. It also influences the expression level of specific genes; however, deposition of H3.3 at transcribed genes is currently thought to occur independently of ATRX. We focused on a set of genes, including the autism susceptibility gene Neuroligin 4 (Nlgn4), that exhibit decreased expression in ATRX-null cells to investigate the mechanisms used by ATRX to promote gene transcription. Overall TERRA levels, as well as DNA methylation and histone modifications at ATRX target genes are not altered and thus cannot explain transcriptional dysregulation.We found thatATRX does not associate with the promoter of these genes, but rather binds within regions of the gene body corresponding to high H3.3 occupancy. These intragenic regions consist of guanine-rich DNA sequences predicted to form non-B DNA structures called G-quadruplexes during transcriptional elongation.We demonstrate thatATRX deficiency corresponds to reduced H3.3 incorporation and stalling ofRNApolymerase II at these G-rich intragenic sites. These findings suggest that ATRX promotes the incorporation of histone H3.3 at particular transcribed genes and facilitates transcriptional elongation through G-rich sequences. The inability to transcribe genes such as Nlgn4 could cause deficits in neuronal connectivity and cognition associated with ATRX mutations in humans

A mouse model of autism implicates endosome pH in the regulation of presynaptic calcium entry.

Psychoactive compounds such as chloroquine and amphetamine act by dissipating the pH gradient across intracellular membranes, but the physiological mechanisms that normally regulate organelle pH remain poorly understood. Interestingly, recent human genetic studies have implicated the endosomal Na+/H+ exchanger NHE9 in both autism spectrum disorders (ASD) and attention deficit hyperactivity disorder (ADHD). Plasma membrane NHEs regulate cytosolic pH, but the role of intracellular isoforms has remained unclear. We now find that inactivation of NHE9 in mice reproduces behavioral features of ASD including impaired social interaction, repetitive behaviors, and altered sensory processing. Physiological characterization reveals hyperacidic endosomes, a cell-autonomous defect in glutamate receptor expression and impaired neurotransmitter release due to a defect in presynaptic Ca2+ entry. Acute inhibition of synaptic vesicle acidification rescues release but without affecting the primary defect due to loss of NHE9