Inactive X chromosome-specific histone H3 modifications and CpG hypomethylation flank a chromatin boundary between an X-inactivated and an escape gene

In mammals, the dosage compensation of sex chromosomes between males and females is achieved by transcriptional inactivation of one of the two X chromosomes in females. However, a number of genes escape X-inactivation in humans. It remains poorly understood how the transcriptional activity of these ‘escape genes’ is maintained despite the chromosome-wide heterochromatin formation. To address this question, we analyzed a putative chromatin boundary between the inactivated RBM10 and an escape gene, UBA1/UBE1. Chromatin immunoprecipitation revealed that trimethylated histone H3 lysine 9 and H4 lysine 20 were enriched in the last exon through the proximal downstream region of RBM10, but were remarkably diminished at ∼2 kb upstream of the UBA1 transcription start site. Whereas RNA polymerase II was not loaded onto the intergenic region, CTCF (CCCTC binding factor) was enriched around the boundary, where some CpG sites were hypomethylated specifically on inactive X. These findings suggest that local DNA hypomethylation and CTCF binding are involved in the formation of a chromatin boundary, which protects the UBA1 escape gene against the chromosome-wide transcriptional silencing

Early Seizures Prematurely Unsilence Auditory Synapses to Disrupt Thalamocortical Critical Period Plasticity

Heightened neural excitability in infancy and childhood results in increased susceptibility to seizures. Such early-life seizures are associated with language deficits and autism that can result from aberrant development of the auditory cortex. Here, we show that early-life seizures disrupt a critical period (CP) for tonotopic map plasticity in primary auditory cortex (A1). We show that this CP is characterized by a prevalence of “silent,” NMDA-receptor (NMDAR)-only, glutamate receptor synapses in auditory cortex that become “unsilenced” due to activity-dependent AMPA receptor (AMPAR) insertion. Induction of seizures prior to this CP occludes tonotopic map plasticity by prematurely unsilencing NMDAR-only synapses. Further, brief treatment with the AMPAR antagonist NBQX following seizures, prior to the CP, pre

The local roots of the participation gap: Inequality and voter turnout

It is generally accepted that the rich are more likely to participate in politics than the poor. It is also generally accepted that the probability than an individual will participate in elections is influenced by the gap between the rich and the poor. There is little agreement, however, about whether inequality across time and space increases or decreases participation. In this paper we examine the impact of inequality across space. We suggest that the impact of inequality depends crucially on whether it is defined in terms of variations between geographical units (‘segregation’) or within geographical units (‘heterogeneity’). Evidence to support this argument is drawn from multi-level British data. Heterogeneity has a mildly positive effect on participation but this effect seems to be outweighed by the negative impact of segregation. The effect of segregation, moreover, is most pronounced among the poorer sections of the population, indicating that geographical isolation among the poor ('ghettoization') leads to lower turnout among these groups

Two families of non-LTR retrotransposons, Syrinx and Daphne, from the Darwinulid ostracod, Darwinula stevensoni

Author Posting. © The Authors, 2005. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Gene 371 (2006): 296-307, doi:10.1016/j.gene.2005.12.007.Two novel families of non-LTR retrotransposons, named Syrinx and Daphne, were cloned and characterized in a putative ancient asexual ostracod Darwinula stevensoni. Phylogenetic analysis reveals that Daphne is the founding member of a novel clade of non-LTR retroelements, which also contains newly described families from the sea urchin and the silkworm and forms a sister clade to L2-like elements. The Syrinx family of non-LTR retrotransposons exhibits evidence of relatively recent activity, manifested in high levels of sequence similarity between individual copies and a three- to ten-fold excess of synonymous substitutions, which is indicative of purifying selection. The Daphne family may have very few copies with intact open reading frames, and exhibits neutral within-family ratio of non-synonymous to synonymous substitutions. It can additionally be characterized by formation of inverted truncated head-to-head structures. All of these features make recent activity less likely than in the Syrinx family. Our results are discussed in light of the evolutionary consequences of long-term asexuality in general and in Darwinula stevensoni in particular.I.S. acknowledges funding from the EC (Marie-Curie grant BIO-4-CT-98-5086) and the Belgian OSTC (MO/36/005), and I.A. would like to thank the U.S. National Science Foundation

Perceptions About Work/Life Balance Among DU Community Members with Young Children

Background: In the past fifty years, families in the USA have changed in configuration, size and dynamics. The percentage of families that do not conform to the traditional family unit (married mother and father with children) has increased as there are more single-parent families, LGBTQ families and interracial families. The proportion of unmarried or divorced families has also increased, as it has the number of married and unmarried couples that opt to not have children and, additionally, more couples are opting for adoption and foster parenting (Pew Research Center 2010). Furthermore, the percentage of households where all the adults work has increased, which impacts the amount and quality of time available for family activities and household chores (Bianchi, Robinson and Milkie 2006). These and other trends have led to the identification of “work-family balance” as an important challenge of our times, one that families have been facing for decades and that institutions are only starting to pay attention to (Hochschild 2013). Although there are many aspects of family life that are challenging to balance with workplace demands, childcare has been specifically identified as one that needs attention (Desilver 2014). Methods: Study goal: To describe the perceptions that some DU community members with children have about work-family balance with attention to challenges, difficulties and institutional responses. Study design: Descriptive, cross-sectional, qualitative study. Population and sample: We recruited 63 University of Denver students (13), staff (14) and faculty (36) who are responsible of parenting at least one child under 10 years of age. We used purposive sampling. which consists in actively finding individuals who meet the criteria. Data collection: Semi structured interviews (January 23-February 8, 2017), in person, audio recorded and transcribed within one week. Participants’ autonomy, confidentiality and anonymity were protected throughout the process. Data analysis: Thematic analysis, which consists in the systematic identification of themes in the interview transcripts, followed by their conceptual organization and hierarchization. Research team: sixty-six undergraduate students taking Cultural Anthropology (ANTH 2010) in winter 2017, four graduate teaching assistants and one course instructor. Findings: Student participants portrayed work/life balance as set of interconnected situations and relations that go from the deeply personal to the interpersonal, communal and institutional. Aiming at capturing such complexity, we organized our findings in four themes: work/life balance, family dynamics, personal challenges and support. Participants told us about their struggles when negotiating work and life responsibilities which often lead to feelings of guilt, which are mediated by their colleagues’ reactions, schedule flexibility, their job situation and the presence or absence of maternity leave. Family dynamics reflected a tension between a narrative of independence and one of dependence in raising children, highlighting the importance of social networks, both of which are also affected by immigration status and intra-household negotiations particularly, Perceptions about work/life balance among DU community members with young children Cultural Anthropology (ANTH 2010) winter 2017 4 with their partners. Personal challenges relate primarily with time management and establishing clear boundaries between work and family, which related to managing emails, organization and scheduling of activities, maintaining a financial balance, and solving transportation needs, all of which were mediated the ability parents have of controlling a flexible work schedule, an ability greatly diminished among students. Support parents need related to child care goes from the one that happens in interpersonal interactions with neighbors, friends, relatives and colleagues, to the institutionalized forms of support, where participants expressed their frustration for the insufficiency of accessible options in Denver, the lack of options at DU, and the inaccessibility of DU’s Fisher Early Learning Center. Conclusions and recommendations: Participant’s ability to control their schedules together with their financial and social capital seem to shape important differences in the ability that parents have for balancing work and life. Students, single parents and recent immigrants seem to have a combination of elements that add to the challenges. At the interpersonal level, simple acts of kindness, sympathy and empathy in the everyday interactions seem to make an important difference to parents. The perception that many of the student participants expressed about the academy not being comfortable with children, families or parents could be addressed by making it normal to talk about all these aspects of life. At the institutional level, efforts could be made at reaching out to parents, especially students and single parents, to offer them guidance and support that is already in place at DU, such as counselling and wellbeing resources, as well as orientation related to institutional policies. Policies related to maternity and paternity leave should be refined to ensure that they do not negatively affect those they are supposed to support. Convenient, affordable and sustainable on-campus child care options should be seriously considered given that they would enhance the possibilities for parents to participate in activities at DU. Events should be organized where members of the DU community have the opportunity to share not as students, staff or faculty, but as members of families

Proteomic Analysis of Pathways Involved in Estrogen-Induced Growth and Apoptosis of Breast Cancer Cells

Estrogen is a known growth promoter for estrogen receptor (ER)-positive breast cancer cells. Paradoxically, in breast cancer cells that have been chronically deprived of estrogen stimulation, re-introduction of the hormone can induce apoptosis.Here, we sought to identify signaling networks that are triggered by estradiol (E2) in isogenic MCF-7 breast cancer cells that undergo apoptosis (MCF-7:5C) versus cells that proliferate upon exposure to E2 (MCF-7). The nuclear receptor co-activator AIB1 (Amplified in Breast Cancer-1) is known to be rate-limiting for E2-induced cell survival responses in MCF-7 cells and was found here to also be required for the induction of apoptosis by E2 in the MCF-7:5C cells. Proteins that interact with AIB1 as well as complexes that contain tyrosine phosphorylated proteins were isolated by immunoprecipitation and identified by mass spectrometry (MS) at baseline and after a brief exposure to E2 for two hours. Bioinformatic network analyses of the identified protein interactions were then used to analyze E2 signaling pathways that trigger apoptosis versus survival. Comparison of MS data with a computationally-predicted AIB1 interaction network showed that 26 proteins identified in this study are within this network, and are involved in signal transduction, transcription, cell cycle regulation and protein degradation.G-protein-coupled receptors, PI3 kinase, Wnt and Notch signaling pathways were most strongly associated with E2-induced proliferation or apoptosis and are integrated here into a global AIB1 signaling network that controls qualitatively distinct responses to estrogen

20-Year Risks of Breast-Cancer Recurrence after Stopping Endocrine Therapy at 5 Years

The administration of endocrine therapy for 5 years substantially reduces recurrence rates during and after treatment in women with early-stage, estrogen-receptor (ER)-positive breast cancer. Extending such therapy beyond 5 years offers further protection but has additional side effects. Obtaining data on the absolute risk of subsequent distant recurrence if therapy stops at 5 years could help determine whether to extend treatment

A Neuron-Glial Perspective for Computational Neuroscience

International audienceThere is growing excitement around glial cells, as compelling evidence point to new, previously unimaginable roles for these cells in information processing of the brain, with the potential to affect behavior and higher cognitive functions. Among their many possible functions, glial cells could be involved in practically every aspect of the brain physiology in health and disease. As a result, many investigators in the field welcome the notion of a Neuron-Glial paradigm of brain function, as opposed to Ramon y Cayal's more classical neuronal doctrine which identifies neurons as the prominent, if not the only, cells capable of a signaling role in the brain. The demonstration of a brain-wide Neuron-Glial paradigm however remains elusive and so does the notion of what neuron-glial interactions could be functionally relevant for the brain computational tasks. In this perspective, we present a selection of arguments inspired by available experimental and modeling studies with the aim to provide a biophysical and conceptual platform to computational neuroscience no longer as a mere prerogative of neuronal signaling but rather as the outcome of a complex interaction between neurons and glial cells

Food, Nutrition and Agrobiodiversity Under Global Climate Change

Available evidence and predictions suggest overall negative effects on agricultural production as a result of climate change, especially when more food is required by a growing population. Information on the effects of global warming on pests and pathogens affecting agricultural crops is limited, though crop–pest models could offer means to predict changes in pest dynamics, and help design sound plant health management practices. Host-plant resistance should continue to receive high priority as global warming may favor emergence of new pest epidemics. There is increased risk, due to climate change, to food and feed contaminated by mycotoxin-producing fungi. Mycotoxin biosynthesis gene-specific microarray is being used to identify food-born fungi and associated mycotoxins, and investigate the influence of environmental parameters and their interactions for control of mycotoxin in food crops. Some crop wild relatives are threatened plant species and efforts should be made for their in situ conservation to ensure evolution of new variants, which may contribute to addressing new challenges to agricultural production. There should be more emphasis on germplasm enhancement to develop intermediate products with specific characteristics to support plant breeding. Abiotic stress response is routinely dissected to component physiological traits. Use of transgene(s) has led to the development of transgenic events, which could provide enhanced adaptation to abiotic stresses that are exacerbated by climate change. Global warming is also associated with declining nutritional quality of food crops. Micronutrient-dense cultivars have been released in selected areas of the developing world, while various nutritionally enhanced lines are in the release pipeline. The high-throughput phenomic platforms are allowing researchers to accurately measure plant growth and development, analyze nutritional traits, and assess response to stresses on large sets of individuals. Analogs for tomorrow’s agriculture offer a virtual natural laboratory to innovate and test technological options to develop climate resilience production systems. Increased use of agrobiodiversity is crucial to coping with adverse impacts of global warming on food and feed production and quality. No one solution will suffice to adapt to climate change and its variability. Suits of technological innovations, including climate-resilient crop cultivars, will be needed to feed 9 billion people who will be living in the Earth by the middle of the twenty-first century