A Novel Gonadotropin-Releasing Hormone 1 (Gnrh1) Enhancer-Derived Noncoding RNA Regulates Gnrh1 Gene Expression in GnRH Neuronal Cell Models.

Gonadotropin-releasing hormone (GnRH), a neuropeptide released from a small population of neurons in the hypothalamus, is the central mediator of the hypothalamic-pituitary-gonadal axis, and is required for normal reproductive development and function. Evolutionarily conserved regulatory elements in the mouse, rat, and human Gnrh1 gene include three enhancers and the proximal promoter, which confer Gnrh1 gene expression specifically in GnRH neurons. In immortalized mouse hypothalamic GnRH (GT1-7) neurons, which show pulsatile GnRH release in culture, RNA sequencing and RT-qPCR revealed that expression of a novel long noncoding RNA at Gnrh1 enhancer 1 correlates with high levels of GnRH mRNA expression. In GT1-7 neurons, which contain a transgene carrying 3 kb of the rat Gnrh1 regulatory region, both the mouse and rat Gnrh1 enhancer-derived noncoding RNAs (GnRH-E1 RNAs) are expressed. We investigated the characteristics and function of the endogenous mouse GnRH-E1 RNA. Strand-specific RT-PCR analysis of GnRH-E1 RNA in GT1-7 cells revealed GnRH-E1 RNAs that are transcribed in the sense and antisense directions from distinct 5' start sites, are 3' polyadenylated, and are over 2 kb in length. These RNAs are localized in the nucleus and have a half-life of over 8 hours. In GT1-7 neurons, siRNA knockdown of mouse GnRH-E1 RNA resulted in a significant decrease in the expression of the Gnrh1 primary transcript and Gnrh1 mRNA. Over-expression of either the sense or antisense mouse GnRH-E1 RNA in immature, migratory GnRH (GN11) neurons, which do not express either GnRH-E1 RNA or GnRH mRNA, induced the transcriptional activity of co-transfected rat Gnrh1 gene regulatory elements, where the induction requires the presence of the rat Gnrh1 promoter. Together, these data indicate that GnRH-E1 RNA is an inducer of Gnrh1 gene expression. GnRH-E1 RNA may play an important role in the development and maturation of GnRH neurons

Neuronal SIRT1 Regulates Metabolic and Reproductive Function and the Response to Caloric Restriction.

Sirt1 is an NAD-dependent, class III deacetylase that functions as a cellular energy sensor. In addition to its well-characterized effects in peripheral tissues, emerging evidence suggests that neuronal Sirt1 activity plays a role in the central regulation of energy balance and glucose metabolism. In this study, we generated mice expressing an enzymatically inactive form (N-MUT) or wild-type (WT) SIRT1 (N-OX) in mature neurons. N-OX male and female mice had impaired glucose tolerance, and N-MUT female, but not male, mice had improved glucose tolerance compared with that of WT littermates. Furthermore, glucose tolerance was improved in all mice with caloric restriction (CR) but was greater in the N-OX mice, who had better glucose tolerance than their littermates. At the reproductive level, N-OX females had impaired estrous cycles, with increased cycle length and more time in estrus. LH and progesterone surges were absent on the evening of proestrus in the N-OX mice, suggesting a defect in spontaneous ovulation, which was confirmed by the ovarian histology revealing fewer corpora lutea. Despite this defect, the mice were still fertile when mated to WT mice on the day of proestrus, indicating that the mice could respond to normal pheromonal or environmental cues. When subjected to CR, the N-OX mice went into diestrus arrest earlier than their littermates. Together, these results suggested that the overexpression of SIRT1 rendered the mice more sensitive to the metabolic improvements and suppression of reproductive cycles by CR, which was independent of circadian rhythms

Assembly of splicing complexes on exon 11 of the human insulin receptor gene does not correlate with splicing efficiency in-vitro

BACKGROUND: Incorporation of exon 11 of the insulin receptor gene is both developmentally and hormonally-regulated. Previously, we have shown the presence of enhancer and silencer elements that modulate the incorporation of the small 36-nucleotide exon. In this study, we investigated the role of inherent splice site strength in the alternative splicing decision and whether recognition of the splice sites is the major determinant of exon incorporation. RESULTS: We found that mutation of the flanking sub-optimal splice sites to consensus sequences caused the exon to be constitutively spliced in-vivo. These findings are consistent with the exon-definition model for splicing. In-vitro splicing of RNA templates containing exon 11 and portions of the upstream intron recapitulated the regulation seen in-vivo. Unexpectedly, we found that the splice sites are occupied and spliceosomal complex A was assembled on all templates in-vitro irrespective of splicing efficiency. CONCLUSION: These findings demonstrate that the exon-definition model explains alternative splicing of exon 11 in the IR gene in-vivo but not in-vitro. The in-vitro results suggest that the regulation occurs at a later step in spliceosome assembly on this exon

Letter to Andrew Inglis Clark, Tasmania from Walter T. Gill, Melbourne 16 June 1884

Discussion by Gill about a case Clark was handling and the help that Gill was able to provide. Mrs Webster is fast becoming friends with Gill's sister and they are 'going in strong' on the Women's Suffrage question. Gill hopes to get a Bill introduced before parliament soon, dealing with the admission question, and if it doesn't happen he will look at South Australia next. C4/C15

Letters to Andrew Inglis Clark, Tasmania from Walter Gill, Melbourne dated June 16 1884

Glad that the case he referred Clark to is likely to be of assistance in his brother's action. Have found a copy of the contract used in that case and will post forthwith. Mrs Webster fast friends with my sister and are going in strong on the 'Womens Suffrage' question. Witton and I are together every Saturday together where we take long walks. C4/C15

Scheduling science on television: A comparative analysis of the representations of science in 11 European countries

While science-in-the-media is a useful vehicle for understanding the media, few scholars have used it that way: instead, they look at science-in-the-media as a way of understanding science-in-the-media and often end up attributing characteristics to science-in-the-media that are simply characteristics of the media, rather than of the science they see there. This point of view was argued by Jane Gregory and Steve Miller in 1998 in Science in Public. Science, they concluded, is not a special case in the mass media, understanding science-in-the-media is mostly about understanding the media (Gregory and Miller, 1998: 105). More than a decade later, research that looks for patterns or even determinants of science-in-the-media, be it in press or electronic media, is still very rare. There is interest in explaining the media’s selection of science content from a media perspective. Instead, the search for, and analysis of, several kinds of distortions in media representations of science have been leading topics of science-in-the-media research since its beginning in the USA at the end of the 1960s and remain influential today (see Lewenstein, 1994; Weigold, 2001; Kohring, 2005 for summaries). Only a relatively small amount of research has been conducted seeking to identify factors relevant to understanding how science is treated by the mass media in general and by television in particular. The current study addresses the lack of research in this area. Our research seeks to explore which constraints national media systems place on the volume and structure of science programming in television. In simpler terms, the main question this study is trying to address is why science-in-TV in Europe appears as it does. We seek to link research focussing on the detailed analysis of science representations on television (Silverstone, 1984; Collins, 1987; Hornig, 1990; Leon, 2008), and media research focussing on the historical genesis and current political regulation of national media systems (see for instance Hallin and Mancini, 2004; Napoli, 2004; Open Society Institute, 2005, 2008). The former studies provide deeper insights into the selection and reconstruction of scientific subject matters, which reflect and – at the same time – reinforce popular images of science. But their studies do not give much attention to production constraints or other relevant factors which could provide an insight into why media treat science as they do. The latter scholars inter alia shed light on distinct media policies in Europe which significantly influence national channel patterns. However, they do not refer to clearly defined content categories but to fairly rough distinctions such as information versus entertainment or fictional versus factual. Accordingly, we know more about historical roots and current practices of media regulation across Europe than we do about the effects of these different regimes on the provision of specific content in European societies

Association between Residences in U.S. Northern Latitudes and Rheumatoid Arthritis: A Spatial Analysis of the Nurses’ Health Study

Background: The etiology of rheumatoid arthritis (RA) remains largely unknown, although epidemiologic studies suggest genetic and environmental factors may play a role. Geographic variation in incident RA has been observed at the regional level. Objective: Spatial analyses are a useful tool for confirming existing exposure hypotheses or generating new ones. To further explore the association between location and RA risk, we analyzed individual-level data from U.S. women in the Nurses’ Health Study, a nationwide cohort study. Methods: Participants included 461 incident RA cases and 9,220 controls with geocoded addresses; participants were followed from 1988 to 2002. We examined spatial variation using addresses at baseline in 1988 and at the time of case diagnosis or the censoring of controls. Generalized additive models (GAMs) were used to predict a continuous risk surface by smoothing on longitude and latitude while adjusting for known risk factors. Permutation tests were conducted to evaluate the overall importance of location and to identify, within the entire study area, those locations of statistically significant risk. Results: A statistically significant area of increased RA risk was identified in the northeast United States (p-value = 0.034). Risk was generally higher at northern latitudes, and it increased slightly when we used the nurses’ 1988 locations compared with those at the time of diagnosis or censoring. Crude and adjusted models produced similar results. Conclusions: Spatial analyses suggest women living in higher latitudes may be at greater risk for RA. Further, RA risk may be greater for locations that occur earlier in residential histories. These results illustrate the usefulness of GAM methods in generating hypotheses for future investigation and supporting existing hypotheses

Complex Odor from Plants under Attack: Herbivore's Enemies React to the Whole, Not Its Parts

Background: Insect herbivory induces plant odors that attract herbivores ’ natural enemies. Assuming this attraction emerges from individual compounds, genetic control over odor emission of crops may provide a rationale for manipulating the distribution of predators used for pest control. However, studies on odor perception in vertebrates and invertebrates suggest that olfactory information processing of mixtures results in odor percepts that are a synthetic whole and not a set of components that could function as recognizable individual attractants. Here, we ask if predators respond to herbivoreinduced attractants in odor mixtures or to odor mixture as a whole. Methodology/Principal Findings: We studied a system consisting of Lima bean, the herbivorous mite Tetranychus urticae and the predatory mite Phytoseiulus persimilis. We found that four herbivore-induced bean volatiles are not attractive in pure form while a fifth, methyl salicylate (MeSA), is. Several reduced mixtures deficient in one component compared to the full spider-mite induced blend were not attractive despite the presence of MeSA indicating that the predators cannot detect this component in these odor mixtures. A mixture of all five HIPV is most attractive, when offered together with the noninduced odor of Lima bean. Odors that elicit no response in their pure form were essential components of the attractive mixture. Conclusions/Significance: We conclude that the predatory mites perceive odors as a synthetic whole and that th