New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

In situ hybridization of oxytocin messenger RNA: Macroscopic distribution and quantitation in rat hypothalamic cell groups

Oxytocin mRNA was detected in the rat hypothalamus by in situ hybridization to a single stranded 35S-labelled DNA probe and the distribution of oxytocin mRNA-containing cell groups was studied at the macroscopic level. Specificity of hybridization was confirmed by comparison to vasopressin mRNA hybridization in parallel tissue sections. Cell groups containing oxytocin mRNA were confined to a set of hypothalamic cell groups, i.c. the supraoptic, paraventricular, anterior commissural nuclei, nucleus circularis and scattered hypothalamic islets. These cell groups displayed similar densities of autoradiographic signals indicating that the oxytocin gene is expressed at approximately the same average level at these various sites

Organization of vasotocin-immunoreactive cells and fibers in the canary brain

The distribution of vasotocin (VT)-immunoreactive neuronal perikarya and fibers in the canary (Serinus canaria) was investigated with immunohistological techniques. The results suggest that most VT-stained cell bodies are located in three diencephalic regions. First, a large number of densely packed neurons are found in the paraventricular nucleus (PVN) and the anterior preoptic nucleus. Neurons here vary widely in size and shape. Small-size rounded neurons and large-size multipolar neurons appear to concentrate in separate subdivisions. Second, a series of loosely organized cell groups of medium- to large-size cells occurs in the lateral parts of the hypothalamus. These aggregates of neurons apparently correspond to subdivisions of the supraoptic nucleus (SON). Third, diffusely distributed, lightly stained cells are found dorsal to the paraventricular nucleus in the dorsal diencephalon. A number of cells of this group seem to be located in the basal septal area and bed nucleus of the stria terminalis. Immunoreactive fibers and varicosities concentrate in brain regions that are associated with neuroendocrine, autonomic, and limbic functions. Axons from the PVN and SON form compact bundles of the hypothalamohypophysial tract in the lateral hypothalamus and then funnel into the internal zone of the medium eminence (ME). Furthermore, a heavy innervation seems to be present in the palisadal, external zone of the ME. A substantial number of fibers appear to leave the PVN toward extrahypothalamic areas. Most extrahypothalamic VT fibers innervate telencephalic and brainstem regions that are thought to be involved in mediation of limbic and autonomic functions. These areas include the lateral and medial septum, the lateral habenula, the substantia grisea centralis, the area ventralis (Tsai), the locus coeruleus, raphe nuclei, the nucleus tractus solitarii, and lateral medulla. In addition, fibers with immunoreactivity for VT innervate structures such as the optic tectum and the nucleus ovoidalis that have been implicated in sensory processing of visual and auditory information. Finally, VT fibers and varicosities occur in centers including the nucleus robustus archistriatalis and nucleus intercollicularis that have been implicated in vocal control

Genes Involved in Initial Follicle Recruitment May Be Associated with Age at Menopause

Context: Timing of menopause is largely influenced by genetic factors. Because menopause occurs when the follicle pool in the ovaries has become exhausted, genes involved in primordial follicle recruitment can be considered as candidate genes for timing of menopause. Objective: The aim was to study the association of 23 tagging single nucleotide polymorphisms in five genes [Anti-Mullerian hormone (AMH), AMH type II receptor (AMHR2), bone morphogenetic protein 15 (BMP15), forkhead transcription factor L2 (FOXL2), and growth differentiation factor-9 (GDF9)] involved in recruitment of the primary follicle pool, including the AMHR2 gene, which has recently been associated with age at menopause. Design: We conducted a cross-sectional association study. Setting and Participants: We studied a population-based sample of 3616 Dutch women with natural menopause. Main Outcome Measure: We measured age at natural menopause. Results: Both studied AMHR2 tagging single nucleotide polymorphisms (rs2002555 and rs11170547) in the AMHR2 gene were associated with age at natural menopause in interaction with parity. Parous rs2002555 G/G carriers had menopause 1 yr later compared with A/A carriers (P = 0.01). For rs11170547, each minor allele (T) was associated with a 0.41-yr later onset of menopause in parous women (P = 0.01). Additionally, rs6521896 in BMP15 was associated with later menopause (beta = 0.41; P = 0.007). Variants in the AMH, FOXL2, and GDF9 genes were not associated with timing of menopause. Conclusions: The present study confirms an earlier finding that variation in the AMHR2 gene modifies the relation between parity and age at natural menopause. In combination with the association of BMP15 with menopausal age, we find that there is evidence that genes involved in primary follicle recruitment influence timing of menopause. (J Clin Endocrinol Metab 96: E473-E479, 2011

“Say no to burqas”: geographies of nation and citizenship in Newtown

This thesis is concerned with the ways in which instances of everyday racism reproduce geographies of national belonging and exclusion in the city, focusing specifically on an activist campaign in Newtown, Australia, which called on the community to ‘Say no to burqas’. The focal point of this one-man campaign was a large, street facing mural, depicting a veiled woman, crossed out inside a red circle. The mural attracted much community opposition, and was defaced over sixty-four times. This thesis deconstructs the ways in which the mural campaign inscribed a particular national imaginary onto Newtown, constituted through the exclusion of the Muslim other; attending to the roots of this imaginary in racialised and gendered regimes of citizenship which privilege white, liberal civility. It goes on to show how the mural both reproduced, and was implicated in, the classed geographies of Australian multiculturalism, which figure the inner city as diverse and cosmopolitan, in opposition to the suburban as a site of ethnic criminality and multicultural failure. Finally, this thesis looks to various instances of organised opposition to the mural as examples of insurgent citizenship, capable of reimagining the relationship between place, nation and political community, in response to the ethical, political and practical task of living together in the multicultural city

Interactions between Genetic Variants in AMH and AMHR2 May Modify Age at Natural Menopause

The onset of menopause has important implications on women’s fertility and health. We previously identified genetic variants in genes involved in initial follicle recruitment as potential modifiers of age at natural menopause. The objective of this study was to extend our previous study, by searching for pairwise interactions between tagging single nucleotide polymorphisms (tSNPs) in the 5 genes previously selected (AMH, AMHR2, BMP15, FOXL2, GDF9). We performed a cross-sectional study among 3445 women with a natural menopause participating in the Prospect-EPIC study, a population-based prospective cohort study, initiated between 1993 and 1997. Based on the model-based multifactor dimensionality reduction (MB-MDR) test with a permutation-based maxT correction for multiple testing, we found a statistically significant interaction between rs10407022 in AMH and rs11170547 in AMHR2 (p = 0.019) associated with age at natural menopause. Rs10407022 did not have a statistically significant main effect. However, rs10407022 is an eQTL SNP that has been shown to influence mRNA expression levels in lymphoblastoid cell lines. This study provides additional insights into the genetic background of age at natural menopause and suggests a role of the AMH signaling pathway in the onset of natural menopause. However, these results remain suggestive and replication by independent studies is necessary