Active Chromatin Marks Are Retained on X Chromosomes Lacking Gene or Repeat Silencing Despite XIST/Xist Expression in Somatic Cell Hybrids

X-chromosome inactivation occurs early in mammalian development and results in the inactive X chromosome acquiring numerous hallmarks of heterochromatin. While XIST is a key player in the inactivation process, the method of action of this ncRNA is yet to be determined.To assess which features of heterochromatin may be directly recruited by the expression and localization of the XIST RNA we have analyzed a mouse/human somatic cell hybrid in which expression of human and mouse XIST/Xist has been induced from the active X by demethylation. Such hybrids had previously been demonstrated to disconnect XIST/Xist expression from gene silencing and we confirm maintenance of X-linked gene expression, even close to the Xist locus, despite the localized expression of mouse Xist.Loss of the active chromatin marks H3 acetylation and H3 lysine 4 methylation was not observed upon XIST/Xist expression, nor was there a gain of DNA methylation; thus these marks of facultative heterochromatin are not solely dependent upon Xist expression. Cot-1 holes, regions of depleted RNA hybridization with a Cot-1 probe, were observed upon Xist expression; however, these were at reduced frequency and intensity in these somatic cells. Domains of human Cot-1 transcription were observed corresponding to the human chromosomes in the somatic cell hybrids. The Cot-1 domain of the X was not reduced with the expression of XIST, which fails to localize to the human X chromosome in a mouse somatic cell background. The human inactive X in a mouse/human hybrid cell also shows delocalized XIST expression and an ongoing Cot-1 domain, despite X-linked gene silencing. These results are consistent with recent reports separating Cot-1 silencing from genic silencing, but also demonstrate repetitive element expression from an otherwise silent X chromosome in these hybrid cells

Evidence for a Novel Marine Harmful Algal Bloom: Cyanotoxin (Microcystin) Transfer from Land to Sea Otters

“Super-blooms” of cyanobacteria that produce potent and environmentally persistent biotoxins (microcystins) are an emerging global health issue in freshwater habitats. Monitoring of the marine environment for secondary impacts has been minimal, although microcystin-contaminated freshwater is known to be entering marine ecosystems. Here we confirm deaths of marine mammals from microcystin intoxication and provide evidence implicating land-sea flow with trophic transfer through marine invertebrates as the most likely route of exposure. This hypothesis was evaluated through environmental detection of potential freshwater and marine microcystin sources, sea otter necropsy with biochemical analysis of tissues and evaluation of bioaccumulation of freshwater microcystins by marine invertebrates. Ocean discharge of freshwater microcystins was confirmed for three nutrient-impaired rivers flowing into the Monterey Bay National Marine Sanctuary, and microcystin concentrations up to 2,900 ppm (2.9 million ppb) were detected in a freshwater lake and downstream tributaries to within 1 km of the ocean. Deaths of 21 southern sea otters, a federally listed threatened species, were linked to microcystin intoxication. Finally, farmed and free-living marine clams, mussels and oysters of species that are often consumed by sea otters and humans exhibited significant biomagnification (to 107 times ambient water levels) and slow depuration of freshwater cyanotoxins, suggesting a potentially serious environmental and public health threat that extends from the lowest trophic levels of nutrient-impaired freshwater habitat to apex marine predators. Microcystin-poisoned sea otters were commonly recovered near river mouths and harbors and contaminated marine bivalves were implicated as the most likely source of this potent hepatotoxin for wild otters. This is the first report of deaths of marine mammals due to cyanotoxins and confirms the existence of a novel class of marine “harmful algal bloom” in the Pacific coastal environment; that of hepatotoxic shellfish poisoning (HSP), suggesting that animals and humans are at risk from microcystin poisoning when consuming shellfish harvested at the land-sea interface

Evolutionary diversity and developmental regulation of X-chromosome inactivation

X-chromosome inactivation (XCI) results in the transcriptional silencing of one X-chromosome in females to attain gene dosage parity between XX female and XY male mammals. Mammals appear to have developed rather diverse strategies to initiate XCI in early development. In placental mammals XCI depends on the regulatory noncoding RNA X-inactive specific transcript (Xist), which is absent in marsupials and monotremes. Surprisingly, even placental mammals show differences in the initiation of XCI in terms of Xist regulation and the timing to acquire dosage compensation. Despite this, all placental mammals achieve chromosome-wide gene silencing at some point in development, and this is maintained by epigenetic marks such as chromatin modifications and DNA methylation. In this review, we will summarise recent findings concerning the events that occur downstream of Xist RNA coating of the inactive X-chromosome (Xi) to ensure its heterochromatinization and the maintenance of the inactive state in the mouse and highlight similarities and differences between mammals

Intimate partner violence against women and its related immigration stressors in Pakistani immigrant families in Germany

Zakar R, Zakria Zakar M, Faist T, Krämer A. Intimate partner violence against women and its related immigration stressors in Pakistani immigrant families in Germany. SpringerPlus. 2012;1(1): 5.This paper addresses the issue of intimate partner violence against women and its related immigration stressors in Pakistani immigrant families in Germany. Drawing on 32 in-depth interviews with Pakistani women in three cities in Germany, we found that psychological violence was the commonly reported violence among the study participants. The data showed that the process of immigration exacerbated tensions between spouses because of various immigration stressors such as threats to cultural identity, children’s socialization, and social isolation. In order to cope with the stressful spousal relations, women applied various indigenous strategies, but avoided seeking help from the host country’s formal care-providing institutions. This study also debunks some stereotypes and popular media clichés about the “victimhood of women from conservative developing countries” and provides an understanding of the issue of intimate partner violence within an immigration context. Further research with a larger sample will be helpful to understand immigration-induced stress and intimate partner violence in immigrant families

Pre-existing diabetes and breast cancer prognosis among elderly women.

BACKGROUND: The objective of this study was to assess the impact of pre-existing diabetes on breast cancer prognosis. METHODS: Women (n=2833) with centrally confirmed invasive breast cancer in the Women's Health Initiative, who were linked to Medicare claims data (CMS) were followed from the date of breast cancer diagnosis to date of death or 20 September 2013. Information on diabetes was identified through the CMS Chronic Condition Warehouse algorithm. Cox proportional hazard regression was used to estimate adjusted hazard ratios for overall mortality. A competing risks model (proportional subdistribution) model was used to estimate hazard ratios for breast cancer-specific mortality. RESULTS: Women with diabetes were more likely to have factors related to delayed diagnosis (less recent mammograms, and more advanced cancer stage) and were less likely to receive radiation therapy. Compared with women without diabetes, women with diabetes had significantly increased risk of overall mortality (HR=1.57, 95% CI: 1.23–2.01) and had nonsignificantly increased risk for breast cancer-specific mortality (HR=1.36, 95% CI: 0.86–2.15) before adjustment for factors related to delayed diagnosis and treatment. Adjustment for these factors resulted in a little change in the association of diabetes with overall mortality risk, but further attenuated the point estimate for breast cancer-specific mortality. CONCLUSIONS: Our study provides additional evidence that pre-existing diabetes increases the risk of total mortality among women with breast cancer. Very large studies with data on breast cancer risk factors, screening and diagnostic delays, treatment choices, and the biological influence of diabetes on breast cancer will be needed to determine whether diabetes also increases the risk for breast cancer-specific mortality