The pluripotency factor Nanog regulates pericentromeric heterochromatin organization in mouse embryonic stem cells.

An open and decondensed chromatin organization is a defining property of pluripotency. Several epigenetic regulators have been implicated in maintaining an open chromatin organization, but how these processes are connected to the pluripotency network is unknown. Here, we identified a new role for the transcription factor NANOG as a key regulator connecting the pluripotency network with constitutive heterochromatin organization in mouse embryonic stem cells. Deletion of Nanog leads to chromatin compaction and the remodeling of heterochromatin domains. Forced expression of NANOG in epiblast stem cells is sufficient to decompact chromatin. NANOG associates with satellite repeats within heterochromatin domains, contributing to an architecture characterized by highly dispersed chromatin fibers, low levels of H3K9me3, and high major satellite transcription, and the strong transactivation domain of NANOG is required for this organization. The heterochromatin-associated protein SALL1 is a direct cofactor for NANOG, and loss of Sall1 recapitulates the Nanog-null phenotype, but the loss of Sall1 can be circumvented through direct recruitment of the NANOG transactivation domain to major satellites. These results establish a direct connection between the pluripotency network and chromatin organization and emphasize that maintaining an open heterochromatin architecture is a highly regulated process in embryonic stem cells.We thank Ludovic Vallier for constitutive Nanog-EpiSC, Gabrielle Brons for 129S2 EpiSC, Prim Singh for H3K9me3 antibody, Maria Elena Torres Padilla for TALE-mClover and luciferase plasmids, Wellcome Trust Sanger Institute for pCyL43 plasmid and Andras Nagy for PB-TET and rtTA plasmids. We are grateful to David Oxley and Judith Webster Novo et al. for mass spectrometry support, Simon Walker for imaging support and Anne Segonds- Pichon for statistical advice. We thank Wolf Reik and Jon Houseley for comments on the manuscript and members of Wolf Reik’s group for helpful discussions. P.J.R.-G. is supported by the Wellcome Trust [WT093736], BBSRC [M022285] and the European Commission Network of Excellence EpiGeneSys [HEALTH-F4-2010-257082]. The work was also supported with funds from the Canadian Institutes of Health Research to J.E. [Team Grant EPS-129129] and D.P.B.-J. D.P.B-J. holds the Canada Research Chair in Molecular and Cellular Imaging. I.C. is supported by the MRC

The Impact of Medical Interpretation Method on Time and Errors

Background: Twenty-two million Americans have limited English proficiency. Interpreting for limited English proficient patients is intended to enhance communication and delivery of quality medical care. Objective: Little is known about the impact of various interpreting methods on interpreting speed and errors. This investigation addresses this important gap. Design: Four scripted clinical encounters were used to enable the comparison of equivalent clinical content. These scripts were run across four interpreting methods, including remote simultaneous, remote consecutive, proximate consecutive, and proximate ad hoc interpreting. The first 3 methods utilized professional, trained interpreters, whereas the ad hoc method utilized untrained staff. Measurements: Audiotaped transcripts of the encounters were coded, using a prespecified algorithm to determine medical error and linguistic error, by coders blinded to the interpreting method. Encounters were also timed. Results: Remote simultaneous medical interpreting (RSMI) encounters averaged 12.72 vs 18.24 minutes for the next fastest mode (proximate ad hoc) (p = 0.002). There were 12 times more medical errors of moderate or greater clinical significance among utterances in non-RSMI encounters compared to RSMI encounters (p = 0.0002). Conclusions: Whereas limited by the small number of interpreters involved, our study found that RSMI resulted in fewer medical errors and was faster than non-RSMI methods of interpreting

Providing High-Quality Care for Limited English Proficient Patients: The Importance of Language Concordance and Interpreter Use

Background: Provider–patient language discordance is related to worse quality care for limited English proficient (LEP) patients who speak Spanish. However, little is known about language barriers among LEP Asian-American patients. Objective: We examined the effects of language discordance on the degree of health education and the quality of interpersonal care that patients received, and examined its effect on patient satisfaction. We also evaluated how the presence/absence of a clinic interpreter affected these outcomes. Design: Cross-sectional survey, response rate 74%. Participants: A total of 2,746 Chinese and Vietnamese patients receiving care at 11 health centers in 8 cities. Measurements: Provider–patient language concordance, health education received, quality of interpersonal care, patient ratings of providers, and the presence/absence of a clinic interpreter. Regression analyses were used to adjust for potential confounding. Results: Patients with language-discordant providers reported receiving less health education (β = 0.17, p < 0.05) compared to those with language-concordant providers. This effect was mitigated with the use of a clinic interpreter. Patients with language-discordant providers also reported worse interpersonal care (β = 0.28, p < 0.05), and were more likely to give low ratings to their providers (odds ratio [OR] = 1.61; CI = 0.97–2.67). Using a clinic interpreter did not mitigate these effects and in fact exacerbated disparities in patients’ perceptions of their providers. Conclusion: Language barriers are associated with less health education, worse interpersonal care, and lower patient satisfaction. Having access to a clinic interpreter can facilitate the transmission of health education. However, in terms of patients’ ratings of their providers and the quality of interpersonal care, having an interpreter present does not serve as a substitute for language concordance between patient and provider

Global Analysis of Extracytoplasmic Stress Signaling in Escherichia coli

The Bae, Cpx, Psp, Rcs, and σE pathways constitute the Escherichia coli signaling systems that detect and respond to alterations of the bacterial envelope. Contributions of these systems to stress response have previously been examined individually; however, the possible interconnections between these pathways are unknown. Here we investigate the dynamics between the five stress response pathways by determining the specificities of each system with respect to signal-inducing conditions, and monitoring global transcriptional changes in response to transient overexpression of each of the effectors. Our studies show that different extracytoplasmic stress conditions elicit a combined response of these pathways. Involvement of the five pathways in the various tested stress conditions is explained by our unexpected finding that transcriptional responses induced by the individual systems show little overlap. The extracytoplasmic stress signaling pathways in E. coli thus regulate mainly complementary functions whose discrete contributions are integrated to mount the full adaptive response

Data from: Phylogeographic and population genetic analyses reveal Pleistocene isolation followed by high gene flow in a wide- ranging, but endangered, freshwater mussel

Freshwater organisms of North America have had their contemporary genetic structure shaped by vicariant events, especially Pleistocene glaciations. Life history traits promoting dispersal and gene flow continue to shape population genetic structure. Cumberlandia monodonta, a widespread but imperiled (IUCN listed as endangered) freshwater mussel, was examined to determine genetic diversity and population genetic structure range-wide. MtDNA sequences and microsatellite loci were used to measure genetic diversity and simulate demographic events during the Pleistocene using approximate Bayesian computation (ABC) to test explicit hypotheses explaining the evolutionary history of current populations. A phylogeny and molecular clock suggested past isolation created two mtDNA lineages during the Pleistocene that are now widespread. Two distinct groups were also detected with microsatellites. ABC simulations indicated the presence of two glacial refugia and post-glacial admixture of them followed by simultaneous dispersal throughout the current range of the species. The Ouachita population is distinct from others and has the lowest genetic diversity, indicating that this is a peripheral population of the species. Gene flow within this species has maintained high levels of genetic diversity in northern populations, however, all population have experienced fragmentation. Extirpation from the center of its range likely has isolated remaining populations due to the geographic distances among them

Origin of Spanish invasion by the zebra mussel, Dreissena polymorpha (Pallas, 1771) revealed by amplified fragment length polymorphism (AFLP) fingerprinting.

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