Alien Registration- Elderkin, Katherine S. (Dexter, Penobscot County)

https://digitalmaine.com/alien_docs/11390/thumbnail.jp

Organization of the AAA(+) adaptor protein PspA is an oligomeric ring

The 25.3 kDa "adaptor" protein, PspA (dphage shock protein A), is found in the cytoplasm and in association with the inner membrane of certain bacteria. PspA plays critical roles in negatively regulating the phage shock response and maintaining membrane integrity, especially during the export of proteins such as virulence factors. Homologues of PspA function exist for thylakoid biogenesis. Here we report the first three-dimensional reconstruction of a PspA assembly from Escherichia coli, visualized by electron microscopy and single particle analysis to a resolution of 30 Angstrom. The assembly forms a 9-fold rotationally symmetric ring with an outer diameter of 200 Angstrom, an inner diameter of 95 Angstrom, and a height of similar to85 Angstrom. The molecular mass of the complex was calculated to be 1023 kDa by size exclusion chromatography, suggesting that each of the nine domains is likely to be composed of four PspA subunits. The functional implications of this PspA structure are discussed in terms of its interaction with the protein export machinery of the bacterial cell and its AAA(+) protein partner, PspF

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 genetic prehistory of southern Africa

Southern and eastern African populations that speak non-Bantu languages with click consonants are known to harbour some of the most ancient genetic lineages in humans, but their relationships are poorly understood. Here, we report data from 23 populations analyzed at over half a million single nucleotide polymorphisms, using a genome-wide array designed for studying human history. The southern African Khoisan fall into two genetic groups, loosely corresponding to the northwestern and southeastern Kalahari, which we show separated within the last 30,000 years. We find that all individuals derive at least a few percent of their genomes from admixture with non-Khoisan populations that began approximately 1,200 years ago. In addition, the east African Hadza and Sandawe derive a fraction of their ancestry from admixture with a population related to the Khoisan, supporting the hypothesis of an ancient link between southern and eastern AfricaComment: To appear in Nature Communication

The route to transcription initiation determines the mode of transcriptional bursting in E. coli

Transcription is fundamentally noisy, leading to significant heterogeneity across bacterial populations. Noise is often attributed to burstiness, but the underlying mechanisms and their dependence on the mode of promotor regulation remain unclear. Here, we measure E. coli single cell mRNA levels for two stress responses that depend on bacterial sigma factors with different mode of transcription initiation (σ70 and σ54). By fitting a stochastic model to the observed mRNA distributions, we show that the transition from low to high expression of the σ70-controlled stress response is regulated via the burst size, while that of the σ54-controlled stress response is regulated via the burst frequency. Therefore, transcription initiation involving σ54 differs from other bacterial systems, and yields bursting kinetics characteristic of eukaryotic systems

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

Dissipation of Proton Motive Force is not Sufficient to Induce the Phage Shock Protein Response in Escherichia coli

Phage shock proteins (Psp) and their homologues are found in species from the three domains of life: Bacteria, Archaea and Eukarya (e.g. higher plants). In enterobacteria, the Psp response helps to maintain the proton motive force (PMF) of the cell when the inner membrane integrity is impaired. The presumed ability of ArcB to sense redox changes in the cellular quinone pool and the strong decrease of psp induction in ΔubiG or ΔarcAB backgrounds suggest a link between the Psp response and the quinone pool. The authors now provide evidence indicating that the physiological signal for inducing psp by secretin-induced stress is neither the quinone redox state nor a drop in PMF. Neither the loss of the H+-gradient nor the dissipation of the electrical potential alone is sufficient to induce the Psp response. A set of electron transport mutants differing in their redox states due to the lack of a NADH dehydrogenase and a quinol oxidase, but retaining a normal PMF displayed low levels of psp induction inversely related to oxidised ubiquinone levels under microaerobic growth and independent of PMF. In contrast, cells displaying higher secretin induced psp expression showed increased levels of ubiquinone. Taken together, this study suggests that not a single but likely multiple signals are needed to be integrated to induce the Psp response

Overcoming language barriers with foreign-language speaking patients: a survey to investigate intra-hospital variation in attitudes and practices

Background Use of available interpreter services by hospital clincial staff is often suboptimal, despite evidence that trained interpreters contribute to quality of care and patient safety. Examination of intra-hospital variations in attitudes and practices regarding interpreter use can contribute to identifying factors that facilitate good practice. The purpose of this study was to describe attitudes, practices and preferences regarding communication with limited French proficiency (LFP) patients, examine how these vary across professions and departments within the hospital, and identify factors associated with good practices. Methods A self-administered questionnaire was mailed to random samples of 700 doctors, 700 nurses and 93 social workers at the Geneva University Hospitals, Switzerland. Results Seventy percent of respondents encounter LFP patients at least once a month, but this varied by department. 66% of respondents said they preferred working with ad hoc interpreters (patient's family and bilingual staff), mainly because these were easier to access. During the 6 months preceding the study, ad hoc interpreters were used at least once by 71% of respondents, and professional interpreters were used at least once by 51%. Overall, only nine percent of respondents had received any training in how and why to work with a trained interpreter. Only 23.2% of respondents said the clinical service in which they currently worked encouraged them to use professional interpreters. Respondents working in services where use of professional interpreters was encouraged were more likely to be of the opinion that the hospital should systematically provide a professional interpreter to LFP patients (40.3%) as compared with those working in a department that discouraged use of professional interpreters (15.5%) and they used professional interpreters more often during the previous 6 months. Conclusion Attitudes and practices regarding communication with LFP patients vary across professions and hospital departments. In order to foster an institution-wide culture conducive to ensuring adequate communication with LFP patients will require both the development of a hospital-wide policy and service-level activities aimed at reinforcing this policy and putting it into practice

Regulation of the co-evolved HrpR and HrpS AAA+ proteins required for Pseudomonas syringae pathogenicity.

Published versio