Cdc13 OB2 Dimerization Required for Productive Stn1 Binding and Efficient Telomere Maintenance

SummaryCdc13 is an essential yeast protein required for telomere length regulation and genome stability. It does so via its telomere-capping properties and by regulating telomerase access to the telomeres. The crystal structure of the Saccharomyces cerevisiae Cdc13 domain located between the recruitment and DNA binding domains reveals an oligonucleotide-oligosaccharide binding fold (OB2) with unusually long loops extending from the core of the protein. These loops are involved in extensive interactions between two Cdc13 OB2 folds leading to stable homodimerization. Interestingly, the functionally impaired cdc13-1 mutation inhibits OB2 dimerization. Biochemical assays indicate OB2 is not involved in telomeric DNA or Stn1 binding. However, disruption of the OB2 dimer in full-length Cdc13 affects Cdc13-Stn1 association, leading to telomere length deregulation, increased temperature sensitivity, and Stn1 binding defects. We therefore propose that dimerization of the OB2 domain of Cdc13 is required for proper Cdc13, Stn1, Ten1 (CST) assembly and productive telomere capping

Mucoactive agents for acute respiratory failure in the critically ill: a systematic review and meta-analysis

Purpose Acute respiratory failure (ARF) is a common cause of admission to intensive care units (ICUs). Mucoactive agents are medications that promote mucus clearance and are frequently administered in patients with ARF, despite a lack of evidence to underpin clinical decision making. The aim of this systematic review was to determine if the use of mucoactive agents in patients with ARF improves clinical outcomes. Methods We searched electronic and grey literature (January 2020). Two reviewers independently screened, selected, extracted data and quality assessed studies. We included trials of adults receiving ventilatory support for ARF and involving at least one mucoactive agent compared with placebo or standard care. Outcomes included duration of mechanical ventilation. Meta-analysis was undertaken using random-effects modelling and certainty of the evidence was assessed using Grades of Recommendation, Assessment, Development and Evaluation. Results Thirteen randomised controlled trials were included (1712 patients), investigating four different mucoactive agents. Mucoactive agents showed no effect on duration of mechanical ventilation (seven trials, mean difference (MD)-1.34, 95% CI-2.97 to 0.29, I 2 =82%, very low certainty) or mortality, hospital stay and ventilator-free days. There was an effect on reducing ICU length of stay in the mucoactive agent groups (10 trials, MD-3.22, 95% CI-5.49 to-0.96, I 2 =89%, very low certainty). Conclusion Our findings do not support the use of mucoactive agents in critically ill patients with ARF. The existing evidence is of low quality. High-quality randomised controlled trials are needed to determine the role of specific mucoactive agents in critically ill patients with ARF. PROSPERO registration number CRD42018095408

RAPID : research on automated plankton identification

Author Posting. © Oceanography Society, 2007. This article is posted here by permission of Oceanography Society for personal use, not for redistribution. The definitive version was published in Oceanography 20, 2 (2007): 172-187.When Victor Hensen deployed the first true plankton1 net in 1887, he and his colleagues were attempting to answer three fundamental questions: What planktonic organisms are present in the ocean? How many of each type are present? How does the plankton’s composition change over time? Although answering these questions has remained a central goal of oceanographers, the sophisticated tools available to enumerate planktonic organisms today offer capabilities that Hensen probably could never have imagined.This material is based upon work supported by the National Science Foundation under Grants OCE-0325018, OCE-0324937, OCE-0325167 and OCE-9423471, and the European Union under grants Q5CR-2002-71699, MAS3-ct98-0188, and MAS2-ct92-0015

Reliability of physical examination of the upper extremity among keyboard operators

Background Physical examination is a traditional outcome measure in epidemiological research. Its value as a reliable measure depends, in part, on the prevalence of positive findings. The purpose of this paper is to determine the empirical reliability of physical examination and anthropometry in a field study of upper extremity disorders among keyboard operators. Methods Two experienced examiners independently performed common provocative tests and procedures in physical examinations of the neck and upper extremity among 160 keyboard operators. Two additional examiners conducted anthropometric surveys among 137 workers. Inter-examiner reliability was assessed with observed agreement, kappa statistics, and intra-class correlations (ICC). Results Observed agreement was between 96% and 100% for neck and upper extremity signs, muscle stretch reflexes, and muscle strength, however, with the exception of provocative tests, reliability statistics were unstable. Among the provocative tests, Phalen and Tinel tests had modest agreement after adjusting for chance (Κ range: 0.20–0.43). The carpal compression test had the best reliability (Κ=0.60 and Κ=0.67, left and right side, respectively). The ICCs for anthropometry ranged from 0.36–0.91. Conclusions Results from the study showed that statistically, except for the carpal compression test, physical examination contributed minimal reliable information. This was attributed mainly to the low prevalence of positive findings, and generally mild nature of upper extremity disorders in this population. The results are the best estimate of what would be found in a field study with experienced examiners. While it may reduce bias, separating physical examination from medical history may contribute to the poor reliability of findings. With a shift toward reliable measures, resources can be allocated to more effective tools, like questionnaires, in epidemiological research of upper extremity disorders among keyboard operators. Am. J. Ind. Med. 37:423–430, 2000. © 2000 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34820/1/12_ftp.pd