DNA end resection by Dna2–Sgs1–RPA and its stimulation by Top3–Rmi1 and Mre11–Rad50–Xrs2

The repair of DNA double-strand breaks (DSBs) by homologous recombination requires processing of broken ends. For repair to start, the DSB must first be resected to generate a 3′-single-stranded DNA (ssDNA) overhang, which becomes a substrate for the DNA strand exchange protein, Rad51 (ref. 1). Genetic studies have implicated a multitude of proteins in the process, including helicases, nucleases and topoisomerases. Here we biochemically reconstitute elements of the resection process and reveal that it requires the nuclease Dna2, the RecQ-family helicase Sgs1 and the ssDNA-binding protein replication protein-A (RPA). We establish that Dna2, Sgs1 and RPA constitute a minimal protein complex capable of DNA resection in vitro. Sgs1 helicase unwinds the DNA to produce an intermediate that is digested by Dna2, and RPA stimulates DNA unwinding by Sgs1 in a species-specific manner. Interestingly, RPA is also required both to direct Dna2 nucleolytic activity to the 5′-terminated strand of the DNA break and to inhibit 3′ to 5′ degradation by Dna2, actions that generate and protect the 3′-ssDNA overhang, respectively. In addition to this core machinery, we establish that both the topoisomerase 3 (Top3) and Rmi1 complex and the Mre11–Rad50–Xrs2 complex (MRX) have important roles as stimulatory components. Stimulation of end resection by the Top3–Rmi1 heterodimer and the MRX proteins is by complex formation with Sgs1 (refs 5, 6), which unexpectedly stimulates DNA unwinding. We suggest that Top3–Rmi1 and MRX are important for recruitment of the Sgs1–Dna2 complex to DSBs. Our experiments provide a mechanistic framework for understanding the initial steps of recombinational DNA repair in eukaryotes

El Niño Modulations Over The Past Seven Centuries (Letter to the editor)

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Um grande surto de Legionella ausente do debate público

The Legionnaires’ disease outbreak that hit Portugal in November 2014 was the third largest worldwide and was declared a “great public health emergency”. Nonetheless, the Portuguese outbreak, despite killing 12 people and infecting 375 others did not promote extensive media coverage, nor did it make it into the political debate. We conducted a quantitative analysis of 83 news pieces on Legionella published in four national newspapers, and interviewed the journalists who covered this outbreak. The communication process was controlled by a small group of official sources and the outbreak was pushed away from news lineups due to two political scandals. The production of another news wave made the outbreak’s news wave to break prematurely.O surto de Legionella que atingiu Portugal em novembro de 2014 foi o terceiro maior em nível mundial, constituindo “uma grande emergência de saúde pública”. Ainda assim, o surto português não promoveu uma longa cobertura mediática, apesar das 12 mortes e 375 pessoas infetadas. Nem entrou no debate político. Fizemos uma análise quantitativa das 83 notícias sobre Legionella publicadas em quatro jornais nacionais, e conduzimos entrevistas com os jornalistas que cobriram este surto. O processo comunicativo foi controlado por um pequeno grupo de fontes oficiais, e o surto foi rapidamente afastado dos alinhamentos noticiosos, sendo substituído por dois escândalos políticos. A produção de outra onda noticiosa fez com que a onda noticiosa do surto de Legionella se quebrasse prematuramente.(undefined)info:eu-repo/semantics/publishedVersio

Evaluation of range of motion restriction within the hip joint

In Total Hip Arthroplasty, determining the impingement free range of motion requirement is a complex task. This is because in the native hip, motion is restricted by both impingement as well as soft tissue restraint. The aim of this study is to determine a range of motion benchmark which can identify motions which are at risk from impingement and those which are constrained due to soft tissue. Two experimental methodologies were used to determine motions which were limited by impingement and those motions which were limited by both impingement and soft tissue restraint. By comparing these two experimental results, motions which were limited by impingement were able to be separated from those motions which were limited by soft tissue restraint. The results show motions in extension as well as flexion combined with adduction are limited by soft tissue restraint. Motions in flexion, flexion combined with abduction and adduction are at risk from osseous impingement. Consequently, these motions represent where the maximum likely damage will occur in femoroacetabular impingement or at most risk of prosthetic impingement in Total Hip Arthroplasty

Risk perceptions starting to shift? U.S. citizens are forming opinions about nanotechnology

This article presents early results from an opinion formation study based on a 76-member panel of U.S. citizens, with comparison data from a group of 177 nanotechnology experts. While initially similar to the expert group in terms of their perceptions of the risks, benefits, and need for regulation characterizing several forms of nanotechnology, the first follow-up survey indicates that the panel is beginning to diverge from the experts, particularly with respect to perceptions of the levels of various “societal” risks that nanotechnology might present. The data suggest that responding to public concerns may involve more than attention to physical risks in areas such as health and environment; concerns about other forms of risk actually appear more salient

El Niño, tropical Atlantic warmth, and Atlantic hurricanes over the past 1500 years

Author Posting. © The Author(s), 2009. This is the author's version of the work. It is posted here by permission of Nature Publishing Group for personal use, not for redistribution. The definitive version was published in Nature 460 (2009): 880-883, doi:10.1038/nature08219.Atlantic Tropical Cyclone (TC) activity, as measured by annual storm counts, reached anomalous levels over the past decade. The short nature of the historical record and potential issues with its reliability in earlier decades, however, has prompted an ongoing debate regarding the reality and significance of the recent rise. Here, we place recent activity in a longer-term context, by comparing two independent estimates of TC activity over the past 1500 years. The first estimate is based on a composite of regional sedimentary evidence of landfalling hurricanes, while the second estimate employs a previously published statistical model of Atlantic TC activity driven by proxy-reconstructions of past climate changes. Both approaches yield consistent evidence of a peak in Atlantic TC activity during Medieval times (around AD 1000) followed by a subsequent lull in activity. The Medieval peak, which rivals or even exceeds (within uncertainties) recent levels of activity, results in the statistical model from a ‘perfect storm’ of La Niña-like climate conditions and relative tropical Atlantic warmth.M.E.M. and Z.Z. acknowledge support from the ATM programme of the National Science Foundation (grant ATM-0542356). J.P.D. acknowledges support from the EAR and OCE programmes of the National Science Foundation (grants EAR-0519118 and OCE-0402746), the Risk Prediction Initiative at the Bermuda Institute for Ocean Sciences, and the Inter-American Institute for Global Change Research

The Effect of Bacterial Infection on the Biomechanical Properties of Biological Mesh in a Rat Model

BACKGROUND: The use of biologic mesh to repair abdominal wall defects in contaminated surgical fields is becoming the standard of practice. However, failure rates and infections of these materials persist clinically. The purpose of this study was to determine the mechanical properties of biologic mesh in response to a bacterial encounter. METHODS: A rat model of Staphylococcus aureus colonization and infection of subcutaneously implanted biologic mesh was used. Samples of biologic meshes (acellular human dermis (ADM) and porcine small intestine submucosa (SIS)) were inoculated with various concentrations of methicillin-resistant Staphylococcus aureus [10(5), 10(9) colony-forming units] or saline (control) prior to wound closure (n = 6 per group). After 10 or 20 days, meshes were explanted, and cultured for bacteria. Histological changes and bacterial recovery together with biomechanical properties were assessed. Data were compared using a 1-way ANOVA or a Mann-Whitney test, with p<0.05. RESULTS: The overall rate of staphylococcal mesh colonization was 81% and was comparable in the ADM and SIS groups. Initially (day 0) both biologic meshes had similar biomechanical properties. However after implantation, the SIS control material was significantly weaker than ADM at 20 days (p = 0.03), but their corresponding modulus of elasticity were similar at this time point (p>0.05). After inoculation with MRSA, a time, dose and material dependent decrease in the ultimate tensile strength and modulus of elasticity of SIS and ADM were noted compared to control values. CONCLUSION: The biomechanical properties of biologic mesh significantly decline after colonization with MRSA. Surgeons selecting a repair material should be aware of its biomechanical fate relative to other biologic materials when placed in a contaminated environment

Inquiry pedagogy to promote emerging proportional reasoning in primary students

Proportional reasoning as the capacity to compare situations in relative (multiplicative) rather than absolute (additive) terms is an important outcome of primary school mathematics. Research suggests that students tend to see comparative situations in additive rather than multiplicative terms and this thinking can influence their capacity for proportional reasoning in later years. In this paper, excerpts from a classroom case study of a fourth-grade classroom (students aged 9) are presented as they address an inquiry problem that required proportional reasoning. As the inquiry unfolded, students' additive strategies were progressively seen to shift to proportional thinking to enable them to answer the question that guided their inquiry. In wrestling with the challenges they encountered, their emerging proportional reasoning was supported by the inquiry model used to provide a structure, a classroom culture of inquiry and argumentation, and the proportionality embedded in the problem context