The crystal structure of the Sgt1-Skp1 complex: the link between Hsp90 and both SCF E3 ubiquitin ligases and kinetochores

The essential cochaperone Sgt1 recruits Hsp90 chaperone activity to a range of cellular factors including SCF E3 ubiquitin ligases and the kinetochore in eukaryotes. In these pathways Sgt1 interacts with Skp1, a small protein that heterodimerizes with proteins containing the F-box motif. We have determined the crystal structure of the interacting domains of Saccharomyces cerevisiae Sgt1 and Skp1 at 2.8 Å resolution and validated the interface in the context of the full-length proteins in solution. The BTB/POZ domain of Skp1 associates with Sgt1 via the concave surface of its TPR domain using residues that are conserved in humans. Dimerization of yeast Sgt1 occurs via an insertion that is absent from monomeric human Sgt1. We identify point mutations that disrupt dimerization and Skp1 binding in vitro and find that the interaction with Skp1 is an essential function of Sgt1 in yeast. Our data provide a structural rationale for understanding the phenotypes of temperature-sensitive Sgt1 mutants and for linking Skp1-associated proteins to Hsp90-dependent pathways

Identification of two novel powdery mildew resistance loci, Ren6 and Ren7, from the wild Chinese grape species Vitis piasezkii

Descriptive statistics of the phenotypic scores within the base mapping population 11-373. Powdery mildew symptoms in the field were evaluated in two subsequent years. Greenhouse, in vitro experiments and the qPCR-based molecular assay were carried out with three to four biological replicates of each seedling plant in 2014. (DOCX 14ย�kb

Global, regional, and national incidence, prevalence, and mortality of HIV, 1980–2017, and forecasts to 2030, for 195 countries and territories: a systematic analysis for the Global Burden of Diseases, Injuries, and Risk Factors Study 2017

Background Understanding the patterns of HIV/AIDS epidemics is crucial to tracking and monitoring the progress of prevention and control efforts in countries. We provide a comprehensive assessment of the levels and trends of HIV/AIDS incidence, prevalence, mortality, and coverage of antiretroviral therapy (ART) for 1980–2017 and forecast these estimates to 2030 for 195 countries and territories. Methods We determined a modelling strategy for each country on the basis of the availability and quality of data. For countries and territories with data from population-based seroprevalence surveys or antenatal care clinics, we estimated prevalence and incidence using an open-source version of the Estimation and Projection Package—a natural history model originally developed by the UNAIDS Reference Group on Estimates, Modelling, and Projections. For countries with cause-specific vital registration data, we corrected data for garbage coding (ie, deaths coded to an intermediate, immediate, or poorly defined cause) and HIV misclassification. We developed a process of cohort incidence bias adjustment to use information on survival and deaths recorded in vital registration to back-calculate HIV incidence. For countries without any representative data on HIV, we produced incidence estimates by pulling information from observed bias in the geographical region. We used a re-coded version of the Spectrum model (a cohort component model that uses rates of disease progression and HIV mortality on and off ART) to produce age-sex-specific incidence, prevalence, and mortality, and treatment coverage results for all countries, and forecast these measures to 2030 using Spectrum with inputs that were extended on the basis of past trends in treatment scale-up and new infections. Findings Global HIV mortality peaked in 2006 with 1·95 million deaths (95% uncertainty interval 1·87–2·04) and has since decreased to 0·95 million deaths (0·91–1·01) in 2017. New cases of HIV globally peaked in 1999 (3·16 million, 2·79–3·67) and since then have gradually decreased to 1·94 million (1·63–2·29) in 2017. These trends, along with ART scale-up, have globally resulted in increased prevalence, with 36·8 million (34·8–39·2) people living with HIV in 2017. Prevalence of HIV was highest in southern sub-Saharan Africa in 2017, and countries in the region had ART coverage ranging from 65·7% in Lesotho to 85·7% in eSwatini. Our forecasts showed that 54 countries will meet the UNAIDS target of 81% ART coverage by 2020 and 12 countries are on track to meet 90% ART coverage by 2030. Forecasted results estimate that few countries will meet the UNAIDS 2020 and 2030 mortality and incidence targets. Interpretation Despite progress in reducing HIV-related mortality over the past decade, slow decreases in incidence, combined with the current context of stagnated funding for related interventions, mean that many countries are not on track to reach the 2020 and 2030 global targets for reduction in incidence and mortality. With a growing population of people living with HIV, it will continue to be a major threat to public health for years to come. The pace of progress needs to be hastened by continuing to expand access to ART and increasing investments in proven HIV prevention initiatives that can be scaled up to have population-level impact

Operation and performance of the ATLAS Tile Calorimeter in Run 1

The Tile Calorimeter is the hadron calorimeter covering the central region of the ATLAS experiment at the Large Hadron Collider. Approximately 10,000 photomultipliers collect light from scintillating tiles acting as the active material sandwiched between slabs of steel absorber. This paper gives an overview of the calorimeter’s performance during the years 2008–2012 using cosmic-ray muon events and proton–proton collision data at centre-of-mass energies of 7 and 8TeV with a total integrated luminosity of nearly 30 fb−1. The signal reconstruction methods, calibration systems as well as the detector operation status are presented. The energy and time calibration methods performed excellently, resulting in good stability of the calorimeter response under varying conditions during the LHC Run 1. Finally, the Tile Calorimeter response to isolated muons and hadrons as well as to jets from proton–proton collisions is presented. The results demonstrate excellent performance in accord with specifications mentioned in the Technical Design Report

Edible bio-based nanostructures: delivery, absorption and potential toxicity

The development of bio-based nanostructures as nanocarriers of bioactive compounds to specific body sites has been presented as a hot topic in food, pharmaceutical and nanotechnology fields. Food and pharmaceutical industries seek to explore the huge potential of these nanostructures, once they can be entirely composed of biocompatible and non-toxic materials. At the same time, they allow the incorporation of lipophilic and hydrophilic bioactive compounds protecting them against degradation, maintaining its active and functional performance. Nevertheless, the physicochemical properties of such structures (e.g., size and charge) could change significantly their behavior in the gastrointestinal (GI) tract. The main challenges in the development of these nanostructures are the proper characterization and understanding of the processes occurring at their surface, when in contact with living systems. This is crucial to understand their delivery and absorption behavior as well as to recognize potential toxicological effects. This review will provide an insight into the recent innovations and challenges in the field of delivery via GI tract using bio-based nanostructures. Also, an overview of the approaches followed to ensure an effective deliver (e.g., avoiding physiological barriers) and to enhance stability and absorptive intestinal uptake of bioactive compounds will be provided. Information about nanostructures potential toxicity and a concise description of the in vitro and in vivo toxicity studies will also be given.Joana T. Martins, Oscar L. Ramos, Ana C. Pinheiro, Ana I. Bourbon, Helder D. Silva and Miguel A. Cerqueira (SFRH/BPD/89992/2012, SFRH/BPD/80766/2011, SFRH/BPD/101181/2014, SFRH/BD/73178/2010, SFRH/BD/81288/2011, and SFRH/BPD/72753/2010, respectively) are the recipients of a fellowship from the Fundacao para a Ciencia e Tecnologia (FCT, POPH-QREN and FSE, Portugal). The authors thank the FCT Strategic Project PEst-OE/EQB/LA0023/2013 and the project "BioInd-Biotechnology and Bioengineering for improved Industrial and Agro-Food processes," REF.NORTE-07-0124-FEDER-000028, co-funded by the Programa Operacional Regional do Norte (ON.2-O Novo Norte), QREN, FEDER. We also thank to the European Commission: BIOCAPS (316265, FP7/REGPOT-2012-2013.1) and Xunta de Galicia: Agrupamento INBIOMED (2012/273) and Grupo con potencial de crecimiento. The support of EU Cost Action FA1001 is gratefully acknowledged

Variables involved in the perception of psychological harassment in the nursing work environment

This is a descriptive-exploratory study with a quantitative approach, with the objective of identifying how nurses perceive psychological harassment at work, the behaviors experienced and the variables involved. In collecting data, two questionnaires were used: one socio-professional and another for identifying the behaviors involving psychological harassment experienced by the subjects in the previous twelve months, along with the duration and frequency of the behaviors. At the end of the questionnaire, a dichotomous question was added, which addressed nurses' perceptions in relation to feeling victimized by psychological harassment at work. Both the questionnaires were applied in electronic and print format between May and September 2010. The data was analyzed through descriptive statistics. The results showed that some of the subjects felt that they were victims of psychological harassment. Only the variables related to characterization of the psychological harassment presented significant association. The following were highlighted among the most-referred-to behaviors: "They question your decisions" and "You receive verbal attacks criticizing work you have done". It's important to open spaces for discussing violence at work, so that managers may establish strategic measures for preventing and containing this type of violence, so as to ensure health, dignity and well-being at work. It is also important to discuss this issue in the academic space, so as to give the theme greater visibility, such that future nurses will be able to identify and appropriately confront this type of violence.Estudio descriptivo-exploratorio de abordaje cuantitativo, con el objetivo de identificar la percepción de enfermeros sobre el asedio moral en el trabajo, las conductas vividas y las variables relacionadas. En la recogida de datos se utilizó un cuestionario socio-profesiográfico y otro para identificar las conductas de asedio moral vividas por los sujetos en los últimos doce meses, el periodo y la frecuencia de las conductas. Al final del cuestionario fue adicionada una cuestión dicotómica relacionada a la percepción del enfermero cuanto a sentirse víctima de asedio moral en el trabajo. Los dos cuestionarios fueran aplicados electrónicamente e impresos entre mayo y septiembre de 2010. Los datos fueran tratados por estadística descriptiva. Los resultados mostraron que los sujetos se sintieron víctimas de asedio moral. Solamente las variables relacionadas a la caracterización del asedio moral presentaron asociación significativa. Entre las conductas más referidas, se destacaron: "Cuestionan las decisiones que usted toma" y "Usted recibe ataques verbales criticando trabajos realizados". Es importante la apertura de espacios de discusión sobre la violencia en el trabajo para que gestores puedan establecer medidas estratégicas de prevención y contención de este tipo de violencia a fin de garantizar la salud, la dignidad y el bienestar del profesional en el trabajo. También es importante discutir el tema en el ámbito académico, con el fin de dar mayor visibilidad a la cuestión, para que los futuras enfermeros puedan identificar y abordar adecuadamente este tipo de violencia.Trata-se de estudo descritivo-exploratório, de abordagem quantitativa, com o objetivo de identificar a percepção de enfermeiros sobre o assédio moral no trabalho, condutas vivenciadas e variáveis envolvidas. Na coleta de dados, utilizaram-se dois questionários: um socioprofissiográfico e outro para identificar as condutas de assédio moral, vivenciadas pelos sujeitos nos últimos 12 meses, o período e a frequência das condutas. Ao final do questionário, foi adicionada uma questão dicotômica que abordava a percepção do enfermeiro em relação a se sentir vítima de assédio moral no trabalho. Ambos os questionários foram aplicados no formato eletrônico e impresso, entre maio e setembro de 2010. Os dados foram tratados por estatística descritiva. Os resultados mostraram que parte dos sujeitos sentiu-se vítima de assédio moral. Somente as variáveis relacionadas à caracterização do assédio moral apresentaram associação significativa. Entre as condutas mais referidas, destacaram-se: "questionam as decisões que você toma" e "você recebe ataques verbais criticando trabalhos realizados". É importante a abertura de espaços para discussão sobre a violência no trabalho, para que gestores possam estabelecer medidas estratégicas de prevenção e contenção desse tipo de violência, a fim de garantir a saúde, a dignidade e o bem-estar no trabalho. Torna-se importante, também, discutir o assunto no espaço acadêmico, a fim de dar maior visibilidade ao tema, para que futuros enfermeiros possam identificar e enfrentar adequadamente esse tipo de violência