24 research outputs found
Nedd8 processing enzymes in Schizosaccharomyces pombe
BACKGROUND: Conjugation of the ubiquitin-like modifier Nedd8 to cullins is critical for the function of SCF-type ubiquitin ligases and thus facilitates ubiquitin conjugation and ultimately degradation of SCF substrates, including several cell cycle regulators. Like ubiquitin, Nedd8 is produced as a precursor that must first be processed before it becomes active. In Saccharomyces cerevisiae this is carried out exclusively by the enzyme Yuh1. RESULTS: Here we show that in the fission yeast, Schizosaccharomyces pombe, the Yuh1 orthologue, Uch1, is not the sole Nedd8 processing enzyme. Instead it appears that deubiquitylating enzymes can efficiently process the Nedd8 precursor in vivo. CONCLUSIONS: Several enzymes contribute to Nedd8 precursor processing including a number of deubiquitylating enzymes
Systematic literature review of determinants of sedentary behaviour in older adults:a DEDIPAC study
BACKGROUND: Older adults are the most sedentary segment of society and high sedentary time is associated with poor health and wellbeing outcomes in this population. Identifying determinants of sedentary behaviour is a necessary step to develop interventions to reduce sedentary time.
METHODS: A systematic literature review was conducted to identify factors associated with sedentary behaviour in older adults. Pubmed, Embase, CINAHL, PsycINFO and Web of Science were searched for articles published between 2000 and May 2014. The search strategy was based on four key elements: (a) sedentary behaviour and its synonyms; (b) determinants and its synonyms (e.g. correlates, factors); (c) types of sedentary behaviour (e.g. TV viewing, sitting, gaming) and (d) types of determinants (e.g. environmental, behavioural). Articles were included in the review if specific information about sedentary behaviour in older adults was reported. Studies on samples identified by disease were excluded. Study quality was rated by means of QUALSYST. The full review protocol is available from PROSPERO (PROSPERO 2014: CRD42014009823). The analysis was guided by the socio-ecological model framework.
RESULTS: Twenty-two original studies were identified out of 4472 returned by the systematic search. These included 19 cross-sectional, 2 longitudinal and 1 qualitative studies, all published after 2011. Half of the studies were European. The study quality was generally high with a median of 82 % (IQR 69-96 %) using Qualsyst tool. Personal factors were the most frequently investigated with consistent positive association for age, negative for retirement, obesity and health status. Only four studies considered environmental determinants suggesting possible association with mode of transport, type of housing, cultural opportunities and neighbourhood safety and availability of places to rest. Only two studies investigated mediating factors. Very limited information was available on contexts and sub-domains of sedentary behaviours.
CONCLUSION: Few studies have investigated determinants of sedentary behaviour in older adults and these have to date mostly focussed on personal factors, and qualitative studies were mostly lacking. More longitudinal studies are needed as well as inclusion of a broader range of personal and contextual potential determinants towards a systems-based approach, and future studies should be more informed by qualitative work
Data-independent proteomic screen identifies novel tamoxifen agonist that mediates drug resistance
A label-free quantitative variation of the recently developed data-independent shotgun proteomic method Precursor Acquisition Independent From Ion Count (PAcIFIC) was used to identify novel proteins implicated in cancer progression and resistance. Specifically, this screen identified the pro-metastatic protein anterior gradient 2 (AGR2) as significantly up-regulated in tamoxifen treated cells. Highlighting the need for direct proteome profiling methods like PAcIFIC, neither data-dependent gas-phase fractionation nor a transcriptomic screen detected AGR2 protein/transcript at significantly up-regulated levels. Further cell-based experiments using human cancer cell lines and in vivo xenografts confirmed the PAcIFIC hypothesis that AGR2 is up-regulated in MCF-7 cells post tamoxifen treatment, and that it is implicated in drug resistance mediation
Advanced practice physiotherapy in patients with musculoskeletal disorders: a systematic review
Com o diabo no corpo: os terrĂveis papagaios do Brasil colĂŽnia
Desde a Antiguidade, papagaios, periquitos e afins (Psittacidae) fascinaram os europeus por seu vivo colorido e uma notĂĄvel capacidade de interação com seres humanos. A descoberta do Novo Mundo nada faria alĂ©m de acrescentar novos elementos ao trĂĄfico de animais exĂłticos hĂĄ muito estabelecido pelos europeus com a Ăfrica e o Oriente. Sem possuir grandes mamĂferos, a AmĂ©rica tropical participaria desse comĂ©rcio com o que tinha de mais atrativo, essencialmente felinos, primatas e aves - em particular os papagaios, os quais eram embarcados em bom nĂșmero. Contudo, a julgar pelos documentos do Brasil colĂŽnia, esses volĂĄteis podiam inspirar muito pouca simpatia, pois nenhum outro animal - exceto as formigas - foi tantas vezes mencionado como praga para a agricultura. AlĂ©m disso, alguns psitĂĄcidas mostravam-se tĂŁo loquazes que inspiravam a sĂ©ria desconfiança de serem animais demonĂacos ou possessos, pois sĂł trĂȘs classes de entidades - anjos, homens e demĂŽnios - possuĂam o dom da palavra. Nos dias de hoje, vĂĄrios representantes dos Psittacidae ainda constituem uma ameaça para a agricultura, enquanto os indivĂduos muito faladores continuam despertando a suspeita de estarem possuĂdos pelo demĂŽnio. Transcendendo a mera curiosidade, essa crença exemplifica o quĂŁo intrincadas podem ser as relaçÔes do homem com o chamado âmundo naturalâ, revelando um universo mais amplo e multifacetado do que se poderia supor a princĂpio. Nesse sentido, a existĂȘncia de aves capazes de falar torna essa relação ainda mais complexa e evidencia que as dificuldades de estabelecer o limite entre o animal e o humano se estendem alĂ©m dos primatas e envolvem as mais inusitadas espĂ©cies zoolĂłgicas.Since ancient times, parrots and their allies (Psittacidae) have fascinated Europeans by their striking colors and notable ability to interact with human beings. The discovery of the New World added new species to the international exotic animal trade, which for many centuries had brought beasts to Europe from Africa and the Orient. Lacking large mammals, tropical America participated in this trade with its most appealing species, essentially felines, primates and birds - especially parrots - which were shipped in large numbers. It should be noted, however, that at times these birds were not well liked. In fact, according to documents from colonial Brazil, only the ants rank higher than parrots as the animals most often mentioned as agricultural pests. On the other hand, some of these birds were so chatty that people suspected them to be demonic or possessed animals, since only three classes of beings - angels, men and demons - have the ability to speak. Nowadays, several Psittacidae still constitute a threat to agriculture, and the suspicion that extremely talkative birds were demon possessed has also survived. More than a joke or a mere curiosity, this belief exemplifies how intricate manâs relationships with the ânatural worldâ may be. In this sense, the existence of birds that are able to speak adds a further twist to these relationships, demonstrating that the problem of establishing a boundary between the animal and the human does not only involve primates, but also includes some unusual zoological species
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Developing Consensus-Based Priority Outcome Domains for Trials in Kidney Transplantation
BackgroundInconsistencies in outcome reporting and frequent omission of patient-centered outcomes can diminish the value of trials in treatment decision making. We identified critically important outcome domains in kidney transplantation based on the shared priorities of patients/caregivers and health professionals.MethodsIn a 3-round Delphi survey, patients/caregivers and health professionals rated the importance of outcome domains for trials in kidney transplantation on a 9-point Likert scale and provided comments. During rounds 2 and 3, participants rerated the outcomes after reviewing their own score, the distribution of the respondents' scores, and comments. We calculated the median, mean, and proportion rating 7 to 9 (critically important), and analyzed comments thematically.ResultsOne thousand eighteen participants (461 [45%] patients/caregivers and 557 [55%] health professionals) from 79 countries completed round 1, and 779 (77%) completed round 3. The top 8 outcomes that met the consensus criteria in round 3 (mean, â„7.5; median, â„8; proportion, >85%) in both groups were graft loss, graft function, chronic rejection, acute rejection, mortality, infection, cancer (excluding skin), and cardiovascular disease. Compared with health professionals, patients/caregivers gave higher priority to 6 outcomes (mean difference of 0.5 or more): skin cancer, surgical complications, cognition, blood pressure, depression, and ability to work. We identified 5 themes: capacity to control and inevitability, personal relevance, debilitating repercussions, gaining awareness of risks, and addressing knowledge gaps.ConclusionsGraft complications and severe comorbidities were critically important for both stakeholder groups. These stakeholder-prioritized outcomes will inform the core outcome set to improve the consistency and relevance of trials in kidney transplantation
Redistribution and entrepreneurship with Schumpeterian growth
Growth, Innovation, Optimal taxation, Occupational choice, H21, O3, O4,
Organizing survival and resistance in austere times: shifting disability activism and care politics in Ontario, Canada
The association between migrant status and transition in an ultra-high risk for psychosis population
Purpose: Migrant status is one of the most replicated and robust risk factors for developing a psychotic disorder. This study aimed to determine whether migrant status in people identified as Ultra-High Risk for Psychosis (UHR) was associated with risk of transitioning to a full-threshold psychotic disorder. Methods: Hazard ratios for the risk of transition were calculated from five large UHR cohorts (n = 2166) and were used to conduct a meta-analysis using the generic inverse-variance method using a random-effects model. Results: 2166 UHR young people, with a mean age of 19.1 years (SD ± 4.5) were included, of whom 221 (10.7%) were first-generation migrants. A total of 357 young people transitioned to psychosis over a median follow-up time of 417 days (I.Q.R.147â756 days), representing 17.0% of the cohort. The risk of transition to a full-threshold disorder was not increased for first-generation migrants, (HR = 1.08, 95% CI 0.62â1.89); however, there was a high level of heterogeneity between studies The hazard ratio for second-generation migrants to transition to a full-threshold psychotic disorder compared to the remainder of the native-born population was 1.03 (95% CI 0.70â1.51). Conclusions: This meta-analysis did not find a statistically significant association between migrant status and an increased risk for transition to a full-threshold psychotic disorder; however, several methodological issues could explain this finding. Further research should focus on examining the risk of specific migrant groups and also ensuring that migrant populations are adequately represented within UHR clinics