1,928 research outputs found
Personality influences individual productivity and wages
Personality has become increasingly important in personnel recruitment, write Maria Cubel, Ana Nuevo-Chiquero, Santiago Sanchez-Pages and Marian Vidal-Fernande
No Pass No Drive: Education and Allocation of Time
Revise and Resubmit to American Economic Journal: Economic Polic
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VCP/p97 regulates Beclin-1-dependent autophagy initiation
Autophagy is an essential cellular process that removes harmful protein species, and autophagy upregulation may be able to protect against neurodegeneration and various pathogens. Here, we have identified the essential protein VCP/p97 as a novel regulator of autophagosome biogenesis, where VCP regulates autophagy induction in two ways, both dependent on Beclin-1. Utilizing small-molecule inhibitors of VCP ATPase activity, we show that VCP stabilizes Beclin-1 levels by promoting the deubiquitinase activity of Ataxin-3 towards Beclin-1. VCP also regulates the assembly and activity of the Beclin-1-containing phosphatidylinositol-3-kinase (PI3K) complex I, thus regulating the production of PI(3)P, a key signaling lipid responsible for the recruitment of downstream autophagy factors. Decreased levels of VCP, or inhibition of its ATPase activity impairs starvation-induced production of PI(3)P and limits downstream recruitment of WIPI2, ATG16L and LC3, thereby decreasing autophagosome formation, illustrating an important role for VCP in early autophagy initiation.We are grateful for funding from the UK Dementia Research Institute (funded by the MRC, Alzheimer’s Research UK and the Alzheimer’s Society) (UKDRI-2002 to DCR), The Tau Consortium, Alzheimer’s Research UK, an anonymous donation to the Cambridge Centre for Parkinson-Plus, AstraZeneca, the Swedish Natural Research Council (VR) (reference 2016–06605; to S.M.H;) and from the European Molecular Biology Organisation (EMBO long-term fellowships, ALTF 1024-2016 and ALTF 135-2016, to SMH and LW; respectively)
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Autophagy regulation by acetylation—implications for neurodegenerative diseases
Funder: UK Dementia Research Institute (funded by the MRC, Alzheimer’s Research UK and the Alzheimer’s Society) Cambridge Centre for Parkinson-Plus National Institute for Health Research Cambridge Biomedical Research CentreAbstract: Posttranslational modifications of proteins, such as acetylation, are essential for the regulation of diverse physiological processes, including metabolism, development and aging. Autophagy is an evolutionarily conserved catabolic process that involves the highly regulated sequestration of intracytoplasmic contents in double-membrane vesicles called autophagosomes, which are subsequently degraded after fusing with lysosomes. The roles and mechanisms of acetylation in autophagy control have emerged only in the last few years. In this review, we describe key molecular mechanisms by which previously identified acetyltransferases and deacetylases regulate autophagy. We highlight how p300 acetyltransferase controls mTORC1 activity to regulate autophagy under starvation and refeeding conditions in many cell types. Finally, we discuss how altered acetylation may impact various neurodegenerative diseases in which many of the causative proteins are autophagy substrates. These studies highlight some of the complexities that may need to be considered by anyone aiming to perturb acetylation under these conditions
The challenge of sustainability: Long-term results from the Fifty-Fifty peer group-based intervention in cardiovascular risk factors.
The Fifty-Fifty trial demonstrated that a peer-group-based intervention was able to improve healthy behaviors in individuals with cardiovascular (CV) risk factors immediately post-intervention.
To determine the long-term sustainability of a one-year peer-group-based intervention focused on CV health and behavior.
A total of 543 adults aged 25 to 50 years with at least 1 CV risk factor were screened and recruited, received initial training through workshops, and were then randomized 1:1 to a peer-group-based intervention group (IG) or a self-management control group (CG) for 12 months. At a median of 52 months from baseline, 321 participants were re-assessed (~60% retention). The primary outcome was the mean change in a composite health score related to blood pressure, exercise, weight, alimentation, and tobacco use (Fuster-BEWAT score [FBS], range 0-15). Intervention effects were assessed using linear-mixed effects models.
The mean age of retained participants was 48.0 years (SD: 5.4), and 73% were female. Consistent with previous results, the change of overall FBS was significantly greater in the IG than in the CG at 12-month follow-up (between-group difference, 0.60 points; 95% CI, 0.08-1.12; P = .025). Assessment of long-term sustainability (52-month follow-up) showed that there were no between-group differences in the mean overall FBS (IG mean score, 8.52; 95% CI, 7.97-9.07 vs CG mean score, 8.51; 95% CI, 7.93-9.10; P = .972) or in the change of overall FBS from screening (IG mean change, 0.64; 95% CI, 0.00-1.28; CG mean change, 0.46; 95% CI, -0.20-1.12; P = .497).
A one-year peer-group-based intervention showed favorable results at immediate post-intervention but did not demonstrate significant differences between the IG and CG at 52 months. Combination of an initial training period (workshops) with the maintenance of peer-support groups or other re-intervention strategies may be required to achieve sustained effects on healthy behaviors.
ClinicalTrials.gov identifier NCT02367963. Registered (https://clinicaltrials.gov/show/NCT02367963).This study was co-funded by the SHE Foundation -“la Caixa” Foundation (LCF/PR/CE16/10700001 and LCF/PR/MS19/12220001) and the Ministry of Health, Social Services and Equality. R.F-J is recipient of funding from the Instituto de Salud Carlos III-Fondo de Investigacion Sanitaria (PI19/01704) co-funded by the European Regional Development Fund/European Social Fund (“A way to make Europe”/“Investing in your future”). The CNIC is supported by the Instituto de Salud Carlos III (ISCIII), the Ministry of Science and Innovation, and the Pro CNIC Foundation and is a Severo Ochoa Center of Excellence (SEV-2015-0505).S
Erratum to: Right fronto-insular white matter tracts link cognitive reserve and pain in migraine patients
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