The SWI͞SNF family of chromatin-remodeling complexes facilitates gene expression by helping transcription factors gain access to their targets in chromatin. SWI͞SNF and Rsc are distinctive members of this family from yeast. They have similar protein components and catalytic activities but differ in biological function. Rsc is required for cell cycle progression through mitosis, whereas SWI͞ SNF is not. Human complexes of this family have also been identified, which have often been considered related to yeast SWI͞SNF. However, all human subunits identified to date are equally similar to components of both SWI͞SNF and Rsc, leaving open the possibility that some or all of the human complexes are rather related to Rsc. Here, we present evidence that the previously identified human SWI͞SNF-B complex is indeed of the Rsc type. It contains six components conserved in both Rsc and SWI͞SNF. Importantly, it has a unique subunit, BAF180, that harbors a distinctive set of structural motifs characteristic of three components of Rsc. Of the two mammalian ATPases known to be related to those in the yeast complexes, human SWI͞SNF-B contains only the homolog that functions like Rsc during cell growth. Immunofluorescence studies with a BAF180 antibody revealed that SWI͞ SNF-B localizes at the kinetochores of chromosomes during mitosis. Our data suggest that SWI͞SNF-B and Rsc represent a novel subfamily of chromatin-remodeling complexes conserved from yeast to human, and could participate in cell division at kinetochores of mitotic chromosomes.
Deposition of α-synuclein aggregates occurs widely in the central and peripheral nervous systems in Parkinson’s disease (PD). Although recent evidence has suggested that cell-to-cell transmission of α-synuclein aggregates drives the progression of PD, the mechanism by which α-synuclein aggregates spread remains undefined. Here, we show that α-synuclein aggregates are perpetually transmitted through a continuous cycle involving uptake of external aggregates, co-aggregation with endogenous α-synuclein, and exocytosis of the co-aggregates. Moreover, we found that glucocerebrosidase depletion, which has previously been strongly associated with PD and increased cognitive impairment, promoted propagation of α-synuclein aggregates. These studies define how α-synuclein aggregates spread among neuronal cells and explain how glucocerebrosidase mutations increase the risk of developing PD and other synucleinopathies.
ObjectiveLack of consensus on the definition of mental health has implications for research, policy and practice. This study aims to start an international, interdisciplinary and inclusive dialogue to answer the question: What are the core concepts of mental health?Design and participants50 people with expertise in the field of mental health from 8 countries completed an online survey. They identified the extent to which 4 current definitions were adequate and what the core concepts of mental health were. A qualitative thematic analysis was conducted of their responses. The results were validated at a consensus meeting of 58 clinicians, researchers and people with lived experience.Results46% of respondents rated the Public Health Agency of Canada (PHAC, 2006) definition as the most preferred, 30% stated that none of the 4 definitions were satisfactory and only 20% said the WHO (2001) definition was their preferred choice. The least preferred definition of mental health was the general definition of health adapted from Huber et al (2011). The core concepts of mental health were highly varied and reflected different processes people used to answer the question. These processes included the overarching perspective or point of reference of respondents (positionality), the frameworks used to describe the core concepts (paradigms, theories and models), and the way social and environmental factors were considered to act. The core concepts of mental health identified were mainly individual and functional, in that they related to the ability or capacity of a person to effectively deal with or change his/her environment. A preliminary model for the processes used to conceptualise mental health is presented.ConclusionsAnswers to the question, ‘What are the core concepts of mental health?’ are highly dependent on the empirical frame used. Understanding these empirical frames is key to developing a useful consensus definition for diverse populations.
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