Wayne S. Fenton, MD, was an accomplished psychiatric researcher, but his colleagues knew him as an equally talented clinician. This memorial recognizes the personal qualities and professional skills that endeared Wayne Fenton to hundreds of mentally ill persons he treated over the course of his professional career. Among these attributes, deep compassion, sincere respect, and tremendous flexibility were hallmarks of an approach that emphasized collaborative, recovery-oriented therapy. Through his actions and writings, Wayne Fenton influenced a generation of mental health professionals who aspire to similar professional excellence in all aspects of clinical care.
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http://dx.doi.org/10.1093/schbul/sbm075 | DOI Listing |
Q Rev Biophys
February 2020
Department of Genetics, Yale School of Medicine, Boyer Center, 295 Congress Avenue, New Haven, CT06510, USA.
This chronologue seeks to document the discovery and development of an understanding of oligomeric ring protein assemblies known as chaperonins that assist protein folding in the cell. It provides detail regarding genetic, physiologic, biochemical, and biophysical studies of these ATP-utilizing machines from both in vivo and in vitro observations. The chronologue is organized into various topics of physiology and mechanism, for each of which a chronologic order is generally followed.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
November 2019
Department of Neurology, Yale University, New Haven, CT 06536;
Parkinson's disease is characterized by the aggregation of the presynaptic protein α-synuclein and its deposition into pathologic Lewy bodies. While extensive research has been carried out on mediators of α-synuclein aggregation, molecular facilitators of α-synuclein disaggregation are still generally unknown. We investigated the role of molecular chaperones in both preventing and disaggregating α-synuclein oligomers and fibrils, with a focus on the mammalian disaggregase complex.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
April 2017
Department of Genetics, Yale University School of Medicine, New Haven, CT 06510;
Recent studies have reported spread of pathogenic proteins in the mammalian nervous system, but whether nonpathogenic ones spread is unknown. We initially investigated whether spread of a mutant amyotrophic lateral sclerosis-associated cytosolic superoxide dismutase 1 (SOD1) protein between motor neurons could be detected in intact chimeric mice. Eight-cell embryos from G85R SOD1YFP and G85R SOD1CFP mice were aggregated, and spinal cords of adult chimeric progeny were examined for motor neurons with cytosolic double fluorescence.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
May 2016
Howard Hughes Medical Institute, Yale School of Medicine, New Haven, CT 06510; Department of Genetics, Yale School of Medicine, New Haven, CT 06510
Recent studies have indicated that mammalian cells contain a cytosolic protein disaggregation machinery comprised of Hsc70, DnaJ homologs, and Hsp110 proteins, the last of which acts to accelerate a rate-limiting step of nucleotide exchange of Hsc70. We tested the ability of transgenic overexpression of a Thy1 promoter-driven human Hsp110 protein, HspA4L (Apg1), in neuronal cells of a transgenic G85R SOD1YFP ALS mouse strain to improve survival. Notably, G85R is a mutant version of Cu/Zn superoxide dismutase 1 (SOD1) that is unable to reach native form and that is prone to aggregation, with prominent YFP-fluorescent aggregates observed in the motor neurons of the transgenic mice as early as 1 mo of age.
View Article and Find Full Text PDFFEBS Lett
February 2015
Department of Genetics, Yale University School of Medicine, New Haven, CT 06510.
A recent hydrogen-deuterium exchange study of folding of the GroEL/GroES-dependent bacterial enzyme DapA has suggested that the DapA folding pathway when free in solution may differ from the folding pathway used in the presence of the GroEL/GroES chaperonin. Here, we have investigated whether DapA aggregation might be occurring in free solution under the conditions of the exchange experiment, as this would confound interpretation of the pathway predictions. Dynamic light scattering (DLS) data, sedimentation analysis and refolding yield indicate that significant aggregation occurs upon dilution of DapA from denaturant, bringing into question the earlier conclusion that different folding pathways occur in the absence and presence of the chaperonin system.
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