Representation of Social Determinants of Health terminology in medical subject headings: impact of added terms.

Objectives: To enhance and evaluate the quality of PubMed search results for Social Determinants of Health (SDoH) through the addition of new SDoH terms to Medical Subject Headings (MeSH).

Materials And Methods: High priority SDoH terms and definitions were collated from authoritative sources, curated based on publication frequencies, and refined by subject matter experts. Descriptive analyses were used to investigate how PubMed search details and best match results were affected by the addition of SDoH concepts to MeSH.

Analysis of the health economics portfolio funded by the National Institutes of Health in response to published guidance.

Health services, economics, and outcomes research (referred to as health economics research hereinafter) is one of the interdisciplinary sciences that the National Institutes of Health (NIH) supports in order to pursue its overall mission to improve health. In 2015, NIH guidance was published to clarify the type of health economics research that NIH would continue to fund. This analysis aimed to determine if there were changes in the number of health economics applications received and funded by NIH after the release of the guidance.

Hsp90 middle domain phosphorylation initiates a complex conformational program to recruit the ATPase-stimulating cochaperone Aha1.

Complex conformational dynamics are essential for function of the dimeric molecular chaperone heat shock protein 90 (Hsp90), including transient, ATP-biased N-domain dimerization that is necessary to attain ATPase competence. The intrinsic, but weak, ATP hydrolyzing activity of human Hsp90 is markedly enhanced by the co-chaperone Aha1. However, the cellular concentration of Aha1 is substoichiometric relative to Hsp90.

Targeting the Hsp40/Hsp70 Chaperone Axis as a Novel Strategy to Treat Castration-Resistant Prostate Cancer.

Castration-resistant prostate cancer (CRPC) is characterized by reactivation of androgen receptor (AR) signaling, in part by elevated expression of AR splice variants (ARv) including ARv7, a constitutively active, ligand binding domain (LBD)-deficient variant whose expression has been correlated with therapeutic resistance and poor prognosis. In a screen to identify small-molecule dual inhibitors of both androgen-dependent and androgen-independent AR gene signatures, we identified the chalcone C86. Binding studies using purified proteins and CRPC cell lysates revealed C86 to interact with Hsp40.

Heat shock protein 90: its inhibition and function.

The molecular chaperone heat shock protein 90 (Hsp90) facilitates metastable protein maturation, stabilization of aggregation-prone proteins, quality control of misfolded proteins and assists in keeping proteins in activation-competent conformations. Proteins that rely on Hsp90 for function are delivered to Hsp90 utilizing a co-chaperone-assisted cycle. Co-chaperones play a role in client transfer to Hsp90, Hsp90 ATPase regulation and stabilization of various Hsp90 conformational states.

Out with the old: Hsp90 finds amino acid residue more useful than co-chaperone protein.

Redundant functions maintained from single to multi-cellular organisms have made an important model for the analysis of conserved com-plex cellular processes. Yeast has been especially useful in understanding the regulation and function of the essential molecular chaperone, Heat Shock Protein 90 (Hsp90). Research focused on Hsp90 has determined that it is highly regulated by both co-chaperones and posttranslational modifications.

An Hsp90 co-chaperone protein in yeast is functionally replaced by site-specific posttranslational modification in humans.

Heat shock protein 90 (Hsp90) is an essential eukaryotic molecular chaperone. To properly chaperone its clientele, Hsp90 proceeds through an ATP-dependent conformational cycle influenced by posttranslational modifications (PTMs) and assisted by a number of co-chaperone proteins. Although Hsp90 conformational changes in solution have been well-studied, regulation of these complex dynamics in cells remains unclear.

Clients Place Unique Functional Constraints on Hsp90.

Heat shock protein 90 kDa (Hsp90) is required for the activation and stabilization of numerous client proteins, but the functional requirements of individual clients remain poorly understood. Utilizing yeast growth assays and mutational analysis, Mishra and colleagues explore the constraints placed on Hsp90 by distinct clients and the relationship between these constraints and overall yeast fitness.

Regulation and function of the human HSP90AA1 gene.

Heat shock protein 90α (Hsp90α), encoded by the HSP90AA1 gene, is the stress inducible isoform of the molecular chaperone Hsp90. Hsp90α is regulated differently and has different functions when compared to the constitutively expressed Hsp90β isoform, despite high amino acid sequence identity between the two proteins. These differences are likely due to variations in nucleotide sequence within non-coding regions, which allows for specific regulation through interaction with particular transcription factors, and to subtle changes in amino acid sequence that allow for unique post-translational modifications.

The Hsp90 cochaperones Cpr6, Cpr7, and Cns1 interact with the intact ribosome.

The abundant molecular chaperone Hsp90 is essential for the folding and stabilization of hundreds of distinct client proteins. Hsp90 is assisted by multiple cochaperones that modulate Hsp90's ATPase activity and/or promote client interaction, but the in vivo functions of many of these cochaperones are largely unknown. We found that Cpr6, Cpr7, and Cns1 interact with the intact ribosome and that Saccharomyces cerevisiae lacking CPR7 or containing mutations in CNS1 exhibited sensitivity to the translation inhibitor hygromycin.

Mutation of essential Hsp90 co-chaperones SGT1 or CNS1 renders yeast hypersensitive to overexpression of other co-chaperones.

The essential molecular chaperone Hsp90 functions with over ten co-chaperones in Saccharomyces cerevisiae, but the in vivo roles of many of these co-chaperones are poorly understood. Two of these co-chaperones, Cdc37 and Sgt1, target specific types of clients to Hsp90 for folding. Other co-chaperones have general roles in supporting Hsp90 function, but the degree of overlapping or competing functions is unclear.

Interaction of heat shock protein 90 and the co-chaperone Cpr6 with Ura2, a bifunctional enzyme required for pyrimidine biosynthesis.

The molecular chaperone heat shock protein 90 (Hsp90) is an essential protein required for the activity and stability of multiple proteins termed clients. Hsp90 cooperates with a set of co-chaperone proteins that modulate Hsp90 activity and/or target clients to Hsp90 for folding. Many of the Hsp90 co-chaperones, including Cpr6 and Cpr7, contain tetratricopeptide repeat (TPR) domains that bind a common acceptor site at the carboxyl terminus of Hsp90.

Chaperoning the chaperone: a role for the co-chaperone Cpr7 in modulating Hsp90 function in Saccharomyces cerevisiae.

Heat-shock protein 90 (Hsp90) of Saccharomyces cerevisiae is an abundant essential eukaryotic molecular chaperone involved in the activation and stabilization of client proteins, including several transcription factors and oncogenic kinases. Hsp90 undergoes a complex series of conformational changes and interacts with partner co-chaperones such as Sba1, Cpr6, Cpr7, and Cns1 as it binds and hydrolyzes ATP. In the absence of nucleotide, Hsp90 is dimerized only at the carboxy-terminus.