Rigorous Analysis of Multimodal HDX-MS Spectra.

An inherent strength of hydrogen/deuterium exchange coupled to mass spectrometry (HDX-MS) is its ability to detect the presence of multiple conformational states of a protein, which often manifest as multimodal isotopic envelopes. However, the statistical considerations for accurate analysis of multimodal spectra have yet to be established. Here we outline an unrestrained binomial distribution fitting approach with the corresponding statistical tests to accurately detect and, when possible, deconvolute isotopic distributions that contain multiple subpopulations.

Recognition of BACH1 quaternary structure degrons by two F-box proteins under oxidative stress.

Ubiquitin-dependent proteolysis regulates diverse cellular functions with high substrate specificity, which hinges on the ability of ubiquitin E3 ligases to decode the targets' degradation signals, i.e., degrons.

Tryptanthrin Analogs Substoichiometrically Inhibit Seeded and Unseeded Tau4RD Aggregation.

Microtubule-associated protein tau is an intrinsically disordered protein (IDP) that forms characteristic fibrillar aggregates in several diseases, the most well-known of which is Alzheimer's disease (AD). Despite keen interest in disrupting or inhibiting tau aggregation to treat AD and related dementias, there are currently no FDA-approved tau-targeting drugs. This is due, in part, to the fact that tau and other IDPs do not exhibit a single well-defined conformation but instead populate a fluctuating conformational ensemble that precludes finding a stable "druggable" pocket.

Development and initial validation of an electronic personal assessment questionnaire for menstrual, pelvic pain and gynaecological hormonal disorders (ePAQ-MPH).

Objective: Menstrual disorders, pelvic-pain and gynaecological hormonal conditions in women can have a significant impact on quality-of-life. Reliable assessment and monitoring of these intimate conditions is challenging. Patient reported outcome measures (PROMs) can be invaluable in providing objective assessment, but no comprehensive PROM assessing all of these conditions and their impact on quality of life is currently available.

Development of Technologic Solutions to Address Complex Local Requirements of an International Prostate Cancer Clinical Quality Registry.

Purpose: To detail the process for importing a defined data set into a centralized global registry via a secure file transfer platform and to understand the barriers to the establishment of a centralized global registry.

Results: A bespoke solution was developed to allow transmission of data from international local data centers to a centralized repository. Data elements included in the import template were drawn from existing International Consortium for Health Outcome Measurement variables and refined to ensure accurate benchmarking as well as feasibility in data completeness.