We present a Web-based application that uses whole-protein masses determined by mass spectrometry to identify putative co- and posttranslational proteolytic cleavages and chemical modifications. The protein cleavage and modification engine (PROCLAME) requires as input an intact mass measurement and a precursor identification based on peptide mass fingerprinting or tandem mass spectrometry. This approach predicts mass-modifying events using a depth-first tree search, bounded by a set of rules controlled by a custom-built fuzzy logic engine, to explore a large number of possible combinations of modifications accounting for the experimental mass. Candidates are saved during a search if they are within a user-specified instrument mass accuracy; the total number of possible candidates searched is based on a specified fuzzy cutoff score. Candidates are scored and ranked using a simple probabilistic model. There is generally not enough information in an intact mass measurement to determine a single unique protein characterization; however, the program provides utility by expediting the identification of sets of putative events consistent with the mass data and ranking them for further investigation. This approach uses a simple, intuitive rule base and lends itself to discovery of unannotated posttranslational events. We have assessed the program with both in silico-generated test data and with published data from an analysis of large ribosomal subunit proteins, both from the yeast S. cerevisiae. Results indicate a high degree of sensitivity and specificity in characterizing proteins whose masses resulted from reasonable proteolysis and covalent modification scenarios. The application is available on the web at http://proclame.unc.edu.
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J Chromatogr B Analyt Technol Biomed Life Sci
December 2024
Clinical Laboratory, Catharina Hospital Eindhoven, Eindhoven 5623 EJ, The Netherlands; Department of Biomedical Engineering, Chemical Biology, Eindhoven University of Technology, Groene Loper 3, Eindhoven 5612 AE, The Netherlands.
Monitoring of kidney function traditionally relies on plasma creatinine concentrations, necessitating invasive blood draws. Non-invasively obtainable biofluids, such as sweat and saliva, present a patient-friendly alternative with potential for continuous monitoring. This study focusses on developing and validating a novel Liquid Chromatography- tandem Mass Spectrometry (LC-MS/MS) assay as a reference test for measuring low creatinine concentrations in sweat and saliva.
View Article and Find Full Text PDFAIDS
November 2024
Division of Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
Objective: Fixed dose combination (FDC) dolutegravir (DTG) plus rilpivirine (RPV) is an approved antiretroviral treatment regimen for people with HIV. The steady-state pharmacokinetics (PK) of FDC DTG+RPV in hemodialysis (HD) has not been previously studied.
Design: We performed a single-center, prospective evaluation of the steady-state PK of FDC DTG +RPV in 4 adults without HIV either requiring HD and in 4 matched participants with normal renal function.
Ann Intern Med
January 2025
Centre of Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital; Division of Experimental Medicine, McGill University; Department of Epidemiology, Biostatistics and Occupational Health, McGill University; Department of Medicine, McGill University; and Division of Cardiology, Jewish General Hospital/McGill University, Montreal, Quebec, Canada (M.J.E.).
Background: Recent randomized controlled trials (RCTs) have investigated glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dual or triple co-agonists for weight loss among adults with overweight or obesity and without diabetes.
Purpose: To assess the efficacy and safety of GLP-1 RAs and co-agonists for the treatment of obesity among adults without diabetes.
Data Sources: MEDLINE, Embase, and Cochrane CENTRAL from inception to 4 October 2024.
J Am Anim Hosp Assoc
January 2025
From the Department of Veterinary Clinical Services, College of Veterinary Medicine, University of Minnesota, St. Paul, Minnesota (N.S., A.H., D.H.).
A 12 yr old female spayed American Staffordshire terrier was referred for stranguria, pollakiuria, and concern for a mass in the trigone of the urinary bladder. A urinalysis and abdominal ultrasound were performed to further investigate the bladder mass. Nematode larvae were identified in the urine, termed microfilaruria, while a caudal abdominal mass was found on ultrasound impinging on the urethra.
View Article and Find Full Text PDFJ Neurosurg Case Lessons
January 2025
Department of Radiology and Biomedical Imaging, University of California, San Francisco, California.
Background: Spinal ependymomas are typically slow-growing tumors with a favorable prognosis. Recently, a new aggressive subtype has emerged with its own distinct histopathological and molecular features characterized by MYCN amplification. However, this subtype of spinal ependymoma is rare, and studies on its imaging characteristics are limited.
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