Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts, United States of America.
Published: February 2013
AI Article Synopsis
Article Abstract
Peptidoglycan hydrolases are a double-edged sword. They are required for normal cell division, but when dysregulated can become autolysins lethal to bacteria. How bacteria ensure that peptidoglycan hydrolases function only in the correct spatial and temporal context remains largely unknown. Here, we demonstrate that dysregulation converts the essential mycobacterial peptidoglycan hydrolase RipA to an autolysin that compromises cellular structural integrity. We find that mycobacteria control RipA activity through two interconnected levels of regulation in vivo-protein interactions coordinate PG hydrolysis, while proteolysis is necessary for RipA enzymatic activity. Dysregulation of RipA protein complexes by treatment with a peptidoglycan synthase inhibitor leads to excessive RipA activity and impairment of correct morphology. Furthermore, expression of a RipA dominant negative mutant or of differentially processed RipA homologues reveals that RipA is produced as a zymogen, requiring proteolytic processing for activity. The amount of RipA processing differs between fast-growing and slow-growing mycobacteria and correlates with the requirement for peptidoglycan hydrolase activity in these species. Together, the complex picture of RipA regulation is a part of a growing paradigm for careful control of cell wall hydrolysis by bacteria during growth, and may represent a novel target for chemotherapy development.
A Delphi consensus-seeking procedure was conducted to validate a list of ICD-9-CM codes that could help identify hospital admissions in which antimicrobials are more likely to be prescribed. The panel agreed to include 2967 codes out of 16229 (18.28%).
Cervical carcinoma has the highest incidence among gynaecological cancers in developing countries where the human papillomavirus (HPV) vaccine is not yet widely used. Cancer stem cells (CSCs) are the key factors affecting treatment efficacy and cancer prognosis. Aldehyde dehydrogenase 1 (ALDH1) is a marker of CSCs, and its expression is closely related to chemotherapy resistance in cervical carcinoma.
Desmans belong to the subfamily Desmaninae, which are members of the family Talpidae. Desmans and moles show limited sexual dimorphism, making unclear sex discrimination by phenotypic assessment. The Iberian desman (Galemys pyrenaicus) is an endangered species with a severe population decline.
The development of proteolysis targeting chimeras (PROTACs), which induce the degradation of target proteins by bringing them into proximity with cellular E3 ubiquitin ligases, has revolutionized drug development. While the human genome encodes more than 600 different E3 ligases, current PROTACs use only a handful of them, drastically limiting their full potential. Furthermore, many PROTAC development campaigns fail because the selected E3 ligase candidates are unable to induce degradation of the particular target of interest.
The rising prevalence and incidence of Type 1 Diabetes (T1D) highlights its impact on quality of life, long-term health complications, and the economic burden it poses across socio-economic strata. Effective management of T1D demands robust self-care skills, which are significantly influenced by health literacy (HL) levels; studies have shown that lower HL is associated with poorer health outcomes. This scoping review protocol is designed to identify literature trends and hidden patterns in research assessing HL among individuals with T1D.
