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Genesis and regulation of C-terminal cyclic imides from protein damage.
Proc Natl Acad Sci U S A
January 2025
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138.
C-Terminal cyclic imides are posttranslational modifications that can arise from spontaneous intramolecular cleavage of asparagine or glutamine residues resulting in a form of irreversible protein damage. These protein damage events are recognized and removed by the E3 ligase substrate adapter cereblon (CRBN), indicating that these aging-related modifications may require cellular quality control mechanisms to prevent deleterious effects. However, the factors that determine protein or peptide susceptibility to C-terminal cyclic imide formation or their effect on protein stability have not been explored in detail.
View Article and Find Full Text PDFBinding mode-guided development of high-performance antibodies targeting site-specific posttranslational modifications.
Proc Natl Acad Sci U S A
January 2025
Laura and Isaac Perlmutter Cancer Center, New York University Langone Health, New York, NY 10016.
Posttranslational modifications (PTMs) of proteins play critical roles in regulating many cellular events. Antibodies targeting site-specific PTMs are essential tools for detecting and enriching PTMs at sites of interest. However, fundamental difficulties in molecular recognition of both PTM and surrounding peptide sequence have hindered the efficient generation of highly sequence-specific anti-PTM antibodies.
View Article and Find Full Text PDFComparative study on blood pressure and metabolic improvements in hypertensive patients using copper bianstone scraping.
Medicine (Baltimore)
January 2025
Nephrology Department, Changzhou Traditional Chinese Medicine Hospital, Changzhou City, China.
To evaluate the effectiveness and feasibility of the copper bianstone scraping combined with Chinese modified termination hypertension dietary therapy program by comparing and analyzing the improvement of blood pressure, blood lipids and blood glucose in hypertensive patients who received copper bianstone scraping combined with Chinese modified termination hypertension dietary therapy intervention. We selected 160 cases of hypertensive patients from July 2022 to March 2024 for the study. They were divided into 80 cases in the comparison group and 80 cases in the observation group according to whether or not they underwent copper bianstone scraping combined with Chinese modified dietary therapy for termination of hypertension.
View Article and Find Full Text PDFTDP43 autoregulation gives rise to dominant negative isoforms that are tightly controlled by transcriptional and post-translational mechanisms.
Cell Rep
January 2025
Neuroscience Graduate Program, University of Michigan, Ann Arbor, MI, USA; Graduate Program in Cell and Molecular Biology, University of Michigan, Ann Arbor, MI, USA; Medical Scientist Training Program, University of Michigan, Ann Arbor, MI, USA; Department of Neurology, University of Michigan, Ann Arbor, MI, USA. Electronic address:
The nuclear RNA-binding protein TDP43 is integrally involved in the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Previous studies uncovered N-terminal TDP43 isoforms that are predominantly cytosolic in localization, prone to aggregation, and enriched in susceptible spinal motor neurons. In healthy cells, however, these shortened (s)TDP43 isoforms are difficult to detect in comparison to full-length (fl)TDP43, raising questions regarding their origin and selective regulation.
View Article and Find Full Text PDFClinical features and prognosis analysis of stage III/IV patients with lung cancer after treatment with toripalimab: A real-world retrospective.
J Cancer Res Ther
December 2024
Medical Integration and Practice Center, Cheeloo College of Medicine, Shandong University, Jinan, China.
Aim: Toripalimab is the first antitumor programmed cell death protein 1 (PD-1) antibody approved in China. For better patient management, it is important to understand the real-world outcomes of toripalimab in treating patients with lung cancer in the real world outside of clinical trials to improve patient care.
Methods: We retrospectively examined the clinical data of 80 patients with lung cancer who received the PD-1 inhibitor (toripalimab).
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