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Rapid Microwave Fixation of the Brain Reveals Seasonal Changes in the Phosphoproteome of Hibernating Thirteen-Lined Ground Squirrels.
ACS Chem Neurosci
January 2025
Department of Chemistry, University of Nebraska-Lincoln, Lincoln, Nebraska 68588, United States.
Hibernating mammals such as the thirteen-lined ground squirrel () experience significant reductions in oxidative metabolism and body temperature when entering a state known as torpor. Animals entering or exiting torpor do not experience permanent loss of brain function or other injuries, and the processes that enable such neuroprotection are not well understood. To gain insight into changes in protein function that occur in the dramatically different physiological states of hibernation, we performed quantitative phosphoproteomics experiments on thirteen-lined ground squirrels that are summer-active, winter-torpid, and spring-active.
View Article and Find Full Text PDFBRAT1 - a new therapeutic target for glioblastoma.
Cell Mol Life Sci
January 2025
Experimental Neurosurgery, Department of Neurosurgery, Neuroscience Center, Goethe University Hospital, Goethe University Frankfurt, 60528, Frankfurt am Main, Germany.
Glioblastoma (GBM), the most malignant primary brain tumor in adults, has poor prognosis irrespective of therapeutic advances due to its radio-resistance and infiltrative growth into brain tissue. The present study assessed functions and putative druggability of BRCA1-associated ATM activator 1 (BRAT1) as a crucial factor driving key aspects of GBM, including enhanced DNA damage response and tumor migration. By a stable depletion of BRAT1 in GBM and glioma stem-like (GSC) cell lines, we observed a delay in DNA double-strand break repair and increased sensitivity to radiation treatment, corroborated by in vitro and in vivo studies demonstrating impaired tumor growth and invasion.
View Article and Find Full Text PDFProfiling Tel1 Signaling Reveals a Non-Canonical Motif Targeting DNA Repair and Telomere Control Machineries.
J Biol Chem
January 2025
Weill Institute for Cell and Molecular Biology, Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY, USA. Electronic address:
The stability of the genome relies on Phosphatidyl Inositol 3-Kinase-related Kinases (PIKKs) that sense DNA damage and trigger elaborate downstream signaling responses. In S. cerevisiae, the Tel1 kinase (ortholog of human ATM) is activated at DNA double strand breaks (DSBs) and short telomeres.
View Article and Find Full Text PDFPhosphoproteomics for studying signaling pathways evoked by hormones of the renin-angiotensin system: A source of untapped potential.
Acta Physiol (Oxf)
February 2025
Department of Molecular Medicine, Cardiovascular and Renal Research Unit, University of Southern Denmark, Odense M, Denmark.
The Renin-Angiotensin System (RAS) is a complex neuroendocrine system consisting of a single precursor protein, angiotensinogen (AGT), which is processed into various peptide hormones, including the angiotensins [Ang I, Ang II, Ang III, Ang IV, Ang-(1-9), Ang-(1-7), Ang-(1-5), etc] and Alamandine-related peptides [Ang A, Alamandine, Ala-(1-5)], through intricate enzymatic pathways. Functionally, the RAS is divided into two axes with opposing effects: the classical axis, primarily consisting of Ang II acting through the AT receptor (ATR), and in contrast the protective axis, which includes the receptors Mas, ATR and MrgD and their respective ligands. A key area of RAS research is to gain a better understanding how signaling cascades elicited by these receptors lead to either "classical" or "protective" effects, as imbalances between the two axes can contribute to disease.
View Article and Find Full Text PDFMultiomics in cancer biomarker discovery and cancer subtyping.
Adv Clin Chem
January 2025
School of Biosystem and Biomedical Science, College of Health Science, Korea University, Seoul, Republic of Korea; Department of Integrated Biomedical and Life Science, Korea University, Seoul, Republic of Korea; BK21FOUR R&E Center for Learning Health Systems, Korea University, Seoul, Republic of Korea; L-HOPE Program for Community-Based Total Learning Health Systems, Korea University, Seoul, Republic of Korea. Electronic address:
The advent of multiomics has ushered in a new era of cancer research characterized by integrated genomic, transcriptomic and proteomic analysis to unravel the complexities of cancer biology and facilitate the discovery of novel biomarkers. This chapter provides a comprehensive overview of the concept of multiomics, detailing the significant advances in the underlying technologies and their contributions to our understanding of cancer. It delves into the evolution of genomics and transcriptomics, breakthroughs in proteomics, and overarching progress in multiomic methodologies, highlighting their collective impact on cancer biomarker discovery.
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