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Protection of β2GPI-Deficient Mice from Thrombosis Reflects a Defect in PAR3-facilitated Platelet Activation.
Blood
January 2025
Cleveland Clinic, Cleveland, Ohio, United States.
Antibodies to β2-glycoprotein I (β2GPI) cause thrombosis in antiphospholipid syndrome, however the role of β2GPI in coagulation in vivo is not understood. To address this issue, we developed β2GPI-deficient mice (Apoh-/-) by deleting exon 2 and 3 of Apoh using CRISPR/Cas9 and compared the development of thrombosis in wild-type (WT) and Apoh-/- mice using rose bengal and FeCl3-induced carotid thrombosis, laser-induced cremaster arteriolar injury, and inferior vena cava (IVC) stasis models. We also compared tail bleeding times and activation of platelets from WT and Apoh-/- mice in the absence and presence of β2GPI.
View Article and Find Full Text PDFDo the Shuffle: Expanding the Synthetic Biology Toolkit for Shufflon-like Recombination Systems.
ACS Synth Biol
January 2025
Department of Life Sciences, Imperial College London, London SW7 2AZ, U.K.
Naturally occurring DNA inversion systems play an important role in the generation of genetic variation and adaptation in prokaryotes. Shufflon invertase (SI) from plasmid R64, recognizing asymmetric sites, has been adopted as a tool for synthetic biology. However, the availability of a single enzyme with moderate rates of recombination has hampered the more widespread use of SIs.
View Article and Find Full Text PDFSmall molecule modulators of B56-PP2A restore 4E-BP function to suppress eIF4E-dependent translation in cancer cells.
J Clin Invest
January 2025
Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, United States of America.
Dysregulated eIF4E-dependent translation is a central driver of tumorigenesis and therapy resistance. eIF4E binding proteins (4E-BP1/2/3) are major negative regulators of eIF4E-dependent translation that are inactivated in tumors through inhibitory phosphorylation or downregulation. Previous studies have linked PP2A phosphatase(s) to activation of 4E-BP1.
View Article and Find Full Text PDFM6a demethylase FTO regulates the oxidative stress, mitochondrial biogenesis of cardiomyocytes and PGC-1a stability in myocardial ischemia-reperfusion injury.
Redox Rep
December 2025
Department of Cardiology, Fujian Medical University Union Hospital, Fuzhou, Fujian, People's Republic of China.
Objective: Myocardial ischemia-reperfusion injury (MIRI) is a highly complex disease with high morbidity and mortality. Studying the molecular mechanism of MIRI and discovering new targets are crucial for the future treatment of MIRI.
Methods: We constructed the MIRI rat model and hypoxia/reoxygenation (H/R) injury cardiomyocytes model.
Emerging Deep Brain Stimulation Targets in the Cerebellum for Tremor.
Cerebellum
January 2025
Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Deep brain stimulation (DBS) for essential tremor is remarkably effective, leading to over 80% reduction in standardized tremor ratings. However, for certain types of tremor, such as those accompanied by ataxia or dystonia, conventional DBS targets have shown poor efficacy. Various rationales for using cerebellar DBS stimulation to treat tremor have been advanced, but the varied approaches leave many questions unanswered: which anatomic target, stimulation settings, and indications seem most promising for this emerging approach.
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