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A Model of Zymogen Factor XII: Insights into Protease Activation.
Blood Adv
January 2025
Vanderbilt University Medical Center, Nashville, Tennessee, United States.
In plasma, the zymogens factor XII (FXII) and prekallikrein reciprocally convert each other to the proteases FXIIa and plasma kallikrein (PKa). PKa cleaves high-molecular-weight kininogen (HK) to release bradykinin, which contributes to regulation of blood vessel tone and permeability. Plasma FXII is normally in a "closed" conformation that limits activation by PKa.
View Article and Find Full Text PDFSurvival and Its Predictors Among Patients Receiving Transarterial Chemoembolization for Hepatocellular Carcinoma in Ethiopia: A 6-Year Follow-Up Study.
JCO Glob Oncol
January 2025
Department of Public Health, Myungsung Medical College, Addis Ababa, Ethiopia.
Purpose: To analyze survival and its predictors among patients with hepatocellular carcinoma (HCC) receiving transarterial chemoembolization (TACE) in Ethiopia.
Materials And Methods: We conducted a retrospective cohort study among patients who received TACE for HCC at MCM Hospital from December 1, 2016, to December 31, 2022. Data were extracted from patients' medical records, and vital status was ascertained from the patients' charts or by phone call to the next of kin.
CBX2 suppresses interferon signaling to diminish tumor immunogenicity via a noncanonical corepressor complex.
Proc Natl Acad Sci U S A
February 2025
State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510050, China.
Chromobox 2 (CBX2), a crucial component of the polycomb repressive complex (PRC), has been implicated in the development of various human cancers. However, its role in the regulation of tumor immunogenicity and immune evasion remains inadequately understood. In this study, we found that ablation of CBX2 led to tumor growth inhibition, activation of the tumor immune microenvironment, and enhanced therapeutic efficacy of anti-PD1 or adoptive T cell therapies by using murine syngeneic tumor models.
View Article and Find Full Text PDFWe lack tools to edit DNA sequences at scales necessary to study 99% of the human genome that is noncoding. To address this gap, we applied CRISPR prime editing to insert recombination handles into repetitive sequences, up to 1697 per cell line, which enables generating large-scale deletions, inversions, translocations, and circular DNA. Recombinase induction produced more than 100 stochastic megabase-sized rearrangements in each cell.
View Article and Find Full Text PDFMultiplex generation and single-cell analysis of structural variants in mammalian genomes.
Science
January 2025
Department of Genome Sciences, University of Washington, Seattle, WA, USA.
Studying the functional consequences of structural variants (SVs) in mammalian genomes is challenging because (i) SVs arise much less commonly than single-nucleotide variants or small indels and (ii) methods to generate, map, and characterize SVs in model systems are underdeveloped. To address these challenges, we developed Genome-Shuffle-seq, a method that enables the multiplex generation and mapping of thousands of SVs (deletions, inversions, translocations, and extrachromosomal circles) throughout mammalian genomes. We also demonstrate the co-capture of SV identity with single-cell transcriptomes, facilitating the measurement of SV impact on gene expression.
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