Purpose: The relationship between different forms of persistent radiation damage in irradiated cells was investigated in order to identify a common underlying mechanism.
Material And Methods: V-79 Chinese hamster cells were irradiated with different doses of X-rays, neutrons and alpha-particles. In the progeny of surviving cells, up to 4 weeks after irradiation, delayed reproductive death, delayed micronuclei, delayed appearance of dicentric chromosomes and delayed apoptosis were investigated in parallel.
Results: A similar dose-response relationship was found for all endpoints, with a steep rise at low doses to a plateau at doses > 3 Gy. The target for inducing genomic instability by alpha-particles is larger than the nucleus. All chromosomes are equally involved in delayed breakage reunion events.
Conclusion: The results indicate that non-lethal radiation damage to an extranuclear target leads to a persistent increase in clastogenic activity in the surviving irradiated cells.
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http://dx.doi.org/10.1080/095530098141078 | DOI Listing |
Nat Genet
January 2025
Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
Huntington's disease, one of more than 50 inherited repeat expansion disorders, is a dominantly inherited neurodegenerative disease caused by a CAG expansion in HTT. Inherited CAG repeat length is the primary determinant of age of onset, with human genetic studies underscoring that the disease is driven by the CAG length-dependent propensity of the repeat to further expand in the brain. Routes to slowing somatic CAG expansion, therefore, hold promise for disease-modifying therapies.
View Article and Find Full Text PDFPLoS Biol
January 2025
RNA Virus Replication Laboratory, The Francis Crick Institute, London, United Kingdom.
Coronaviruses express their structural and accessory genes via a set of subgenomic RNAs, whose synthesis is directed by transcription regulatory sequences (TRSs) in the 5' genomic leader and upstream of each body open reading frame. In SARS-CoV-2, the TRS has the consensus AAACGAAC; upon searching for emergence of this motif in the global SARS-CoV-2 sequences, we find that it evolves frequently, especially in the 3' end of the genome. We show well-supported examples upstream of the Spike gene-within the nsp16 coding region of ORF1b-which is expressed during human infection, and upstream of the canonical Envelope gene TRS, both of which have evolved convergently in multiple lineages.
View Article and Find Full Text PDFInt J Colorectal Dis
January 2025
Internal Medicine, Jilin Cancer Hospital, Changchun, China.
Purpose: This phase II study is designed to evaluate the combination therapy involving suvemcitug and envafolimab with FOLFIRI in microsatellite-stable or mismatch repair-proficient (MSS/pMMR) colorectal cancer (CRC) in the second-line treatment setting.
Methods: This study is a non-randomized, open-label prospective study comprising multiple cohorts (NCT05148195). Here, we only report the data from the CRC cohort.
Biotechnol J
January 2025
Department of Chemical and Biomolecular Engineering, University of Delaware, Newark, Delaware, USA.
The implementation of site-specific integration (SSI) systems in Chinese hamster ovary (CHO) cells for the production of monoclonal antibodies (mAbs) can alleviate concerns associated with production instability and reduce cell line development timelines. SSI cell line performance is driven by the interaction between genomic integration location, clonal background, and the transgene expression cassette, requiring optimization of all three parameters to maximize productivity. Systematic comparison of these parameters has been hindered by SSI platforms involving low-throughput enrichment strategies, such as cell sorting.
View Article and Find Full Text PDFCell Commun Signal
January 2025
Department of Pathology, Functional RNomics Research Center, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul, 06591, South Korea.
Background: Gastric cancer remains a significant global health challenge, characterized by poor prognosis and high mortality rates. Mitotic integrity and genomic stability are crucial in maintaining cellular homeostasis and preventing tumorigenesis. The transcription factor NKX6.
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