To elucidate the molecular mechanism of the integration of long interspersed elements (LINEs), we characterized the 5' ends of more than 200 LINE de novo retrotransposition events into chicken DT40 or human HeLa cells. Human L1 inserts produced 15-bp target-site duplications (TSDs) and zebrafish ZfL2-1 inserts produced 5-bp TSDs in DT40 cells, suggesting that TSD length depends on the LINE species. Further analysis of 5' junctions revealed that the 5'-end-joining pathways of LINEs can be divided into two fundamental types-annealing or direct. We also found that the generation of 5' inversions depends on host and LINE species. These results led us to propose a new model for 5'-end joining, the type of which is determined by the extent of exposure of 3' overhangs generated after the second-strand cleavage and by the involvement of host factors.
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http://dx.doi.org/10.1093/nar/gku1067 | DOI Listing |
Phys Med Biol
January 2025
National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba, 263-8555, JAPAN.
PET has become an important clinical modality but is limited to imaging positron emitters. Recently, PET imaging withZr, which has a half-life of 3 days, has attracted much attention in immuno-PET to visualize immune cells and cancer cells by targeting specific antibodies on the cell surface. However,Zr emits a single gamma ray at 909 keV four times more frequently than positrons, causing image quality degradation in conventional PET.
View Article and Find Full Text PDFDrug Deliv Transl Res
January 2025
Leicester Institute of Pharmaceutical, Health and Social Care Innovations, Leicester School of Pharmacy, De Montfort University, Leicester, LE1 9BH, UK.
The use of dissolving microneedle arrays (dMNA) for intradermal and transdermal drug delivery has been a growing trend in the field for the past decades. However, a lack of specific regulatory standards still hinders their clinical development and translation to market. It is also well-known that dMNA composition significantly impacts their performance, with each new formulation potentially presenting a challenge for developers, manufacturers and regulatory agencies.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
University of Michigan Medical School, Ann Arbor, MI, USA.
Background: The transfer of mitochondrial DNA into the nuclear genomes of eukaryotes (Numts) has been linked to lifespan in non-human species and recently demonstrated to occur in rare instances from one human generation to the next.
Method: Here we investigated numtogenesis dynamics in humans in two ways. First, we quantified Numts in 1,187 post-mortem brain and blood samples from different individuals.
Alzheimers Dement
December 2024
TauC3 Biologics Limited, London, United Kingdom.
Background: Tau abnormalities are a central feature of Alzheimer's disease (AD) and the defining feature of non-AD tauopathies, which include frontotemporal lobar degeneration (FTLD) due to Pick's disease (PiD) or Mapt mutations (FTLD-tau), as well as progressive supranuclear palsy (PSP), corticobasal degeneration (CBD) and others. Mapt transcripts undergo alternative splicing to produce 6 distinct isoforms. Exon 2 splicing produces 0, 1 or 2 inserts; exclusion or inclusion of exon 10 results in 3-repeat (3R) or 4-repeat (4R) forms, respectively.
View Article and Find Full Text PDFFront Fungal Biol
December 2024
Department of Biological Sciences, University of Notre Dame, Notre Dame, IN, United States.
The antimicrobial peptide (AMP) circularized bacteriocin enterocin AS-48 produced by sp. exhibits broad-spectrum antibacterial activity via dimer insertion into the plasma membrane to form membrane pore structures, compromising membrane integrity and leading to bactericidal activity. A specific alpha-helical region of enterocin AS-48 has been shown to be responsible for the membrane-penetrating activity of the peptide.
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