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In the Transchem project, rainbow trout genitors were exposed to environmental concentrations of pendimethalin over a period of 18 months and two new first generations of offspring, F1_2013 and F1_2014, were obtained. We investigated the impact of direct chemical exposure on juveniles as well as the potential cumulative transgenerational and direct effects on the larval development and on the pathogen susceptibility of offspring. Depending on the chemical treatment or not of the adults, their offspring were distributed in the tanks of our experimental system, in two batches i.e. juveniles from the control genitors (G-) and others from the contaminated ones (G+), and then, half of the tanks were exposed daily to pendimethalin (Off+) while the others were used as controls (Off-). Viral challenges were performed on the offspring, before and after three months of direct chemical exposure, with strains of infectious hematopoietic necrosis virus (IHNV), viral haemorrhagic septicemia virus (VHSV) and sleeping disease alphavirus (SDV). Direct and transgenerational macroscopic effects were observed on offspring, with a percentage of abnormalities in offspring derived from the genitors exposed to pendimethalin (G+) significantly higher compared to those from the genitors from non-exposed group (G-). Before the direct chemical exposure, similar kinetics of mortality was observed between the offspring from the contaminated or control genitors after VHSV infection. With IHNV, the G+ group died in a slightly larger proportion compared to the G- group and seroconversion was greater for the G- group. For the SDV challenge, the mortality was delayed for the G+ offspring compared to the G- and seroconversion reached 65% in the G+ group compared to 45% in the G-, with similar antibody titres. After three months of direct chemical exposure, kinetics of mortality induced by IHNV infection were similar for all groups studied. Infection with SDV resulted in a cumulative mortality of 40% for the G- groups (Off- and Off+), significantly higher than those observed from the contaminated genitors G+. Proportion of seropositivity for SDV varied from 24 to 47% depending on the group, with very low quantities of secreted antibodies. Lastly, the direct exposure of offspring could impact the capacity of fish to adapt their haematological parameters to environmental and physiological changes, and underlines the potential toxic effects on the next generations.
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http://dx.doi.org/10.1016/j.aquatox.2018.07.003 | DOI Listing |
Nat Rev Mol Cell Biol
September 2025
Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA, USA.
The defining property of eukaryotic cells is the storage of heritable genetic material in a nuclear compartment. For eukaryotic cells to carry out the myriad biochemical processes necessary for their function, macromolecules must be efficiently exchanged between the nucleus and cytoplasm. The nuclear pore complex (NPC) - which is a massive assembly of ~35 different proteins present in multiple copies totalling ~1,000 protein subunits and architecturally conserved across eukaryotes - establishes a size-selective channel for regulated bidirectional transport of folded macromolecules and macromolecular assemblies across the nuclear envelope.
View Article and Find Full Text PDFBiotechnol Lett
September 2025
Department of Chemical Engineering, Hongik University, Sangsu-dong, Mapo-gu, Seoul, 04066, Republic of Korea.
The cell surface display system employs carrier proteins to present target proteins on the outer membrane of cells. This system enables functional proteins to be exposed on the exterior of living cells without cell lysis, allowing direct interaction with the surrounding environment. A major limitation of conventional approaches is the difficulty in displaying large-sized enzymes or antibodies, despite their critical roles in applications requiring functional domains that must remain intact, such as catalytic or antigen-binding sites.
View Article and Find Full Text PDFNat Biomed Eng
September 2025
Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.
Phenotype-driven approaches identify disease-counteracting compounds by analysing the phenotypic signatures that distinguish diseased from healthy states. Here we introduce PDGrapher, a causally inspired graph neural network model that predicts combinatorial perturbagens (sets of therapeutic targets) capable of reversing disease phenotypes. Unlike methods that learn how perturbations alter phenotypes, PDGrapher solves the inverse problem and predicts the perturbagens needed to achieve a desired response by embedding disease cell states into networks, learning a latent representation of these states, and identifying optimal combinatorial perturbations.
View Article and Find Full Text PDFNat Cell Biol
September 2025
Department of Medicine, Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Durotaxis, cell migration along stiffness gradients, is linked to embryonic development, tissue repair and disease. Despite solid in vitro evidence, its role in vivo remains largely speculative. Here we demonstrate that durotaxis actively drives disease progression in vivo in mouse models of lung fibrosis and metastatic pancreatic cancer.
View Article and Find Full Text PDFJ Org Chem
September 2025
Jiangsu Key Laboratory of Green Synthetic Chemistry for Functional Materials, School of Chemistry and Materials Science, Jiangsu Normal University, Xuzhou, Jiangsu 221116, PR China.
A convenient protocol for the synthesis of selenated benzoxepine derivatives via iron(III)-catalyzed 7-endo-trig cyclization has been first established via reaction of 1,7-diene containing nonactivated allyl and dialkyl diselenides under room temperature and air conditions. Research has shown that different dialkyl diselenides could react with a wide range of 1,7-diene to achieve seven-membered products in good to excellent yields. Furthermore, this synthesis was directed to obtain the desired target products, indicating that this approach has an excellent chemical selectivity.
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