The molecular mechanisms leading to infantile epileptic spasm syndrome (IESS) remain obscure. The only common factor seems to be that the spasms are restricted to a limited period of infancy, during a certain maturational state. Here the current literature regarding the biochemical mechanisms of brain maturation in IESS is reviewed, and various hypotheses of the pathophysiology are put together. They include: (1) imbalance of inhibitory (NGF, IGF-1, ACTH, GABA) and excitatory factors (glutamate, nitrites) which distinguishes the different etiological subgroups, (2) abnormality of the hypothalamic pituitary adrenal (HPA) axis linking insults and early life stress, (3) inflammation (4) yet poorly known genetic and epigenetic factors, and (5) glucocorticoid and vigabatrin action on brain development, pinpointing at molecular targets of the pathophysiology from another angle. An altered maturational process may explain why so many, seemingly independent etiological factors lead to the same clinical syndrome and frequently to developmental delay. Understanding these factors can provide ideas for novel therapies.
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http://dx.doi.org/10.1016/j.seizure.2023.01.004 | DOI Listing |
Nat Chem Biol
January 2025
Department of Microbiology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.
Diverse bacteria and archaea use atmospheric CO as an energy source for long-term survival. Bacteria use [MoCu]-CO dehydrogenases (Mo-CODH) to convert atmospheric CO to carbon dioxide, transferring the obtained electrons to the aerobic respiratory chain. However, it is unknown how these enzymes oxidize CO at low concentrations and interact with the respiratory chain.
View Article and Find Full Text PDFNat Commun
January 2025
Biophysics Graduate Group, University of California, Davis, CA, USA.
P-cadherin, a crucial cell-cell adhesion protein which is overexpressed in numerous malignant cancers, is a popular target for drug delivery antibodies. However, molecular guidelines for engineering antibodies that can be internalized upon binding to P-cadherin are unknown. Here, we use a combination of biophysical, biochemical, and cell biological methods to demonstrate that trapping the P-cadherin extracellular region in an X-dimer adhesive conformation triggers cadherin endocytosis via an outside-in signaling mechanism.
View Article and Find Full Text PDFEnviron Pollut
January 2025
Heilongjiang River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Harbin 150070, China. Electronic address:
Cr(VI) is widely used in industry and has high toxicity, making it one of the most common environmental pollutants. Long-term exposure to Cr(VI) can cause metabolic disorders and tissue damage. However, the effects of Cr(VI) on liver and gut microbes in fish have rarely been reported.
View Article and Find Full Text PDFJ Biol Chem
January 2025
Department of Molecular Biology and Genetics, Aarhus University, Universitetsbyen 81, 8000 Aarhus C, Denmark. Electronic address:
Outer dynein arms (ODAs) are essential for ciliary motility and are preassembled in the cytoplasm before trafficking into cilia by intraflagellar transport (IFT). ODA16 is a key adaptor protein that links ODAs to the IFT machinery via a direct interaction with the IFT46 protein. However, the molecular mechanisms regulating the assembly, transport, and release of ODAs remain poorly understood.
View Article and Find Full Text PDFJ Ethnopharmacol
January 2025
Chongqing Key Laboratory of New Drug Screening from Traditional Chinese Medicine, Integrative Science Center of Germplasm Creation in Western China (Chongqing) Science City & Southwest University, SWU-TAAHC Medicinal Plant Joint R&D Centre, College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, P.R. China. Electronic address:
Ethnopharmacological Relevance: The roots of Oxybaphus himalaicus Edgew. is a traditional Tibetan herbal medicine with kidney reinforcing and tonifying effects, which is commonly applied to treat nephritis. Boeravinone C has been identified as one of the primary constituents of O.
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