Unit activity was recorded from the motor cortex of eight freely moving rabbits in order to examine the acute effect of ethanol (1 g kg-1) on organization of unit activity and to compare it with our earlier results from the limbic cortex. The rabbits performed a food-acquisition task in the experimental cage. Unit activity was recorded during behaviour in the control experiment followed by the alcohol experiment on the next day. After ethanol, behavioural mistakes and the duration of the behavioural cycle significantly increased. In the control experiments activation of 58% of the units had no constant relation to the phases of the behavioural cycle (non-involved units), whereas 42% of the units were constantly activated during certain phases (involved units). Two per cent of the latter units were activated in relation to newly learned behavioural acts (e.g. pedal pressing; L units), 28% in relation to food seizure and/or grinding (S units) and 12% in relation to certain movements during different behavioural acts (M units). Ethanol had no effect on the number of active units and the same relation between the number of non-involved and involved units or between the number of different types of involved units was found. However, the number of involved units decreased in the upper and increased in the lower cortical layers. Also the number of units with low background frequency increased, although the frequency within activations did not change. In our earlier study the number of active units in the limbic cortex decreased after ethanol by one third and the relation between the number of L and M units was reversed.(ABSTRACT TRUNCATED AT 250 WORDS)
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Proc Natl Acad Sci U S A
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Institute of Science and Technology Austria, AT-3400 Klosterneuburg, Austria.
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View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Department of Immunology and Regenerative Biology, Weizmann Institute of Science, Rehovot 7610001, Israel.
Malignant gliomas are heterogeneous tumors, mostly incurable, arising in the central nervous system (CNS) driven by genetic, epigenetic, and metabolic aberrations. Mutations in isocitrate dehydrogenase (IDH1/2) enzymes are predominantly found in low-grade gliomas and secondary high-grade gliomas, with IDH1 mutations being more prevalent. Mutant-IDH1/2 confers a gain-of-function activity that favors the conversion of a-ketoglutarate (α-KG) to the oncometabolite 2-hydroxyglutarate (2-HG), resulting in an aberrant hypermethylation phenotype.
View Article and Find Full Text PDFNatural killer (NK) cells have proven to be safe and effective immunotherapies, associated with favorable treatment responses in chronic myeloid leukemia (CML). Augmenting NK cell function with oncological drugs could improve NK cell-based immunotherapies. Here, we used a high-throughput drug screen consisting of over 500 small-molecule compounds to systematically evaluate the effects of oncological drugs on primary NK cells against CML cells.
View Article and Find Full Text PDFPLoS Comput Biol
January 2025
IRSD-Institut de Recherche en Santé Digestive, Université de Toulouse, INSERM, INRAE, ENVT, UPS, Toulouse, France.
Understanding the interplay between biology and mechanics in tissue architecture is challenging, particularly in terms of 3D tissue organization. Addressing this challenge requires a biological model enabling observations at multiple levels from cell to tissue, as well as theoretical and computational approaches enabling the generation of a synthetic model that is relevant to the biological model and allowing for investigation of the mechanical stresses experienced by the tissue. Using a monolayer human colon epithelium organoid as a biological model, freely available tools (Fiji, Cellpose, Napari, Morphonet, or Tyssue library), and the commercially available Abaqus FEM solver, we combined vertex and FEM approaches to generate a comprehensive viscoelastic finite element model of the human colon organoid and demonstrated its flexibility.
View Article and Find Full Text PDFJ Am Chem Soc
January 2025
Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands.
is a Gram-positive bacterium that is responsible for severe nosocomial infections. The rise of multidrug-resistant strains, which can pose significant health threats, prompts the development of new treatment interventions, and much attention has been directed at the development of prophylactic and therapeutic vaccination strategies. Capsular polysaccharides (CPs) are key protective elements of the cell wall and have been proposed as promising candidate antigens.
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