I.M. Sechenov First Moscow State Medical University

About: I.M. Sechenov First Moscow State Medical University is a education organization based out in Moscow, Russia. It is known for research contribution in the topics: Medicine & Population. The organization has 7984 authors who have published 9355 publications receiving 68997 citations.

Cadherin-13 is a critical regulator of GABAergic modulation in human stem-cell-derived neuronal networks

Abstract: Activity in the healthy brain relies on a concerted interplay of excitation (E) and inhibition (I) via balanced synaptic communication between glutamatergic and GABAergic neurons. A growing number of studies imply that disruption of this E/I balance is a commonality in many brain disorders; however, obtaining mechanistic insight into these disruptions, with translational value for the patient, has typically been hampered by methodological limitations. Cadherin-13 (CDH13) has been associated with autism and attention-deficit/hyperactivity disorder. CDH13 localizes at inhibitory presynapses, specifically of parvalbumin (PV) and somatostatin (SST) expressing GABAergic neurons. However, the mechanism by which CDH13 regulates the function of inhibitory synapses in human neurons remains unknown. Starting from human-induced pluripotent stem cells, we established a robust method to generate a homogenous population of SST and MEF2C (PV-precursor marker protein) expressing GABAergic neurons (iGABA) in vitro, and co-cultured these with glutamatergic neurons at defined E/I ratios on micro-electrode arrays. We identified functional network parameters that are most reliably affected by GABAergic modulation as such, and through alterations of E/I balance by reduced expression of CDH13 in iGABAs. We found that CDH13 deficiency in iGABAs decreased E/I balance by means of increased inhibition. Moreover, CDH13 interacts with Integrin-β1 and Integrin-β3, which play opposite roles in the regulation of inhibitory synaptic strength via this interaction. Taken together, this model allows for standardized investigation of the E/I balance in a human neuronal background and can be deployed to dissect the cell-type-specific contribution of disease genes to the E/I balance.

Quasi-2D Co3O4 nanoflakes as an efficient gas sensor versus alcohol VOCs

Abstract: Here, we study quasi-two-dimensional crystals of Co3O4 grown by electrochemical synthesis on Pt electrodes with a nanoflake morphology to serve as a gas sensor. When synthesizing in aqueous electrolytes under applied electrical bias, the material follows a self-hierarchical architecture to primarily appear as the hexagonal nanoflakes α-Co(OH)2. After heating up to 300 °C in air, the as-synthesized material transforms to Co3O4, preserving the original hierarchical morphology. The Co3O4 nanoflakes have been found to have remarkable chemiresistive response when exposed to various kinds of alcohol vapors, at low ppm concentrations in a mixture with air, over a wide range of temperatures up to 300 °C with a detection limit down to the ppb range with direct dependence on the molecule weight of the alcohol. We explain the observed features of the gas response of the Co3O4 nanoflakes by a shift in the electron density under the chemisorption of VOCs, verified by DFT calculations.

Podoplanin regulates the migration of mesenchymal stromal cells and their interaction with platelets.

Abstract: Mesenchymal stromal cells (MSCs) upregulate podoplanin at sites of infection, chronic inflammation and cancer. Here, we investigated the functional consequences of podoplanin expression on the migratory potential of MSCs and their interactions with circulating platelets. Expression of podoplanin significantly enhanced the migration of MSCs compared to MSCs lacking podoplanin. Rac-1 inhibition altered the membrane localisation of podoplanin and in turn significantly reduced MSC migration. Blocking Rac-1 activity had no effect on the migration of MSCs lacking podoplanin, indicating that it was responsible for regulation of migration through podoplanin. When podoplanin-expressing MSCs were seeded on the basal surface of a porous filter, they were able to capture platelets perfused over the uncoated apical surface and induce platelet aggregation. Similar microthrombi were observed when endothelial cells (ECs) were co-cultured on the apical surface. Confocal imaging shows podoplanin-expressing MSCs extending processes into the EC layer, and these processes could interact with circulating platelets. In both models, platelet aggregation induced by podoplanin-expressing MSCs was inhibited by treatment with recombinant soluble C-type lectin-like receptor 2 (CLEC-2; encoded by the gene Clec1b). Thus, podoplanin may enhance the migratory capacity of tissue-resident MSCs and enable novel interactions with cells expressing CLEC-2.