Observation of Collider Muon Neutrinos with the SND@LHC Experiment.

We report the direct observation of muon neutrino interactions with the SND@LHC detector at the Large Hadron Collider. A dataset of proton-proton collisions at sqrt[s]=13.6  TeV collected by SND@LHC in 2022 is used, corresponding to an integrated luminosity of 36.

Effects of Different Modes of Hypobaric Hypoxia on the Content of Epigenetic Factors in the Rat in Neurons of Rat Neocortex.

We studied the effects of different modes of hypobaric hypoxia on the content of epigenetic factors acH3K24, meH3K9, and meDNA modulating conformational characteristics of chromatin and gene expression in neurons of associative complex of rat parietal neocortex. Severe destructive hypoxia dramatically reduced the level of acH3K24 in 3 h after the end of exposure and increased meH3K9 and meDNA content. By contrast, 3-fold (but not single) adaptive exposure to moderate hypobaric hypoxia that produced a neuroprotective effect enhanced neuronal acH3K24 expression and decreased both meH3K9 and meDNA levels.

Cerebral Mechanisms of Hypoxic/Ischemic Postconditioning.

This review analyzes recent data on mechanisms of cerebral hypoxia and the protective methods of hypoxic and ischemic postconditioning, as well as their interrelationship with the key mechanisms responsible for neuroprotection and neuroplasticity. Upregulation of expression of antiapoptotic factors and neurotrophins and modulation of activity of several protein kinases and transcription factors such as hypoxia-inducible factor-1 (HIF-1) are considered as the most important aspects in the neuroprotective potential of postconditioning. The presented information indicates substantial transformative promise of the noninvasive techniques of hypoxic postconditioning as well as significant similarity between the adaptive pathways activated by various postconditioning methods, which are far from being fully understood.

[Current Theory on the Cerebral Mechanisms of Hypoxic PRE- and Postconditioning].

An exposure of the organism to several episodes of mild hypoxia results in the development of brain hypoxic/ischemic tolerance, as well as cross-tolerance to the stressful factors of psychoemotional nature. Such kind of preconditioning by mild hypoxia functions as “alarm signalization” by I.P.

Effects of Hypobaric Hypoxia in Various Modes on Expression of Neurogenesis Marker NeuroD2 in the Dentate Gyrus of Rats Hippocampus.

The expression of neurogenesis marker--NeuroD2 transcription factor--in the hippocampal dentate gyrus was studied in rats exposed to severe destructive hypoxia, a single or three episodes of moderate hypobaric hypoxia, preconditioned severe hypoxia, and severe hypoxia followed by 3 sessions of postconditioning by moderate hypobaric hypoxia. All the studied hypoxic exposure modes led to an increase of NeuroD2 level. Three-fold moderate hypoxia per se and in the preconditioning mode (followed by exposure to severe hypoxia) produced most pronounced up-regulatory effect on NeuroD2 expression.

Acetylation of histones in neocortex and hippocampus of rats exposed to different modes of hypobaric hypoxia: Implications for brain hypoxic injury and tolerance.

Acetylation of nucleosome histones results in relaxation of DNA and its availability for the transcriptional regulators, and is generally associated with the enhancement of gene expression. Although it is well known that activation of a variety of pro-adaptive genes represents a key event in the development of brain hypoxic/ischemic tolerance, the role of epigenetic mechanisms, in particular histone acetylation, in this process is still unexplored. The aim of the present study was to investigate changes in acetylation of histones in vulnerable brain neurons using original well-standardized model of hypobaric hypoxia and preconditioning-induced tolerance of the brain.

Current insights into the molecular mechanisms of hypoxic pre- and postconditioning using hypobaric hypoxia.

Exposure of organisms to repetitive mild hypoxia results in development of brain hypoxic/ischemic tolerance and cross-tolerance to injurious factors of a psycho-emotional nature. Such preconditioning by mild hypobaric hypoxia functions as a "warning" signal which prepares an organism, and in particular the brain, to subsequent more harmful conditions. The endogenous defense processes which are mobilized by hypoxic preconditioning and result in development of brain tolerance are based on evolutionarily acquired gene-determined mechanisms of adaptation and neuroprotection.

Reconstruction of novel transcription factor regulons through inference of their binding sites.

Background: In most sequenced organisms the number of known regulatory genes (e.g., transcription factors (TFs)) vastly exceeds the number of experimentally-verified regulons that could be associated with them.

Hypobaric Preconditioning Modifies Group I mGluRs Signaling in Brain Cortex.

The study assessed involvement of Ca(2+) signaling mediated by the metabotropic glutamate receptors mGluR1/5 in brain tolerance induced by hypoxic preconditioning. Acute slices of rat piriform cortex were tested 1 day after exposure of adult rats to mild hypobaric hypoxia for 2 h at a pressure of 480 hPa once a day for three consecutive days. We detected 44.

[MORPHOLOGICAL DIFFERENCES BETWEEN THE EFFECTS OF VARIOUS MODES OF PRECONDITIONING AIMED AT CORRECTING THE DAMAGE TO THE HIPPOCAMPAL NEURONS BY SEVERE HYPOBARIC HYPOXIA].

In 5 groups of rats (6 animals in each), the changes of neurons in hippocampal fields CA1 and CA4 were studied 7 days after severe hypobaric hypoxia (180 mm Hg, for 3 h) preceded by various numbers (1, 3 and 6) of sessions of preconditioning (PC) by mild hypobaric hypoxia (360 mm Hg, for 2 h, 24 h prior to severe hypoxia). It was found that a single session of PC did not prevent the damage to the structure of neurons and their death after exposure to severe hypoxia. Meanwhile, 6, and especially 3 sessions of PC induced protective mechanisms of neuronal damage prevention.

[Effect of hypoxic postconditioning on the expression of antiapoptotic protein Bcl-2 and neurotrophin BDNF in CA1 hippocampal field of rats surviving severe hypoxia].

Using the method of quantitative immunohistochemistry, the expression of antiapoptotic protein Bcl-2 and neurotrophin BDNF was studied in CA1 hippocampal field of rats that survived severe hypoxia (SH), the damaging effects of which were compensated by subsequent three postconditioning (PC) sessions of mild hypobaric hypoxia (360 mm Hg, 2 hours, three times with 24 hour intervals). It was shown that the expression of the proteins studied was decreased in rat hippocampus after SH. Hypoxic postconditioning which improved the structural and functional rehabilitation after SH, was shown to up-regulate the expression of Bcl-2 and BDNF in hippocampal CA1 neurons in rats that survived SH.

Neocortical pCREB and BDNF expression under different modes of hypobaric hypoxia: role in brain hypoxic tolerance in rats.

Preconditioning with repetitive mild hypobaric hypoxia is known to increase tolerance of susceptible brain neurons to severe hypoxia, whereas a single trial of mild hypoxia has been ineffective. In the present study, the effects of three-trial and one-trial hypobaric preconditioning on the expression of the protective transcription factor phosphorylated CREB (pCREB) and neurotrophin BDNF, before and after severe hypobaric hypoxia, have been comparatively studied in the neocortex of rats. As revealed by quantitative immunocytochemistry, the severe hypobaric hypoxia (180 Torr, 3h) substantially down-regulated the levels of pCREB and BDNF in cortical neurons assessed 24h after the treatment.

[Hypoxic preconditioning modifies the activity of pro- and antioxidant systems in rat hippocampus].

The effects of repetitive mild hypobaric hypoxic preconditioning upon pro- and antioxidant systems in rat hippocampus were studied. It was found that three-trial preconditioning by mild hypobaric hypoxia (360 mm Hg, 2 h) induced moderate oxidative stress immediately after the last preconditioning trial. In addition, it down-regualted the levels of peptide antioxidants (Trx-1, Trx-2, Cu,Zn-SOD) and several lipid peroxidation products 24 h later.

[Changes in the expression of Bcl-2 antiapoptotic protein in rat neocortex and hippocampus under the influence of various modes of hypobaric hypoxia].

Using immunocytochemical method, the level of expression of Bcl-2 antiapoptotic factor was studied in neurons of the neocortex and hippocampus in 72 male Wistar rats exposed to damaging severe hypoxia (SH), moderate hypobaric hypoxia (MHH), as well as their combination. After SH (180 mmHg) Bcl-2 expression in the neurons of the brain regions examined was reduced or. unchanged.

Designing DNA barcodes orthogonal in melting temperature by simulated annealing optimization.

Molecular barcode arrays are widely employed in the analysis of large strain libraries, whereby probes linked to unique oligonucleotides ("antitags") are used to detect selected DNA targets ("tags") by highly specific hybridization. One of the major problems for such screen designs is thus insuring a high degree of probe-target specificity and a low level of nonspecific binding (in sum, "orthogonality") across the entire tag population ("collection"). Several approaches have been previously proposed for designing orthogonal DNA tags by-among others-focusing on their individual or pair-wise structures, such as Smith Waterman sequence similarity, the widely used nearest neighbor method, and full thermodynamic estimates of sequences.

[A comparison of a neuroprotective effects of hypoxic postconditioning and cerebrolysin in the experimental model].

Hypoxic postconditioning using episodes of mild hypobaric hypoxia is a new neuroprotective technique. We compared the neuroprotective efficacy of hypoxic postconditioning and cerebrolysin in a model of posthypoxic pathology in rats. Animals that survived the severe hypoxia (180 Torr, 3 h) were exposed to hypoxic postconditioning or received cerebrolysin.

[Effects of several modes of hypobaric hypoxia on expression profiles of corticosteroid receptors in rat hippocampus].

Gluco- and mineralocorticoid receptors are believed to play important roles in mechanisms of the hypothalamic-pituitary-adrenal axis (HPA) regulation, neuronal death/survival, as well as learning and memory processes. Imbalanced levels of MR and GR result in impairment of HPA activity and can promote neuronal injury and loss following exposures to extreme factors. In the present study, using quantitative immunohistochemistry, the comparative analysis of the effects of hypobaric hypoxia in several modes on expression profiles of GR and MR in dorsal (CA1) and ventral (dentate gyrus) hippocampus was performed.

[Pattern of neuronal expression of transcription factors NF-kappaB under different modes of hypobaric hypoxia].

Transcription factor NF-kappaB plays a pivotal role in mechanisms of brain neuron survival and degeneration under injurious stimuli, first of all different types of hypoxia. In the present work, using quantitative immunohystochemistry, we provide analysis of expression of different subunits of NF-kappaB (p65 and c-Rel) in the rat neocortex in response to severe injurious hypobaric hypoxia (HH) or after a single or multiple sessions of mild protective HH. Severe hypoxia (SH), resulting in loss of brain neurons, has no effect on the level of expression of p65 but suppresses expression of c-Rel.

Inference of gene regulatory networks from genome-wide knockout fitness data.

Motivation: Genome-wide fitness is an emerging type of high-throughput biological data generated for individual organisms by creating libraries of knockouts, subjecting them to broad ranges of environmental conditions, and measuring the resulting clone-specific fitnesses. Since fitness is an organism-scale measure of gene regulatory network behaviour, it may offer certain advantages when insights into such phenotypical and functional features are of primary interest over individual gene expression. Previous works have shown that genome-wide fitness data can be used to uncover novel gene regulatory interactions, when compared with results of more conventional gene expression analysis.

[Participation of metabotropic glutamate receptors of the brain in mechanizms of hypoxic signaling].

Group I of metabotropic glutamate receptors (ImGluRs) are a family of G-protein-coupled receptors which activate a multitude of signaling pathways important for modulating neuronal excitability and synaptic plasticity as well as anti- and prosurvival pathways initiated by hypoxia. However these functions are still not complete and sometimes controversial. The present work is a review of data concerning involvement of ImGluRs in mechanisms of cell response to hypoxia.

[Signal molecular and hormonal mechanisms of formation of the hypoxic preconditioning protective effects].

In the review, results of the long-standing authors'studies and literature data concerning one of the underresearched aspects of actual problem of induced brain tolerance to injurious factors - "preventive" signal function of the hypoxic preconditioning, as well as molecular and hormonal mechanisms underlying its protective effects are presented. Hypoxic preconditioning by using of mild hypobaric hypoxia in special mode mobilizes evolutionary acquired genome determined defense mechanisms of brain neurons and whole organism. This process involves an activation of multiple intracellular components, as well as hypothalamic-pituitary-adrenal axis.

[Urothelial tumor of the urinary bladder: immunohistochemical features].

Morphological and clinical characteristics of the urinary bladder cancers (UBC) are important diagnostics and prognostic criteria, however the possibilities of biopsy using/for prognosis of recidivation or efficiency of UBC treatment are limited. The most popular diagnostic and prognostic immunohistochemical markers are the regulators of cell cycle (P53, P21, Ki-67) and cytokeratins. In order to revealed immunohistochemical criteria, objectively reflected the malignancy of UBC, we studied the expression level of P53, proliferative index of Ki-67 and the malignant of UBC according to CK20 in the biopsy of 32 patients with superficial UBC.