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The glymphatic-lymphatic fluid transport system (GLFTS) consists of glymphatic pathway and cerebrospinal fluid (CSF) lymphatic outflow routes, allowing biological liquids from the brain parenchyma to access the CSF along with perivascular space and to be cleaned out of the skull through lymphatic vessels. It is known that increased local pressure due to physical compression of tissue improves lymphatic transport in peripheral organs, but little is known about the exact relationship between increased intracranial pressure (IICP) and GLFTS. In this study, we verify our hypothesis that IICP significantly impacts GLFTS, and this effect depends on severity of the IICP. Using a previously developed inflating balloon model to induce IICP and inject fluorescent tracers into the cisterna magna, we found significant impairment of the glymphatic circulation after IICP. We further found that cerebrovascular occlusion occurred, and cerebrovascular pulsation decreased after IICP. IICP also interrupted the drainage of deep cervical lymph nodes and dorsal meningeal lymphatic function, enhancing spinal lymphatic outflow to the sacral lymph nodes. Notably, these effects were associated with the severity of IICP. Thus, our findings proved that the intensity of IICP significantly impacts GLFTS. This may have translational applications for preventing and treating related neurological disorders.

Complement system plays an important role in the immune defense against pathogens; however, recent studies demonstrated an important role of complement subunits C1q, C4, and C3 in normal functions of the central nervous system (CNS) such as non-functional synapse elimination (synapse pruning), and during various neurologic pathologies. Humans have two forms of C4 protein encoded by C4A and C4B genes that share 99.5% homology, while mice have only one C4B gene that is functionally active in the complement cascade. Overexpression of the human C4A gene was shown to contribute to the development of schizophrenia by mediating extensive synapse pruning through the activation C1q-C4-C3 pathway, while C4B deficiency or low levels of C4B expression were shown to relate to the development of schizophrenia and autism spectrum disorders possibly via other mechanisms not related to synapse elimination. To investigate the potential role of C4B in neuronal functions not related to synapse pruning, we compared wildtype (WT) mice with C3- and C4B- deficient animals for their susceptibility to pentylenetetrazole (PTZ)- induced epileptic seizures. We found that C4B (but not C3)–deficient mice were highly susceptible to convulsant and subconvulsant doses of PTZ when compared to WT controls. Further gene expression analysis revealed that in contrast to WT or C3-deficient animals, C4B-deficient mice failed to upregulate expressions of multiple immediate early genes (IEGs) Egrs1-4, c-Fos, c-Jus, FosB, Npas4, and Nur77 during epileptic seizures. Moreover, C4B-deficient mice had low levels of baseline expression of Egr1 on mRNA and protein levels, which was correlated with the cognitive problems of these animals. C4-deficient animals also failed to upregulate several genes downstream of IEGs such as BDNF and pro-inflammatory cytokines IL-1β, IL-6, and TNF. Taken together, our study demonstrates a new role of C4B in the regulation of expression of IEGs and their downstream targets during CNS insults such as epileptic seizures.

The purpose of the study is to identify the reasons for the low availability of helth care to the population of municipal districts of the Saratov region. Material and methods. For the study, official data from the Federal State Statistics Service, the Central Research Institute for the Management and Informatization of Healthcare of the Ministry of Health of the Russian Federation and the Unified Interdepartmental Information and Statistical System for 2014-2019 were taken. The optimal volumes of health care in inpatient and outpatient settings were calculated in accordance with the orders of the Ministry of Health of the Russian Federation and the Decrees of the Government of the Russian Federation. Results. During the study in the region, the reasons for the low availability of health care to residents of municipal districts were identified: lack of human resources in municipal medical organizations, low population density of municipal districts, low recommended staffing standards for specialists in accordance with the Procedures for organizing medical care. Limitations. The main demographic indicators, indicators of resource provision and performance indicators of medical institutions in the Saratov region for 2014-2019 were studied. A comparative analysis of the cost of training programs for highly qualified personnel in the residency of the Saratov State Medical University named after V.I. Razumovsky of general practitioners and the most demanded specialties in municipal outpatient medical organizations in the region. Conclusion. As a result of the study, the reasons for the low availability of health care to the population of the municipal districts of the region were identified and possible ways to overcome them were proposed.

Cyanobacteria produce a wide range of structurally diverse cyanotoxins and bioactive cyanopeptides in freshwater, marine, and terrestrial ecosystems. The health significance of these metabolites, which include genotoxic- and neurotoxic agents, is confirmed by continued associations between the occurrence of animal and human acute toxic events and, in the long term, by associations between cyanobacteria and neurodegenerative diseases. Major mechanisms related to the neurotoxicity of cyanobacteria compounds include (1) blocking of key proteins and channels; (2) inhibition of essential enzymes in mammalian cells such as protein phosphatases and phosphoprotein phosphatases as well as new molecular targets such as toll-like receptors 4 and 8. One of the widely discussed implicated mechanisms includes a misincorporation of cyanobacterial non-proteogenic amino acids. Recent research provides evidence that non-proteinogenic amino acid BMAA produced by cyanobacteria have multiple effects on translation process and bypasses the proof-reading ability of the aminoacyl-tRNA-synthetase. Aberrant proteins generated by non-canonical translation may be a factor in neuronal death and neurodegeneration. We hypothesize that the production of cyanopeptides and non-canonical amino acids is a more general mechanism, leading to mistranslation, affecting protein homeostasis, and targeting mitochondria in eukaryotic cells. It can be evolutionarily ancient and initially developed to control phytoplankton communities during algal blooms. Outcompeting gut symbiotic microorganisms may lead to dysbiosis, increased gut permeability, a shift in blood-brain-barrier functionality, and eventually, mitochondrial dysfunction in high-energy demanding neurons. A better understanding of the interaction between cyanopeptides metabolism and the nervous system will be crucial to target or to prevent neurodegenerative diseases.

The paper presents the results of comprehensive studies of the efficiency of the propagation of a pulsed electron beam through a mixture of gases: titanium tetrachloride and hydrogen, titanium tetrachloride and methane, titanium tetrachloride and oxygen. These substances are the initial reagents or products of plasma-chemical reactions of the synthesis process using pulsed electron beams. The energy distribution over the beam cross section is uniform, and the temperature decreases with distance from the geometric center. The efficiency of the process of dissipation of the energy of a pulsed electron beam during its passage through gas compositions has been studied depending on the energy of the beam electrons (350–450 keV). The studies were carried out on a test bench including a TEA-500 pulsed electron accelerator, a drift chamber, and a sectioned cut-off calorimeter with a beam charge control function. The research results are of practical importance and are the main ones in the technological processes of pulsed plasma-chemical synthesis of carbon-containing nanocomposites.

In electrostatic tandem charged particle accelerators, gas stripping targets are used to convert negative ions into positive ones. Partial ionization of the gas by ions leads to the formation of an undesirable beam of stripping gas ions in the accelerating channels. In this work, the current of a beam of argon ions produced in a tandem accelerator with vacuum insulation was measured by mass spectroscopy. It is shown that the current of argon ions is 2000 times smaller than the current of the proton beam. The reliability of the measurements is provided by visualization of an argon ion beam on the surface of a lithium target and is also confirmed by an experiment with increased gas injection and an estimate of the possible contribution of the proton beam. It is shown that such a small value of the argon ion current does not pose a danger either as a source of additional heating of a lithium target, or as an additional load of a high-voltage power supply, and therefore does not require the previously proposed means for its suppression.

Object and purpose of research. This paper discusses numerical simulation possibilities in terms of stress-strain monitoring for marine engineering structures. This approach can simulate the behavior of strain gauges for both elastic and plastic material behavior. Materials and methods. FEM-based simulation of strain gauge operation process taking into account geometric and physical non-linearity. Main results. Development of refined FE models for sensor installation area of stress-strain monitoring system. Numerical simulation of uniaxial and triaxial strain gauge operation. Time histories of strain gauge readings for linear and non-linear behavior of material. Sensitivity analysis of strain gauges in terms of various strain types. Update of strain gauge arrangement for the best description of structural strains. Conclusion. These results demonstrate and confirm a strong potential of numerical models in development of stress-strain monitoring systems for engineering structures. Simulating strain gauge operation, these models make it possible to determine global strained state of given structure as per strain gauging data for some of its areas.

This paper discusses two approaches to FEM-based calculation of marine propulsion shafts made of polymeric composites: one approach represents the composite as a homogeneous material, whereas the other approach represents it as a real sandwich structure made up by monolayers with different properties.

The paper investigates the capabilities of modern numerical simulation methods for ice interaction of ships moving in level ice sheet. This approach could possibly yield a more accurate and clear picture of this process, enabling simulations of a wide range of related phenomena with little or no full-scale measurement data available. Materials and methods. To simulate ice failure process, this paper follows the finite element method and coupling element methodology. Main results. The bending of a cantilever rectangular ice sample has been numerically simulated, with investigation of its cracking and breaking behavior by means of pre-developed models. It has also been studied how ice resistance of advanced ice-breaking vessels depends on the angles between their velocity vectors and their CLs. The results of this study made it possible to assess the influence of heading angle on ice resistance. The study also described characteristic forms of ice failure and the broken ice behavior at different ship speeds and explored various methods for water medium consideration in terms of their accuracy and computer resources required. It was established that water medium effect upon ship movement in the conditions discussed in this paper can be taken into account as per a simplified procedure. Conclusion. This paper demonstrates and confirms the potential of numerical models in ice interaction simulations for ships and offshore platforms to estimate their ice performance and ice strength.

IntroductionCoagulation parameters are important determinants for COVID-19 infection. We conducted meta-analysis to assess the association between early hemostatic parameters and infection severity.MethodsElectronic search was made for papers that addressed clinical characteristics of COVID-19 patients and disease severity. Results were filtered using exclusion and inclusion criteria and then pooled into a meta-analysis to estimate the standardized mean difference (SMD) with 95% confidence interval (CI) for D-dimers, fibrinogen, prothrombin time, platelet count (PLT), activated partial thromboplastin time. To explore the heterogeneity and robustness of our fundings, sensitivity and subgroup analyses were conducted. Publication bias was assessed with contour-enhanced funnel plots and Egger's test by linear regression. Coagulation parameters data from retrospective cohort study of 451 patients with COVID-19 at National Research Center for Cardiac Surgery were included in meta-analysis of published studies.ResultsOverall, 41 original studies (17,601 patients) on SARS-CoV-2 were included. For the two groups of patients, stratified by severity, we identified that D-dimers, fibrinogen, activated partial thromboplastin time, and prothrombin time were significantly higher in the severe group [SMD 0.6985 with 95%CI (0.5155; 0.8815); SMD 0.661 with 95%CI (0.3387; 0.9833); SMD 0.2683 with 95%CI (0.1357; 0.4009); SMD 0.284 with 95%CI (0.1472; 0.4208)]. In contrast, PLT was significantly lower in patients with more severe cases of COVID-19 [SMD −0.1684 with 95%CI (−0.2826; −0.0542)]. Neither the analysis by the leave-one-out method nor the influence diagnostic have identified studies that solely cause significant change in the effect size estimates. Subgroup analysis showed no significant difference between articles originated from different countries but revealed that severity assessment criteria might have influence over estimated effect sizes for platelets and D-dimers. Contour-enhanced funnel plots and the Egger's test for D-dimers and fibrinogen revealed significant asymmetry that might be a sign of publication bias.ConclusionsThe hemostatic laboratory parameters, with exception of platelets, are significantly elevated in patients with severe COVID-19. The two variables with strongest association to disease severity were D-dimers and fibrinogen levels. Future research should aim outside conventional coagulation tests and include analysis of clotting formation and platelet/platelet progenitors characteristics.

IntroductionCoagulation parameters are important determinants for COVID-19 infection. We conducted meta-analysis to assess the early hemostatic parameters in retrospective studies in association with severity of infection.MethodsOvid, PubMed, Web of Sciences, and Google Scholar were searched for research articles that addressed clinical characteristics of COVID-19 patients and disease severity. Results were filtered using exclusion and inclusion criteria and then pooled into a meta-analysis to estimate the standardized mean difference with 95% CI for each of five coagulation parameters (D-dimers, fibrinogen, prothrombin time, platelets count, activated partial thromboplastin time). Two authors independently extracted data and assessed study quality. To explore the heterogeneity and robustness of our fundings, sensitivity and subgroup analyses were conducted. Publication bias was assessed with contour-enhanced funnel plots and Egger test by linear regression.ResultsOverall, 41 original studies (17601 patients) on SARS-CoV2 were included. For the two groups of patients, stratified by severity, we identified that D-dimers, fibrinogen, activated partial thromboplastin time, and prothrombin time were significantly higher in the severe group (SMD 0.6985 with 95%CI [0.5155; 0.8815]); SMD 0.661with 95%CI [0.3387; 0.9833]; SMD 0.2683 with 95%CI [0.1357; 0.4009]; SMD 0.284 with 95%CI [0.1472; 0.4208]). In contrast, PLT was significantly lower in patients with more severe cases of COVID-19 (SMD −0.1684 with 95%CI [-0.2826; −0.0542]). Neither the analysis by the leave-one-out method nor the influence diagnostic have identified studies that solely cause significant change in the effect size estimates. Subgroup analysis showed no significant difference between articles originated from different countries but revealed that severity assessment criteria might have influence over estimated effect sizes for platelets and D-dimers. Contour-enhanced funnel plots and the Egger test for D-dimers and fibrinogen revealed significant asymmetry that might be a sign of publication bias.ConclusionsThe standard coagulation laboratory parameters with exception of platelets counts are significantly elevated in patients with severe COVID-19. However, fibrinolysis shutdown requires evaluation outside conventional coagulation tests and analysis of additional specific markers related to clotting formation and PLT characteristics. We hypothesize that a proportion and parameters of immature reticulated platelets may serve as additional biomarkers for prediction of adverse events.

Gangliosides are glycosphingolipids, which are abundant in brain, are known to modulate ion channels and cell-to-cell communication. Deficiencies can result in aberrant myelination and altered immune responses, which can give rise to neurodevelopmental psychiatric disorders. However, to date, little mechanistic data is available on how ganglioside deficiencies contribute to the behavioural disorders. In humans, the loss of lactosylceramide-alpha-2,3-sialyltransferase (ST3Gal5) leads to a severe neuropathology, but in ST3Gal5 knock-out (St3gal5−/−) mice the absence of GM3 and associated a-, b- and c-series gangliosides is partially compensated by 0-series gangliosides and there is no overt behavioural phenotype. Here, we sought to examine the behavioural and molecular consequences of GM3 loss more closely. Mutants of both sexes exhibited impaired conditioned taste aversion in an inhibitory learning task and anxiety-like behaviours in the open field, moderate motor deficits, abnormal social interactions, excessive grooming and rearing behaviours. Taken together, the aberrant behaviours are suggestive of an autism spectrum disorder (ASD)-like syndrome. Molecular analysis showed decreased gene and protein expression of proteolipid protein-1 (Plp1) and over expression of proinflammatory cytokines, which has been associated with ASD-like syndromes. The inflammatory and behavioural responses to lipopolysaccharide (LPS) were also altered in the St3gal5−/− mice compared to wild-type, which is indicative of the importance of GM3 gangliosides in regulating immune responses. Together, the St3gal5−/− mice display ASD-like behavioural features, altered response to systemic inflammation, signs of hypomyelination and neuroinflammation, which suggests that deficiency in a- and b-series gangliosides could contribute to the development of an ASD-like pathology in humans., Highlights • St3gal5−/− mice exhibit aberrant social, motor and cognitive behavior that is reminiscent of ASD-like syndrome. • Interleukin1β is upregulated in the brain and spleen of St3gal5−/− of both sexes. • Mutants display reduced gene and protein expression of the myelin protein Plp1. • LPS induces sex-dependent abnormalities in the inflammatory response and social behavior in the St3gal5−/− mice. • St3gal5−/− mice can be used to study the behavioural consequence of a- and b-series ganglioside deficiency

Detection of antineutrino by the reaction of the inverse β-decay can be used for an independent monitoring of a nuclear reactor power. DANSS detector is located directly under a commercial WWER-1000 reactor and counts up to 5000 antineutrino per day, providing the accuracy of 1.5% in 2 days of the flux measurement. A powerful system of the passive and active shielding in combination with the fine spatial segmentation of the detector allows to diminish the contribution of the background processes to a level, negligible in comparison to the statistical error. The influence of the nuclear fuel composition on the neutrino flux can be accounted for based on the input from the NPP staff.

Late Mesozoic Upper Amga alkaline rocks are located in the Amga tectonic melange zone within the Aldan-Stanovoy shield, Russia. The main phases of the Upper Amga complex consist of alkaline syenite intrusions as well as the lamprophyre dikes and sills. The mineralogical features indicate that the lamprophyre may belong to minette. Recent geological works revealed the linear and area-specific geochemical gold anomalies in association with late Mesozoic alkaline magmatism in the Upper Amga gold district. The age of the syenite intrusions is 131.4 ± 1.5 (2.9) Ma, and the lamprophyre sills and dikes were formed at 134.9 ± 1.6, 132.3 ± 1.5 and 117.7 ± 3.4 Ma. The mineralization is represented by the REE-Ti-Th, polymetallic (sulfide) and telluride-gold types in the quartz-calcite-chlorite alteration of the main magmatic phases of the alkaline rocks. The fluid inclusions study shows that the sulfides were formed from hydrothermal fluids of CO2-N2-NaCl-H2O composition at temperatures ranging from 390 to 340 °C, with 44–22.7 wt% NaCl-eq, whereas the epithermal telluride-gold mineralization originated from low-temperature CO2 ± N2-NaCl-H2O fluids, with the homogenization temperature of 230–210 °C and a of 9.2–3.3 wt% NaCl-eq.

The N-S trending Central-Aldan magnesiocarbonatite province is located in the Aldan-Stanovoy shield (South Yakutia, Russia). Several apatite-dolomitic carbonatite occurrences were studied: Seligdar, Muostalaah, Ust-Chulman and Birikeen. Mineralogical and petrographic investigations indicate intense hydrothermal-metasomatic alteration and metamorphism, which are reflected in the evolution of the mineral parageneses. The primary minerals are fluorapatite, magnetite, ilmenite, dolomite, K-feldspar, phlogopite and accessory zircon, titanite, baddeleyite and thorite. The hydrothermal-metasomatic minerals are quartz, calcite and siderite aggregates with haematite, monazite-(Ce), xenotime-(Y), rutile-(Nb), barite-(Sr), anhydrite, ancylite-(Ce) and rare sulphide mineral phases. Alkaline rocks associated with the Muostalaah complex, were also studied. The following U-Pb ages have been obtained (Ma): 1930 ± 7 for Muostalaah alkaline basic rocks, 1906 ± 6 for Muostalaah carbonatites, and 1880 ± 13 and 1878 ± 17 for Seligdar and Ust-Chulman carbonatites, respectively.

Apatite-bearing ore occurrence Muostalaah and phosphate deposit Birikeen are magnesiocarbonatite complexes of the Seligdar type, located within the Nimnyrskaya submeridional metallogenic domain in the Aldan-Stanovoy shield in South Yakutia, Russia. This study presents geochemical characteristics of carbonatites and adjacent apatite-bearing silicate rocks of the Birikeen apatite deposit and Muostalaah apatite occurrence. Comparison of these complexes with the Seligdar deposit and other magnesiocarbonatite complexes of the world was made. Based on the chemical analysis of the petrogenic components of the Muostalaah and Biriken carbonatites, it was concluded that these rocks belong to magnesiocarbonatites, similar to the magnesiocarbonatites of the Seligdar deposit. The chondrite-normalized REE spectra of magnesiocarbonatites and apatite rocks are characterized by LREE enrichment relative to HREE with average La/Yb(cn) ratios of 45 and 100 for the Muostalaah and Birikeen rocks, respectively. Most of the REE patterns are within the field of the world magnesiocarbonatites. The trace-elements abundances of carbonatites and apatite rocks record negative Nb, Pb, Sr, Zr, Hf and Ti anomalies and Th, U and REE enrichment. Сoncentrations of Th, U, Zr, and Hf are characterized by a wide spread of values. The trace-element patterns of the Birikeen and Muostalaah carbonatites are generally similar to the patterns of the world magnesiocarbonatites, including Seligdar rocks. Based on the results of isotopic studies of the Sm/Nd and Rb/Sr systems, it was concluded that the primary melts for the Muostalah and Birikeen carbonatites were formed from a long-lived enriched mantle source that separated from the depleted mantle in the Late Archean.

Novel NaIL detector (5 × 6 inch) was investigated for its neutron detection in wide energy range. It has been found that the detector together with its known ability to detect the γ-radiation it also allows to distinguish neutron signals in three quasi-independent ways. It is sensitive to neutron fluxes on a level down to 10-3 cm-2 s-1. In this work intrinsic α-background and neutron detection sensitivity for the NaIL detector were obtained. Experimental data was compared with results of Geant4 Monte Carlo (MC).

A deficiency in GM3-derived gangliosides, resulting from a lack of lactosylceramide-alpha-2,3-sialyltransferase (ST3GAL5), leads to severe neuropathology, including epilepsy and metabolic abnormalities. Disruption of ganglioside production by this enzyme may also have a role in the development of neuropsychiatric disorders. ST3Gal5 knock-out (St3gal5−/−) mice lack a-, b-, and c-series gangliosides, but exhibit no overt neuropathology, possibly owing to the production of compensatory 0-series glycosphingolipids. Here, we sought to investigate the possibility that St3gal5−/− mice might exhibit attention-deficit/hyperactivity disorder (ADHD)-like behaviours. In addition, we evaluated potential metabolic and electroencephalogram (EEG) abnormalities. St3gal5−/− mice were subjected to behavioural testing, glucose tolerance tests, and the levels of expression of brain and peripheral A and B isoforms of the insulin receptor (IR) were measured. We found that St3gal5−/− mice exhibit locomotor hyperactivity, impulsivity, neophobia, and anxiety-like behavior. The genotype also altered blood glucose levels and glucose tolerance. A sex bias was consistently found in relation to body mass and peripheral IR expression. Analysis of the EEG revealed an increase in amplitude in St3gal5−/− mice. Together, St3gal5−/− mice exhibit ADHD-like behaviours, altered metabolic and EEG measures providing a useful platform for better understanding of the contribution of brain gangliosides to ADHD and associated comorbidities.

The inmate subculture in Russia has a lot of common characteristics with such kind of subcultures in other countries all over the world. It is widely discussed whether inmate subculture is much more dangerous for the society than the criminal or gang subcultures and whether it can influence the traditional culture up to the point of the traditional value system destruction. There is a consensus between the researchers that the possible damage caused by the inmate culture depends on its penetration rate in traditional culture, which is unique for every society. It can be supposed that the high level of potential cultural damage differs Russian inmate subculture from the others. Inmate subculture is of great interest for all modern science. Despite the large number of the studies dedicated to the inmate subculture, it can be hardly named at least one, which is based on the system analysis and uses its methods. In presented research, the authors attempted to discuss the possibility of applying the set-theoretic analysis for inmate subculture taking into consideration the open systems synthetic characteristics. The article analyses the emergence, inseparability, inherency and expediency of the inmate subculture. The possibilities of applying this method as countermeasures against the inmate subculture spread are shown.

KEY POINTS Alzheimer's disease (AD) patients and transgenic mice have beta-amyloid (Aβ) aggregation in the gastrointestinal (GI) tract. It is possible that Aβ from the periphery contributes to the load of Aβ in the brain, as Aβ has prion-like properties. The present investigations demonstrate that Aβ injected into the GI tract of ICR mice is internalised into enteric cholinergic neurons; at 1 month, administration of Aβ into the body of the stomach and the proximal colon was observed to partly redistribute to the fundus and jejunum; at 1 year, vagal and cerebral β-amyloidosis was present, and mice exhibited GI dysfunction and cognitive deficits. These data reveal a previously undiscovered mechanism that potentially contributes to the development of AD. ABSTRACT Alzheimer's disease (AD) is the most common age-related cause of dementia, characterised by extracellular beta-amyloid (Aβ) plaques and intracellular phosphorylated tau tangles in the brain. Aβ deposits have also been observed in the gastrointestinal (GI) tract of AD patients and transgenic mice, with overexpression of amyloid precursor protein. In the present studies, we investigate whether intra-GI administration of Aβ can potentially induce amyloidosis in the central nervous system (CNS) and AD-related pathology such as dementia. We micro-injected Aβ1-42 oligomers (4 μg per site, five sites) or vehicle (saline, 5 μl) into the gastric wall of ICR mice under general anaesthesia. Immunofluorescence staining and in vivo imaging showed that HiLyte Fluor 555-labelled Aβ1-42 had migrated within 3 h via the submucosa to nearby areas and was internalised into cholinergic neurons. At 1 month, HiLyte Fluor 555-labelled Aβ1-42 in the body of the stomach and proximal colon had partly re-distributed to the fundus and jejunum. At 1 year, the jejunum showed functional alterations in neuromuscular coupling (P

Background In Alzheimer's diseases, beta-amyloid may act as prion-like protein and migrate from the gastrointestinal tract towards the brain. Soy flavonoids have been identified as neuroprotective against cognitive loss in human. Diet with soy flavonoids may be used to slow down the progression of Alzheimer's diseases. Methods and results We performed in-vitro tissue culture experiments using myenteric plexus longitudinal muscle layers isolated from the ileum and colon of ICR mice. Beta-amyloid can be taken up into myenteric neurons and induce neuron degeneration, which is protected by flavonoids compounds, including daidzein, genistein, glycitein and luteolin. We also administered oligomeric beta-amyloid (1–42) (total dose: 8 μg) into the gastrointestinal walls of ICR mice and conducted memory tests and gastrointestinal function assessments after 6 and 12 months. Mice treated with beta-amyloid exhibited minor learning deficits in a T-maze memory test at 6 months and significant memory impairment in a novel object recognition task at 12 months. These impairments were prevented by soy flavonoids. Tracking studies performed using fluorescently tagged beta-amyloid found that, beta-amyloid injected at the stomach can aggregate within the layer of myenteric neurons and migrate to the jejunum or via the vagus nerves to the brain after 1 month. Reductions in the gastrointestinal tissue weight and the spontaneous ileal contraction frequency were also observed at 6 and 12 months, respectively. Conclusion Our findings indicate that beta-amyloid can migrate from the gastrointestinal tract to the brain to induce cognitive impairments. Furthermore, chronic soy flavonoids in drinking water have protective actions.

International audience; In this work, we report the production process of a low-radioactive NH4Cl inorganic flux. A γ-ray screening with ultra-low background HPGe spectrometer at LSM underground laboratory and ICP-MS elemental analysis have been performed to estimate the radioactivity level and composition of the final product.

It is generally accepted that inflammation within the CNS contributes to neurodegeneration after traumatic brain injury (TBI), but it is not clear how inflammation is initiated in the absence of infection and whether this neuroinflammation is predominantly beneficial or detrimental. We have previously found that brain-enriched glycosphingolipids within neuronal lipid rafts (NLR) induced platelet degranulation and secretion of neuro-transmitters and pro-inflammatory factors. In the present study, we compared TBI-induced inflammation and neurodegeneration in wild-type vs. St3gal5 deficient (ST3(-/-)) mice that lack major CNS-specific glycosphingolipids. After TBI, microglial activation and CNS macrophage infiltration were substantially reduced in ST3(-/-) animals. However, ST3(-/-) mice had a larger area of CNS damage with marked neuronal/axonal loss. The interaction of platelets with NLR stimulated neurite growth, increased the number of PSD95-positive dendritic spines, and intensified neuronal activity. Adoptive transfer and blocking experiments provide further that platelet-derived serotonin and platelet activating factor plays a key role in the regulation of sterile neuroinflammation,hemorrhage and neuronal plasticity after TBI.

In contrast to peripheral macrophages, microglia in the central nervous system (CNS) exhibit a specific deactivated phenotype; however, it is not clear how this phenotype is maintained. Two alternative hypotheses were postulated recently: (a) microglia differ from peripheral macrophages being derived from the yolk sac (YS), whereas peripheral macrophages originate from bone marrow (BM); (b) microglia acquire a specific phenotype under the influence of the CNS microenvironment. We have previously shown that microglia express miR‐124, which was also induced in BM‐derived macrophages co‐cultured with a neurons. We here investigated the possibility of horizontal transfer of the neuron‐specific microRNAs miR‐124 and miR‐9 from primary neurons to microglia/macrophages. We found that after incubation with neuronal conditioned media (NCM), macrophages downregulated activation markers MHC class II and CD45. Neither cultured adult microglia nor YS‐ and BM‐derived macrophages demonstrated intrinsic levels of miR‐124 expression. However, after incubation with NCM, miR‐124 was induced in both YS‐ and BM‐derived macrophages. Biochemical analysis demonstrated that the NCM contained miR‐124 and miR‐9 in complex with small proteins, large high‐density lipoproteins (HDLs), and exosomes. MiR‐124 and miR‐9 were promptly released from neurons, and this process was inhibited by tetrodotoxin, indicating an important role of neuronal electric activity in secretion of these microRNAs. Incubation of macrophages with exogenous miR‐124 resulted in efficient translocation of miR‐124 into the cytoplasm. This study demonstrates an important role of neuronal miRNAs in communication of neurons with microglia, which favors the hypothesis that microglia acquire a specific phenotype under the influence of the CNS microenvironment.

Platelets, or thrombocytes, are important players in inflammation, wound healing, initiation of immune response and regeneration in the organism. Disruption of the blood-brain barrier occurs during certain neurological disorders, such as brain trauma, Alzheimer’s disease or stroke, when blood cells including platelets can invade nervous tissue. However, the role of platelets in the context of neuroinflammation remains understudied. Recent studies have shown that activated platelets release a wide set of coagulative and vascular factors during neurovascular pathologies in the central nervous system. Moreover, platelets stimulate immunity and regulate inflammation in the central nervous system. Trophic and growth factors stored in platelets may play a role in neuronal regeneration. Activated platelets release neurotransmitters, serotonin, dopamine, histamine, and glutamate, and can modify neuronal cell activity in neuropathologies. This review focuses on the major aspects and mechanisms of platelet functions in neuroinflammation, and therapeutic potential of platelets for treatment of neurodegenerative disorders.

Copyright © John Wiley & Sons, Inc. All rights reserved., While the insulin receptor (IR) was found in the CNS decades ago, the brain was long considered to be an insulin-insensitive organ. This view is currently revisited, given emerging evidence of critical roles of IR-mediated signaling in development, neuroprotection, metabolism, and plasticity in the brain. These diverse cellular and physiological IR activities are distinct from metabolic IR functions in peripheral tissues, thus highlighting region specificity of IR properties. This particularly concerns the fact that two IR isoforms, A and B, are predominantly expressed in either the brain or peripheral tissues, respectively, and neurons express exclusively IR-A. Intriguingly, in comparison with IR-B, IR-A displays high binding affinity and is also activated by low concentrations of insulin-like growth factor-2 (IGF-2), a regulator of neuronal plasticity, whose dysregulation is associated with neuropathologic processes. Deficiencies in IR activation, insulin availability, and downstream IR-related mechanisms may result in aberrant IR-mediated functions and, subsequently, a broad range of brain disorders, including neurodevelopmental syndromes, neoplasms, neurodegenerative conditions, and depression. Here, we discuss findings on the brain-specific features of IR-mediated signaling with focus on mechanisms of primary receptor activation and their roles in the neuropathology. We aimed to uncover the remaining gaps in current knowledge on IR physiology and highlight new therapies targeting IR, such as IR sensitizers., The work reported here was supported by the European Community (EC: the European Union's Seventh Framework Programme (FP7/2007–2013) under Grant No. 602805 (Aggressotype), the Horizon 2020 Research and Innovation Programme under Grant No. 728018 (Eat2beNICE), the “5-100” Russian Academic Excellence Project (to KPL and TS), and the German Research Foundation (DFG: SFB TRR58-A05 to KPL).

The first results of neutron-flux measurements at the LSM underground laboratory (Modane, France) using a new sensitive method are presented. Neutrons are detected by counting delayed γγ coincidences in the 127I(n, γ)128I reaction. It is shown that this approach makes it possible to measure thermal-neutron fluxes at a level of 10–6 neutron cm–2 s–1.

Glycogen synthase kinase 3 (GSK3) has been linked to the mechanisms of stress, mood regulation, and the effects of antidepressants. The functions of the GSK3 beta isoform have been extensively investigated, but little is known about the a-isoform, although they may functionally related. In a recently established modified swim test with a third delayed swim exposure, brain GSK3 beta mRNA expression positively correlated with floating behaviour on the third test. A two-week-long pretreatment regime with imipramine (7.5 mg/kg/day) or thiamine (200 mg/kg/ day), which is known to have antidepressant properties, reduced the GSK3 beta over-expression and decreased floating behaviour on Day 5. GSK3 alpha mRNA levels were measured in the hippocampus and prefrontal cortex on Days 1, 2 and 5. GSK3 alpha expression was decreased in the prefrontal cortex on Day 2 and increased on Day 5. In this model, GSK3 alpha mRNA changes were prevented by imipramine or thiamine treatment. There was a significant correlation between the expression of the two isoforms in the prefrontal cortex on Day 2 in untreated group. These results provide the first evidence for the potential involvement of GSK3 alpha in depressive-like behaviours and as a target of anti-depressant therapy. Furthermore, the correlations suggest some cross-talk may exist between the two GSK3 isoforms.

The negative societal impacts associated with the increasing prevalence of violence and aggression is increasing, and, with this rise, is the need to understand the molecular and cellular changes that underpin ultrasound-induced aggressive behavior. In mice, stress-induced aggression is known to alter AMPA receptor subunit expression, plasticity markers, and oxidative stress within the brain. Here, we induced aggression in BALB/c mice using chronic ultrasound exposure and examined the impact of the psychoactive anti-oxidant compounds thiamine (vitamin B1), and its derivative benfotiamine, on AMPA receptor subunit expression, established plasticity markers, and oxidative stress. The administration of thiamine or benfotiamine (200 mg/kg/day) in drinking water decreased aggressive behavior following 3-weeks of ultrasound exposure and benfotiamine, reduced floating behavior in the swim test. The vehicle-treated ultrasound-exposed mice exhibited increases in protein carbonyl and total glutathione, altered AMPA receptor subunits expression, and decreased expression of plasticity markers. These ultrasound-induced effects were ameliorated by thiamine and benfotiamine treatment; in particular both antioxidants were able to reverse ultrasound-induced changes in GluA1 and GluA2 subunit expression, and, within the prefrontal cortex, significantly reversed the changes in protein carbonyl and polysialylated form of neural cell adhesion molecule (PSA-NCAM) expression levels. Benfotiamine was usually more efficacious than thiamine. Thus, the thiamine compounds were able to counteract ultrasound-induced aggression, which was accompanied by the normalization of markers that have been showed to be associated with ultrasound-induced aggression. These commonly used, orally-active compounds may have considerable potential for use in the control of aggression within the community.This article is part of the Special Issue entitled 'Current status of the neurobiology of aggression and impulsivity'.

The article is devoted to the study of five reactive power compensator circuits. The schemes based on the reactive voltage inverter and three different AC voltage regulator circuits are presented. Simulation, calculation of the grid current quality by the direct method, a comparative assessment of the component elements’ cost for the considered circuits are suggested.

Emotional stress is a form of stress evoked by processing negative mental experience rather than an organic or physical disturbance and is a frequent cause of neuropsychiatric pathologies, including depression. Susceptibility to emotional stress is commonly regarded as a human-specific trait that is challenging to model in other species. Recently, we showed that a 3-week-long exposure to ultrasound of unpredictable alternating frequencies within the ranges of 20-25 kHz and 25-45 kHz can induce depression-like characteristics in laboratory mice and rats. In an anti-depressant sensitive manner, exposure decreases sucrose preference, elevates behavioural despair, increases aggression, and alters serotonin-related gene expression. To further investigate this paradigm, we studied depression/distress-associated markers of neuroinflammation, neuroplasticity, oxidative stress and the activity of glycogen synthase kinase-3 (GSK-3) isoforms in the hippocampus of male mice. Stressed mice exhibited a decreased density of Ki67-positive and DCX-positive cells in the subgranular zone of hippocampus, and altered expression of brain-derived neurotrophic factor (BDNF), its receptor TrkB, and anti-apoptotic protein kinase B phosphorylated at serine 473 (AktpSer473). The mice also exhibited increased densities of Iba-1-positive cells, increased oxidative stress, increased levels of interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6) in the hippocampus and plasma, and elevated activity of GSK-3 isoforms. Together, the results of our investigation have revealed that unpredictable alternating ultrasound evokes behavioural and molecular changes that are characteristic of the depressive syndrome and validates this new and simple method of modeling emotional stress in rodents.

The paper offers a comprehensive set of characteristics of integrated security systems for electronic document management, which allows conducting research on the degree of protection of such systems from external and internal threats from the point of view of system analysis and modeling their functioning in various conditions. Classification descriptions are given and data analysis is performed when modeling decision-making processes in integrated security systems on the example of responding to threats of information leakage through parametric channels. The optimal set of response measures is given for performing illegal actions by an attacker to intercept information via parametric channels when using the corresponding modes of operation of the TCP Protocol. The type of analytical models of performance characteristics of measures to respond to threats of information leakage through parametric channels is determined by the functional model of such measures. The resulting system-level characteristics of effective response to the threat of information leakage on parametric channels is based on the stochastic representation of the conditions for timely interventions.

An experimental facility for testing and calibrating nuclear planetology instruments has been constructed in partnership between the Space Research Institute (Moscow) and the Joint Institute for Nuclear Research. A model of Martian soil with a size of 3.82 × 3.21 m2 and an overall mass of about 30 t is assembled from silicate glass. Glass is chosen in order to imitate absolutely dry soil close in composition to the Martian one. The heterogeneous model allows one to imitate the average elemental composition of Martian soil in the best possible way by adding layers of the necessary materials to it. Near-surface water ice is simulated by polyethylene layers buried at different depths within the glass model. A portable neutron generator is used as the neutron source for testing active neutron and gamma spectrometers. The facility is radiation-hazardous and is thus equipped with interlock and radiation monitoring systems in accordance with the effective regulations.