Pharmacodynamics of the Glutamate Receptor Antagonists in the Rat Barrel Cortex

Epipial application is one of the approaches for drug delivery into the cortex. However, passive diffusion of epipially applied drugs through the cortical depth may be slow, and different drug concentrations may be achieved at different rates across the cortical depth. Here, we explored the pharmacodynamics of the inhibitory effects of epipially applied ionotropic glutamate receptor antagonists CNQX and dAPV on sensory-evoked and spontaneous activity across layers of the cortical barrel column in urethane-anesthetized rats. The inhibitory effects of CNQX and dAPV were observed at concentrations that were an order higher than in slices in vitro, and they slowly developed from the cortical surface to depth after epipial application. The level of the inhibitory effects also followed the surface-to-depth gradient, with full inhibition of sensory evoked potentials (SEPs) in the supragranular layers and L4 and only partial inhibition in L5 and L6. During epipial CNQX and dAPV application, spontaneous activity and the late component of multiple unit activity (MUA) during sensory-evoked responses were suppressed faster than the short-latency MUA component. Despite complete suppression of SEPs in L4, sensory-evoked short-latency multiunit responses in L4 persisted, and they were suppressed by further addition of lidocaine suggesting that spikes in thalamocortical axons contribute ∼20% to early multiunit responses. Epipial CNQX and dAPV also completely suppressed sensory-evoked very fast (∼500 Hz) oscillations and spontaneous slow wave activity in L2/3 and L4. However, delta oscillations persisted in L5/6. Thus, CNQX and dAPV exert inhibitory actions on cortical activity during epipial application at much higher concentrations than in vitro, and the pharmacodynamics of their inhibitory effects is characterized by the surface-to-depth gradients in the rate of development and the level of inhibition of sensory-evoked and spontaneous cortical activity

Anion-mediated photophysical behavior in a C60 fullerene [3]rotaxane shuttle

By addressing the challenge of controlling molecular motion, mechanically interlocked molecular machines are primed for a variety of applications in the field of nanotechnology. Specifically, the designed manipulation of communication pathways between electron donor and acceptor moieties that are strategically integrated into dynamic photoactive rotaxanes and catenanes may lead to efficient artificial photosynthetic devices. In this pursuit, a novel [3]rotaxane molecular shuttle consisting of a four-station bis-naphthalene diimide (NDI) and central C60 fullerene bis-triazolium axle component and two mechanically bonded ferrocenyl-functionalized isophthalamide anion binding site-containing macrocycles is constructed using an anion template synthetic methodology. Dynamic coconformational anion recognition-mediated shuttling, which alters the relative positions of the electron donor and acceptor motifs of the [3]rotaxane’s macrocycle and axle components, is demonstrated initially by 1H NMR spectroscopy. Detailed steady-state and time-resolved UV–vis–IR absorption and emission spectroscopies as well as electrochemical studies are employed to further probe the anion-dependent positional macrocycle–axle station state of the molecular shuttle, revealing a striking on/off switchable emission response induced by anion binding. Specifically, the [3]rotaxane chloride coconformation, where the ferrocenyl-functionalized macrocycles reside at the center of the axle component, precludes electron transfer to NDI, resulting in the switching-on of emission from the NDI fluorophore and concomitant formation of a C60 fullerene-based charge-separated state. By stark contrast, in the absence of chloride as the hexafluorophosphate salt, the ferrocenyl-functionalized macrocycles shuttle to the peripheral NDI axle stations, quenching the NDI emission via formation of a NDI-containing charge-separated state. Such anion-mediated control of the photophysical behavior of a rotaxane through molecular motion is unprecedented

Large-scale analysis of structural brain asymmetries in schizophrenia via the ENIGMA consortium

Left-right asymmetry is an important organizing feature of the healthy brain that may be altered in schizophrenia, but most studies have used relatively small samples and heterogeneous approaches, resulting in equivocal findings. We carried out the largest case-control study of structural brain asymmetries in schizophrenia, using MRI data from 5,080 affected individuals and 6,015 controls across 46 datasets in the ENIGMA consortium, using a single image analysis protocol. Asymmetry indexes were calculated for global and regional cortical thickness, surface area, and subcortical volume measures. Differences of asymmetry were calculated between affected individuals and controls per dataset, and effect sizes were meta-analyzed across datasets. Small average case-control differences were observed for thickness asymmetries of the rostral anterior cingulate and the middle temporal gyrus, both driven by thinner left-hemispheric cortices in schizophrenia. Analyses of these asymmetries with respect to the use of antipsychotic medication and other clinical variables did not show any significant associations. Assessment of age- and sex-specific effects revealed a stronger average leftward asymmetry of pallidum volume between older cases and controls. Case-control differences in a multivariate context were assessed in a subset of the data (N = 2,029), which revealed that 7% of the variance across all structural asymmetries was explained by case-control status. Subtle case-control differences of brain macro-structural asymmetry may reflect differences at the molecular, cytoarchitectonic or circuit levels that have functional relevance for the disorder. Reduced left middle temporal cortical thickness is consistent with altered left-hemisphere language network organization in schizophrenia

Cortical brain abnormalities in 4474 individuals with schizophrenia and 5098 control subjects via the enhancing neuro Imaging genetics through meta analysis (ENIGMA) Consortium

BACKGROUND: The profile of cortical neuroanatomical abnormalities in schizophrenia is not fully understood, despite hundreds of published structural brain imaging studies. This study presents the first meta-analysis of cortical thickness and surface area abnormalities in schizophrenia conducted by the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) Schizophrenia Working Group. METHODS: The study included data from 4474 individuals with schizophrenia (mean age, 32.3 years; range, 11-78 years; 66% male) and 5098 healthy volunteers (mean age, 32.8 years; range, 10-87 years; 53% male) assessed with standardized methods at 39 centers worldwide. RESULTS: Compared with healthy volunteers, individuals with schizophrenia have widespread thinner cortex (left/right hemisphere: Cohen's d = -0.530/-0.516) and smaller surface area (left/right hemisphere: Cohen's d = -0.251/-0.254), with the largest effect sizes for both in frontal and temporal lobe regions. Regional group differences in cortical thickness remained significant when statistically controlling for global cortical thickness, suggesting regional specificity. In contrast, effects for cortical surface area appear global. Case-control, negative, cortical thickness effect sizes were two to three times larger in individuals receiving antipsychotic medication relative to unmedicated individuals. Negative correlations between age and bilateral temporal pole thickness were stronger in individuals with schizophrenia than in healthy volunteers. Regional cortical thickness showed significant negative correlations with normalized medication dose, symptom severity, and duration of illness and positive correlations with age at onset. CONCLUSIONS: The findings indicate that the ENIGMA meta-analysis approach can achieve robust findings in clinical neuroscience studies; also, medication effects should be taken into account in future genetic association studies of cortical thickness in schizophrenia

Improving the energy efficiency of wide crossings of overhead power lines

The use of new generation wires in the design of wide spans of overhead power lines over water barriers and large gorges can increase their transmission capacity and increase reliability. However, when large currents flow, load losses in line also increase. Thus, it is necessary to obtain a methodology for technical and economic comparison of design options for overhead power lines over large crossings, which enables to determine the most cost-effective version of the project with high mechanical reliability. For comparative analysis, five options for wide spans of overhead power lines over the river with new-generation wires of Russian production were compiled: Aluminium Alloy Conductor Steel Reinforced, Z-type (high conductivity), Thermal-Resistant Conductor, Aluminium Compozite Core Conductor, ASk2y. Option with Aluminium Conductor Steel Reinforced wire was taken as the source. For the first option, the crossing scheme E-A-A-E was selected, for the remaining options E-I-I-E scheme was considered. For the modes of maximum loads, minimum temperature and average annual conditions, the mechanical calculation of wires was carried out using the method of permissible stresses. The wire bending deflections were determined in accordance with the theory of the catenary curve. The method of integrated indicators was used to perform a technical and economic comparison of these options. The calculation results showed that among the proposed options, the most optimal is a crossing with the ACCC wire having minimum relative investment per 1 MW of transmitted electricity and minimal power loss. The transmission capacity of the line with this wire is increased by 1.8 times, and the cost of crossing is reduced by 16%. Due to the compact design of wire, the probability of ice formation on wire is reduced, and the reduced bending deflection reduces the probability of wire break due to natural environmental influences

The Effects of NMDA Receptor Blockade on Sensory-Evoked Responses in Superficial Layers of the Rat Barrel Cortex

International audienceTransmission of excitation from L4 to L2/3 is a part of a canonical circuit of cortical sensory signal processing. While synapses from L4 to L2/3 are mediated by both AMPA and NMDA glutamate receptors, previous studies suggested that sensory-evoked excitation of neurons in supragranular layers is almost entirely mediated by NMDA receptors. Here, we readdressed this question using extracellular recordings of sensory-evoked potentials (SEPs) and multiple unit activity (MUA) in the rat barrel cortex. We found that blockade of NMDA receptors using the selective antagonist dAPV profoundly inhibited the late part of L2/3 SEP, the associated sink, and MUA response but did not affect its initial part. Our results indicate that both non-NMDA and NMDA receptors are involved in sensory signal transmission from L4 to L2/3. While non-NMDA receptors mediate fast transmission of sensory signals, NMDA-Rs are importantly involved in the generation of the late phase of the sensory-evoked response in supragranular layers

Моделированиe Сферы Обращения С Отходами Производства И Потребления

The article shows how the digitalization of industry influences the development of the economy and is able to change the structure of the world economic system, which includes the potential of buyers, the structure of industry sectors, and the significance of the state. The beneficial effects of the industry digitalization can be noted in all layers of society, from individual buyers to the state in general. The purpose of the work is to analyze the level of digitalization of industrial enterprises and the development of measures to improve this process, as well as to assess the impact of digitalization on the economic security of the state. When working on the topic, various general research methods were employed including analysis of legal documentation, classification, and generalization. The peculiarity of the industry digitalization is that the main resource is the knowledge, information, and technical and technological part of the digital base.El artículo muestra cómo la digitalización de la industria afecta el desarrollo de la economía y puede cambiar la estructura del sistema económico global, que incluye el potencial de los compradores, la estructura de las industrias y la importancia del estado. Los efectos positivos de la digitalización de la industria están presentes en absolutamente todas las capas, desde los clientes individuales hasta el estado en su conjunto. El propósito del trabajo es analizar el estado del nivel de digitalización de una empresa industrial y desarrollar medidas para aumentarlo y evaluar el impacto de la digitalización para garantizar la seguridad económica del estado. Al escribir el trabajo, se utilizaron varios métodos generales de investigación científica, análisis de documentos reglamentarios, clasificación, generalización. Una característica de la digitalización de la industria es que el principal recurso es el conocimiento, la información y la parte técnica y tecnológica de la base digital.Отходы являются одной из причин нарушения естественных биогеохимических циклов, занимают значительные территории для складирования, загрязняют вредными и токсичными веществами, пылью, газообразными выделениями атмосферу, почву, поверхностные и подземные воды, регулирование их потоков является важной необходимостью для обеспечения благоприятной среды обитания человека. Влияние ситуации в сфере образования отходов на общую экологическую обстановку критично, что обуславливает необходимость учета данного фактора при оценке экономического развития. Экологическая ситуация в России многими экологами оценивается как стабильно негативная, не претерпевающая серьезных улучшений. По данным Росстата за последнее десятилетие сократились ежегодные сбросы в водоемы сточных вод (на 15,7% с 2005 по 2015 гг) и загрязняющих атмосферу веществ (на 12,7% за этот же период), что объясняется кризисными явлениями в экономике (в 2008 и 2015 годах) и некоторым ужесточением природоохранного законодательства (повышением платежей за негативное воздействие на окружающую природную среду). В статье рассматриваются методические подходы к анализу и прогнозированию процессов, происходящих в сфере обращения с отходами производства и потребления. Приведены результаты прогноза объемов накопленных отходов с использованием динамической модели межотраслевого баланса. Рассчитаны показатели полной отходоемкости по видам экономической деятельности