Nitric oxide mediates local activity-dependent excitatory synapse development

Learning related paradigms play an important role in shaping the development and specificity of synaptic networks, notably by regulating mechanisms of spine growth and pruning. The molecular events underlying these synaptic rearrangements remain poorly understood. Here we identify NO signaling as a key mediator of activity-dependent excitatory synapse development. We find that chronic blockade of NO production in vitro and in vivo interferes with the development of hippocampal and cortical excitatory spine synapses. The effect results from a selective loss of activity-mediated spine growth mechanisms and is associated with morphological and functional alterations of remaining synapses. These effects of NO are mediated by a cGMP cascade and can be reproduced or prevented by postsynaptic expression of vasodilator-stimulated phosphoprotein phospho-mimetic or phospho-resistant mutants. In vivo analyses show that absence of NO prevents the increase in excitatory synapse density induced by environmental enrichment and interferes with the formation of local clusters of excitatory synapses. We conclude that NO plays an important role in regulating the development of excitatory synapses by promoting local activity-dependent spine-growth mechanisms

Inhibition of T-type calcium channels protects neurons from delayed ischemia-induced damage.Mol

Abstract: 174 words Introduction: 536 word

Observer-based speed estimation for vector controlled induction motors

A speed observer for field-oriented controlled induction drives is presented. The proposed solution exploits the concept of the classic full-order flux observer which is adaptive to the rotor resistance variations. Due to the structural similarity of the rotor speed and active rotor resistance in motor model, the speed observer can be designed using similar structure. The observer guarantees local asymptotic estimation of the rotor fluxes, stator currents and rotor speed in all operating conditions, excluding DC stator excitation. The stability properties of the observer are studied using Lyapunov’s second method. It is experimentally shown that the observer provides an acceptable dynamics of the speed estimation if speed is slowly varying. The proposed observer is suitable for the applications with medium requirements for speed regulation performance

Peculiarities of structure and phase composition of V-Ti-Cr alloy obtained by sintering technique

Abstract Alloy of the V-Ti-Cr system is a promising material exploited under high radiation and in corrosion environment. We sintered V-4.9Ti-4.8Cr alloy from particles with original average size of 30, 280 and 200 μm, respectively for vanadium, titanium and chromium powders, by pressing of the powder mixture and its further sintering. The studies were undertaken using the methods of X-ray structural analysis, scanning electron microscopy with an energy dispersive analyzer and transmission electron microscopy. It was established that the structure of the alloy represented matrix grains (BCC solid solution), along the boundaries and at junctions of which the groups of oxycarbonitride particles of V, Ti, Cr (C,N,O) type of the variable elemental composition were arranged. The particles possessed a plate-like (0.4 x 2.0 μm) and rounded (0.5 μm) shape. The solid solution of the alloy was heterogeneous by concentration. This was evidenced by the complications of the diffraction patterns obtained from the corresponding sections of the structure. These were cords of main reflexes, satellites and emergence of a moire banded contrast in separate sections of the sample. Inside the matrix grains, there were nanoparticles (15 μm) of carbide V55Cr25C20, being a source of elastic internal local stresses

Моделирование управления потоками данных в корпоративных IP-сетях

Розглянуто моделі трьох методів управління мережевим трафіком, що забезпечують недопущення перевантажень телекомунікаційних каналів. В основу апаратної моделі лягла технологія обмеження потоків даних через мережеві вузли. Програмна модель є регулятором, який на основі порівняння вхідного та бажаного значень завантаженості каналів виробляє команди для джерел трафіку. Третя модель використовує методи теорії автоматичного управління для обмеження потоків трафіку, а саме оптимальний по швидкодії регулятор. Наводиться структура і опис всіх цих моделей, а також проаналізовані переваги та недоліки кожної з моделей за такими критеріями: швидкодія регулятора, тобто швидкість, з якою регулятор виробляє необхідну керуючу дію; вплив затримок передачі даних на своєчасність регулюючої дії; види трафіку, які здатен регулювати регулятор; простота розрахунку та реалізації регулятора; ефективне використання наявних мережевих ресурсів.Three network traffic management models preventing telecommunication links overloads have been considered here. Hardware model is based upon limitation of data streams flowing through network nodes. Program model is presented by a controller which by means of comparing input and desired values of channel load generates commands for the traffic sources. The third model uses the methods of automatic control theory to manage the flow of traffic, in particular the regulator with optimal performance. The structure and description of all models, as well as the advantages and disadvantages of each model, by such criteria: speed of controller (the speed with which the controller produces management commands); the impact of data transferring delays on the timeliness of the managing; types of traffic which can be managed by the controller; simplicity of controller's calculation and implementation; effective use of available network resources, are included.Рассмотрены модели трех методов управления сетевым трафиком, которые обеспечивают недопущение перегрузок телекоммуникационных каналов. В основу аппаратной модели легла технология ограничения потоков данных, проходящих через сетевые узлы. Программная модель является регулятором, который на основе сравнения входного и желаемого значений загруженности каналов вырабатывает команды для источников трафика. Третья модель использует методы теории автоматичного управления для ограничения потоков трафика, а именно оптимальный по быстродействию регулятор. Приводится структура и описание всех этих моделей, а также проанализированы преимущества и недостатки каждой моделей по следующим критериям: быстродействие регулятора, то есть скорость, с которой регулятор вырабатывает необходимое управляющее воздействие; влияние задержек передачи данных на своевременность регулирующего воздействия; виды трафика, которые способен ограничивать регулятор; простота расчета и реализации регулятора; эффективное использование имеющихся сетевых ресурсов

A Mathematical model for Astrocytes mediated LTP at Single Hippocampal Synapses

Many contemporary studies have shown that astrocytes play a significant role in modulating both short and long form of synaptic plasticity. There are very few experimental models which elucidate the role of astrocyte over Long-term Potentiation (LTP). Recently, Perea & Araque (2007) demonstrated a role of astrocytes in induction of LTP at single hippocampal synapses. They suggested a purely pre-synaptic basis for induction of this N-methyl-D- Aspartate (NMDA) Receptor-independent LTP. Also, the mechanisms underlying this pre-synaptic induction were not investigated. Here, in this article, we propose a mathematical model for astrocyte modulated LTP which successfully emulates the experimental findings of Perea & Araque (2007). Our study suggests the role of retrograde messengers, possibly Nitric Oxide (NO), for this pre-synaptically modulated LTP.Comment: 51 pages, 15 figures, Journal of Computational Neuroscience (to appear

МОРФОЛОГИЧЕСКИЕ ПРЕДИКТОРЫ ФУНКЦИИ ПОЧЕЧНОГО АЛЛОТРАНСПЛАНТАТА (ПАТ) В ПЕРВЫЙ ГОД ПОСЛЕ ОПЕРАЦИИ

The retrospective analysis of the influence of histological changes in donor kidneys on the KAG function during first year was conducted in 75 recipients of a cadaveric kidney. The state of tubuli, glomeruli, interstitium, vessels was assessed semiquantitatively in the material of «0»-biopsies. The endpoints were serum creatinine and glomerular filtration rate at 3, 6 and 12 months. KAG function in the first year is programmed by histological changes in all compartments of donor kidney. Influence of histological changes is time-dependent: the effect of ischemic damage shows up quickly, but disappeared after 6 months; the effect of arteriolohyalinosis and arteriosclerosis begins to show up later – since 6 months; changes in glomeruli have influence on a KAG function in 3 months and 1 year; interstitial fibrosis in cortex and medulla negatively influences KAG function on the extent of all first year. Our data argue for the necessity of «0»-biopsies examination for the prediction of KAG subsequent function. Проведен ретроспективный анализ влияния гистологических изменений в донорской почке на функцию ПАТ в течение первого года у 75 реципиентов трупной почки. В гистологических срезах «0»-биопсий ме- тодом полуколичественной оценки характеризовали состояние клубочков, канальцев, сосудов и стромы. Оценивали уровень креатинина крови и скорость клубочковой фильтрации в 3, 6 и 12 месяцев. Функция ПАТ в первый год его жизни программируется морфологическими изменениями во всех компартментах донорской почки. Влияние этих изменений времязависимо: эффект ишемического повреждения прояв- ляется в 3 месяца, но нивелируется после 6 месяцев; эффект артериологиалиноза и артериосклероза на- чинает проявляться с 6 месяцев; изменения в клубочках оказывают влияние на функцию ПАТ в 3 месяца и в 1 год; интерстициальный фиброз коркового и мозгового вещества негативно влияет на функцию ПАТ на протяжении всего первого года. Считаем целесообразным гистологическое исследование «0»-биопсий для прогнозирования последующей функции ПАТ.

How “Humane” Is Your Endpoint?—Refining the Science-Driven Approach for Termination of Animal Studies of Chronic Infection

Public concern on issues such as animal welfare or the scientific validity and clinical value of animal research is growing, resulting in increasing regulatory demands for animal research. Abiding to the most stringent animal welfare standards, while having scientific objectives as the main priority, is often challenging. To do so, endpoints of studies involving severe, progressive diseases need to be established considering how early in the disease process the scientific objectives can be achieved. We present here experimental studies of tuberculosis (TB) in mice as a case study for an analysis of present practice and a discussion of how more refined science-based endpoints can be developed. A considerable proportion of studies in this field involve lethal stages, and the establishment of earlier, reliable indicators of disease severity will have a significant impact on animal welfare. While there is an increasing interest from scientists and industry in moving research in this direction, this is still far from being reflected in actual practice. We argue that a major limiting factor is the absence of data on biomarkers that can be used as indicators of disease severity. We discuss the possibility of complementing the widely used weight loss with other relevant biomarkers and the need for validation of these parameters as endpoints. Promotion of ethical guidelines needs to be coupled with systematic research in order to develop humane endpoints beyond the present euthanasia of moribund animals. Such research, as we propose here for chronic infection, can show the way for the development and promotion of welfare policies in other fields of research. Research on chronic infection relies heavily on the use of animals, as only the integral animal body can model the full aspect of an infection. That animals are generally made to develop a disease in infection studies exacerbates the tension between human benefit and animal well-being, which characterizes all biomedical research with animals. Scientists typically justify animal research with reference to potential human benefits, but if accepting the assumption that human benefits can offset animal suffering, it still needs to be argued that the same benefits could not be achieved with less negative effects on animal welfare. Reducing the animal welfare problems associated with research (“refinement” [1]) is therefore crucial in order to render animal-based research less of an ethical problem and to assure public trust in research. Studies that are designed to measure time of death or survival percentages present a particularly challenging situation in which at least some of the animals are made to die from the disease. These studies are frequent in experimental research on severe infections. The scientific community, industry, and regulatory authorities have responded to the ethical concerns over studies in which animals die from severe disease by developing new policies and guidelines for the implementation of humane endpoints as a key refinement measure (e.g., [2]–[4]). The most widely used definition considers a humane endpoint to be the earliest indicator in an animal experiment of severe pain, severe distress, suffering, or impending death [5], underlining that ideally such indicators should be identified before the onset of the most severe effects. Euthanizing animals, rather than awaiting their “spontaneous” death, is important to avoid unnecessary suffering in studies in which data on survival is thought to be required for scientific or legal reasons. However, several questions remain open regarding how humane endpoints are to be applied to address real animal welfare problems. We used TB experiments in mice as a case study to highlight the potential to establish biomarkers of disease progress that can replace survival time as a measure of disease severity.Fundação para a Ciência e Tecnologia (SFRH/BD/38337/2007)