Flux control of cytochrome c oxidase in human skeletal muscle

In the present work, by titrating cytochrome c oxidase (COX) with the specific inhibitor KCN, the flux control coefficient and the metabolic reserve capacity of COX have been determined in human saponin-permeabilized muscle fibers. In the presence of the substrates glutamate and malate, a 2.3 ± 0.2-fold excess capacity of COX was observed in ADP-stimulated human skeletal muscle fibers. This value was found to be dependent on the mitochondrial substrate supply. In the combined presence of glutamate, malate, and succinate, which supported an approximately 1.4-fold higher rate of respiration, only a 1.4 ± 0.2-fold excess capacity of COX was determined. In agreement with these findings, the flux control of COX increased, in the presence of the three substrates, from 0.27 ± 0.03 to 0.36 ± 0.08. These results indicate a tight in vivo control of respiration by COX in human skeletal muscle. This tight control may have significant implications for mitochondrial myopathies. In support of this conclusion, the analysis of skeletal muscle fibers from two patients with chronic progressive external ophthalmoplegia, which carried deletions in 11 and 49% of their mitochondrial DNA, revealed a substantially lowered reserve capacity and increased flux control coefficient of COX, indicating severe rate limitations of oxidative phosphorylation by this enzyme

Система сбора, хранения и анализа информации, полученной при тестировании контрольно-проверочной аппаратуры космических аппаратов

Статья посвящена изучению и анализу существующих систем сбора, хранения и анализа информации, полученной при работе с космическими аппаратами, а так же описанию структуры создаваемой системы для работы с контрольно-проверочной аппаратурой. В статье описаны недостатки известных систем и обоснование необходимости создания новой. В работе представлено описание создаваемой системы "Пион"

Cognitive Profiles of Amyotrophic Lateral Sclerosis Differ in Resting-State Functional Connectivity: An fMRI Study

BackgroundHalf of all amyotrophic lateral sclerosis-frontotemporal spectrum disorder (ALS-FTSD) patients are classified as cognitively impaired, of which 10% have frontotemporal dementia (FTD), and an additional 40% suffer from a frontotemporal syndrome not severe enough to be described as dementia (cognitively impaired/ALSci). As changes in cerebral function measured by resting-state magnet resonance imaging (rs-fMRI) are known in ALS, we investigated whether group differences in resting-state functional connectivity (RSFC) networks could be observed between ALS patients with different cognitive profiles against healthy controls (HC). Furthermore, we correlated cognition and motor functioning with network connectivity.MethodsHealthy controls, 69, and 97 ALS patients underwent functional MRI scanning and cognitive assessment. The ALS patients were categorized as non-impaired (ALSni; n = 68), cognitively impaired (ALSci; n = 21), and ALS-FTD (n = 8). Group differences in connectivity of the default mode network (DMN), motor network (MN), and ventral attention network (VAN) were investigated using a full-factorial model; correlations between global cognitive performance, shifting, and motor symptom severity were established using Pearson’s correlation.ResultsAt a liberal alpha level of uncorrected p < 0.005 and a cluster size exceeding 20 voxels, we found widespread decreases in functional connectivity in all three networks when comparing ALS patients to HC. Similar patterns of hypoconnectivity in the bilateral motor cortices and frontotemporal emerged when comparing the ALSci and ALS-FTD patients to those not cognitively impaired. Hyperconnectivity in the DMN temporal gyrus correlated with worse global cognition; moreover, hyperconnectivity in the VAN thalamus, insula, and putamen correlated with worse shifting ability. Better-preserved motor function correlated with higher MN connectivity. Only the motor-related effects prevailed at a more conservative significance level of pFDR< 0.001.ConclusionResting-state functional connectivity differs between cognitive profiles of ALS and is directly associated with clinical presentation, specifically with motor function, and cognitive shifting

Global Hippocampal Volume Reductions and Local CA1 Shape Deformations in Amyotrophic Lateral Sclerosis

There is increasing evidence for hippocampal involvement in Amyotrophic Lateral Sclerosis (ALS). Recent neuroimaging studies have been focused on disease-related hippocampal volume alterations while changes in hippocampal shape have been investigated less frequently. Here, we aimed to characterize the patterns of hippocampal degeneration using both an automatic and manual volumetric and surface-based approach in a group of 31 patients with ALS and 29 healthy controls. Irrespective of the segmentation type, left, and right hippocampal volumes were significantly reduced in ALS compared to controls. Local shape alterations were identified in the hippocampal head region of patients with ALS that corresponds to the cornu ammonis field 1 (CA1), a region known to be involved in novelty detection, memory processing, and integration of hippocampal input and output information. The results suggest a global hippocampal volume loss in ALS that is complemented by local shape deformations in a highly interconnected region within the hippocampus

Исследование алгоритмов функционирования СМО с использованием библиотеки SimEvents

Выпускная квалификационная работа 80 с., 18 рис., 6 табл., 21 источник. Объект исследования — модель управления графитовыми стержнями в ядерном реакторе. Цель работы — разработка модели управления замедляющими стержнями в реакторе с использованием библиотеки SimEvents. Изучены принципы имитационного моделирования с помощью библиотек SimEvents, Simulink. Разработана модель управления графитовыми стержнями в реакторе, получены параметры системы, проведен их анализ. Модель может использоваться как имитатор физического процесса в атомном производстве. Имитационная модель дает подтверждение расчетов, прогноз работы системы, позволяет исследовать работу в критических режимах. Планируется изучение новых характеристик системы, разработка более сложной модели, параметров, влияющих на новую модельGraduation qualification project consist of 80 p., 18 fig., 6 tab., 21 sources. The object of this study is graphite rods’s control model in nuclear reactors. The purpose of work – graphite rods’s control model development using SimEvents in nuclear reactors. Is studied the simulation principles using libraries SimEvents, Simulink. Are obtained the model of the control rods in the reactor graphite, the system parameters , their analysis was carried out. The model can be used as a simulator of a physical process in nuclear industry. A simulation model provides evidence calculations, the forecast of the system, allows you to explore the critical operation. It is planned to study the characteristics of the new system, the development of a more complex model, the parameters affecting a mode

Extramitochondrial Ca2+ in the Nanomolar Range Regulates Glutamate-Dependent Oxidative Phosphorylation on Demand

We present unexpected and novel results revealing that glutamate-dependent oxidative phosphorylation (OXPHOS) of brain mitochondria is exclusively and efficiently activated by extramitochondrial Ca2+ in physiological concentration ranges (S0.5 = 360 nM Ca2+). This regulation was not affected by RR, an inhibitor of the mitochondrial Ca2+ uniporter. Active respiration is regulated by glutamate supply to mitochondria via aralar, a mitochondrial glutamate/aspartate carrier with regulatory Ca2+-binding sites in the mitochondrial intermembrane space providing full access to cytosolic Ca2+. At micromolar concentrations, Ca2+ can also enter the intramitochondrial matrix and activate specific dehydrogenases. However, the latter mechanism is less efficient than extramitochondrial Ca2+ regulation of respiration/OXPHOS via aralar. These results imply a new mode of glutamate-dependent OXPHOS regulation as a demand-driven regulation of mitochondrial function. This regulation involves the mitochondrial glutamate/aspartate carrier aralar which controls mitochondrial substrate supply according to the level of extramitochondrial Ca2+

Cognitive and behavioural but not motor impairment increases brain age in amyotrophic lateral sclerosis

Age is the most important single risk factor of sporadic amyotrophic lateral sclerosis. Neuroimaging together with machine-learning algorithms allows estimating individuals' brain age. Deviations from normal brain-ageing trajectories (so called predicted brain age difference) were reported for a number of neuropsychiatric disorders. While all of them showed increased predicted brain-age difference, there is surprisingly few data yet on it in motor neurodegenerative diseases. In this observational study, we made use of previously trained algorithms of 3377 healthy individuals and derived predicted brain age differences from volumetric MRI scans of 112 amyotrophic lateral sclerosis patients and 70 healthy controls. We correlated predicted brain age difference scores with voxel-based morphometry data and multiple different motoric disease characteristics as well as cognitive/behavioural changes categorized according to Strong and Rascovsky. Against our primary hypothesis, there was no higher predicted brain-age difference in the amyotrophic lateral sclerosis patients as a group. None of the motoric phenotypes/characteristics influenced predicted brain-age difference. However, cognitive/behavioural impairment led to significantly increased predicted brain-age difference, while slowly progressive as well as cognitive/behavioural normal amyotrophic lateral sclerosis patients had even younger brain ages than healthy controls. Of note, the cognitive/behavioural normal amyotrophic lateral sclerosis patients were identified to have increased cerebellar brain volume as potential resilience factor. Younger brain age was associated with longer survival. Our results raise the question whether younger brain age in amyotrophic lateral sclerosis with only motor impairment provides a cerebral reserve against cognitive and/or behavioural impairment and faster disease progression. This new conclusion needs to be tested in subsequent samples. In addition, it will be interesting to test whether a potential effect of cerebral reserve is specific for amyotrophic lateral sclerosis or can also be found in other neurodegenerative diseases with primary motor impairment

Differential involvement of forearm muscles in ALS does not relate to sonographic structural nerve alterations

We aimed to assess whether differential peripheral nerve involvement parallels dissociated forearm muscle weakness in amyotrophic lateral sclerosis (ALS).The analysis comprised 41 ALS patients and 18 age-, sex-, height- and weight-matched healthy controls. Strength of finger-extension and -flexion was measured using the Medical Research Council (MRC) scale. Radial, median and ulnar nerve sonographic cross-sectional area (CSA) and echogenicity, expressed by the hypoechoic fraction (HF), were determined.In ALS, finger extensors were significantly weaker than finger flexors. Sonographic evaluation revealed peripheral nerve atrophy, affecting various nerve segments in ALS. HF was unaltered.This systematic study confirmed a long-observed physical examination finding in ALS - weakness in finger-extension out of proportion to finger-flexion. This phenomenon was not related to any particular sonographic pattern of upper limb peripheral nerve alteration.In ALS, dissociated forearm muscle weakness could aid in the disease's diagnosis. Nerve ultrasound did not provide additional information on the differential involvement of finger-extension and finger-flexion strength