Research of microdeformation and stress in details of agricultural machines by implementing holography

The article presents theoretical and experimental studies of microstrains and stresses in the details of agricultural machines by the implementation of holography. В статье представлены теоретические и экспериментальные исследования микродеформаций и напряжений в деталях сельскохозяйственных машин с применением голографии

АССОЦИАЦИИ БИОМОЛЕКУЛ, СВЯЗАННЫХ С СЕКРЕТОРНОЙ АКТИВНОСТЬЮ ВИСЦЕРАЛЬНЫХ АДИПОЦИТОВ, С ЭЛЕКТРОФИЗИОЛОГИЧЕСКИМИ ПРИЗНАКАМИ МЕТАБОЛИЧЕСКИХ НАРУШЕНИЙ МИОКАРДА У ЛИЦ ДО 45 ЛЕТ

Highlights ECG signs of metabolic cardiomyopathies in men aged 25–44 years, regardless of age and waist circumference, are directly associated with the serum adipsin concentration and inversely associated with the concentration of glucagon-like peptide 1 in the blood.ECG signs of metabolic cardiomyopathies in women aged 25–44 years are directly associated with the serum c-peptide concentration and inversely associated with the concentration of glucose-dependent insulinotropic polypeptide 1 in the blood. AbstractAim. To study the relationship between electrophysiological signs of metabolic cardiomyopathy (MC) and biomolecules associated with the secretory activity of visceral adipocytes in persons aged 25–44 years residing in Novosibirsk.Methods. The study included 1 198 subjects. A single-stage survey of a random sample of the 25–44-year-old population of Novosibirsk (49,7% men, 50,3% women) was conducted. During the examination, among other things, a resting 12-lead ECGs was recorded, and later the ECGs were classified according to Minnesota Code categories. Five ECG signs of MC were analysed: 1) ST-segment displaced above baseline (ST-segment elevation); 2) ST-segment displaced below baseline (ST-segment depression); 3) T wave changes; 4) TV1>TV6 patterns and 5) ECG signs of left ventricular hypertrophy. Serum concentrations of biomolecules associated with the secretory activity of visceral adipocytes were determined by multiplex analysis.Results. The results of multivariate logistic regression analysis showed that the ECG signs of MC in men aged 25–44 years, regardless of age and waist circumference, are directly associated with the serum adipsin concentration (Exp B 1,039, 95% CI 1,002–1,077, p = 0.039) and inversely associated with the concentration of glucagon-like peptide 1 in the blood (Exp B 0.999, 95% CI 0.998–1,000, p = 0.042). ECG signs of MC in women aged 25–44 years are directly associated with the serum peptide concentration (Exp B 1,439, 95% CI 1,082–1,915, p = 0.012) and inversely associated with the concentration of glucose-dependent insulinotropic polypeptide in the blood (Exp B 0.986, 95% CI 0.978–0.995, p = 0.001).Conclusion. The results obtained reflect the significant influence of these biomolecules associated with the secretory activity of visceral adipocytes on the occurrence of ECG signs of MC in young people aged 25–44 years.Основные положенияЭКГ-признаки метаболических нарушений миокарда у мужчин 25–44 лет независимо от возраста и окружности талии прямо ассоциированы с концентрацией в крови адипсина и обратно – с концентрацией глюкагоноподобного пептида 1.ЭКГ-признаки метаболических нарушений миокарда у женщин 25–44 лет прямо ассоциированы с концентрацией в крови C-пептида и обратно – с концентрацией глюкозозависимого инсулинотропного полипептида 1. Цель. Изучить ассоциации электрофизиологических признаков метаболических нарушений миокарда (МНМ) с биомолекулами, связанными с секреторной активностью висцеральных адипоцитов, у лиц 25–44 лет, проживающих в Новосибирске.Материалы и методы. Проведено одномоментное обследование случайной выборки населения Новосибирска в возрасте 25–44 лет (1 198 человек, 49,7% мужчин и 50,3% женщин). При обследовании в том числе проведена запись электрокардиограммы (ЭКГ) в покое в 12 стандартных отведениях с последующим кодированием по Миннесотскому коду. Проанализированы пять ЭКГ-признаков МНМ: смещение сегмента ST выше изолинии, депрессия сегмента ST ниже изолинии, изменения зубца Т, синдром TV1>TV6 и ЭКГ-признаки гипертрофии левого желудочка. В крови обследованных методом мультиплексного анализа определены концентрации биомолекул, ассоциированных с секреторной активностью висцеральных адипоцитов.Результаты. Результаты многофакторного логистического регрессионного анализа показали, что ЭКГ-признаки МНМ у мужчин 25–44 лет независимо от возраста и окружности талии прямо ассоциированы с концентрацией в крови адипсина (Exp B 1,039, 95% доверительный интервал (ДИ) 1,002–1,077; p = 0,039) и обратно – с концентрацией в крови глюкагоноподобного пептида 1 (Exp B 0,999, 95% ДИ 0,998–1,000; p = 0,042). Наличие ЭКГ-признаков МНМ у женщин 25–44 лет прямо ассоциировано с концентрацией в крови С-пептида (Exp B 1,439, 95% ДИ 1,082–1,915; p = 0,012) и обратно – с концентрацией в крови глюкозозависимого инсулинотропного полипептида (Exp B 0,986, 95% ДИ 0,978–0,995; p = 0,001).Заключение. Полученные результаты отражают значимое влияние биомолекул, ассоциированных с секреторной активностью висцеральных адипоцитов, на возникновение у людей 25–44 лет ЭКГ-признаков МНМ

Human Umbilical Cord Blood Cells Restore Brain Damage Induced Changes in Rat Somatosensory Cortex

Intraperitoneal transplantation of human umbilical cord blood (hUCB) cells has been shown to reduce sensorimotor deficits after hypoxic ischemic brain injury in neonatal rats. However, the neuronal correlate of the functional recovery and how such a treatment enforces plastic remodelling at the level of neural processing remains elusive. Here we show by in-vivo recordings that hUCB cells have the capability of ameliorating the injury-related impairment of neural processing in primary somatosensory cortex. Intact cortical processing depends on a delicate balance of inhibitory and excitatory transmission, which is disturbed after injury. We found that the dimensions of cortical maps and receptive fields, which are significantly altered after injury, were largely restored. Additionally, the lesion induced hyperexcitability was no longer observed in hUCB treated animals as indicated by a paired-pulse behaviour resembling that observed in control animals. The beneficial effects on cortical processing were reflected in an almost complete recovery of sensorimotor behaviour. Our results demonstrate that hUCB cells reinstall the way central neurons process information by normalizing inhibitory and excitatory processes. We propose that the intermediate level of cortical processing will become relevant as a new stage to investigate efficacy and mechanisms of cell therapy in the treatment of brain injury

Dose-dependent expression of claudin-5 is a modifying factor in schizophrenia

Schizophrenia is a neurodevelopmental disorder that affects up to 1% of the general population. Various genes show associations with schizophrenia and a very weak nominal association with the tight junction protein, claudin-5, has previously been identified. Claudin-5 is expressed in endothelial cells forming part of the blood-brain barrier (BBB). Furthermore, schizophrenia occurs in 30% of individuals with 22q11 deletion syndrome (22q11DS), a population who are haploinsufficient for the claudin-5 gene. Here, we show that a variant in the claudin-5 gene is weakly associated with schizophrenia in 22q11DS, leading to 75% less claudin-5 being expressed in endothelial cells. We also show that targeted adeno-associated virus-mediated suppression of claudin-5 in the mouse brain results in localized BBB disruption and behavioural changes. Using an inducible ‘knockdown’ mouse model, we further link claudin-5 suppression with psychosis through a distinct behavioural phenotype showing impairments in learning and memory, anxiety-like behaviour and sensorimotor gating. In addition, these animals develop seizures and die after 3–4 weeks of claudin-5 suppression, reinforcing the crucial role of claudin-5 in normal neurological function. Finally, we show that anti-psychotic medications dose-dependently increase claudin-5 expression in vitro and in vivo while aberrant, discontinuous expression of claudin−5 in the brains of schizophrenic patients post mortem was observed compared to age-matched controls. Together, these data suggest that BBB disruption may be a modifying factor in the development of schizophrenia and that drugs directly targeting the BBB may offer new therapeutic opportunities for treating this disorder

Experimental concepts for toxicity prevention and tissue restoration after central nervous system irradiation

Several experimental strategies of radiation-induced central nervous system toxicity prevention have recently resulted in encouraging data. The present review summarizes the background for this research and the treatment results. It extends to the perspectives of tissue regeneration strategies, based for example on stem and progenitor cells. Preliminary data suggest a scenario with individually tailored strategies where patients with certain types of comorbidity, resulting in impaired regeneration reserve capacity, might be considered for toxicity prevention, while others might be "salvaged" by delayed interventions that circumvent the problem of normal tissue specificity. Given the complexity of radiation-induced changes, single target interventions might not suffice. Future interventions might vary with patient age, elapsed time from radiotherapy and toxicity type. Potential components include several drugs that interact with neurodegeneration, cell transplantation (into the CNS itself, the blood stream, or both) and creation of reparative signals and a permissive microenvironment, e.g., for cell homing. Without manipulation of the stem cell niche either by cell transfection or addition of appropriate chemokines and growth factors and by providing normal perfusion of the affected region, durable success of such cell-based approaches is hard to imagine

Brain inflammation is accompanied by peripheral inflammation in Cstb(-/-) mice, a model for progressive myoclonus epilepsy

Progressive myoclonus epilepsy of Unverricht-Lundborg type (EPM1) is an autosomal recessively inherited childhood-onset neurodegenerative disorder, characterized by myoclonus, seizures, and ataxia. Mutations in the cystatin B gene (CSTB) underlie EPM1. The CSTB-deficient (Cstb(-/-)) mouse model recapitulates key features of EPM1, including myoclonic seizures. The mice show early microglial activation that precedes seizure onset and neuronal loss and leads to neuroinflammation. We here characterized the inflammatory phenotype of Cstb(-/-) mice in more detail. We found higher concentrations of chemokines and pro-inflammatory cytokines in the serum of Cstb(-/-) mice and higher CXCL13 expression in activated microglia in Cstb(-/-) compared to control mouse brains. The elevated chemokine levels were not accompanied by blood-brain barrier disruption, despite increased brain vascularization. Macrophages in the spleen and brain of Cstb(-/-) mice were predominantly pro-inflammatory. Taken together, these data show that CXCL13 expression is a hallmark of microglial activation in Cstb(-/-)mice and that the brain inflammation is linked to peripheral inflammatory changes, which might contribute to the disease pathology of EPM1.Peer reviewe

Neurovascular unit dysfunction with blood-brain barrier hyperpermeability contributes to major depressive disorder: a review of clinical and experimental evidence

About one-third of people with major depressive disorder (MDD) fail at least two antidepressant drug trials at 1 year. Together with clinical and experimental evidence indicating that the pathophysiology of MDD is multifactorial, this observation underscores the importance of elucidating mechanisms beyond monoaminergic dysregulation that can contribute to the genesis and persistence of MDD. Oxidative stress and neuroinflammation are mechanistically linked to the presence of neurovascular dysfunction with blood-brain barrier (BBB) hyperpermeability in selected neurological disorders, such as stroke, epilepsy, multiple sclerosis, traumatic brain injury, and Alzheimer’s disease. In contrast to other major psychiatric disorders, MDD is frequently comorbid with such neurological disorders and constitutes an independent risk factor for morbidity and mortality in disorders characterized by vascular endothelial dysfunction (cardiovascular disease and diabetes mellitus). Oxidative stress and neuroinflammation are implicated in the neurobiology of MDD. More recent evidence links neurovascular dysfunction with BBB hyperpermeability to MDD without neurological comorbidity. We review this emerging literature and present a theoretical integration between these abnormalities to those involving oxidative stress and neuroinflammation in MDD. We discuss our hypothesis that alterations in endothelial nitric oxide levels and endothelial nitric oxide synthase uncoupling are central mechanistic links in this regard. Understanding the contribution of neurovascular dysfunction with BBB hyperpermeability to the pathophysiology of MDD may help to identify novel therapeutic and preventative approaches