Electrophysiological and Morphological Properties of Embryonic Neocortical Grafts Developing in Different Regions of the Host Rat Brain

Parallel morphological and electrophysiological studies of embryonic neocortical tissue (primordia of anterior parietal–presumptive sensorimotor–cortex) grafted into different regions of the host adult brain (sensori-motor cortex, caudate-putamen, septum or thalamus) were carried out to investigate to what extent the properties of transplanted embryonic neocortex–an advanced organizational form of neuronal tissue–are affected by homotopic or heterotopic surroundings

Модернизация авиационного стрелкового прицела путем комплексирования информационных каналов

Стаття присвячена підвищенню ефективності вітчизняного авіаційного парку внаслідок модернізації авіаційного стрілецького прицілу. Одним з головних напрямків модернізації є комплексування інформаційних каналів в прицілі. Існуючі варіанти комплексування не дають очікуваного підвищення ефективності із-за великих похибок або значних габаритів блоків прицілу. Метою даної роботи є аналіз можливих варіантів комплексування інформації в прицілі для його модернізації з огляду на можливість їх реалізації. Була запропонована схема комбінованої візирної головки з рідкокристалічним індикатором для комплексування інформації в прицілі. Попередні розрахунки підтверджують можливість практичної реалізації запропонованого рішення. Надалі передбачається допрацьовувати схему комплексування у напрямі оцінки її конструктивного втілення.The article is devoted the increase of efficiency of domestic aviation park due to modernization of aviation sight. Information fusion is one of main sight modernization directions. The existent variants of information fusion in sight do not give the expected increasing of efficiency on account of large errors or considerable sizes of sight units. The purpose of this work is an analysis of possible variants of information fusion in a sight for it's modernization, taking into account possibility of their realization. The chart of the combined liquid-crystal viewfinder was offered for information fusion. Previous calculations confirm possibility of practical realization of the decision. In future it is foreseen to finish off the fusion chart to estimate its structural embodiment.Статья посвящена повышению эффективности отечественного авиационного парка за счет модернизации авиационного стрелкового прицела. Одним из главных направлений модернизации является комплексирование информационных каналов в прицеле. Существующие варианты комплексирования не дают ожидаемого повышения эффективности из-за больших погрешностей или значительных габаритов блоков прицела. Целью данной работы является анализ возможных вариантов комплексирования информации в прицеле для его модернизации, учитывая возможность их реализации. Была предложена схема комбинированной визирной головки с жидкокристаллическим индикатором для комплексирования информации в прицеле. Предыдущие расчеты подтверждают возможность практической реализации предложенного решения. В дальнейшем предусматривается дорабатывать схему комплексирования в направлении оценки ее конструктивного воплощения

TGFβ signaling is associated with changes in inflammatory gene expression and perineuronal net degradation around inhibitory neurons following various neurological insults

Brain damage due to stroke or traumatic brain injury (TBI), both leading causes of serious long-term disability, often leads to the development of epilepsy. Patients who develop post-injury epilepsy tend to have poor functional outcomes. Emerging evidence highlights a potential role for blood- brain barrier (BBB) dysfunction in the development of post-injury epilepsy. However, common mechanisms underlying the pathological hyperexcitability are largely unknown. Here, we show that comparative transcriptome analyses predict remodeling of extracellular matrix (ECM) as a common response to different types of injuries. ECM-related transcriptional changes were induced by the serum protein albumin via TGFβ signaling in primary astrocytes. In accordance with transcriptional responses, we found persistent degradation of protective ECM structures called perineuronal nets (PNNs) around fast-spiking inhibitory interneurons, in a rat model of TBI as well as in brains of human epileptic patients. Exposure of a naïve brain to albumin was sufficient to induce the transcriptional and translational upregulation of molecules related to ECM remodeling and the persistent breakdown of PNNs around fast-spiking inhibitory interneurons, which was contingent on TGFβ signaling activation. Our findings provide insights on how albumin extravasation that occurs upon BBB dysfunction in various brain injuries can predispose neural circuitry to the development of chronic inhibition deficits

Contribution of the massive photon decay channel to neutrino cooling of neutron stars

We consider massive photon decay reactions via intermediate states of electron-electron-holes and proton-proton-holes into neutrino-antineutrino pairs in the course of neutron star cooling. These reactions may become operative in hot neutron stars in the region of proton pairing where the photon due to the Higgs-Meissner effect acquires an effective mass $m_{\gamma}$ that is small compared to the corresponding plasma frequency. The contribution of these reactions to neutrino emissivity is calculated; it varies with the temperature and the photon mass as $T^{3/2}m_{\gamma}^{7/2} e^{-m_{\gamma}/T}$ for $T < m_{\gamma}$. Estimates show that these processes appear as extra efficient cooling channels of neutron stars at temperatures $T \simeq (10^9-10^{10})$ K.Comment: accepted to publication in Zh. Eksp. Teor. Fiz. (JETP

Reduction of Weak Interaction Rates in Neutron Stars by Nucleon Spin Fluctuations: Degenerate Case

Nucleon spin fluctuations in a dense medium reduce the ``naive'' values of weak interaction rates (neutrino opacities, neutrino emissivities). We extend previous studies of this effect to the degenerate case which is appropriate for neutron stars a few ten seconds after formation. If neutron-neutron interactions by a one-pion exchange potential are the dominant cause of neutron spin fluctuations, a perturbative calculation of weak interaction rates is justified for T\alt 3m/(4\pi\alpha_\pi^2)\approx 1 MeV, where $m$ is the neutron mass and $\alpha_\pi\approx15$ the pion fine-structure constant. At higher temperatures, the application of Landau's theory of Fermi liquids is no longer justified, i.e. the neutrons cannot be viewed as simple quasiparticles in any obvious sense.Comment: 5 pages, RevTex, no figures, to be published in PR

Involvment of Cytosolic and Mitochondrial GSK-3β in Mitochondrial Dysfunction and Neuronal Cell Death of MPTP/MPP+-Treated Neurons

Aberrant mitochondrial function appears to play a central role in dopaminergic neuronal loss in Parkinson's disease (PD). 1-methyl-4-phenylpyridinium iodide (MPP+), the active metabolite of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), is a selective inhibitor of mitochondrial complex I and is widely used in rodent and cell models to elicit neurochemical alterations associated with PD. Recent findings suggest that Glycogen Synthase Kinase-3β (GSK-3β), a critical activator of neuronal apoptosis, is involved in the dopaminergic cell death. In this study, the role of GSK-3β in modulating MPP+-induced mitochondrial dysfunction and neuronal death was examined in vivo, and in two neuronal cell models namely primary cultured and immortalized neurons. In both cell models, MPTP/MPP+ treatment caused cell death associated with time- and concentration-dependent activation of GSK-3β, evidenced by the increased level of the active form of the kinase, i.e. GSK-3β phosphorylated at tyrosine 216 residue. Using immunocytochemistry and subcellular fractionation techniques, we showed that GSK-3β partially localized within mitochondria in both neuronal cell models. Moreover, MPP+ treatment induced a significant decrease of the specific phospho-Tyr216-GSK-3β labeling in mitochondria concomitantly with an increase into the cytosol. Using two distinct fluorescent probes, we showed that MPP+ induced cell death through the depolarization of mitochondrial membrane potential. Inhibition of GSK-3β activity using well-characterized inhibitors, LiCl and kenpaullone, and RNA interference, prevented MPP+-induced cell death by blocking mitochondrial membrane potential changes and subsequent caspase-9 and -3 activation. These results indicate that GSK-3β is a critical mediator of MPTP/MPP+-induced neurotoxicity through its ability to regulate mitochondrial functions. Inhibition of GSK-3β activity might provide protection against mitochondrial stress-induced cell death

Overexpression of Myocilin in the Drosophila Eye Activates the Unfolded Protein Response: Implications for Glaucoma

Glaucoma is the world's second leading cause of bilateral blindness with progressive loss of vision due to retinal ganglion cell death. Myocilin has been associated with congenital glaucoma and 2-4% of primary open angle glaucoma (POAG) cases, but the pathogenic mechanisms remain largely unknown. Among several hypotheses, activation of the unfolded protein response (UPR) has emerged as a possible disease mechanism.We used a transgenic Drosophila model to analyze whole-genome transcriptional profiles in flies that express human wild-type or mutant MYOC in their eyes. The transgenic flies display ocular fluid discharge, reflecting ocular hypertension, and a progressive decline in their behavioral responses to light. Transcriptional analysis shows that genes associated with the UPR, ubiquitination, and proteolysis, as well as metabolism of reactive oxygen species and photoreceptor activity undergo altered transcriptional regulation. Following up on the results from these transcriptional analyses, we used immunoblots to demonstrate the formation of MYOC aggregates and showed that the formation of such aggregates leads to induction of the UPR, as evident from activation of the fluorescent UPR marker, xbp1-EGFP. CONCLUSIONS / SIGNIFICANCE: Our results show that aggregation of MYOC in the endoplasmic reticulum activates the UPR, an evolutionarily conserved stress pathway that culminates in apoptosis. We infer from the Drosophila model that MYOC-associated ocular hypertension in the human eye may result from aggregation of MYOC and induction of the UPR in trabecular meshwork cells. This process could occur at a late age with wild-type MYOC, but might be accelerated by MYOC mutants to account for juvenile onset glaucoma

A Dominant-Negative Mutation of Mouse Lmx1b Causes Glaucoma and Is Semi-lethal via LBD1-Mediated Dimerisation

Mutations in the LIM-homeodomain transcription factor LMX1B cause nail-patella syndrome, an autosomal dominant pleiotrophic human disorder in which nail, patella and elbow dysplasia is associated with other skeletal abnormalities and variably nephropathy and glaucoma. It is thought to be a haploinsufficient disorder. Studies in the mouse have shown that during development Lmx1b controls limb dorsal-ventral patterning and is also required for kidney and eye development, midbrain-hindbrain boundary establishment and the specification of specific neuronal subtypes. Mice completely deficient for Lmx1b die at birth. In contrast to the situation in humans, heterozygous null mice do not have a mutant phenotype. Here we report a novel mouse mutant Icst, an N-ethyl-N-nitrosourea-induced missense substitution, V265D, in the homeodomain of LMX1B that abolishes DNA binding and thereby the ability to transactivate other genes. Although the homozygous phenotypic consequences of Icst and the null allele of Lmx1b are the same, heterozygous Icst elicits a phenotype whilst the null allele does not. Heterozygous Icst causes glaucomatous eye defects and is semi-lethal, probably due to kidney failure. We show that the null phenotype is rescued more effectively by an Lmx1b transgene than is Icst. Co-immunoprecipitation experiments show that both wild-type and Icst LMX1B are found in complexes with LIM domain binding protein 1 (LDB1), resulting in lower levels of functional LMX1B in Icst heterozygotes than null heterozygotes. We conclude that Icst is a dominant-negative allele of Lmx1b. These findings indicate a reassessment of whether nail-patella syndrome is always haploinsufficient. Furthermore, Icst is a rare example of a model of human glaucoma caused by mutation of the same gene in humans and mice