Clonally diverse T cell homeostasis is maintained by a common program of cell-cycle control

Lymphopenia induces T cells to undergo cell divisions as part of a homeostatic response mechanism. The clonal response to lymphopenia is extremely diverse, and it is unknown whether this heterogeneity represents distinct mechanisms of cell-cycle control or whether a common mechanism can account for the diversity. We addressed this question by combining in vivo and mathematical modeling of lymphopenia-induced proliferation (LIP) of two distinct T cell clonotypes. OT-I T cells undergo rapid LIP accompanied by differentiation that superficially resembles Ag-induced proliferation, whereas F5 T cells divide slowly and remain naive. Both F5 and OT-I LIP responses were most accurately described by a single stochastic division model where the rate of cell division was exponentially decreased with increasing cell numbers. The model successfully identified key biological parameters of the response and accurately predicted the homeostatic set point of each clone. Significantly, the model was successful in predicting interclonal competition between OT-I and F5 T cells, consistent with competition for the same resource(s) required for homeostatic proliferation. Our results show that diverse and heterogenous clonal T cell responses can be accounted for by a single common model of homeostasis

Анализ мер центральности узлов сетей на основе метода главных компонент

Анализ сетей разнообразной природы, которыми являются сети цитирования, а также социальные или информационно-коммуникационные сети, включает изучение топологических свойств, позволяющих оценивать взаимосвязи между узлами сети и различные характеристики, такие как плотность и диаметр сети, связанные подгруппы узлов и тому подобное. Для этого сеть представляется в виде графа – совокупности вершин и ребер между ними. Одной из важнейших задач анализа сетей является оценивание значимости узла (или в терминах теории графов – вершины). Для этого разработаны различные меры центральности, позволяющие оценить степень значимости вершин сетевого графа в структуре рассматриваемой сети. Существующее многообразие мер центральности порождает проблему выбора той, которая наиболее полно описывает значимость центральность узла. Актуальность работы обусловлена необходимостью анализа мер центральности для определения значимости вершин, что является одной из основных задач изучения сетей (графов) в практических приложениях. Проведенное исследование позволило с использованием метода главных компонент среди известных мер центральности выявить коллинеарные меры, которые в дальнейшем можно исключать из рассмотрения. Это позволяет уменьшить вычислительную сложность расчетов, что особенно важно для сетей с большим числом узлов, и повысить достоверность интерпретации получаемых результатов при оценивании значимости узла в рамках анализируемой сети при решении практических задач. Выявлены закономерности представления различных мер центральности в пространстве главных компонент, что позволяет классифицировать их с точки зрения близости образов узлов сети, формируемых в определяемом применяемыми мерами центральности пространстве

Plasticity of Adipose Tissue-Derived Stem Cells and Regulation of Angiogenesis

Adipose tissue is recognized as an important organ with metabolic, regulatory, and plastic roles. Adipose tissue-derived stem cells (ASCs) with self-renewal properties localize in the stromal vascular fraction (SVF) being present in a vascular niche, thereby, contributing to local regulation of angiogenesis and vessel remodeling. In the past decades, ASCs have attracted much attention from biologists and bioengineers, particularly, because of their multilineage differentiation potential, strong proliferation, and migration abilities in vitro and high resistance to oxidative stress and senescence. Current data suggest that the SVF serves as an important source of endothelial progenitors, endothelial cells, and pericytes, thereby, contributing to vessel remodeling and growth. In addition, ASCs demonstrate intriguing metabolic and interlineage plasticity, which makes them good candidates for creating regenerative therapeutic protocols, in vitro tissue models and microphysiological systems, and tissue-on-chip devices for diagnostic and regeneration-supporting purposes. This review covers recent achievements in understanding the metabolic activity within the SVF niches (lactate and NAD+ metabolism), which is critical for maintaining the pool of ASCs, and discloses their pro-angiogenic potential, particularly, in the complex therapy of cardiovascular and cerebrovascular diseases

26th Annual Computational Neuroscience Meeting (CNS*2017): Part 3 - Meeting Abstracts - Antwerp, Belgium. 15–20 July 2017

This work was produced as part of the activities of FAPESP Research,\ud Disseminations and Innovation Center for Neuromathematics (grant\ud 2013/07699-0, S. Paulo Research Foundation). NLK is supported by a\ud FAPESP postdoctoral fellowship (grant 2016/03855-5). ACR is partially\ud supported by a CNPq fellowship (grant 306251/2014-0)

Analysis of structure-forming role of phosphogypsum in the production of nonfired cementless building composites

The working hypothesis is the development of the theory of disperse system aggregative stability considering the condensation processes of structure-forming of nonfired cementless building materials on the basis of phosphogypsum. The results of phisicomechanical and physicochemical analyses of Uvarovo chemical plant phosphogypsum are presented. To define the properties of phosphogypsum and phosphogypsum-based composite modern methods of analysis were applied with the use of the following equipment: the universal electromechanical test system Instron, the automatic diffractometer PANalytical EMPYREAN, the device for synchronic thermal analysis. The results of the research showed that the first endoeffects of Uvarovo chemical plant phosphogypsum have the dehydration energy of more than 200 joule/g, and they do not get lost within the time; this proves of the cementing properties of phosphogypsum. Due to the analysis of the differential scanning calorimetry results of phosphogypsum, pressed at 5 Mpa, it was found out that at the models compression the dehydration energy increases, and the correlation between the changes of water films’ thickness and dehydration energy can be observed. With the decrease of water films’ thickness we can observe the increase of dehydration energy with the simultaneous increase of the structure density and its transformation into a monolithic structure

Analysis of structure-forming role of phosphogypsum in the production of nonfired cementless building composites

The working hypothesis is the development of the theory of disperse system aggregative stability considering the condensation processes of structure-forming of nonfired cementless building materials on the basis of phosphogypsum. The results of phisicomechanical and physicochemical analyses of Uvarovo chemical plant phosphogypsum are presented. To define the properties of phosphogypsum and phosphogypsum-based composite modern methods of analysis were applied with the use of the following equipment: the universal electromechanical test system Instron, the automatic diffractometer PANalytical EMPYREAN, the device for synchronic thermal analysis. The results of the research showed that the first endoeffects of Uvarovo chemical plant phosphogypsum have the dehydration energy of more than 200 joule/g, and they do not get lost within the time; this proves of the cementing properties of phosphogypsum. Due to the analysis of the differential scanning calorimetry results of phosphogypsum, pressed at 5 Mpa, it was found out that at the models compression the dehydration energy increases, and the correlation between the changes of water films’ thickness and dehydration energy can be observed. With the decrease of water films’ thickness we can observe the increase of dehydration energy with the simultaneous increase of the structure density and its transformation into a monolithic structure

Extracellular S100β Disrupts Bergman Glia Morphology and Synaptic Transmission in Cerebellar Purkinje Cells

Astrogliosis is a pathological process that affects the density, morphology, and function of astrocytes. It is a common feature of brain trauma, autoimmune diseases, and neurodegeneration including spinocerebellar ataxia type 1 (SCA1), a poorly understood neurodegenerative disease. S100β is a Ca 2+ binding protein. In SCA1, excessive excretion of S100β by reactive astrocytes and its uptake by Purkinje cells has been demonstrated previously. Under pathological conditions, excessive extracellular concentration of S100β stimulates the production of proinflammatory cytokines and induces apoptosis. We modeled astrogliosis by S100β injections into cerebellar cortex in mice. Injections of S100β led to significant changes in Bergmann glia (BG) cortical organization and affected their processes. S100β also changed morphology of the Purkinje cells (PCs), causing a significant reduction in the dendritic length. Moreover, the short-term synaptic plasticity and depolarization-induced suppression of synaptic transmission were disrupted after S100β injections. We speculate that these effects are the result of Ca 2+ -chelating properties of S100β protein. In summary, exogenous S100β induced astrogliosis in cerebellum could lead to neuronal dysfunction, which resembles a natural neurodegenerative process. We suggest that astrocytes play an essential role in SCA1 pathology, and that astrocytic S100β is an important contributor to this process

Extracellular S100β Disrupts Bergman Glia Morphology and Synaptic Transmission in Cerebellar Purkinje Cells

Astrogliosis is a pathological process that affects the density, morphology, and function of astrocytes. It is a common feature of brain trauma, autoimmune diseases, and neurodegeneration including spinocerebellar ataxia type 1 (SCA1), a poorly understood neurodegenerative disease. S100β is a Ca2+ binding protein. In SCA1, excessive excretion of S100β by reactive astrocytes and its uptake by Purkinje cells has been demonstrated previously. Under pathological conditions, excessive extracellular concentration of S100β stimulates the production of proinflammatory cytokines and induces apoptosis. We modeled astrogliosis by S100β injections into cerebellar cortex in mice. Injections of S100β led to significant changes in Bergmann glia (BG) cortical organization and affected their processes. S100β also changed morphology of the Purkinje cells (PCs), causing a significant reduction in the dendritic length. Moreover, the short-term synaptic plasticity and depolarization-induced suppression of synaptic transmission were disrupted after S100β injections. We speculate that these effects are the result of Ca2+-chelating properties of S100β protein. In summary, exogenous S100β induced astrogliosis in cerebellum could lead to neuronal dysfunction, which resembles a natural neurodegenerative process. We suggest that astrocytes play an essential role in SCA1 pathology, and that astrocytic S100β is an important contributor to this process

Indirect Negative Effect of Mutant Ataxin-1 on Short- and Long-Term Synaptic Plasticity in Mouse Models of Spinocerebellar Ataxia Type 1

Spinocerebellar ataxia type 1 (SCA1) is an intractable progressive neurodegenerative disease that leads to a range of movement and motor defects and is eventually lethal. Purkinje cells (PC) are typically the first to show signs of degeneration. SCA1 is caused by an expansion of the polyglutamine tract in the ATXN1 gene and the subsequent buildup of mutant Ataxin-1 protein. In addition to its toxicity, mutant Ataxin-1 protein interferes with gene expression and signal transduction in cells. Recently, it is evident that ATXN1 is not only expressed in neurons but also in glia, however, it is unclear the extent to which either contributes to the overall pathology of SCA1. There are various ways to model SCA1 in mice. Here, functional deficits at cerebellar synapses were investigated in two mouse models of SCA1 in which mutant ATXN1 is either nonspecifically expressed in all cell types of the cerebellum (SCA1 knock-in (KI)), or specifically in Bergmann glia with lentiviral vectors expressing mutant ATXN1 under the control of the astrocyte-specific GFAP promoter. We report impairment of motor performance in both SCA1 models. In both cases, prominent signs of astrocytosis were found using immunohistochemistry. Electrophysiological experiments revealed alteration of presynaptic plasticity at synapses between parallel fibers and PCs, and climbing fibers and PCs in SCA1 KI mice, which is not observed in animals expressing mutant ATXN1 solely in Bergmann glia. In contrast, short- and long-term synaptic plasticity was affected in both SCA1 KI mice and glia-targeted SCA1 mice. Thus, non-neuronal mechanisms may underlie some aspects of SCA1 pathology in the cerebellum. By combining the outcomes of our current work with our previous data from the B05 SCA1 model, we further our understanding of the mechanisms of SCA1