Chronic viral infection promotes sustained Th1-derived immunoregulatory IL-10 via BLIMP-1

During the course of many chronic viral infections, the antiviral T cell response becomes attenuated through a process that is regulated in part by the host. While elevated expression of the immunosuppressive cytokine IL-10 is involved in the suppression of viral-specific T cell responses, the relevant cellular sources of IL-10, as well as the pathways responsible for IL-10 induction, remain unclear. In this study, we traced IL-10 production over the course of chronic lymphocytic choriomeningitis virus (LCMV) infection in an IL-10 reporter mouse line. Using this model, we demonstrated that virus-specific T cells with reduced inflammatory function, particularly Th1 cells, display elevated and sustained IL-10 expression during chronic LCMV infection. Furthermore, ablation of IL-10 from the T cell compartment partially restored T cell function and reduced viral loads in LCMV-infected animals. We found that viral persistence is needed for sustained IL-10 production by Th1 cells and that the transcription factor BLIMP-1 is required for IL-10 expression by Th1 cells. Restimulation of Th1 cells from LCMV-infected mice promoted BLIMP-1 and subsequent IL-10 expression, suggesting that constant antigen exposure likely induces the BLIMP-1/IL-10 pathway during chronic viral infection. Together, these data indicate that effector T cells self-limit their responsiveness during persistent viral infection via an IL-10-dependent negative feedback loop.This work was supported by an Australian NHMRC Overseas Biomedical Postdoctoral Fellowship (to I.A. Parish); a Yale School of Medicine Brown-Coxe Postdoctoral Fellowship (to I.A. Parish); the Alexander von Humboldt Foundation (SKA2010, to P.A. Lang); a CIHR grant (to P.S. Ohashi); and by the Howard Hughes Medical Institute and NIH grant RO1AI074699 (to S.M. Kaech). P.S. Ohashi holds a Canada Research Chair in Autoimmunity and Tumor immunity

Torsion pairs and rigid objects in tubes

We classify the torsion pairs in a tube category and show that they are in bijection with maximal rigid objects in the extension of the tube category containing the Pruefer and adic modules. We show that the annulus geometric model for the tube category can be extended to the larger category and interpret torsion pairs, maximal rigid objects and the bijection between them geometrically. We also give a similar geometric description in the case of the linear orientation of a Dynkin quiver of type A.Comment: 25 pages, 13 figures. Paper shortened. Minor errors correcte

On quiver Grassmannians and orbit closures for representation-finite algebras

We show that Auslander algebras have a unique tilting and cotilting module which is generated and cogenerated by a projective-injective; its endomorphism ring is called the projective quotient algebra. For any representation- nite algebra, we use the projective quotient algebra to construct desingularizations of quiver Grassmannians, orbit closures in representation varieties, and their desingularizations. This generalizes results of Cerulli Irelli, Feigin and Reineke

Технология синтеза и очистки гликолида

Данная работа посвящена технологии получения и очистки гликолида, как мономера для биоразлагаемых полимеров. Основные потери продукта происходят на стадии получения и очистки мономера. Потери составляют порядка 50-60 %. Целью данной работы является выбор оптимального пути и очистки гликолида. В данной работе проведён и представлен всесторонний литературный обзор по методам получения гликолевой кислоты, гликолида, очистки и полимеризации гликолида. Сравнивались различные катализаторы на стадиях поликонденсации, деполимеризации и полимеризации гликолида. В работе описаны характеристики сырья, описаны способы получения, очистки и полимеризации гликолида. Изложены методики анализа гликолида.This paper is devoted to the technology of production and purification of glycolide as a monomer for biodegradable polymers. The main product losses occur at the stage of monomer production and purification. Losses are about 50-60%. The purpose of this work is to choose the optimal path and purification of glycolide. In this paper, we conducted and presented a comprehensive literature review on methods for producing glycolic acid, glycolide, and purification and polymerization of glycolide. Different catalysts were compared at the stages of glycolide polycondensation, depolymerization, and polymerization. The work describes the characteristics of the raw materials, describes the methods of production, purification, and polymerization of glycolide

Cycle-finite module categories

We describe the structure of module categories of finite dimensional algebras over an algebraically closed field for which the cycles of nonzero nonisomorphisms between indecomposable finite dimensional modules are finite (do not belong to the infinite Jacobson radical of the module category). Moreover, geometric and homological properties of these module categories are exhibited

Hirnorganoide – Modellsysteme des menschlichen Gehirns

This is the final version. Available from Deutsche Akademie der Naturforscher Leopoldina via the DOI in this record. Hirnorganoide sind Gewebestrukturen aus dem Labor, die Teile der Hirnfunktion imitieren. Sie eröffnen als vereinfachtes Modellsystem einen experimentellen Zugang zu Fragen rund um die Entwicklung und die Funktion des menschlichen Gehirns. Während die Forschung an menschlichen lebenden Gehirnen aus ethischen Gründen enge Grenzen hat und Tiermodelle viele Fragen nur bedingt beantworten können, bieten Hirnorganoide neue Forschungsmöglichkeiten. In der Stellungnahme „Hirnorganoide ‒ Modellsysteme des menschlichen Gehirns“ der Nationalen Akademie der Wissenschaften Leopoldina beschreiben Wissenschaftlerinnen und Wissenschaftler die Möglichkeiten dieses Forschungsgebietes und erörtern, ob es aus ethischen oder juristischen Gründen stärker reguliert werden sollte

Human embryonic stem cell-derived neurons establish region-specific, long-range projections in the adult brain

While the availability of pluripotent stem cells has opened new prospects for generating neural donor cells for nervous system repair, their capability to integrate with adult brain tissue in a structurally relevant way is still largely unresolved. We addressed the potential of human embryonic stem cell-derived long-term self-renewing neuroepithelial stem cells (lt-NES cells) to establish axonal projections after transplantation into the adult rodent brain. Transgenic and species-specific markers were used to trace the innervation pattern established by transplants in the hippocampus and motor cortex. In vitro, lt-NES cells formed a complex axonal network within several weeks after the initiation of differentiation and expressed a composition of surface receptors known to be instrumental in axonal growth and pathfinding. In vivo, these donor cells adopted projection patterns closely mimicking endogenous projections in two different regions of the adult rodent brain. Hippocampal grafts placed in the dentate gyrus projected to both the ipsilateral and contralateral pyramidal cell layers, while axons of donor neurons placed in the motor cortex extended via the external and internal capsule into the cervical spinal cord and via the corpus callosum into the contralateral cortex. Interestingly, acquisition of these region-specific projection profiles was not correlated with the adoption of a regional phenotype. Upon reaching their destination, human axons established ultrastructural correlates of synaptic connections with host neurons. Together, these data indicate that neurons derived from human pluripotent stem cells are endowed with a remarkable potential to establish orthotopic long-range projections in the adult mammalian brain

Tripotential Differentiation of Adherently Expandable Neural Stem (NS) Cells

BACKGROUND: A recent study has shown that pure neural stem cells can be derived from embryonic stem (ES) cells and primary brain tissue. In the presence of fibroblast growth factor 2 (FGF2) and epidermal growth factor (EGF), this population can be continuously expanded in adherent conditions. In analogy to continuously self-renewing ES cells, these cells were termed ‘NS’ cells (Conti et al., PLoS Biol 3: e283, 2005). While NS cells have been shown to readily generate neurons and astrocytes, their differentiation into oligodendrocytes has remained enigmatic, raising concerns as to whether they truly represent tripotential neural stem cells. METHODOLOGY/PRINCIPAL FINDINGS: Here we provide evidence that NS cells are indeed tripotent. Upon proliferation with FGF2, platelet-derived growth factor (PDGF) and forskolin, followed by differentiation in the presence of thyroid hormone (T3) and ascorbic acid NS cells efficiently generate oligodendrocytes (∼20%) alongside astrocytes (∼40%) and neurons (∼10%). Mature oligodendroglial differentiation was confirmed by transplantation data showing that NS cell-derived oligodendrocytes ensheath host axons in the brain of myelin-deficient rats. CONCLUSIONS/SIGNIFICANCE: In addition to delineating NS cells as a potential donor source for myelin repair, our data strongly support the view that these adherently expandable cells represent bona fide tripotential neural stem cells

The proteome of neural stem cells from adult rat hippocampus

BACKGROUND: Hippocampal neural stem cells (HNSC) play an important role in cerebral plasticity in the adult brain and may contribute to tissue repair in neurological disease. To describe their biological potential with regard to plasticity, proliferation, or differentiation, it is important to know the cellular composition of their proteins, subsumed by the term proteome. RESULTS: Here, we present for the first time a proteomic database for HNSC isolated from the brains of adult rats and cultured for 10 weeks. Cytosolic proteins were extracted and subjected to two-dimensional gel electrophoresis followed by protein identification through mass spectrometry, database search, and gel matching. We could map about 1141 ± 209 (N = 5) protein spots for each gel, of which 266 could be identified. We could group the identified proteins into several functional categories including metabolism, protein folding, energy metabolism and cellular respiration, as well as cytoskeleton, Ca(2+ )signaling pathways, cell cycle regulation, proteasome and protein degradation. We also found proteins belonging to detoxification, neurotransmitter metabolism, intracellular signaling pathways, and regulation of DNA transcription and RNA processing. CONCLUSIONS: The HNSC proteome database is a useful inventory which will allow to specify changes in the cellular protein expression pattern due to specific activated or suppressed pathways during differentiation or proliferation of neural stem cells. Several proteins could be identified in the HNSC proteome which are related to differentiation and plasticity, indicating activated functional pathways. Moreover, we found a protein for which no expression has been described in brain cells before