Thymic epithelial cells in age-dependent involution

Aging involves morphological and functional alterations within the microenvironment of the thymus where heterogenous populations of thymic epithelial cells (TEC) play the main roles. The studies performed to date on thymic involution signalize a disturbed interaction between individual thymic compartments that disrupt thymocyte-TEC interactions and, as a sequele, disturb differentiation of both TEC and thymocytes. The process of aging affects the various subsets of TEC at different periods of life. Changes in different subsets of TEC are documented on the basis of their phenotypical characteristics, involving morphological analysis and immunocytochemistry. The character and kinetics of changes in TEC are typical for individual subsets and probably sex-dependent. In the course of life, the involutionary changes, expressed by disorganised thymic structure and function, are accompanied by changes in medullary TEC, manifested by alterations in the differentiation process of the cells. In parallel, at the same stage of individual life, the aging process induces increased proliferative and secretory activity of subseptal TEC, which seem to functionally replace medullary TEC. Structural and phenotypic modifications of TEC are locally controlled by complex sets of different factors and seem to represent a morphological adaptation of the gland to the process of aging. Microsc. Res. Tech. 62:488-500, 2003.     

Role of growth factors and their receptors in gastric ulcer healing

The repair of gastric ulcers requires the reconstitution of epithelial structures and the underlying connective tissue, including vessels and muscle layers. Several growth factors have been implicated in this process, since they are able to regulate important cell functions, such as cell proliferation, migration, differentiation, secretion, and degradation of extracellular matrix, all of which are essential during tissue healing. Epidermal growth factor (EGF), transforming growth factor-alpha (TGF-alpha), hepatocyte growth factor (HGF), and trefoil factors (TFFs) are mainly involved in the reconstitution of the epithelial structures. Platelet derived growth factor (PDGF), basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), and transforming growth factor-beta (TGF-beta) play a major role in the reconstitution of connective tissue, including vessels and smooth muscle cells, and provide the extracellular matrix substrate for cell migration and differentiation. The expression of these growth factors and their receptors is increased during ulcer healing and, in some cases, intracellular signaling related to receptor binding and transduction has been demonstrated. EGF, TGF-alpha and TFFs are normally present either in the gastric juice or in the mucosa, and may exert their effects immediately after damage, before newly synthesized EGF and TFFs are released from the ulcer margin. The inhibition of their effects by neutralizing antibodies may result in delayed ulcer healing, while the administration of recombinant or natural analogues may improve ulcer repair. In this review, we will summarize the basic molecular characteristics of some of these growth factors, and will discuss available evidence supporting their role in the ulcer repair process.     

Age-dependent changes in thymic macrophages and dendritic cells

Aging is characterized by the decline and deregulation of several physiological systems, especially the immune system. The involution of the thymus gland has been identified as one of the key events that precedes the age-related decline in immune function. Whereas the decrease in thymocyte numbers and in the thymic output during thymus atrophy has been analyzed by various authors, very little information is available about the age-associated modifications in thymic macrophages and dendritic cells. Here we present evidence that these thymic stromal cell components are only slightly affected by age.     

Growth factors, CD34 positive cells, and fibrin network analysis in concentrated growth factors fraction

An interesting clinical option for optimizing healing tissue is the use of platelet concentrate. Platelets contain high quantities of growth factors, among these TGF-β1 and VEGF, which are known to be implicated in tissue regeneration. CGF is produced by processing blood samples with a special centrifuge device; three layers are formed: top acellular plasma (PPP), middle CGF and bottom red blood cells (RBC) layers. Given that to date there are no data concerning the biological characteristic of CGF, the aim of this study was to evaluate the presence of TGF-β1 and VEGF in CGF and also in PPP and RBC layers. In addition, since circulating stem cells are recruited from blood to injured tissue for healing we also evaluated the presence of CD34 positive cells. Our data show the presence of TGF-β1 and VEGF in CGF and RBC layers. In addition, we show CD34 positive cells in CGF.     

Role of growth factors and their receptors in proliferation of microvascular endothelial cells

Investigations over the last decade have established the essential role of growth factors and their receptors during angiogenesis. The biological significance of VEGF, EGF, and bFGF is mediated by their receptors, which belong to the family of tyrosine kinase receptors: Flt-1 (VEGFR-1), KDR (VEGFR-2), EGFR, FGFR-1, FGFR-2, FGFR-3, and FGFR-4. Deeper understanding of the mechanism of activation of these growth factor receptors has allowed the development of a new pharmacological strategy aimed at controlling cancer cell proliferation. The results of a large body of preclinical as well as early clinical studies conducted suggest that targeting the growth factor receptors could represent a significant contribution to cancer therapy.     

Angiogenesis in wound repair: angiogenic growth factors and the extracellular matrix

Angiogenesis is critical to wound repair. Newly formed blood vessels participate in provisional granulation tissue formation and provide nutrition and oxygen to growing tissues. In addition, inflammatory cells require the interaction with and transmigration through the endothelial basement membrane to enter the site of injury. Angiogenesis, in response to tissue injury, is a dynamic process that is highly regulated by signals from both serum and the surrounding extracellular matrix (ECM) environment. Vascular endothelial growth factor, angiopoietin, fibroblast growth factor, and transforming growth factor beta are among those most potent angiogenic cytokines in wound angiogenesis. The cooperative regulation of them is essential for wound repair. Migration of endothelial cells and development of new capillary vessels during wound repair is dependent on not only the cells and cytokines present but also the production and organization of ECM components both in granulation tissue and in endothelial basement membrane. The ECM regulates angiogenesis by providing scaffold support and signaling roles. They also serve as a reservoir and modulator for growth factors. Laminins are the major noncollagenous ECM of endothelial basement membrane. Two newly recognized laminins, 8 and 10, are the major laminins produced by human dermal microvascular endothelial cells. Laminin 10 is highly expressed in blood vessels around skin wounds. Laminin 8 promotes dermal endothelial cell attachment, migration, and tubule formation. Integrins with either beta 1 or alpha v subunits are the major cellular surface receptors for ECM molecules and mediate the interactions between cells and ECM during wound angiogenesis.     

锂离子电池芯体卷绕设备的设计与分析

介绍了一种用于生产锂离子电池芯体卷绕设备的机械结构,重点对卷绕设备极片送料机构和芯体卷绕换位机构进行了设计和分析,同时对纸管机控制系统也做了介绍.     

Involvement of human intracisternal A-type retroviral particles in autoimmunity

Prior studies have linked retroviruses to various arthropathies and autoimmune diseases. Sj?gren's syndrome (SS), a systemic autoimmune disease, is characterized by aggressive infiltration of lymphocytes into the salivary and lacrimal glands, resulting in destruction of the glands and dry mouth and eyes (sicca syndrome). The infiltrating lymphocytes in SS may become overtly malignant, and thus, the incidence of lymphoma is greatly increased in SS patients. A human intracisternal A-type retroviral particle type I (HIAP-I) has been isolated from persons with SS. HIAP-I shares a limited number of antigenic epitopes with human immunodeficiency virus (HIV), but is distinguishable from HIV by morphological, physical, and biochemical criteria. A substantial majority of patients with SS or systemic lupus erythematosus (SLE) have serum antibodies to the proteins of this human retrovirus. Fewer than 3% of the normal blood donor population have antibodies to any HIAP-associated proteins. A second type of a human intracisternal A-type retrovirus, HIAP-II, was detected in a subset of patients with idiopathic CD4 lymphocytopenia (ICL), an AIDS-like immunodeficiency disease. Most HIAP-II positive ICL patients were also antinuclear antibody positive. Reviewed here are additional studies from several laboratories suggesting that HIAP or related viruses may be involved in SLE and other autoimmune conditions. Additionally, results of comprehensive surveys of autoimmune patients to determine seroreactivity to HIAP, and other human retroviruses, including HIV and human T-lymphotropic virus type I, are reported.     

Involvement of PCH family proteins in cytokinesis and actin distribution

Pombe Cdc15 homology (PCH) proteins constitute an extensive protein family whose members have been found in diverse eukaryotic organisms. These proteins are characterized by the presence of several conserved sequence and structural motifs. Recent studies in yeast and mammalian cultured cells have implicated these proteins in actin-based processes, in particular, cytokinesis. Here we review the recent findings on the in vivo localization, function, and binding partners of PCH family members. We also provide new microscopy data regarding the in vivo dynamics of a budding yeast PCH protein involved in cytokinesis.     

Involvement of the choroid plexus in central nervous system inflammation

During inflammatory conditions in the central nervous system (CNS), immune cells immigrate into the CNS and can be detected in the CNS parenchyma and in the cerebrospinal fluid (CSF). The most comprehensively investigated model for CNS inflammation is experimental autoimmune encephalomyelitis (EAE), which is considered the prototype model for the human disease multiple sclerosis (MS). In EAE autoagressive CD4(+), T cells gain access to the CNS and initiate the molecular and cellular events leading to edema, inflammation, and demyelination in the CNS. The endothelial blood-brain barrier (BBB) has been considered the obvious place of entry for the circulating immune cells into the CNS. A role of the choroid plexus in the pathogenesis of EAE or MS, i.e., as an alternative entry site for circulating lymphocytes directly into the CSF, has not been seriously considered before. However, during EAE, we observed massive ultrastructural changes within the choroid plexus, which are different from changes observed during hypoxia. Using immunohistochemistry and in situ hybridization, we observed expression of VCAM-1 and ICAM-1 in the choroid plexus and demonstrated their upregulation and also de novo expression of MAdCAM-1 during EAE. Ultrastructural studies revealed polar localization of ICAM-1, VCAM-1, and MAdCAM-1 on the apical surface of choroid plexus epithelial cells and their complete absence on the fenestrated endothelial cells within the choroid plexus parenchyme. Furthermore, ICAM-1, VCAM-1, and MAdCAM-1 expressed in choroid plexus epithelium mediated binding of lymphocytes via their known ligands. In vitro, choroid plexus epithelial cells can be induced to express ICAM-1, VCAM-1, MAdCAM-1, and, additionally, MHC class I and II molecules on their surface. Taken together, our observations imply a previously unappreciated function of the choroid plexus in the immunosurveillance of the CNS.     

Crack growth pattern prediction in a thin walled cylinder based on closed form thermo-elastic stress intensity factors

Circumferential crack growth pattern in a thin-walled cylinder is studied. Thermo-elastic stresses in a cylinder subjected to thermomechanical loads are extracted. Closed form thermo-elastic stress intensity factor for cracked cylinder are derived using weight function method. An algorithm is developed to simulate different crack growth patterns utilizing a very high efficiency weight function method. This would lessen the taken time for the analyses compared to other numerical methods such as FEM. Results show that while the load effect on cylinder subjected to thermal load lead to the crack growth in small aspect ratio, in cylinder subjected to mechanical loads, it would lead to the growth of crack in large aspect ratio. The results show that, apart from load effects, the cylinders containing initial semi-circular crack have the longest life among the cylinders containing initial semi-elliptical crack with the same initial depth.     

供应商参与产品协同开发的任务分配优化

从制造企业的视角出发,针对供应商参与产品协同开发的特点以及任务分配的一般要求,构建了基于双层规划的产品协同开发任务分配模型。分别以战略紧密程度最大化和开发时间最短作为模型的上下层目标,并以战略供应商战略地位、单个供应商所能承担的子任务数量、开发时间以及开发成本作为模型的约束条件。结合直觉模糊理论,将其转化为直觉模糊双层规划模型;并采用量子遗传算法对实例进行求解,实现了子任务的优化分配,不仅保证了产品开发的完成时间,而且确保了制造企业与供应商的紧密合作。     

抗坏血酸诱导的玉米幼苗耐热性及其与抗坏血酸过氧化物酶的关系

外源抗坏血酸（AsA）预处理可显著增强玉米幼苗的耐热性。外源抗坏血酸预处理后,提高了玉米幼苗内源AsA含量和抗坏血酸过氧化物酶（APX）的活性,且外源AsA预处理过的幼苗在高温处理期间能保持相对较高的AsA含量和APX活力。     

大学生课外参与投入的适度性研究

学生课外参与投入是影响学生发展的重要因素。本文首先从经济学视角分析了学生课外参与投入对学生发展的影响机制,提出课外参与存在适度性的假设,并利用“2008年首都高校学生发展调查”数据建立计量模型,通过多元回归分析证明了课外参与投入适度性的存在。研究结果显示,学生自学和课外活动参与等课外参与投入存在适度区间且对学生全面发展的作用边际递减,课外自学、课外活动参与、积极课堂参与对学生不同维度发展的影响方向和程度不同,不同类型院校学生课外自学和课外活动参与投入对学生发展的影响存在差异。基于以上发现,分别针对学生个人和高等院校在课堂以外领域的行为提出了建议。     

Anti-aging effects of caloric restriction: Involvement of neuroendocrine adaptation by peripheral signaling

Many hormonal signals from peripheral tissues contribute to the regulation of energy homeostasis and food intake. These regulators including leptin, insulin, and ghrelin, modulate the orexigenic and anorexigenic neuropeptide expression in hypothalamic nuclei. The anti-aging effects of caloric restriction have been explained from an evolutional viewpoint of the adaptive response of the neuroendocrine and metabolic response systems to maximize survival during periods of food shortage. In organisms, excess energy is stored in adipose tissues as a triglyceride preparation for such survival situations. Adipose tissue has recently been recognized as an endocrine organ, and leptin, as secreted by adipocyte, seems to be an especially important factor for the adaptive response to fasting and neuroendocrine alterations under caloric restriction. In this review, we discuss the potential involvement of neuroendocrine modulators in longevity and the anti-aging effects of caloric restriction.     

Role of insulin-like growth factor binding protein-3 in breast cancer cell growth

The mitogenic effects of insulin-like growth factors (IGFs) are regulated by a family of insulin-like growth factor binding proteins (IGFBPs). One member of this family, IGFBP-3, mediates the growth-inhibitory and apoptosis-inducing effects of a number of growth factors and hormones such as transforming growth factor-beta, retinoic acid, and 1,25-dihydroxyvitamin D3. IGFBP-3 may act in an IGF-dependent manner by attenuating the interaction of pericellular IGFs with the type-I IGF receptor. It may also act in an IGF-independent manner by initiating intracellular signaling from a cell surface receptor, or by direct nuclear action, or both. The possibility of a membrane-bound receptor is strengthened by recent studies which have identified members of the transforming growth factor-beta receptor family as having a role, either directly or indirectly, in signaling from the cell surface by IGFBP-3. A number of growth factors and hormones stimulate the expression and secretion of cellular IGFBP-3, which then signals from the cell surface to bring about some of the effects attributed to the primary agents. Within the cell, the apoptosis-inducing tumor suppressor, p53, can also induce IGFBP-3 expression and secretion. Since IGFBP-3 upregulates the cell cycle inhibitor, p21(Waf1), and increases the ratio of proapoptotic to antiapoptotic members of the Bcl family, it appears to exert the same effects on major downstream targets of cell signaling as p53 does. The nuclear localization of IGFBP-3 has been described in a number of cell types. IGFBP-3 may act to import IGFs or other nuclear localization signal-deficient signaling molecules into the nucleus. It may also act directly in the nucleus by enhancing the activity of retinoid X receptor-alpha and thereby promote apoptosis. All of the above phenomena will be discussed with particular emphasis on the growth of breast cancer cells.