Advances in Neuroimmune Biology最新文献

{"title":"Growth and Lactogenic Hormones and Adaptive Immunocompetence","authors":"I. Bérczi","doi":"10.3233/NIB-012910","DOIUrl":"https://doi.org/10.3233/NIB-012910","url":null,"abstract":"Adaptive immune reactions are based on lymphocyte proliferation, and are regulated by mechanisms which are involved in growth regulation of all cells in higher animals. Growth and lactogenic hormones (GLH) or type I cytokines (TICTK) are of fundamental importance for the development and function of the immune system and indeed for the entire organism. GLH/TICTK deliver the competence signal first to lymphocytes and other cells, which enable the cells to receive stromal or adherence signals that decide what the cell will do next, proliferate, differentiate, or function. This group of signals control cell growth, is delivered by cell-to-cell and cell-to-matrix signalling. Adhesion molecules, tissue bound hormones, cytokines and matrix components mediate these signals. The antigen receptor belongs to the Immunoglobulin Family of adhesion molecules. Hence the antigen signal is capable to activate specifically the immune response, it can inhibit it also. Within the immune system antigen presentation represents the adhesion signal for which cell-to-cell interaction by adhesion molecules is obligatory. Adhesion molecules are fundamental to the organization of multi-cellular organisms and the signals delivered by them serve the basis of species, organ and tissue specific recognition. This recognition system has been perfected during evolution from self-recognition to individually specific antigen recognition. This system also plays a role in the elimination of degenerated and neoplastic cells. Cell-to-cell signaling has a dominant power over other signals to commit the cell to proliferation. The mitotic cycle is then completed by cytokine signals. Cytokines are tissue hormones which are usually, but not always, secreted by the same cells that deliver the second signal. IGF-I and insulin fulfil frequently this role, but cytokines may also deliver this third signal. The nature and combination of these three groups of signals will determine the fate of each cell, which may be survival, proliferation, differentiation and function or alternately apoptosis. Hormones and neurotransmitters, that alter signal delivery, modulate further this basic pattern of animal cell growth. It is concluded that GLH/TICTK maintain immunocompetence, which enables the immune system to respond to specific antigenic and mitogenic stimuli. Competence signalling comes from either the CNS or by TICTK, which is an autologous signal by the immune system. This dual signalling secures that the immune system is capable of surviving major disasters in the personal history of the host. Indeed memory T and B ells survive autonomously, and live trough major catastrophic events, and when the disaster is over, memory cells regenerate the adaptive immune system and bring back homeostasis of immune function which is the prerequisite for healing and homeostasis of the entire organism. The hypothalamic hormone, vasopressin (VP) regulates healing and recovery from disease.","PeriodicalId":38645,"journal":{"name":"Advances in Neuroimmune Biology","volume":"3 1","pages":"301-312"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3233/NIB-012910","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70143967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adipose Cell-Derived Stem Cells: Neurogenic and Immunomodulatory Potentials","authors":"M. I. Arribas, Jonathan Jones, S. Martinez, E. Roche","doi":"10.3233/NIB-2012-012037","DOIUrl":"https://doi.org/10.3233/NIB-2012-012037","url":null,"abstract":"Mesenchymal stem cells can be isolated from numerous adult and fetal tissues, such as the bone marrow and fat. In vitro, these cells can be induced to differentiate into various mesodermal cell types, such as osteocytes, adipocytes, chondrocytes and myoblasts. Also, they can be transdifferentiated into other non-mesodermal cell types, including the neuroectoderm. However, numerous articles question the validity of these cell products as actual neurons. On the other hand, there is increasing evidence that these stem cells, rather than transdifferentiate, activate regeneration processes by releasing certain neurotrophic factors, which activate host progenitors. Also, in this work we will discuss how stem cells regulate immune response and alloantigen recognition. This property could have important implications in autoimmune neurodegenerative disorders as well as other pathologies. Altogether, mesenchymal stem cells are interesting candidates for cell therapy by promoting trophic effects or by modulating the immune system function. Nevertheless, the transdifferentiation/transdetermination of mesenchymal stem cells into non-mesodermic cell types remains an open question.","PeriodicalId":38645,"journal":{"name":"Advances in Neuroimmune Biology","volume":"3 1","pages":"19-30"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3233/NIB-2012-012037","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70147378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Autoantibodies and Natural Catalytic Antibodies in Health, Multiple Sclerosis, and Some Other Diseases","authors":"G. Nevinsky, V. Buneva","doi":"10.3233/NIB-2012-012042","DOIUrl":"https://doi.org/10.3233/NIB-2012-012042","url":null,"abstract":"In patients with autoimmune disease (AD) viral, and bacterial diseases autoantibodies (Abs) directed to polysaccha- rides, nucleic acids, proteins, peptides, and nucleoprotein complexes may emerge. Some of these autoantibodies show enzyme activity and may perform catalytic functions (abzymes; Abzs). Such Abs can have the catalytic activity of idiotypic and/or antiidiotypic Abs. Healthy humans usually do not develop Abzs. Detection of Abzs is the earliest indicator for the development of ADs. Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system. MS pathogenesis is not clear. Destruction of myelin by inflammation caused by AI reactions has been proposed. However, poly-specific DNA-binding Abs are present in MS patients. IgG Abzs from MS patients hydrolyzed DNA, RNA, polysaccharides, and myelin basic protein. This fact may be important for MS pathogenesis. Here we discuss catalytic antibodies (Abzs) in MS and those in other autoimmune diseases.","PeriodicalId":38645,"journal":{"name":"Advances in Neuroimmune Biology","volume":"3 1","pages":"157-182"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3233/NIB-2012-012042","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70147496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanisms of Psychogenic Fever","authors":"T. Oka, K. Oka","doi":"10.3233/NIB-2012-011030","DOIUrl":"https://doi.org/10.3233/NIB-2012-011030","url":null,"abstract":"Psychogenic fever is a psychosomatic disease especially seen in young adults. However, the mechanisms explaining how psychological stress increases core body temperature (Tc) in these patients are not yet fully understood. Therefore, this article reviews the current understanding of the mechanisms of stress-induced hyperthermia and the distinctive effects of acute, repeated, or chronic stress on Tc in laboratory animals. Acute exposure to anxiety-provoking stress induces a transient, monophasic increase in Tc. In contrast, repeated stress either induces anticipatory hyperthermia, reduces diurnal changes in Tc, or slightly increases Tc throughout the day. Chronically stressed animals also show depressive-like behaviors and display an enhanced hyperthermic response to a novel stress. A fearful experience in the past induces conditioned hyperthermia to the fear context. The high Tc that psychogenic fever patients develop may be a complex of many kinds of hyperthermic responses previously modeled in animals. Animal studies also show that psychological stress increases Tc via mechanisms distinct from infectious fever, which requires proinflammatory mediators. However, psychological stress and immune insults may increase Tc via a common efferent pathway, i.e., the rostral medullary raphe region-sympathetic nervous system circuit.","PeriodicalId":38645,"journal":{"name":"Advances in Neuroimmune Biology","volume":"3 1","pages":"3-17"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3233/NIB-2012-011030","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70147165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of peripheral and brain-derived dopamine (DA) in immune regulation","authors":"B. Tóth, M. Vecsernyés, T. Zelles, K. Kádár, G. Nagy","doi":"10.3233/NIB-2012-012044","DOIUrl":"https://doi.org/10.3233/NIB-2012-012044","url":null,"abstract":"There is a well-defined influence of dopamine (DA) within the immune system. It can be synthesized not only in neurons, but also in immune cells, especially in T cells. In addition, these cell are bearing an active uptake mechanism, which could serve another source of DA. Therefore, it is highly likely that a functional DA-erg autocrine/paracrine regulatory loop exists, where lymphocytes-derived DA acting through its own receptors, also expressed on the same cells, can have an influence on its own function. However, the possibility that immune cell derived DA may act in accordance with DA secreted by other sources, i.e. from sympathetic terminals, cannot be ruled out. In harmony with these observations have provided evidences for the existence of a functional DA-erg system in the thymus, indicating that DA may have also a role in the maturation and selection of a certain subpopulation of lymphocytes as well. Based upon all of this information and evidences, for being able to summarize this topic, a much broader survey, including all direct and indirect immune-modulatory role of DA is required. Therefore, in this review we are going to discuss the most relevant aspects of this regulatory function. Facts and theories based upon experimental (pre-clinical) data are extended with the evidences accumulated by clinical observations.","PeriodicalId":38645,"journal":{"name":"Advances in Neuroimmune Biology","volume":"3 1","pages":"111-155"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3233/NIB-2012-012044","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70147575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dopamine in Immunoregulation","authors":"I. Bérczi, T. Katafuchi","doi":"10.3233/NIB-2012-012046","DOIUrl":"https://doi.org/10.3233/NIB-2012-012046","url":null,"abstract":"In this issue Toth et al. [1] discusses the role of peripheral and brain derived dopamine (DA) in immune regulation. Here we consider briefly the possible way by which hormones and other central regulatory factors act peripherally in vivo. During the early years of the nineteenth centaury Endocrinologists recognized first when searching for the origin of hormones, that “everything is made everywhere”. This rule was true for all hormones and neurotransmitters that have been examined. This phenomenon has been re-discovered since that time over and over again. DA exerts an inhibitory effect on prolactin (PRL) and growth hormone (GH) secretion. This effect is very powerful. In rats treatment with bromocriptine (a DA agonist drug), inhibited completely the adaptive immune function (ADIM) [2]. The rule in the Neuroimmune Supersystem [3] is that mediators are shared: so classical hormones and neuropeptides are made in the immune system and everywhere else, lymphokines were discovered in the immune system first, but then were found in many other tissues and cells so their name was changed to cytokines, which implies tissue hormones. Sharing makes communication instantaneously possible [3]. Dopamine is no exception to this rule. It is made in the central nervous system (CNS) but also in various cell types in the immune system, and in many other tissue and organs in the body. In short, dopamine is made everywhere and acts everywhere [1]. One may argue that dopamine is a powerful immunoregulator, it can act centrally by inhibiting PRL secretion, and also acts peripherally by paracrine/autocrine (P/A) regulation. Yes indeed, this is very important from the point of usefulness. But how the central and peripheral mechanisms work under homeostatic conditions? There are myriads of mediators produced centrally, peripherally, and receptors are expressed and may be activated everywhere. This may lead to a very chaotic situation, signals are delivered everywhere; cells could go crazy under such bombarding. It was proposed that membrane bound receptors will cap on one pole of the cell surface after activation by specific ligands. Such receptors are phosphorylated by protein kinases and de-phoshorylated by phosphatases, which happens competitively at the same time. If phosphorylation is stronger the cell will be activated, if de-phosphorylation is stronger, the cells will be inhibited [4]. But there are many other mediators that do not use this signal transmission pathway. Alternate mechanisms are used by some membrane receptors. Also, there are cytoplasmic and nuclear receptors, which definitely would not be controlled by this kind of regulation [5]. It is important that every regulatory circuit has positive and negative signals and the signals will balance out physiologically, possibly under CNS control. The fact is that in spite of the countless mediators, receptors and signaling, the organism remains normal, all functions are in harmony and in homeostasis. The cla","PeriodicalId":38645,"journal":{"name":"Advances in Neuroimmune Biology","volume":"3 1","pages":"109-110"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3233/NIB-2012-012046","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70147713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Healing Power of Vasopressin","authors":"I. Bérczi, A. Quintanar, E. Villalobos-Hernández, R. Campos, K. Kovacs","doi":"10.3233/NIB-2012-012047","DOIUrl":"https://doi.org/10.3233/NIB-2012-012047","url":null,"abstract":"","PeriodicalId":38645,"journal":{"name":"Advances in Neuroimmune Biology","volume":"3 1","pages":"217-224"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3233/NIB-2012-012047","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70147739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adaptive and Innate Immunity and Acute Illness","authors":"I. Bérczi, A. Stephano","doi":"10.3233/NIB-012911","DOIUrl":"https://doi.org/10.3233/NIB-012911","url":null,"abstract":"The adaptive immune system (ADIM) involves the bone marrow that produce bone marrow derived (B) lymphocytes, and also release precursor cells for thymus derived (T) lymphocytes. B cell produce antibodies and regulate antibody formation, T cells mediate cellular immunity by killer T cells, and T cells mediating delayed type hypersensitivity. During an ADIM response, T and B lymphocytes proliferate, and their receptors undergo somatic mutation and clonal selection in order to generate highly specific antigen receptors. Seven to ten days needed for an adaptive immune response to develop. Antigen presenting cells (APC) initiate the ADIM response. Innate immunity (INIM) protects us for life. Innate antigen receptors are germ line coded, constant and polyspecific. The bone marrow produces monocyte/macrophages which recognize antigen, CD5+ B lymphocytes producing polyreactive natural antibodies, and polymorhonuclear granulocytes which are phagocytic cells. Natural killer, NK and NKT cells, and suppres- sor/regulatory T (Ts/r) cells are thymus derived. Cytokines are produced by monocytee/macrophages, NK, NKT Ts/r cells. The liver produces acute phase proteins (APP). Complement, properdin, defensins, scavenger receptors, enzymes and numerous other substances function as APP. The INIM system is capable of instantaneous defense at any time even under adverse conditions it will protect the host. During homeostasis both the adaptive and innate immune systems are regulated by vasopressin (VP) and everything works in harmony. During acute illness immune derived cytokines induce the acute phase response (APR), which is an emergency defense reaction against life threatening insults. During APR the INIM system is stimulated rapidly (maximum ∼1000 times, within 24-48 hours) and take over host defense as the ADIM system is not capable for a rapid response, and it is suppressed. Major endocrine, metabolic, and immune alterations take place. The HPA axis, sympathetic nervous system, glucocorticoids, catecholamines, pro-inflammatory cytokines, the brain, liver and white blood cells mediate APR. Fever and catabolism are hallmarks of APR. APR is the last effort by the organism to survive a life threatening event. In the overwhelming majority, febrile illness will be followed by recovery, which indicates the efficiency of this reaction. As a rule acute febrile illness will subside and chronic inflammatory disease will follow. During chronic inflammation VP becomes the hypothalamic regulator of immune and inflammatory process. Recovery will follow in most instances. The neuroendocrine, metabolic and immune abnormalities will be normalized and VP will serve as the hypothalamic factor regulating bodily functions during homeostasis. In cases when chronic stress does not subside, the INIM system will remain activated, and because of the excess energy requirement of this system cachexia may develop, which may be a lethal condition.","PeriodicalId":38645,"journal":{"name":"Advances in Neuroimmune Biology","volume":"3 1","pages":"277-285"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3233/NIB-012911","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70144108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroimmune Biology of Mast Cells","authors":"E. Salinas","doi":"10.3233/NIB-2012-012032","DOIUrl":"https://doi.org/10.3233/NIB-2012-012032","url":null,"abstract":"Mast cells (MCs) are immune cells derived from hematopoietic progenitor cells in bone marrow, which complete their maturation within tissues. They are widely distributed throughout the body, but strategically in high amounts in skin and mucosal surfaces. MCs can store in their granules and rapidly release a wide variety of biologically active molecules and also synthesize de novo and release an additional group of inflammatory mediators and growth factors. Some of the biological functions of these MCs-mediators are related to host defense against pathogens, inflammation, tissue remodeling and homeostasis. The MCs proximity to nerve fibers in the skin and the fact that they produce and respond to several neuropeptides, suggest the existence of an intensive bidirectional crosstalk between MCs and nerve fibers that mediates many processes in health and disease. MCs- neuron interaction is involved in neurogenic inflammation, tissue remodeling, pruritus and ultraviolet radiation (UVR)-induced immunosuppression. Evidence indicates that mast cells also participate in the development and progression of skin disorders that involves hyperproliferation and inflammation, such as allergic cutaneous reactions. Therefore, it is important to know the details of this intricate interaction to understand the exact participation of MCs in physiologic and pathologic processes.","PeriodicalId":38645,"journal":{"name":"Advances in Neuroimmune Biology","volume":"3 1","pages":"57-72"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3233/NIB-2012-012032","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70147210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New aspects of the immunoregulation by the hypothalamo-pituitary-adrenal (HPA) axis","authors":"M. Vecsernyés, K. Kovács, B. Tóth, L. Welke, G. Nagy","doi":"10.3233/NIB-012907","DOIUrl":"https://doi.org/10.3233/NIB-012907","url":null,"abstract":"One of the basic neuro-immune-endocrine interaction is the hypothalamo-pituitary-adrenal axis (HPA) to harmonize immune response to inflammatory stressors. Immune defense mechanisms mediated by cytokines and other humoral factors play particularly important roles in this communication. They are also potent activators in the CNS and factors of the HPA axis, like an increased secretion of glucocorticoids (GC). They can act as major feedback regulator of the vertebrate immune response via suppression of a wide range of cytokines, as well as interferons. Increases in systemic GC levels, however, often play dual role: do not suppress all cytokines since inhibition of a particular cytokine may result in elevated production of others. External stimuli/acute stress can compromise activation of the HPA axis and activate immune processes for defense, redirecting leukocytes from the circulation to the environment/organism interface. Overall it results in release of danger-associated molecular patterns (DAMPs) to activate cells of the innate immune system, which is resolved by neural, hormonal or immune mechanisms. The chronic stress leads to chronic immune arousal and subsequent sterile, low-grade inflammation, which has been identified in most \"stress-related or \"civilized\" disorders in humans. The role of pituitary-gonadal axis in the activation of HPA axis results in a gender difference in HPA response to immunological challenges: e.g. can be varied during the estrus cycle, pregnancy or lactation. That corresponds to the results of recent experimental data that reveals an important role of certain neurotramsitters (such as dopamine) in immune regulation. Internal constitutional-factors of neuro-immune-endocrine interaction, such as corticotropin-releasing hormone (CRH) and its receptors (CRF-R1 and CRF-R2), melanocortin peptides, glucocorticoids or pro-inflammatory cytokines can also act as an immunoregulator, since their receptors is present in lymphoid organs, also in peripheral blood and organs that are enhanced under inflammatory conditions. In spite of series experimental data, the role of CRH and other members of its family, as well as its receptors in inflammation are still controversial. This dual role may be due to different CRF receptors and altered functionality. There are several putative mechanisms or \"ports of entry\", in which the cytokines may affect HPA activity and CRH release. Some influences of cytokines on the HPA axis may be exerted by an indirect way. The aim of our review was to summarize and outline of key interacting agents based upon recent experimental results.","PeriodicalId":38645,"journal":{"name":"Advances in Neuroimmune Biology","volume":"3 1","pages":"287-295"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3233/NIB-012907","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70143616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}