Добірка наукової літератури з теми "C8DTCA"

Prion diseases are fatal infectious neurodegenerative disorders in human and animals caused by misfolding of the cellular prion protein (PrPC) into the pathological isoform PrPSc. Elucidating the molecular and cellular mechanisms underlying prion propagation may help to develop disease interventions. Cell culture systems for prion propagation have greatly advanced molecular insights into prion biology, but translation of in vitro to in vivo findings is often disappointing. A wider range of cell culture systems might help overcome these shortcomings. Here, we describe an immortalized mouse neuronal astrocyte cell line (C8D1A) that can be infected with murine prions. Both PrPC protein and mRNA levels in astrocytes were comparable with those in neuronal and non-neuronal cell lines permitting persistent prion infection. We challenged astrocytes with three mouse-adapted prion strains (22L, RML, and ME7) and cultured them for six passages. Immunoblotting results revealed that the astrocytes propagated 22L prions well over all six passages, whereas ME7 prions did not replicate, and RML prions replicated only very weakly after five passages. Immunofluorescence analysis indicated similar results for PrPSc. Interestingly, when we used prion conversion activity as a readout in real-time quaking-induced conversion assays with RML-infected cell lysates, we observed a strong signal over all six passages, comparable with that for 22L-infected cells. These data indicate that the C8D1A cell line is permissive to prion infection. Moreover, the propagated prions differed in conversion and proteinase K–resistance levels in these astrocytes. We propose that the C8D1A cell line could be used to decipher prion strain biology.

Abstract Solanum mauritianum, commonly known as “Tabaquillo”, was one of the most used plants by tribes from South America as a remedy for headaches. Based on this ethnopharmacological use, a bioguided isolation of compounds with anti-inflammatory and anti-Alzheimer’s activities from S. mauritianum was carried out by measuring the inhibition of NF-κB in C8D1A, Neuro-2a, and EOC 13.31 cells, and by measuring the inhibition of acetylcholinesterase and β-amyloid. This allowed the isolation and characterisation by nuclear magnetic resonance and mass spectrometry of four compounds (1–4). Compounds 1–4 showed NF-κB inhibitory activity with IC50 values of 9.13–9.96, 17.17–17.77, 2.41–2.79, and 1.59–1.93 µM, respectively, while celastrol (the positive control) had an IC50 value of 7.41 µM. Likewise, compounds 1–4 showed anti-Alzheimer’s activity, inhibiting the acetylcholinesterase by 40.33, 20.57, 61.26, and 83.32%, respectively, while galantamine (positive control) showed an inhibition of 90.38%. In addition, concerning the inhibition of β-amyloid aggregation, compounds 1–4 showed an inhibition of 47, 23, 65, and 93%, respectively, while curcumin (positive control) had an inhibition of 71.19%.

Abstract TLR3 (Toll-like receptor 3) belongs to the family of receptors involved in innate immune response. Present in endosomal compartment in cells, TLR3 recognizes the dsRNA (double-stranded RNA), viral nucleic acid or intermediate during viral replication and initiates signal transduction leading to inflammatory response. However, the first steps of signaling cascade occurring in cells immediately after TLR3 stimulation are still not well understood and require careful attention. In this paper we demonstrate that after poly(I:C) (dsRNA mimetic) stimulation of murine microglial cells (C8D1A cell line) tyrosine kinase Syk interacts with Hrs (hepatocyte growth factor regulated tyrosine kinase substrate), one of the ESCRT-0 (endosomal sorting complex required for transportation-0) components. This protein complex was recently implicated in trafficking of other endosomal TLRs, TLR7 and TLR9, and plays a possible role in the TLR3 signaling. Phosphorylation of Hrs, which is a very likely result of Hrs-Syk interaction, also takes place after poly(I:C) stimulation, strongly suggesting that an association between activated TLR3 and ESCRT-0 exists. Therefore, Hrs may influence TLR3 signaling pathways, but this requires further investigation.

Abstract TLR3 (Toll-like receptor 3) belongs to the subfamily of TLRs that reside in the endosomal compartment of the cell. It recognizes dsRNA (double-stranded RNA) of viruses and initiates a signaling pathway leading to generation of antiviral molecules such as type I interferons. Precursor TLR3 present in mammalian cells has a size of approximately 110 kDa, however, recent findings show that the TLR3 may also occur in two progeny forms: C-terminal and N-terminal, appearing after cleavage of TLR3 in specific conditions by cysteine proteases – cathepsins. Furthermore, cleaved and/or associated TLR3 molecules may represent the primary form of the receptor and are capable of binding the TLR3 ligand. Our results show that in C8D1A murine astrocyte cell line, cleavage of TLR3 is time- and dose-dependent upon stimulation with poly(I:C) (polyinosinic:polycytidylic acid, synthetic dsRNA analogue). The cleavage process promotes and increases expression of the progeny receptor forms. Presentation of TLR3 in such manner may modulate the level of response to viral dsRNA, especially in central nervous system cells, however, this requires further investigation.

Abstract CGRP (calcitonin gene related protein) is a neuropeptide expressed by primary sensory neurons upon infection. LP-BM5 retrovirus infection induces profound immunodeficiency in B6 mice and has been used as a murine model of HIV infection. Previously, we showed that LP-BM5 induced increased CGRP expression in the spinal cords of infected mice. In vitro studies indicated a microglia dependent, CGRP-induced reduction of LP-BM5 viral loads in primary mixed glial cells. To further delineate CGRP’s effects on glial cells, we treated specific murine cell lines (C8D1A astrocyte cell line and C8B4 microglia cell line) with LP-BM5 and CGRP. We found that LP-BM5 was capable of infecting both microglia and astrocytes individually and PCR detection for selected CGRP receptor components indicated the presence of CGRP receptor in both cell lines. CGRP’s antiviral effect was observed in both astrocytes and microglia, however a lower dose of CGRP was required for microglia. Western blot analysis suggested differential changes in CGRP downstream signaling pathways in astrocyte vs. microglia upon CGRP treatment. In addition, type I interferons known for their antiviral properties were elevated in astrocytes following CGRP treatment. We propose that CGRP mediated signaling pathways may mediate type I interferon production thus further promote antiviral responses.

AbstractThe synthetase 3β-hydroxysterol-Δ24 reductase (DHCR24) is a key regulator involved in cholesterol synthesis and homeostasis. A growing body of evidence indicates that DHCR24 is downregulated in the brain of various models of Alzheimer’s disease (AD), such as astrocytes isolated from AD mice. For the past decades, astrocytic tau pathology has been found in AD patients, while the origin of phosphorylated tau in astrocytes remains unknown. A previous study suggests that downregulation of DHCR24 is associated with neuronal tau hyperphosphorylation. Herein, the present study is to explore whether DHCR24 deficiency can also affect tau phosphorylation in astrocytes. Here, we showed that DHCR24 knockdown could induce tau hyperphosphorylation at Thr181, Ser199, Thr231, Ser262, and Ser396 sites in C8D1A astrocytes. Meanwhile, we found that DHCR24-silencing cells had reduced the level of free cholesterol in the plasma membrane and intracellular organelles, as well as cholesterol esters. Furthermore, reduced cellular cholesterol level caused a decreased level of the caveolae-associated protein, cavin1, which disrupted lipid rafts/caveolae and activated rafts/caveolae-dependent Ras/MEK/ERK signaling pathway. In contrast, overexpression of DHCR24 prevented the overactivation of Ras/MEK/ERK signaling by increasing cellular cholesterol content, therefore decreasing tau hyperphosphorylation in C8D1A astrocytes. Herein, we firstly found that DHCR24 knockdown can lead to tau hyperphosphorylation in the astrocyte itself by activating lipid raft-dependent Ras/MEK/ERK signaling, which might contribute to the pathogenesis of AD and other degenerative tauopathies.

Objective: It has been reported that carnitine deficiency is observed in various viral infections and in the follow-up of the prognosis of some diseases. In this cross-sectional study, we aimed to determine how carnitine ester derivatives change in HIV-positive patients. Material and Method: In this study, 25 HIV-infected patients who applied to Harran University Faculty of Medicine Education Research and Practice Hospital Infectious Diseases and Clinical Microbiology Outpatient Clinic and who did not receive any antiretroviral treatment, as well as 25 healthy volunteers were included in the study. Carnitine ester levels in serum samples were measured by Liquid Chromatography-Mass Spectrometry/Mass Spectrometry (LC-MS/MS) method (Shimadzu North America, Columbia, MD, USA). Results: While suberoylcarnitine (C8DC), myristoleylcarnitine (C14:1), tetradecadienoylcarnitine (C14:2), palmitoleylcarnitine (C16:1), and linoleylcarnitine (C18:2) levels in HIV+ patients were quite low compared to the control group, tiglylcarnitine (C5:1) levels were high (p ≤ 0.05). In addition, C5:1 and C14:2 index parameters according to VIP score, and C5:1 and C14:1/C16 index parameters according to ROC analysis were determined as markers with high potential to distinguish HIV+ patients from healthy volunteers. Conclusion: This study showed that acylcarnitine derivatives might be altered in HIV+ patients, and the results obtained may contribute to a better understanding of carnitine metabolism.

Background: Routine screening for hereditary disorders in newborns includes screening for treatable metabolic and endocrine disorders, such as biotidinase deficiency, galactosemia, maple syrup urine disease, hypothyroidism, and cystic fibrosis. Incorrect test results may be encountered due to the use of vitamin K. To investigate the interference effect of vitamin K on neonatal screening tests and to raise awareness of erroneous measurements. Methods: Heel blood samples were taken from 25 newborns born in a neonatal intensive care unit. Dry blood C0, C2, C3, C4, C4DC, C5:1, C5OH, C5DC, C6, C6DC, C8, C8:1, C8DC, C10, C10:1, C10DC, C12, C14, C14:1, C14:2, C16, C16:1, C18, C18:1, C18:2, C18:OH, methylglutaryl, valine, leucine/isoleucine, methionine, phenylalanine, argininosuccinic acid, aspartate, alanine, arginine, citrulline, glycine, ornithine, and glutamate tests were studied using the tandem mass spectrometry (MS) method. The results of the heel blood samples obtained before and after the application of vitamin K1 (Phyto menadione) were compared. Results: In two studies conducted with in vitro and in vivo tests, C0, C2, C3, C4, C4DC, C5, C5OH, C6, C8, C10, C10:1, C14, C16, C16:1, C18, C18:1, methylglutaryl, phenylalanine, argininosuccinic acid, tyrosine, aspartate, arginine, citrulline, glycine, and glutamine were all significantly elevated (p < 0.05). Conclusion: Heel blood samples may yield false results due to vitamin K administration. In the case of doubtful results, a new sample should be taken and the measurement should be repeated.

This thesis is an examination of the structure of irreducible continua, with a particular emphasis on local connectedness and monotone maps. A continuum is irreducible if there exist a pair of points such that no proper subcontinuum contains both, with the arc being the most basic example. Being irreducible has a number of interesting implications for a continuum, both locally and globally, and it is these consequences we shall focus on. As mentioned above, the arc is the most straightforward example of an irreducible continuum. Indeed, an intuitive understanding of an irreducible continuum would be that it is structured like an arc, with the points of irreducibility at either end joined by a subspace with no loops or offshoots. In Chapter 2 we will see that for a certain class of continua this intuition is well founded by constructing a monotone map from an irreducible continuum onto an arc. This monotone map will preserve much of the structure of our continuum and as such will provide an insight into that structure. We will next examine a generalisation of irreducibility which considers finite sets of points rather than just pairs. A number of classical results will be re-examined in this light in Chapter 3. While the majority of these theorems will be shown to have close parallels in higher finite and infinite irreducibility there will be several which do not hold without further conditions on the continuum. Such anomalies will be particularly prevalent in continua which have indecomposable subcontinua dominating their structure. In Chapter 4 monotone maps will be constructed for finitely irreducible continua similar to the map to an arc mentioned previously. Chapters 7 and 8 will generalise irreducibility further to the infinite case and we will again construct monotone maps preserving the structure of our continuum. Along with the arc, another highly significant irreducible continuum is the sin 1 x continuum. Chapter 5 will focus on this continuum, which will be the basis for a nested sequence of continua. A number of results concerning continuous images of these continua will be presented before using the sequence of continua to define an indecomposable continuum. This continuum will be investigated, and it will be shown that the union of our nested continua form a composant of the indecomposable continuum. In Chapter 6 we will turn to the question of compactifications. If a space X is connected then any metric compactification of X will be a continuum. This chapter will answer the question of when a compactification is an irreducible continuum, with the remainder of the compactification consisting of all of the irreducible points. A list of properties will given such that a continuum has such a compactification if and only if it has each property on the list. It will also be demonstrated that each of these properties is independent of the others. Finally, in Chapter 9 we will revisit the idea of structure-preserving monotone maps, but this time in continua which are not irreducible. Motivated by the fibres of the maps in previous chapters, we will introduce two categories of subcontinua of a continuum X. The first will be nowhere dense subcontinua which are maximal with this property and the second will be subcontinua about which X is locally connected and which are minimal with this property. Continua in which every point lies in a maximal nowhere dense subcontinuum will be examined, as well as spaces in which every point lies in a unique minimal subcontinuum about which X is locally connected. We will also look at the properties of monotone maps arising from partitions of X into such subcontinua, and will prove that if every point of X lies in a maximal nowhere dense subcontinuum then the resulting quotient space will be one dimensional.

This thesis is a collection of three essays with contributions to the empirical literature on banking and the lending channel of monetary policy. The first essay on monetary policy identification addresses the endogeneity of the monetary policy measure employed in most bank level studies of the lending channel. It shows how an identified, exogenous measure of policy evokes different lending dynamics in U.S. commercial banks compared to the standard endogenous measure of monetary policy. The second essay empirically assesses the impact of financial deregulation on the lending channel in the U.S. In particular, it analyses how the gradual phasing out of deposit rate ceilings commonly known as Regulation Q significantly altered bank level frictions as well as the transmission of monetary policy to individual bank lending. While the first two essays consider U.S. bank level data, the third essay analyses individual bank level lending responses in the euro area. Its contribution lies in the construction of a range of exogenous and unanticipated monetary policy shocks as well as in the introduction of a financial conditions index into standard lending regressions. It finds that the lending responses of individual banks to monetary policy do not support the existence of a separate lending channel in the euro area. Further, equilibrium lending responses to policy as measured by a range of policy shocks is non-linear in financial conditions. Specifically, financial conditions as measured by the relative performance of a broad index of euro area banking stocks to the overall euro area stock market reverse the impact of monetary policy on lending.

Corporate social responsibility (CSR) has an ever-increasing role in the way commercial businesses operate. Team sport organisations are not immune to this trend. CSR is a strategic issue for sport organisations, with professional teams across a range of sports and national contexts now modifying their organisational structure by establishing charitable foundations tasked with delivering their CSR content. These structural changes inevitably bring in new organisational actors who, in varying degrees, influence ̀the actual implementation of CSR in the professional sports team context. Organisational complexity is therefore increasing regarding CSR, as is the need to capture its elements at both cross-organisational and individual levels. This is especially important given that, unlike mainstream (corporate) foundations that deal directly with a ‘parent’ company, professional sport leagues often mandate the implementation of CSR through central funding mechanisms. This in turn emphasises the intricacy of the process and the dynamics amongst organisational actors at various levels. To date, no studies have attempted to address this complexity. The present thesis aims to help fill the gap by examining the managerial decision-making process in the organisational context of charitable foundations established by English professional football clubs. The current study employs a grounded theory methodology as it aims to develop a substantive theory of how managers responsible for the formulation and implementation of CSR-related programmes in English football make professional decisions. The research utilises the Straussian variant of grounded theory, which accepts that humans shape their institutions as much as institutions shape people. The study also seeks cognitive similarity, a concept that implies some form of similar attribution of meaning, understanding or interpretation amongst individuals in multiple organisations. Although its purpose was to develop an individual-based substantive theory grounded in the way managers make decisions regarding CSR, throughout the focus has been on decision-making itself rather than on the individuals who facilitate this process. The study is populated with the top two divisions of English football and employs two data collection techniques: organisational documents and semi-structured interviews. The fieldwork took place in three different phases, with the first ̀consisting of two sub-phases. Phase 1a emphasised the analysis of organisational documents (a total of 25 documents from 16 football organisations), while the following phases of the fieldwork were based on constant comparative data analysis from 32 interviews. The theoretical framework that emerged from this study is one of assessable transcendence; in a conceptually abstract fashion, ‘assessable transcendence’ concerns a process that, fortified ̀by passion, contingent on trust, sustained by communication and substantiated by factual performance, enables the formulation and implementation of CSR-related programmes in this context. The social process that emerged from this study, therefore, consists of an intrinsic (that is, passion) and an extrinsic (that is, trust) stimulus, both of which are central components of the micro-social process transcending. These two stimuli, however, require the support of both internal and external communication (abstractly expressed through the micro-social process manoeuvring), and thus all three together form a ‘coalition’ which can enhance both business and social performance (largely expressed by the first ̀two micro-social processes, namely safeguarding and harmonising). Accordingly, two interrelated aspects of the decision-making process constitute a common thread in this research: (a) the recognition that social consciousness stimulates the process of assessable transcendence in an indispensable and limitless way, and (b) an understanding that transcendence cannot occur without either continuous achievement or the dissemination of concrete ‘CSR impact’ in social and business forms alike (hence assessable). The significance of this doctoral thesis for the sport management literature is four-fold. First, it focuses on the individual level of analysis, thereby offering a framework that explains the decision-making of those individuals responsible for the application of CSR in professional team sport organisations. By doing so, it bridges the micro/macro divide by integrating the micro-domain’s focus on individuals (i.e., foundation managers) with those of the meso- and macro- domains. Second, it moves away from mono-theoretical approaches that have been mainly used for the examination of CSR in the sporting context. By doing so, it illustrates that different, and often opposing, theoretical approaches may be needed in order to fully capture and theoretically explain the way in which the CSR practice occurs. Third, it shifts the focus of scholarly activity away from CSR content-based research towards more process-oriented approaches. CSR content research does little to explain how professional teams achieve and maintain such positioning through deliberate and trial-and-error CSR actions initiated by the individuals therein. Fourth, an in relation to the previous point, it employs a process-oriented methodology (namely, grounded theory) whose utilisation in sport management research has been either non-existent or a ‘pick and mix’ practice. By doing so, the current thesis responds to calls for internal consistency and methodological coherence, thereby adding to the limited number of studies that have utilised this methodology in a rounded manner. The theoretical framework presented in this dissertation has emerged from exploratory study. As such, the four micro-social processes, their associative meanings and, more importantly, the four principal concepts that hold assessable transcendence are regarded as tentative and require substantiation through further research. To this end, a number of research propositions are offered that can serve as a starting point towards a continued exploration of those moderating and mediating factors on the formulation and implementation of CSR in team sport organisations.

碩士
國立臺灣大學
心理學研究所
93
The present study explored the role of cognition in the psychopathology of panic disorder. Specifically, the effects of anxiety sensitivity, controllability, and predictability during the biological challenge tests were investigated. The sample consisted of 96 undergraduate students selected from a large sample by anxiety sensitivity index, and was divided into high and low anxiety sensitivity groups with 48 subjects in each group. Subjects in each group were randomly assigned to one of four different cognitive manipulations. They underwent a biological challenge tests and completed subjective units of distress scale, checklist of catastrophic cognitions and bodily sensations, subjective controllability rating, and subjective predictability rating. An anxiety sensitivity × controllability × predictability factorial design was performed. Results showed that cognitive factors did play significant roles in the development of panic attacks. Meanwhile, the person-in-situation interactional approach could be verified. It revealed that the present study could enhance our understanding of the psychopathology of panic disorder and make some contributions to the cognitive behavior therapy of anxiety disorders.

碩士
銘傳大學
諮商與工商心理學系碩士班
106
Religious bullying can be easily obscured. Religious books, spiritual masters or simply strong believers can be the origin of bullying. This study intended to explore the psychological impacts of Christians, Buddhists, and Taoist believers who have experienced religious bullying. A questionnaire survey on religious bullying has been conducted. A total of 530 samples were collected via web survey, 230 effective questionnaires were obtained. Among all the respondents, 85 people have experienced religious bullying. The results show that most of religious bullying coming from clergy and believers. The three most frequent types of bullying are oral, spiritual and relational bullying. The highest length of bullying is more than five years and less than one year. The findings of this study revealed that although different in religious beliefs, and yet similar in the types of bullying used by the perpetrators. We also found that there were positive correlations among four PTSD diagnostic groups, and neglect, sexual and relational bullying related to significant degree of trauma. Implications and suggestions in counseling are discussed. This research disclosed some realities of religious bullying which had not been studied in the past, hoping it is the first step toward zero-tolerance to religious bullying.