542 research outputs found

    Phenotypic and Functional Characterization of Human Memory T Cell Responses to Burkholderia pseudomallei

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    Copyright: © 2009 Tippayawat et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background: Infection with the Gram-negative bacterium Burkholderia pseudomallei is an important cause of community-acquired lethal sepsis in endemic regions in southeast Asia and northern Australia and is increasingly reported in other tropical areas. In animal models, production of interferon-gamma (IFN-γ) is critical for resistance, but in humans the characteristics of IFN-γ production and the bacterial antigens that are recognized by the cell-mediated immune response have not been defined. Methods: Peripheral blood from 133 healthy individuals who lived in the endemic area and had no history of melioidosis, 60 patients who had recovered from melioidosis, and 31 other patient control subjects were stimulated by whole bacteria or purified bacterial proteins in vitro, and IFN-γ responses were analyzed by ELISPOT and flow cytometry. Findings: B. pseudomallei was a potent activator of human peripheral blood NK cells for innate production of IFN-γ. In addition, healthy individuals with serological evidence of exposure to B. pseudomallei and patients recovered from active melioidosis developed CD4+ (and CD8+) T cells that recognized whole bacteria and purified proteins LolC, OppA, and PotF, members of the B. pseudomallei ABC transporter family. This response was primarily mediated by terminally differentiated T cells of the effector–memory (TEMRA) phenotype and correlated with the titer of anti-B. pseudomallei antibodies in the serum. Conclusions: Individuals living in a melioidosis-endemic region show clear evidence of T cell priming for the ability to make IFN-γ that correlates with their serological status. The ability to detect T cell responses to defined B. pseudomallei proteins in large numbers of individuals now provides the opportunity to screen candidate antigens for inclusion in protein or polysaccharide–conjugate subunit vaccines against this important but neglected disease

    Hypoxia induces rapid, STAT3 and ROS dependent, mitochondrial translocation of RelA(p65) and IκBα

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    \ua9 2019 The Author(s).The nuclear factor-κB (NF-κB) family of transcription factors can directly or indirectly regulate many important areas of biology, including immunity, inflammation and cell survival. One intriguing aspect of NF-κB crosstalk with other cell signalling pathways is its regulation of mitochondrial biology, including biogenesis, metabolism and apoptosis. In addition to regulating the expression of mitochondrial genes encoded in the nucleus, NF-κB signalling components are also found within mitochondria themselves and associated with mitochondrial DNA. However, complete biochemical analysis of mitochondrial and sub-mitochondrial localisation of all NF-κB subunits has not been undertaken. Here, we show that only the RelA NF-κB subunit and its inhibitor IκBα reside within mitochondria, whilst p50 is found in the endoplasmic reticulum (ER). Fractionation of mitochondria revealed that only RelA was found in the mitoplast, the location of the mtDNA. We demonstrate that hypoxia leads to a very rapid but transient accumulation of RelA and IκBα in mitochondria. This effect required reactive oxygen species (ROS) but was not dependent on the hypoxia sensing transcription factor subunit HIF1α or intracellular Ca2+ release. We also observed rapid mitochondrial localisation of transcription factor STAT3 following hypoxia. Inhibition of STAT3 blocked RelA and IκBα mitochondrial localisation revealing a previously unknown aspect of crosstalk between these key cellular regulators

    The ARRIVE Essential 10: author checklist- The effect of 10% ointment concentration of ethyl acetate subfraction of meniran (Phyllanthusniruri L.) leaves on excision wound healing in white male rats

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    The ARRIVE Essential 10: author checklist- The effect of 10% ointment concentration of ethyl acetate subfraction of meniran (Phyllanthusniruri L.) leaves on excision wound healing in white male rat

    PENGARUH KEBIASAAN BELAJAR TERHADAP HASIL BELAJAR DENGAN LINGKUNGAN KELUARGA SEBAGAI VARIABEL MODERATOR (SYSTEMATIC LITERATURE REVIEW)

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    Rela Regina Riani (1600723). “PENGARUH KEBIASAAN BELAJAR TERHADAP HASIL BELAJAR DENGAN LINGKUNGAN KELUARGA SEBAGAI VARIABEL MODERATOR (Systematic Literature Review)”. Di bawah Bimbingan Dosen Pembimbing I : Dr. Sumartini, MP., dan Dosen Pembimbing II: Dr. Siti Parhah, S.Pd, M.SE. ABSTRAK Tujuan penelitian ini untuk mengetahui pengaruh kebiasaan belajar terhadap hasil belajar siswa, serta lingkungan keluarga sebagai variabel moderator. Penelitian ini menganalisis beberapa artikel tentang kebiasaan belajar berpengaruh terhadap peningkatan hasil belajar, serta lingkungan keluarga memperkuat pengaruh kebiasaan belajar terhadap hasil belajar. Pencarian artikel dilakukan pada publikasi online seperti APA PsycNet, Elsevier, ERIC, Taylor and Prancis, Academia, Global Journal for Research Analysis (GJRA), IISTE, Sage Pub, Emerald, yang diterbitkan antara tahun 2013-2020. Penulis memperoleh 10 artikel yang memenuhi syarat berdasarkan karakteristik pemilihan artikel relevan yang telah ditentukan. Temuan artikel menunjukan bahwa kebiasaan belajar berpengaruh positif terhadap hasil belajar siswa. Hal ini disebabkan karena kebiasaan belajar baik akan cenderung lebih berhasil dalam proses pembelajarannya baik kebiasaan belajar disekolah, kebiasaan dirumah, kebiasaan belajar kelompok, kebiasaan belajar dalam memahami buku yang akan berpengaruh terhadap hasil belajar. Selain itu, ditemukan bahwa lingkungan keluarga dapat memperkuat pengaruh kebiasaan belajar terhadap hasil belajar siswa. Hal ini disebabkan karena lingkungan keluarga yang harmonis dan menyenangkan, ditambah dengan perhatian orang tua yang cukup dapat mendorong siswa dalam membentuk kebiasaan belajar. Respon dari lingkungan keluarga juga menjadi bahan informasi bagi anak untuk menilai siapa dirinya, dimana hal tersebut akan membuat siswa lebih yakin terhadap kebiasaan belajar yang dilakukannya, sehingga siswa dapat mencapai hasil belajar yang optimal. Kata Kunci: Kebiasaan Belajar, Hasil Belajar, Lingkungan Keluarga Rela Regina Riani (1600723). “ THE INFLUENCE OF STUDY HABIT ON LEARNING OUTCOMES WITH THE FAMILY ENVIRONMENT AS A MODERATOR VARIABLE (Systematic Literature Review)”. Under Supervisor I : Dr. Sumartini, MP., and Dosen Pembimbing II: Dr. Siti Parhah, S.Pd, M.SE. ABSTRACT The purpose of this study was to determine the effect of study habits on student learning outcomes, as well as the family environment as a moderating variable. This study analyzes several articles on study habits that affect learning outcomes, and the family environment strengthens the influence of study habits on learning outcomes. Article searches were conducted on online publications such as APA PsycNet, Elsevier, ERIC, Taylor and France, Academia, Global Journal for Research Analysis (GJRA), IISTE, Sage Pub, Emerald, published between 2013-2020. The author obtained 10 articles that met the requirements based on the characteristics of the selection of relevant articles that had been determined. The findings of the article show that study habits have a positive effect on student learning outcomes. This is because good study habits will tend to be more successful in the learning process, both study habits at school, habits at home, group study habits, study habits in understanding books that will affect learning outcomes. In addition, it was found that the family environment can strengthen the influence of study habits on student learning outcomes. This is because a harmonious and pleasant family environment, coupled with sufficient parental attention can encourage students to form study habits. Responses from the family environment also become information material for children to assess who they are, where this will make students more confident in their study habits, so that students can achieve optimal learning outcomes. Keywords: Study Habits, Learning Outcomes, Family Environmen

    Deletion of vitamin D receptor leads to premature emphysema/COPD by increased matrix metalloproteinases and lymphoid aggregates formation

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    Deficiency of vitamin D is associated with accelerated decline in lung function. Vitamin D is a ligand for nuclear hormone vitamin D receptor (VDR), and upon binding it modulates various cellular functions. The level of VDR is reduced in lungs of patients with chronic obstructive pulmonary disease (COPD) which led us to hypothesize that deficiency of VDR leads to significant alterations in lung phenotype that are characteristics of COPD/emphysema associated with increased inflammatory response. We found that VDR knock-out (VDR(-/-)) mice had increased influx of inflammatory cells, phospho-acetylation of nuclear factor-kappaB (NF-κB) associated with increased proinflammatory mediators, and up-regulation of matrix metalloproteinases (MMPs) MMP-2, MMP-9, and MMP-12 in the lung. This was associated with emphysema and decline in lung function associated with lymphoid aggregates formation compared to WT mice. These findings suggest that deficiency of VDR in mouse lung can lead to an early onset of emphysema/COPD because of chronic inflammation, immune dysregulation, and lung destruction

    Pioneers of Library Movement in Pakistan

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    The paper aims to describe in brief the contribution of seven leaders of Pakistan librarianship, viz. K.B. Khalifa M. Asadullah, Prof. Dr. Abdul Moid, Dr. Abdus Subuh Qasimi, Muhammad Shafi, Fazal Elahi, Khawaja Nur Elahi and S. V. Hussain. The early library developments are given for better understanding of the role of these leaders

    A comparative case study of coordination mechanisms in Design and Build BIM-based projects in the Netherlands

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    BIM implementation can affect the project coordination mechanisms in unexpected ways, even in widely-applied project procurement structures. Apart from the chosen procurement approach, the BIM technology and the distribution of roles in the project team influence and shape the project coordination. This paper aims to explore the emerging coordination structures and processes from BIM implementation in design-build procurement. An exploratory comparative case study has been undertaken. The findings included two main coordination mechanisms: a centralized and decentralized structure and a hierarchical ver-sus participative decision-making processes. These two patterns subsequently open a debate about the rela-tions between BIM implementation and business models in AEC and particularly the emergence of specialized all-around BIM firms versus BIM-knowledgeable engineering firms.Accepted Author ManuscriptDesign & Construction Managemen

    HSCARG Regulates NF-kappa B Activation by Promoting the Ubiquitination of RelA or COMMD1

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    The redox sensor protein HSCARG translocates from the cytoplasm to the nucleus in response to decreased cellular NADPH or increased nitric oxide, and is involved in protein regulation. However, the regulatory mechanism of HSCARG has remained elusive. In this report, through a yeast two-hybrid screen, HSCARG was found to associate with the copper metabolism gene MURR1 domain containing protein 1 (COMMD1), an inhibitor of NF-kappa B, and negatively regulate COMMD1 by accelerating its ubiquitination and proteasome-dependent degradation. Interestingly, we observed that HSCARG also blocked basal and stimulus-coupled NF-kappa B activation by promoting ubiquitination and degradation of the NF-kappa B subunit RelA. Further analyses showed that in cells under normal conditions, HSCARG localized mainly in the cytoplasm and acted as a negative regulator of COMMD1, and was distributed in the nucleus in small quantities to inhibit NF-kappa B. Although in response to intracellular redox changes by dehydroepiandrosterone or S-nitroso-N-acetylpenicillamine treatment, a large amount of HSCARG translocated to the nucleus, which terminated NF-kappa B activation. Meanwhile, COMMD1 was restored due to decreased cytoplasmic HSCARG levels and negatively regulated NF-kappa B as well. Thus, NF-kappa B activation was terminated efficiently. Our results indicate that HSCARG plays critical roles in regulation of NF-kappa B in response to cellular redox changes by promoting ubiquitination and proteolysis of RelA or COMMD1.Biochemistry & Molecular BiologySCI(E)EIPubMed13ARTICLE2717998-1800628

    The Worldview and the Author´s (Self)Reflection in Czech Contemporary Historiography

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    Cílem studie je představit možnosti, jak na základě publikovaných autorských textů zkoumat světový názor historiků a historiček, zejména v oboru soudobých dějin, kde lze předpokládat vliv jejich hodnotového horizontu na interpretaci relativně nedávné minulosti. Autor nejprve vymezuje pojetí světového názoru vzhledem ke stanovenému záměru a zdůvodňuje analytické užití tohoto pojmu v historiografickém textu, v daném kontextu se také zamýšlí nad vztahem paměti, dějin a historiografie. Konstatuje, že poměrně málo českých historiků a historiček dosud reflektuje vztah (individuální či kolektivní) paměti a práce dějepisce, zvláště s ohledem na jeho pozici v současné společnosti, která bývá často redukována na roli objektivního „objevitele historické pravdy“. Taková (sebe)reflexe předpokládá přiznání vlivu individuálního světového názoru historika (komplexu názorů a postojů formovaných výchovou, vzděláním, vzpomínkami, generační příslušností a podobně) na jeho vědeckou činnost. Autor studie nabízí dvě možné a vzájemně se doplňující cesty k poznání historikova světového názoru: jednak prostřednictvím vlastních svědectví a prohlášení z jeho osobněji laděných textů a egodokumentů (eseje, rozhovory, vzpomínky, příspěvky na sociálních sítích), jednak analýzou jeho vědeckých textů (časopiseckých studií, knižních monografií, recenzí). Oba přístupy autor dokumentuje na konkrétních příkladech z produkce historiků a historiček českých soudobých dějin. V závěru studie pak nastiňuje cíle a smysl zkoumání historikova světového názoru.The aim of this study is to present the opportunities for research into the worldview of historians, especially historians focused on contemporary history, where it can be assumed that their set of values may influence their interpretation of the rela-tively recent past. The author first defines the notion of worldview and justifies the analytical use of this concept in historiographical texts. He also considers the relationship between memory, history and historiography in the given context. The author states that not many Czech historians have so far reflected on the relationship between (individual and collective) memory and the work of the historian, especially with regard to his or her position in contemporary society, which is often reduced to the role of an objective “discoverer of historical truth”. Such (self)reflection presupposes the acknowledgement of the influence of the historian’s individual worldview (a complex of opinions and attitudes shaped by upbringing, education, memories, generational affiliation and so on) on his or her scholarly activity. The author of the study offers two possible and complementary ways to learn about the historian’s worldview: first, through his or her own testimonies and statements from more personal texts and ego-documents (essays, interviews, memoirs or social me-dia posts), and second, through the analysis of his or her scholarly texts (journal studies, monographs and book reviews). The author demonstrates both approaches with concrete examples of works by historians of Czech contemporary history and concludes by outlining the aims and purpose of examining the historian’s worldview. © 2022, Institute of Contemporary History of the Czech Academy of Sciences. All rights reserved
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