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Oxidative Stress and Mitochondrial Injury in Chronic Multisymptom Conditions: From Gulf War Illness to Autism Spectrum Disorder Nature Precedings
Beatrice A. Golomb.
Background: Overlapping chronic multisymptom illnesses (CMI) include Chronic Fatigue Syndrome (CFS), fibromyalgia, irritable bowel syndrome, multiple chemical sensitivity, and Gulf War illness (GWI), and subsets of autism spectrum disorder (ASD). GWI entails a more circumscribed set of experiences that may provide insights of relevance to overlapping conditions.
Objectives: To consolidate evidence regarding a role for oxidative stress and mitochondrial dysfunction (OSMD), as primary mediators in CMI, using GWI as a departure point.
Methods: Exposure relations, character, timecourse and multiplicity of symptoms, and objective correlates of GWI are compared to expectation for OSMD. Objective correlates of OSMD in GWI and...
Tipo: Manuscript Palavras-chave: Immunology; Molecular Cell Biology.
Ano: 2012 URL: http://precedings.nature.com/documents/6847/version/1
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Female Scent Signals Enhances Male Resistance to Influenza Nature Precedings
Ekaterina A. Litvinova; Elena P. Goncharova; Alla M. Zaidman; Marina A. Zenkova; Mikhail P. Moshkin.
Scent of receptive females as signal to reproduction stimulate male mice to olfactory search of a potential breeding partner^1, 2^. This searching behavior is coupled with infection risk due to bacterial contamination of the fecal and urine scent marks^4^. The theoretical consideration of host evolution under inevitable parasitic pressures, including helminthes, bacteria, virus etc., predicts adaptations that help protect against parasites associated with breeding^7^. In this study, we propose that acceptation of female signals by male mice leads to adaptive redistribution of immune defense directed to protection against respiratory infection risks. Our results reveal migration of macrophages and neutrophils to upper airways upon exposure to female odor...
Tipo: Manuscript Palavras-chave: Ecology; Immunology.
Ano: 2009 URL: http://precedings.nature.com/documents/3311/version/1
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Mutations in the _SC4MOL_ gene encoding a novel methyl sterol oxidase cause autosomal recessive psoriasisiform dermatitis, microcephaly and developmental delay Nature Precedings
Miao He; Lisa Kratz; Jushua Michel; Abbe Vallejo; Laura Ferris; Richard Kelley; Jacqueline Hoover; Michael Gibson; Gerard Vockley.
Disorders of cholesterol biosynthesis have clinical manifestations involving skeleton, eyes, neurologic development, and skin. We describe a patient with congenital cataracts, developmental delay, microcephaly, and low serum cholesterol who developed severe psoriasiform dermatitis and arthralgias beginning at age 3. Her brain MRI indicatedminor gliosis. Quantitative sterol analysis of patient plasma and skin showed marked elevation of 4alpha-methyl- and 4, 4'-dimethylsterols, indicating a deficiency in the first step of sterol C4 demethylation in cholesterol biosynthesis. Molecular studies showed mutations in _SC4MOL_, a gene predicted to encode a sterol C4 methyl oxidase. Thus, our patient has a previously undescribed inborn error of cholesterol...
Tipo: Manuscript Palavras-chave: Genetics & Genomics; Immunology.
Ano: 2008 URL: http://precedings.nature.com/documents/2163/version/1
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Clonal origin of Epstein-Barr virus-infected T/NK-cell subpopulations in chronic active Epstein-Barr virus infection Nature Precedings
Shouichi Ohga; Masataka Ishimura; Goichi Toshimoto; Toshihiro Miyamoto; Hidetoshi Takada; Tamami Tanaka; Koichi Ohshima; Ken-Ichi Imadome; Yasunobu Abe; Koichi Akashi; Toshiro Hara.
Clonal expansion of Epstein-Barr virus (EBV) infected B-cells occasionally occurs in immunocompromized subjects. EBV-infected T/natural killer (NK)-cells proliferate in patients with chronic active EBV infection (CAEBV) that is a rare mononucleosis syndrome. It is classified into either T-cell type or NK-cell type according to the primary target of infection, while the pathogenesis remains unclear. To search the clonal origin of EBV-infected T/NK-cells, virus distribution and clonotype were assessed by using highly purified cell fractions obtained from 6 patients. Patient 1 had a monoclonal proliferation of EBV-infected T-cell receptor Vδ2/Vγ9-expressing cells, and carried lower copy number of EBV in αβT-cells....
Tipo: Manuscript Palavras-chave: Immunology; Microbiology.
Ano: 2010 URL: http://precedings.nature.com/documents/4238/version/1
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Immunogens and Antigen Processing: Report from a Global HIV Vaccine Enterprise Working Group Nature Precedings
John Mascola; Richter C. King; Ralph Steinman; the Working Group convened by the Global HIV Vaccine Enterprise.
The Global HIV Vaccine Enterprise convened a meeting of a Working Group in July 2009 to discuss recent progress in rational design of the components of an HIV vaccine, such as inserts, vectors and adjuvants,and in understanding antigen processing and presentation to T and B cells. This Report summarizes the key points of that discussion, and subsequent discussions with the Chairs of the other Enterprise Working Groups, the Enterprise Science Committee, the Enterprise Council and the broader scientific community during open sessions at scientific conferences.
Tipo: Manuscript Palavras-chave: Immunology; Microbiology.
Ano: 2010 URL: http://precedings.nature.com/documents/4796/version/2
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Structural requirements for the binding affinity of some small, non–peptide C5a receptor antagonists Nature Precedings
Haiying Xie; Weiming Wang; Ziqiang Xie; Hong Chen; Kexian Chen.
Complement anaphylatoxin 5a (C5a) has been recognized as a potent therapeutic target for anti-inflammatory therapy, thus, blocking the action of C5a on its binding receptors may provide an effective treatment of a variety of inflammatory diseases. However, there have been few clinically available non-peptide C5a receptor antagonists disclosed at present. In pursuit of better anti-inflammatory drugs, quantitative structure–activity relationship studies were carried out in a series of non-peptide C5a receptor antagonists with binding activity using different physicochemical descriptors. The conventional best 2D-QSAR models were developed using a training set of 35 molecules and an external test set of 8 molecules by genetic function approximation...
Tipo: Manuscript Palavras-chave: Chemistry; Immunology; Pharmacology; Bioinformatics.
Ano: 2011 URL: http://precedings.nature.com/documents/6630/version/1
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Proteins of the XMRV retrovirus implicated in chronic fatigue syndrome and prostate cancer are homologous to human proteins relevant to both diseases. Nature Precedings
Christopher Carter.
The XMRV retrovirus has been implicated in chronic fatigue syndrome and prostate cancer. A homology search comparing retroviral with human proteins revealed short contiguous amino acid strings (typically 5-8 aa) matching human proteins whose dysfunction might be expected to cause fatigue, including mitochondrial proteins related to oxidative phosphorylation, glutamate receptors and their synaptic scaffolds, muscular acetylcholine receptor scaffolds and structural proteins, components of the immune system, and phosphatidylinositol signalling inter alia. Viral proteins are also homologous to members of the oestrogen, peroxisome proliferator, and CREB activated receptor networks, all of which are implicated in prostate cancer, and to a protein, SRCAP, that...
Tipo: Manuscript Palavras-chave: Cancer; Immunology; Microbiology; Neuroscience.
Ano: 2010 URL: http://precedings.nature.com/documents/4669/version/1
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Screening of actinobacteria for antimicrobial activities by a modified "Cross-Streak" method Nature Precedings
Nandkumar Kamat; Sonashia Velho-Pereira.
New molecule discovery from natural sources, such as that of actinobacteria, has proved to be an interesting area in antibiotic research, as most of these antibiotics are difficult to synthesize. Out of 30 actinobacterial cultures screened for antimicrobial activity, 28 cultures were found to produce active products against various pathogenic microorganisms such as Gram-negative, Gram-positive bacteria and yeast, using a ‘modified cross streak method.' The modified method helped in easy quantification of results and also in ruling out probable mutual antibiosis. 53%, 13% and 10% of tested actinobacterial strains belonging to Streptomyces, Micromonospora and Actinomadura genera, respectively, showed the ability of producing antimicrobial...
Tipo: Manuscript Palavras-chave: Biotechnology; Cancer; Chemistry; Immunology; Microbiology; Pharmacology; Bioinformatics.
Ano: 2012 URL: http://precedings.nature.com/documents/6765/version/1
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Complex Systems Analysis of Cell Cycling Models in Carcinogenesis Nature Precedings
I. C. Baianu.
A new approach to the modular, complex systems analysis of nonlinear dynamics in cell cycling network transformations involved in carcinogenesis is proposed. Carcinogenesis is a complex process that involves dynamically inter-connected biomolecules in the intercellular, membrane, cytosolic, nuclear and nucleolar compartments that form numerous inter-related pathways referred to as networks.
The variable biotopology of such dynamic networks is highly complex, and has a number of interesting properties that can be formally characterized at one level of organization by mathematical structures called 'biogroupoids'. 
One such family of pathways contains the cell cyclins. Cyclins are proteins that link several...
Tipo: Manuscript Palavras-chave: Biotechnology; Cancer; Chemistry; Developmental Biology; Genetics & Genomics; Immunology; Molecular Cell Biology; Pharmacology; Bioinformatics; Evolutionary Biology.
Ano: 2011 URL: http://precedings.nature.com/documents/6205/version/1
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High efficiency transfection of thymic epithelial cell lines and primary thymic epithelial cells by Nucleofection Nature Precedings
Richard T. O'Neil; Qiaozhi Wei; Brian G. Condie.
Thymic epithelial cells (TECs) are required for the development and differentiation of T cells and are sufficient for the positive and negative selection of developing T cells. Although TECs play a critical role in T cell biology, simple, efficient and readily scalable methods for the transfection of TEC lines and primary TECs have not been described. We tested the efficiency of Nucleofection for the transfection of 4 different mouse thymic epithelial cell lines that had been derived from cortical or medullary epithelium. We also tested primary mouse thymic epithelial cells isolated from fetal and postnatal stages. We found that Nucleofection was highly efficient for the transfection of thymic epithelial cells, with transfection efficiencies of 30-70% for...
Tipo: Manuscript Palavras-chave: Biotechnology; Genetics & Genomics; Immunology; Molecular Cell Biology.
Ano: 2011 URL: http://precedings.nature.com/documents/6283/version/1
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Production of Transgenic Cloned Miniature Pigs with Membrane-bound Human Fas Ligand (FasL) by Somatic Cell Nuclear Transfer Nature Precedings
Jae Goo Seol; Soo Hyun Kim; Dong-Il Jin; Seung Pyo Hong; Ji Yeon Yoo; Ki Myung Choi; Young Chul Park; Yun Jin Yun; Kwang Wook Park; Jae Young Heo.
Cell-mediated xenograft rejection, including NK cells and CD8+ CTL, is a major obstacle in successful pig-to-human xenotransplantation. Human CD8+ CTL and NK cells display high cytotoxicity for pig cells, mediated at least in part by the Fas/FasL pathway. To prevent cell-mediated xenocytotoxicity, a membrane-bound form of human FasL (mFasL) was generated as an inhibitor for CTL and NK cell cytotoxicity that could not be cleaved by metalloproteinase to produce putative soluble FasL. We produced two healthy transgenic pigs harboring the mFasL gene via somatic cell nuclear transfer (SCNT). In a cytotoxicity assay using transgenic clonal cell lines and transgenic pig ear cells, the rate of CD8+ CTL-mediated cytotoxicity was significantly reduced in transgenic...
Tipo: Manuscript Palavras-chave: Biotechnology; Developmental Biology; Immunology.
Ano: 2010 URL: http://precedings.nature.com/documents/4539/version/1
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Electron microscopy analysis of FcRγ localization after its capture by T cells by trogocytosis Nature Precedings
Stephanie Balor; Marc Daëron; Pierre Bruhns; Denis Hudrisier.
T cells acquire various proteins from their cellular partners by the process of trogocytosis. We recently demonstrated that the FcγRIIIA receptor and its associated FcRγ are captured by T cells during their co-culture with FcγR-expressing target cells upon both antigen- or antibody-mediated stimulation. Interestingly, we found that FcR captured by T cells could bind ligands but did not transmit detectable intracellular signals or signaling-depending functions upon ligand binding suggesting their improper integration in the recipient T cell membrane. In this study, we provide morphological data in support of this hypothesis. Indeed, we show that the FcRγ-subunit, which we used as a fusion to GFP, was clearly present...
Tipo: Manuscript Palavras-chave: Immunology.
Ano: 2009 URL: http://precedings.nature.com/documents/3824/version/1
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Immunogenicity of human spermatozoa Nature Precedings
Jhinuk Chatterjee.
Investigation and experimental design of the study was basically aimed at developing insight into the antigenicity of spermatozoa-associated proteins. Apart from studying the natural antigenicity of washed whole spermatozoa, their immunogenicity was also demonstrated _in vitro_. The whole live spermatozoa were immobilized and agglutinated _in vitro_ by the antibodies they induced in the laboratory model - a female rabbit. A regular immunization routine induced a high titre of antisperm polyclonal antibodies. To prepare a spermatozoa specific antigen which will not produce a cross-reacting antibody against other human tissues, only the motile and live spermatozoa were selected for antigen preparation. In investigation the laboratory-bred female rabbits were...
Tipo: Manuscript Palavras-chave: Immunology.
Ano: 2008 URL: http://precedings.nature.com/documents/1855/version/1
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Novel approaches, including systems biology, to HIV vaccine research and development: Report from a Global HIV Vaccine Enterprise Working Group Nature Precedings
Bali Pulendran; Rino Rappuoli; Alan Aderem; the Working Group convened by the Global HIV Vaccine Enterprise.
The Global HIV Vaccine Enterprise convened a two-day workshop on August 10-11 2009, at the Fred Hutchison Cancer Research Center offices in Seattle, WA, to discuss the application of novel approaches,including systems biology, to HIV vaccine research and development. The goals of this Working Group were to identify key scientific issues and opportunities that have emerged since the Enterprise Scientific Strategic Plan1 was published in 2005, and to make recommendations to Enterprise stakeholders.
Tipo: Manuscript Palavras-chave: Biotechnology; Immunology; Microbiology; Bioinformatics.
Ano: 2010 URL: http://precedings.nature.com/documents/4798/version/1
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The Immune Response in Patients with SARS: differential gene expression profiling. Nature Precedings
Peter Natesan Pushparaj; Jayapal J. Manikandan; Alirio Jose A. J. Melendez.
Severe acute respiratory syndrome (SARS) emerged in 2003, as a new epidemic form of life-threatening infection. As of 26th September 2003, there were 8422 cases of SARS from 29 countries with 908 deaths (WHO). However, the pathogenesis of SARS is poorly understood. To understand the host response to this pathogen, we profiled the gene expression patterns of peripheral blood mononuclear cells (PBMC) from SARS patients compared to healthy controls using one of the latest techniques, high density oligonucleotide expression probe array (HG-Focus array, Gene Chip, Affymetrix, Santa Clara, CA). High-density oligonucleotide microarray is a promising approach for high throughput analysis. It has been extensively
used in many areas of biomedical...
Tipo: Poster Palavras-chave: Immunology; Molecular Cell Biology; Bioinformatics.
Ano: 2007 URL: http://precedings.nature.com/documents/1145/version/1
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High-Throughput Transcriptome Profiling Of Human Mesenchymal Stem Cells Reveals A Role For Wnt/GSK-3 Signaling In Their Hypoimmunomodulation Nature Precedings
Gurudutta Gangenahalli; Neeraj Satija; Farhat Afrin; Rajender Prasad Tripathi.
Mesenchymal stem cells (MSCs) are gaining importance among clinicians following recent demonstration of safe allogeneic transplantation due to their ability to modulate the immune response. However,the molecular machinery regulating the expression of immunomodulatory factors in MSCs is unknown. We, therefore, inhibited glycogen synthase kinase-3 (GSK-3),a Wnt signaling inhibitor, to elucidate the role of Wnt signaling in mediating immunoregulatory effects of human MSCs using gene expression profiling. Our results highlight enhanced ability of GSK-3 inhibitor (lithium) treated MSCs to evade immune response as a result of decreased expression of immune stimulatory cytokines and chemokines.
Tipo: Manuscript Palavras-chave: Biotechnology; Developmental Biology; Immunology; Molecular Cell Biology.
Ano: 2011 URL: http://precedings.nature.com/documents/5512/version/1
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Antibody responses to a Cryptosporidium parvum rCP15/60 vaccine Nature Precedings
Alexandra J. Burton; Daryl V. Nydam; Gary Jones; Jennifer Zambriski; Thomas C. Linden; Graham Cox; Randy Davis; Alicia Brown; Dwight D. Bowman.
Cryptosporidium parvum is a zoonotic apicomplexa-protozoan pathogen that causes gastroenteritis and diarrhoea in mammals worldwide. The organism is transmitted by ingestion of oocysts, which are shed in faeces, and completes its lifecycle in a single host.^1^ C. parvum is ubiquitous on dairy operations worldwide and is one of the leading causes of diarrhoea in calves on these farms.^2,3^ Here, for the first time, we describe the antibody response in a large group of cows to a recombinant C. parvum oocyst surface protein (rCP15/60) vaccine and the antibody response in calves fed rCP15/60-immune colostrum produced by these vaccinated cows. Results of recent genotype surveys indicate that calves are the only major reservoir for C. parvum infections in...
Tipo: Manuscript Palavras-chave: Immunology.
Ano: 2009 URL: http://precedings.nature.com/documents/3988/version/1
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Identification of MHC Class II Binders/ Non-binders using Negative Selection Algorithm Nature Precedings
S.S. Soam; Feroz Khan; Bharat Bhasker; B. N. Mishra.
The identification of major histocompatibility complex (MHC) class-II restricted peptides is an important goal in human immunological research leading to peptide based vaccine design. These MHC class–II peptides are predominantly recognized by CD4+ T-helper cells, which when turned on, have profound immune regulatory effects. Thus, prediction of such MHC class-II binding peptides is very helpful towards epitope-based vaccine design. HLA-DR proteins were found to be associated with autoimmune diseases e.g. HLA-DRB1*0401 with rheumatoid arthritis. It is important for the treatment of autoimmune diseases to determine which peptides bind to MHC class II molecules. The experimental methods for identification of these peptides are both time consuming...
Tipo: Manuscript Palavras-chave: Immunology; Bioinformatics.
Ano: 2011 URL: http://precedings.nature.com/documents/6608/version/1
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Steroidal anti inflammatory drug betamethasone significantly alters level of striatal dopamine in a rat model of Parkinson’s disease Nature Precedings
Mehdi Shafiee Ardestani; Hasan Mehrab; Amin Geravand; Nasir Mohajer; Mostafa Saffari.
Many scientific efforts have been well done to investigate the effects of anti inflammatory agents on the degenerative brain diseases such as Parkinson’s (PD) or Alzheimer’s disease and their affiliated sings. Previously we showed the effectiveness of steroids on rigidity of PD and in the study for further mechanistic investigation of that observation the microdialysis technique was employed to determine the striatal dopamine changes in parkinsonian rats after administration of betamethasone (0.12, 0.24 mg/kg) respectively. Our findings showed us the significant increase in the striatal dopaminergic neurotransmission (P<0.05) after administration of betamethasone comparing to the controls. These observations suggest a new...
Tipo: Manuscript Palavras-chave: Chemistry; Immunology; Neuroscience; Pharmacology.
Ano: 2008 URL: http://precedings.nature.com/documents/2330/version/1
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Alzheimer's disease is TH17 related autoimmune disease against misfoded beta amyloid Nature Precedings
Wan-Jiung(Wan-Chung) Hu.
Alzheimer's disease is a common neurodegenerative disorder. However, its exact etiology is still unknown. There were several mechanisms proposed such as the tau hypothesis and amyloid hypothesis. However, there is evidence challenging the above two hypotheses. Here, I propose the immune-amyloid hypothesis as a mechanism for Alzheimer's disease. Th17 related autoimmunity contributes to the disease pathogenesis. Accumulation of misfolded beta amyloid can trigger heat shock protein which in turn induces TH17 immunity. By microarray analysis of peripheral blood mononuclear cells, there is up-regulation of many TH17 related molecules after Alzheimer's disease. After knowing the exact disease pathogenesis, we can develop new...
Tipo: Manuscript Palavras-chave: Genetics & Genomics; Immunology; Neuroscience; Bioinformatics.
Ano: 2011 URL: http://precedings.nature.com/documents/5934/version/1
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