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Immune system modeling

Claudia Balducci, Angelisa Frasca, Margherita Zotti, Pietro La Vitola, Emanuela Mhillaj, Emanuele Grigoli, Martina Iacobellis, Federica Grandi, Massimo Messa, Laura Colombo, Monica Molteni, Luigia Trabace, Carlo Rossetti, Mario Salmona, Gianluigi Forloni
[Background] Amyloid-β oligomers (AβO) are species mainly involved in the synaptic and cognitive dysfunction in Alzheimer's disease. Although their action has been described mainly at neuronal level, it is now clear that glial cells govern synaptic activity in their resting state, contributing to new learning and memory establishment. In contrast, when activated, they may lead to synaptic and cognitive dysfunction. Using a reliable acute AβO-mediated mouse model of AD, we explored whether the memory alteration AβOs induce relies on the activation of glial cells, and if Toll-like receptor 4 (TLR4), pivotal in the initiation of an immune response, is involved...
October 14, 2016: Brain, Behavior, and Immunity
Mohammad Reza Safari, Soudeh Ghafouri-Fard, Rezvan Noroozi, Arezou Sayad, Mir Davood Omrani, Alireza Komaki, Mohammad Mahdi Eftekharian, Mohammad Taheri
Autism Spectrum Disorders (ASD) are a group of heterogeneous neurodevelopmental disorders associated with immune system dysregulation. There are supporting evidences for the role of Forkhead Box P3 (FOXP3) gene as a lineage specification factor of regulatory T cells in the pathogenesis of ASD. The aim of this study was to explore possible relationship between genetic variants rs2232365 and rs3761548 of FOXP3 and ASD in 523 ASD patients versus 472 control individuals. Allele frequency analyses showed significant overpresentation of rs2232365-G allele in cases versus controls...
October 14, 2016: Gene
Keren Turjeman, Yechezkel Barenholz
BACKGROUND: Steroids are the most efficacious anti-inflammatory agents. However, their toxicities and side-effects compromise their clinical application. Various strategies and major efforts were dedicated for formulating viable liposomal glucocorticosteroids (GCs), so far none of these were approved. OBJECTIVES: To evaluate these approaches for formulating GC-delivery systems, especially liposomes, and with focus on the Barenholz Lab experience. METHODS: We developed PEGylated nano-liposomes (NSSL) remotely loaded with water-soluble amphipathic weak acid GC-prodrugs...
October 18, 2016: Journal of Drug Targeting
Hiroshi Yamazaki
Research over the past 30 years has elucidated the roles of polymorphic human liver cytochrome P450 (P450) enzymes associated with toxicological and/or pharmacological actions. Thalidomide exerts its various pharmacological and toxic actions in primates through multiple mechanisms, including nonspecific modification of many protein networks after bioactivation by autoinduced human P450 enzymes. To overcome species-differences between rodents, currently, nonhuman primates and/or mouse models with transplanted human hepatocytes are used...
October 17, 2016: Chemical Research in Toxicology
Duncan K Ralph, Frederick A Matsen
The human immune system depends on a highly diverse collection of antibody-making B cells. B cell receptor sequence diversity is generated by a random recombination process called "rearrangement" forming progenitor B cells, then a Darwinian process of lineage diversification and selection called "affinity maturation." The resulting receptors can be sequenced in high throughput for research and diagnostics. Such a collection of sequences contains a mixture of various lineages, each of which may be quite numerous, or may consist of only a single member...
October 2016: PLoS Computational Biology
Yong Yu, Jason C H Tsang, Cui Wang, Simon Clare, Juexuan Wang, Xi Chen, Cordelia Brandt, Leanne Kane, Lia S Campos, Liming Lu, Gabrielle T Belz, Andrew N J McKenzie, Sarah A Teichmann, Gordon Dougan, Pentao Liu
Innate lymphoid cells (ILCs) functionally resemble T lymphocytes in cytotoxicity and cytokine production but lack antigen-specific receptors, and are important regulators in immune response and tissue homeostasis(1, 2). ILCs are generated from common lymphoid progenitors (CLPs), which are subsequently committed to innate lymphoid lineages in the α lymphoid progenitor (αLP), early innate lymphoid progenitor (EILP), common helper innate lymphoid progenitor (CHILP) and innate lymphoid cell progenitor (ILCP) compartments(3, 4, 5, 6, 7, 8)...
September 29, 2016: Nature
Xiuhong Cai, Xiang Li, Hong Qi, Fang Wei, Jianyong Chen, Jianwei Shuai
The gating properties of the inositol 1, 4, 5-trisphosphate (IP3) receptor (IP3R) are determined by the binding and unbinding capability of Ca(2+) ions and IP3 messengers. With the patch clamp experiments, the stationary properties have been discussed for Xenopus oocyte type-1 IP3R (Oo-IP3R1), type-3 IP3R (Oo-IP3R3) and Spodoptera frugiperda IP3R (Sf-IP3R). In this paper, in order to provide insights about the relation between the observed gating characteristics and the gating parameters in different IP3Rs, we apply the immune algorithm to fit the parameters of a modified DeYoung-Keizer model...
October 17, 2016: Physical Biology
Hong Zhang, Peng He, Rongzhong Huang, Lin Sun, Siwen Liu, Jingjing Zhou, Yujie Guo, Deyu Yang, Peng Xie
MicroRNAs (miRNAs) are recognized as important regulators of gene expression via translational depression or mRNA degradation. Previously, dysregulated miRNAs have been found in neurodegenerative and neuropsychiatric disorders. Borna disease virus (BDV) is a neurotropic, negative single‑stranded RNA virus, which may be a cause of human neuropsychiatric disease. BDV is regarded as an ideal model to analyze the molecular mechanisms of mental disorders caused by viral infection. In the present study, 10 miRNAs were dysregulated in human oligodendrocytes (OL cells) infected with the BDV strain, Hu‑H1 (OL/BDV)...
October 13, 2016: Molecular Medicine Reports
Neha Chaturvedi, Praveen K Bharti, Archana Tiwari, Neeru Singh
Transmission blocking malaria vaccines are aimed to block the development and maturity of sexual stages of parasite within mosquitoes. The vaccine candidate antigens (Pfs25, Pfs48/45, Pfs230) that have shown transmission blocking immunity in model systems are in different stages of development. These antigens are immunogenic with limited genetic diversity. Pfs25 is a leading candidate and currently in phase I clinical trial. Efforts are now focused on the cost-effective production of potent antigens using safe adjuvants and optimization of vaccine delivery system that are capable of inducing strong immune responses...
June 2016: Indian Journal of Medical Research
Lijun Du, John J Kim, Jinhua Shen, Ning Dai
The barrier function of the intestine is essential for maintaining the normal homeostasis of the gut and mucosal immune system. Abnormalities in intestinal barrier function expressed by increased intestinal permeability have long been observed in various gastrointestinal disorders such as Crohn's disease (CD), ulcerative colitis (UC), celiac disease, and irritable bowel syndrome (IBS). Imbalance of metabolizing junction proteins and mucosal inflammation contributes to intestinal hyperpermeability. Emerging studies exploring in vitro and in vivo model system demonstrate that Rho-associated coiled-coil containing protein kinase- (ROCK-) and myosin light chain kinase- (MLCK-) mediated pathways are involved in the regulation of intestinal permeability...
2016: Gastroenterology Research and Practice
Laura A Thompson, Tracy A Romano
Increased pressure, associated with diving, can alter cell function through several mechanisms and has been shown to impact immune functions performed by peripheral blood mononuclear cells (PBMC) in humans. While marine mammals possess specific adaptations which protect them from dive related injury, it is unknown how their immune system is adapted to the challenges associated with diving. The purpose of this study was to measure PBMC activation (IL2R expression) and Concanavalin A induced lymphocyte proliferation (BrdU incorporation) in belugas following in vitro pressure exposures during baseline, Out of Water Examination (OWE) and capture/release conditions...
2016: Frontiers in Physiology
Ragnhild Reehorst Lereim, Eystein Oveland, Yichuan Xiao, Øivind Torkildsen, Stig Wergeland, Kjell-Morten Myhr, Shao-Cong Sun, Frode S Berven
The ubiquitin ligase Peli1 has previously been suggested as a potential treatment target in multiple sclerosis. In the multiple sclerosis disease model, experimental autoimmune encephalomyelitis, Peli1 knock-out led to less activated microglia and less inflammation in the central nervous system. Despite being important in microglia, Peli1 expression has also been detected in glial and neuronal cells. In the present study the overall brain proteomes of Peli1 knock-out mice and wild-type mice were compared prior to experimental autoimmune encephalomyelitis induction, at onset of the disease and at disease peak...
September 2016: Journal of Proteomics & Bioinformatics
Mahesh Kudrimoti, Amarintha Curtis, Samar Azawi, Francis Worden, Sanford Katz, Douglas Adkins, Marcelo Bonomi, Jenna Elder, Stephen T Sonis, Richard Straube, Oreola Donini
Dusquetide, a novel Innate Defense Regulator, modulates the innate immune system at a key convergence point in intracellular signaling pathways and has demonstrated activity in both reducing inflammation and increasing clearance of bacterial infection. Innate immunity has also been implicated in the pathogenesis of oral mucositis (OM), a universal toxicity of chemoradiation therapy (CRT). Testing the hypothesis that dusquetide can mitigate the development and duration of OM, preclinical studies have been completed and correlated with interim results from a Phase 2 clinical study in patients undergoing CRT for head and neck cancer...
October 13, 2016: Journal of Biotechnology
Joanne E Sordillo, Yanjiao Zhou, Michael J McGeachie, John Ziniti, Nancy Lange, Nancy Laranjo, Jessica R Savage, Vincent Carey, George O'Connor, Megan Sandel, Robert Strunk, Leonard Bacharier, Robert Zeiger, Scott T Weiss, George Weinstock, Diane R Gold, Augusto A Litonjua
BACKGROUND: The gut microbiome in infancy influences immune system maturation, and may have an important impact allergic disease risk. OBJECTIVE: To determine how prenatal and early life factors impact the gut microbiome in a relatively large, ethnically diverse study population of infants at 3-6 months of age, who were enrolled in VDAART, a clinical trial of vitamin D supplementation in pregnancy to prevent asthma and allergies in offspring. METHODS: We performed 16S rRNA gene sequencing on 333 infants' stool samples...
October 13, 2016: Journal of Allergy and Clinical Immunology
Siyang Yan, Amanda C Kentner
Exposure to painful procedures and/or stressors during the early neonatal period can reprogram the underlying neurocircuitry involved in nociception and neuropathic pain perception. The reprogramming of these systems can result in an enduring elevation in sensitivity towards mechanical and thermal stimuli. Recent evidence suggests that exposure to mild inflammatory mediators during the neonatal period can induce similar pain responses in both adolescent and adult rats. Therefore, we sought to profile changes in the expression of several genes across brain areas involved in the active modulation of nociception and neuropathic pain using a well-recognized model of neonatal inflammation...
October 11, 2016: Brain, Behavior, and Immunity
Guillermo S Romano Ibarra, Biswajit Paul, Blythe D Sather, Patrick M Younan, Karen Sommer, John P Kowalski, Malika Hale, Barry Stoddard, Jordan Jarjour, Alexander Astrakhan, Hans-Peter Kiem, David J Rawlings
A naturally occurring 32-base pair deletion of the HIV-1 co-receptor CCR5 has demonstrated protection against HIV infection of human CD4(+) T cells. Recent genetic engineering approaches using engineered nucleases to disrupt the gene and mimic this mutation show promise for HIV therapy. We developed a megaTAL nuclease targeting the third extracellular loop of CCR5 that we delivered to primary human T cells by mRNA transfection. The CCR5 megaTAL nuclease established resistance to HIV in cell lines and disrupted the expression of CCR5 on primary human CD4(+) T cells with a high efficiency, achieving up to 80% modification of the locus in primary cells as measured by molecular analysis...
August 23, 2016: Molecular Therapy. Nucleic Acids
Maria C Cenit, Pilar Codoñer-Franch, Yolanda Sanz
Gut microbiota shapes the development of the mucosal immune system and may provide protection against immune-mediated diseases. Celiac disease (CD) is a chronic inflammatory condition triggered by dietary gluten proteins, recently associated with gut microbiota alterations in cross-sectional studies comparing patients and controls. Whether or not these differences are causally related to the disease has yet to be elucidated, but evaluation of specific bacteria isolated from CD patients in experimental models suggests that they can promote an adverse response to dietary gluten, whereas other commensal bacteria can be protective...
November 2016: Journal of Clinical Gastroenterology
Massimo Marzorati, Tom Van de Wiele
The gastrointestinal tract (GIT) hosts the most complex microbial community in the human body. Given the extensive metabolic potential which is present in this community, this additional organ is of key importance to maintain a healthy status and several diseases are frequently correlated with an alteration of the composition/functionality of the gut microbiota. Consequently, there is a great interest in identifying potential approaches that could modulate the microbiota and its metabolism to bring about a positive health effect...
November 2016: Journal of Clinical Gastroenterology
Urszula Ledzewicz, Heinz Schaettler
We review results about the structure of administration of chemotherapeutic anti-cancer treatment that we have obtained from an analysis of minimally parameterized mathematical models using methods of optimal control. This is a branch of continuous-time optimization that studies the minimization of a performance criterion imposed on an underlying dynamical system subject to constraints. The scheduling of anti-cancer treatments has all the features of such a problem: treatments are administered in time and the interactions of the drugs with the tumor and its microenvironment determine the efficacy of therapy...
2016: Advances in Experimental Medicine and Biology
Ardeshir Kianercy, Kenneth J Pienta
Bone, which includes several cell populations and numerous cytokines and chemokines that provide cell-cell signaling, is a common destination for many cancer metastases. Bone metastasis skews this signaling to develop vicious cycles between immune, bone and cancer populations that lead to abnormal bone remodeling during cancer niche construction. Temporal models utilize positive feedback systems as an integrative tool providing insights into the rate-limiting processes that determine multiple stages of the bone metastasis...
2016: Advances in Experimental Medicine and Biology
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