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https://www.readbyqxmd.com/read/28340349/structure-reveals-mechanisms-of-viral-suppressors-that-intercept-a-crispr-rna-guided-surveillance-complex
#1
Saikat Chowdhury, Joshua Carter, MaryClare F Rollins, Sarah M Golden, Ryan N Jackson, Connor Hoffmann, Lyn'Al Nosaka, Joseph Bondy-Denomy, Karen L Maxwell, Alan R Davidson, Elizabeth R Fischer, Gabriel C Lander, Blake Wiedenheft
Genetic conflict between viruses and their hosts drives evolution and genetic innovation. Prokaryotes evolved CRISPR-mediated adaptive immune systems for protection from viral infection, and viruses have evolved diverse anti-CRISPR (Acr) proteins that subvert these immune systems. The adaptive immune system in Pseudomonas aeruginosa (type I-F) relies on a 350 kDa CRISPR RNA (crRNA)-guided surveillance complex (Csy complex) to bind foreign DNA and recruit a trans-acting nuclease for target degradation. Here, we report the cryo-electron microscopy (cryo-EM) structure of the Csy complex bound to two different Acr proteins, AcrF1 and AcrF2, at an average resolution of 3...
March 23, 2017: Cell
https://www.readbyqxmd.com/read/28340257/cd8-positive-t-cell-leukoencephalitis-with-astrocytopathy-clinically-presenting-as-neuromyelitis-optica
#2
Diana L Thomas, Jody Manners, Daniel Marker, Joseph Mettenburg, Geoffrey Murdoch, Bryan Stevens, Guoji Wang, Clayton Wiley
We describe a novel disease entity with the clinical and radiologic presentation of neuromyelitis optica (NMO) and widespread CD8-positive T-cell leukoencephalitis and astrocytopathy. The 59-year-old female patient had a complex 2-year neurological history that included early changes in cognition and memory, progressive lower extremity motor dysfunction, and multimodal sensory involvement. MRI of the spinal cord showed increased T2 signal in the central cord extending from C2 through T4. MRI of the brain showed symmetric radial enhancement in periventricular deep white matter without evidence of demyelinating lesions...
March 16, 2017: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/28339574/arm-paralysis-after-routine-childhood-vaccinations-application-of-advanced-molecular-methods-to-the-causality-assessment-of-an-adverse-event-after-immunization
#3
Jana Shaw, Neal A Halsey, Adriana Weinberg, D Scott Schmid, Kirsten St George, William C Weldon, Michael Jordan, Patrick W Bryant, Philip S LaRussa, Deborah Y Bradshaw, Theresa Harrington, Anne Gershon
Post-licensure surveillance for adverse events following immunizations (AEFI) can identify rare complications of vaccinations and rigorous vaccine adverse event causality assessments can help to identify possible causal relationships. We report the development of arm paralysis after varicella vaccination in a 1-year-old child. Paralysis was initially presumed to be due to vOka because of the temporal relationship between vaccination and onset of arm weakness; however, molecular studies identified wild-type varicella zoster virus VZV (WT-VZV) in the CSF, leading the authors to conclude that WT-VZV was the probable cause...
January 25, 2017: Journal of the Pediatric Infectious Diseases Society
https://www.readbyqxmd.com/read/28339466/in-silico-search-for-modifier-genes-associated-with-pancreatic-and-liver-disease-in-cystic-fibrosis
#4
Pascal Trouvé, Emmanuelle Génin, Claude Férec
Cystic Fibrosis is the most common lethal autosomal recessive disorder in the white population, affecting among other organs, the lung, the pancreas and the liver. Whereas Cystic Fibrosis is a monogenic disease, many studies reveal a very complex relationship between genotype and clinical phenotype. Indeed, the broad phenotypic spectrum observed in Cystic Fibrosis is far from being explained by obvious genotype-phenotype correlations and it is admitted that Cystic Fibrosis disease is the result of multiple factors, including effects of the environment as well as modifier genes...
2017: PloS One
https://www.readbyqxmd.com/read/28339063/viral-and-host-factors-associated-with-outcomes-of-hepatitis-c-virus-infection-review
#5
Zehui Yan, Yuming Wang
Hepatitis C virus (HCV) infection is a major health issue globally. Owing to the progress made in host genetics and HCV molecular virology, emerging data have suggested that the natural course and treatment response in patients with HCV infection are largely determined by complex host‑viral interactions. HCV genotype is the most important viral factor predicting the response to pegylated interferon‑α plus ribavirin therapy. The subtype of HCV genotype 1 is the key viral factor that predicts the efficacy of direct‑acting antiviral therapy...
March 22, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28338245/infective-capacity-of-cryptococcus-neoformans-and-cryptococcus-gattii-in-a-human-astrocytoma-cell-line
#6
M C Olave, J C Vargas-Zambrano, A M Celis, E Castañeda, J M González
Pathogenesis of cryptococcosis in the central nervous system (CNS) is a topic of ongoing research, including the mechanisms by which this fungus invades and infects the brain. Astrocytes, the most common CNS cells, play a fundamental role in the local immune response. Astrocytes might participate in cryptococcosis either as a host or by responding to fungal antigens. To determine the infectivity of Cryptococcus neoformans var. grubii and Cryptococcus gattii in a human astrocytoma cell line and the induction of major histocompatibility complex (MHC) molecules...
March 24, 2017: Mycoses
https://www.readbyqxmd.com/read/28337984/lipid-dependent-conformational-dynamics-underlie-the-functional-versatility-of-t-cell-receptor
#7
Xingdong Guo, Chengsong Yan, Hua Li, Wenmao Huang, Xiaoshan Shi, Min Huang, Yingfang Wang, Weiling Pan, Mingjun Cai, Lunyi Li, Wei Wu, Yibing Bai, Chi Zhang, Zhijun Liu, Xinyan Wang, Xiaohui F Zhang, Chun Tang, Hongda Wang, Wanli Liu, Bo Ouyang, Catherine C Wong, Yi Cao, Chenqi Xu
T-cell receptor-CD3 complex (TCR) is a versatile signaling machine that can initiate antigen-specific immune responses based on various biochemical changes of CD3 cytoplasmic domains, but the underlying structural basis remains elusive. Here we developed biophysical approaches to study the conformational dynamics of CD3ε cytoplasmic domain (CD3εCD). At the single-molecule level, we found that CD3εCD could have multiple conformational states with different openness of three functional motifs, i.e., ITAM, BRS and PRS...
March 24, 2017: Cell Research
https://www.readbyqxmd.com/read/28337940/genome-wide-analysis-of-lps-induced-inflammatory-response-in-the-rat-ventral-hippocampus-modulatory-activity-of-the-antidepressant-agomelatine
#8
Andrea Carlo Rossetti, Maria Serena Paladini, Giorgio Racagni, Marco Andrea Riva, Annamaria Cattaneo, Raffaella Molteni
OBJECTIVES: Several studies reported that antidepressant drugs have immune-regulatory effects by acting on specific inflammatory mediators. However, considering the highly complex nature of the inflammatory response, we have adopted an unbiased genome-wide strategy to investigate the immune-regulatory activity of the antidepressant agomelatine in modulating the response to an acute inflammatory challenge. METHODS: Microarray analysis was used to identify genes modulated in the ventral hippocampus of adult rats chronically treated with agomelatine (40 mg/kg, os) before being challenged with a single injection of lipopolysaccharide (LPS; 250 μg/kg, i...
March 24, 2017: World Journal of Biological Psychiatry
https://www.readbyqxmd.com/read/28337911/mathematical-model-of-serodiagnostic-immunochromatographic-assay
#9
Dmitriy V Sotnikov, Anatoly V Zherdev, Boris B Dzantiev
This article describes the mathematical model for an immunochromatographic assay for the detection of specific immunoglobulins against a target antigen (antibodies) in blood/serum (serodiagnosis). The model utilizes an analytical (non-numerical) approach and allows the calculation of the kinetics of immune complexes' formation in a continuous-flow system using commonly available software, such as Microsoft Excel. The developed model could identify the nature of the influence of immunochemical interaction constants and reagent concentrations on the kinetics of the formation of the detected target complex...
March 24, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28337880/effects-of-anesthesia-using-propofol-and-etomidate-on-t-lymphocyte-subpopulation-of-infectious-shock-patients-in-perioperative-period
#10
Y Wang, J Zhang, S J Zhang
Infectious or septic shock is induced when a toxic microorganism invades blood circulation in the human body. Emergency operation is an effective method for treating infectious shock in the early stages although the use of anesthesia is more complex due to the internal disorders caused by the disease. This study explored the effects of propofol and etomidate anesthesia on the cellular immune function (T lymphocyte subpopulation) of infectious shock patients, aiming to provide a basis for the selection of the proper anesthetic method...
January 2017: Journal of Biological Regulators and Homeostatic Agents
https://www.readbyqxmd.com/read/28337326/crystal-structures-of-erap2-complexed-with-inhibitors-reveal-pharmacophore-requirements-for-optimizing-inhibitor-potency
#11
Anastasia Mpakali, Petros Giastas, Rebecca Deprez-Poulain, Athanasios Papakyriakou, Despoina Koumantou, Ronan Gealageas, Sofia Tsoukalidou, Dionisios Vourloumis, Irene M Mavridis, Efstratios Stratikos, Emmanuel Saridakis
Endoplasmic reticulum aminopeptidase 2 assists with the generation of antigenic peptides for presentation onto Major Histocompatibility Class I molecules in humans. Recent evidence has suggested that the activity of ERAP2 may contribute to the generation of autoimmunity, thus making ERAP2 a possible pharmacological target for the regulation of adaptive immune responses. To better understand the structural elements of inhibitors that govern their binding affinity to the ERAP2 active site, we cocrystallized ERAP2 with a medium activity 3,4-diaminobenzoic acid inhibitor and a poorly active hydroxamic acid derivative...
March 9, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28337224/gut-mesenchymal-stromal-cells-in-immunity
#12
REVIEW
Valeria Messina, Carla Buccione, Giulia Marotta, Giovanna Ziccheddu, Michele Signore, Gianfranco Mattia, Rossella Puglisi, Benedetto Sacchetti, Livia Biancone, Mauro Valtieri
Mesenchymal stromal cells (MSCs), first found in bone marrow (BM), are the structural architects of all organs, participating in most biological functions. MSCs possess tissue-specific signatures that allow their discrimination according to their origin and location. Among their multiple functions, MSCs closely interact with immune cells, orchestrating their activity to maintain overall homeostasis. The phenotype of tissue MSCs residing in the bowel overlaps with myofibroblasts, lining the bottom walls of intestinal crypts (pericryptal) or interspersed within intestinal submucosa (intercryptal)...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28337212/identification-of-norway-spruce-myb-bhlh-wdr-transcription-factor-complex-members-linked-to-regulation-of-the-flavonoid-pathway
#13
Miguel Nemesio-Gorriz, Peter B Blair, Kerstin Dalman, Almuth Hammerbacher, Jenny Arnerup, Jan Stenlid, Shahid M Mukhtar, Malin Elfstrand
Transcription factors (TFs) forming MYB-bHLH-WDR complexes are known to regulate the biosynthesis of specialized metabolites in angiosperms through an intricate network. These specialized metabolites participate in a wide range of biological processes including plant growth, development, reproduction as well as in plant immunity. Studying the regulation of their biosynthesis is thus essential. While MYB (TFs) have been previously shown to control specialized metabolism (SM) in gymnosperms, the identity of their partners, in particular bHLH or WDR members, has not yet been revealed...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28336871/magnetic-nanovectors-for-the-development-of-dna-blood-stage-malaria-vaccines
#14
Fatin M Nawwab Al-Deen, Sue D Xiang, Charles Ma, Kirsty Wilson, Ross L Coppel, Cordelia Selomulya, Magdalena Plebanski
DNA vaccines offer cost, flexibility, and stability advantages, but administered alone have limited immunogenicity. Previously, we identified optimal configurations of magnetic vectors comprising superparamagnetic iron oxide nanoparticles (SPIONs), polyethylenimine (PEI), and hyaluronic acid (HA) to deliver malaria DNA encoding Plasmodium yoelii (Py) merozoite surface protein MSP119 (SPIONs/PEI/DNA + HA gene complex) to dendritic cells and transfect them with high efficiency in vitro. Herein, we evaluate their immunogenicity in vivo by administering these potential vaccine complexes into BALB/c mice...
February 10, 2017: Nanomaterials
https://www.readbyqxmd.com/read/28335993/biomaterials-innovation-for-next-generation-ex%C3%A2-vivo-immune-tissue-engineering
#15
REVIEW
Ankur Singh
Primary and secondary lymphoid organs are tissues that facilitate differentiation of B and T cells, leading to the induction of adaptive immune responses. These organs are present in the body from birth and are also recognized as locations where self-reactive B and T cells can be eliminated during the natural selection process. Many insights into the mechanisms that control the process of immune cell development and maturation in response to infection come from the analysis of various gene-deficient mice that lack some or all hallmark features of lymphoid tissues...
March 15, 2017: Biomaterials
https://www.readbyqxmd.com/read/28335859/making-it-new-again-insight-into-liver-development-regeneration-and-disease-from-zebrafish-research
#16
Shuang Wang, Sophie R Miller, Elke A Ober, Kirsten C Sadler
The adult liver of most vertebrates is predominantly comprised of hepatocytes. However, these cells must work in concert with biliary, stellate, vascular, and immune cells to accomplish the vast array of hepatic functions required for physiological homeostasis. Our understanding of liver development was accelerated as zebrafish emerged as an ideal vertebrate system to study embryogenesis. Through work in zebrafish and other models, it is now clear that the cells in the liver develop in a coordinated fashion during embryogenesis through a complex yet incompletely understood set of molecular guidelines...
2017: Current Topics in Developmental Biology
https://www.readbyqxmd.com/read/28335781/tailored-design-of-nkt-stimulatory-glycolipids-for-polarization-of-immune-responses
#17
REVIEW
Jung-Tung Hung, Jing-Rong Huang, Alice L Yu
Natural killer T (NKT) cell is a distinct population of T lymphocytes that can rapidly release massive amount of Th1 and Th2 cytokines upon the engagement of their T cell receptor with glycolipids presented by CD1d. The secreted cytokines can promote cell-mediated immunity to kill tumor cells and intracellular pathogens, or suppress autoreactive immune cells in autoimmune diseases. Thus, NKT cell is an attractive target for developing new therapeutics to manipulate immune system. The best-known glycolipid to activate NKT cells is α-galactosylceramide (α-GalCer), which has been used as a prototype for designing new NKT stimulatory glycolipids...
March 23, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/28335454/porcine-rotaviruses-epidemiology-immune-responses-and-control-strategies
#18
REVIEW
Anastasia N Vlasova, Joshua O Amimo, Linda J Saif
Rotaviruses (RVs) are a major cause of acute viral gastroenteritis in young animals and children worldwide. Immunocompetent adults of different species become resistant to clinical disease due to post-infection immunity, immune system maturation and gut physiological changes. Of the 9 RV genogroups (A-I), RV A, B, and C (RVA, RVB, and RVC, respectively) are associated with diarrhea in piglets. Although discovered decades ago, porcine genogroup E RVs (RVE) are uncommon and their pathogenesis is not studied well...
March 18, 2017: Viruses
https://www.readbyqxmd.com/read/28335329/nanoparticle-based-delivery-of-anaplasma-marginale-membrane-proteins-virb9-1-and-virb10-produced-in-the-pichia-pastoris-expression-system
#19
Bing Zhang, Antonio S Cavallaro, Karishma T Mody, Jun Zhang, James R Deringer, Wendy C Brown, Timothy J Mahony, Chengzhong Yu, Neena Mitter
Bovine anaplasmosis or cattle-tick fever is a tick-borne haemolytic disease caused by the rickettsial haemoparasite Anaplasma marginale in tropical and subtropical areas of the world. While difficult to express, the proteins VirB9-1 and VirB10 are immunogenic components of the outer membrane type IV secretion system that have been identified as candidate antigens for vaccines targeting of A. marginale. Soluble VirB9-1 and VirB10 were successfully expressed using Pichia pastoris. When formulated with the self-adjuvanting silica vesicles, SV-100 (diameter: 50 nm, and pore entrance size: 6 nm), 200 µg of VirB9-1 and VirB10 were adsorbed per milligram of nanoparticle...
November 5, 2016: Nanomaterials
https://www.readbyqxmd.com/read/28335003/identification-of-genetic-variants-affecting-vitamin-d-receptor-binding-and-associations-with-autoimmune-disease
#20
Giuseppe Gallone, Wilfried Haerty, Giulio Disanto, Sreeram V Ramagopalan, Chris P Ponting, Antonio J Berlanga-Taylor
Large numbers of statistically significant associations between sentinel SNPs and case-control status have been replicated by genome-wide association studies. Nevertheless, few underlying molecular mechanisms of complex disease are currently known. We investigated whether variation in binding of a transcription factor, the vitamin D receptor (VDR) whose activating ligand vitamin D has been proposed as a modifiable factor in multiple disorders, could explain any of these associations. VDR modifies gene expression by binding DNA as a heterodimer with the Retinoid X receptor (RXR)...
March 9, 2017: Human Molecular Genetics
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