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https://www.readbyqxmd.com/read/29908240/the-gabaergic-gudden-s-dorsal-tegmental-nucleus-a-new-relay-for-serotonergic-regulation-of-sleep-wake-behavior-in-the-mouse
#1
Marine Chazalon, Sylvie Dumas, Jean-François Bernard, Iman Sahly, François Tronche, Alban de Kerchove d'Exaerde, Michel Hamon, Joëlle Adrien, Véronique Fabre, Patricia Bonnavion
Serotonin (5-HT) neurons are involved in wake promotion and exert a strong inhibitory influence on rapid eye movement (REM) sleep. Such effects have been ascribed, at least in part to the action of 5-HT at post-synaptic 5-HT1A receptors (5-HT1A R) in the brainstem, a major wake/REM sleep regulatory center. However, the neuroanatomical substrate through which 5-HT1A R influence sleep remains elusive. We therefore investigated whether a brainstem structure containing a high density of 5-HT1A R mRNA, the GABAergic Gudden's dorsal tegmental nucleus (DTg), may contribute to 5-HT-mediated regulatory mechanisms of sleep-wake stages...
June 13, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29908209/the-second-generation-thiazolide-haloxanide-is-a-potent-inhibitor-of-avian-influenza-virus-replication
#2
Simone La Frazia, Sara Piacentini, Anna Riccio, Jean Francois Rossignol, M Gabriella Santoro
The emergence of new avian influenza virus (AIV) strains able to infect humans represents a serious threat to global human health. In addition to surveillance and vaccine development, antiviral therapy remains crucial for AIV control; however, the increase in drug-resistant AIV strains underscores the need for novel approaches to anti-influenza chemotherapy. We have previously shown that the thiazolide anti-infective nitazoxanide (NTZ) inhibits influenza A/PuertoRico/8/1934(H1N1) virus replication, and this effect was associated with inhibition of viral hemagglutinin (HA) maturation...
June 13, 2018: Antiviral Research
https://www.readbyqxmd.com/read/29905807/the-loss-of-function-s267f-variant-in-hbv-receptor-ntcp-reduces-human-risk-to-hbv-infection-and-disease-progression
#3
Ping An, Zheng Zeng, Cheryl A Winkler
Background: Sodium taurocholate cotransporting polypeptide (NTCP, SLC10A1) was recently identified as a hepatocyte receptor for infection of Hepatitis B virus (HBV). The natural S267F variant in NTCP causes a loss of HBV receptor function of NTCP. Objective: We assessed the association of S267F with HBV resistance, HBV infection clearance, and HBV-related cirrhosis and HCC. Methods: We tested the effects of S267F in 1117 Han Chinese patients with various HBV infection outcomes using multivariate logistic regression analysis...
June 14, 2018: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29905080/conformation-dependent-interactions-between-hiv-1-envelope-glycoproteins-and-broadly-neutralizing-antibodies
#4
Juliana Flemming, Lisa Wiesen, Alon Herschhorn
The human immunodeficiency virus type 1 (HIV-1) envelope glycoproteins (Env) mediate virus entry and are the target of neutralizing antibodies. Binding of the metastable HIV-1 Env trimer to the CD4 receptor triggers structural rearrangements that mediate Env conformational transitions from a closed conformation to a more open state through an intermediate step. Recent studies have revealed new insights on the dynamics, regulation and molecular mechanisms of Env transitions along the entry pathway. Here we provide an overview of the current knowledge on Env conformational dynamics and the relationship between Env conformational states and neutralization selectivity of the broadly neutralizing antibodies (bNAbs) that develop in 10-20% of infected individuals and may provide guidance for the development of an effective HIV-1 vaccine...
June 15, 2018: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/29904904/ilixadencel-an-allogeneic-cell-based-anticancer-immune-primer-for-intratumoral-administration
#5
Alex Karlsson-Parra, Juliana Kovacka, Emilia Heimann, Margareth Jorvid, Sijme Zeilemaker, Sharon Longhurst, Peter Suenaert
Intratumoral administration of an immune primer is a therapeutic vaccine strategy aimed to trigger dendritic cell (DC)-mediated cross-presentation of cell-associated tumor antigens to cytotoxic CD8+ T cells without the need for tumor antigen characterization. The prevailing view is that these cross-presenting DCs have to be directly activated by pathogen-associated molecular patterns (PAMPS), including Toll-like receptor ligands or live microbial agents like oncolytic viruses. Emerging data are however challenging this view, indicating that the cross-presenting machinery in DCs is suboptimally activated by direct PAMP recognition, and that endogenous inflammatory factors are the main drivers of DC-mediated cross-presentation within the tumor...
June 14, 2018: Pharmaceutical Research
https://www.readbyqxmd.com/read/29903906/parkin-negatively-regulates-the-antiviral-signaling-pathway-by-targeting-traf3-for-degradation
#6
Di Xin, Haiyan Gu, Enping Liu, Qinmiao Sun
Chronic neuroinflammation is a characteristic of Parkinson's disease (PD). Previous investigations have shown that Parkin gene mutations are related to the early-onset recessive form of PD and isolated juvenile-onset PD. Further, Parkin plays important roles in mitochondrial quality control and cytokine-induced cell death. However, whether Parkin regulates other cellular events is still largely unknown. In this study, we performed overexpression and knockout experiments, and found that Parkin negatively regulates antiviral immune responses against RNA and DNA viruses...
June 14, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29902708/enhanced-antiviral-immunity-against-bombyx-mori-cytoplasmic-polyhedrosis-virus-via-overexpression-of-peptidoglycan-recognition-protein-s2-in-transgenic-silkworms
#7
Ping Zhao, Fei Xia, Liang Jiang, Huizhen Guo, Guowen Xu, Qiang Sun, Bingbing Wang, Yumei Wang, Zhongyan Lu, Qingyou Xia
In insect innate immunity, peptidoglycan recognition proteins act as pattern recognition receptors, helping hosts combat invasive microorganisms. Bombyx mori cytoplasmic polyhedrosis virus (BmCPV) is the main silkworm pathogen that invades the midgut columnar cell layer. We previously reported that B. mori peptidoglycan recognition protein S2 (BmPGRP-S2) was upregulated in silkworm larvae after BmCPV infection. Here, we constructed a transgenic vector overexpressing BmPGRP-S2 under the control of a midgut-specific promoter...
May 30, 2018: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/29902449/timing-of-gestational-exposure-to-zika-virus-is-associated-with-postnatal-growth-restriction-in-a-murine-model
#8
Gregory C Valentine, Maxim D Seferovic, Stephanie W Fowler, Angela M Major, Rodion Gorchakov, Rebecca Berry, Alton G Swennes, Kristy O Murray, Melissa A Suter, Kjersti M Aagaard
BACKGROUND: Vertical transmission of Zika virus (ZIKV) leads to infection of neuroprogenitor cells and destruction of brain parenchyma. Recent evidence suggests that the timing of infection as well as host factors may affect vertical transmission. As a result, congenital ZIKV infection may only become clinically apparent in the postnatal period. OBJECTIVES: We sought to develop an outbred mouse model of ZIKV vertical transmission to determine if the timing of gestational ZIKV exposure yields phenotypic differences at birth and through adolescence...
June 11, 2018: American Journal of Obstetrics and Gynecology
https://www.readbyqxmd.com/read/29900580/designing-b-and-t-cell-multi-epitope-based-subunit-vaccine-using-immunoinformatics-approach-to-control-zika-virus-infection
#9
Rajan Kumar Pandey, Rupal Ojha, Amit Mishra, Vijay Kumar Prajapati
The Zika virus is a rapidly spreading Aedes mosquito-borne sickness, which creates an unanticipated linkage birth deformity and neurological turmoil. This study represents the use of the combinatorial immunoinformatics approach to develop a multiepitope subunit vaccine using the structural and nonstructural proteins of the Zika virus. The designed subunit vaccine consists of cytotoxic T-lymphocyte and helper T-lymphocyte epitopes accompanied by suitable adjuvant and linkers. The presence of humoral immune response specific B-cell epitopes was also confirmed by B-cell epitope mapping among vaccine protein...
June 14, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29900506/the-role-of-flaviviral-proteins-in-the-induction-of-innate-immunity
#10
L Cedillo-Barrón, J García-Cordero, G Shrivastava, S Carrillo-Halfon, M León-Juárez, J Bustos Arriaga, Pc León Valenzuela, B Gutiérrez Castañeda
Flaviviruses are positive, single-stranded, enveloped cytoplasmic sense RNA viruses that cause a variety of important diseases worldwide. Among them, Zika virus, West Nile virus, Japanese encephalitis virus, and Dengue virus have the potential to cause severe disease. Extensive studies have been performed to elucidate the structure and replication strategies of flaviviruses, and current studies are aiming to unravel the complex molecular interactions between the virus and host during the very early stages of infection...
2018: Sub-cellular Biochemistry
https://www.readbyqxmd.com/read/29900503/the-bacteriophage-head-to-tail-interface
#11
Paulo Tavares
Many icosahedral viruses use a specialized portal vertex for genome encapsidation in the viral capsid (or head). This structure then controls release of the viral genetic information to the host cell at the beginning of infection. In tailed bacteriophages, the portal system is connected to a tail device that delivers their genome to the bacterial cytoplasm. The head-to-tail interface is a multiprotein complex that locks the viral DNA inside the phage capsid correctly positioned for egress and that controls its ejection when the viral particle interacts with the host cell receptor...
2018: Sub-cellular Biochemistry
https://www.readbyqxmd.com/read/29899740/gmp-grade-manufacturing-of-t-cells-engineered-to-express-a-defined-%C3%AE-%C3%AE-tcr
#12
Trudy Straetemans, Guido J J Kierkels, Ruud Doorn, Koen Jansen, Sabine Heijhuurs, Joao M Dos Santos, Anna D D van Muyden, Henri Vie, Béatrice Clemenceau, Reinier Raymakers, Moniek de Witte, Zsolt Sebestyén, Jürgen Kuball
γ9δ2T cells play a critical role in daily cancer immune surveillance by sensing cancer-mediated metabolic changes. However, a major limitation of the therapeutic application of γ9δ2T cells is their diversity and regulation through innate co-receptors. In order to overcome natural obstacles of γ9δ2T cells, we have developed the concept of T cells engineered to express a defined γδT cell receptor (TEGs). This next generation of chimeric antigen receptor engineered T (CAR-T) cells not only allows for targeting of hematological but also of solid tumors and, therefore, overcomes major limitations of many CAR-T and γδT cell strategies...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29899171/novel-approaches-for-the-treatment-of-familial-hypercholesterolemia-current-status-and-future-challenges
#13
Long Jiang, Lu-Ya Wang, Xiao-Shu Cheng
Familial hypercholesterolemia (FH) is an autosomal-dominant disorder that is characterized by high plasma low-density lipoprotein cholesterol (LDL-c) levels and an increased risk of cardiovascular disease. Despite the use of high-dose statins and the recent addition of proprotein convertase subtilisin/kexin type 9 inhibitors as a treatment option, many patients with homozygous FH fail to achieve optimal reductions of LDL-c levels. Gene therapy has become one of the most promising research directions for contemporary life sciences and is a potential treatment option for FH...
June 13, 2018: Journal of Atherosclerosis and Thrombosis
https://www.readbyqxmd.com/read/29899108/a-kaposi-s-sarcoma-associated-herpesvirus-infection-mechanism-is-independent-of-integrins-%C3%AE-3%C3%AE-1-%C3%AE-v%C3%AE-3-and-%C3%AE-v%C3%AE-5
#14
Allison Alwan TerBush, Florianne Hafkamp, Hee Jun Lee, Laurent Coscoy
Host receptor usage by KSHV has been best studied using primary microvascular endothelial and fibroblast cells, although the virus infects a wide variety of cell types in culture and in natural infections. In these two infection models, KSHV adheres to the cell though heparan sulfate (HS) binding, then interacts with a complex of EphA2, xct, and integrins α3β1, αVβ3, αVβ5 to catalyze viral entry. We dissected this receptor complex at the genetic level with CRISPR-Cas9 to precisely determine receptor usage in two epithelial cell lines...
June 13, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29899084/pharmacologic-depletion-of-microglia-increases-viral-load-in-the-brain-and-enhances-mortality-in-murine-models-of-flavivirus-induced-encephalitis
#15
Scott Seitz, Penny Clarke, Kenneth L Tyler
Flaviviruses account for most arthropod-borne cases of human encephalitis in the world. However the exact mechanisms of injury to the central nervous system (CNS) during Flavivirus infections remain poorly understood. Microglia are the resident immune cell of the CNS and are important for multiple functions, including control of viral pathogenesis. Utilizing a pharmacologic method of microglia depletion (PLX5622, Plexxikon Inc, an inhibitor of colony stimulating factor 1 receptor) we sought to determine the role of microglia in Flaviviral pathogenesis...
June 13, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29898782/expression-of-human-cd46-and-trans-complementation-by-murine-adenovirus-1-fails-to-allow-productive-infection-by-a-group-b-oncolytic-adenovirus-in-murine-cancer-cells
#16
Janet Lei, Egon J Jacobus, William K Taverner, Kerry D Fisher, Silvio Hemmi, Katy West, Lorna Slater, Fred Lilley, Alice Brown, Brian Champion, Margaret R Duffy, Len W Seymour
BACKGROUND: Oncolytic viruses are currently experiencing accelerated development in several laboratories worldwide, with some forty-seven clinical trials currently recruiting. Many oncolytic viruses combine targeted cytotoxicity to cancer cells with a proinflammatory cell lysis. Due to their additional potential to express immunomodulatory transgenes, they are also often known as oncolytic viral vaccines. However, several types of oncolytic viruses are human-specific and the lack of suitable immune-competent animal models complicates biologically relevant evaluation of their vaccine potential...
June 13, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29896660/the-role-of-hsv-glycoproteins-in-mediating-cell-entry
#17
Jun Arii, Yasushi Kawaguchi
The successful entry of herpes simplex virus (HSV) into a cell is a complex process requiring the interaction of several surface viral glycoproteins with host cell receptors. These viral glycoproteins are currently thought to work sequentially to trigger fusogenic activity, but the process is complicated by the fact that each glycoprotein is known to interact with a range of target cell surface receptor molecules. The glycoproteins concerned are gB, gD, and gH/gL, with at least four host cell receptor molecules known to bind to gB and gD alone...
2018: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29896169/the-appropriate-combination-of-hemagglutinin-and-neuraminidase-prompts-the-predominant-h5n6-highly-pathogenic-avian-influenza-virus-in-birds
#18
Xiuhui Wang, Zhaoyong Zeng, Zaoyue Zhang, Yi Zheng, Bo Li, Guanming Su, Huanan Li, Lihong Huang, Wenbao Qi, Ming Liao
Haemagglutinin (HA) and neuraminidase (NA) are two vital surface glycoproteins of influenza virus. The HA of H5N6 highly pathogenic avian influenza virus is divided into Major/H5 and Minor/H5, and its NA consists of short stalk NA and full-length stalk NA. The strain combined with Major/H5 and short stalk NA account for 76.8% of all strains, and the proportion was 23.0% matched by Minor/H5 and full-length stalk NA. Our objective was to investigate the influence of HA-NA matching on the biological characteristics and the effects of the epidemic trend of H5N6 on mice and chickens...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29896090/activation-of-dorsomedial-hypothalamic-neurons-promotes-physical-activity-and-decreases-food-intake-and-body-weight-in-zucker-fatty-rats
#19
Ni Zhang, Liang Yang, Lanting Guo, Sheng Bi
Previous reports have shown that running wheel activity or voluntary exercise prevents hyperphagia and obesity in various animal models of obesity, but such effects seem only minimal in obese animals lacking leptin or leptin receptors. The mechanisms underlying this ineffectiveness remain unclear. Here, we identified the action of neuronal activation in the dorsomedial hypothalamus (DMH) in modulating physical activity, food intake and body weight using leptin receptor mutant obese Zucker ( Lepr(fa) , ZF) and Koletsky ( Lepr(fak) , SHROB) rats...
2018: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29894816/design-and-evaluation-of-a-cxcr4-targeting-peptide-4dv3-as-an-hiv-entry-inhibitor-and-a-ligand-for-targeted-drug-delivery
#20
In Heon Lee, Matthew S Palombo, Xiaoping Zhang, Zoltan Szekely, Patrick J Sinko
The feasibility of utilizing the cell surface chemokine receptor CXCR4 for human immunodeficiency virus (HIV) entry inhibition and as an intracellular portal for targeted drug delivery was evaluated. Novel DV3 ligands (1DV3, 2DV3, and 4DV3) were designed, synthesized and conjugated to various probes (fluorescein isothiocyanate (FITC) or biotin) and cargos with sizes ranging from 10 to 50 nm (polyethylene glycol (PEG), streptavidin, and a polymeric nanoparticle). 4DV3 conjugated probes inhibited HIV-1 entry into the CXCR4-expressing reporter cell line TZM-bl (IC50 at 553 nM) whereas 1DV3 and 2DV3 did not...
June 9, 2018: European Journal of Pharmaceutics and Biopharmaceutics
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