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https://www.readbyqxmd.com/read/28432975/vaccination-strategies-against-zika-virus
#1
REVIEW
Estefania Fernandez, Michael S Diamond
The epidemic emergence of Zika virus (ZIKV) in 2015-2016 has been associated with congenital malformations and neurological sequela. Current efforts to develop a ZIKV vaccine build on technologies that successfully reduced infection or disease burden against closely related flaviviruses or other RNA viruses. Subunit-based (DNA plasmid and modified mRNA), viral vectored (adeno- and measles viruses) and inactivated viral vaccines are already advancing to clinical trials in humans after successful mouse and non-human primate studies...
April 19, 2017: Current Opinion in Virology
https://www.readbyqxmd.com/read/28432928/a-humanized-mouse-based-hiv-1-viral-outgrowth-assay-with-higher-sensitivity-than-in-vitro-qvoa-in-detecting-latently-infected-cells-from-individuals-on-art-with-undetectable-viral-loads
#2
Paige Charlins, Kimberly Schmitt, Leila Remling-Mulder, Louise E Hogan, Emily Hanhauser, Kristen S Hobbs, Frederick Hecht, Steven G Deeks, Timothy J Henrich, Ramesh Akkina
Assays that can verify full viral eradication are essential in the context of achieving a cure for HIV/AIDS. In vitro quantitative viral out growth assays (qVOA) are currently the gold standard for measuring latent HIV-1 but these assays often fail to detect very low levels of replication-competent virus. Here we investigated an alternative in vivo approach for sensitive viral detection using humanized mice (hmVOA). Peripheral blood CD4+ T cell samples from HIV subjects on stable ART with undetectable viral loads by RT-PCR were first assayed by in vitro qVOA...
April 19, 2017: Virology
https://www.readbyqxmd.com/read/28432872/human-effector-memory-t-helper-cells-engage-with-mouse-macrophages-and-cause-graft-versus-host-like-pathology-in-skin-of-humanized-mice-used-in-a-nonclinical-immunization-study
#3
Bala S Sundarasetty, Valery Volk, Sebastian J Theobald, Susanne Rittinghausen, Dirk Schaudien, Vanessa Neuhaus, Constanca Figueiredo, Andreas Schneider, Laura Gerasch, Adele Mucci, Thomas Moritz, Constantin von Kaisenberg, Loukia M Spineli, Katherina Sewald, Armin Braun, Henning Weigt, Arnold Ganser, Renata Stripecke
Humanized mice engrafted with human hematopoietic stem cells and developing functional human T-cell adaptive responses are in critical demand to test human-specific therapeutics. We previously showed that humanized mice immunized with long-lived induced-dendritic cells loaded with the pp65 viral antigen (iDCpp65) exhibited a faster development and maturation of T cells. Herein, we evaluated these effects in a long-term (36 weeks) nonclinical model using two stem cell donors to assess efficacy and safety. Relative to baseline, iDCpp65 immunization boosted the output of effector memory CD4(+) T cells in peripheral blood and lymph nodes...
April 19, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28432860/high-ki-67-expression-is-associated-with-prolactin-secreting-pituitary-adenomas
#4
Bogdan Bălinişteanu, Anca Maria Cîmpean, Amalia Raluca Ceauşu, Ana Silvia Corlan, Eugen Melnic, Marius Raica
Pituitary adenomas represent the third most common primary intracranial tumor in neurosurgical practice. To understand the biological behaviour of the pituitary adenomas previous studies have determined the tumor proliferation rate using monoclonal antibodies targeted against the Ki-67 antigen. The aim of this study was to correlate the Ki-67 index with hormonal profiles of pituitary adenomas. The study included 50 pituitary adenoma cases. For histopathologic evaluation, the sections were stained with routine hematoxylin and eosin method...
April 22, 2017: Bosnian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/28432467/renal-skin-syndromes
#5
REVIEW
Cristina Has, Yinghong He
Renal-skin syndroms are a group of genetic disorders with renal and cutaneous manifestations that target molecular components present in both organs. Inherited renal-skin syndromes are mainly associated with defects of cell-matrix adhesion. We provide a non-exhaustive overview of the main molecular players at cell-matrix adhesions in mouse models and in human genetic disorders affecting kidney and skin. Renal and urinary tract involvement is described in all four major epidermolysis bullosa types and, in particular, in junctional subtypes and in recessive dystrophic epidermolysis bullosa...
April 22, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28432455/dual-activation-of-toll-like-receptors-7-and-9-impairs-the-efficacy-of-antitumor-vaccines-in-murine-models-of-metastatic-breast-cancer
#6
Mariela A Moreno Ayala, María Florencia Gottardo, María Soledad Gori, Alejandro Javier Nicola Candia, Carla Caruso, Andrea De Laurentiis, Mercedes Imsen, Slobodanka Klein, Elisa Bal de Kier Joffé, Gabriela Salamone, Maria G Castro, Adriana Seilicovich, Marianela Candolfi
PURPOSE: Since combination of Toll-like receptor (TLR) ligands could boost antitumor immunity, we evaluated the efficacy of dendritic cell (DC) vaccines upon dual activation of TLR9 and TLR7 in breast cancer models. METHODS: DCs were generated from mouse bone marrow or peripheral blood from healthy human donors and stimulated with CpG1826 (mouse TLR9 agonist), CpG2006 or IMT504 (human TLR9 agonists) and R848 (TLR7 agonist). Efficacy of antitumor vaccines was evaluated in BALB/c mice bearing metastatic mammary adenocarcinomas...
April 21, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28432397/downregulation-of-neuropilin-1-on-macrophages-modulates-antibody-mediated-tumoricidal-activity
#7
Kosuke Kawaguchi, Eiji Suzuki, Mariko Nishie, Isao Kii, Tatsuki R Kataoka, Masahiro Hirata, Masashi Inoue, Fengling Pu, Keiko Iwaisako, Moe Tsuda, Ayane Yamaguchi, Hironori Haga, Masatoshi Hagiwara, Masakazu Toi
Neuropilin-1 (NRP-1)-expressing macrophages are engaged in antitumor immune functions via various mechanisms. In this study, we investigated the role of NRP-1 on macrophages in antibody-mediated tumoricidal activity. Treatment of macrophages with NRP-1 knockdown or an anti-NRP-1-neutralizing antibody significantly suppressed antibody-dependent cellular cytotoxicity and modulated cytokine secretion from macrophages in vitro. Furthermore, in vivo studies using a humanized mouse model bearing human epidermal growth factor receptor-2 (HER2)-positive breast cancer xenografts showed that antibody-mediated antitumor activity and tumor infiltration of CD4(+) T lymphocytes were significantly downregulated when peripheral blood mononuclear cells in which NRP-1 was knocked down were co-administered with an anti-HER2 antibody...
April 21, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28432353/severe-hearing-loss-and-outer-hair-cell-death-in-homozygous-foxo3-knockout-mice-after-moderate-noise-exposure
#8
Felicia Gilels, Stephen T Paquette, Holly J Beaulac, Anwen Bullen, Patricia M White
Noise induced hearing loss (NIHL) is a disease that affects millions of Americans. Identifying genetic pathways that influence recovery from noise exposure is an important step forward in understanding NIHL. The transcription factor Foxo3 integrates the cellular response to oxidative stress and plays a role in extending lifespan in many organisms, including humans. Here we show that Foxo3 is required for auditory function after noise exposure in a mouse model system, measured by ABR. Absent Foxo3, outer hair cells are lost throughout the middle and higher frequencies...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28432296/aminoglycosides-but-not-ptc124-ataluren-rescue-nonsense-mutations-in-the-leptin-receptor-and-in-luciferase-reporter-genes
#9
Florian Bolze, Sabine Mocek, Anika Zimmermann, Martin Klingenspor
In rare cases, monogenetic obesity is caused by nonsense mutations in genes regulating energy balance. A key factor herein is the leptin receptor. Here, we focus on leptin receptor nonsense variants causing obesity, namely the human W31X, murine Y333X and rat Y763X mutations, and explored their susceptibilities to aminoglycoside and PTC124 mediated translational read-through in vitro. In a luciferase based assay, all mutations - when analysed within the mouse receptor - were prone to aminoglycoside mediated nonsense suppression with the highest susceptibility for W31X, followed by Y763X and Y333X...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28432191/gene-expression-effects-of-glucocorticoid-and-mineralocorticoid-receptor-agonists-and-antagonists-on-normal-human-skeletal-muscle
#10
Jessica A Chadwick, James Spencer Hauck, Celso E Gomez-Sanchez, Elise P Gomez-Sanchez, Jill A Rafael-Fortney
Mineralocorticoid and glucocorticoid receptors are closely related steroid hormone receptors that regulate gene expression through many of the same hormone response elements. However, their transcriptional activities and effects in skeletal muscles are largely unknown. We recently identified mineralocorticoid receptors (MR) in skeletal muscles after finding that combined treatment with the angiotensin-converting enzyme inhibitor lisinopril and MR antagonist spironolactone was therapeutic in Duchenne muscular dystrophy mouse models...
April 21, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/28432145/bacterial-siderophores-hijack-neutrophil-functions
#11
Piu Saha, Beng San Yeoh, Rodrigo A Olvera, Xia Xiao, Vishal Singh, Deepika Awasthi, Bhagawat C Subramanian, Qiuyan Chen, Madhu Dikshit, Yanming Wang, Carole A Parent, Matam Vijay-Kumar
Neutrophils are the primary immune cells that respond to inflammation and combat microbial transgression. To thrive, the bacteria residing in their mammalian host have to withstand the antibactericidal responses of neutrophils. We report that enterobactin (Ent), a catecholate siderophore expressed by Escherichia coli, inhibited PMA-induced generation of reactive oxygen species (ROS) and neutrophil extracellular traps (NETs) in mouse and human neutrophils. Ent also impaired the degranulation of primary granules and inhibited phagocytosis and bactericidal activity of neutrophils, without affecting their migration and chemotaxis...
April 21, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28432124/regulation-of-neurite-morphogenesis-by-interaction-between-r7-regulator-of-g-protein-signaling-complexes-and-g-protein-subunit-g%C3%AE-13
#12
Stephanie L Scherer, Matthew D Cain, Stanley M Kanai, Kevin M Kaltenbronn, Kendall J Blumer
The R7 regulator of G protein signaling family (R7-RGS) critically regulates nervous system development and function. Mice lacking all R7-RGS subtypes exhibit diverse neurological phenotypes, and humans bearing mutations in the retinal R7-RGS isoform RGS9-1 have vision deficits. Although each R7-RGS subtype forms heterotrimeric complexes with Gβ5 and R7-RGS binding protein (R7BP) that regulate G protein-coupled receptor signaling by accelerating deactivation of Gi/o α-subunits, several neurological phenotypes of R7-RGS knockout mice are not readily explained by dysregulated Gi/o signaling...
April 21, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28432078/effect-of-4-5-6-7-8-tetrahydro-5-5-8-8-tetramethyl-2-naphthalenyl-carbamoyl-benzoic-acid-am80-on-alveolar-regeneration-in-adiponectin-deficient-mice-showing-a-chronic-obstructive-pulmonary-disease-like-pathophysiology
#13
Hitomi Sakai, Michiko Horiguchi, Tomomi Akita, Chihiro Ozawa, Mai Hirokawa, Yuki Oiso, Harumi Kumagai, Yoshito Takeda, Isao Tachibana, Norikazu Maeda, Chikamasa Yamashita
Chronic obstructive pulmonary disease (COPD) is an intractable pulmonary disease that causes widespread and irreversible alveolar collapse. Although COPD occurs worldwide, only symptomatic therapy is currently available. The objective of the present study was the development of therapeutic agents to eradicate COPD. Therefore, we focused on 4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl) carbamoyl] benzoic acid (Am80), which is a derivative of all-trans retinoic acid. We evaluated the effects of Am80 on alveolar repair in a novel COPD model of adiponectin-deficient mice...
April 21, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28431986/ninj2-a-novel-regulator-of-endothelial-inflammation-and-activation
#14
Jingjing Wang, Jingjing Fa, Pengyun Wang, Xinzhen Jia, Huixin Peng, Jing Chen, Yifan Wang, Chenhui Wang, Qiuyun Chen, Xin Tu, Qing K Wang, Chengqi Xu
Previous genetic studies suggested that variants in NINJ2 (encode ninjurin2) confer risk to ischemic stroke or large artery atherosclerotic stroke. However, the underlying mechanisms of NINJ2 in ischemic stroke or atherosclerosis are still unknown. In this study, we hypothesized that NINJ2 may play a role in endothelial inflammation and activation, and regulate the process of atherosclerosis. Here, we demonstrated that NINJ2 can regulate the expression of a panel of genes that are associated with inflammation and atherosclerosis (e...
April 18, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28431931/peroxiredoxin-5-promotes-the-epithelial-mesenchymal-transition-in-colon-cancer
#15
Hye-Mi Ahn, Jin-Woo Yoo, Seunghoon Lee, Hong Jun Lee, Hyun-Shik Lee, Dong-Seok Lee
Globally, colorectal cancer (CRC) is common cause of cancer-related deaths. The high mortality rate of patients with colon cancer is due to cancer cell invasion and metastasis. Initiation of the epithelial-to-mesenchymal transition (EMT) is essential for the tumorigenesis. Peroxiredoinxs (PRX1-6) have been reported to be overexpressed in various tumor tissues, and involved to be responsible for tumor progression. However, the exact role of PRX5 in colon cancer remains to be investigated enhancing proliferation and promoting EMT properties...
April 18, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28431892/a-humanized-hla-dr4-mouse-model-for-autoimmune-myocarditis
#16
M Emrah Şelli, Anita C Thomas, David C Wraith, Andrew C Newby
Myocarditis, the principal cause of dilated cardiomyopathy and heart failure in young adults, is associated with autoimmunity to human cardiac α-myosin (hCAM) and the DR4 allele of human major histocompatibility II (MHCII). We developed an hCAM-induced myocarditis model in human HLA-DR4 transgenic mice that lack all mouse MHCII genes, demonstrating that immunization for 3weeks significantly increased splenic T-cell proliferative responses and titres of IgG1 and IgG2c antibodies, abolished weight gain, provoked cardiac inflammation and significantly impaired cardiac output and fractional shortening, by echocardiography, compared to adjuvant-injected mice...
April 18, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28431857/modeling-human-infertility-with-pluripotent-stem-cells
#17
Di Chen, Joanna J Gell, Yu Tao, Enrique Sosa, Amander T Clark
Human fertility is dependent upon the correct establishment and differentiation of the germline. This is because no other cell type in the body is capable of passing a genome and epigenome from parent to child. Terminally differentiated germline cells in the adult testis and ovary are called gametes. However, the initial specification of germline cells occurs in the embryo around the time of gastrulation. Most of our knowledge regarding the cell and molecular events that govern human germline specification involves extrapolating scientific principles from model organisms, most notably the mouse...
April 13, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28431735/characterization-of-an-amyloid-only-transgenic-b6c3-tg-appswe-psen1de9-85dbo-mmjax-mouse-model-of-alzheimer-s-disease
#18
G S Finnie, R Gunnarsson, J Manavis, P C Blumbergs, K A Mander, S Edwards, C Van den Heuvel, J W Finnie
The spatiotemporal pattern of cerebral amyloid deposition, detectable as light microscopically recognizable aggregates in an 'amyloid only' transgenic mouse model of Alzheimer's disease, B6C3-Tg(APPswe,PSEN1dE9)85Dbo/Mmjax, is reported for the first time in this strain. Monoclonal and polyclonal antibodies were used to detect amyloid deposition immunohistochemically in brains collected from these mice at 3-12 months of age. Amyloid aggregates (20-200 μm) were first found in serial, whole coronal sections of brain at 4 months of age and these increased progressively, plateauing at 11-12 months...
April 18, 2017: Journal of Comparative Pathology
https://www.readbyqxmd.com/read/28431583/overexpression-of-mir-584-5p-inhibits-proliferation-and-induces-apoptosis-by-targeting-ww-domain-containing-e3-ubiquitin-protein-ligase-1-in-gastric-cancer
#19
Qing Li, Zheng Li, Song Wei, Weizhi Wang, Zheng Chen, Lei Zhang, Liang Chen, Bowen Li, Guangli Sun, Jianghao Xu, Qiang Li, Lu Wang, Zhipeng Xu, Yiwen Xia, Diancai Zhang, Hao Xu, Zekuan Xu
BACKGROUND: MicroRNAs are endogenously expressed, small non-coding RNAs that modulate gene expression by targeting specific mRNAs, resulting in translational repression or mRNA degradation. Although miR-584-5p has been reported to play a vital role in various malignancies, its role and the molecular mechanisms underlying the effects of miR-584-5p in gastric cancer (GC) remain to be clarified. In this study, we investigated the role of miR-584-5p in GC. METHODS: The expression of miR-584-5p and its specific target gene were determined in human GC specimens and cell lines by microRNA real-time polymerase chain reaction (RT-PCR), quantitative RT-PCR (qRT-PCR) and Western blot...
April 21, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28431555/reduction-of-pulmonary-toxicity-of-metal-oxide-nanoparticles-by-phosphonate-based-surface-passivation
#20
Xiaoming Cai, Anson Lee, Zhaoxia Ji, Cynthia Huang, Chong Hyun Chang, Xiang Wang, Yu-Pei Liao, Tian Xia, Ruibin Li
BACKGROUND: The wide application of engineered nanoparticles has induced increasing exposure to humans and environment, which led to substantial concerns on their biosafety. Some metal oxides (MOx) have shown severe toxicity in cells and animals, thus safe designs of MOx with reduced hazard potential are desired. Currently, there is a lack of a simple yet effective safe design approach for the toxic MOx. In this study, we determined the key physicochemical properties of MOx that lead to cytotoxicity and explored a safe design approach for toxic MOx by modifying their hazard properties...
April 21, 2017: Particle and Fibre Toxicology
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