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https://www.readbyqxmd.com/read/28229966/extra-oviductal-expression-of-oviductal-glycoprotein-1-in-mouse-detection-in-testis-epididymis-and-ovary
#1
Saniya Laheri, Deepak Modi, Purvi Bhatt
Oviductal glycoprotein 1 (OVGP1), also called oviductin, is an oviduct-specific protein and is suggested to play a role in fertilization. Traditionally, Ovgp1 has been shown to be exclusively expressed by the oviduct; however, recent studies have demonstrated its expression in some cancers. This observation led us to hypothesize that Ovgp1 might have some extra-oviductal expression. In the current study, we evaluated the mRNA and protein expression of Ovgp1 in normal reproductive tissues of male and female mice...
March 2017: Journal of Biosciences
https://www.readbyqxmd.com/read/28229588/intra-and-inter-subunit-ion-pair-interactions-determine-the-ability-of-apolipoprotein-c-ll-mutants-to-form-hybrid-amyloid-fibrils
#2
Nevena Todorova, Courtney O Zlatic, Yu Mao, Irene Yarovsky, Geoffrey John Howlett, Paul R Gooley, Michael D W Griffin
The apolipoprotein family is structurally defined by amphipathic α-helical regions that interact with lipid surfaces. In the absence of lipid, human apolipoprotein (apo) C-II also forms well-defined amyloid fibrils with cross-β structure. Formation of this β-structure is accompanied by the burial of two charged residues, K30 and D69 that form an ion-pair within the amyloid fibril core. Molecular dynamics (MD) simulations indicate these buried residues form both intra- and inter-subunit ion-pair interactions that stabilize the fibril...
February 23, 2017: Biochemistry
https://www.readbyqxmd.com/read/28228639/grin1-mutation-associated-with-intellectual-disability-alters-nmda-receptor-trafficking-and-function
#3
Wenjuan Chen, Christine Shieh, Sharon A Swanger, Anel Tankovic, Margaret Au, Marianne McGuire, Michele Tagliati, John M Graham, Suneeta Madan-Khetarpal, Stephen F Traynelis, Hongjie Yuan, Tyler Mark Pierson
N-methyl-d-aspartate receptors (NMDARs) play important roles in brain development and neurological disease. We report two individuals with similar dominant de novo GRIN1 mutations (c.1858 G>A and c.1858 G>C; both p.G620R). Both individuals presented at birth with developmental delay and hypotonia associated with behavioral abnormalities and stereotypical movements. Recombinant NMDARs containing the mutant GluN1-G620R together with either GluN2A or GluN2B were evaluated for changes in their trafficking to the plasma membrane and their electrophysiological properties...
February 23, 2017: Journal of Human Genetics
https://www.readbyqxmd.com/read/28228479/unraveling-the-structural-basis-of-grazoprevir-potency-against-clinically-relevant-substitutions-in-hepatitis-c-virus-ns3-4a-protease-from-genotype-1a
#4
Zhuyan Guo, Stuart Black, Yuan Hu, Patricia McMonagle, Paul Ingravallo, Robert Chase, Stephanie Curry, Ernest Asante-Appiah
Grazoprevir is a potent pan-genotype, macrocyclic inhibitor of hepatitis C virus (HCV) NS3/4A protease and was developed for treating chronic HCV infection. In HCV genotype (GT) 1a, grazoprevir maintains potent activity against a majority of NS3 resistance-associated amino acid substitutions including the highly prevalent and naturally-occurring Q80K polymorphism that impacts simeprevir, another NS3/4A protease inhibitor. The basis for an unexpected difference in the clinical impact of some NS3 substitutions was investigated...
February 21, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28223334/corneal-surface-glycosylation-is-modulated-by-il-1r-and-pseudomonas-aeruginosa-challenge-but-is-insufficient-for-inhibiting-bacterial-binding
#5
Amber L Jolly, Paresh Agarwal, Matteo M E Metruccio, David R Spiciarich, David J Evans, Carolyn R Bertozzi, Suzanne M J Fleiszig
Cell surface glycosylation is thought to be involved in barrier function against microbes at mucosal surfaces. Previously we showed that the epithelium of healthy mouse corneas becomes vulnerable to P. aeruginosa adhesion if it lacks the innate defense protein MyD88 (myeloid differentiation primary response gene 88), or after superficial injury by blotting with tissue paper. Here we explored their effect on corneal surface glycosylation using a metabolic label, tetra-acetylated N-azidoacetylgalactosamine (Ac4GalNAz)...
February 21, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28221763/inactivation-clearance-and-functional-effects-of-lung-instilled-short-and-long-silver-nanowires-in-rats
#6
Kian Fan Chung, Joanna Seiffert, Shu Chen, Ioannis G Theodorou, Angela Erin Goode, Bey Fen Leo, Catriona M McGilvery, Farhana Hussain, Coen Wiegman, Christos Rossios, Jie Zhu, Jicheng Gong, Farid Tariq, Vladimir Yufit, Alexander J Monteith, Teruo Hashimoto, Jeremy N Skepper, Mary P Ryan, Junfeng Jim Zhang, Teresa D Tetley, Alexandra E Porter
There is a potential for silver nanowires (AgNWs) to be inhaled but there is little information on their health effects and their chemical transformation inside the lungs in vivo. We studied the effects of short (S-AgNWs; 1.5µm) and long (L-AgNWs; 10 µm) nanowires instilled into the lungs of Sprague-Dawley rats. S- and L-AgNWs were phagocytosed and degraded by macrophages; there was no frustrated phagocytosis. Interestingly, both AgNWs were internalized in alveolar Type II epithelial cells (ATII), with precipitation of Ag2S on their surface as secondary Ag2S nanoparticles...
February 21, 2017: ACS Nano
https://www.readbyqxmd.com/read/28218617/chimeric-protein-repair-of-laminin-polymerization-ameliorates-muscular-dystrophy-phenotype
#7
Karen K McKee, Stephanie C Crosson, Sarina Meinen, Judith R Reinhard, Markus A Rüegg, Peter D Yurchenco
Mutations in laminin α2-subunit (Lmα2, encoded by LAMA2) are linked to approximately 30% of congenital muscular dystrophy cases. Mice with a homozygous mutation in Lama2 (dy2J mice) express a nonpolymerizing form of laminin-211 (Lm211) and are a model for ambulatory-type Lmα2-deficient muscular dystrophy. Here, we developed transgenic dy2J mice with muscle-specific expression of αLNNd, a laminin/nidogen chimeric protein that provides a missing polymerization domain. Muscle-specific expression of αLNNd in dy2J mice resulted in strong amelioration of the dystrophic phenotype, manifested by the prevention of fibrosis and restoration of forelimb grip strength...
February 20, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28218496/functional-analysis-of-bioactivated-surfaces
#8
Selgai Haidari, Marko Boskov, Ulrike Schillinger, Klaus-Dietrich Wolff, Christian Plank, Andreas Kolk
Common scaffold surfaces, such as titanium, can have side effects, e.g., infections, cytotoxicity, impaired osseointegration or low regeneration rates for bone tissue. These effects lead to poor implant integration or even implant loss. Therefore, bioactive implants are promising instruments in tissue regeneration. Osteoinductive elements, such as growth factors and anti-infectives, support wound healing and bone growth and thereby enable faster osseointegration, even in elderly patients. In this study, titanium surfaces were coated with a poly-(D,L-lactide) (PDLLA) layer containing different concentrations of copolymer-protected gene vectors (COPROGs) to locally provide bone morphogenetic protein-2 (BMP-2) or activated anti-infective agents, such as chlorhexidine gluconate, triclosan and metronidazole, to prevent peri-implantitis...
February 20, 2017: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/28216572/in-vitro-characterization-of-the-two-stage-non-classical-reassembly-pathway-of-s-layers
#9
Andreas Breitwieser, Jagoba Iturri, Jose-Luis Toca-Herrera, Uwe B Sleytr, Dietmar Pum
The recombinant bacterial surface layer (S-layer) protein rSbpA of Lysinibacillus sphaericus CCM 2177 is an ideal model system to study non-classical nucleation and growth of protein crystals at surfaces since the recrystallization process may be separated into two distinct steps: (i) adsorption of S-layer protein monomers on silicon surfaces is completed within 5 min and the amount of bound S-layer protein sufficient for the subsequent formation of a closed crystalline monolayer; (ii) the recrystallization process is triggered-after washing away the unbound S-layer protein-by the addition of a CaCl₂ containing buffer solution, and completed after approximately 2 h...
February 14, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28216187/recombinant-proteins-of-zaire-ebolavirus-induce-potent-humoral-and-cellular-immune-responses-and-protect-against-live-virus-infection-in-mice
#10
Axel T Lehrer, Teri-Ann S Wong, Michael M Lieberman, Tom Humphreys, David E Clements, Russell R Bakken, Mary Kate Hart, William D Pratt, John M Dye
Infections with filoviruses in humans are highly virulent, causing hemorrhagic fevers which result in up to 90% mortality. In addition to natural infections, the ability to use these viruses as bioterrorist weapons is of significant concern. Currently, there are no licensed vaccines or therapeutics available to combat these infections. The pathogenesis of disease involves the dysregulation of the host's immune system, which results in impairment of the innate and adaptive immune responses, with subsequent development of lymphopenia, thrombocytopenia, hemorrhage, and death...
February 16, 2017: Vaccine
https://www.readbyqxmd.com/read/28215617/genetic-engineering-alveolar-macrophages-for-host-resistance-to-prrsv
#11
REVIEW
Randall S Prather, Kristin M Whitworth, Susan K Schommer, Kevin D Wells
Standard strategies for control of porcine reproductive and respiratory syndrome virus (PRRSV) have not been effective, as vaccines have not reduced the prevalence of disease and many producers depopulate after an outbreak. Another method of control would be to prevent the virus from infecting the pig. The virus was thought to infect alveolar macrophages by interaction with a variety of cell surface molecules. One popular model had PRRSV first interacting with heparin sulfate followed by binding to sialoadhesin and then being internalized into an endosome...
February 10, 2017: Veterinary Microbiology
https://www.readbyqxmd.com/read/28213380/complex-formation-with-pentraxin-2-regulates-factor-x-plasma-levels-and-macrophage-interactions
#12
Vincent Muczynski, Gabriel Aymé, Véronique Regnault, Marc Vasse, Delphine Borgel, Paulette Legendre, Amine Bazaa, Amélie Harel, Cécile Loubière, Peter J Lenting, Cécile V Denis, Olivier D Christophe
Recently, we have identified scavenger receptor-AI (SR-AI) as a receptor for coagulation factor X (FX), mediating the formation of a FX-reservoir at the macrophage-surface (Muczynski, Blood 2016 127:778). Here, we demonstrate that the FX/SR-AI-complex comprises a third protein, pentraxin-2. The presence of pentraxin-2 is essential to prevent internalization of FX by SR-AI, while the presence of FX is needed to interfere with internalization of pentraxin-2. Binding studies showed that FX, SR-AI and pentraxin-2 independently bind to each other (Kd,app: 0...
February 17, 2017: Blood
https://www.readbyqxmd.com/read/28211679/site-directed-immobilization-of-bmp-2-two-approaches-for-the-production-of-innovative-osteoinductive-scaffolds
#13
Barbara Tabisz, Werner Schmitz, Michael Schmitz, Tessa Luehmann, Eva Heusler, Jens-Christoph Rybak, Lorenz Meinel, Juliane E Fiebig, Thomas D Mueller, Joachim Nickel
The regenerative potential of bone is strongly impaired in pathological conditions, such as nonunion fractures. To support bone regeneration various scaffolds have been developed in the past, which have been functionalized with osteogenic growth factors such as bone morphogenetic proteins (BMPs). However, most of them required supra-physiological levels of these proteins leading to burst releases, thereby causing severe side effects. Site-specific, covalent coupling of BMP2 to implant materials might be an optimal strategy in order to overcome these problems...
February 17, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/28209987/targeting-phospholipase-d-in-cancer-infection-and-neurodegenerative-disorders
#14
REVIEW
H Alex Brown, Paul G Thomas, Craig W Lindsley
Lipid second messengers have essential roles in cellular function and contribute to the molecular mechanisms that underlie inflammation, malignant transformation, invasiveness, neurodegenerative disorders, and infectious and other pathophysiological processes. The phospholipase D (PLD) isoenzymes PLD1 and PLD2 are one of the major sources of signal-activated phosphatidic acid (PtdOH) generation downstream of a variety of cell-surface receptors, including G protein-coupled receptors (GPCRs), receptor tyrosine kinases (RTKs) and integrins...
February 17, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/28208267/highly-selective-capture-surfaces-on-medical-wires-for-fishing-tumor-cells-in-whole-blood
#15
Frank D Scherag, Robert Niestroj-Pahl, Solveigh Krusekopf, Klaus Lücke, Thomas Brandstetter, Jürgen Rühe
The detection of circulating tumor cells (CTCs) in the blood of cancer patients is a challenging task. CTCs are, especially at the early stages of cancer development, extremely rare cells hidden in a vast background of regular blood cells. We describe a new strategy for the isolation of CTCs from whole blood. The key component is a medical wire coated with a multilayer assembly that allows highly specific capture of EpCAM (epithelial cell adhesion molecule) positive CTCs from blood. The assembly is generated in a layer-by-layer fashion through photochemically induced C,H insertion reactions and consists of a protective layer, which shields the contacting solution from the metal, a protein resistant layer, which prevents nonspecific interactions with proteins and a layer containing the EpCAM antibodies...
February 7, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28203230/the-major-immediate-early-protein-ie2-of-human-cytomegalovirus-is-sufficient-to-induce-proteasomal-degradation-of-cd83-on-mature-dendritic-cells
#16
Christiane S Heilingloh, Linda Grosche, Mirko Kummer, Petra Mühl-Zürbes, Lisa Kamm, Myriam Scherer, Melanie Latzko, Thomas Stamminger, Alexander Steinkasserer
Human cytomegalovirus (HCMV) is the prototypic beta-herpesvirus and widespread throughout the human population. While infection is asymptomatic in healthy individuals, it can lead to high morbidity and mortality in immunocompromised persons. Importantly, HCMV evolved multiple strategies to interfere with immune cell function in order to establish latency in infected individuals. As mature DCs (mDCs) are antigen-presenting cells able to activate naïve T cells they play a crucial role during induction of effective antiviral immune responses...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28202751/superiority-in-rhesus-macaques-of-targeting-hiv-1-env-gp140-to-cd40-versus-lox-1-in-combination-with-replication-competent-nyvac-kc-for-induction-of-env-specific-antibody-and-t-cell-responses
#17
Gerard Zurawski, Xiaoying Shen, Sandra Zurawski, Georgia D Tomaras, David C Montefiori, Mario Roederer, Guido Ferrari, Christine Lacabaratz, Peter Klucar, Zhiqing Wang, Kathryn E Foulds, Shing-Fen Kao, Xuesong Yu, Alicia Sato, Nicole L Yates, Celia LaBranche, Sherry Stanfield-Oakley, Karen Kibler, Bertram Jacobs, Andres Salazar, Steve Self, Jimmy Fulp, Raphael Gottardo, Lindsey Galmin, Deborah Weiss, Anthony Cristillo, Giuseppe Pantaleo, Yves Levy
We compared the HIV-1-specific immune responses generated by targeting HIV-1 envelope protein (Env gp140) to either CD40 or LOX-1, two endocytic receptors on dendritic cells (DCs), in Rhesus macaques primed with a poxvirus vector (NYVAC-KC) expressing Env gp140. The DC-targeting vaccines, humanized recombinant monoclonal antibodies fused to Env gp140, were administered as a boost with poly ICLC adjuvant either alone or co-administered with the NYVAC-KC vector. All the DC-targeting vaccine administrations with poly ICLC increased the low-level serum anti-Env IgG responses elicited by NYVAC-KC priming significantly more (up to P =0...
February 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28202635/short-term-subclinical-zinc-deficiency-in-weaned-piglets-affects-cardiac-redox-metabolism-and-zinc-concentration
#18
Daniel Brugger, Wilhelm M Windisch
Background: Subclinical zinc deficiency (SZD) represents the common zinc malnutrition phenotype. However, its association with oxidative stress is not well understood. The heart muscle may be a promising target for studying early changes in redox metabolism.Objective: We investigated the effects of short-term SZD on cardiac redox metabolism in weaned piglets.Methods: Forty-eight weaned German Large White × Landrace × Piétrain piglets (50% castrated males and 50% females; body weight of 8.5 kg) were fed diets with different zinc concentrations for 8 d...
February 15, 2017: Journal of Nutrition
https://www.readbyqxmd.com/read/28199361/bombyx-mori-and-aedes-aegypti-form-multi-functional-immune-complexes-that-integrate-pattern-recognition-melanization-coagulants-and-hemocyte-recruitment
#19
Dennis R Phillips, Kevin D Clark
The innate immune system of insects responds to wounding and pathogens by mobilizing multiple pathways that provide both systemic and localized protection. Key localized responses in hemolymph include melanization, coagulation, and hemocyte encapsulation, which synergistically seal wounds and envelop and destroy pathogens. To be effective, these pathways require a targeted deposition of their components to provide protection without compromising the host. Extensive research has identified a large number of the effectors that comprise these responses, but questions remain regarding their post-translational processing, function, and targeting...
2017: PloS One
https://www.readbyqxmd.com/read/28196872/muc16-regulates-tspyl5-for-lung-cancer-cell-growth-and-chemoresistance-by-suppressing-p53
#20
Imayavaramban Lakshmanan, Shireen Salfity, Parthasarathy Seshacharyulu, Satyanarayana Rachagani, Abigail Thomas, Srustidhar Das, Prabin D Majhi, Rama Krishna Nimmakayala, Raghupathy Vengoji, Subodh M Lele, Moorthy P Ponnusamy, Surinder K Batra, Apar Kishor Ganti
PURPOSE: MUC16, a tumor biomarker and cell surface associated mucin, is overexpressed in various cancers; however, its role in lung cancer pathogenesis is unknown. Here, we have explored the mechanistic role of MUC16 in lung cancer. EXPERIMENTAL DESIGN: To identify the functional role of MUC16, stable knockdown was carried in lung cancer cells with two different shRNAs. Clinical significance of MUC16 was evaluated in lung cancer patient's tissues using IHC. We have generated genetically engineered mouse model (KrasG12D; AdCre) to evaluate the preclinical significance of MUC16...
February 14, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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