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https://www.readbyqxmd.com/read/29777446/the-degree-of-hiv-1-amino-acid-variability-is-strictly-related-to-different-disease-progression-rates
#1
Rossana Scutari, Monica Faieta, Roberta D'Arrigo, Lavinia Fabeni, Cristina Mussini, Andrea Cossarizza, Claudio Casoli, Carlo Federico Perno, Valentina Svicher, Claudia Alteri, Stefano Aquaro
The aim of this study is to evaluate the amino acid variability of HIV-1 Gp41, C2-V3, and Nef in a group of patients characterized by different disease progression rates. HIV-1 sequences were collected from 19 Long term non progressor patients (LTNPs), 9 slow progressors (SPs), and 11 rapid progressors (RPs). Phylogenetic trees were estimated by MEGA 6. Differences in amino acid variability among sequences belonging to the 3 groups have been evaluated by amino acid divergence, Shannon entropy analysis, and the number of amino acid mutations (defined as amino acid variations compared with HxB2)...
May 17, 2018: Virus Genes
https://www.readbyqxmd.com/read/29769335/bag2-is-a-component-of-a-cytosolic-extraction-machinery-that-promotes-membrane-penetration-of-a-nonenveloped-virus
#2
Allison Dupzyk, Billy Tsai
During entry, the nonenveloped polyomavirus (PyV) SV40 traffics from the cell surface to the endoplasmic reticulum (ER) where it penetrates the ER membrane to reach the cytosol; the virus then transports into the nucleus to cause infection. Although a coherent understanding of SV40's host entry is emerging, how the virus is ejected from the ER into the cytosol remains mysterious. Our previous analyses revealed that the cytosolic Hsc70-SGTA-Hsp105 complex binds to and extracts SV40 from the ER into the cytosol...
May 16, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29760693/treatment-intensification-in-hiv-infected-patients-is-associated-with-reduced-frequencies-of-regulatory-t-cells
#3
Eva M Grützner, Tanja Hoffmann, Eva Wolf, Elke Gersbacher, Ashley Neizert, Renate Stirner, Ramona Pauli, Albrecht Ulmer, Jürgen Brust, Johannes R Bogner, Hans Jaeger, Rika Draenert
In untreated HIV infection, the efficacy of T cell responses decreases over the disease course, resulting in disease progression. The reasons for this development are not completely understood. However, immunosuppressive cells are supposedly crucially involved. Treatment strategies to avoid the induction of these cells preserve immune functions and are therefore the object of intense research efforts. In this study, we assessed the effect of treatment intensification [=5-drug antiretroviral therapy (ART)] on the development of suppressive cell subsets...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29735715/znrf3-functions-in-mammalian-sex-determination-by-inhibiting-canonical-wnt-signaling
#4
Abigail Harris, Pam Siggers, Silvia Corrochano, Nick Warr, Danielle Sagar, Daniel T Grimes, Makoto Suzuki, Rebecca D Burdine, Feng Cong, Bon-Kyoung Koo, Hans Clevers, Isabelle Stévant, Serge Nef, Sara Wells, Raja Brauner, Bochra Ben Rhouma, Neïla Belguith, Caroline Eozenou, Joelle Bignon-Topalovic, Anu Bashamboo, Ken McElreavey, Andy Greenfield
Mammalian sex determination is controlled by the antagonistic interactions of two genetic pathways: The SRY-SOX9-FGF9 network promotes testis determination partly by opposing proovarian pathways, while RSPO1/WNT-β-catenin/FOXL2 signals control ovary development by inhibiting SRY-SOX9-FGF9. The molecular basis of this mutual antagonism is unclear. Here we show that ZNRF3, a WNT signaling antagonist and direct target of RSPO1-mediated inhibition, is required for sex determination in mice. XY mice lacking ZNRF3 exhibit complete or partial gonadal sex reversal, or related defects...
May 7, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29682200/small-molecule-cxcr4-antagonists-block-the-hiv-1-nef-cxcr4-axis-and-selectively-initiate-the-apoptotic-program-in-breast-cancer-cells
#5
Ming-Bo Huang, Kyle E Giesler, Brooke M Katzman, Anthony R Prosser, Valarie Truax, Dennis C Liotta, Lawrence J Wilson, Vincent C Bond
The chemokine receptor CXCR4 plays an integral role in the development of highly metastatic breast cancer and in the pathogenesis of chronic HIV infection. In this study, we compared the effects of CXCR4 antagonists on apoptosis induction in hematopoietic cells and in tumor cells. We incubated cells expressing CXCR4 with a series of CXCR4 antagonists and subsequently exposed the cultures to a pro-apoptotic peptide derived from the HIV-1 Nef protein (NefM1). The NefM1 peptide contains residues 50-60 of Nef and was previously shown to be the sequence necessary for Nef to initiate the apoptotic program through CXCR4 signaling...
March 30, 2018: Oncotarget
https://www.readbyqxmd.com/read/29679260/slow-release-of-hiv-1-protein-nef-from-vesicle-like-structures-is-inhibited-by-cytosolic-calcium-elevation-in-single-human-microglia
#6
Matjaž Stenovec, Eva Lasič, Pia Pužar Dominkuš, Saša Trkov Bobnar, Robert Zorec, Metka Lenassi, Marko Kreft
Once infected by HIV-1, microglia abundantly produce accessory protein Nef that enhances virus production and infectivity, but little is known about its intracellular compartmentalization, trafficking mode(s), and release from microglia. Here, we transfected immortalized human microglia with a plasmid encoding Nef tagged with green fluorescent protein (Nef.GFP) to biochemically and microscopically identify Nef.GFP-associated cellular compartments and examine their mobility and Nef release from cultured cells...
April 21, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29669829/incomplete-downregulation-of-cd4-expression-affects-hiv-1-env-conformation-and-adcc-responses
#7
Jérémie Prévost, Jonathan Richard, Halima Medjahed, Audrey Alexander, Jennifer Jones, John C Kappes, Christina Ochsenbauer, Andrés Finzi
HIV-1 infected cells expressing envelope glycoproteins (Env) in the CD4-bound conformation on their surface are targeted by antibody-dependent cellular cytotoxicity (ADCC) mediated by CD4-induced (CD4i) antibodies and HIV+ sera. By downregulating the surface expression of CD4, Nef prevents Env-CD4 interaction thus protecting HIV-1-infected cells from ADCC. HIV-1 infectious molecular clones (IMC) are widely used to measure ADCC. In order to facilitate the identification of infected cells and high-throughput ADCC analysis, reporter genes (e...
April 18, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29664970/correction-a-single-%C3%AE-octyl-glucoside-molecule-induces-hiv-1-nef-dimer-formation-in-the-absence-of-partner-protein-binding
#8
(no author information available yet)
[This corrects the article DOI: 10.1371/journal.pone.0192512.].
2018: PloS One
https://www.readbyqxmd.com/read/29663512/specific-biomarkers-of-myocardial-inflammation-and-remodeling-processes-as-predictors-of-mortality-in-high-risk-patients-undergoing-percutaneous-mitral-valve-repair-mitraclip
#9
Oliver Dörr, Claudia Walther, Christoph Liebetrau, Till Keller, Hannes Tabert, Niklas Boeder, Matthias Bayer, Pascal Bauer, Helge Möllmann, Luise Gaede, Christian Troidl, Sandra Voss, Timm Bauer, Christian W Hamm, Holger Nef
BACKGROUND: Specific matrix metalloproteinases (MMP-2, MMP-9) and inflammatory biomarkers (hsCRP, IL-6) were found to be consistently up-regulated in severe mitral valve regurgitation (MR) and are associated with mortality in heart failure patients. The aim of the present study was to examine the prognostic value of biomarkers of cardiac inflammation and remodeling processes in predicting mortality in patients with MR undergoing percutaneous mitral valve repair (PMVR). HYPOTHESIS: We hypothesize that increased cardiac inflammation and extracellular matrix turnover is predictive for mortality in patients with severe mitral regurgitation undergoing MitraClip...
April 17, 2018: Clinical Cardiology
https://www.readbyqxmd.com/read/29661911/patl2-is-a-key-actor-of-oocyte-maturation-whose-invalidation-causes-infertility-in-women-and-mice
#10
Marie Christou-Kent, Zine-Eddine Kherraf, Amir Amiri-Yekta, Emilie Le Blévec, Thomas Karaouzène, Béatrice Conne, Jessica Escoffier, Said Assou, Audrey Guttin, Emeline Lambert, Guillaume Martinez, Magalie Boguenet, Selima Fourati Ben Mustapha, Isabelle Cedrin Durnerin, Lazhar Halouani, Ouafi Marrakchi, Mounir Makni, Habib Latrous, Mahmoud Kharouf, Charles Coutton, Nicolas Thierry-Mieg, Serge Nef, Serge P Bottari, Raoudha Zouari, Jean Paul Issartel, Pierre F Ray, Christophe Arnoult
The genetic causes of oocyte meiotic deficiency (OMD), a form of primary infertility characterised by the production of immature oocytes, remain largely unexplored. Using whole exome sequencing, we found that 26% of a cohort of 23 subjects with OMD harboured the same homozygous nonsense pathogenic mutation in PATL2 , a gene encoding a putative RNA-binding protein. Using Patl2 knockout mice, we confirmed that PATL2 deficiency disturbs oocyte maturation, since oocytes and zygotes exhibit morphological and developmental defects, respectively...
April 16, 2018: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/29652795/counteracting-akt-activation-by-hiv-protease-inhibitors-in-monocytes-macrophages
#11
Sébastien Pasquereau, Amit Kumar, Wasim Abbas, Georges Herbein
Akt signaling plays a central role in many biological processes that are key players in human immunodeficiency virus 1 (HIV-1) pathogenesis. The persistence of latent reservoirs in successfully treated patients, mainly located in macrophages and latently infected resting CD4+ T cells, remains a major obstacle in HIV-1 eradication. We assessed the in vitro effects of an HIV protease inhibitor (PI) and a non-nucleoside reverse transcriptase inhibitor (NNRTI) on HIV-1 Nef-induced Akt activation in macrophages and on HIV-1 reactivation in U1 monocytoid cells...
April 13, 2018: Viruses
https://www.readbyqxmd.com/read/29649071/predictors-of-early-scaffold-thrombosis-results-from-the-multicenter-prospective-german-austrian-absorb-registry
#12
Jochen Wöhrle, Holger M Nef, Christoph Naber, Stephan Achenbach, Thomas Riemer, Julinda Mehilli, Thomas Münzel, Steffen Schneider, Sinisa Markovic, Julia Seeger, Wolfgang Rottbauer, Thomas Pfannebecker, Gert Richardt, Ralf Zahn, Tommaso Gori, Johannes Kastner, Axel Schmermund, Christian W Hamm
BACKGROUND: In randomized clinical trials, the risk of thrombotic events with the absorb bioresorbable vascular scaffold (BVS) was significantly higher than with metallic drug-eluting stents. We evaluated predictors of scaffold thrombosis in the large-scale, multicenter German-Austrian ABSORB RegIstRy. METHODS AND RESULTS: 3178 patients with treatment of 4252 lesions using 5020 scaffolds were included. Follow-up rate at 6 months was 97.4%. Forty-five (1.42%) patients experienced definite/probable scaffold thrombosis during follow-up...
April 11, 2018: Coronary Artery Disease
https://www.readbyqxmd.com/read/29643760/a-comparison-of-low-complexity-real-time-feature-extraction-for-neuromorphic-speech-recognition
#13
Jyotibdha Acharya, Aakash Patil, Xiaoya Li, Yi Chen, Shih-Chii Liu, Arindam Basu
This paper presents a real-time, low-complexity neuromorphic speech recognition system using a spiking silicon cochlea, a feature extraction module and a population encoding method based Neural Engineering Framework (NEF)/Extreme Learning Machine (ELM) classifier IC. Several feature extraction methods with varying memory and computational complexity are presented along with their corresponding classification accuracies. On the N-TIDIGITS18 dataset, we show that a fixed bin size based feature extraction method that votes across both time and spike count features can achieve an accuracy of 95% in software similar to previously report methods that use fixed number of bins per sample while using ~3× less energy and ~25× less memory for feature extraction (~1...
2018: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/29622141/clinical-angiographic-and-procedural-correlates-of-very-late-absorb-scaffold-thrombosis-multistudy-registry-results
#14
Stephen G Ellis, Tommaso Gori, Patrick W Serruys, Holger Nef, Giuseppe Steffenino, Salvatore Brugaletta, Thomas Munzel, Cordula Feliz, Götz Schmidt, Manel Sabaté, Yoshinobu Onuma, R J van Geuns, Run-Lin Gao, Maurizio Menichelli, Dean J Kereiakes, Gregg W Stone, Luca Testa, Takeshi Kimura, Alexandre Abizaid
OBJECTIVES: The aim of this study was to identify independent correlates of very late scaffold thrombosis (VLST) from an analysis of consecutively treated patients from 15 multicenter studies. BACKGROUND: Recent analyses suggest an increased risk for VLST with the Absorb Bioresorbable Vascular Scaffold compared with drug-eluting stents, but insights as to correlates of risk are limited. METHODS: A total of 55 patients were identified with scaffold thrombosis...
April 9, 2018: JACC. Cardiovascular Interventions
https://www.readbyqxmd.com/read/29608912/glomerular-mitochondrial-changes-in-hiv-associated-renal-injury
#15
Joseph L Bryant, Poornachander R Guda, Girma Asemu, Rogin Subedi, Sugata Ray, Omar S Khalid, Vivek Shukla, Dhruvil Patel, Harry Davis, Vamshi K C Nimmagadda, Tapas K Makar
HIV-associated nephropathy (HIVAN) is an AIDs-related disease of the kidney. HIVAN is characterized by severe proteinuria, podocyte hyperplasia, collapse, glomerular, and tubulointerstitial damage. HIV-1 transgenic (Tg26) mouse is the most popular model to study the HIV manifestations that develop similar renal presentations as HIVAN. Viral proteins, including Tat, Nef, and Vpr play a significant role in renal cell damage. It has been shown that mitochondrial changes are involved in several kidney diseases, and therefore, mitochondrial dysfunction may be implicated in the pathology of HIVAN...
March 30, 2018: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/29600767/identification-and-characterization-of-positively-selected-mutations-in-nef-of-four-hiv-1-major-subtypes-from-los-alamos-national-laboratory
#16
Elnaz Shadabi, Binhua Liang, Francis A Plummer, Ma Luo
BACKGROUND: Human immunodeficiency virus-1 (HIV-1) mutates rapidly to escape host immune pressure. This results in the generation of positively selected mutations (PSM) throughout the viral genome. Escape mutations in Nef, one of the accessory proteins of HIV-1, which plays an important role in viral pathogenicity have previously been identified in several large cohort studies, but the evolution of PSMs overtime in various HIV-1 subtypes remains unknown. METHODS: 161 clade A1, 3093 clade B, 647 clade C and 115 clade D HIV-1 nef sequences were obtained from the HIV Database of Los Alamos National Laboratory and aligned using MEGA 6...
March 30, 2018: Current HIV Research
https://www.readbyqxmd.com/read/29588370/intrinsic-properties-and-plasma-membrane-trafficking-route-of-src-family-kinase-sh4-domains-sensitive-to-retargeting-by-hiv-1-nef
#17
Amanda J Chase, Rebecka Wombacher, Oliver T Fackler
The HIV-1 pathogenicity factor Nef enhances viral replication by modulating multiple host cell pathways, including tuning the activation state of infected CD4 T lymphocytes to optimize virus spread. For this, Nef inhibits anterograde transport of the Src family kinase (SFK) Lck toward the plasma membrane (PM). This leads to retargeting of the kinase to the trans-Golgi network (TGN), while the intracellular transport of a related SFK, Fyn, is unaffected by Nef. The 18 amino acid SH4 domain membrane anchor of Lck is necessary and sufficient for Nef-mediated retargeting, but other details of this process are not known...
March 27, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29570055/a-low-power-current-reuse-analog-front-end-for-high-density-neural-recording-implants
#18
Masoud Rezaei, Esmaeel Maghsoudloo, Cyril Bories, Yves De Koninck, Benoit Gosselin
Studying brain activity in vivo requires collecting bioelectrical signals from several microelectrodes simultaneously in order to capture neuron interactions. In this work, we present a new current-reuse analog front-end (AFE), which is scalable to very large numbers of recording channels, thanks to its small implementation silicon area and its low-power consumption. This current-reuse AFE, which is including a low-noise amplifier (LNA) and a programmable gain amplifier (PGA), employs a new fully differential current-mirror topology using fewer transistors, and improving several design parameters, such as power consumption and noise, over previous current-reuse amplifier circuit implementations...
April 2018: IEEE Transactions on Biomedical Circuits and Systems
https://www.readbyqxmd.com/read/29562571/value-of-three-dimensional-speckle-tracking-imaging-for-predicting-left-ventricular-function-after-non-st-segment-elevation-myocardial-infarction-with-percutaneous-coronary-intervention
#19
Yongjuan Luo, Yujie Liu, Xin Guan, Ying Zhang, Jing Li
BACKGROUND: Percutaneous coronary intervention (PCI) is the recommended treatment for high risk patients with non-ST-segment elevation myocardial infarction (NSTEMI). OBJECTIVE: To investigate the application of three dimensional-speckle tracking imaging (3D-STI) on patients diagnosed with NSTEMI undergoing PCI. METHODS: Forty-four NSTEMI patients and 20 healthy subjects that received basic clinical and laboratory examinations were included in our study...
2018: Journal of X-ray Science and Technology
https://www.readbyqxmd.com/read/29559570/uninfected-bystander-cells-impact-the-measurement-of-hiv-specific-antibody-dependent-cellular-cytotoxicity-responses
#20
Jonathan Richard, Jérémie Prévost, Amy E Baxter, Benjamin von Bredow, Shilei Ding, Halima Medjahed, Gloria G Delgado, Nathalie Brassard, Christina M Stürzel, Frank Kirchhoff, Beatrice H Hahn, Matthew S Parsons, Daniel E Kaufmann, David T Evans, Andrés Finzi
The conformation of the HIV-1 envelope glycoprotein (Env) substantially impacts antibody recognition and antibody-dependent cellular cytotoxicity (ADCC) responses. In the absence of the CD4 receptor at the cell surface, primary Envs sample a "closed" conformation that occludes CD4-induced (CD4i) epitopes. The virus controls CD4 expression through the actions of Nef and Vpu accessory proteins, thus protecting infected cells from ADCC responses. However, gp120 shed from infected cells can bind to CD4 present on uninfected bystander cells, sensitizing them to ADCC mediated by CD4i antibodies (Abs)...
March 20, 2018: MBio
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