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https://www.readbyqxmd.com/read/28530637/cell-penetrating-peptides-selectively-targeting-smad3-inhibit-profibrotic-tgf-%C3%AE-signaling
#1
Jeong-Han Kang, Mi-Yeon Jung, Xueqian Yin, Mahefatiana Andrianifahanana, Danielle M Hernandez, Edward B Leof
TGF-β is considered a master switch in the pathogenesis of organ fibrosis. The primary mediators of this activity are the SMAD proteins, particularly SMAD3. In the current study, we have developed a cell-penetrating peptide (CPP) conjugate of the HIV TAT protein that is fused to an aminoterminal sequence of sorting nexin 9 (SNX9), which was previously shown to bind phosphorylated SMAD3 (pSMAD3). We determined that specifically preventing the nuclear import of pSMAD3 using the TAT-SNX9 peptide inhibited profibrotic TGF-β activity in murine cells and human lung fibroblasts as well as in vivo with no demonstrable toxicity...
May 22, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28522581/conformational-dynamics-of-the-frameshift-stimulatory-structure-in-hiv-1
#2
Dustin B Ritchie, Tonia R Cappellano, Collin Tittle, Negar Rezajooei, Logan Rouleau, William Ka Sikkema, Michael T Woodside
Programmed ribosomal frameshifting (PRF) in HIV-1 is thought to be stimulated by a hairpin in the mRNA, although a pseudoknot-like triplex has also been proposed. Because the conformational dynamics of the stimulatory structure under tension applied by the ribosomal helicase during translation may play an important role in PRF, we used optical tweezers to apply tension to the HIV stimulatory structure and monitor its unfolding and refolding dynamics. The folding and unfolding kinetics and energy landscape of the hairpin were measured by ramping the force on the hairpin up and down, providing a detailed biophysical characterisation...
May 18, 2017: RNA
https://www.readbyqxmd.com/read/28521213/phylogenetic-analysis-of-an-epidemic-outbreak-of-acute-hepatitis-c-in-hiv-infected-patients-by-ultra-deep-pyrosequencing
#3
Noelia Caro-Pérez, María Martínez-Rebollar, Josep Gregori, Josep Quer, Patricia González, Martina Gambato, Neris García-González, Fernando González-Candelas, Josep Costa, Juan Ignacio Esteban, Josep Mallolas, Xavier Forns, Montse Laguno, Sofía Pérez-Del-Pulgar
BACKGROUND: The incidence of acute hepatitis C (AHC) among HIV-infected men who have sex with men (MSM) has increased significantly in the last 10 years. Several studies point to a social and sexual network of HIV-positive MSM that extends internationally. OBJECTIVES: The aim of our study was to investigate the dynamics of HCV transmission in an outbreak of AHC in HIV-infected MSM in Barcelona by ultra-deep pyrosequencing. STUDY DESIGN: Between 2008 and 2013, 113 cases of AHC in HIV-infected MSM were diagnosed in the Infectious Diseases Unit, Hospital Clínic, Barcelona...
May 10, 2017: Journal of Clinical Virology: the Official Publication of the Pan American Society for Clinical Virology
https://www.readbyqxmd.com/read/28515481/conserved-presence-of-g-quadruplex-forming-sequences-in-the-long-terminal-repeat-promoter-of-lentiviruses
#4
Rosalba Perrone, Enrico Lavezzo, Giorgio Palù, Sara N Richter
G-quadruplexes (G4s) are secondary structures of nucleic acids that epigenetically regulate cellular processes. In the human immunodeficiency lentivirus 1 (HIV-1), dynamic G4s are located in the unique viral LTR promoter. Folding of HIV-1 LTR G4s inhibits viral transcription; stabilization by G4 ligands intensifies this effect. Cellular proteins modulate viral transcription by inducing/unfolding LTR G4s. We here expanded our investigation on the presence of LTR G4s to all lentiviruses. G4s in the 5'-LTR U3 region were completely conserved in primate lentiviruses...
May 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28514279/impact-of-alemtuzumab-on-hiv-persistence-in-an-hiv-infected-individual-on-antiretroviral-therapy-with-sezary-syndrome
#5
Thomas Aagaard Rasmussen, James McMahon, J Judy Chang, Jori Symons, Michael Roche, Ashanti Dantanarayana, Afam Okoye, Bonnie Hiener, Sarah Palmer, Wen Shi Lee, Stephen Kent, Carrie Van Der Weyden, H Miles Prince, Paul U Cameron, Sharon R Lewin
OBJECTIVE: To study the effects of alemtuzumab on HIV persistence in an HIV-infected individual on antiretroviral therapy (ART) with Sezary syndrome, a rare malignancy of CD4+ T-cells DESIGN:: Case report. METHODS: Blood was collected 30 and 18 months prior to presentation with Sezary syndrome, at the time of presentation and during alemtuzumab. T-cell subsets in malignant (CD7-CD26-TCR-VBeta2+) and non-malignant cells were quantified by flow cytometry. HIV-DNA in total CD4+ T-cells, in sorted malignant and non-malignant CD4+ T-cells was quantified by PCR and clonal expansion of HIV-DNA assessed by full-length next-generation sequencing...
May 16, 2017: AIDS
https://www.readbyqxmd.com/read/28513635/the-impact-of-dark-chocolate-intake-on-arterial-elasticity-in-individuals-with-hiv-aids-undergoing-art-a-randomized-double-blind-crossover-trial
#6
Andrea Mariana Nunes da Costa Teixeira, Liania Alves Luzia, Suelen Jorge de Souza, Aline de Almeida Petrilli, Patrícia de Moraes Pontilho, Jose Maria Pacheco de Souza, Aluísio Augusto Cotrim Segurado, Priscila Efraim, Camila de Melo Picone, Patrícia Helen de Carvalho Rondo
An increase in the frequency of cardiovascular diseases has been observed in the HIV/AIDS population. Studies involving healthy subjects or subjects with other diseases have shown benefits of chocolate supplementation on endothelial function and vasodilation. We evaluate the impact of chocolate consumption on arterial elasticity in people living with human immunodeficiency virus - PLHIV. A double-blind, crossover trial including 110 PLHIV (19 to 59 years) on antiretroviral therapy - ART for at least 6 months and with a viral load of <500 copies per mL was conducted...
May 17, 2017: Food & Function
https://www.readbyqxmd.com/read/28513417/carriage-of-extended-spectrum-beta-lactamase-producing-enterobacteriaceae-in-hiv-infected-children-in-zimbabwe
#7
S M S Wilmore, K Kranzer, A Williams, B Makamure, A F Nhidza, J Mayini, T Bandason, J Metcalfe, M P Nicol, I Balakrishnan, M J Ellington, N Woodford, S Hopkins, T D McHugh, R A Ferrand
BACKGROUND: Antimicrobial resistance is an emerging global health issue. Data on the epidemiology of multidrug-resistant organisms are scarce for Africa, especially in HIV-infected individuals who often have frequent contact with healthcare. We investigated the prevalence of extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) carriage in stool among HIV-infected children attending an HIV outpatient department in Harare, Zimbabwe. METHODS: We recruited children who were stable on antiretroviral therapy (ART) attending a HIV clinic from August 2014 to June 2015...
May 2017: Journal of Medical Microbiology
https://www.readbyqxmd.com/read/28511091/molecular-cloning-and-characterization-of-dngr-1-in-rhesus-macaques
#8
Wen-Rong Yao, Lei Yu, Dong Li, Gui-Bo Yang
DC, NK lectin group receptor-1 (DNGR-1), also known as C-type lectin domain family 9 member A (CLEC9A), is a promising target for immunological therapeutics and vaccination against tumors and viruses. However, little is known about its property in rhesus macaques. In this study, we cloned rhesus macaque DNGR-1 cDNA, and found that its coding region could encode a 241-amino acid polypeptide with 91.7% sequence identity and similar antigenicity to that of humans. Both free and cell surface rhesus macaque DNGR-1 expressed in vitro could bind to apoptotic/dead cells induced by serum deprivation or freeze-thaw, and to pyroptotic cells stimulated with PMA and LPS...
May 13, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28509569/hiv-1-crf07_bc-with-a-seven-amino-acid-deletion-in-the-gag-p6-region-dominates-in-hiv-1-infected-men-who-have-sex-with-men-in-china
#9
Yue Wu, Haiying Wang, Xuqi Ren, Zhengwei Wan, Guifang Hu, Shixing Tang
We examined sequence variation in the HIV-1 gag p6 region from 27 individuals infected with HIV-1 CRF07_BC. An additional 269 gag p6 sequences of CRF07_BC from the Los Alamos National Laboratory database were also analyzed. A unique deletion of seven amino acid (aa) (p6Δ7) (aa 30-36, PIDKELY, in the HXB2 genome) was observed to exist exclusively in CRF07_BC. Indeed, 54.1% (160/296) of the CRF07_BC sequences contained the p6Δ7 mutation. The prevalence of the p6Δ7 mutation was 37.2% (29/78) and 92.3% (48/52) in CRF07_BC-infected intravenous drug users and men who have sex with men (MSM), respectively...
May 16, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28508728/high-frequency-of-identical-clonal-immunoglobulin-dna-in-pre-treatment-tumor-and-plasma-from-untreated-patients-with-hiv-associated-lymphoma-prospective-multicenter-trial-of-the-aids-malignancies-consortium-amc-064
#10
Nina D Wagner-Johnston, Shelly Lensing, Ariela Noy, Lee Ratner, David Henry, Jeannette Y Lee, Sylvia Silver, Malek Faham, Richard F Ambinder
Patients with HIV are at increased risk for developing B-cell lymphomas likely due in part to chronic antigen stimulation leading to clonal immunoglobulin (Ig) gene rearrangements. Next-generation sequencing (NGS)-based identification of circulating Ig clonotypes has not been well-characterized in HIV-related lymphomas. The AIDS Malignancies Consortium (AMC) enrolled 51 untreated patients with HIV-related B-cell lymphomas and analyzed paired tumor/plasma specimens for Ig clonotypes using an NGS approach (AMC064, NCT00981097)...
May 16, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28505418/how-mutations-can-resist-drug-binding-yet-keep-hiv-1-protease-functional
#11
Rajeswari Appadurai, Sanjib Senapati
HIV-1 protease is an important drug target for AIDS therapy. Nearly ten small molecule drugs have been approved by FDA. However, prolonged usage of these drugs produced protease mutants that are insusceptible to many of these drugs. The mutated proteases however continue to cleave the substrate peptides and thus remain largely functional. This poses a major challenge in the treatment strategies. Thus it has become imperative to understand how these mutations induce drug resistance while maintaining the enzymatic activity of this protein...
May 15, 2017: Biochemistry
https://www.readbyqxmd.com/read/28505234/increased-risk-for-meningococcal-disease-among-men-who-have-sex-with-men-in-the-united-states-2012-2015
#12
Temitope A Folaranmi, Cecilia B Kretz, Hajime Kamiya, Jessica R MacNeil, Melissa J Whaley, Amy Blain, Mike Antwi, Marie Dorsinville, Massimo Pacilli, Shamika Smith, Rachel Civen, Van Ngo, Kathleen Winter, Kathleen Harriman, Xin Wang, Virginia B Bowen, Manisha Patel, Stacey Martin, Lara Misegades, Sarah A Meyer
Background: Several clusters of serogroup C meningococcal disease among men who have sex with men (MSM) have been reported in the United States in recent years. The epidemiology and risk of meningococcal disease among MSM is not well-described. Methods: All meningococcal disease cases among men aged 18-64 years reported to the National Notifiable Disease Surveillance System between January 2012 and June 2015 were reviewed. Characteristics of meningococcal disease cases among MSM and men not known to be MSM (non-MSM) were described...
May 13, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28503428/soluble-expression-of-recomb-inant-cmyc-klf4-oct4-and-sox2-proteins-in-bacteria-and-transduction-into-living-cells
#13
Guo-Dan Liu, Shi-Feng Zhou, Xu-Chen Ding, Chun-Lai Fang, Shu-Yong Mi, Xiang-Chun Gao, Qing Han
AIM: To develop a new method to produce recombinant reprogramming proteins, cMyc, Klf4, Oct4, and Sox2, in soluble format with low cost for the generation of induced pluripotent stem cells (iPSCs). METHODS: A short polypeptide sequence derived from the HIV trans-activator of transcription protein (TAT) and the nucleus localization signal (NLS) polypeptide were fused to the N terminus of the reprogramming proteins and they were constructed into pCold-SUMO vector which can extremely improve the solubility of recombinant proteins...
2017: International Journal of Ophthalmology
https://www.readbyqxmd.com/read/28503119/targeting-hiv-1-envelope-proteins-using-a-fragment-discovery-all-atom-computational-algorithm
#14
Michael H Peters
INTRODUCTION: HIV viral envelope proteins are targets for small inhibitor molecules aimed at disrupting the cellular entry process. Potential peptide-class inhibitor molecules (rDNA drugs) have been previously identified, with mixed results, through biomimicry and phage display experimental methods. Here we describe a new approach based on computational fragment discovery. The method has the potential to not only optimize peptide binding affinity but also to rapidly produce alternative inhibitors against mutated strains...
April 2017: Current Enzyme Inhibition
https://www.readbyqxmd.com/read/28502791/single-strand-consensus-sequencing-reveals-that-hiv-type-but-not-subtype-significantly-impacts-viral-mutation-frequencies-and-spectra
#15
Jonathan M O Rawson, Daryl M Gohl, Sean R Landman, Megan E Roth, Morgan E Meissner, Tara S Peterson, James S Hodges, Kenneth B Beckman, Louis M Mansky
A long-standing question of human immunodeficiency virus (HIV) genetic variation and evolution has been whether differences exist in mutation rate and/or mutation spectra among HIV types (i.e., HIV-1 versus HIV-2) as well as among HIV groups (i.e., HIV-1 groups M-P and HIV-2 groups A-H) and HIV-1 Group M subtypes (i.e., subtypes A-D, F-H, and J-K). To address this, a new single-strand consensus sequencing assay was developed for the determination of HIV mutation frequencies and spectra using the Illumina sequencing platform...
May 11, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28500746/higher-viral-load-and-genetic-diversity-of-hiv-1-in-the-seminal-compartments-than-in-the-blood-of-seven-chinese-homosexual-men-with-early-hiv-1-infection
#16
Yan-Mei Jiao, Guang-Lei Chen, Wei-Jun Zhu, Hui-Huang Huang, Jun-Liang Fu, Wei-Wei Chen, Ming Shi, Tong Zhang, Hao Wu, Fu-Sheng Wang
To date, there have been no reports characterizing the Human Immunodeficiency Virus-1 (HIV-1) in the semen of Chinese men having sex with men (MSM) with early infection of HIV-1.We examined genetic diversity and viral load of HIV-1 in the seminal compartments and blood of Chinese MSM with early HIV-1 infection in this study. Viral load and genetic diversity of HIV-1 in paired samples of semen and blood were analyzed in seven homosexual patients who were with early HIV-1 infection. Levels of HIV-1 RNA and DNA were tested by real-time PCR assays...
May 13, 2017: Microbiology and Immunology
https://www.readbyqxmd.com/read/28500726/mutations-associated-with-drug-resistance-and-prevalence-of-vaccine-escape-mutations-in-patients-with-chronic-hepatitis-b-infection
#17
Maria Isabel Magalhães A Dos Santos, Sidelcina Pacheco Rugiere, Andreas Stocker, Maria Isabel Schinoni, Raymundo Paraná, Mitermayer G Reis, Luciano K Silva
BACKGROUND: The Brazilian public health system (SUS) has provided antiviral drugs for chronic hepatitis B treatment for over 10 years, but a system for monitoring for drug-related resistance mutations is not available. OBJECTIVES: Determine the presence of HBV mutations associated with resistance to nucleos(t)ide analogs among 81 patients with chronic HBV infection in Salvador - BA - Brazil. STUDY DESIGN: HBV-DNA was PCR amplified with primers deduced from the rt domain at the HBV P gene, the sequence extended 1032 bp (from amino acid 1 to 344 - rt domain)...
May 13, 2017: Journal of Medical Virology
https://www.readbyqxmd.com/read/28499845/exploring-resistance-pathways-for-first-generation-ns3-4a-protease-inhibitors-boceprevir-and-telaprevir-using-bayesian-network-learning
#18
Lize Cuypers, Pieter Libin, Yoeri Schrooten, Kristof Theys, Velia Chiara Di Maio, Valeria Cento, Maja M Lunar, Frederik Nevens, Mario Poljak, Francesca Ceccherini-Silberstein, Ann Nowé, Kristel Van Laethem, Anne-Mieke Vandamme
Resistance-associated variants (RAVs) have been shown to influence treatment response to direct-acting antivirals (DAAs) and first generation NS3/4A protease inhibitors (PIs) in particular. Interpretation of hepatitis C virus (HCV) genotypic drug resistance remains a challenge, especially in patients who previously failed DAA therapy and need to be retreated with a second DAA based regimen. Bayesian network (BN) learning on HCV sequence data from patients treated with DAAs could provide insight in resistance pathways against PIs for HCV subtypes 1a and 1b, in a similar way as applied before for HIV...
May 9, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/28499138/human-pegivirus-1-in-the-csf-of-patients-with-hiv-associated-neurocognitive-disorder-hand-may-be-derived-from-blood-in-highly-viraemic-patients
#19
Diana Hardie, Heidi Smuts
BACKGROUND: Human pegivirus-1 (HPgV-1) infection in the brain has not been extensively examined and its association with disease remains unconfirmed. In a high throughput sequencing study to look for infectious agents that could play a role in HIV-associated neurocognitive disorder (HAND), this virus was detected in 3 of 8 CSF samples. OBJECTIVES: To determine the significance of this finding, additional patients were screened and the viral load and viral diversity in blood and CSF were examined...
April 6, 2017: Journal of Clinical Virology: the Official Publication of the Pan American Society for Clinical Virology
https://www.readbyqxmd.com/read/28494325/hiv-1-integrase-inhibitor-resistance-among-treatment-na%C3%A3-ve-patients-in-the-west-of-scotland
#20
A Bradley-Stewart, C Urcia, A MacLean, C Aitken, R Gunson
BACKGROUND: Transmitted integrase inhibitor resistance is rare, with only a small number of cases reported world-wide to date. OBJECTIVES: The aim of this study was to assess whether transmitted integrase inhibitor resistance has occurred in Scotland and if so, could there be a case for performing genotypic integrase resistance testing at baseline. STUDY DESIGN: The study population consisted of 106 treatment naïve, newly diagnosed, HIV positive patients...
April 23, 2017: Journal of Clinical Virology: the Official Publication of the Pan American Society for Clinical Virology
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