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https://www.readbyqxmd.com/read/29789565/the-wide-utility-of-rabbits-as-models-of-human-diseases
#1
REVIEW
Pedro J Esteves, Joana Abrantes, Hanna-Mari Baldauf, Lbachir BenMohamed, Yuxing Chen, Neil Christensen, Javier González-Gallego, Lorenzo Giacani, Jiafen Hu, Gilla Kaplan, Oliver T Keppler, Katherine L Knight, Xiang-Peng Kong, Dennis K Lanning, Jacques Le Pendu, Ana Lemos de Matos, Jia Liu, Shuying Liu, Ana M Lopes, Shan Lu, Sheila Lukehart, Yukari C Manabe, Fabiana Neves, Grant McFadden, Ruimin Pan, Xuwen Peng, Patricia de Sousa-Pereira, Ana Pinheiro, Masmudur Rahman, Natalie Ruvoën-Clouet, Selvakumar Subbian, Maria Jesús Tuñón, Wessel van der Loo, Michael Vaine, Laura E Via, Shixia Wang, Rose Mage
Studies using the European rabbit Oryctolagus cuniculus contributed to elucidating numerous fundamental aspects of antibody structure and diversification mechanisms and continue to be valuable for the development and testing of therapeutic humanized polyclonal and monoclonal antibodies. Additionally, during the last two decades, the use of the European rabbit as an animal model has been increasingly extended to many human diseases. This review documents the continuing wide utility of the rabbit as a reliable disease model for development of therapeutics and vaccines and studies of the cellular and molecular mechanisms underlying many human diseases...
May 22, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29787233/controlling-the-replication-of-a-genomically-recoded-hiv-1-with-a-functional-quadruplet-codon-in-mammalian-cells
#2
Yan Chen, Yanmin Wan, Nanxi Wang, Zhe Yuan, Wei Niu, Qingsheng Li, Jiantao Guo
Large efforts have been devoted to the genetic code engineering in the past decade, aiming for unnatural amino acid mutagenesis. Recently, an increasing number of studies were reported to employ quadruplet codons to encode unnatural amino acids. We and others have demonstrated that the quadruplet decoding efficiency could be significantly enhanced by an extensive engineering of tRNAs bearing an extra nucleotide in their anticodon loops. In this work, we report the identification of tRNA mutants derived from directed evolution to efficiently decode a UAGA quadruplet codon in mammalian cells...
May 22, 2018: ACS Synthetic Biology
https://www.readbyqxmd.com/read/29785877/hepatitis-b-virus-lymphotropism-emerging-details-and-challenges
#3
Shivali S Joshi, Carla S Coffin
The hepatitis B virus (HBV) is predominantly a hepatotropic virus but also infects cells of the lymphatic system. HBV genomes (DNA, messenger (m)RNA, covalently closed circular (ccc) DNA) and proteins have been found in extrahepatic sites such as peripheral blood mononuclear cells (PBMC), lymph nodes, spleen, bone marrow and cerebrospinal fluid. HBV entry into hepatocytes occurs by binding of the HBV preS1 surface protein to its specific receptor, the bile acid transporter, sodium taurocholate co-transporting polypeptide (NTCP)...
May 22, 2018: Biotechnology & Genetic Engineering Reviews
https://www.readbyqxmd.com/read/29769038/impact-of-new-daa-therapy-on-real-clinical-practice-a-multicenter-region-wide-cohort-study
#4
Simone Lanini, Paola Scognamiglio, Alessandra Mecozzi, Lorella Lombardozzi, Vincenzo Vullo, Mario Angelico, Antonio Gasbarrini, Gloria Taliani, Adolfo Francesco Attili, Carlo Federico Perno, Adriano De Santis, Vincenzo Puro, Fabio Cerqua, Gianpiero D'Offizi, Adriano Pellicelli, Orlando Armignacco, Francesco Saverio Mennini, Massimo Siciliano, Enrico Girardi, Vincenzo Panella, Giuseppe Ippolito
BACKGROUND: Management of chronic hepatitis C (CHC) has significantly accelerated in the last few years. Currently, second generation direct acting antivirals (DAAs) promise clearance of infection in most of patients. Here we present the results of the first analysis carried out on data of Lazio clinical network for DAAs. METHODS: The study was designed as a multicenter cohort: a) to assess the evolution of treatment during the first 24 months of the activity of the Clinical Network; b) to report overall efficacy of treatments; c) to analyze potential factors associated with lack of virological response at 12 weeks after therapy (SVR12); d) to evaluate the variation of ALT at baseline and 12 weeks after therapy in those who achieved SVR12 in comparison to those who did not...
May 16, 2018: BMC Infectious Diseases
https://www.readbyqxmd.com/read/29768547/clinical-outcomes-and-risk-factors-for-death-from-disseminated-histoplasmosis-in-patients-with-aids-who-visited-a-high-complexity-hospital-in-campo-grande-ms-brazil
#5
Barbara Cristina Scarcelli Boigues, Anamaria Mello Miranda Paniago, Gláucia Moreira Espíndola Lima, Maina de Oliveira Nunes, Silvia Naomi de Oliveira Uehara
INTRODUCTION: Disseminated histoplasmosis (DH) is a systemic mycosis caused by Histoplasma capsulatum (H. capsulatum) and is characterized by progressive and fatal evolution in immunocompromised patients. Moreover, it is considered an AIDS-defining disease. METHODS: We performed an observational, analytical, retrospective study to identify the clinical outcomes and risk factors for death from DH in patients with AIDS at an infectious diseases service facility in Brazil between September 2011 and July 2016...
March 2018: Revista da Sociedade Brasileira de Medicina Tropical
https://www.readbyqxmd.com/read/29765018/tracking-hiv-1-recombination-to-resolve-its-contribution-to-hiv-1-evolution-in-natural-infection
#6
Hongshuo Song, Elena E Giorgi, Vitaly V Ganusov, Fangping Cai, Gayathri Athreya, Hyejin Yoon, Oana Carja, Bhavna Hora, Peter Hraber, Ethan Romero-Severson, Chunlai Jiang, Xiaojun Li, Shuyi Wang, Hui Li, Jesus F Salazar-Gonzalez, Maria G Salazar, Nilu Goonetilleke, Brandon F Keele, David C Montefiori, Myron S Cohen, George M Shaw, Beatrice H Hahn, Andrew J McMichael, Barton F Haynes, Bette Korber, Tanmoy Bhattacharya, Feng Gao
Recombination in HIV-1 is well documented, but its importance in the low-diversity setting of within-host diversification is less understood. Here we develop a novel computational tool (RAPR (Recombination Analysis PRogram)) to enable a detailed view of in vivo viral recombination during early infection, and we apply it to near-full-length HIV-1 genome sequences from longitudinal samples. Recombinant genomes rapidly replace transmitted/founder (T/F) lineages, with a median half-time of 27 days, increasing the genetic complexity of the viral population...
May 15, 2018: Nature Communications
https://www.readbyqxmd.com/read/29758235/innovation-and-trends-in-the-development-and-approval-of-antiviral-medicines-1987-2017-and-beyond
#7
REVIEW
Shuvam Chaudhuri, Julian A Symons, Jerome Deval
2017 marked the 30th anniversary of the approval of zidovudine (AZT) as the first HIV/AIDS therapy. Since then, more than eighty antiviral drugs have received FDA approval, half of which treat HIV infection. Here, we provide a retrospective analysis of approved antiviral drugs, including therapeutics against other major chronic infections such as hepatitis B and C, and herpes viruses, over the last thirty years. During this time, only a few drugs were approved to treat acute viral infections, mainly influenza...
May 15, 2018: Antiviral Research
https://www.readbyqxmd.com/read/29757635/accurate-measurement-of-residual-dipolar-couplings-in-large-rnas-by-variable-flip-angle-nmr
#8
Jan Marchant, Ad Bax, Michael F Summers
NMR approaches using nucleotide-specific deuterium labeling schemes have enabled structural studies of biologically relevant RNAs of increasing size and complexity. Although local structure is well-determined using these methods, definition of global structural features, including relative orientations of independent helices, remains a challenge. Residual dipolar couplings, a potential source of orientation information, have not been obtainable for large RNAs due to poor sensitivity resulting from rapid heteronuclear signal decay...
May 14, 2018: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29747434/the-impact-of-human-papilloma-viruses-matrix-metallo-proteinases-and-hiv-protease-inhibitors-on-the-onset-and-progression-of-uterine-cervix-epithelial-tumors-a-review-of-preclinical-and-clinical-studies
#9
REVIEW
Giovanni Barillari, Paolo Monini, Cecilia Sgadari, Barbara Ensoli
Infection of uterine cervix epithelial cells by the Human Papilloma Viruses (HPV) is associated with the development of dysplastic/hyperplastic lesions, termed cervical intraepithelial neoplasia (CIN). CIN lesions may regress, persist or progress to invasive cervical carcinoma (CC), a leading cause of death worldwide. CIN is particularly frequent and aggressive in women infected by both HPV and the Human Immunodeficiency Virus (HIV), as compared to the general female population. In these individuals, however, therapeutic regimens employing HIV protease inhibitors (HIV-PI) have reduced CIN incidence and/or clinical progression, shedding light on the mechanism(s) of its development...
May 9, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29747123/hiv-aspartyl-protease-inhibitors-modify-the-percentage-of-activated-leukocytes-as-well-as-serum-levels-of-il-17a-and-no-during-experimental-leishmaniasis
#10
Daniele Luísa Ribeiro Alvarenga, Amanda Helen Dos Santos Silva, Jacqueline Araújo Fiuza, Soraya Torres Gaze, Jaquelline Germano de Oliveira, Rodrigo Corrêa Oliveira, Carlos Eduardo Calzavara-Silva, Marcelo Antônio Pascoal-Xavier, Érica Alessandra Rocha Alves
HIV aspartyl protease inhibitors are able to modulate multiple defense mechanisms. However, their influence on the immune response against Leishmania has rarely been investigated. The aim of our study was to investigate whether in vivo treatment with HIV aspartyl protease inhibitors is able to modulate the immune response during Leishmania infection. Using Leishmania (L.) amazonensis-infected mice, we analyzed the disease evolution and parasite load, immunophenotypic profiles of splenic T and B lymphocytes, numbers of lymphoid aggregates in the spleen, percentages of circulating atypical lymphocytes and reactive monocytes, and serum levels of cytokines and nitric oxide (NO) after 30 days of oral treatment with lopinavir/ritonavir (LPV/RTV) or atazanavir (ATV)...
May 7, 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29733983/evolutionary-dynamics-of-hepatitis-c-virus-in-a-chronic-hiv-co-infected-patient-and-its-correlation-with-the-immune-status
#11
Andrés Carlos Alberto Culasso, María Cecilia Monzani, Patricia Baré, Rodolfo Hector Campos
The HCV evolutionary dynamics play a key role in the infection onset, maintenance of chronicity, pathogenicity, and drug resistance variants fixation, and are thought to be one of the main caveats in the development of an effective vaccine. Previous studies in HCV/HIV co-infected patients suggest that a decline in the immune status is related with increases in the HCV intra-host genetic diversity. However, these findings are based on single point sequence diversity measures or coalescence analyses in several virus-host interactions...
May 4, 2018: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/29733244/novel-dna-aptamers-against-ccl21-protein-characterization-and-biomedical-applications-for-targeted-drug-delivery-to-t-cell-rich-zones
#12
Louis Chonco, Gerónimo Fernández, Rahul Kalhapure, María J Hernáiz, Cecilia García-Oliva, Victor M Gonzalez, M Elena Martín, Thirumala Govender, Raveen Parboosing
The chemokine (C-C motif) ligand 21 (CCL21) is a cytokine that attracts CCR7-positive cells to the T cell (paracortical) zone of lymph nodes by directional migration of these cells along the CCL21 gradient. In this article, we sought to mimic this chemotactic mechanism, by identifying a novel aptamer that binds CCL21 with high affinity. In vitro selection of DNA aptamers was performed by the Systematic Evolution of Ligands by Exponential Enrichment. Quantitative polymerase chain reaction (qPCR) and enzyme-linked oligonucleotide assay were used to screen for high-affinity aptamers against human and mouse CCL21 protein, respectively...
May 7, 2018: Nucleic Acid Therapeutics
https://www.readbyqxmd.com/read/29727445/the-htlv-1-gp21-fusion-peptide-inhibits-antigen-specific-t-cell-activation-in-vitro-and-in-mice
#13
Etai Rotem, Omri Faingold, Meital Charni, Yoel A Klug, Daniel Harari, Liraz Shmuel-Galia, Alon Nudelman, Varda Rotter, Yechiel Shai
The ability of the Lentivirus HIV-1 to inhibit T-cell activation by its gp41 fusion protein is well documented, yet limited data exists regarding other viral fusion proteins. HIV-1 utilizes membrane binding region of gp41 to inhibit T-cell receptor (TCR) complex activation. Here we examined whether this T-cell suppression strategy is unique to the HIV-1 gp41. We focused on T-cell modulation by the gp21 fusion peptide (FP) of the Human T-lymphotropic Virus 1 (HTLV-1), a Deltaretrovirus that like HIV infects CD4+ T-cells...
May 4, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29723682/intra-host-sequence-variability-in-human-papillomavirus
#14
Racheal S Dube Mandishora, Kristina S Gjøtterud, Sonja Lagström, Babill Stray-Pedersen, Kerina Duri, Nyasha Chin'ombe, Mari Nygård, Irene Kraus Christiansen, Ole Herman Ambur, Mike Z Chirenje, Trine B Rounge
Human papillomaviruses (HPVs) co-evolve slowly with the human host and each HPV genotype displays epithelial tropisms. We assessed the evolution of intra HPV genotype variants within samples, and their association to anogenital site, cervical cytology and HIV status. Variability in the L1 gene of 35 HPV genotypes was characterized phylogenetically using maximum likelihood, and portrayed by phenotype. Up to a thousand unique variants were identified within individual samples. In-depth analyses of the most prevalent genotypes, HPV16, HPV18 and HPV52, revealed that the high diversity was dominated by a few abundant variants...
April 30, 2018: Papillomavirus Research
https://www.readbyqxmd.com/read/29720497/molecular-mechanisms-for-species-differences-in-organic-anion-transporter-1-oat1-implications-for-renal-drug-toxicity
#15
Ling Zou, Adrian Stecula, Anshul Gupta, Bhagwat Prasad, Huan-Chieh Chien, Sook Wah Yee, Li Wang, Jashvant D Unadkat, Simone H Stahl, Katherine S Fenner, Kathleen M Giacomini
Species differences in renal drug transporters continue to plague drug development with animal models failing to adequately predict renal drug toxicity. For example, adefovir, a renally excreted antiviral drug, failed clinical studies for HIV due to pronounced nephrontoxicity in humans. In this study, we demonstrated that there are large species differences in the kinetics of interactions of a key class of antiviral drugs, acyclic nucleoside phosphonates (ANPs), with OAT1 (SLC22A6) and identified a key amino acid residue responsible for these differences...
May 2, 2018: Molecular Pharmacology
https://www.readbyqxmd.com/read/29718409/the-puzzle-of-hiv-neutral-and-selective-evolution
#16
Thomas Leitner
HIV is one of the fastest evolving organisms known. It evolves about 1 million times faster than its host, humans. Because HIV establishes chronic infections, with continuous evolution, its divergence within a single infected human surpasses the divergence of the entire humanoid history. Yet, it is still the same virus, infecting the same cell types and using the same replication machinery year after year. Hence, one would think that most mutations that HIV accumulates are neutral. But the picture is more complicated than that...
April 27, 2018: Molecular Biology and Evolution
https://www.readbyqxmd.com/read/29708995/temporal-evolution-of-hiv-sero-discordancy-patterns-among-stable-couples-in-sub-saharan-africa
#17
Susanne F Awad, Hiam Chemaitelly, Laith J Abu-Raddad
INTRODUCTION: Objective was to examine the temporal variation of HIV sero-discordancy in select representative countries (Kenya, Lesotho, Mali, Niger, Tanzania, and Zimbabwe) in sub-Saharan Africa at different HIV epidemic scales. A sero-discordant couple is defined as a stable couple (SC) in which one partner is HIV-positive while the other is HIV-negative. METHODS: A deterministic compartmental mathematical model was constructed to describe HIV transmission dynamics...
2018: PloS One
https://www.readbyqxmd.com/read/29707599/prevalence-and-evolution-of-renal-impairment-in-people-living-with-hiv-in-rural-tanzania
#18
Herry Mapesi, Aneth V Kalinjuma, Alphonce Ngerecha, Fabian Franzeck, Christoph Hatz, Marcel Tanner, Michael Mayr, Hansjakob Furrer, Manuel Battegay, Emilio Letang, Maja Weisser, Tracy R Glass
Background: We assessed the prevalence, incidence, and predictors of renal impairment among people living with HIV (PLWHIV) in rural Tanzania. Methods: In a cohort of PLWHIV aged ≥15 years enrolled from January 2013 to June 2016, we assessed the association between renal impairment (estimated glomerural filtration rate < 90 mL/min/1.73 m2 ) at enrollment and during follow-up with demographic and clinical characteristcis using logistic regression and Cox proportional hazards models...
April 2018: Open Forum Infectious Diseases
https://www.readbyqxmd.com/read/29705074/kidney-transplantation-in-hiv-positive-patients-a-single-center-16-year-experience
#19
Gregory E Malat, Suzanne M Boyle, Rahul M Jindal, Stephen Guy, Gary Xiao, Meera N Harhay, Dong H Lee, Karthik M Ranganna, Mysore S Anil Kumar, Alden M Doyle
Hahnemann University Hospital has performed 120 kidney transplantations in human immunodeficiency virus (HIV)-positive individuals during the last 16 years. Our patient population represents ∼10% of the entire US population of HIV-positive kidney recipients. In our earlier years of HIV transplantation, we noted increased rejection rates, often leading to graft failure. We have established a multidisciplinary team and over the years have made substantial protocol modifications based on lessons learned. These modifications affected our approach to candidate evaluation, donor selection, perioperative immunosuppression, and posttransplantation monitoring and resulted in excellent posttransplantation outcomes, including 100% patient and graft survival at 1 year and patient and graft survival at 3 years of 100% and 96%, respectively...
April 25, 2018: American Journal of Kidney Diseases: the Official Journal of the National Kidney Foundation
https://www.readbyqxmd.com/read/29688540/selection-and-neutral-mutations-drive-pervasive-mutability-losses-in-long-lived-anti-hiv-b-cell-lineages
#20
Marcos C Vieira, Daniel Zinder, Sarah Cobey
High-affinity antibodies arise within weeks of infection from the evolution of B-cell receptors under selection to improve antigen recognition. This rapid adaptation is enabled by the distribution of highly mutable "hotspot" motifs in B-cell receptor genes. High mutability in antigen-binding regions (complementarity determining regions [CDRs]) creates variation in binding affinity, whereas low mutability in structurally important regions (framework regions [FRs]) may reduce the frequency of destabilizing mutations...
May 1, 2018: Molecular Biology and Evolution
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