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https://www.readbyqxmd.com/read/27894306/first-phase-i-human-clinical-trial-of-a-killed-whole-hiv-1-vaccine-demonstration-of-its-safety-and-enhancement-of-anti-hiv-antibody-responses
#1
Eunsil Choi, Chad J Michalski, Seung Ho Choo, Gyoung Nyoun Kim, Elizabeth Banasikowska, Sangkyun Lee, Kunyu Wu, Hwa-Yong An, Anthony Mills, Stefan Schneider, U Fritz Bredeek, Daniel R Coulston, Shilei Ding, Andrés Finzi, Meijuan Tian, Katja Klein, Eric J Arts, Jamie F S Mann, Yong Gao, C Yong Kang
BACKGROUND: Vaccination with inactivated (killed) whole-virus particles has been used to prevent a wide range of viral diseases. However, for an HIV vaccine this approach has been largely negated due to inherent safety concerns, despite the ability of killed whole-virus vaccines to generate a strong, predominantly antibody-mediated immune response in vivo. HIV-1 Clade B NL4-3 was genetically modified by deleting the nef and vpu genes and substituting the coding sequence for the Env signal peptide with that of honeybee melittin signal peptide to produce a less virulent and more replication efficient virus...
November 28, 2016: Retrovirology
https://www.readbyqxmd.com/read/27888040/evidence-that-hidden-hearing-loss-underlies-amplitude-modulation-encoding-deficits-in-individuals-with-and-without-tinnitus
#2
Brandon T Paul, Ian C Bruce, Larry E Roberts
Damage to auditory nerve fibers that expresses with suprathreshold sounds but is hidden from the audiogram has been proposed to underlie deficits in temporal coding ability observed among individuals with otherwise normal hearing, and to be present in individuals experiencing chronic tinnitus with clinically normal audiograms. We tested whether these individuals may have hidden synaptic losses on auditory nerve fibers with low spontaneous rates of firing (low-SR fibers) that are important for coding suprathreshold sounds in noise while high-SR fibers determining threshold responses in quiet remain relatively unaffected...
November 23, 2016: Hearing Research
https://www.readbyqxmd.com/read/27885426/prospective-cohort-study-assessing-chronic-pain-in-patients-following-minor-surgery-for-breast-cancer
#3
Régis Fuzier, Floriane Puel, Philippe Izard, Agnès Sommet, Sébastien Pierre
PURPOSE: Pain after tumorectomy and sentinel lymph node dissection is poorly reported in the literature. We carried out a prospective survey aimed at assessing pain three months after such minor surgery for breast cancer. METHODS: The study was approved by the local ethics committee. Most surgeries followed a standard protocol involving general anesthesia with no regional analgesia technique, laryngeal mask, sufentanil and propofol for induction, and multimodal analgesia during the postoperative period...
November 24, 2016: Journal of Anesthesia
https://www.readbyqxmd.com/read/27881646/activation-and-inactivation-of-primary-human-immunodeficiency-virus-hiv-1-envelope-glycoprotein-trimers-by-cd4-mimetic-compounds
#4
Navid Madani, Amy M Princiotto, Connie Zhao, Fatemeh Jahanbakhshsefidi, Max Mertens, Alon Herschhorn, Bruno Melillo, Amos B Smith, Joseph Sodroski
: Human immunodeficiency virus (HIV-1) entry into cells is mediated by the viral envelope glycoproteins (Env), a trimer of three gp120 exterior glycoproteins and three gp41 transmembrane glycoproteins. The metastable Env is triggered to undergo entry-related conformational changes when gp120 binds sequentially to the receptors, CD4 and CCR5, on the target cell. Small-molecule CD4-mimetic compounds (CD4mc) bind gp120 and act as competitive inhibitors of gp120-CD4 engagement. Some CD4mc have been shown to trigger Env prematurely, initially activating Env function, followed by rapid and irreversible inactivation...
November 23, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27854239/kshv-entry-and-trafficking-in-target-cells-hijacking-of-cell-signal-pathways-actin-and-membrane-dynamics
#5
REVIEW
Binod Kumar, Bala Chandran
Kaposi's sarcoma associated herpesvirus (KSHV) is etiologically associated with human endothelial cell hyperplastic Kaposi's sarcoma and B-cell primary effusion lymphoma. KSHV infection of adherent endothelial and fibroblast cells are used as in vitro models for infection and KSHV enters these cells by host membrane bleb and actin mediated macropinocytosis or clathrin endocytosis pathways, respectively. Infection in endothelial and fibroblast cells is initiated by the interactions between multiple viral envelope glycoproteins and cell surface associated heparan sulfate (HS), integrins (α3β1, αVβ3 and αVβ5), and EphA2 receptor tyrosine kinase (EphA2R)...
November 14, 2016: Viruses
https://www.readbyqxmd.com/read/27846256/safety-and-immunogenicity-of-a-rad35-enva-prototype-hiv-1-vaccine-in-combination-with-rad5-enva-in-healthy-adults-vrc-012
#6
Michelle C Crank, Eleanor M P Wilson, Laura Novik, Mary E Enama, Cynthia S Hendel, Wenjuan Gu, Martha C Nason, Robert T Bailer, Gary J Nabel, Adrian B McDermott, John R Mascola, Richard A Koup, Julie E Ledgerwood, Barney S Graham
BACKGROUND: VRC 012 was a Phase I study of a prototype recombinant adenoviral-vector serotype-35 (rAd35) HIV vaccine, the precursor to two recently published clinical trials, HVTN 077 and 083. On the basis of prior evaluation of multiclade rAd5 HIV vaccines, Envelope A (EnvA) was selected as the standard antigen for a series of prototype HIV vaccines to compare various vaccine platforms. In addition, prior studies of rAd5-vectored vaccines suggested pre-existing human immunity may be a confounding factor in vaccine efficacy...
2016: PloS One
https://www.readbyqxmd.com/read/27834890/measurement-of-low-carbon-economy-efficiency-with-a-three-stage-data-envelopment-analysis-a-comparison-of-the-largest-twenty-co%C3%A2-emitting-countries
#7
Xiang Liu, Jia Liu
This paper employs a three-stage approach to estimate low carbon economy efficiency in the largest twenty CO₂ emitting countries from 2000 to 2012. The approach includes the following three stages: (1) use of a data envelopment analysis (DEA) model with undesirable output to estimate the low carbon economy efficiency and calculate the input and output slacks; (2) use of a stochastic frontier approach to eliminate the impacts of external environment variables on these slacks; (3) re-estimation of the efficiency with adjusted inputs and outputs to reflect the capacity of the government to develop a low carbon economy...
November 9, 2016: International Journal of Environmental Research and Public Health
https://www.readbyqxmd.com/read/27816499/effects-of-noise-exposure-on-young-adults-with-normal-audiograms-i-electrophysiology
#8
Garreth Prendergast, Hannah Guest, Kevin J Munro, Karolina Kluk, Agnès Léger, Deborah A Hall, Michael G Heinz, Christopher J Plack
Noise-induced cochlear synaptopathy has been demonstrated in numerous rodent studies. In these animal models, the disorder is characterized by a reduction in amplitude of wave I of the auditory brainstem response (ABR) to high-level stimuli, whereas the response at threshold is unaffected. The aim of the present study was to determine if this disorder is prevalent in young adult humans with normal audiometric hearing. One hundred and twenty six participants (75 females) aged 18-36 were tested. Participants had a wide range of lifetime noise exposures as estimated by a structured interview...
November 2, 2016: Hearing Research
https://www.readbyqxmd.com/read/27815131/sensory-coding-and-cognitive-processing-of-sound-in-veterans-with-blast-exposure
#9
Scott Bressler, Hannah Goldberg, Barbara Shinn-Cunningham
Recent anecdotal reports from VA audiology clinics as well as a few published studies have identified a sub-population of Service Members seeking treatment for problems communicating in everyday, noisy listening environments despite having normal to near-normal hearing thresholds. Because of their increased risk of exposure to dangerous levels of prolonged noise and transient explosive blast events, communication problems in these soldiers could be due to either hearing loss (traditional or "hidden") in the auditory sensory periphery or from blast-induced injury to cortical networks associated with attention...
November 2, 2016: Hearing Research
https://www.readbyqxmd.com/read/27812330/contributions-of-sensory-coding-and-attentional-control-to-individual-differences-in-performance-in-spatial-auditory-selective-attention-tasks
#10
Lengshi Dai, Barbara G Shinn-Cunningham
Listeners with normal hearing thresholds (NHTs) differ in their ability to steer attention to whatever sound source is important. This ability depends on top-down executive control, which modulates the sensory representation of sound in the cortex. Yet, this sensory representation also depends on the coding fidelity of the peripheral auditory system. Both of these factors may thus contribute to the individual differences in performance. We designed a selective auditory attention paradigm in which we could simultaneously measure envelope following responses (EFRs, reflecting peripheral coding), onset event-related potentials (ERPs) from the scalp (reflecting cortical responses to sound) and behavioral scores...
2016: Frontiers in Human Neuroscience
https://www.readbyqxmd.com/read/27798680/loukoumasomes-are-distinct-subcellular-structures-from-rods-and-rings-and-are-structurally-associated-with-map2-and-the-nuclear-envelope-in-retinal-cells
#11
Jake W Noble, Diana V Hunter, Calvin D Roskelley, Edward K L Chan, Julia Mills
"Rods and rings" (RR) and loukoumasomes are similarly shaped, subcellular macromolecular structures with as yet unknown function. RR, so named because of their shape, are formed in response to inhibition in the GTP or CTP synthetic pathways and are highly enriched in the two key enzymes of the nucleotide synthetic pathway. Loukoumasomes also occur as linear and toroidal bodies and were initially inferred to be the same as RR, largely due to their shared shape and size and the fact that it was unclear if they shared the same subcomponents...
2016: PloS One
https://www.readbyqxmd.com/read/27796471/deletion-of-degq-gene-enhances-outer-membrane-vesicle-production-of-shewanella-oneidensis-cells
#12
Yoshihiro Ojima, Thivagaran Mohanadas, Kosei Kitamura, Shota Nunogami, Reiki Yajima, Masahito Taya
Shewanella oneidensis is a Gram-negative facultative anaerobe that can use a wide variety of terminal electron acceptors for anaerobic respiration. In this study, S. oneidensis degQ gene, encoding a putative periplasmic serine protease, was cloned and expressed. The activity of purified DegQ was inhibited by diisopropyl fluorophosphate, a typical serine protease-specific inhibitor, indicating that DegQ is a serine protease. In-frame deletion and subsequent complementation of the degQ were carried out to examine the effect of envelope stress on the production of outer membrane vesicles (OMVs)...
October 31, 2016: Archives of Microbiology
https://www.readbyqxmd.com/read/27794347/relative-contribution-of-envelope-and-fine-structure-to-the-subcortical-encoding-of-noise-degraded-speech
#13
Gavin M Bidelman
Brainstem frequency-following responses (FFR) were elicited to the speech token /ama/ in noise containing only envelope (ENV) or fine structure (TFS) cues to assess the relative contribution of these temporal features to the neural encoding of degraded speech. Successive cue removal weakened FFRs with noise having the most deleterious effect on TFS coding. Neuro-acoustic and response-to-response correlations revealed speech-FFRs are dominated by stimulus ENV for clean speech, with TFS making a stronger contribution in moderate noise levels...
October 2016: Journal of the Acoustical Society of America
https://www.readbyqxmd.com/read/27768891/cross-neutralizing-and-protective-human-antibody-specificities-to-poxvirus-infections
#14
Iuliia Gilchuk, Pavlo Gilchuk, Gopal Sapparapu, Rebecca Lampley, Vidisha Singh, Nurgun Kose, David L Blum, Laura J Hughes, Panayampalli S Satheshkumar, Michael B Townsend, Ashley V Kondas, Zachary Reed, Zachary Weiner, Victoria A Olson, Erika Hammarlund, Hans-Peter Raue, Mark K Slifka, James C Slaughter, Barney S Graham, Kathryn M Edwards, Roselyn J Eisenberg, Gary H Cohen, Sebastian Joyce, James E Crowe
Monkeypox (MPXV) and cowpox (CPXV) are emerging agents that cause severe human infections on an intermittent basis, and variola virus (VARV) has potential for use as an agent of bioterror. Vaccinia immune globulin (VIG) has been used therapeutically to treat severe orthopoxvirus infections but is in short supply. We generated a large panel of orthopoxvirus-specific human monoclonal antibodies (Abs) from immune subjects to investigate the molecular basis of broadly neutralizing antibody responses for diverse orthopoxviruses...
October 20, 2016: Cell
https://www.readbyqxmd.com/read/27733645/high-ebv-load-and-genomic-diversity-are-associated-with-generation-of-gp350-specific-neutralizing-antibodies-following-acute-infectious-mononucleosis
#15
Eric R Weiss, Galit Alter, Javier Gordon Ogembo, Jennifer L Henderson, Barbara Tabak, Yasin Bakiş, Mohan Somasundaran, Manuel Garber, Liisa Selin, Katherine Luzuriaga
: The Epstein Barr virus (EBV) gp350 glycoprotein interacts with the cellular receptor to mediate viral entry and is thought to be the major target for neutralizing antibodies. To better understand the role of EBV-specific antibodies in the control of viral replication and evolution of sequence diversity, we measured EBV gp350-specific antibody responses and sequenced the gp350 gene in samples obtained from individuals experiencing primary EBV infection (acute infectious mononucleosis; AIM) and again 6 months later (convalescence, CONV)...
October 12, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27729633/hepatitis-b-surface-antigen-titer-is-a-good-indicator-of-durable-viral-response-after-entecavir-off-treatment-for-chronic-hepatitis-b
#16
Han Ah Lee, Yeon Seok Seo, Seung Woon Park, Sang Jung Park, Tae Hyung Kim, Sang Jun Suh, Young Kul Jung, Ji Hoon Kim, Hyunggin An, Hyung Joon Yim, Jong Eun Yeon, Kwan Soo Byun, Soon Ho Um
BACKGROUND/AIMS: Clear indicators for stopping antiviral therapy in chronic hepatitis B (CHB) patients are not yet available. Since the level of hepatitis B surface antigen (HBsAg) is correlated with covalently closed circular DNA, the HBsAg titer might be a good indicator of the off-treatment response. This study aimed to determine the relationship between the HBsAg titer and the entecavir (ETV) off-treatment response. METHODS: This study analyzed 44 consecutive CHB patients (age, 44...
September 2016: Clinical and Molecular Hepatology
https://www.readbyqxmd.com/read/27717282/multi-responsive-turn-on-nanocarriers-for-efficient-site-specific-gene-delivery-in-vitro-and-in-vivo
#17
Yiyan He, Jie Zhou, Shengnan Ma, Yu Nie, Dong Yue, Qian Jiang, Aisha Roshan Mohamed Wali, James Zhenggui Tang, Zhongwei Gu
Systemic gene delivery is a complicated and multistep process that confronts numerous biological barriers. It remains a formidable challenge to exploit a single gene carrier with multiple features to combat all obstacles collectively. Herein, a multi-responsive "turn-on" polyelectrolyte complex (DNA/OEI-SSx /HA-SS-COOH, DSS) delivery system is demonstrated with a sequential self-assembly of disulfide-conjugated oligoethylenimine (OEI-SSx ) and disulfide bond-modified hyaluronic acid envelope (HA-SS-COOH) that can combat multiple biological barriers collectively when administered intravenously...
November 2016: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/27645386/transcriptional-responses-of-escherichia-coli-to-a-small-molecule-inhibitor-of-lolcde-an-essential-component-of-the-lipoprotein-transport-pathway
#18
Christian Lorenz, Thomas J Dougherty, Stephen Lory
: In Gram-negative bacteria, a dedicated machinery consisting of LolABCDE components targets lipoproteins to the outer membrane. We used a previously identified small-molecule inhibitor of the LolCDE complex of Escherichia coli to assess the global transcriptional consequences of interference with lipoprotein transport. Exposure of E. coli to the LolCDE inhibitor at concentrations leading to minimal and significant growth inhibition, followed by transcriptome sequencing, identified a small group of genes whose transcript levels were decreased and a larger group whose mRNA levels increased 10- to 100-fold compared to those of untreated cells...
December 1, 2016: Journal of Bacteriology
https://www.readbyqxmd.com/read/27645216/reverberation-limits-the-release-from-informational-masking-obtained-in-the-harmonic-and-binaural-domains
#19
Mickael L D Deroche, John F Culling, Mathieu Lavandier, Vincent L Gracco
A difference in fundamental frequency (ΔF0) and a difference in spatial location (ΔSL) are two cues known to provide masking releases when multiple speakers talk at once in a room. We examined situations in which reverberation should have no effect on the mechanisms underlying the releases from energetic masking produced by these two cues. Speech reception thresholds using both unpredictable target sentences and the coordinate response measure followed a similar pattern. Both ΔF0s and ΔSLs provided masking releases in the presence of nonspeech maskers (matched in excitation pattern and temporal envelope to the speech maskers) that, as intended, were robust to reverberation...
September 19, 2016: Attention, Perception & Psychophysics
https://www.readbyqxmd.com/read/27633665/effect-of-hiv-1-envelope-cytoplasmic-tail-on-adenovirus-primed-virus-encoded-virus-like-particle-immunizations
#20
Anne-Marie C Andersson, Emeline Ragonnaud, Kelly E Seaton, Sheetal Sawant, Antonella Folgori, Stefano Colloca, Celia Labranche, David C Montefiori, Georgia D Tomaras, Peter J Holst
The low number of envelope (Env) spikes presented on native HIV-1 particles is a major impediment for HIV-1 prophylactic vaccine development. We designed virus-like particle encoding adenoviral vectors utilizing SIVmac239 Gag as an anchor for full length and truncated HIV-1 M consensus Env. Truncated Env overexpressed VRC01 and 17b binding antigen on the surface of transduced cells while the full length Env vaccine presented more and similar amounts of antigen binding to the trimer conformation sensitive antibodies PGT151 and PGT145, respectively...
October 17, 2016: Vaccine
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