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https://www.readbyqxmd.com/read/28774415/new-treatments-to-reach-functional-cure-virological-approaches
#1
REVIEW
David Durantel
Current therapies of chronic hepatitis B (CHB) remain limited to pegylated-interferon-alpha (pegIFN-α) or any of the five approved nucleos(t)ide analogues (NA). If viral suppression can be achieved in the majority of patients with the high-barrier-to-resistance new-generation of NA, i.e. entecavir and tenofovir, HBsAg loss is achieved by PEG-IFN-α and/or NA in only 10% of patients, after a 5-year follow-up. Attempts to improve the response by administering two different NA or a combination of NA and PEG-IFN-α have not provided a dramatic increase in the rate of "functional cure"...
June 2017: Best Practice & Research. Clinical Gastroenterology
https://www.readbyqxmd.com/read/28758637/dna-prime-protein-boost-vaccination-elicits-robust-humoral-response-in-rhesus-macaques-using-oligomeric-simian-immunodeficiency-virus-envelope-and-advax-delta-inulin-adjuvant
#2
Veena Menon, Victor I Ayala, Sneha P Rangaswamy, Irene Kalisz, Stephen Whitney, Lindsey Galmin, Asma Ashraf, Celia LaBranche, David Montefiori, Nikolai Petrovsky, Vaniambadi S Kalyanaraman, Ranajit Pal
The partial success of the RV144 trial underscores the importance of envelope-specific antibody responses for an effective HIV-1 vaccine. Oligomeric HIV-1 envelope proteins delivered with a potent adjuvant are expected to elicit strong antibody responses with broad neutralization specificity. To test this hypothesis, two SIV envelope proteins were formulated with delta inulin-based adjuvant (Advax) and used to immunize nonhuman primates. Oligomeric gp140-gp145 from SIVmac251 and SIVsmE660 was purified to homogeneity...
July 31, 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28753474/age-related-changes-in-envelope-following-responses-at-equalized-peripheral-or-central-activation
#3
Jesyin Lai, Alexandra L Sommer, Edward L Bartlett
Previous work has debated about the comparisons of hearing abilities faced with alterations in hearing thresholds and evoked potentials between groups following acoustic trauma- or age-related changes. This study compares envelope-following responses (EFRs) of young and aged rats when sound levels were matched according to (1) wave I amplitudes of auditory brainstem responses (ABRs) elicited by 8-kHz tones or (2) EFR amplitudes evoked by sinusoidally amplitude-modulated (SAM) tones at 100% depth. Matched wave I amplitudes across age corresponded to approximately 20-dB sound level differences...
June 24, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28738408/cgas-surveillance-of-micronuclei-links-genome-instability-to-innate-immunity
#4
Karen J Mackenzie, Paula Carroll, Carol-Anne Martin, Olga Murina, Adeline Fluteau, Daniel J Simpson, Nelly Olova, Hannah Sutcliffe, Jacqueline K Rainger, Andrea Leitch, Ruby T Osborn, Ann P Wheeler, Marcin Nowotny, Nick Gilbert, Tamir Chandra, Martin A M Reijns, Andrew P Jackson
DNA is strictly compartmentalized within the nucleus to prevent autoimmunity; despite this, cyclic GMP-AMP synthase (cGAS), a cytosolic sensor of double-stranded DNA, is activated in autoinflammatory disorders and by DNA damage. Precisely how cellular DNA gains access to the cytoplasm remains to be determined. Here, we report that cGAS localizes to micronuclei arising from genome instability in a mouse model of monogenic autoinflammation, after exogenous DNA damage and spontaneously in human cancer cells. Such micronuclei occur after mis-segregation of DNA during cell division and consist of chromatin surrounded by its own nuclear membrane...
July 24, 2017: Nature
https://www.readbyqxmd.com/read/28721397/hivis-dna-or-hivisopt-dna-priming-followed-by-cmdr-vaccinia-based-boosts-induce-both-humoral-and-cellular-murine-immune-responses-to-hiv
#5
J Hinkula, S Petkov, K Ljungberg, D Hallengärd, A Bråve, M Isaguliants, T Falkeborn, S Sharma, V Liakina, M Robb, M Eller, B Moss, G Biberfeld, E Sandström, C Nilsson, K Markland, P Blomberg, B Wahren
BACKGROUND: In order to develop a more effective prophylactic HIV-1 vaccine it is important optimize the components, improve Envelope glycoprotein immunogenicity as well as to explore prime-boost immunization schedules. It is also valuable to include several HIV-1 subtype antigens representing the world-wide epidemic. METHODS: HIVIS-DNA plasmids which include Env genes of subtypes A, B and C together with Gag subtypes A and B and RTmut/Rev of subtype B were modified as follows: the Envelope sequences were shortened, codon optimized, provided with an FT4 sequence and an immunodominant region mutated...
June 2017: Heliyon
https://www.readbyqxmd.com/read/28716582/a-probabilistic-poisson-based-model-accounts-for-an-extensive-set-of-absolute-auditory-threshold-measurements
#6
Peter Heil, Artur Matysiak, Heinrich Neubauer
Thresholds for detecting sounds in quiet decrease with increasing sound duration in every species studied. The neural mechanisms underlying this trade-off, often referred to as temporal integration, are not fully understood. Here, we probe the human auditory system with a large set of tone stimuli differing in duration, shape of the temporal amplitude envelope, duration of silent gaps between bursts, and frequency. Duration was varied by varying the plateau duration of plateau-burst (PB) stimuli, the duration of the onsets and offsets of onset-offset (OO) stimuli, and the number of identical bursts of multiple-burst (MB) stimuli...
June 27, 2017: Hearing Research
https://www.readbyqxmd.com/read/28698284/breaching-peripheral-tolerance-promotes-the-production-of-hiv-1-neutralizing-antibodies
#7
Kristin M S Schroeder, Amanda Agazio, Pamela J Strauch, Sean T Jones, Scott B Thompson, Michael S Harper, Roberta Pelanda, Mario L Santiago, Raul M Torres
A subset of characterized HIV-1 broadly neutralizing antibodies (bnAbs) are polyreactive with additional specificities for self-antigens and it has been proposed immunological tolerance may present a barrier to their participation in protective humoral immunity. We address this hypothesis by immunizing autoimmune-prone mice with HIV-1 Envelope (Env) and characterizing the primary antibody response for HIV-1 neutralization. We find autoimmune mice generate neutralizing antibody responses to tier 2 HIV-1 strains with alum treatment alone in the absence of Env...
August 7, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28688560/speech-evoked-auditory-brainstem-responses-in-children-with-hearing-loss
#8
Amineh Koravand, Rida Al Osman, Véronique Rivest, Catherine Poulin
OBJECTIVE: The main objective of the present study was to investigate subcortical auditory processing in children with sensorineural hearing loss. METHODS: Auditory Brainstem Responses (ABRs) were recorded using click and speech/da/stimuli. Twenty-five children, aged 6-14 years old, participated in the study: 13 with normal hearing acuity and 12 with sensorineural hearing loss. RESULTS: No significant differences were observed for the click-evoked ABRs between normal hearing and hearing-impaired groups...
August 2017: International Journal of Pediatric Otorhinolaryngology
https://www.readbyqxmd.com/read/28686908/a-longitudinal-study-investigating-neural-processing-of-speech-envelope-modulation-rates-in-children-with-a-family-risk-for-dyslexia
#9
Astrid De Vos, Sophie Vanvooren, Jolijn Vanderauwera, Pol Ghesquière, Jan Wouters
Recent evidence suggests that a fundamental deficit in the synchronization of neural oscillations to temporal information in speech may underlie phonological processing problems in dyslexia. Since previous studies were performed cross-sectionally in school-aged children or adults, developmental aspects of neural auditory processing in relation to reading acquisition and dyslexia remain to be investigated. The present longitudinal study followed 68 children during development from pre-reader (5 years old) to beginning reader (7 years old) and more advanced reader (9 years old)...
August 2017: Cortex; a Journal Devoted to the Study of the Nervous System and Behavior
https://www.readbyqxmd.com/read/28683405/stiffening-of-bacteria-cells-as-a-first-manifestation-of-bactericidal-attack
#10
Katarzyna Pogoda, Ewelina Piktel, Piotr Deptuła, Paul B Savage, Małgorzata Lekka, Robert Bucki
Development of new antibacterial agents requires generation of new methods that will allow characterization of mechanisms of novel antibacterial actions as well as observation of pathogen susceptibility to antibiotics. A family of synthetic cationic lipids, such as ceragenins, which mimic the action of membrane-targeting natural cationic antibacterial peptides, shows promise as a new family of bactericidal agents. Here we report that treatment of Bacillus subtillis cells with human cathelicidin LL-37 and ceragenins CSA-13 and CSA-131 (1-100μg/mL) leads to physicochemical changes of bacterial cells surface...
June 27, 2017: Micron: the International Research and Review Journal for Microscopy
https://www.readbyqxmd.com/read/28655419/neural-representations-of-concurrent-sounds-with-overlapping-spectra-in-rat-inferior-colliculus-comparisons-between-temporal-fine-structure-and-envelope
#11
Lu Luo, Qian Wang, Liang Li
Perceptual segregation of multiple sounds, which overlap in both time and spectra, into individual auditory streams is critical for hearing in natural environments. Some cues such as interaural time disparities (ITDs) play an important role in the segregation, especially when sounds are separated in space. In this study, we investigated the neural representation of two uncorrelated narrowband noises that shared the identical spectrum in the rat inferior colliculus (IC) using frequency-following-response (FFR) recordings, when the ITD for each noise stimulus was manipulated...
June 17, 2017: Hearing Research
https://www.readbyqxmd.com/read/28643570/home-based-neurologic-music-therapy-for-arm-hemiparesis-following-stroke-results-from-a-pilot-feasibility-randomized-controlled-trial
#12
Alexander J Street, Wendy L Magee, Andrew Bateman, Michael Parker, Helen Odell-Miller, Jorg Fachner
OBJECTIVE: To assess the feasibility of a randomized controlled trial to evaluate music therapy as a home-based intervention for arm hemiparesis in stroke. DESIGN: A pilot feasibility randomized controlled trial, with cross-over design. Randomization by statistician using computer-generated, random numbers concealed in opaque envelopes. SETTING: Participants' homes across Cambridgeshire, UK. SUBJECTS: Eleven people with stroke and arm hemiparesis, 3-60 months post stroke, following discharge from community rehabilitation...
June 1, 2017: Clinical Rehabilitation
https://www.readbyqxmd.com/read/28630358/assessing-the-safety-and-immunogenicity-of-recombinant-vesicular-stomatitis-virus-ebola-vaccine-in-healthy-adults-a-randomized-clinical-trial
#13
RANDOMIZED CONTROLLED TRIAL
May S ElSherif, Catherine Brown, Donna MacKinnon-Cameron, Li Li, Trina Racine, Judie Alimonti, Thomas L Rudge, Carol Sabourin, Peter Silvera, Jay W Hooper, Steven A Kwilas, Nicole Kilgore, Christopher Badorrek, W Jay Ramsey, D Gray Heppner, Tracy Kemp, Thomas P Monath, Teresa Nowak, Shelly A McNeil, Joanne M Langley, Scott A Halperin
BACKGROUND: The 2013-2016 Ebola virus outbreak in West Africa was the most widespread in history. In response, alive attenuated recombinant vesicular stomatitis virus (rVSV) vaccine expressing Zaire Ebolavirus glycoprotein (rVSVΔG-ZEBOV-GP) was evaluated in humans. METHODS: In a phase 1, randomized, dose-ranging, observer-blind, placebo-controlled trial, healthy adults aged 18-65 years were randomized into 4 groups of 10 to receive one of 3 vaccine doses or placebo...
June 19, 2017: CMAJ: Canadian Medical Association Journal, Journal de L'Association Medicale Canadienne
https://www.readbyqxmd.com/read/28607776/could-lc-ne-dependent-adjustment-of-neural-gain-drive-functional-brain-network-reorganization
#14
REVIEW
Carole Guedj, David Meunier, Martine Meunier, Fadila Hadj-Bouziane
The locus coeruleus-norepinephrine (LC-NE) system is thought to act at synaptic, cellular, microcircuit, and network levels to facilitate cognitive functions through at least two different processes, not mutually exclusive. Accordingly, as a reset signal, the LC-NE system could trigger brain network reorganizations in response to salient information in the environment and/or adjust the neural gain within its target regions to optimize behavioral responses. Here, we provide evidence of the co-occurrence of these two mechanisms at the whole-brain level, in resting-state conditions following a pharmacological stimulation of the LC-NE system...
2017: Neural Plasticity
https://www.readbyqxmd.com/read/28596770/a-phase-1-human-immunodeficiency-virus-vaccine-trial-for-cross-profiling-the-kinetics-of-serum-and-mucosal-antibody-responses-to-cn54gp140-modulated-by-two-homologous-prime-boost-vaccine-regimens
#15
Sven Kratochvil, Paul F McKay, Jakub T Kopycinski, Cynthia Bishop, Peter John Hayes, Luke Muir, Christopher L Pinder, Deniz Cizmeci, Deborah King, Yoann Aldon, Bruce D Wines, P Mark Hogarth, Amy W Chung, Stephen J Kent, Kathrin Held, Christof Geldmacher, Len Dally, Nelson S Santos, Tom Cole, Jill Gilmour, Sarah Fidler, Robin J Shattock
A key aspect to finding an efficacious human immunodeficiency virus (HIV) vaccine is the optimization of vaccine schedules that can mediate the efficient maturation of protective immune responses. In the present study, we investigated the effect of alternate booster regimens on the immune responses to a candidate HIV-1 clade C CN54gp140 envelope protein, which was coadministered with the TLR4-agonist glucopyranosyl lipid A-aqueous formulation. Twelve study participants received a common three-dose intramuscular priming series followed by a final booster at either 6 or 12 months...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28592540/covalent-linkage-of-hiv-1-trimers-to-synthetic-liposomes-elicits-improved-b-cell-and-antibody-responses
#16
Shridhar Bale, Geraldine Goebrecht, Armando Stano, Richard Wilson, Takayuki Ota, Karen Tran, Jidnyasa Ingale, Michael B Zwick, Richard T Wyatt
We have demonstrated that a liposomal array of well-ordered trimers enhances B cell activation, germinal center formation, and the elicitation of tier-2 autologous neutralizing antibodies. Previously, we coupled well-ordered cleavage-independent NFL trimers via their C-terminal polyhistidine tails to nickel lipids integrated into the lipid bilayer. Despite favorable in vivo effects, concern remained over the potentially longer-term in vivo instability of noncovalent linkage of the trimers to the liposomes. Accordingly, we tested both cobalt coupling and covalent linkage of the trimers to the liposomes by reengineering the polyhistidine tail to include a free cysteine on each protomer of model BG505 NFL trimers to allow covalent linkage...
August 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28590113/dacarbazine-loaded-hollow-mesoporous-silica-nanoparticles-grafted-with-folic-acid-for-enhancing-antimetastatic-melanoma-response
#17
Qianqian Liu, Nan Xu, Liping Liu, Jun Li, Yamin Zhang, Chen Shen, Khurram Shezad, Lianbin Zhang, Jintao Zhu, Juan Tao
Dacarbazine (DTIC) is one of the most important chemotherapeutic agents for the treatment of melanoma; however, its poor solubility, photosensitivity, instability, and serious toxicity to normal cells limit its clinical applications. In this article, we present a rationally designed nanocarrier based on hollow mesoporous silica nanoparticles (HMSNs) for the encapsulation and targeted release of DTIC for eradicating melanoma. The nanocarrier (DTIC@HMLBFs) is prepared by modifying HMSNs with carboxyl groups to enhance the loading of DTIC, followed by further enveloping of folic acid-grafted liposomes, which act as a melanoma active target for controlled and targeted drug release...
June 21, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28542576/ebola-virus-glycoprotein-directly-triggers-t-lymphocyte-death-despite-of-the-lack-of-infection
#18
Mathieu Iampietro, Patrick Younan, Andrew Nishida, Mukta Dutta, Ndongala Michel Lubaki, Rodrigo I Santos, Richard A Koup, Michael G Katze, Alexander Bukreyev
Fatal outcomes of Ebola virus (EBOV) infections are typically preceded by a 'sepsis-like' syndrome and lymphopenia despite T cells being resistant to Ebola infection. The mechanisms that lead to T lymphocytes death remain largely unknown; however, the degree of lymphopenia is highly correlative with fatalities. Here we investigated whether the addition of EBOV or its envelope glycoprotein (GP) to isolated primary human CD4+ T cells induced cell death. We observed a significant decrease in cell viability in a GP-dependent manner, which is suggestive of a direct role of GP in T cell death...
May 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28539447/a-map-of-the-arenavirus-nucleoprotein-host-protein-interactome-reveals-that-jun%C3%A3-n-virus-selectively-impairs-the-antiviral-activity-of-double-stranded-rna-activated-protein-kinase-pkr
#19
Benjamin R King, Dylan Hershkowitz, Philip L Eisenhauer, Marion E Weir, Christopher M Ziegler, Joanne Russo, Emily A Bruce, Bryan A Ballif, Jason Botten
Arenaviruses are enveloped negative-strand RNA viruses that cause significant human disease. These viruses encode only four proteins to accomplish the viral life cycle, so each arenavirus protein likely plays unappreciated accessory roles during infection. Here we used immunoprecipitation and mass spectrometry to identify human proteins that interact with the nucleoproteins (NPs) of the Old World arenavirus lymphocytic choriomeningitis virus (LCMV) and the New World arenavirus Junín virus (JUNV) strain Candid #1...
August 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28514687/particulate-array-of-well-ordered-hiv-clade-c-env-trimers-elicits-neutralizing-antibodies-that-display-a-unique-v2-cap-approach
#20
Paola Martinez-Murillo, Karen Tran, Javier Guenaga, Gustaf Lindgren, Monika Àdori, Yu Feng, Ganesh E Phad, Néstor Vázquez Bernat, Shridhar Bale, Jidnyasa Ingale, Viktoriya Dubrovskaya, Sijy O'Dell, Lotta Pramanik, Mats Spångberg, Martin Corcoran, Karin Loré, John R Mascola, Richard T Wyatt, Gunilla B Karlsson Hedestam
The development of soluble envelope glycoprotein (Env) mimetics displaying ordered trimeric symmetry has ushered in a new era in HIV-1 vaccination. The recently reported native, flexibly linked (NFL) design allows the generation of native-like trimers from clinical isolates at high yields and homogeneity. As the majority of infections world-wide are of the clade C subtype, we examined responses in non-human primates to well-ordered subtype C 16055 trimers administered in soluble or high-density liposomal formats...
May 16, 2017: Immunity
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