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https://www.readbyqxmd.com/read/28747274/efficacy-safety-and-effect-on-sexual-behaviour-of-on-demand-pre-exposure-prophylaxis-for-hiv-in-men-who-have-sex-with-men-an-observational-cohort-study
#1
Jean-Michel Molina, Isabelle Charreau, Bruno Spire, Laurent Cotte, Julie Chas, Catherine Capitant, Cecile Tremblay, Daniela Rojas-Castro, Eric Cua, Armelle Pasquet, Camille Bernaud, Claire Pintado, Constance Delaugerre, Luis Sagaon-Teyssier, Soizic Le Mestre, Christian Chidiac, Gilles Pialoux, Diane Ponscarme, Julien Fonsart, David Thompson, Mark A Wainberg, Veronique Doré, Laurence Meyer
BACKGROUND: Data for on-demand pre-exposure prophylaxis (PrEP) are scarce. We implemented a cohort study to assess its efficacy, safety, and effect on sexual behaviour. METHODS: We invited men and transgender women who have sex with men, previously enrolled in the randomised placebo-controlled ANRS IPERGAY trial at seven sites (six in France and one in Canada), to participate in an open-label extension with on-demand tenofovir disoproxil fumarate (300 mg) and emtricitabine (200 mg) to be taken before and after sexual intercourse...
July 21, 2017: Lancet HIV
https://www.readbyqxmd.com/read/28745057/a-nanoscale-ion-pump-derived-from-a-biological-water-channel
#2
Karl Decker, Martin Anthony Page, Aleksei Aksimentiev
Biological molecular machines perform the work of supporting life at the smallest of scales, including the work of shuttling ions across cell boundaries and against chemical gradients. Systems of artificial channels at the nanoscale can likewise control ionic concentration by way of ionic current rectification, species selectivity, and voltage gating mechanisms. Here, we theoretically show that a voltage-gated, ion species-selective and rectifying ion channel can be built using components of a biological water channel aquaporin...
July 26, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28743278/status-of-insecticide-resistance-in-anopheles-mosquitoes-in-ubon-ratchathani-province-northeastern-thailand
#3
Anchana Sumarnrote, Hans J Overgaard, Nattapol Marasri, Bénédicte Fustec, Kanutcharee Thanispong, Theeraphap Chareonviriyaphap, Vincent Corbel
BACKGROUND: Malaria is common in hilly, forested areas along national borders in Southeast Asia. Insecticide resistance in malaria vectors has been detected in a few countries in the Greater Mekong sub-region (GMS), representing a threat to malaria control and prevention. This study aims to determine the insecticide resistance status of Anopheles mosquitoes in Ubon Ratchathani province, northeastern Thailand, where increasing number of malaria cases were reported recently. METHODS: Mosquitoes were collected in 2013-2015 using human landing and cattle bait collections in six sites during both the rainy and dry seasons...
July 25, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28740864/metal-nanoparticle-film-based-room-temperature-coulomb-transistor
#4
Svenja Willing, Hauke Lehmann, Mirjam Volkmann, Christian Klinke
Single-electron transistors would represent an approach to developing less power-consuming microelectronic devices if room temperature operation and industry-compatible fabrication were possible. We present a concept based on stripes of small, self-assembled, colloidal, metal nanoparticles on a back-gate device architecture, which leads to well-defined and well-controllable transistor characteristics. This Coulomb transistor has three main advantages. By using the scalable Langmuir-Blodgett method, we combine high-quality chemically synthesized metal nanoparticles with standard lithography techniques...
July 2017: Science Advances
https://www.readbyqxmd.com/read/28739256/palmitoylation-of-ca-2-channel-subunit-cav%C3%AE-2a-induces-pancreatic-beta-cell-toxicity-via-ca-2-overload
#5
Abdulla S Kazim, Petter Storm, Enming Zhang, Erik Renström
High blood glucose triggers the release of insulin from pancreatic beta cells, but if chronic, causes cellular stress, partly due to impaired Ca(2+) homeostasis. Ca(2+) influx is controlled by voltage-gated calcium channels (CaV) and high density of CaV in the plasma membrane could lead to Ca(2+) overload. Trafficking of the pore-forming CaVα1 subunit to the plasma membrane is regulated by auxiliary subunits, such as the CaVβ2a subunit. This study investigates, using Ca(2+) imaging and immunohistochemistry, the role of palmitoylation of CaVβ2a in maintaining Ca(2+) homeostasis and beta cell function...
July 21, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28737906/role-of-the-protein-dimeric-interface-in-allosteric-inhibition-of-n-acetyl-aspartate-hydrolysis-by-human-aspartoacylase
#6
Ekaterina D Kots, Sofya V Lushchekina, Sergey D Varfolomeev, Alexander V Nemukhin
The results of molecular modeling suggest a mechanism of allosteric inhibition upon hydrolysis of N-acetyl-aspartate (NAA), one of the most abundant amino acid derivatives in brain, by human aspartoacylase (hAsp). Details of this reaction are important to suggest the practical ways to control the enzyme activity. Search for allosteric sites using the Allosite web server and SiteMap analysis allowed us to identify substrate binding pockets located at the interface between the subunits of the hAsp dimer molecule...
July 24, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28737747/a-spatially-localized-architecture-for-fast-and-modular-dna-computing
#7
Gourab Chatterjee, Neil Dalchau, Richard A Muscat, Andrew Phillips, Georg Seelig
Cells use spatial constraints to control and accelerate the flow of information in enzyme cascades and signalling networks. Synthetic silicon-based circuitry similarly relies on spatial constraints to process information. Here, we show that spatial organization can be a similarly powerful design principle for overcoming limitations of speed and modularity in engineered molecular circuits. We create logic gates and signal transmission lines by spatially arranging reactive DNA hairpins on a DNA origami. Signal propagation is demonstrated across transmission lines of different lengths and orientations and logic gates are modularly combined into circuits that establish the universality of our approach...
July 24, 2017: Nature Nanotechnology
https://www.readbyqxmd.com/read/28737173/coherent-superpositions-of-three-states-for-phosphorous-donors-in-silicon-prepared-using-thz-radiation
#8
S Chick, N Stavrias, K Saeedi, B Redlich, P T Greenland, G Matmon, M Naftaly, C R Pidgeon, G Aeppli, B N Murdin
Superposition of orbital eigenstates is crucial to quantum technology utilizing atoms, such as atomic clocks and quantum computers, and control over the interaction between atoms and their neighbours is an essential ingredient for both gating and readout. The simplest coherent wavefunction control uses a two-eigenstate admixture, but more control over the spatial distribution of the wavefunction can be obtained by increasing the number of states in the wavepacket. Here we demonstrate THz laser pulse control of Si:P orbitals using multiple orbital state admixtures, observing beat patterns produced by Zeeman splitting...
July 24, 2017: Nature Communications
https://www.readbyqxmd.com/read/28737061/functional-and-structural-alterations-in-the-migraine-cerebellum
#9
Jan Mehnert, Arne May
The cerebellum plays an important role in pain processing but its function in headache and specifically in migraine is not known. We therefore compared 54 migraineurs with pairwise matched healthy controls in a magnetic resonance imaging study on neuronal cerebellar activity in response to nociceptive trigeminal sensation and also investigated possible structural alterations. Headache frequency, disease duration, and the proximity to a migraine attack were used as co-factors. Migraine patients showed functional and structural alterations in the posterior part of the cerebellum, namely crus I and crus II...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28736919/a-g326e-substitution-in-the-glutamate-gated-chloride-channel-3-glucl3-of-the-two-spotted-spider-mite-tetranychus-urticae-abolishes-the-agonistic-activity-of-macrocyclic-lactones
#10
Catherine Mermans, Wannes Dermauw, Sven Geibel, Thomas Van Leeuwen
BACKGROUND: The macrocyclic lactones abamectin and milbemectin are frequently used to control phytophagous mites such as Tetranychus urticae. Consequently, resistance has developed and was genetically linked with substitutions in the glutamate-gated chloride channel (GluCl) subunits TuGluCl1 and TuGluCl3. Here, we functionally validated a G326E substitution in TuGluCl3 by functional expression in Xenopus laevis oocytes followed by two-electrode voltage-clamp electrophysiology. RESULTS: Homomeric wild-type and mutated GluCl3 were successfully expressed...
July 24, 2017: Pest Management Science
https://www.readbyqxmd.com/read/28735901/mechanisms-of-pannexin1-channel-gating-and-regulation
#11
REVIEW
Paige Whyte-Fagundes, Georg Zoidl
Pannexins are a family of integral membrane proteins with distinct post-translational modifications, sub-cellular localization and tissue distribution. Panx1 is the most studied and best-characterized isoform of this gene family. The ubiquitous expression, as well as its function as a major ATP release and nucleotide permeation channel, makes Panx1 a primary candidate for participating in the pathophysiology of CNS disorders. While many investigations revolve around Panx1 functions in health and disease, more recently, details started emerging about mechanisms that control Panx1 channel activity...
July 20, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28735752/conformational-changes-of-cftr-upon-phosphorylation-and-atp-binding
#12
Zhe Zhang, Fangyu Liu, Jue Chen
The cystic fibrosis transmembrane conductance regulator (CFTR) is an anion channel evolved from an ATP-binding cassette transporter. CFTR channel gating is strictly coupled to phosphorylation and ATP hydrolysis. Previously, we reported essentially identical structures of zebrafish and human CFTR in the dephosphorylated, ATP-free form. Here, we present the structure of zebrafish CFTR in the phosphorylated, ATP-bound conformation, determined by cryoelectron microscopy to 3.4 Å resolution. Comparison of the two conformations shows major structural rearrangements leading to channel opening...
July 18, 2017: Cell
https://www.readbyqxmd.com/read/28734106/insecticide-resistance-in-trialeurodes-vaporariorum-populations-and-novel-diagnostics-for-kdr-mutations
#13
Despoina Evr Kapantaidaki, Eldem Sadikoglou, Dimitra Tsakireli, Vasileios Kampanis, Marianna Stavrakaki, Corinna Schorn, Aris Ilias, Maria Riga, George Tsiamis, Ralf Nauen, George Skavdis, John Vontas, Anastasia Tsagkarakou
BACKGROUND: Neonicotinoids, pyrethroids and ketoenols, are currently used for the control of Trialeurodes vaporariorum (Hemiptera: Aleyrodidae). In this study, insecticide resistance status and mechanisms were investigated by classical bioassays and molecular techniques. RESULTS: Dose response bioassays were performed on 19 Greek populations, among the 35 different whitefly populations used for the whole analysis. Resistance factors scaled up to 207-, 4657- and 59- fold, for imidacloprid, bifenthrin and spiromesifen, respectively...
July 22, 2017: Pest Management Science
https://www.readbyqxmd.com/read/28734079/post-translational-palmitoylation-controls-the-voltage-gating-and-lipid-raft-association-of-calhm1-channel
#14
Akiyuki Taruno, Hongxin Sun, Koichi Nakajo, Tatsuro Murakami, Yasuyoshi Ohsaki, Mizuho A Kido, Fumihito Ono, Yoshinori Marunaka
Emerging roles of CALHM1, a recently discovered voltage-gated ion channel, include purinergic neurotransmission of tastes in taste buds and memory formation in the brain, highlighting its physiological importance. However, the regulatory mechanisms of the CALHM1 channel remain entirely unexplored, hindering full understanding of its contribution in vivo. In fact, the different gating properties of CALHM1 in vivo and in vitro suggest undiscovered regulatory mechanisms. Here, in searching for post-translational regulatory mechanisms, we discovered the regulation of CALHM1 gating and association with lipid microdomains via protein S-palmitoylation, the only reversible lipid modification of proteins on cysteine residues...
July 22, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28733618/cellular-interfaces-with-hydrogen-bonded-organic-semiconductor-hierarchical-nanocrystals
#15
Mykhailo Sytnyk, Marie Jakešová, Monika Litviňuková, Oleksandr Mashkov, Dominik Kriegner, Julian Stangl, Jana Nebesářová, Frank W Fecher, Wolfgang Schöfberger, Niyazi Serdar Sariciftci, Rainer Schindl, Wolfgang Heiss, Eric Daniel Głowacki
Successful formation of electronic interfaces between living cells and semiconductors hinges on being able to obtain an extremely close and high surface-area contact, which preserves both cell viability and semiconductor performance. To accomplish this, we introduce organic semiconductor assemblies consisting of a hierarchical arrangement of nanocrystals. These are synthesised via a colloidal chemical route that transforms the nontoxic commercial pigment quinacridone into various biomimetic three-dimensional arrangements of nanocrystals...
July 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28733581/structural-determinants-at-the-m2-muscarinic-receptor-modulate-the-rgs4-girk-response-to-pilocarpine-by-impairment-of-the-receptor-voltage-sensitivity
#16
I-Shan Chen, Kazuharu Furutani, Yoshihisa Kurachi
Membrane potential controls the response of the M2 muscarinic receptor to its ligands. Membrane hyperpolarization increases response to the full agonist acetylcholine (ACh) while decreasing response to the partial agonist pilocarpine. We previously have demonstrated that the regulator of G-protein signaling (RGS) 4 protein discriminates between the voltage-dependent responses of ACh and pilocarpine; however, the underlying mechanism remains unclear. Here we show that RGS4 is involved in the voltage-dependent behavior of the M2 muscarinic receptor-mediated signaling in response to pilocarpine...
July 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28733580/implementing-a-universal-gate-set-on-a-logical-qubit-encoded-in-an-oscillator
#17
Reinier W Heeres, Philip Reinhold, Nissim Ofek, Luigi Frunzio, Liang Jiang, Michel H Devoret, Robert J Schoelkopf
A logical qubit is a two-dimensional subspace of a higher dimensional system, chosen such that it is possible to detect and correct the occurrence of certain errors. Manipulation of the encoded information generally requires arbitrary and precise control over the entire system. Whether based on multiple physical qubits or larger dimensional modes such as oscillators, the individual elements in realistic devices will always have residual interactions, which must be accounted for when designing logical operations...
July 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28732776/rad-gtpase-is-essential-for-the-regulation-of-bone-density-and-bone-marrow-adipose-tissue-in-mice
#18
Catherine N Withers, Drew M Brown, Innocent Byiringiro, Matthew R Allen, Keith W Condon, Jonathan Satin, Douglas A Andres
The small GTP-binding protein Rad (RRAD, Ras associated with diabetes) is the founding member of the RGK (Rad, Rem, Rem2, and Gem/Kir) family that regulates cardiac voltage-gated Ca(2+) channel function. However, its cellular and physiological functions outside of the heart remain to be elucidated. Here we report that Rad GTPase function is required for normal bone homeostasis in mice, as Rad deletion results in significantly lower bone mass and higher bone marrow adipose tissue (BMAT) levels. Dynamic histomorphometry in vivo and primary calvarial osteoblast assays in vitro demonstrate that bone formation and osteoblast mineralization rates are depressed, while in vitro osteoclast differentiation is increased, in the absence of Rad...
July 18, 2017: Bone
https://www.readbyqxmd.com/read/28732773/efficacy-of-oral-pre-exposure-prophylaxis-prep-for-hiv-among-women-with-abnormal-vaginal-microbiota-a-post-hoc-analysis-of-the-randomised-placebo-controlled-partners-prep-study
#19
Renee Heffron, R Scott McClelland, Jennifer E Balkus, Connie Celum, Craig R Cohen, Nelly Mugo, Elizabeth Bukusi, Deborah Donnell, Jairam Lingappa, James Kiarie, Tina Fiedler, Matthew Munch, David N Fredricks, Jared M Baeten
BACKGROUND: Daily oral tenofovir-based pre-exposure prophylaxis (PrEP) is high efficacious for HIV prevention among women with high adherence. However, the effect of abnormal vaginal microbiota on PrEP efficacy is of concern. We investigated whether bacterial vaginosis modified the efficacy of oral PrEP. METHODS: We used prospectively collected data from women in the Partners PrEP Study, a placebo-controlled trial of daily oral PrEP (either tenofovir monotherapy or a combination of tenofovir and emtricitabine) in HIV serodiscordant couples aged 18 years or older in Kenya and Uganda that showed high efficacy in women...
July 18, 2017: Lancet HIV
https://www.readbyqxmd.com/read/28731153/altered-profile-of-mrna-expression-in-atrioventricular-node-of-streptozotocin%C3%A2-induced-diabetic-rats
#20
Frank Christopher Howarth, Khatija Parekh, Petrilla Jayaprakash, Edward Samuel Inbaraj, Murat Oz, Halina Dobrzynski, Thomas Edward Adrian
Prolonged action potential duration, reduced action potential firing rate, upstroke velocity and rate of diastolic depolarization have been demonstrated in atrioventricular node (AVN) cells from streptozotocin (STZ)‑induced diabetic rats. To further clarify the molecular basis of these electrical disturbances, the mRNA profiles encoding a variety of proteins associated with the generation and conduction of electrical activity in the AVN, were evaluated in the STZ‑induced diabetic rat heart. Expression of mRNA was measured in AVN biopsies using reverse transcription‑quantitative polymerase chain reaction techniques...
July 20, 2017: Molecular Medicine Reports
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