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Thomas Briese, David T Williams, Vishal Kapoor, Sinead M Diviney, Andrea Certoma, Jianning Wang, Cheryl A Johansen, Rashmi Chowdhary, John S Mackenzie, W Ian Lipkin
The Mapputta group comprises antigenically related viruses indigenous to Australia and Papua New Guinea that are included in the family Bunyaviridae but not currently assigned to a specific genus. We determined and analyzed the genome sequences of five Australian viruses isolated from mosquitoes collected during routine arbovirus surveillance in Western Australia (K10441, SW27571, K13190, and K42904) and New South Wales (12005). Based on matching sequences of all three genome segments to prototype MRM3630 of Trubanaman virus (TRUV), NB6057 of Gan Gan virus (GGV), and MK7532 of Maprik virus (MPKV), isolates K13190 and SW27571 were identified as TRUV, 12005 as GGV, and K42904 as a Mapputta group virus from Western Australia linking GGV and MPKV...
2016: PloS One
Kristin Forner, Carl Roos, David Dahlgren, Filippos Kesisoglou, Moritz A Konerding, Johanna Mazur, Hans Lennernäs, Peter Langguth
CONTEXT: Prediction of the in vivo absorption of poorly soluble drugs may require simultaneous dissolution/permeation experiments. In vivo predictive media have been modified for permeation experiments with Caco-2 cells, but not for excised rat intestinal segments. OBJECTIVE: The present study aimed to improve the setup of dissolution/permeation experiments with excised rat intestinal segments by assessing suitable donor and receiver media. METHODS: The regional compatibility of rat intestine in Ussing chambers with modified Fasted and Fed State Simulated Intestinal Fluids (Fa/FeSSIFmod) as donor media was evaluated via several parameters that reflect the viability of the excised intestinal segments...
October 20, 2016: Drug Development and Industrial Pharmacy
Deborah S Bower, David M Scheltinga, Simon Clulow, John Clulow, Craig E Franklin, Arthur Georges
Freshwater biota experience physiological challenges in regions affected by salinization, but often the effects on particular species are poorly understood. Freshwater turtles are of particular concern as they appear to have limited ability to cope with environmental conditions that are hyperosmotic to their body fluids. Here, we determined the physiological responses of two Australian freshwater chelid turtles, Emydura macquarii and Chelodina expansa, exposed to freshwater (0‰) and brackish water (15‰, representing a hyperosmotic environment)...
2016: Conservation Physiology
Andrea J Morash, Sara R C Mackellar, Louise Tunnah, David A Barnett, Kilian M Stehfest, Jayson M Semmens, Suzanne Currie
Estuarine habitats are frequently used as nurseries by elasmobranch species for their protection and abundant resources; however, global climate change is increasing the frequency and severity of environmental challenges in these estuaries that may negatively affect elasmobranch physiology. Hyposmotic events are particularly challenging for marine sharks that osmoconform, and species-specific tolerances are not well known. Therefore, we sought to determine the effects of an acute (48 h) ecologically relevant hyposmotic event (25...
2016: Conservation Physiology
David Harrison
Hypertension remains an enormous health care burden that affects one third of the population. Despite its prevalence the cause of most cases of hypertension remains unknown. Our laboratory has defined a novel mechanism for hypertension involving adaptive immunity. We found that mice lacking lymphocytes (RAG-1 mice) develop blunted hypertensive responses to a variety of stimuli including chronic angiotensin II infusion, DOCA-salt challenge and norepinephrine infusion. Adoptive transfer of T cells, but not B cells, restores the hypertensive responses to these stimuli...
September 2016: Journal of Hypertension
David John Webb
Treatment-resistant hypertension (TRH) is defined as the failure to achieve an office BP target of <140/90 mmHg (<130/80 mmHg in patients with chronic kidney disease (CKD) or diabetes) in patients with hypertension (HT), despite adherence to at least 3 antihypertensive medications at optimal tolerated doses, ideally including a diuretic (Calhoun et al., Circulation 2008). TRH identifies patients with hard-to-treat HT, who might benefit from specialist investigation and treatment. Although some studies put the prevalence of TRH as >10%, these levels may be inflated by white-coat hypertension and poor adherence...
September 2016: Journal of Hypertension
John Rathbone, Richard Franklin, Clinton Gibbs, David Williams
Signs of Irukandji syndrome (IS) suggest an underlying catecholamine storm with research demonstrating that Carukia barnesi venom causes a significant rise in adrenaline/noradrenaline serum levels. A systematic review was undertaken to ascertain the current evidence in treating IS with magnesium salts. A literature search was conducted using Scopus, Medline and ScienceDirect. Further articles were discarded via title description and/or abstract details. The remaining were read in full, and those identified as not having sufficient information regarding magnesium and patient outcomes were removed...
October 17, 2016: Emergency Medicine Australasia: EMA
Billie A Gould, Yani Chen, David B Lowry
The early stages of speciation are often characterized by the formation of partially reproductively isolated ecotypes, which evolve as a byproduct of divergent selective forces that are endemic to different habitats. Identifying the genomic regions, genes, and ultimately functional polymorphisms that are involved in the processes of ecotype formation is inherently challenging, as there are likely to be many different loci involved in the process. To localize candidate regions of the genome contributing to ecotype formation, we conducted whole genome pooled-sequencing (pool-seq) with 47 coastal perennial and 50 inland annual populations of the yellow monkeyflower, Mimulus guttatus...
October 16, 2016: Molecular Ecology
Hayden Wilson, David Mycock, Isabel M Weiersbye
Tamarix usneoides is a halophyte tree endemic to south-western Africa. This species is known to excrete a range of ions from specialised glandular structures on its leaves. To understand the mechanisms involved in the transport, sequestration and excretion of ions by the glands, a study was performed on salt gland distribution and ultrastructure. The glands are vesiculated trichomes, comprised of eight cells viz., two basal collecting cells and six excretory cells, partially bounded by a secondary cell wall which, could serve as an impermeable barrier, forcing excess ions to move from the apoplast of the surrounding tissue into the cytoplasm of the basal excretory cells...
October 14, 2016: International Journal of Phytoremediation
Ka Wai Fung, David W Wright, Jayesh Gor, Marcus J Swann, Stephen J Perkins
During the activation of complement C4 to C4b, the exposure of its thioester domain (TED) is crucial for the attachment of C4b to activator surfaces. In the C4b crystal structure, TED forms an Arg(104)-Glu(1032) salt bridge to tether its neighbouring macroglobulin (MG1) domain. Here, we examined the C4b domain structure to test whether this salt bridge affects its conformation. Dual polarisation interferometry of C4b immobilised at a sensor surface showed that the maximum thickness of C4b increased by 0.46 nm with increase in NaCl concentration from 50 mM to 175 mM NaCl...
October 13, 2016: Biochemical Journal
Benjamin P Partlow, Mehran Bagheri, James L Harden, David L Kaplan
Native silk fibers exhibit strength and toughness that rival those of the best synthetic fibers. Importantly, the silkworm is able to spin these fibers using only water as a solvent with fine control of applied shear, drawing, pH and salt concentrations to efficiently convert the spinning dope into a fiber. This is in contrast to synthetic polymers that often require organic solvents and extreme processing conditions. Further insight is still needed into the mechanisms by which silkworms are capable of spinning such tough fibers...
October 13, 2016: Biomacromolecules
Joseph Michael Autry, David D Thomas, L Michel Espinoza-Fonseca
We have performed μs molecular dynamics simulation (MDS) to identify structural mechanisms for sarcolipin (SLN) uncoupling of Ca(2+) transport from ATP hydrolysis for the sarcoplasmic reticulum Ca(2+)-ATPase (SERCA). SLN regulates muscle metabolism and energy expenditure to provide resistance against diet-induced obesity and extreme cold. MDS demonstrates that the cytosolic domain of SLN induces a salt bridge-mediated structural rearrangement in the energy-transduction domain of SERCA. We propose that this structural change uncouples SERCA by perturbing Ca(2+) occlusion at residue E309 in transport site II, thus facilitating cytosolic Ca(2+) backflux...
October 12, 2016: Biochemistry
Dana Krepel, David Gomez, Stefan Klumpp, Yaakov Levy
The key feature explaining the rapid recognition by a protein of its DNA target site lies in the combination of one- and three-dimensional (1D and 3D) diffusion, which allows efficient scanning of the many alternative sites. This facilitated diffusion mechanism is expected to be affected by cellular conditions, particularly crowding, given that up to 40% of the total cellular volume may by occupied by macromolecules. Using coarse-grained molecular dynamics and Monte-Carlo simulations, we show that the crowding particles can enhance facilitated diffusion and accelerate search kinetics...
October 10, 2016: Journal of Physical Chemistry. B
Damiano Cattaneo, Laura J McCormick, David B Cordes, Alexandra M Z Slawin, Russell E Morris
Two salts of the chlorhexidine di-cation (H2CHx(2+)) - (H2CHx)(SO4)·3H2O and (H2CHx)(CO3)·4H2O - have been synthesised and characterised crystallographically.
October 5, 2016: Journal of Molecular Structure
Bachir Bensenane, Zouhair Asfari, Carlos Platas-Iglesias, David Esteban-Gómez, Fatiha Djafri, Mourad Elhabiri, Loïc J Charbonnière
The syntheses of two new ligands based on a calix[4]arene scaffold in the cone conformation functionalized on the phenolic positions 1 and 3 by diethylthiophosphonates (L1) or tetra(tri)thioethyleneglycol (L2) crowns are described. Together with ligand L3, the parent calix[4]arene substituted by a penta(tetra)thioethyleneglycol crown, the spectroscopic properties of the ligands were determined by means of UV-Vis absorption spectroscopy and steady-state and time-resolved fluorescence spectroscopy, showing that the ligands display modest but non-negligible intrinsic fluorescence properties (ϕfluo = 0...
September 27, 2016: Dalton Transactions: An International Journal of Inorganic Chemistry
David A Hirsh, Aaron J Rossini, Lyndon Emsley, Robert W Schurko
In this work, we show how to obtain efficient dynamic nuclear polarization (DNP) enhanced (35)Cl solid-state NMR (SSNMR) spectra at 9.4 T and demonstrate how they can be used to characterize the molecular-level structure of hydrochloride salts of active pharmaceutical ingredients (APIs) in both bulk and low wt% API dosage forms. (35)Cl SSNMR central-transition powder patterns of chloride ions are typically tens to hundreds of kHz in breadth, and most cannot be excited uniformly with high-power rectangular pulses or acquired under conditions of magic-angle spinning (MAS)...
September 21, 2016: Physical Chemistry Chemical Physics: PCCP
Yu-Su Chen, David W Allen, Graham J Tizzard, Mateusz B Pitak, Simon J Coles, Neil A Cross, Neil Bricklebank
The ability of phosphonium cations to act as intracellular transport vectors is well-established. Phosphonioalkylthiosulfate zwitterions, and ω-thioacetylalkylphosphonium salts, which act as 'masked thiolate' ligands, are useful precursors for the formation of phosphonium-functionalised gold nanoparticles, enabling the nanoparticles to be transported into cells for diagnostic and therapeutic purposes. In this study we have completed cytotoxicity studies of ω-thioacetylpropylphosphonium salts derived from triphenylphosphine and tri(4-fluorophenyl)phosphine, which show that the compounds are only toxic towards PC3 prostate cancer cells at high concentrations and at prolonged incubation periods and display IC50 values of 67 μM and 252 μM respectively, significantly higher than those of other phosphonium salts...
August 18, 2016: European Journal of Medicinal Chemistry
Thilina Jayarathne, Camille M Sultana, Christopher Lee, Francesca Malfatti, Joshua L Cox, Matthew A Pendergraft, Kathryn A Moore, Farooq Azam, Alexei V Tivanski, Christopher David Cappa, Timothy H Bertram, Vicki H Grassian, Kimberly Ann Prather, Elizabeth A Stone
Sea spray aerosol (SSA) is a globally important source of particulate matter. A mesocosm study was performed to determine the relative enrichment of saccharides and inorganic ions in nascent fine (PM2.5) and coarse (PM10-2.5) SSA and sea surface microlayer (SSML) relative to bulk seawater. Saccharides comprise a significant fraction of organic matter in fine and coarse SSA (11% and 27%, respectively). Relative to sodium, individual saccharides were enriched 14-1314 times in fine SSA, 3-138 times in coarse SSA, but only up to 1...
October 6, 2016: Environmental Science & Technology
Yandong Huang, Wei Chen, David L Dotson, Oliver Beckstein, Jana Shen
Escherichia coli NhaA is a prototype sodium-proton antiporter, which has been extensively characterized by X-ray crystallography, biochemical and biophysical experiments. However, the identities of proton carriers and details of pH-regulated mechanism remain controversial. Here we report constant pH molecular dynamics data, which reveal that NhaA activation involves a net charge switch of a pH sensor at the entrance of the cytoplasmic funnel and opening of a hydrophobic gate at the end of the funnel. The latter is triggered by charging of Asp164, the first proton carrier...
October 6, 2016: Nature Communications
Shulin Shi, Tao Wang, Ziru Chen, Zhong Tang, Zhongchang Wu, David E Salt, Dai-Yin Chao, Fangjie Zhao
Rice is a major dietary source of the toxic metalloid arsenic. Reducing its accumulation in rice grain is of critical importance to food safety. Rice roots take up arsenate and arsenite depending on the prevailing soil conditions. The first step of arsenate detoxification is its reduction to arsenite, but the enzyme(s) catalyzing this reaction in rice remains unknown. Here, we identify OsHAC1;1 and OsHAC1;2 as arsenate reductases in rice. OsHAC1;1 and OsHAC1;2 are able to complement an Escherichia coli mutant lacking the endogenous arsenate reductase and to reduce arsenate to arsenite...
October 4, 2016: Plant Physiology
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