Interpreting spatial patterns in redox and coupled water-nitrogen fluxes in the streambed of a gaining river reach

Water pathways through permeable riverbeds are multi-dimensional, including lateral hyporheic exchange flows as well as vertical (upwelling and downwelling) fluxes. The influence of different pathways of water on solute patterns and the supply of nitrate and other redox-sensitive chemical species in the riverbed is poorly understood but could be environmentally significant. For example, nitrate-rich upwelling water in the gaining reaches of groundwater-fed rivers has the potential to supply significant quantities of nitrate through the riverbed to surface waters, constraining opportunities to deliver the goals of the EU Water Framework Directive to achieve ‘good ecological status’. We show that patterns in porewater chemistry in the armoured river bed of a gaining reach (River Leith, Cumbria) reflect the spatial variability in different sources of water; oxic conditions being associated with preferential discharge from groundwater and reducing conditions with longitudinal and lateral fluxes of water due to water movement from riparian zones and/or hyporheic exchange flows. Our findings demonstrate the important control of both vertical and lateral water fluxes on patterns of redox-sensitive chemical species in the river bed. Furthermore, under stable, baseflow conditions (<Q90) a zone of preferential discharge, comprising 20 % of the reach by area contributes 4–9 % of the total nitrate being transported through the reach in surface water, highlighting the need to understand the spatial distribution of such preferential discharge locations at the catchment scale to establish their importance for nitrate delivery to the stream channel

Diffusive equilibrium in thin-films (DET) provides evidence of suppression of hyporheic exchange and large-scale nitrate transformation in a groundwater-fed river

The hyporheic zone of riverbed sediments has the potential to attenuate nitrate from upwelling, polluted groundwater. However, the coarse-scale (5 – 10 cm) measurement of nitrogen biogeochemistry in the hyporheic zone can often mask fine-scale (<1 cm) biogeochemical patterns, especially in near-surface sediments, leading to incomplete or inaccurate representation of the capacity of the hyporheic zone to transform upwelling NO3-. In this study, we utilised diffusive equilibrium in thin-films (DET) samplers to capture high resolution (cm-scale) vertical concentration profiles of NO3-, SO42-, Fe and Mn in the upper 15 cm of armoured and permeable riverbed sediments. The goal was to test whether nitrate attenuation was occurring in a sub-reach characterised by strong vertical (upwelling) water fluxes. The vertical concentration profiles obtained from DET samplers indicate considerable cm-scale variability in NO3- (4.4 ± 2.9 mg N/L), SO42- (9.9 ± 3.1 mg/L) and dissolved Fe (1.6 ± 2.1 mg/L) and Mn (0.2 ± 0.2 mg/L). However, the overall trend suggests the absence of substantial net chemical transformations and surface-subsurface water mixing in the shallow sediments of our sub-reach under baseflow conditions. The significance of this is that upwelling NO3--rich groundwater does not appear to be attenuated in the riverbed sediments at <15 cm depth as might occur where hyporheic exchange flows deliver organic matter to the sediments for metabolic processes. It would appear that the chemical patterns observed in the shallow sediments of our sub-reach are not controlled exclusively by redox processes and / or hyporheic exchange flows. Deeper-seated groundwater fluxes and hydro-stratigraphy may be additional important drivers of chemical patterns in the shallow sediments of our study sub-reach. This article is protected by copyright. All rights reserved

Elevated arousal at time of decision-making is not the arbiter of risk avoidance in chickens

The somatic marker hypothesis proposes that humans recall previously experienced physiological responses to aid decision-making under uncertainty. However, little is known about the mechanisms used by non-human animals to integrate risk perception with predicted gains and losses. We monitored the behaviour and physiology of chickens when the choice between a high-gain (large food quantity), high-risk (1 in 4 probability of receiving an air-puff) option (HGRAP) or a low-gain (small food quantity), no-risk (of an air-puff) (LGNAP) option. We assessed when arousal increased by considering different stages of the decision-making process (baseline, viewing, anticipation, reward periods) and investigated whether autonomic responses influenced choice outcome both immediately and in the subsequent trial. Chickens were faster to choose and their heart-rate significantly increased between the viewing and anticipation (post-decision, pre-outcome) periods when selecting the HGRAP option. This suggests that they responded physiologically to the impending risk. Additionally, arousal was greater following a HGRAP choice that resulted in an air-puff, but this did not deter chickens from subsequently choosing HGRAP. In contrast to human studies, we did not find evidence that somatic markers were activated during the viewing period, suggesting that arousal is not a good measure of avoidance in non-human animals

Design of an electrochemical micromachining machine

Electrochemical micromachining (μECM) is a non-conventional machining process based on the phenomenon of electrolysis. μECM became an attractive area of research due to the fact that this process does not create any defective layer after machining and that there is a growing demand for better surface integrity on different micro applications including microfluidics systems, stress-free drilled holes in automotive and aerospace manufacturing with complex shapes, etc. This work presents the design of a next generation μECM machine for the automotive, aerospace, medical and metrology sectors. It has three axes of motion (X, Y, Z) and a spindle allowing the tool-electrode to rotate during machining. The linear slides for each axis use air bearings with linear DC brushless motors and 2-nm resolution encoders for ultra precise motion. The control system is based on the Power PMAC motion controller from Delta Tau. The electrolyte tank is located at the rear of the machine and allows the electrolyte to be changed quickly. This machine features two process control algorithms: fuzzy logic control and adaptive feed rate. A self-developed pulse generator has been mounted and interfaced with the machine and a wire ECM grinding device has been added. The pulse generator has the possibility to reverse the pulse polarity for on-line tool fabrication.The research reported in this paper is supported by the European Commission within the project “Minimizing Defects in Micro-Manufacturing Applications (MIDEMMA)” (FP7-2011-NMPICT- FoF-285614)

Loss-of-function mutations in SLC30A8 protect against type 2 diabetes.

Neðst á síðunni er hægt að nálgast greinina í heild sinni með því að smella á hlekkinn View/OpenLoss-of-function mutations protective against human disease provide in vivo validation of therapeutic targets, but none have yet been described for type 2 diabetes (T2D). Through sequencing or genotyping of ~150,000 individuals across 5 ancestry groups, we identified 12 rare protein-truncating variants in SLC30A8, which encodes an islet zinc transporter (ZnT8) and harbors a common variant (p.Trp325Arg) associated with T2D risk and glucose and proinsulin levels. Collectively, carriers of protein-truncating variants had 65% reduced T2D risk (P = 1.7 × 10(-6)), and non-diabetic Icelandic carriers of a frameshift variant (p.Lys34Serfs*50) demonstrated reduced glucose levels (-0.17 s.d., P = 4.6 × 10(-4)). The two most common protein-truncating variants (p.Arg138* and p.Lys34Serfs*50) individually associate with T2D protection and encode unstable ZnT8 proteins. Previous functional study of SLC30A8 suggested that reduced zinc transport increases T2D risk, and phenotypic heterogeneity was observed in mouse Slc30a8 knockouts. In contrast, loss-of-function mutations in humans provide strong evidence that SLC30A8 haploinsufficiency protects against T2D, suggesting ZnT8 inhibition as a therapeutic strategy in T2D prevention.US National Institutes of Health (NIH) Training 5-T32-GM007748-33 Doris Duke Charitable Foundation 2006087 Fulbright Diabetes UK Fellowship BDA 11/0004348 Broad Institute from Pfizer, Inc. NIH U01 DK085501 U01 DK085524 U01 DK085545 U01 DK085584 Swedish Research Council Dnr 521-2010-3490 Dnr 349-2006-237 European Research Council (ERC) GENETARGET T2D GA269045 ENGAGE 2007-201413 CEED3 2008-223211 Sigrid Juselius Foundation Folkh lsan Research Foundation ERC AdG 293574 Research Council of Norway 197064/V50 KG Jebsen Foundation University of Bergen Western Norway Health Authority Lundbeck Foundation Novo Nordisk Foundation Wellcome Trust WT098017 WT064890 WT090532 WT090367 WT098381 Uppsala University Swedish Research Council and the Swedish Heart- Lung Foundation Academy of Finland 124243 102318 123885 139635 Finnish Heart Foundation Finnish Diabetes Foundation, Tekes 1510/31/06 Commission of the European Community HEALTH-F2-2007-201681 Ministry of Education and Culture of Finland European Commission Framework Programme 6 Integrated Project LSHM-CT-2004-005272 City of Kuopio and Social Insurance Institution of Finland Finnish Foundation for Cardiovascular Disease NIH/NIDDK U01-DK085545 National Heart, Lung, and Blood Institute (NHLBI) National Institute on Minority Health and Health Disparities N01 HC-95170 N01 HC-95171 N01 HC-95172 European Union Seventh Framework Programme, DIAPREPP Swedish Child Diabetes Foundation (Barndiabetesfonden) 5U01DK085526 DK088389 U54HG003067 R01DK072193 R01DK062370 Z01HG000024info:eu-repo/grantAgreement/EC/FP7/20201

The Concise Guide to PHARMACOLOGY 2015/16:Ligand-gated ion channels

The Concise Guide to PHARMACOLOGY 2015/16 provides concise overviews of the key properties of over 1750 human drug targets with their pharmacology, plus links to an open access knowledgebase of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. The full contents can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.13349/full. Ligand-gated ion channels are one of the eight major pharmacological targets into which the Guide is divided, with the others being: ligand-gated ion channels, voltage-gated ion channels, other ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The Concise Guide is published in landscape format in order to facilitate comparison of related targets. It is a condensed version of material contemporary to late 2015, which is presented in greater detail and constantly updated on the website www.guidetopharmacology.org, superseding data presented in the previous Guides to Receptors & Channels and the Concise Guide to PHARMACOLOGY 2013/14. It is produced in conjunction with NC-IUPHAR and provides the official IUPHAR classification and nomenclature for human drug targets, where appropriate. It consolidates information previously curated and displayed separately in IUPHAR-DB and GRAC and provides a permanent, citable, point-in-time record that will survive database updates

The Concise Guide to PHARMACOLOGY 2015/16:Nuclear hormone receptors

The Concise Guide to PHARMACOLOGY 2015/16 provides concise overviews of the key properties of over 1750 human drug targets with their pharmacology, plus links to an open access knowledgebase of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. The full contents can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.13352/full. Nuclear hormone receptors are one of the eight major pharmacological targets into which the Guide is divided, with the others being: G protein-coupled receptors, ligand-gated ion channels, voltage-gated ion channels, other ion channels, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The Concise Guide is published in landscape format in order to facilitate comparison of related targets. It is a condensed version of material contemporary to late 2015, which is presented in greater detail and constantly updated on the website www.guidetopharmacology.org, superseding data presented in the previous Guides to Receptors & Channels and the Concise Guide to PHARMACOLOGY 2013/14. It is produced in conjunction with NC-IUPHAR and provides the official IUPHAR classification and nomenclature for human drug targets, where appropriate. It consolidates information previously curated and displayed separately in IUPHAR-DB and GRAC and provides a permanent, citable, point-in-time record that will survive database updates

The Concise Guide to PHARMACOLOGY 2015/16:Enzymes

The Concise Guide to PHARMACOLOGY 2015/16 provides concise overviews of the key properties of over 1750 human drug targets with their pharmacology, plus links to an open access knowledgebase of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. The full contents can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.13354/full. G protein-coupled receptors are one of the eight major pharmacological targets into which the Guide is divided, with the others being: G protein-coupled receptors, ligand-gated ion channels, voltage-gated ion channels, other ion channels, nuclear hormone receptors, catalytic receptors and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The Concise Guide is published in landscape format in order to facilitate comparison of related targets. It is a condensed version of material contemporary to late 2015, which is presented in greater detail and constantly updated on the website www.guidetopharmacology.org, superseding data presented in the previous Guides to Receptors & Channels and the Concise Guide to PHARMACOLOGY 2013/14. It is produced in conjunction with NC-IUPHAR and provides the official IUPHAR classification and nomenclature for human drug targets, where appropriate. It consolidates information previously curated and displayed separately in IUPHAR-DB and GRAC and provides a permanent, citable, point-in-time record that will survive database updates

The Concise Guide to PHARMACOLOGY 2015/16:Transporters

The Concise Guide to PHARMACOLOGY 2015/16 provides concise overviews of the key properties of over 1750 human drug targets with their pharmacology, plus links to an open access knowledgebase of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. The full contents can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.13355/full. G protein-coupled receptors are one of the eight major pharmacological targets into which the Guide is divided, with the others being: G protein-coupled receptors, ligand-gated ion channels, voltage-gated ion channels, other ion channels, nuclear hormone receptors, catalytic receptors and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The Concise Guide is published in landscape format in order to facilitate comparison of related targets. It is a condensed version of material contemporary to late 2015, which is presented in greater detail and constantly updated on the website www.guidetopharmacology.org, superseding data presented in the previous Guides to Receptors & Channels and the Concise Guide to PHARMACOLOGY 2013/14. It is produced in conjunction with NC-IUPHAR and provides the official IUPHAR classification and nomenclature for human drug targets, where appropriate. It consolidates information previously curated and displayed separately in IUPHAR-DB and GRAC and provides a permanent, citable, point-in-time record that will survive database updates

The Concise Guide to PHARMACOLOGY 2015/16:Catalytic receptors

The Concise Guide to PHARMACOLOGY 2015/16 provides concise overviews of the key properties of over 1750 human drug targets with their pharmacology, plus links to an open access knowledgebase of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. The full contents can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.13353/full. G protein-coupled receptors are one of the eight major pharmacological targets into which the Guide is divided, with the others being: G protein-coupled receptors, ligand-gated ion channels, voltage-gated ion channels, other ion channels, nuclear hormone receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The Concise Guide is published in landscape format in order to facilitate comparison of related targets. It is a condensed version of material contemporary to late 2015, which is presented in greater detail and constantly updated on the website www.guidetopharmacology.org, superseding data presented in the previous Guides to Receptors &amp; Channels and the Concise Guide to PHARMACOLOGY 2013/14. It is produced in conjunction with NC-IUPHAR and provides the official IUPHAR classification and nomenclature for human drug targets, where appropriate. It consolidates information previously curated and displayed separately in IUPHAR-DB and GRAC and provides a permanent, citable, point-in-time record that will survive database updates.</p