Effect of heme and non-heme ligands on subunit dissociation of normal and carboxypeptidase-digested hemoglobin. Gel filtration and flash photolysis studies.

The dissociation of normal and carboxypeptidase-digested human hemoglobin has been studied by gel filtration under several experimental conditions. These include (a) different derivatives, notably deoxy-, oxy-, and CO-hemoglobin, (b) changes in solvent composition and in pH, and (c) addition of inositol hexaphosphate. In normal hemoglobin, in agreement with previous results, the deoxygenated derivative is much less dissociated than the oxy or CO ones. This difference is observed also in some of the digested hemoglobins, but tends to vanish in those proteins in which, as a result of extensive digestion, the conformational change accompanying ligand binding is abolished. The dissociation of normal and digested hemoglobins is affected by solvent composition, is at a minimum at pH near 8, and is decreased by the addition of inositol hexaphosphate. Parallel flash photolysis experiments, performed under conditions identical with those used in the gel filtration studies, indicate that the appearance of quickly reacting material parallels dissociation into dimers in normal hemoglobin. Both in normal and digested hemoglobins conditions which decrease dissociation decrease the fraction of rapidly reacting material. In the digested hemoglobins the fraction of rapidly reacting material may be much higher than can be accounted for by the amount of dimers, indicating in these cases that the tetramers may be rapidly reacting. The data point once again to the critical role of the COOH-terminal residues in maintaining the subunit structure of hemoglobin and the interaction effects associated with it

New approaches to the restoration of shallow marginal peatlands

ArticleGlobally, the historic and recent exploitation of peatlands through management practices such as agricultural reclamation, peat harvesting or forestry, have caused extensive damage to these ecosystems. Their value is now increasingly recognised, and restoration and rehabilitation programmes are underway to improve some of the ecosystem services provided by peatlands: blocking drainage ditches in deep peat has been shown to improve the storage of water, decrease carbon losses in the long-term, and improve biodiversity. However, whilst the restoration process has benefitted from experience and technical advice gained from restoration of deep peatlands, shallow peatlands have received less attention in the literature, despite being extensive in both uplands and lowlands. Using the experience gained from the restoration of the shallow peatlands of Exmoor National Park (UK), and two test catchments in particular, this paper provides technical guidance which can be applied to the restoration of other shallow peatlands worldwide. Experience showed that integrating knowledge of the historical environment at the planning stage of restoration was essential, as it enabled the effective mitigation of any threat to archaeological features and sites. The use of bales, commonly employed in other upland ecosystems, was found to be problematic. Instead, ‘leaky dams’ or wood and peat combination dams were used, which are both more efficient at reducing and diverting the flow, and longer lasting than bale dams. Finally, an average restoration cost (£306 ha-1) for Exmoor, below the median national value across the whole of the UK, demonstrates the cost-effectiveness of these techniques. However, local differences in peat depth and ditch characteristics (i.e. length, depth and width) between sites affect both the feasibility and the cost of restoration. Overall, the restoration of shallow peatlands is shown to be technically viable; this paper provides a template for such process over analogous landscapes.South West WaterUniversity of ExeterTechnology Strategy BoardNERCKnowledge Transfer Partnership programm

Hypoxia Promotes Atrial Tachyarrhythmias via Opening of ATP-Sensitive Potassium Channels

BACKGROUND: Hypoxia-ischemia predisposes to atrial arrhythmia. Atrial ATP-sensitive potassium channel (KATP) modulation during hypoxia has not been explored. We investigated the effects of hypoxia on atrial electrophysiology in mice with global deletion of KATP pore-forming subunits. METHODS: Whole heart KATP RNA expression was probed. Whole-cell KATP current and action potentials were recorded in isolated wild-type (WT), Kir6.1 global knockout (6.1-gKO), and Kir6.2 global knockout murine atrial myocytes. Langendorff-perfused hearts were assessed for atrial effective refractory period (ERP), conduction velocity, wavefront path length (WFPL), and arrhymogenicity under normoxia/hypoxia using a microelectrode array and programmed electrical stimulation. Heart histology was assessed. RESULTS: Expression patterns were essentially identical for all KATP subunit RNA across human heart, whereas in mouse, Kir6.1 and SUR2 (sulphonylurea receptor) were higher in ventricle than atrium, and Kir6.2 and SUR1 were higher in atrium. Compared with WT, Kir6.2 global knockout atrial myocytes had reduced tolbutamide-sensitive current and action potentials were more depolarized with slower upstroke and reduced peak amplitude. Action potential duration was prolonged in 6.1-gKO atrial myocytes, absent of changes in other ion channel gene expression or atrial myocyte hypertrophy. In Langendorff-perfused hearts, baseline atrial ERP was prolonged and conduction velocity reduced in both KATP knockout mice compared with WT, without histological fibrosis. Compared with baseline, hypoxia led to conduction velocity slowing, stable ERP, and WFPL shortening in WT and 6.1-gKO hearts, whereas WFPL was stable in Kir6.2 global knockout hearts due to ERP prolongation with conduction velocity slowing. Tolbutamide reversed hypoxia-induced WFPL shortening in WT and 6.1-gKO hearts through ERP prolongation. Atrial tachyarrhythmias inducible with programmed electrical stimulation during hypoxia in WT and 6.1-gKO mice correlated with WFPL shortening. Spontaneous arrhythmia was not seen. CONCLUSIONS: KATP block/absence leads to cellular and tissue level atrial electrophysiological modification. Kir6.2 global knockout prevents hypoxia-induced atrial WFPL shortening and atrial arrhythmogenicity to programmed electrical stimulation. This mechanism could be explored translationally to treat ischemically driven atrial arrhythmia

The extraordinary linear polarisation structure of the southern Centaurus A lobe revealed by ASKAP

We present observations of linear polarisation in the southern radio lobe of Centaurus A, conducted during commissioning of the Australian Square Kilometre Array Pathfinder (ASKAP) telescope. We used 16 antennas to observe a 30 square degree region in a single 12 hour pointing over a 240 MHz band centred on 913 MHz. Our observations achieve an angular resolution of $26\times33$ arcseconds (480 parsecs), a maximum recoverable angular scale of 30 arcminutes, and a full-band sensitivity of 85 \muupJy beam$^{-1}$. The resulting maps of polarisation and Faraday rotation are amongst the most detailed ever made for radio lobes, with of order 10$^5$ resolution elements covering the source. We describe several as-yet unreported observational features of the lobe, including its detailed peak Faraday depth structure, and intricate networks of depolarised filaments. These results demonstrate the exciting capabilities of ASKAP for widefield radio polarimetry.Comment: 10 pages, 6 figures. Accepted in "The Power of Faraday Tomography" special issue of Galaxie

Pilot and quantitative evaluation of the TARGET acne toolkit by UK pharmacy professionals working in general practice

Background: Acne vulgaris (acne) is a common skin condition sometimes needing topical or oral antibiotic treatment. Pharmacists and pharmacy technicians (together known as pharmacy professionals) working in general practice are well placed to ensure their appropriate use. Aim: To pilot an evidence-based intervention (‘How to…’ tool) to review treatments in the management of acne and evaluate the capability, opportunity, motivation and behaviour (COM-B) of pharmacy professionals working in general practice before and after the use of this tool. Design and Setting: An electronic questionnaire was developed asking UK-based pharmacy professionals to rate their agreement with 21 predefined statements on a 5-point Likert scale related to the COM-B model. Method: Participants were sent an initial survey, given time to access and use the ‘How to…’ resources and then sent a follow-up survey two weeks later. Results: 141 pharmacy professionals completed the initial survey; 19 completed the follow-up survey. The initial survey found capability on the 5-point Likert scale in managing acne, including long-term antibiotic review was low (2.79, SD 1.23). Of those that completed both surveys, implementation of the acne ‘How to’ tool significantly improved capability, opportunity and motivation; capability improved the most: 3.68 (SD 0.40) to 4.11 (SD 0.29); p<0.001. The ‘How to’ resources were rated as being useful and supportive to help pharmacy professionals in all areas of managing acne. Conclusion: The acne ‘How to’ resources are demonstrated as being able to improve capability of managing acne and should be utilised in general practice to improve acne management

Fair game: exploring the dynamics, perception and environmental impact of ‘surplus’ wild foods in England 10kya-present

This paper brings together zooarchaeological data from Neolithic to Post-medieval sites in England to explore the plasticity of cultural attitudes to the consumption of wild animals. It shows how, through time, game has been considered variously as ‘tabooed’ and ‘edible’, each having implications for patterns of biodiversity and wildlife management. The essential points being made are that deeper-time studies can reveal how human perceptions of ‘surplus foods’ have the potential to both create and remedy problems of environmental sustainability and food security. Perhaps more significantly, this paper argues that understanding the bio-cultural past of edible wild animal species has the potential to transform human attitudes to game in the present. This is important at a time when food security and the production of surplus are pressing national and global concerns

Reliability of race assessment based on the race of the ascendants: a cross-sectional study

BACKGROUND: Race is commonly described in epidemiological surveys based on phenotypic characteristics. Training of interviewers to identify race is time-consuming and self identification of race might be difficult to interpret. The aim of this study was to determine the agreement between race definition based on the number of ascendants with black skin colour, with the self-assessment and observer's assessment of the skin colour. METHODS: In a cross-sectional study of 50 women aged 14 years or older, from an outpatient clinic of an University affiliated hospital, race was assessed through observation and the self-assignment of the colour of skin and by the number of black ascendants including parents and grandparents. Reliability was measured through Kappa coefficient. RESULTS: Agreement beyond chance between self-assigned and observed skin colour was excellent for white (0.75 95% CI 0.72–0.78) and black women (0.89 95% CI 0.71–0.79), but only good for participants with mixed colour (0.61 95% CI 0.58–0.64), resulting in a global kappa of 0.75 (95% CI 0.71–0.79). However, only a good agreement for mixed women was obtained. The presence of 3 or more black ascendants was highly associated with observed and self-assessed black skin colour. Most women self-assigned or observed as white had no black ascendants. CONCLUSIONS: The assessment of race based on the race of ascendants showed reasonable agreement with the ascertainment done by trained interviewers and with the self-report of race. This method may be considered for evaluation of race in epidemiological surveys, since it is less time-consuming than the evaluation by interviewers

Feedback in W49A diagnosed with radio recombination lines and models

We present images of radio recombination lines (RRLs) at wavelengths around 17 cm from the star-forming region W49A to determine the kinematics of ionized gas in the THOR survey (The H I/OH/Recombination line survey of the inner Milky Way) at an angular resolution of 16.′′8 x 13.′′8. The distribution of ionized gas appears to be affected by feedback processes from the star clusters in W49A. The velocity structure of the RRLs shows a complex behavior with respect to the molecular gas. We find a shell-like distribution of ionized gas as traced by RRL emission surrounding the central cluster of OB stars in W49A. We describe the evolution of the shell with the recent feedback model code WARPFIELD that includes the important physical processes and has previously been applied to the 30 Doradus region in the Large Magellanic Cloud. The cloud structure and dynamics of W49A are in agreement with a feedback-driven shell that is re-collapsing. The shell may have triggered star formation in other parts of W49A. We suggest that W49A is a potential candidate for star formation regulated by feedback-driven and re-collapsing shells.We would like to thank the referee for the detailed, helpful, and insightful comments, which considerably improved the paper. M.R.R. is a fellow of the International Max Planck Research School for Astronomy and Cosmic Physics (IMPRS) at the University of Heidelberg. H.B., M.R.R., Y.W., J.S. and J.C.M. acknowledge support from the European Research Council under the Horizon 2020 Framework Program via the ERC Consolidator Grant CSF-648505. M.R.R., D.R., H.B., E.W.P., S.C.O.G. and R.S.K. acknowledge support from the Deutsche Forschungsgemeinschaft (DFG) via Sonderforschungsbereich (SFB) 881 “The Milky Way System” (sub-projects B1, B2 and B8). S.C.O.G., E.W.P. and R.S.K. further acknowledge support from the DFG via Priority Program SPP 1573 “Physics of the Interstellar Medium” (grant numbers KL1358/18.1, KL 1358/19.2, and GL 668/2–1) and from the European Research Council via the ERC Advanced Grant STARLIGHT (project number 339177). The research was carried out in part at the Jet Propulsion Laboratory, which is operated forNASA by the California Institute of Technology. R.J.S. acknowledges support from an STFC Ernest Rutherford fellowship. S.E.R. acknowledges support from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement # 706390. F.B. acknowledges funding from the European Union’s Horizon 2020 research and innovation programme (grant agreement No 726384 – EMPIRE)

The HI/OH/Recombination line survey of the inner Milky Way (THOR): data release 2 and HI overview

Context. The Galactic plane has been observed extensively by a large number of Galactic plane surveys from infrared to radio wavelengths at an angular resolution below 4000. However, a 21 cm line and continuum survey with comparable spatial resolution is lacking. Aims. The first half of THOR data (l = 14.0◦−37.9◦, and l = 47.1◦−51.2◦ , |b| ≤ 1.25◦ ) has been published in our data release 1 paper. With this data release 2 paper, we publish all the remaining spectral line data and Stokes I continuum data with high angular resolution (1000-4000), including a new H I dataset for the whole THOR survey region (l = 14.0−67.4◦ and |b| ≤ 1.25◦). As we published the results of OH lines and continuum emission elsewhere, we concentrate on the H I analysis in this paper. Methods. With the Karl G. Jansky Very Large Array (VLA) in C-configuration, we observed a large portion of the first Galactic quadrant, achieving an angular resolution of ≤4000. At L Band, the WIDAR correlator at the VLA was set to cover the 21 cm H I line, four OH transitions, a series of Hnα radio recombination lines (RRLs; n = 151 to 186), and eight 128 MHz-wide continuum spectral windows, simultaneously. Results. We publish all OH and RRL data from the C-configuration observations, and a new H I dataset combining VLA C+D+GBT (VLA D-configuration and GBT data are from the VLA Galactic Plane Survey) for the whole survey. The H I emission shows clear filamentary substructures at negative velocities with low velocity crowding. The emission at positive velocities is more smeared-out, likely due to higher spatial and velocity crowding of structures at the positive velocities. Compared to the spiral arm model of the Milky Way, the atomic gas follows the Sagittarius and Perseus Arm well, but with significant material in the inter-arm regions. With the C-configuration-only H I+continuum data, we produce an H I optical depth map of the THOR areal coverage from 228 absorption spectra with the nearest-neighbor method. With this τ map, we corrected the H I emission for optical depth, and the derived column density is 38% higher than the column density with optically thin assumption. The total H I mass with optical depth correction in the survey region is 4.7 x 108 M, 31% more than the mass derived assuming the emission is optically thin. If we applied this 31% correction to the whole Milky Way, the total atomic gas mass would be 9.4-10.5 x 109 M. Comparing the H I with existing CO data, we find a significant increase in the atomic-to-molecular gas ratio from the spiral arms to the inter-arm regions. Conclusions. The high-sensitivity and resolution THOR H I dataset provides an important new window on the physical and kinematic properties of gas in the inner Galaxy. Although the optical depth we derive is a lower limit, our study shows that the optical depth correction is significant for H I column density and mass estimation. Together with the OH, RRL and continuum emission from the THOR survey, these new H I data provide the basis for high-angular-resolution studies of the interstellar medium in different phasesY.W., H.B., S.B., and J.D.S. acknowledge support from the European Research Council under the Horizon 2020 Framework Program via the ERC Consolidator Grant CSF-648505. H.B., S.C.O.G., and R.S.K. acknowledge support from the Deutsche Forschungsgemeinschaft in the Collaborative Research Center (SFB 881) “The Milky Way System” (subproject B1, B2, B8