An examination of chemistry and transport processes in the tropical lower stratosphere using observations of long-lived and short-lived compounds obtained during STRAT and POLARIS

A suite of compounds with a wide range of photochemical lifetimes (3 months to several decades) was measured in the tropical and midlatitude upper troposphere and lower stratosphere during the Stratospheric Tracers of Atmospheric Transport (STRAT) experiment (fall 1995 and winter, summer, and fall 1996) and the Photochemistry of Ozone Loss in the Arctic Region in Summer (POLARIS) deployment in late summer 1997. These species include various chlorofluorocarbons, hydrocarbons, halocarbons, and halons measured in whole air samples and CO measured in situ by tunable diode laser spectroscopy. Mixing ratio profiles of long-lived species in the tropical lower stratosphere are examined using a one-dimensional (1-D) photochemical model that includes entrainment from the extratropical stratosphere and is constrained by measured concentrations of OH. Profiles of tracers found using the 1-D model agree well with all the observed tropical profiles for an entrainment time scale of 8.5-4+6 months, independent of altitude between potential temperatures of 370 and 500 K. The tropical profile of CO is used to show that the annually averaged ascent rate profile, on the basis of a set of radiative heating calculations, is accurate to approximately ±44%, a smaller uncertainty than found by considering the uncertainties in the radiative model and its inputs. Tropical profiles of ethane and C2Cl4 reveal that the concentration of Cl is higher than expected on the basis of photochemical model simulations using standard gas phase kinetics and established relationships between total inorganic chlorine and CFC-11. Our observations suggest that short-lived organic chlorinated compounds and HCl carried across the tropical tropopause may provide an important source of inorganic chlorine to the tropical lower stratosphere that has been largely unappreciated in previous studies. The entrainment timescale found here is considerably less than the value found by a similar study that focused on observations obtained in the lower stratosphere during 1994. Several possible explanations for this difference are discussed. Copyright 1999 by the American Geophysical Union

Identification and characterization of the intracellular poly-3-hydroxybutyrate depolymerase enzyme PhaZ of Sinorhizobium meliloti

<p>Abstract</p> <p>Background</p> <p><it>S. meliloti </it>forms indeterminate nodules on the roots of its host plant alfalfa (<it>Medicago sativa</it>). Bacteroids of indeterminate nodules are terminally differentiated and, unlike their non-terminally differentiated counterparts in determinate nodules, do not accumulate large quantities of Poly-3-hydroxybutyrate (PHB) during symbiosis. PhaZ is in intracellular PHB depolymerase; it represents the first enzyme in the degradative arm of the PHB cycle in <it>S. meliloti </it>and is the only enzyme in this half of the PHB cycle that remains uncharacterized.</p> <p>Results</p> <p>The <it>S. meliloti phaZ </it>gene was identified by <it>in silico </it>analysis, the ORF was cloned, and a <it>S. meliloti phaZ </it>mutant was constructed. This mutant exhibited increased PHB accumulation during free-living growth, even when grown under non-PHB-inducing conditions. The <it>phaZ </it>mutant demonstrated no reduction in symbiotic capacity; interestingly, analysis of the bacteroids showed that this mutant also accumulated PHB during symbiosis. This mutant also exhibited a decreased capacity to tolerate long-term carbon starvation, comparable to that of other PHB cycle mutants. In contrast to other PHB cycle mutants, the <it>S. meliloti phaZ </it>mutant did not exhibit any decrease in rhizosphere competitiveness; however, this mutant did exhibit a significant increase in succinoglycan biosynthesis.</p> <p>Conclusions</p> <p><it>S. meliloti </it>bacteroids retain the capacity to synthesize PHB during symbiosis; interestingly, accumulation does not occur at the expense of symbiotic performance. <it>phaZ </it>mutants are not compromised in their capacity to compete for nodulation in the rhizosphere, perhaps due to increased succinoglycan production resulting from upregulation of the succinoglycan biosynthetic pathway. The reduced survival capacity of free-living cells unable to access their accumulated stores of PHB suggests that PHB is a crucial metabolite under adverse conditions.</p

The South Asian genome

Genetics of disease Microarrays Variant genotypes Population genetics Sequence alignment AllelesThe genetic sequence variation of people from the Indian subcontinent who comprise one-quarter of the world's population, is not well described. We carried out whole genome sequencing of 168 South Asians, along with whole-exome sequencing of 147 South Asians to provide deeper characterisation of coding regions. We identify 12,962,155 autosomal sequence variants, including 2,946,861 new SNPs and 312,738 novel indels. This catalogue of SNPs and indels amongst South Asians provides the first comprehensive map of genetic variation in this major human population, and reveals evidence for selective pressures on genes involved in skin biology, metabolism, infection and immunity. Our results will accelerate the search for the genetic variants underlying susceptibility to disorders such as type-2 diabetes and cardiovascular disease which are highly prevalent amongst South Asians.Whole genome sequencing to discover genetic variants underlying type-2 diabetes, coronary heart disease and related phenotypes amongst Indian Asians. Imperial College Healthcare NHS Trust cBRC 2011-13 (JS Kooner [PI], JC Chambers)

Reducing vortex density in superconductors using the ratchet effect

A serious obstacle that impedes the application of low and high temperature superconductor (SC) devices is the presence of trapped flux. Flux lines or vortices are induced by fields as small as the Earth's magnetic field. Once present, vortices dissipate energy and generate internal noise, limiting the operation of numerous superconducting devices. Methods used to overcome this difficulty include the pinning of vortices by the incorporation of impurities and defects, the construction of flux dams, slots and holes and magnetic shields which block the penetration of new flux lines in the bulk of the SC or reduce the magnetic field in the immediate vicinity of the superconducting device. Naturally, the most desirable would be to remove the vortices from the bulk of the SC. There is no known phenomenon, however, that could form the basis for such a process. Here we show that the application of an ac current to a SC that is patterned with an asymmetric pinning potential can induce vortex motion whose direction is determined only by the asymmetry of the pattern. The mechanism responsible for this phenomenon is the so called ratchet effect, and its working principle applies to both low and high temperature SCs. As a first step here we demonstrate that with an appropriate choice of the pinning potential the ratchet effect can be used to remove vortices from low temperature SCs in the parameter range required for various applications.Comment: 7 pages, 4 figures, Nature (in press

Identification of Specific Circular RNA Expression Patterns and MicroRNA Interaction Networks in Mesial Temporal Lobe Epilepsy

Circular RNAs (circRNAs) regulate mRNA translation by binding to microRNAs (miRNAs), and their expression is altered in diverse disorders, including cancer, cardiovascular disease, and Parkinson’s disease. Here, we compare circRNA expression patterns in the temporal cortex and hippocampus of patients with pharmacoresistant mesial temporal lobe epilepsy (MTLE) and healthy controls. Nine circRNAs showed significant differential expression, including circRNA-HOMER1, which is expressed in synapses. Further, we identified miRNA binding sites within the sequences of differentially expressed (DE) circRNAs; expression levels of mRNAs correlated with changes in complementary miRNAs. Gene set enrichment analysis of mRNA targets revealed functions in heterocyclic compound binding, regulation of transcription, and signal transduction, which maintain the structure and function of hippocampal neurons. The circRNA–miRNA–mRNA interaction networks illuminate the molecular changes in MTLE, which may be pathogenic or an effect of the disease or treatments and suggests that DE circRNAs and associated miRNAs may be novel therapeutic targets

The Relationship between Asthma and Depression in Primary Care Patients: A Historical Cohort and Nested Case Control Study

Asthma and depression are common health problems in primary care. Evidence of a relationship between asthma and depression is conflicting. Objectives: to determine 1. The incidence rate and incidence rate ratio of depression in primary care patients with asthma compared to those without asthma, and 2. The standardized mortality ratio of depressed compared to non-depressed patients with asthma.A historical cohort and nested case control study using data derived from the United Kingdom General Practice Research Database. Participants: 11,275 incident cases of asthma recorded between 1/1/95 and 31/12/96 age, sex and practice matched with non-cases from the database (ratio 1∶1) and followed up through the database for 10 years. 1,660 cases were matched by date of asthma diagnosis with 1,660 controls. Main outcome measures: number of cases diagnosed with depression, the number of deaths over the study period.The rate of depression in patients with asthma was 22.4/1,000 person years and without asthma 13.8 /1,000 person years. The incident rate ratio (adjusted for age, sex, practice, diabetes, cardiovascular disease, cerebrovascular disease, smoking) was 1.59 (95% CI 1.48–1.71). The increased rate of depression was not associated with asthma severity or oral corticosteroid use. It was associated with the number of consultations (odds ratio per visit 1.09; 95% CI 1.07–1.11). The age and sex adjusted standardized mortality ratio for depressed patients with asthma was 1.87 (95% CI: 1.54–2.27).Asthma is associated with depression. This was not related to asthma severity or oral corticosteroid use but was related to service use. This suggests that a diagnosis of depression is related to health seeking behavior in patients with asthma. There is an increased mortality rate in depressed patients with asthma. The cause of this needs further exploration. Consideration should be given to case-finding for depression in this population

Change in non-alcoholic beverage sales following a 10-pence levy on sugar-sweetened beverages within a national chain of restaurants in the UK: interrupted time series analysis of a natural experiment

This is the final published version. Available from BMJ Publishing Group via the DOI in this record.The dataset used within this study is commercially sensitive and is owned by a third-party. The data provider (Jamie’s Italian) will accept requests to access to sales data used in the analyses presented here. These requests should be made in writing to the Jamie Oliver Food Foundation (http://www. jamieoliverfoodfoundation.org.uk).Background This study evaluates changes in sales of non-alcoholic beverages in Jamie’s Italian, a national chain of commercial restaurants in the UK, following the introduction of a £0.10 per-beverage levy on sugarsweetened beverages (SSBs) and supporting activity including beverage menu redesign, new products and establishment of a children’s health fund from levy proceeds. Methods We used an interrupted time series design to quantify changes in sales of non-alcoholic beverages 12 weeks and 6 months after implementation of the levy, using itemised electronic point of sale data. Main outcomes were number of SSBs and other nonalcoholic beverages sold per customer. Linear regression and multilevel random effects models, adjusting for seasonality and clustering, were used to investigate changes in SSB sales across all restaurants (n=37) and by tertiles of baseline restaurant SSB sales per customer. Results Compared with the prelevy period, the number of SSBs sold per customer declined by 11.0% (−17.3% to −4.3%) at 12 weeks and 9.3% (−15.2% to −3.2%) at 6months. For non-levied beverages, sales per customer of children’s fruit juice declined by 34.7% (−55.3% to −4.3%) at 12 weeks and 9.9% (−16.8% to −2.4%) at 6months. At 6months, sales per customer of fruit juice increased by 21.8% (14.0% to 30.2%) but sales of diet cola (−7.3%; −11.7% to −2.8%) and bottled waters (−6.5%; −11.0% to −1.7%) declined. Changes in sales were only observed in restaurants in the medium and high tertiles of baseline SSB sales per customer. Conclusions Introduction of a £0.10 levy on SSBs alongside complementary activities is associated with declines in SSB sales per customer in the short and medium term, particularly in restaurants with higher baseline sales of SSBsNational Institute for Health Research (NIHR)Medical Research Council (MRC)Centre for Diet and Activity Research (CEDAR), a UKCRC Public Health Research Centre of ExcellenceUK Clinical Research CollaborationBritish Heart FoundationCancer Research UKEconomic and Social Research Council (ESRC)Wellcome Trus

Links between traumatic brain injury and ballistic pressure waves originating in the thoracic cavity and extremities

Identifying patients at risk of traumatic brain injury (TBI) is important because research suggests prophylactic treatments to reduce risk of long-term sequelae. Blast pressure waves can cause TBI without penetrating wounds or blunt force trauma. Similarly, bullet impacts distant from the brain can produce pressure waves sufficient to cause mild to moderate TBI. The fluid percussion model of TBI shows that pressure impulses of 15-30 psi cause mild to moderate TBI in laboratory animals. In pigs and dogs, bullet impacts to the thigh produce pressure waves in the brain of 18-45 psi and measurable injury to neurons and neuroglia. Analyses of research in goats and epidemiological data from shooting events involving humans show high correlations (r > 0.9) between rapid incapacitation and pressure wave magnitude in the thoracic cavity. A case study has documented epilepsy resulting from a pressure wave without the bullet directly hitting the brain. Taken together, these results support the hypothesis that bullet impacts distant from the brain produce pressure waves that travel to the brain and can retain sufficient magnitude to induce brain injury. The link to long-term sequelae could be investigated via epidemiological studies of patients who were gunshot in the chest to determine whether they experience elevated rates of epilepsy and other neurological sequelae

Steady-state modulation of voltage-gated K+ channels in rat arterial smooth muscle by cyclic AMP-dependent protein kinase and protein phosphatase 2B

Voltage-gated potassium channels (Kv) are important regulators of membrane potential in vascular smooth muscle cells, which is integral to controlling intracellular Ca2+ concentration and regulating vascular tone. Previous work indicates that Kv channels can be modulated by receptor-driven alterations of cyclic AMP-dependent protein kinase (PKA) activity. Here, we demonstrate that Kv channel activity is maintained by tonic activity of PKA. Whole-cell recording was used to assess the effect of manipulating PKA signalling on Kv and ATP-dependent K+ channels of rat mesenteric artery smooth muscle cells. Application of PKA inhibitors, KT5720 or H89, caused a significant inhibition of Kv currents. Tonic PKA-mediated activation of Kv appears maximal as application of isoprenaline (a β-adrenoceptor agonist) or dibutyryl-cAMP failed to enhance Kv currents. We also show that this modulation of Kv by PKA can be reversed by protein phosphatase 2B/calcineurin (PP2B). PKA-dependent inhibition of Kv by KT5720 can be abrogated by pre-treatment with the PP2B inhibitor cyclosporin A, or inclusion of a PP2B auto-inhibitory peptide in the pipette solution. Finally, we demonstrate that tonic PKA-mediated modulation of Kv requires intact caveolae. Pre-treatment of the cells with methyl-β-cyclodextrin to deplete cellular cholesterol, or adding caveolin-scaffolding domain peptide to the pipette solution to disrupt caveolae-dependent signalling each attenuated PKA-mediated modulation of the Kv current. These findings highlight a novel, caveolae-dependent, tonic modulatory role of PKA on Kv channels providing new insight into mechanisms and the potential for pharmacological manipulation of vascular tone