Loss of very-long O-antigen chains optimizes capsule-mediated immune evasion by Salmonella enterica serovar Typhi.

UnlabelledExpression of capsular polysaccharides is a variable trait often associated with more-virulent forms of a bacterial species. For example, typhoid fever is caused by the capsulated Salmonella enterica serovar Typhi, while nontyphoidal Salmonella serovars associated with gastroenteritis are noncapsulated. Here we show that optimization of the immune evasive properties conferred by the virulence-associated (Vi) capsular polysaccharide involved an additional alteration to the cell envelope of S. Typhi, namely inactivation of the fepE gene, encoding the regulator of very-long O-antigen chains. Introduction of the capsule-encoding viaB locus into the nontyphoidal S. enterica serovar Typhimurium reduced complement deposition in vitro and intestinal inflammation in a mouse colitis model. However, both phenotypes were markedly enhanced when the viaB locus was introduced into an S. Typhimurium fepE mutant, which lacks very-long O-antigen chains. Collectively, these data suggest that during the evolution of the S. Typhi lineage, loss of very-long O-antigen chains by pseudogene formation was an adaptation to maximize the anti-inflammatory properties of the Vi capsular polysaccharide.ImportanceGenomic comparison illustrates that acquisition of virulence factors by horizontal gene transfer is an important contributor to the evolution of enteric pathogens. Acquisition of complex virulence traits commonly involves horizontal transfer of a large gene cluster, and integration of the gene cluster into the host genome results in the formation of a pathogenicity island. Acquisition of the virulence-associated (Vi) capsular polysaccharide encoded by SPI7 (Salmonella pathogenicity island 7) was accompanied in the human-adapted Salmonella enterica serovar Typhi by inactivation of the fepE gene, encoding the regulator of very-long O-antigen chains. We show that the resulting loss of very-long O-antigen chains was an important mechanism for maximizing immune evasion mediated by the Vi capsular polysaccharide. These data suggest that successful incorporation of a capsular polysaccharide requires changes in the cell envelope of the hosting pathogen

Life-cycle energy analysis of building integrated photovoltaic systems (BiPVs) with heat recovery unit

Building integrated photovoltaic (BiPV) systems generate electricity, but also heat, which is typically wasted and also reduces the efficiency of generation. A heat recovery unit can be combined with a BiPV system to take advantage of this waste heat, thus providing cogeneration. Two different photovoltaic (PV) cell types were combined with a heat recovery unit and analysed in terms of their life-cycle energy consumption to determine the energy payback period. A net energy analysis of these PV systems has previously been performed, but recent improvements in the data used for this study allow for a more comprehensive assessment of the combined energy used throughout the entire life-cycle of these systems to be performed. Energy payback periods between 4 and 16.5 years were found, depending on the BiPV system. The energy embodied in PV systems is significant, emphasised here due to the innovative use of national average input&ndash;output (I&ndash;O) data to fill gaps in traditional life-cycle inventories, i.e. hybrid analysis. These findings provide an insight into the net energy savings that are possible with a well-designed and managed BiPV system.<br /

Very long O-antigen chains enhance fitness during Salmonella-induced colitis by increasing bile resistance.

Intestinal inflammation changes the luminal habitat for microbes through mechanisms that have not been fully resolved. We noticed that the FepE regulator of very long O-antigen chain assembly in the enteric pathogen Salmonella enterica serotype Typhimurium (S. Typhimurium) conferred a luminal fitness advantage in the mouse colitis model. However, a fepE mutant was not defective for survival in tissue, resistance to complement or resistance to polymyxin B. We performed metabolite profiling to identify changes in the luminal habitat that accompany S. Typhimurium-induced colitis. This analysis suggested that S. Typhimurium-induced colitis increased the luminal concentrations of total bile acids. A mutation in fepE significantly reduced the minimal inhibitory concentration (MIC) of S. Typhimurium for bile acids in vitro. Oral administration of the bile acid sequestrant cholestyramine resin lowered the concentrations of total bile acids in colon contents during S. Typhimurium infection and significantly reduced the luminal fitness advantage conferred by the fepE gene in the mouse colitis model. Collectively, these data suggested that very long O-antigen chains function in bile acid resistance of S. Typhimurium, a property conferring a fitness advantage during luminal growth in the inflamed intestine

Gut inflammation provides a respiratory electron acceptor for Salmonella.

Salmonella enterica serotype Typhimurium (S. Typhimurium) causes acute gut inflammation by using its virulence factors to invade the intestinal epithelium and survive in mucosal macrophages. The inflammatory response enhances the transmission success of S. Typhimurium by promoting its outgrowth in the gut lumen through unknown mechanisms. Here we show that reactive oxygen species generated during inflammation react with endogenous, luminal sulphur compounds (thiosulphate) to form a new respiratory electron acceptor, tetrathionate. The genes conferring the ability to use tetrathionate as an electron acceptor produce a growth advantage for S. Typhimurium over the competing microbiota in the lumen of the inflamed gut. We conclude that S. Typhimurium virulence factors induce host-driven production of a new electron acceptor that allows the pathogen to use respiration to compete with fermenting gut microbes. Thus the ability to trigger intestinal inflammation is crucial for the biology of this diarrhoeal pathogen

Phenological changes in the Southern Hemisphere

Current evidence of phenological responses to recent climate change is substantially biased towards northern hemisphere temperate regions. Given regional differences in climate change, shifts in phenology will not be uniform across the globe, and conclusions drawn from temperate systems in the northern hemisphere might not be applicable to other regions on the planet. We conduct the largest meta-analysis to date of phenological drivers and trends among southern hemisphere species, assessing 1208 long-term datasets from 89 studies on 347 species. Data were mostly from Australasia (Australia and New Zealand), South America and the Antarctic/subantarctic, and focused primarily on plants and birds. This meta-analysis shows an advance in the timing of spring events (with a strong Australian data bias), although substantial differences in trends were apparent among taxonomic groups and regions. When only statistically significant trends were considered, 82% of terrestrial datasets and 42% of marine datasets demonstrated an advance in phenology. Temperature was most frequently identified as the primary driver of phenological changes; however, in many studies it was the only climate variable considered. When precipitation was examined, it often played a key role but, in contrast with temperature, the direction of phenological shifts in response to precipitation variation was difficult to predict a priori . We discuss how phenological information can inform the adaptive capacity of species, their resilience, and constraints on autonomous adaptation. We also highlight serious weaknesses in past and current data collection and analyses at large regional scales (with very few studies in the tropics or from Africa) and dramatic taxonomic biases. If accurate predictions regarding the general effects of climate change on the biology of organisms are to be made, data collection policies focussing on targeting data-deficient regions and taxa need to be financially and logistically supported

Long-term outcomes of patients undergoing endovascular infrainguinal interventions with single-vessel peroneal artery runoff

ObjectivesRecent reports have shown promising early results after endovascular revascularization (percutaneous transluminal angioplasty [PTA]/stent) of patients with peroneal artery-only runoff (PAOR), although the long-term durability is unclear. This study evaluated long-term primary patency and limb salvage of PTA/stent in patients with single-vessel runoff and critical limb ischemia to determine if the peroneal artery yields inferior results.MethodsFrom January 2002 to December 2007, 1075 infrainguinal PTA/stent procedures were performed in 920 patients. The study cohort comprised 201 limbs in 187 patients with single-vessel runoff and critical limb ischemia. End points included primary patency, assisted patency, limb salvage, and survival. Long-term outcomes were determined by Kaplan-Meier life-table and multivariate Cox regression analyses.ResultsThere were 104 PAOR and 97 limbs with single-vessel posterior or anterior tibial artery runoff (non-PAOR). Median follow-up was 25 months (range, 0-75 months). PAOR patients tended to be older (77.36 ± 0.92 vs 72.65 ± 1.18 years, P = .002) and were more likely to be taking clopidogrel at presentation (88% vs 76%; P = .04). There were no statistically significant differences in 5-year primary patency (26% ± 6.8% vs 30% ± 7.6%; P = .79), assisted patency (75% ± 8.8% vs 81% ± 7.0%; P = .77), limb salvage (74% ± 8.0% vs 75% ± 7.1%; P = .47), and survival (38% ± 7.7% vs 47% ± 6.6%; P = .99) between the PAOR and the non-PAOR groups, respectively. On Cox regression multivariate analysis, total occlusions predicted decreased assisted patency (hazard ratio, 2.99; 95% confidence interval, 1.21-7.41; P = .02), whereas younger age predicted poor limb salvage (hazard ratio, 0.97; 95% confidence interval, 0.94-0.99; P = .04). PAOR was not an independent predictor of any outcome on multivariate analysis.ConclusionsPatients with PAOR have similar long-term outcomes to patients with non-PAOR. Thus, infrainguinal endovascular revascularization can be considered a first-line therapy for patients with PAOR and critical limb ischemia

Coordination when there are restricted and unrestricted options

One might expect that, in pure coordination games, coordination would become less frequent as the number of options increases. Contrary to this expectation, we report an experiment which found more frequent coordination when the option set was unrestricted than when it was restricted. To try to explain this result, we develop a method for eliciting the general rules that subjects use to identify salient options in restricted and unrestricted sets. We find that each such rule, if used by all subjects, would generate greater coordination in restricted sets. However, subjects tend to apply different rules to restricted and unrestricted sets

Ultraviolet Imaging Observations of the cD Galaxy in Abell 1795: Further Evidence for Massive Star Formation in a Cooling Flow

We present images from the Ultraviolet Imaging Telescope of the Abell 1795 cluster of galaxies. We compare the cD galaxy morphology and photometry of these data with those from existing archival and published data. The addition of a far--UV color helps us to construct and test star formation model scenarios for the sources of UV emission. Models of star formation with rates in the range \sim5-20M_{\sun}yr$^{-1}$ indicate that the best fitting models are those with continuous star formation or a recent ($\sim4$ Myr old) burst superimposed on an old population. The presence of dust in the galaxy, dramatically revealed by HST images complicates the interpretation of UV data. However, we find that the broad--band UV/optical colors of this cD galaxy can be reasonably matched by models using a Galactic form for the extinction law with $E_{B-V}=0.14$. We also briefly discuss other objects in the large UIT field of view.Comment: To appear in the Astrophysical Journal. 14 AAS preprint style pages plus 7 figure

ROSAT observations of X-ray emission from planetary nebulae

We have searched the entire ROSAT archive for useful observations to study X-ray emission from Galactic planetary nebulae (PNs). The search yields a sample of 63 PNs, which we call the ROSAT PN sample. About 20-25% of this sample show X-ray emission; these include 13 definite detections and three possible detections (at a 2-sigma level). All X-ray sources in these PNs are concentrated near the central stars. Only A 30, BD+30 3639, and NGC 6543 are marginally resolved by the ROSAT instruments. Three types of X-ray spectra are seen in PNs. Type 1 consists of only soft X-ray emission (<0.5 keV), peaks at 0.1-0.2 keV, and can be fitted by blackbody models at temperatures 1-2 10^5 K. Type 2 consists of harder X-ray emission, peaks at >0.5 keV, and can be fitted by thin plasma emission models at temperatures of a few 10^6 K. Type 3 is a composite of a bright Type 1 component and a fainter Type 2 component. Unresolved soft sources with Type 1 spectra or the soft component of Type 3 spectra are most likely photospheric emission from the hot central stars. Absorption cross sections are large for these soft-energy photons; therefore, only large, tenuous, evolved PNs with hot central stars and small absorption column densities have been detected. The origin of hard X-ray emission from PNs is uncertain. PNs with Type 2 spectra are small, dense, young nebulae with relatively cool (<<10^5 K) central stars, while PNs with Type 3 X-ray spectra are large, tenuous, evolved nebulae with hot central stars. The hard X-ray luminosities are also different between these two types of PNs, indicating perhaps different origins of their hard X-ray emission. Future Chandra and XMM observations with high spatial and spectral resolution will help to understand the origin of hard X-ray emission from PNs.Comment: To be published in The Astrophysical Journal Supplement Series. 21 pages, 7 figures, 5 table

Liaison psychiatry—measurement and evaluation of service types, referral patterns and outcomes (LP-MAESTRO): a protocol

Introduction: We describe the protocol for a project that will use linkage of routinely collected NHS data to answer a question about the nature and effectiveness of liaison psychiatry services in acute hospitals in England. Methods and analysis: The project will use three data sources: (1) Hospital Episode Statistics (HES), a database controlled by NHS Digital that contains patient data relating to emergency department (ED), inpatient and outpatient episodes at hospitals in England; (2) ResearchOne, a research database controlled by The Phoenix Partnership (TPP) that contains patient data relating to primary care provided by organisations using the SystmOne clinical information system and (3) clinical databases controlled by mental health trusts that contain patient data relating to care provided by liaison psychiatry services. We will link patient data from these sources to construct care pathways for patients who have been admitted to a particular hospital and determine those patients who have been seen by a liaison psychiatry service during their admission. Patient care pathways will form the basis of a matched cohort design to test the effectiveness of liaison intervention. We will combine healthcare utilisation within care pathways using cost figures from national databases. We will compare the cost of each care pathway and the impact of a broad set of health-related outcomes to obtain preliminary estimates of cost-effectiveness for liaison psychiatry services. We will carry out an exploratory incremental cost-effectiveness analysis from a whole system perspective. Ethics and dissemination: Individual patient consent will not be feasible for this study. Favourable ethical opinion has been obtained from the NHS Research Ethics Committee (North of Scotland) (REF: 16/NS/0025) for Work Stream 2 (phase 1) of the Liaison psychiatry—measurement and evaluation of service types, referral patterns and outcomes study. The Confidentiality Advisory Group at the Health Research Authority determined that Section 251 approval under Regulation 5 of the Health Service (Control of Patient Information) Regulations 2002 was not required for the study ‘on the basis that there is no disclosure of patient identifiable data without consent’ (REF: 16/CAG/0037). Results of the study will be published in academic journals in health services research and mental health. Details of the study methodology will also be published in an academic journal. Discussion papers will be authored for health service commissioners