As Arctic regions warm and frozen soils thaw, the large organic carbon pool stored in permafrost becomes increasingly vulnerable to decomposition or transport. The transfer of newly mobilized carbon ...to the atmosphere and its potential influence upon climate change will largely depend on the degradability of carbon delivered to aquatic ecosystems. Dissolved organic carbon (DOC) is a key regulator of aquatic metabolism, yet knowledge of the mechanistic controls on DOC biodegradability is currently poor due to a scarcity of long-term data sets, limited spatial coverage of available data, and methodological diversity. Here, we performed parallel biodegradable DOC (BDOC) experiments at six Arctic sites (16 experiments) using a standardized incubation protocol to examine the effect of methodological differences commonly used in the literature. We also synthesized results from 14 aquatic and soil leachate BDOC studies from across the circum-arctic permafrost region to examine pan-arctic trends in BDOC. An increasing extent of permafrost across the landscape resulted in higher DOC losses in both soil and aquatic systems. We hypothesize that the unique composition of (yedoma) permafrost-derived DOC combined with limited prior microbial processing due to low soil temperature and relatively short flow path lengths and transport times, contributed to a higher overall terrestrial and freshwater DOC loss. Additionally, we found that the fraction of BDOC decreased moving down the fluvial network in continuous permafrost regions, i.e. from streams to large rivers, suggesting that highly biodegradable DOC is lost in headwater streams. We also observed a seasonal (January-December) decrease in BDOC in large streams and rivers, but saw no apparent change in smaller streams or soil leachates. We attribute this seasonal change to a combination of factors including shifts in carbon source, changing DOC residence time related to increasing thaw-depth, increasing water temperatures later in the summer, as well as decreasing hydrologic connectivity between soils and surface water as the thaw season progresses. Our results suggest that future climate warming-induced shifts of continuous permafrost into discontinuous permafrost regions could affect the degradation potential of thaw-released DOC, the amount of BDOC, as well as its variability throughout the Arctic summer. We lastly recommend a standardized BDOC protocol to facilitate the comparison of future work and improve our knowledge of processing and transport of DOC in a changing Arctic.
Hepatocellular carcinoma (HCC) develops on the background of chronic hepatitis. Leukocytes found within the HCC microenvironment are implicated as regulators of tumour growth. We show that ...diethylnitrosamine (DEN)-induced murine HCC is attenuated by antibody-mediated depletion of hepatic neutrophils, the latter stimulating hepatocellular ROS and telomere DNA damage. We additionally report a previously unappreciated tumour suppressor function for hepatocellular nfkb1 operating via p50:p50 dimers and the co-repressor HDAC1. These anti-inflammatory proteins combine to transcriptionally repress hepatic expression of a S100A8/9, CXCL1 and CXCL2 neutrophil chemokine network. Loss of nfkb1 promotes ageing-associated chronic liver disease (CLD), characterized by steatosis, neutrophillia, fibrosis, hepatocyte telomere damage and HCC. Nfkb1(S340A/S340A)mice carrying a mutation designed to selectively disrupt p50:p50:HDAC1 complexes are more susceptible to HCC; by contrast, mice lacking S100A9 express reduced neutrophil chemokines and are protected from HCC. Inhibiting neutrophil accumulation in CLD or targeting their tumour-promoting activities may offer therapeutic opportunities in HCC.
The VLT Survey Telescope ATLAS Shanks, T; Metcalfe, N; Chehade, B ...
Monthly Notices of the Royal Astronomical Society,
08/2015, Volume:
451, Issue:
4
Journal Article
Peer reviewed
Open access
The VLT Survey Telescope ATLAS survey is an optical ugriz survey aiming to cover ≈4700 deg2 of the southern sky to similar depths as the Sloan Digital Sky Survey (SDSS). From reduced images and ...object catalogues provided by the Cambridge Astronomical Surveys Unit, we first find that the median seeing ranges from 0.8 arcsec FWHM (full width at half-maximum) in i to 1.0 arcsec in u, significantly better than the 1.2–1.5 arcsec seeing for SDSS. The 5σ mag limit for stellar sources is r
AB
= 22.7 and in all bands these limits are at least as faint as SDSS. SDSS and ATLAS are more equivalent for galaxy photometry except in the z band where ATLAS has significantly higher throughput. We have improved the original ESO magnitude zero-points by comparing m < 16 star magnitudes with the AAVSO Photometric All-Sky Survey in gri, also extrapolating into u and z, resulting in zero-points accurate to ≈ ± 0.02 mag. We finally compare star and galaxy number counts in a 250 deg2 area with SDSS and other count data and find good agreement. ATLAS data products can be retrieved from the ESO Science Archive, while support for survey science analyses is provided by the OmegaCAM Science Archive, operated by the Wide-Field Astronomy Unit in Edinburgh.
High‐latitude northern rivers export globally significant quantities of dissolved organic carbon (DOC) to the Arctic Ocean. Climate change, and its associated impacts on hydrology and potential ...mobilization of ancient organic matter from permafrost, is likely to modify the flux, composition, and thus biogeochemical cycling and fate of exported DOC in the Arctic. This study examined DOC concentration and the composition of dissolved organic matter (DOM) across the hydrograph in Siberia's Kolyma River, with a particular focus on the spring freshet period when the majority of the annual DOC load is exported. The composition of DOM within the Kolyma basin was characterized using absorbance‐derived measurements (absorbance coefficienta330, specific UV absorbance (SUVA254), and spectral slope ratio SR) and fluorescence spectroscopy (fluorescence index and excitation‐emission matrices (EEMs)), including parallel factor analyses of EEMs. Increased surface runoff during the spring freshet led to DOM optical properties indicative of terrestrial soil inputs with high humic‐like fluorescence, SUVA254, and low SRand fluorescence index (FI). Under‐ice waters, in contrast, displayed opposing trends in optical properties representing less aromatic, lower molecular weight DOM. We demonstrate that substantial losses of DOC can occur via biological (∼30% over 28 days) and photochemical pathways (>29% over 14 days), particularly in samples collected during the spring freshet. The emerging view is therefore that of a more dynamic and labile carbon pool than previously thought, where DOM composition plays a fundamental role in controlling the fate and removal of DOC at a pan‐Arctic scale.
Key Points
DOM concentration and composition varies markedly over the hydrograph
DOC in the Kolyma is shown to be both biologically and photochemically labile
DOM composition is seen to control DOC loss within Arctic Rivers
The genetic diversity in Australian populations of Xanthomonas species associated with bacterial leaf spot in tomato, capsicum and chilli were compared to worldwide bacterial populations. The aim of ...this study was to confirm the identities of these Australian Xanthomonas species and classify them in comparison to overseas isolates. Analysis of whole genome sequence allows for the investigation of bacterial population structure, pathogenicity and gene exchange, resulting in better management strategies and biosecurity.
Phylogenetic analysis of the core genome alignments and SNP data grouped strains in distinct clades. Patterns observed in average nucleotide identity, pan genome structure, effector and carbohydrate active enzyme profiles reflected the whole genome phylogeny and highlight taxonomic issues in X. perforans and X. euvesicatoria. Circular sequences with similarity to previously characterised plasmids were identified, and plasmids of similar sizes were isolated. Potential false positive and false negative plasmid assemblies were discussed. Effector patterns that may influence virulence on host plant species were analysed in pathogenic and non-pathogenic xanthomonads.
The phylogeny presented here confirmed X. vesicatoria, X. arboricola, X. euvesicatoria and X. perforans and a clade of an uncharacterised Xanthomonas species shown to be genetically distinct from all other strains of this study. The taxonomic status of X. perforans and X. euvesicatoria as one species is discussed in relation to whole genome phylogeny and phenotypic traits. The patterns evident in enzyme and plasmid profiles indicate worldwide exchange of genetic material with the potential to introduce new virulence elements into local bacterial populations.
Emerging data suggest that different indices of glycaemia are risk factors for clinical events. The aim of this analysis was to investigate the relationship between fasting plasma glucose or glycated ...haemoglobin (GHb) levels and incident cardiovascular (CV) outcomes, death, heart failure and overt nephropathy in diabetic and non-diabetic individuals enrolled in the Heart Outcomes Prevention Evaluation (HOPE) study.
The adjusted 4.5-year risk of CV events (myocardial infarction or stroke or CV death), heart failure, death and overt nephropathy was analysed in relation to baseline and updated GHb levels (in 3,529 diabetic HOPE study participants) and baseline fasting plasma glucose levels (in 1,937 non-diabetic and 1,013 diabetic participants).
In diabetic participants, a 1% absolute rise in the updated GHb predicted future CV events (relative risk RR=1.07, 95% CI 1.01-1.13; p=0.014), death (RR=1.12, 95% CI 1.05-1.19; p=0.0004), heart failure (RR=1.20, 95% CI 1.08-1.33; p=0.0008) and overt nephropathy (RR=1.26, 95% CI 1.17-1.36; p<0.0001) after adjusting for age, sex, diabetes duration, blood pressure, WHR, hyperlipidaemia and ramipril. Similarly, a 1 mmol/l rise in fasting plasma glucose was related to an increased risk of CV outcomes (RR=1.09, 95% CI 1.05-1.13; p<0.0001), death (RR=1.06, 95% CI 1.01-1.12; p=0.017), heart failure (RR=1.16, 95% CI 1.06-1.13; p=0.0007) and overt nephropathy (RR=1.34, 95% CI 1.23-1.45; p<0.0001) in the group composed of diabetic and non-diabetic individuals. The significant relationship between fasting plasma glucose and CV outcomes persisted after adjustment for diabetes status (RR=1.06, 95% CI 1.00-1.12; p=0.043).
There is an independent progressive relationship between indices of glycaemia and incident CV events, renal disease and death. Clinical trials of glucose lowering to prevent these outcomes in diabetic and non-diabetic individuals are indicated.
Osimertinib is a potent, third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI). The multi-arm phase Ib TATTON study (NCT02143466) was designed to assess the safety ...and tolerability of osimertinib in combination with other targeted therapies: selumetinib (MEK1/2 inhibitor), savolitinib (MET-TKI), or durvalumab anti-programmed cell death ligand 1 (anti-PD-L1) monoclonal antibody.
Patients with advanced EGFR-mutant non-small-cell lung cancer and disease progression on a prior EGFR-TKI were enrolled and allocated to dose-escalating cohorts combining osimertinib 80 mg orally (p.o.) once a day with selumetinib (25–75 mg p.o. twice a day; continuous or intermittent), savolitinib (600–800 mg p.o. once a day), or durvalumab (3–10 mg/kg intravenous every 2 weeks).
At data cut-off (28 February 2018), 77 patients were enrolled and received osimertinib plus selumetinib (n = 36), savolitinib (n = 18), or durvalumab (n = 23). Most common adverse events (any grade), occurring in ≥20% of patients across dose groups, were: selumetinib arm—diarrhea (75%), rash (58%), nausea (47%); savolitinib arm—nausea (67%), rash (56%), vomiting (50%); durvalumab arm—rash (48%), vomiting (43%), diarrhea (39%). Dose-limiting toxicities were reported in the selumetinib 25 mg (n = 1), 50 mg (n = 1), and 75 mg (n = 4) continuous-dose groups, savolitinib 600 mg (n = 1) and 800 mg dose groups (n = 2), and durvalumab 10 mg/kg (n = 1) dose group. The objective response rate was 42% (95% confidence interval 26% to 59%), 44% (22% to 69%), and 43% (23% to 66%) in the selumetinib, savolitinib, and durvalumab arms, respectively.
Our results demonstrate the feasibility of combining osimertinib 80 mg with selumetinib or savolitinib at identified tolerable, active doses. A combination of osimertinib with durvalumab was not feasible due to increased reporting of interstitial lung disease. Osimertinib-based combination therapies represent a compelling approach now being further investigated.
NCT02143466.
•Patients with advanced EGFR-mutant NSCLC received osimertinib 80 mg combined with selumetinib, savolitinib or durvalumab.•Feasible dosing strategies were identified for osimertinib plus selumetinib or savolitinib.•Osimertinib plus durvalumab was not feasible due to increased reporting of interstitial lung disease.•Responses were seen in all treatment arms, warranting further analysis of the feasible combinations identified.•Osimertinib-based combinations represent a compelling approach now being investigated broadly to further improve outcomes.
The WFCAM Science Archive Hambly, N. C.; Collins, R. S.; Cross, N. J. G. ...
Monthly Notices of the Royal Astronomical Society,
02/2008, Volume:
384, Issue:
2
Journal Article
Peer reviewed
Open access
We describe the WFCAM Science Archive, which is the primary point of access for users of data from the wide-field infrared camera WFCAM on the United Kingdom Infrared Telescope (UKIRT), especially ...science catalogue products from the UKIRT Infrared Deep Sky Survey. We describe the database design with emphasis on those aspects of the system that enable users to fully exploit the survey data sets in a variety of different ways. We give details of the database-driven curation applications that take data from the standard nightly pipeline-processed and calibrated files for the production of science-ready survey data sets. We describe the fundamentals of querying relational databases with a set of astronomy usage examples, and illustrate the results.
The First Data Release (DR1) of the United Kingdom Infrared Telescope Infrared Deep Sky Survey (UKIDSS) took place on 2006 July 21. The UKIDSS is a set of five large near-infrared surveys, covering a ...complementary range of areas, depths and Galactic latitudes. The DR1 is the first large release of survey-quality data from the UKIDSS and includes 320 deg2 of multicolour data to (Vega) K= 18, complete (depending on the survey) in three to five bands from the set ZYJHK, together with 4 deg2 of deep JK data to an average depth K= 21. In addition, the release includes a similar quantity of data with incomplete filter coverage. In JHK, in regions of low extinction, the photometric uniformity of the calibration is better than 0.02 mag in each band. The accuracy of the calibration in ZY remains to be quantified, and the same is true of JHK in regions of high extinction. The median image full width at half-maximum across the data set is 0.82 arcsec. We describe changes since the Early Data Release in the implementation, pipeline and calibration, quality control, and archive procedures. We provide maps of the areas surveyed, and summarize the contents of each of the five surveys in terms of filters, areas and depths. The DR1 marks completion of 7 per cent of the UKIDSS seven-year goals.
Temperature is an important determinant of malaria transmission. Recent work has shown that mosquito and parasite biology are influenced not only by average temperature, but also by the extent of the ...daily temperature variation. Here we examine how parasite development within the mosquito (Extrinsic Incubation Period) is expected to vary over time and space depending on the diurnal temperature range and baseline mean temperature in Kenya and across Africa. Our results show that under cool conditions, the typical approach of using mean monthly temperatures alone to characterize the transmission environment will underestimate parasite development. In contrast, under warmer conditions, the use of mean temperatures will overestimate development. Qualitatively similar patterns hold using both outdoor and indoor temperatures. These findings have important implications for defining malaria risk. Furthermore, understanding the influence of daily temperature dynamics could provide new insights into ectotherm ecology both now and in response to future climate change.
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