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An Antibody-Based Leukocyte-Capture Microarray for the Diagnosis of Systemic Lupus Erythematosus
The diagnosis of Systemic Lupus Erythematosus (SLE) is challenging due to its heterogeneous clinical presentation and the lack of robust biomarkers to distinguish it from other autoimmune diseases. Further, currently used laboratory tests do not readily distinguish active and inactive disease. Several groups have attempted to apply emerging high throughput profiling technologies to diagnose and monitor SLE. Despite showing promise, many are expensive and technically challenging for routine clinical use. The goal of this work is to develop a better diagnostic and monitoring tool for SLE. We report a highly customisable antibody microarray that consists of a duplicate arrangement of 82 antibodies directed against surface antigens on peripheral blood mononuclear cells (PMBCs). This high-throughput array was used to profile SLE patients (n = 60) with varying disease activity, compared to healthy controls (n = 24), patients with rheumatoid arthritis (n = 25), and other autoimmune diseases (n = 28). We used a computational algorithm to calculate a score from the entire microarray profile and correlated it with SLE disease activity. Our results demonstrate that leukocyte-capture microarray profiles can readily distinguish active SLE patients from healthy controls (AUROC = 0.84). When combined with the standard laboratory tests (serum anti-dsDNA, complements C3 and C4), the microarrays provide significantly increased discrimination. The antibody microarrays can be enhanced by the addition of other markers for potential application to the diagnosis and stratification of SLE, paving the way for the customised and accurate diagnosis and monitoring of SLE
The Potential Impact of Nuclear Conflict on Ocean Acidification
We demonstrate that the global cooling resulting from a range of nuclear conflict scenarios would temporarily increase the pH in the surface ocean by up to 0.06 units over a 5-year period, briefly alleviating the decline in pH associated with ocean acidification. Conversely, the global cooling dissolves atmospheric carbon into the upper ocean, driving a 0.1 to 0.3 unit decrease in the aragonite saturation state (Ωarag) that persists for ∼10 years. The peak anomaly in pH occurs 2 years post conflict, while the Ωarag anomaly peaks 4- to 5-years post conflict. The decrease in Ωarag would exacerbate a primary threat of ocean acidification: the inability of marine calcifying organisms to maintain their shells/skeletons in a corrosive environment. Our results are based on sensitivity simulations conducted with a state-of-the-art Earth system model integrated under various black carbon (soot) external forcings. Our findings suggest that regional nuclear conflict may have ramifications for global ocean acidification
Prolonged viral replication and longitudinal viral dynamic differences among respiratory syncytial virus infected infants
© 2017 2017 International Pediatric Research Foundation, Inc. BackgroundLongitudinal respiratory syncytial virus (RSV) dynamics have not been well studied despite the existence of factors favoring prolonged RSV replication including high mutation rates allowing rapid evolution and potential escape from immune control. We therefore measured viral load in previously RSV-naive infants over prolonged time spans.MethodsDuring 2014-2015, quantitative nasal aspirates were collected from 51 RSV-PCR+ infants. Multiple parallel assessments of viral loads were quantified at each collected time point using a well-validated real-time quantitative reverse transcriptase polymerase chain reaction assay. After observing viral load rebound phenomenon in some infants, the viral dynamics of 27 infants with sufficient longitudinal viral load data points were analyzed using the pre-defined criteria for viral rebound. Additional analyses were performed comparing age with viral rebound, viral clearance rates, and viral load area-under-the-curve (AUC VL).ResultsThe 51 infants (303 nasal aspirate samples; mean of 5.9 per patient) exhibited slower than expected viral clearance. Lower age trended toward slower viral clearance and greater AUC VL. Six infants had detectable viral loads ≥1 month after symptom onset. Ten of twenty-seven evaluable subjects exhibited viral rebound and this rebound was age-dependent (P=0.0259). All but one rebounder were rebound; likely representing viral mutational immune escape
Effects of Tectonics and Large Scale Climatic Changes On the Evolutionary History of \u3ci\u3eHyalomma\u3c/i\u3e ticks
Hyalomma Koch, 1844 are ixodid ticks that infest mammals, birds and reptiles, to which 27 recognized species occur across the Afrotropical, Palearctic and Oriental regions. Despite their medical and veterinary importance, the evolutionary history of the group is enigmatic. To investigate various taxonomic hypotheses based on morphology, and also some of the mechanisms involved in the diversification of the genus, we sequenced and analysed data derived from two mtDNA fragments, three nuclear DNA genes and 47 morphological characters. Bayesian and Parsimony analyses based on the combined data (2242 characters for 84 taxa) provided maximum resolution and strongly supported the monophyly of Hyalomma and the subgenus Euhyalomma Filippova, 1984 (including H. punt Hoogstraal, Kaiser and Pedersen, 1969). A predicted close evolutionary association was found between morphologically similar H. dromedarii Koch, 1844, H. somalicum Tonelli Rondelli, 1935, H. impeltatum Schulze and Schlottke, 1929 and H. punt, and together they form a sister lineage to H. asiaticum Schulze and Schlottke, 1929, H. schulzei Olenev, 1931 and H. scupense Schulze, 1919. Congruent with morphological suggestions, H. anatolicum Koch, 1844, H. excavatum Koch, 1844 and H. lusitanicum Koch, 1844 form a clade and so also H. glabrum Delpy, 1949, H. marginatum Koch, 1844, H. turanicum Pomerantzev, 1946 and H. rufipes Koch, 1844. Wide scale continental sampling revealed cryptic divergences within African H. truncatum Koch, 1844 and H. rufipes and suggested that the taxonomy of these lineages is in need of a revision. The most basal lineages in Hyalomma represent taxa currently confined to Eurasia and molecular clock estimates suggest that members of the genus started to diverge approximately 36.25 million years ago (Mya). The early diversification event coincides well with the collision of the Indian and Eurasian Plates, an event that was also characterized by large scale faunal turnover in the region. Using S-Diva, we also propose that the closure of the Tethyan seaway allowed for the genus to first enter Africa approximately 17.73 Mya. In concert, our data supports the notion that tectonic events and large scale global changes in the environment contributed significantly to produce the rich species diversity currently found in the genus Hyalomma
Marine wild-capture fisheries after nuclear war
Unidad de excelencia María de Maeztu CEX2019-000940-MIdentificadors digitals: Digital object identifier for the 'European Research Council' (http://dx.doi.org/10.13039/501100000781) Digital object identifier for 'Horizon 2020' (http://dx.doi.org/10.13039/501100007601) - BIGSEA projectNuclear war, beyond its devastating direct impacts, is expected to cause global climatic perturbations through injections of soot into the upper atmosphere. Reduced temperature and sunlight could drive unprecedented reductions in agricultural production, endangering global food security. However, the effects of nuclear war on marine wild-capture fisheries, which significantly contribute to the global animal protein and micronutrient supply, remain unexplored. We simulate the climatic effects of six war scenarios on fish biomass and catch globally, using a state-of-the-art Earth system model and global process-based fisheries model. We also simulate how either rapidly increased fish demand (driven by food shortages) or decreased ability to fish (due to infrastructure disruptions), would affect global catches, and test the benefits of strong prewar fisheries management. We find a decade-long negative climatic impact that intensifies with soot emissions, with global biomass and catch falling by up to 18 ± 3% and 29 ± 7% after a US-Russia war under business-as-usual fishing-similar in magnitude to the end-of-century declines under unmitigated global warming. When war occurs in an overfished state, increasing demand increases short-term (1 to 2 y) catch by at most ∼30% followed by precipitous declines of up to ∼70%, thus offsetting only a minor fraction of agricultural losses. However, effective prewar management that rebuilds fish biomass could ensure a short-term catch buffer large enough to replace ∼43 ± 35% of today's global animal protein production. This buffering function in the event of a global food emergency adds to the many previously known economic and ecological benefits of effective and precautionary fisheries management
Marine wild-capture fisheries after nuclear war
Nuclear war, beyond its devastating direct impacts, is expected to cause global climatic perturbations through injections of soot into the upper atmosphere. Reduced temperature and sunlight could drive unprecedented reductions in agricultural production, endangering global food security. However, the effects of nuclear war on marine wild-capture fisheries, which significantly contribute to the global animal protein and micronutrient supply, remain unexplored. We simulate the climatic effects of six war scenarios on fish biomass and catch globally, using a state-of-the-art Earth system model and global process-based fisheries model. We also simulate how either rapidly increased fish demand (driven by food shortages) or decreased ability to fish (due to infrastructure disruptions), would affect global catches, and test the benefits of strong prewar fisheries management. We find a decade-long negative climatic impact that intensifies with soot emissions, with global biomass and catch falling by up to 18 ± 3% and 29 ± 7% after a US–Russia war under business-as-usual fishing—similar in magnitude to the end-of-century declines under unmitigated global warming. When war occurs in an overfished state, increasing demand increases short-term (1 to 2 y) catch by at most ∼30% followed by precipitous declines of up to ∼70%, thus offsetting only a minor fraction of agricultural losses. However, effective prewar management that rebuilds fish biomass could ensure a short-term catch buffer large enough to replace ∼43 ± 35% of today’s global animal protein production. This buffering function in the event of a global food emergency adds to the many previously known economic and ecological benefits of effective and precautionary fisheries management
Caterpillars on a Phytochemical Landscape: The Case of Alfalfa and the Melissa Blue Butterfly
Modern metabolomic approaches that generate more comprehensive phytochemical profiles than were previously available are providing new opportunities for understanding plant‐animal interactions. Specifically, we can characterize the phytochemical landscape by asking how a larger number of individual compounds affect herbivores and how compounds covary among plants. Here we use the recent colonization of alfalfa (Medicago sativa) by the Melissa blue butterfly (Lycaeides melissa) to investigate the effects of indivdiual compounds and suites of covarying phytochemicals on caterpillar performance. We find that survival, development time, and adult weight are all associated with variation in nutrition and toxicity, including biomolecules associated with plant cell function as well as putative anti‐herbivore action. The plant‐insect interface is complex, with clusters of covarying compounds in many cases encompassing divergent effects on different aspects of caterpillar performance. Individual compounds with the strongest associations are largely specialized metabolites, including alkaloids, phenolic glycosides, and saponins. The saponins are represented in our data by more than 25 individual compounds with beneficial and detrimental effects on L. melissa caterpillars, which highlights the value of metabolomic data as opposed to approaches that rely on total concentrations within broad defensive classes
Influences of seasonality and habitat quality on Great Lakes coastal wetland fish community composition and diets
Great Lakes coastal wetlands (GLCW) have been severely degraded by anthropogenic activity over the last several decades despite their critical role in fish production. Many Great Lakes fish species use coastal wetland habitats for spawning, feeding, shelter, and nurseries throughout the year. The goal of our study was to compare GLCW fish community composition in the spring, summer, and fall months and investigate how water quality relates to fish diversity, the presence of functional groups, and juvenile fish diets. We summarized fish data collected from GLCW across the basin and used the coastal wetland monitoring program’s water quality-land use indicator to quantify water quality. Basin-wide, we found taxonomic and functional group differences in community composition among three sampling seasons, as well as across the range of water quality. Water quality was positively associated with the abundance of small cyprinids and the relative abundance of some habitat and reproductive specialists. Seasonal differences were also observed for many of these functional groups, with more temperature- and pollution- sensitive fishes captured in the spring and more nest-spawning fishes captured in the summer and fall. In our diet study, we found that age-0 fish primarily consumed zooplankton in the fall, whereas age-1 fish primarily consumed macroinvertebrates in the spring. Moreover, wetland quality was positively associated with trichopteran prey abundance. We concluded that taxonomic and functional composition of fish communities in GLCW vary markedly with respect to water quality and season. Thus, a full understanding of communities across a gradient of quality requires multi-season sampling
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