Contemporary climate change in Alaska has resulted in amplified rates of press and pulse disturbances that drive ecosystem change with significant consequences for socio‐environmental systems. ...Despite the vulnerability of Arctic and boreal landscapes to change, little has been done to characterize landscape change and associated drivers across northern high‐latitude ecosystems. Here we characterize the historical sensitivity of Alaska's ecosystems to environmental change and anthropogenic disturbances using expert knowledge, remote sensing data, and spatiotemporal analyses and modeling. Time‐series analysis of moderate—and high‐resolution imagery was used to characterize land‐ and water‐surface dynamics across Alaska. Some 430,000 interpretations of ecological and geomorphological change were made using historical air photos and satellite imagery, and corroborate land‐surface greening, browning, and wetness/moisture trend parameters derived from peak‐growing season Landsat imagery acquired from 1984 to 2015. The time series of change metrics, together with climatic data and maps of landscape characteristics, were incorporated into a modeling framework for mapping and understanding of drivers of change throughout Alaska. According to our analysis, approximately 13% (~174,000 ± 8700 km2) of Alaska has experienced directional change in the last 32 years (±95% confidence intervals). At the ecoregions level, substantial increases in remotely sensed vegetation productivity were most pronounced in western and northern foothills of Alaska, which is explained by vegetation growth associated with increasing air temperatures. Significant browning trends were largely the result of recent wildfires in interior Alaska, but browning trends are also driven by increases in evaporative demand and surface‐water gains that have predominately occurred over warming permafrost landscapes. Increased rates of photosynthetic activity are associated with stabilization and recovery processes following wildfire, timber harvesting, insect damage, thermokarst, glacial retreat, and lake infilling and drainage events. Our results fill a critical gap in the understanding of historical and potential future trajectories of change in northern high‐latitude regions.
Arctic and boreal landscapes have experienced unprecedented changes in recent decades that have significant consequences for socio‐environmental systems. Despite a legacy of studies that have documented the heightened sensitivity of northern landscapes to change, characterization and prognosis of ecosystem change has remained elusive. Here, we combine remote sensing and climate reanalysis data into an integrated modeling framework to fingerprint the historical (1984–2015) sensitivity of Alaska's ecosystems to changing environmental conditions and disturbances. Our results fill a critical gap in the understanding of the historical and potential future trajectories of change in Alaska, with direct relevance to other northern high‐latitude regions.
Objectives/Hypothesis
To determine the relationship between body mass index along with other anthropomorphic variables as they relate to tracheal airway dimensions.
Study Design
Retrospective case ...series.
Methods
This was a radiographic study of 123 consecutive hospitalized patients undergoing tracheotomy over a 4‐year period (2007–2011). We measured airway dimensions in axial computed tomography imaging and made comparisons with height, weight, body mass index, gender, and age. Measurements were taken at the first tracheal ring level including anterior‐posterior length, width, and calculated area. We expected higher body mass index not to be a good predictor of larger airway dimensions.
Results
The linear regression model showed body mass index was significantly inversely related to tracheal width after controlling for gender and age (P = .0389). For every 1 kg/m2 increase in body mass index, the tracheal width decreased by 0.05 mm. There was a trend for airway area to diminish with increasing body mass index.
Conclusions
These results are consistent with the hypothesis that obese patients do not have larger airways. Our study indicated a trend toward smaller airways as body mass index increased. Specifically, as body mass index increases, tracheal width appears to decrease. This information should help medical professionals avoid the tendency to use a larger tube to secure the airway of an obese patient. Hopefully, this will result in further research into the field and may prevent future airway injuries in a society where obesity has become epidemic.
Level of Evidence
4 Laryngoscope, 125:1093–1097, 2015
Chronic exposure to drugs of abuse or stress regulates transcription factors, chromatin-modifying enzymes and histone post-translational modifications in discrete brain regions. Given the promiscuity ...of the enzymes involved, it has not yet been possible to obtain direct causal evidence to implicate the regulation of transcription and consequent behavioral plasticity by chromatin remodeling that occurs at a single gene. We investigated the mechanism linking chromatin dynamics to neurobiological phenomena by applying engineered transcription factors to selectively modify chromatin at a specific mouse gene in vivo. We found that histone methylation or acetylation at the Fosb locus in nucleus accumbens, a brain reward region, was sufficient to control drug- and stress-evoked transcriptional and behavioral responses via interactions with the endogenous transcriptional machinery. This approach allowed us to relate the epigenetic landscape at a given gene directly to regulation of its expression and to its subsequent effects on reward behavior.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Neutrophil extracellular traps (NETs) are decondensed chromatin networks released by neutrophils that can trap and kill pathogens but can also paradoxically promote biofilms. The mechanism of NET ...functions remains ambiguous, at least in part, due to their complex and variable compositions. To unravel the antimicrobial performance of NETs, a minimalistic NET‐like synthetic structure, termed “microwebs,” is produced by the sonochemical complexation of DNA and histone. The prepared microwebs have structural similarity to NETs at the nanometer to micrometer dimensions but with well‐defined molecular compositions. Microwebs prepared with different DNA to histone ratios show that microwebs trap pathogenic Escherichia coli in a manner similar to NETs when the zeta potential of the microwebs is positive. The DNA nanofiber networks and the bactericidal histone constituting the microwebs inhibit the growth of E. coli. Moreover, microwebs work synergistically with colistin sulfate, a common and a last‐resort antibiotic, by targeting the cell envelope of pathogenic bacteria. The synthesis of microwebs enables mechanistic studies not possible with NETs, and it opens new possibilities for constructing biomimetic bacterial microenvironments to better understand and predict physiological pathogen responses.
Microwebs with bacteria trapping and killing functions are designed to mimic neutrophil extracellular traps—an immune defense weapon to fight against invading pathogens. The composition–structure–function relationship of the synthetic structure is discussed, and the collaborative action between microwebs and antibiotics allows better elimination of pathogenic bacteria, Escherichia coli.
Distance sampling is widely used to estimate animal population densities by accounting for imperfect detection of individuals with increasing distance from an observer. Distance sampling assumes that ...distances are measured without error; however, it is often applied to human estimated distances, which are known to be inconsistent, inaccurate, and biased. We present an objective technique for estimating distance to vocalizing individuals that relies on the relative sound level (RSL) of the vocalization extracted from autonomous recording unit (ARU) recordings and show the error is less than human estimated error extracted from a literature case study. RSL predicted distances can be obtained by manual measurement in sound viewing software, or automatically with automated signal recognition software. We built calibration datasets of Ovenbirds (Seiurus aurocapilla) and Common Nighthawks (Chordeiles minor) recorded at known distances and used regression of RSL from those recordings to predict distance. There was no error bias of RSL predicted distances when compared to known distances for Common Nighthawk, minimal error bias for Ovenbird, and error from all RSL predicted distances was less than human estimated error extracted from the literature. We then simulated ARU point count surveys with a known density and estimated that density with distance sampling to test whether RSL distance prediction does not violate the assumption that distances are measured without error. There was no difference in density estimates from known distance and density estimates obtained from RSL predicted distance, while density estimates contaminated with human estimated error were significantly lower than density estimates from known distance. We found that a calibration dataset of approximately 300 vocalizations was suitable to minimize error for both species, and so conclude that RSL distance prediction is an accessible method of improving distance estimates relative to human estimation. We provide general recommendations on how to collect calibration recordings for the application of RSL distance prediction to other species and areas.
We present an objective technique for estimating distance to vocalizing individuals that relies on the relative sound level (RSL) of the vocalization extracted from autonomous recording unit (ARU) recordings and show it has less error than human estimated distances. We found there was no error bias of RSL predicted distances when compared to known distances for Common Nighthawk, minimal error bias for Ovenbird, and all RSL predicted distances had less error than human estimated distances extracted from the literature. We conclude that RSL distance prediction improves distance estimates relative to human estimation. RSL can be retrieved through automatic signal recognition, which increases processing efficiency and can increase the number of observations available for distance sampling wildlife populations.
Given the complex nature of the responses that can occur in host-pathogen interactions, dual transcriptomics offers a powerful method of elucidating these interactions during infection. The gene ...expression patterns of Aspergillus fumigatus conidia or host cells have been reported in a number of previous studies, but each focused on only one of the interacting organisms. In the present study, we profiled simultaneously the transcriptional response of both A. fumigatus and human airway epithelial cells (AECs).
16HBE14o- transformed bronchial epithelial cells were incubated with A. fumigatus conidia at 37°C for 6 hours, followed by genome-wide transcriptome analysis using human and fungal microarrays. Differentially expressed gene lists were generated from the microarrays, from which biologically relevant themes were identified. Human and fungal candidate genes were selected for validation, using RT-qPCR, in both 16HBE14o- cells and primary AECs co-cultured with conidia.
We report that ontologies related to the innate immune response are activated by co-incubation with A. fumigatus condia, and interleukin-6 (IL-6) was confirmed to be up-regulated in primary AECs via RT-qPCR. Concomitantly, A. fumigatus was found to up-regulate fungal pathways involved in iron acquisition, vacuolar acidification, and formate dehydrogenase activity.
To our knowledge, this is the first study to apply a dual organism transcriptomics approach to interactions of A. fumigatus conidia and human airway epithelial cells. The up-regulation of IL-6 by epithelia and simultaneous activation of several pathways by fungal conidia warrants further investigation as we seek to better understand this interaction in both health and disease. The cellular response of the airway epithelium to A. fumigatus is important to understand if we are to improve host-pathogen outcomes.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Using structure-guided design, several cell based assays, and microdosed positron emission tomography (PET) imaging, we identified a series of highly potent, selective, and brain-penetrant ...oxazole-4-carboxamide-based inhibitors of glycogen synthase kinase-3 (GSK-3). An isotopologue of our first-generation lead, 3HPF-367, demonstrates selective and specific target engagement in vitro, irrespective of the activation state. We discovered substantial ubiquitous GSK-3-specific radioligand binding in Tg2576 Alzheimer’s disease (AD), suggesting application for these compounds in AD diagnosis and identified 11COCM-44 as our lead GSK-3 radiotracer, with optimized brain uptake by PET imaging in nonhuman primates. GSK-3β-isozyme selectivity was assessed to reveal OCM-51, the most potent (IC50 = 0.030 nM) and selective (>10-fold GSK-3β/GSK-3α) GSK-3β inhibitor known to date. Inhibition of CRMP2T514 and tau phosphorylation, as well as favorable therapeutic window against WNT/β-catenin signaling activation, was observed in cells.
Established in 1952, the programme of surveillance and Confidential Enquiries into Maternal Deaths in the UK is the longest running such programme worldwide. Although more recently instituted, ...surveillance and confidential enquiries into perinatal deaths are also now well established nationally. Recent changes to funding and commissioning of the Enquiries have enabled both a reinvigoration of the processes and improvements to the methodology with an increased frequency of future reporting. Close engagement with stakeholders and a regulator requirement for doctors to participate have both supported the impetus for involvement of all professionals leading to greater potential for improved quality of care for women and babies.
Nontyphoidal Salmonella (NTS) is a major cause of bacteraemia in Africa. The disease typically affects HIV-infected individuals and young children, causing substantial morbidity and mortality. Here ...we present a genome-wide association study (180 cases, 2677 controls) and replication analysis of NTS bacteraemia in Kenyan and Malawian children. We identify a locus in STAT4, rs13390936, associated with NTS bacteraemia. rs13390936 is a context-specific expression quantitative trait locus for STAT4 RNA expression, and individuals carrying the NTS-risk genotype demonstrate decreased interferon-γ (IFNγ) production in stimulated natural killer cells, and decreased circulating IFNγ concentrations during acute NTS bacteraemia. The NTS-risk allele at rs13390936 is associated with protection against a range of autoimmune diseases. These data implicate interleukin-12-dependent IFNγ-mediated immunity as a determinant of invasive NTS disease in African children, and highlight the shared genetic architecture of infectious and autoimmune disease.
Abstract
We use JWST NIRCam short-wavelength photometry to capture a transit lightcurve of the exoplanet HAT-P-14 b to assess performance as part of instrument commissioning. The short-wavelength ...precision is 152 ppm per 27 s integration as measured over the full time series compared to a theoretical limit of 107 ppm, after corrections to spatially correlated 1/f noise. Persistence effects from charge trapping are well fit by an exponential function with short characteristic timescales, settling on the order of 5–15 minutes. The short-wavelength defocused photometry is also uniquely well suited to measure the real-time wave-front error of JWST. Analysis of the images and reconstructed wave-front maps indicates that two different hexagonal primary mirror segments exhibited “tilt events,” where they changed orientation rapidly in less than ∼1.4 s. In some cases, the magnitude and timing of the flux jumps caused by tilt events can be accurately predicted with a telescope model. These tilt events can be sensed by simultaneous longer-wavelength NIRCam grism spectral images alone in the form of changes to the point-spread function, diagnosed from the full width at half maximum. They can also be sensed with the fine guidance sensor instrument from difference images. Tilt events possibly from sudden releases of stress in the backplane structure behind the mirrors were expected during the commissioning period because they were found in ground-based testing. Tilt events have shown signs of decreasing in frequency but have not disappeared completely. The detectors exhibit some minor (less than 1%) deviations from linear behavior in the first few groups of each integration, potentially impacting absolute fluxes and transit depths on bright targets, where only a handful of groups are possible. Overall, the noise is within 50% of the theoretical photon noise and read noise. This bodes well for high-precision measurements of transiting exoplanets and other time variable targets.
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