BenevolentAI's knowledge graph is a large repository of structured medical information, including numerous connections extracted from scientific literature by machine learning.2 Together with ...customisations bespoke to 2019-nCoV, we used BenevolentAI to search for approved drugs that could help, focusing on those that might block the viral infection process. The receptor that 2019-nCoV uses to infect lung cells might be ACE2, a cell-surface protein on cells in the kidney, blood vessels, heart, and, importantly, lung AT2 alveolar epithelial cells (figure). By contrast, one of the six high-affinity AAK1-binding drugs was the janus kinase inhibitor baricitinib, which also binds the cyclin G-associated kinase, another regulator of endocytosis. Because the plasma concentration of baricitinib on therapeutic dosing (either as 2 mg or 4 mg once daily) is sufficient to inhibit AAK1, we suggest it could be trialled, using an appropriate patient population with 2019-nCoV acute respiratory disease, to reduce both the viral entry and the inflammation in patients, using endpoints such as the MuLBSTA score, an early warning model for predicting mortality in viral pneumonia.7 JS is editor-in-chief of Oncogene.
Long hydroclimate records are essential elements for the assessment and management of changing freshwater resources. These records are especially important in transboundary watersheds where ...international cooperation is required in the joint planning and management process of shared basins. Dendrochronological techniques were used to develop a multicentury record of April 1 snow water equivalent (SWE) for the Stikine River basin in northern British Columbia, Canada, from moisture‐sensitive white spruce (Picea glauca) tree rings. Explaining 43% of the instrumental SWE variability, to our knowledge, this research represents the first attempt to develop long‐term snowpack reconstructions in northern British Columbia. The results indicated that 15 extreme low April 1 SWE events occurred from 1789 to the beginning of the instrumental record in 1974. The reconstruction record also shows that the occurrence of hydrological extremes in the Stikine River basin is characterized by persistent below‐average periods in SWE consistent with phase shifts of the Pacific Decadal Oscillation (PDO). Spectral analyses indicate a very distinct in‐phase (positive) relationship between the multidecadal frequencies of variability (~40 years) extracted from the SWE tree‐ring reconstruction and other reconstructed winter and spring PDO indices. Comparison of the reconstructed SWE record with other tree‐ring‐derived PDO proxy records shows coherence at multidecadal frequencies of variability. The research has significant implications for regional watershed management by highlighting the hydrological response of the Stikine River basin to prior climate changes.
Going for gold: The first thermally stable gold(III) hydride (C N C)*AuH is presented. It undergoes regioselective insertions with allenes to give gold(III) vinyl complexes, and reductive ...condensation with (C N C)*AuOH to the air‐stable AuII product, (C N C)*2Au2, with a short nonbridged gold–gold bond.
This study examines spatially variable stand structure and fire–climate relationships at a low elevation forest–grassland ecotone in west central British Columbia, Canada. Fire history ...reconstructions were based on samples from 92 fire-scarred trees and stand demography from 27 plots collected over an area of about 7 km2. We documented historical chronologies of widespread fires and localized grassland fires between AD 1600 and 1900. Relationships between fire events, reconstructed values of the Palmer Drought Severity Index, and annual precipitation were examined using superposed epoch and bivariate event analyses. Widespread fires occurred during warm, dry years and were preceded by multiple anomalously dry, warm years. Localized fires that affected only grassland-proximal forests were more frequent than widespread fires. These localized fires showed a lagged, positive relationship with wetter conditions. The landscape pattern of forest structure provided further evidence of complex fire activity with multiple plots shown to have experienced low-, mixed-, and/or high-severity fires over the last four centuries. We concluded that this forest–grassland ecotone was characterized by fires of mixed severity, dominated by frequent, low-severity fires punctuated by widespread fires of moderate to high severity. This landscape-level variability in fire–climate relationships and patterns in forest structure has important implications for fire and grassland management in west central British Columbia and similar environments elsewhere. Forest restoration techniques such as prescribed fire and thinning are oftentimes applied at the forest–grassland ecotone on the basis that historically high frequency, low-severity fires defined the character of past fire activity. This study provides forest managers and policy makers with important information on mixed-severity fire activity at a low elevation forest–grassland ecotone, a crucial prerequisite for the effective management of these complex ecosystems.
A central challenge in global change research is the projection of the future behavior of a system based upon past observations. Tree‐ring data have been used increasingly over the last decade to ...project tree growth and forest ecosystem vulnerability under future climate conditions. But how can the response of tree growth to past climate variation predict the future, when the future does not look like the past? Space‐for‐time substitution (SFTS) is one way to overcome the problem of extrapolation: the response at a given location in a warmer future is assumed to follow the response at a warmer location today. Here we evaluated an SFTS approach to projecting future growth of Douglas‐fir (Pseudotsuga menziesii), a species that occupies an exceptionally large environmental space in North America. We fit a hierarchical mixed‐effects model to capture ring‐width variability in response to spatial and temporal variation in climate. We found opposing gradients for productivity and climate sensitivity with highest growth rates and weakest response to interannual climate variation in the mesic coastal part of Douglas‐fir's range; narrower rings and stronger climate sensitivity occurred across the semi‐arid interior. Ring‐width response to spatial versus temporal temperature variation was opposite in sign, suggesting that spatial variation in productivity, caused by local adaptation and other slow processes, cannot be used to anticipate changes in productivity caused by rapid climate change. We thus substituted only climate sensitivities when projecting future tree growth. Growth declines were projected across much of Douglas‐fir's distribution, with largest relative decreases in the semiarid U.S. Interior West and smallest in the mesic Pacific Northwest. We further highlight the strengths of mixed‐effects modeling for reviving a conceptual cornerstone of dendroecology, Cook's 1987 aggregate growth model, and the great potential to use tree‐ring networks and results as a calibration target for next‐generation vegetation models.
We evaluated a space‐for‐time substitution approach to projecting future growth of Douglas‐fir. Fitting a hierarchical mixed‐effects model, we found opposing gradients of productivity and climate sensitivity, with highest growth rates and weakest responses to interannual climate variability in the mesic coastal part of Douglas‐fir's range; narrower rings and stronger climate sensitivity occurred across the semi‐arid interior. Ring‐width response to spatial versus temporal temperature variation was opposite in sign, suggesting that spatial variation in productivity, caused by local adaptation and other slow processes, cannot be used to anticipate changes in productivity caused by rapid climate change.
Recent snow droughts in southwestern British Columbia (BC), Canada, have reduced seasonal streamflow during the typically dry late‐spring and summer months, leading to socio‐economic and ecological ...impacts that draw attention to the impending consequences of climate change. Knowledge of annual winter snowfall variability within this region is largely derived from a sparse network of short‐duration (≤50 years) snow survey stations. In this paper, we develop an annual April 1 snow water equivalent (SWE) reconstruction from living tree‐ring chronologies that offer a perspective on long‐term natural snowpack variability. The dendrohydrological model estimates the first principal component April 1 SWE for the southwestern regions of BC to 1711. Spectral analysis identified dominant multidecadal April 1 SWE variability over the pre‐instrumental period. The reconstruction successfully captures known instrumental period influences of La Niña oscillations on reconstructed SWE, suggesting that our tree‐ring based the reconstruction has the potential to provide insights on pre‐instrumental ocean–atmosphere links with southwestern BC snowpack dynamics. Runs analysis suggests pre‐instrumental snow droughts have been more than twice as long in duration and severity than during the observed period which indicates the instrumental record may not capture the full range of April 1 SWE variability. The reconstruction provides the first high‐resolution description of SWE over the past 300 years in southwestern BC and is of immediate use to regional water resource managers.
April 1 snow water equivalent reconstructed from tree‐rings in southwestern British Columbia reveals snow droughts (sub‐20th percentile) can be longer in duration and higher in magnitude than the instrumental record may show.
Little is known about the presence, distribution, age, or activity of rock glaciers in the British Columbia Coast Mountains of western Canada. Reflecting debris accumulation and mass wasting under a ...periglacial climate, these rock glaciers describe a geomorphic response to permafrost regimes that may or may not presently exist. An inventory of rock glacier landforms in the eastern front ranges of the Coast Mountains, using high-resolution Google Earth imagery, documented 165 rock glaciers between lat. 50°10ʹ and 52°08ʹ N. The majority of these rock glaciers occur at sites positioned between 1,900 and 2,300 m above sea level, where rain shadow effects and continental air masses result in persistent dry, cold conditions. Morphology and field observation suggest that these features contain intact ice. The rock glaciers occupy predominately northwest- to northeast-facing slopes, with talus-derived rock glaciers largely restricted to north-facing slopes. Glacier-derived features outnumber talus-derived features by a ratio of 5:1. Several of the inventoried rock glaciers were located up valley from presumed Younger Dryas terminal moraines, indicating that they formed after 9390 BP. Dendrogeomorphological investigations at one rock glacier record contemporary activity that resulted in 1.3 cm/yr of frontal advance since AD 1674. This inventory is the first to document the presence of rock glaciers in the Coast Mountains and supports preliminary understandings of permafrost distribution in the southwestern Canadian Cordillera.
•Historical summer streamflow among four watersheds is modeled using dendrohydrology.•64% of the flow variance is explained, prioritizing accuracy in lowest-flow years.•Recent streamflow droughts are ...not as severe as natural historical droughts.•Managers likely underestimate worst-case scenario droughts based on hydrometric data.•Reconstruction of small, temperate basins is possible using our approach.
Recent streamflow droughts in south coastal British Columbia have had major socioeconomic and ecological impacts. Increasing drought severity under projected climate change poses serious water management challenges, particularly in the small coastal watersheds that serve as primary water sources for most communities in the region. A 332-year dendrohydrological record of regionalized mean summer streamflow for four watersheds is analyzed to place recent drought magnitudes in a long-term perspective. We present a novel approach for optimizing tree-ring based reconstructions in small watersheds in temperate environments, combining winter snow depth and summer drought sensitive proxies as model predictors. The reconstruction model, estimated by regression of observed flows on Tsuga mertensiana ring-width variables and a tree-ring derived paleorecord of the Palmer Drought Severity Index, explains 64% of the regionalized streamflow variance. The model is particularly accurate at estimating lowest flow events, and provides the strongest annually resolved paleohydrological record in British Columbia. The extended record suggests that since 1658 sixteen natural droughts have occurred that were more extreme than any within the instrumental period. Flow-duration curves show more severe worst-case scenario droughts and a higher probability of those droughts in the long-term reconstruction than in the hydrometric data. Such curves also highlight the value of dendrohydrology for probabilistic drought assessment. Our results suggest current water management strategies based on worst-case scenarios from historical gauge data likely underestimate the potential magnitudes of natural droughts. If the low-flow magnitudes anticipated under climate change co-occur with lowest possible natural flows, streamflow drought severities in small watersheds in south coastal British Columbia could exceed any of those experienced in the past ∼350years.
Diet-induced obesity (DIO) is a significant health concern which has been linked to structural and functional changes in the gut microbiota. Exercise (Ex) is effective in preventing obesity, but ...whether Ex alters the gut microbiota during development with high fat (HF) feeding is unknown.
Determine the effects of voluntary Ex on the gastrointestinal microbiota in LF-fed mice and in HF-DIO.
Male C57BL/6 littermates (5 weeks) were distributed equally into 4 groups: low fat (LF) sedentary (Sed) LF/Sed, LF/Ex, HF/Sed and HF/Ex. Mice were individually housed and LF/Ex and HF/Ex cages were equipped with a wheel and odometer to record Ex. Fecal samples were collected at baseline, 6 weeks and 12 weeks and used for bacterial DNA isolation. DNA was subjected both to quantitative PCR using primers specific to the 16S rRNA encoding genes for Bacteroidetes and Firmicutes and to sequencing for lower taxonomic identification using the Illumina MiSeq platform. Data were analyzed using a one or two-way ANOVA or Pearson correlation.
HF diet resulted in significantly greater body weight and adiposity as well as decreased glucose tolerance that were prevented by voluntary Ex (p<0.05). Visualization of Unifrac distance data with principal coordinates analysis indicated clustering by both diet and Ex at week 12. Sequencing demonstrated Ex-induced changes in the percentage of major bacterial phyla at 12 weeks. A correlation between total Ex distance and the ΔCt Bacteroidetes: ΔCt Firmicutes ratio from qPCR demonstrated a significant inverse correlation (r2 = 0.35, p = 0.043).
Ex induces a unique shift in the gut microbiota that is different from dietary effects. Microbiota changes may play a role in Ex prevention of HF-DIO.
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