Antarctic ocean and sea ice response to ozone depletion: a two timescale problem

The response of the Southern Ocean to a repeating seasonal cycle of ozone loss is studied in two coupled climate models and found to comprise both fast and slow processes. The fast response is similar to the inter-annual signature of the Southern Annular Mode (SAM) on Sea Surface Temperature (SST), on to which the ozone-hole forcing projects in the summer. It comprises enhanced northward Ekman drift inducing negative summertime SST anomalies around Antarctica, earlier sea ice freeze-up the following winter, and northward expansion of the sea ice edge year-round. The enhanced northward Ekman drift, however, results in upwelling of warm waters from below the mixed layer in the region of seasonal sea ice. With sustained bursts of westerly winds induced by ozone-hole depletion, this warming from below eventually dominates over the cooling from anomalous Ekman drift. The resulting slow-timescale response (years to decades) leads to warming of SSTs around Antarctica and ultimately a reduction in sea-ice cover year-round. This two-timescale behavior - rapid cooling followed by slow but persistent warming - is found in the two coupled models analysed, one with an idealized geometry, the other a complex global climate model with realistic geometry. Processes that control the timescale of the transition from cooling to warming, and their uncertainties are described. Finally we discuss the implications of our results for rationalizing previous studies of the effect of the ozone-hole on SST and sea-ice extent. %Interannual variability in the Southern Annular Mode (SAM) and sea ice covary such that an increase and southward shift in the surface westerlies (a positive phase of the SAM) coincides with a cooling of Sea Surface Temperature (SST) around 70-50$^\circ$S and an expansion of the sea ice cover, as seen in observations and models alike. Yet, in modeling studies, the Southern Ocean warms and sea ice extent decreases in response to sustained, multi-decadal positive SAM-like wind anomalies driven by 20th century ozone depletion. Why does the Southern Ocean appear to have disparate responses to SAM-like variability on interannual and multidecadal timescales? Here it is demonstrated that the response of the Southern Ocean to ozone depletion has a fast and a slow response. The fast response is similar to the interannual variability signature of the SAM. It is dominated by an enhanced northward Ekman drift, which transports heat northward and causes negative SST anomalies in summertime, earlier sea ice freeze-up the following winter, and northward expansion of the sea ice edge year round. The enhanced northward Ekman drift causes a region of Ekman divergence around 70-50$^\circ$S, which results in upwelling of warmer waters from below the mixed layer. With sustained westerly wind enhancement in that latitudinal band, the warming due to the anomalous upwelling of warm waters eventually dominates over the cooling from the anomalous Ekman drift. Hence, the slow response ultimately results in a positive SST anomaly and a reduction in the sea ice cover year round. We demonstrate this behavior in two models: one with an idealized geometry and another, more detailed, global climate model. However, the models disagree on the timescale of transition from the fast (cooling) to the slow (warming) response. Processes that controls this transition and their uncertainties are discussed

Antarctic Ocean and Sea Ice Response to Ozone Depletion: A Two-Time-Scale Problem

The response of the Southern Ocean to a repeating seasonal cycle of ozone loss is studied in two coupled climate models and is found to comprise both fast and slow processes. The fast response is similar to the interannual signature of the southern annular mode (SAM) on sea surface temperature (SST), onto which the ozone hole forcing projects in the summer. It comprises enhanced northward Ekman drift, inducing negative summertime SST anomalies around Antarctica, earlier sea ice freeze-up the following winter, and northward expansion of the sea ice edge year-round. The enhanced northward Ekman drift, however, results in upwelling of warm waters from below the mixed layer in the region of seasonal sea ice. With sustained bursts of westerly winds induced by ozone hole depletion, this warming from below eventually dominates over the cooling from anomalous Ekman drift. The resulting slow time-scale response (years to decades) leads to warming of SSTs around Antarctica and ultimately a reduction in sea ice cover year-round. This two-time-scale behavior—rapid cooling followed by slow but persistent warming—is found in the two coupled models analyzed: one with an idealized geometry and the other with a complex global climate model with realistic geometry. Processes that control the time scale of the transition from cooling to warming and their uncertainties are described. Finally the implications of these results are discussed for rationalizing previous studies of the effect of the ozone hole on SST and sea ice extent.United States. National Aeronautics and Space Administration. Modeling, Analysis, and Prediction Program (Grant)National Science Foundation (U.S.) (Frontiers in Earth System Dynamics Project

Lesser prairie-chicken fence collision risk across its northern distribution

Livestock fences have been hypothesized to significantly contribute to mortality of lesser prairie-chickens (Tympanuchus pallidicinctus); however, quantification of mortality due to fence collisions is lacking across their current distribution. Variation in fence density, landscape composition and configuration, and land use could influence collision risk of lesser prairie-chickens. We monitored fences within 3 km of known leks during spring and fall and surveyed for signs of collision occurrence within 20 m of fences in 6 study sites in Kansas and Colorado, USA during 2013 and 2014. We assessed mortality locations of radio-tagged birds (n = 286) for evidence of fence collisions and compared distance to fence relative to random points. Additionally, we quantified locations, propensity, and frequency of fences crossed by lesser prairie-chickens. We tested for landscape and vegetative characteristics that influenced fence-cross propensity and frequency of global positioning system (GPS)-marked birds. A minimum of 12,706 fence crossings occurred by GPS-marked lesser prairie-chickens. We found 3 carcasses and 12 additional possible instances of evidence of collision during >2,800 km of surveyed fences. We found evidence for a single suspected collision based on carcass evidence for 148 mortalities of transmittered birds. Mortality locations of transmittered birds were located at distances from fences 15% farther than expected at random. Our data suggested minimal biological significance and indicated that propensity and frequency of fence crossings were random processes. Lesser prairie-chickens do not appear to be experiencing significant mortality risk due to fence collisions in Kansas and Colorado. Focusing resources on other limiting factors (i.e., habitat quality) has greater potential for impact on population demography than fence marking and removal.Keywords: Colorado, lesser prairie-chicken, management, Kansas, fences, mortality, Tympanuchus pallidicinctusKeywords: Colorado, lesser prairie-chicken, management, Kansas, fences, mortality, Tympanuchus pallidicinctu

Predicting Bison Migration out of Yellowstone National Park Using Bayesian Models

Long distance migrations by ungulate species often surpass the boundaries of preservation areas where conflicts with various publics lead to management actions that can threaten populations. We chose the partially migratory bison (Bison bison) population in Yellowstone National Park as an example of integrating science into management policies to better conserve migratory ungulates. Approximately 60% of these bison have been exposed to bovine brucellosis and thousands of migrants exiting the park boundary have been culled during the past two decades to reduce the risk of disease transmission to cattle. Data were assimilated using models representing competing hypotheses of bison migration during 1990–2009 in a hierarchal Bayesian framework. Migration differed at the scale of herds, but a single unifying logistic model was useful for predicting migrations by both herds. Migration beyond the northern park boundary was affected by herd size, accumulated snow water equivalent, and aboveground dried biomass. Migration beyond the western park boundary was less influenced by these predictors and process model performance suggested an important control on recent migrations was excluded. Simulations of migrations over the next decade suggest that allowing increased numbers of bison beyond park boundaries during severe climate conditions may be the only means of avoiding episodic, large-scale reductions to the Yellowstone bison population in the foreseeable future. This research is an example of how long distance migration dynamics can be incorporated into improved management policies

Allosteric Interactions between the Myristate- and ATP-Site of the Abl Kinase

Abl kinase inhibitors targeting the ATP binding pocket are currently employed as potent anti-leukemogenic agents but drug resistance has become a significant clinical limitation. Recently, a compound that binds to the myristate pocket of Abl (GNF-5) was shown to act cooperatively with nilotinib, an ATP-competitive inhibitor to target the recalcitrant “T315I” gatekeeper mutant of Bcr-Abl. To uncover an explanation for how drug binding at a distance from the kinase active site could lead to inhibition and how inhibitors could combine their effects, hydrogen exchange mass spectrometry (HX MS) was employed to monitor conformational effects in the presence of both dasatinib, a clinically approved ATP-site inhibitor, and GNF-5. While dasatinib binding to wild type Abl clearly influenced Abl conformation, no binding was detected between dasatinib and T315I. GNF-5, however, elicited the same conformational changes in both wild type and T315I, including changes to dynamics within the ATP site located approximately 25 Å from the site of GNF-5 interaction. Simultaneous binding of dasatinib and GNF-5 to T315I caused conformational and/or dynamics changes in Abl such that effects of dasatinib on T315I were the same as when it bound to wild type Abl. These results provide strong biophysical evidence that allosteric interactions play a role in Abl kinase downregulation and that targeting sites outside the ATP binding site can provide an important pharmacological tool to overcome mutations that cause resistance to ATP-competitive inhibitors

Presence of Symptoms 6 Weeks After COVID-19 Among Vaccinated and Unvaccinated US Healthcare Personnel: A Prospective Cohort Study

OBJECTIVES: Although COVID-19 vaccines offer protection against infection and severe disease, there is limited information on the effect of vaccination on prolonged symptoms following COVID-19. Our objective was to determine differences in prevalence of prolonged symptoms 6 weeks after onset of COVID-19 among healthcare personnel (HCP) by vaccination status, and to assess differences in timing of return to work. DESIGN: Cohort analysis of HCP with COVID-19 enrolled in a multicentre vaccine effectiveness study. HCP with COVID-19 between December 2020 and August 2021 were followed up 6 weeks after illness onset. SETTING: Health systems in 12 US states. PARTICIPANTS: HCP participating in a vaccine effectiveness study were eligible for inclusion if they had laboratory-confirmed symptomatic SARS-CoV-2 with mRNA vaccination (symptom onset ≥14 days after two doses) or no prior vaccination. Among 681 eligible participants, 419 (61%) completed a follow-up survey to assess symptoms reported 6 weeks after illness onset. EXPOSURES: Two doses of a COVID-19 mRNA vaccine compared with no COVID-19 vaccine. MAIN OUTCOME MEASURES: Prevalence of symptoms 6 weeks after onset of COVID-19 illness and days to return to work. RESULTS: Among 419 HCP with COVID-19, 298 (71%) reported one or more COVID-like symptoms 6 weeks after illness onset, with a lower prevalence among vaccinated participants compared with unvaccinated participants (60.6% vs 79.1%; adjusted risk ratio 0.70, 95% CI 0.58 to 0.84). Following their illness, vaccinated HCP returned to work a median 2.0 days (95% CI 1.0 to 3.0) sooner than unvaccinated HCP (adjusted HR 1.37, 95% CI 1.04 to 1.79). CONCLUSIONS: Receipt of two doses of a COVID-19 mRNA vaccine among HCP with COVID-19 illness was associated with decreased prevalence of COVID-like symptoms at 6 weeks and earlier return to work

Differential sensitivity of Src-family kinases to activation by SH3 domain displacement

Src-family kinases (SFKs) are non-receptor protein-tyrosine kinases involved in a variety of signaling pathways in virtually every cell type. The SFKs share a common negative regulatory mechanism that involves intramolecular interactions of the SH3 domain with the PPII helix formed by the SH2-kinase linker as well as the SH2 domain with a conserved phosphotyrosine residue in the C-terminal tail. Growing evidence suggests that individual SFKs may exhibit distinct activation mechanisms dictated by the relative strengths of these intramolecular interactions. To elucidate the role of the SH3:linker interaction in the regulation of individual SFKs, we used a synthetic SH3 domain-binding peptide (VSL12) to probe the sensitivity of downregulated c-Src, Hck, Lyn and Fyn to SH3-based activation in a kinetic kinase assay. All four SFKs responded to VSL12 binding with enhanced kinase activity, demonstrating a conserved role for SH3:linker interaction in the control of catalytic function. However, the sensitivity and extent of SH3-based activation varied over a wide range. In addition, autophosphorylation of the activation loops of c-Src and Hck did not override regulatory control by SH3:linker displacement, demonstrating that these modes of activation are independent. Our results show that despite the similarity of their downregulated conformations, individual Src-family members show diverse responses to activation by domain displacement which may reflect their adaptation to specific signaling environments in vivo. © 2014 Moroco et al

Risk of Recurrent Arterial Ischemic Stroke in Childhood: A Prospective International Study.

Background and purposePublished cohorts of children with arterial ischemic stroke (AIS) in the 1990s to early 2000s reported 5-year cumulative recurrence rates approaching 20%. Since then, utilization of antithrombotic agents for secondary stroke prevention in children has increased. We sought to determine rates and predictors of recurrent stroke in the current era.MethodsThe Vascular Effects of Infection in Pediatric Stroke (VIPS) study enrolled 355 children with AIS at 37 international centers from 2009 to 2014 and followed them prospectively for recurrent stroke. Index and recurrent strokes underwent central review and confirmation, as well as central classification of causes of stroke, including arteriopathies. Other predictors were measured via parental interview or chart review.ResultsOf the 355 children, 354 survived their acute index stroke, and 308 (87%) were treated with an antithrombotic medication. During a median follow-up of 2.0 years (interquartile range, 1.0-3.0), 40 children had a recurrent AIS, and none had a hemorrhagic stroke. The cumulative stroke recurrence rate was 6.8% (95% confidence interval, 4.6%-10%) at 1 month and 12% (8.5%-15%) at 1 year. The sole predictor of recurrence was the presence of an arteriopathy, which increased the risk of recurrence 5-fold when compared with an idiopathic AIS (hazard ratio, 5.0; 95% confidence interval, 1.8-14). The 1-year recurrence rate was 32% (95% confidence interval, 18%-51%) for moyamoya, 25% (12%-48%) for transient cerebral arteriopathy, and 19% (8.5%-40%) for arterial dissection.ConclusionsChildren with AIS, particularly those with arteriopathy, remain at high risk for recurrent AIS despite increased utilization of antithrombotic agents. Therapies directed at the arteriopathies themselves are needed

The transcriptional architecture of early human hematopoiesis identifies multilevel control of lymphoid commitment.

Understanding how differentiation programs originate from the gene-expression 'landscape' of hematopoietic stem cells (HSCs) is crucial for the development of new clinical therapies. We mapped the transcriptional dynamics underlying the first steps of commitment by tracking transcriptome changes in human HSCs and eight early progenitor populations. We found that transcriptional programs were extensively shared, extended across lineage-potential boundaries and were not strictly lineage affiliated. Elements of stem, lymphoid and myeloid programs were retained in multilymphoid progenitors (MLPs), which reflected a hybrid transcriptional state. By functional single cell analysis, we found that the transcription factors Bcl-11A, Sox4 and TEAD1 (TEF1) governed transcriptional networks in MLPs, which led to B cell specification. Overall, we found that integrated transcriptome approaches can be used to identify previously unknown regulators of multipotency and show additional complexity in lymphoid commitment