Overexpression of genes that respond to drought stress is a seemingly attractive approach for improving drought resistance in crops. However, the consequences for both water-use efficiency and ...productivity must be considered if agronomic utility is sought. Here, we characterize two tomato (Solarium lycopersicum) lines (sp12 and sp5) that overexpress a gene encoding 9-cisepoxycarotenoid dioxygenase, the enzyme that catalyzes a key rate-limiting step in abscisic acid (ABA) biosynthesis. Both lines contained more ABA than the wild type, with sp5 accumulating more than sp12. Both had higher transpiration efficiency because of their lower stomatal conductance, as demonstrated by increases in δ¹³C and δ¹ɸO, and also by gravimetric and gas-exchange methods. They also had greater root hydraulic conductivity. Under well-watered glasshouse conditions, mature sp5 plants were found to have a shoot biomass equal to the wild type despite their lower assimilation rate per unit leaf area. These plants also had longer petioles, larger leaf area, increased specific leaf area, and reduced leaf epinasty. When exposed to root-zone water deficits, line sp12 showed an increase in xylem ABA concentration and a reduction in stomatal conductance to the same final levels as the wild type, but from a different basal level. Indeed, the main difference between the high ABA plants and the wild type was their performance under well- watered conditions: the former conserved soil water by limiting maximum stomatal conductance per unit leaf area, but also, at least in the case of sp5, developed a canopy more suited to light interception, maximizing assimilation per plant, possibly due to improved turgor or suppression of epinasty.
The cellular prion protein (PrPC) comprises two domains: a globular C-terminal domain and an unstructured N-terminal domain. Recently, copper has been observed to drive tertiary contact in PrPC, ...inducing a neuroprotective cis interaction that structurally links the protein's two domains. The location of this interaction on the C terminus overlaps with the sites of human pathogenic mutations and toxic antibody docking. Combined with recent evidence that the N terminus is a toxic effector regulated by the C terminus, there is an emerging consensus that this cis interaction serves a protective role, and that the disruption of this interaction by misfolded PrP oligomers may be a cause of toxicity in prion disease. We demonstrate here that two highly conserved histidines in the C-terminal domain of PrPC are essential for the protein's cis interaction, which helps to protect against neurotoxicity carried out by its N terminus. We show that simultaneous mutation of these histidines drastically weakens the cis interaction and enhances spontaneous cationic currents in cultured cells, the first C-terminal mutant to do so. Whereas previous studies suggested that Cu2+ coordination was localized solely to the protein's N-terminal domain, we find that both domains contribute equatorially coordinated histidine residue side-chains, resulting in a novel bridging interaction. We also find that extra N-terminal histidines in pathological familial mutations involving octarepeat expansions inhibit this interaction by sequestering copper from the C terminus. Our findings further establish a structural basis for PrPC's C-terminal regulation of its otherwise toxic N terminus.
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•The two domains of the cellular prion protein are tethered together by a copper ion.•This tethering is the basis of the protein's neuroprotective cis interaction.•Disruption of this interaction explains the toxicity of prion diseases.•Disruption may explain prion protein mediated toxicity in Alzheimer's disease
Marked activation of the sympathetic nervous system occurs during and after noncardiac surgery. Low-dose clonidine, which blunts central sympathetic outflow, may prevent perioperative myocardial ...infarction and death without inducing hemodynamic instability.
We performed a blinded, randomized trial with a 2-by-2 factorial design to allow separate evaluation of low-dose clonidine versus placebo and low-dose aspirin versus placebo in patients with, or at risk for, atherosclerotic disease who were undergoing noncardiac surgery. A total of 10,010 patients at 135 centers in 23 countries were enrolled. For the comparison of clonidine with placebo, patients were randomly assigned to receive clonidine (0.2 mg per day) or placebo just before surgery, with the study drug continued until 72 hours after surgery. The primary outcome was a composite of death or nonfatal myocardial infarction at 30 days.
Clonidine, as compared with placebo, did not reduce the number of primary-outcome events (367 and 339, respectively; hazard ratio with clonidine, 1.08; 95% confidence interval CI, 0.93 to 1.26; P=0.29). Myocardial infarction occurred in 329 patients (6.6%) assigned to clonidine and in 295 patients (5.9%) assigned to placebo (hazard ratio, 1.11; 95% CI, 0.95 to 1.30; P=0.18). Significantly more patients in the clonidine group than in the placebo group had clinically important hypotension (2385 patients 47.6% vs. 1854 patients 37.1%; hazard ratio 1.32; 95% CI, 1.24 to 1.40; P<0.001). Clonidine, as compared with placebo, was associated with an increased rate of nonfatal cardiac arrest (0.3% 16 patients vs. 0.1% 5 patients; hazard ratio, 3.20; 95% CI, 1.17 to 8.73; P=0.02).
Administration of low-dose clonidine in patients undergoing noncardiac surgery did not reduce the rate of the composite outcome of death or nonfatal myocardial infarction; it did, however, increase the risk of clinically important hypotension and nonfatal cardiac arrest. (Funded by the Canadian Institutes of Health Research and others; POISE-2 ClinicalTrials.gov number, NCT01082874.).
Abstract
Background
Cardiovascular disease (CVD) is the leading cause of death in patients with chronic obstructive pulmonary disease (COPD) and such patients tend to carry a heavy burden of risk ...factors for CVD. There is little information on the documentation and management of CVD risk factors in COPD patients.
Aim
To audit the recording and management of CVD risk factors in 200 COPD patients attending the respiratory out-patient clinics at two University teaching hospitals.
Design
Retrospective analysis of hospital records.
Results
While there was reasonable recording of a history of CVD risk factors such as hypertension and hyperlipidaemia, the actual recording of risk factor levels was poor-blood pressure and heart rate were recorded in less than half of subjects; lipids, waist circumference, HbA1c and height were essentially not recorded at all.
Conclusions
Best practice guidelines and standard operating procedures for CVD risk factor recording and control require to be developed if the major cause of death in COPD subjects, CVD, is to be addressed. An outline for a standard operating procedure is presented in the Appendix. Serial audits will be required to assess the efficacy of such measures.
Context.
Type Ibn supernovae (SNe Ibn) are a rare class of stripped envelope supernovae interacting with a helium-rich circumstellar medium (CSM). The majority of the SNe Ibn reported in the ...literature display a surprising homogeneity in their fast-evolving lightcurves and are typically found in actively starforming spiral galaxies.
Aims.
We present the discovery and the study of SN 2020bqj (ZTF20aalrqbu), a SN Ibn with a long-duration peak plateau lasting 40 days and hosted by a faint low-mass galaxy. We aim to explain its peculiar properties using an extensive photometric and spectroscopic data set.
Methods.
We compare the photometric and spectral evolution of SN 2020bqj with regular SNe Ibn from the literature, as well as with other outliers in the SN Ibn subclass. We fit the bolometric and multi-band lightcurves with powering mechanism models such as radioactive decay and CSM interaction. We also model the host galaxy of SN 2020bqj.
Results.
The risetime, peak magnitude and spectral features of SN 2020bqj are consistent with those of most SNe Ibn, but the SN is a clear outlier in the subclass based on its bright, long-lasting peak plateau and the low mass of its faint host galaxy. We show through modeling that the lightcurve of SN 2020bqj can be powered predominantly by shock heating from the interaction of the SN ejecta and a dense CSM, combined with radioactive decay. The peculiar Type Ibn SN 2011hw is a close analog to SN 2020bqj in terms of lightcurve and spectral evolution, suggesting a similar progenitor and CSM scenario. In this scenario a very massive progenitor star in the transitional phase between a luminous blue variable and a compact Wolf-Rayet star undergoes core-collapse, embedded in a dense helium-rich CSM with an elevated opacity compared to normal SNe Ibn, due to the presence of residual hydrogen. This scenario is consistent with the observed properties of SN 2020bqj and the modeling results.
Conclusions.
SN 2020bqj is a compelling example of a transitional SN Ibn/IIn based on not only its spectral features, but also its lightcurve, host galaxy properties and the inferred progenitor properties. The strong similarity with SN 2011hw suggests this subclass may be the result of a progenitor in a stellar evolution phase that is distinct from those of progenitors of regular SNe Ibn.
The use of positron emission tomography (PET) in early-phase development of novel drugs targeting the central nervous system, is well established for the evaluation of brain penetration and target ...engagement. However, when novel targets are involved a suitable PET ligand is not always available. We demonstrate an alternative approach that evaluates the attenuation of amphetamine-induced synaptic dopamine release by a novel agonist of the orphan G-protein-coupled receptor GPR139 (TAK-041). GPR139 agonism is a novel candidate mechanism for the treatment of schizophrenia and other disorders associated with social and cognitive dysfunction. Ten healthy volunteers underwent
CPHNO PET at baseline, and twice after receiving an oral dose of d-amphetamine (0.5 mg/kg). One of the post-d-amphetamine scans for each subject was preceded by a single oral dose of TAK-041 (20 mg in five; 40 mg in the other five participants). D-amphetamine induced a significant decrease in
CPHNO binding potential relative to the non-displaceable component (BP
) in all regions examined (16-28%), consistent with increased synaptic dopamine release. Pre-treatment with TAK-041 significantly attenuated the d-amphetamine-induced reduction in BP
in the a priori defined regions (putamen and ventral striatum: 26% and 18%, respectively). The reduction in BP
was generally higher after the 40 mg than the 20 mg TAK-041 dose, with the difference between doses reaching statistical significance in the putamen. Our findings suggest that TAK-041 enters the human brain and interacts with GPR139 to affect endogenous dopamine release.
CPHNO PET is a practical method to detect the effects of novel drugs on the brain dopaminergic system in healthy volunteers, in the early stages of drug development.
Examining the factors that influence contemporary genetic patterns is important given the alarming rate at which natural environments are changing. In particular habitat fragmentation and climate ...change are expected to influence the distribution and diversity of natural populations. In this study we used both mitochondrial control region (mtDNA) and microsatellite data to answer the following questions about genetic diversity and divergence in mountain chickadees (Poecile gambeli) a resident bird species in western North America: (1) Do populations exhibit similar levels of genetic diversity across the range? (2) What is the genetic affinity of western populations in Oregon and Washington? (3) Do genetic patterns exhibit isolation by distance, or are genetic patterns more heavily influenced by habitat discontinuity? We tested the effects of isolation by distance and habitat distribution on genetic structure by analyzing 266 samples from 17 sites across western Canada and the United States. We found a near significant relationship between genetic diversity and latitude, however, our results indicate that overall, latitude is not a strong predictor of genetic diversity. Our analyses of populations in Oregon and Washington revealed a mismatch between patterns detected with mtDNA and microsatellite data. In particular, Washington clustered with the Coast Range/Cascades/Rocky Mountain mtDNA group, but with populations in southern Oregon/California based on microsatellite data. These results suggest the presence of a contact zone in Washington between the two mtDNA clades Coast Range/Cascades/Rocky Mountain and southern Oregon/California clades. Finally, our study revealed a greater effect of isolation by distance than isolation by habitat for both mtDNA and microsatellite data. Overall the isolation by distance signal was greater for mtDNA than microsatellite patterns. The greater signal of isolation by distance on mtDNA patterns likely reflects the strong effects of Pleistocene glaciations in shaping genetic patterns in western North America.
There is mounting evidence that associates brain injury and offending behaviour, and there is a need to understand the epidemiology of head injury in prisoners in order to plan interventions to ...reduce associated disability and risk of reoffending. This is the first study to determine the lifetime prevalence of hospitalised head injury (HHI) in a national population of current prison inmates. In addition characteristics of prisoners with HHI and were compared to prisoners without HHI to discover whether those with HI differed demographically.
Whole life hospital records of everyone aged 35 years or younger and resident in a prison in Scotland on a census date in 2015 were electronically linked via their unique NHS identifier and checked for ICD-9 and 10 codes for head injury. Using a case-control design, these data were compared with a sample from the general population matched 3:1 for age, gender and area-based social deprivation. Comparison of demographic variables was made between prisoners with and without HHI.
HHI was found in 24.7% (1,080/4,374) of prisoners and was significantly more prevalent than found in the matched general population sample (18.2%; 2394/13122; OR 2.10; 95%CI 1.87, 2.16). The prevalence of HHI in prisoners and controls was similar with the exception of a higher risk of HHI in prisoners in lower deprivation quintiles. Having three or more HHI was more common in prisoners (OR 3.04; 95%CI 2.33, 3.97) as were HHI with ICD codes for intracranial injuries (OR 1.81; 95% CI 1.54, 2.11), suggesting that more severe HHI is more prevalent in prisoners than the general population. The distributions within demographic variables and the characteristics of HHI admissions in prisoners with and without a history of HHI were similar.
Prisoners in Scotland aged 35 years or younger have a higher lifetime prevalence of HHI than the general population and are more likely to have had repeated HI or intracranial injuries. Further work is required to elucidate the correspondence between self-report of HI and hospitalised records and to ascertain persisting effects of HI in prisoners and the need for services to reduce associated disability and risk of reoffending.
The properties of supersonic, compressible plasma turbulence determine the behavior of many terrestrial and astrophysical systems. In the interstellar medium and molecular clouds, compressible ...turbulence plays a vital role in star formation and the evolution of our galaxy. Observations of the density and velocity power spectra in the Orion B and Perseus molecular clouds show large deviations from those predicted for incompressible turbulence. Hydrodynamic simulations attribute this to the high Mach number in the interstellar medium (ISM), although the exact details of this dependence are not well understood. Here we investigate experimentally the statistical behavior of boundary-free supersonic turbulence created by the collision of two laser-driven high-velocity turbulent plasma jets. The Mach number dependence of the slopes of the density and velocity power spectra agree with astrophysical observations, and supports the notion that the turbulence transitions from being Kolmogorov-like at low Mach number to being more Burgers-like at higher Mach numbers.
Monitoring of self‐potentials (SPs) in the Chalk of England has shown that a consistent electrical potential gradient exists within a coastal groundwater borehole previously affected by seawater ...intrusion (SI) and that this gradient is absent in boreholes further inland. Furthermore, a small but characteristic reduction in this gradient was observed several days prior to SI occurring. We present results from a combined hydrodynamic and electrodynamic model, which matches the observed phenomena for the first time and sheds light on the source mechanisms for the spatial and temporal distribution of SP. The model predictions are highly sensitive to the relative contribution of electrochemical exclusion and diffusion potentials, the exclusion efficiency, in different rock strata. Geoelectric heterogeneity, largely due to marls and hardgrounds with a relatively high exclusion efficiency, was the key factor in controlling the magnitude of the modeled SP gradient ahead of the saline front and its evolution prior to breakthrough. The model results suggest that, where sufficient geoelectric heterogeneity exists, borehole SP may be used as an early warning mechanism for SI.
Key Points
Existing traditional methods for predicting seawater intrusion in coastal boreholes are inadequate
Recent data suggest that borehole self‐potentials respond to an approaching saline front several days in advance of breakthrough
A numerical model of self‐potentials suggests that the precursor is a response to seawater filling fractures near the base of the borehole
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