Climate change and land‐use change are leading drivers of biodiversity decline, affecting demographic parameters that are important for population persistence. For example, scientists have speculated ...for decades that climate change may skew adult sex ratios in taxa that express temperature‐dependent sex determination (TSD), but limited evidence exists that this phenomenon is occurring in natural settings. For species that are vulnerable to anthropogenic land‐use practices, differential mortality among sexes may also skew sex ratios. We sampled the spotted turtle (Clemmys guttata), a freshwater species with TSD, across a large portion of its geographic range (Florida to Maine), to assess the environmental factors influencing adult sex ratios. We present evidence that suggests recent climate change has potentially skewed the adult sex ratio of spotted turtles, with samples following a pattern of increased proportions of females concomitant with warming trends, but only within the warmer areas sampled. At intermediate temperatures, there was no relationship with climate, while in the cooler areas we found the opposite pattern, with samples becoming more male biased with increasing temperatures. These patterns might be explained in part by variation in relative adaptive capacity via phenotypic plasticity in nest site selection. Our findings also suggest that spotted turtles have a context‐dependent and multi‐scale relationship with land use. We observed a negative relationship between male proportion and the amount of crop cover (within 300 m) when wetlands were less spatially aggregated. However, when wetlands were aggregated, sex ratios remained consistent. This pattern may reflect sex‐specific patterns in movement that render males more vulnerable to mortality from agricultural machinery and other threats. Our findings highlight the complexity of species' responses to both climate change and land use, and emphasize the role that landscape structure can play in shaping wildlife population demographics.
Our findings suggest climate change has skewed the adult spotted turtle sex ratio (species with temperature‐dependent sex determination), with a pattern of increased female‐bias concomitant with warming trends, but only within warmer areas sampled. This pattern might be explained in part by variation in relative adaptive capacity via phenotypic plasticity in nest site selection. We also observed context‐dependent land‐use relationships whereby the effect of crop cover on sex ratio was modulated by wetland configuration. Samples were more female biased when wetlands were less aggregated, suggesting inter‐wetland movements by males may increase vulnerability to machinery and other threats.
To assess the efficacy of health coaching (HC) delivered through videoconferencing (VC) to favorably change physical activity (PA), weight, and metabolic markers in adults with high body mass index ...(BMI).
Thirty adults (BMI ≥30 kg/m
) were randomly assigned to one of three groups: VC, in-person (IP), or control group (CG). Participants received wireless watches and weight scales to sync with their personal smartphones; recorded data were wirelessly uploaded to a secure database. Participants assigned to VC and IP received individualized HC by a multidisciplinary team (registered dietitian, exercise physiologist, and medical doctor) based on data uploaded over the 12-week intervention. Steps/day and weight loss were analyzed through analyses of covariance.
Within- and between-group changes in weight (kg), glucose, insulin, hemoglobin A1c (HbA1c), and Homeostasis Model Assessment estimate of insulin resistance (HOMA-IR) were analyzed through analyses of variance. Weight loss was greater (p < 0.05) for VC (8.23 ± 4.5 kg; 7.7%) than IP (3.2 ± 2.6 kg; 3.4%) and CG (2.9 ± 3.9 kg; 3.3%), respectively. Steps/day were significantly higher in VC than IP at week 4 and VC was significantly higher than the CG at weeks 6, 8, 9, and 11 (p ≤ 0.05). No within- or between-group differences were found for glucose, insulin, or HbA1C. HOMA-IR decreased for VC only (p ≤ 0.05).
Our innovative, multidisciplinary, telemedicine HC delivered through VC led to more favorable changes in weight loss, PA (steps/day), and HOMA-IR than IP or no HC. VC may be an economical approach to improve health and promote behavior change in obese adults.
ClinicalTrials.gov identifier NCT03278951.
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•A library of ester-prodrugs of ethambutol was synthesized.•Selective o-acylation was used to generate derivatives in one step.•Esterified derivatives were deactivated relative to ...ethambutol.•Incubation with a general serine hydrolase restored ethambutol-like activity.
M. tuberculosis contains an unusually high number of serine hydrolases by proteome percentage compared to other common bacteria or humans. This letter describes a method to probe the global substrate specificity of mycobacterial serine hydrolases with ester-protected prodrugs of ethambutol, a first-line antibiotic treatment for TB. These compounds were synthesized directly from ethambutol using a selective o-acylation to yield products in high yield and purity with minimal workup. A library of derivatives was screened against M. smegmatis, a non-infectious model for M. tuberculosis, which displayed significantly lowered biological activity compared to ethambutol. Incubation with a general serine hydrolase reactivated each derivative to near-ethambutol levels, demonstrating that esterification of ethambutol should provide a simple screen for mycobacterial hydrolase activity.
Neurotoxicity or immune effector cell-associated neurotoxicity syndrome (ICANS) is the second most common acute toxicity after chimeric antigen receptor (CAR) T-cell therapy. However, there are ...limited data on the clinical and radiologic correlates of ICANS. We conducted a cohort analysis of 100 consecutive patients with relapsed or refractory large B-cell lymphoma (LBCL) treated with standard of care axicabtagene ciloleucel (axi-cel). ICANS was graded according to an objective grading system. Neuroimaging studies and electroencephalograms (EEGs) were reviewed by an expert neuroradiologist and neurologist. Of 100 patients included in the study, 68 (68%) developed ICANS of any grade and 41 (41%) had grade ≥3. Median time to ICANS onset was 5 days, and median duration was 6 days. ICANS grade ≥3 was associated with high peak ferritin (P= .03) and C-reactive protein (P= .001) levels and a low peak monocyte count (P= .001) within the 30 days after axi-cel infusion. Magnetic resonance imaging was performed in 38 patients with ICANS and revealed 4 imaging patterns with features of encephalitis (n = 7), stroke (n = 3), leptomeningeal disease (n = 2), and posterior reversible encephalopathy syndrome (n = 2). Abnormalities noted on EEG included diffuse slowing (n = 49), epileptiform discharges (n = 6), and nonconvulsive status epilepticus (n = 8). Although reversible, grade ≥3 ICANS was associated with significantly shorter progression-free (P= .02) and overall survival (progression being the most common cause of death;P= .001). Our results suggest that imaging and EEG abnormalities are common in patients with ICANS, and high-grade ICANS is associated with worse outcome after CAR T-cell therapy in LBCL patients.
•Characteristic clinical, electroencephalographic, and radiological features are observed in patients with LBCL who develop ICANS.•Survival outcomes are worse for patients with LBCL who develop high-grade ICANS.
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Abstract
The Lunar Laser Ranging (LLR) retroreflector arrays have been on the Moon for half a century. During that time, the laser range uncertainty has improved by a factor of 100. Consequently, the ...science results have also improved by orders of magnitude. New retroreflectors are scheduled to go to the Moon on Commercial Lander Payload Services missions and the Lunar Geophysical Network mission. The new retroreflectors are single 10 cm corner cube retroreflectors that will not spread the laser pulse during reflection like the existing arrays do. Due to the orbital and Earth rotational speeds, there is a velocity aberration of 0.″8–1.″5 for existing stations. Larger corner cubes require attention to ensure that the spread of possible velocity aberration displacements is optimally contained within the diffraction pattern. The diffraction pattern can be changed by making one or more of the rear dihedral angles slightly different from 90°. Improvements in the equipment at the LLR stations and improvements in the data analysis software are also desirable. Future possibilities are described.
Resveratrol and epigallocatechin-3-gallate (EGCG) are important candidates as chemopreventive agents by virtue of their ability to induce apoptosis in cancer cells. Casein kinase 2 (CK2) is a ...ubiquitous protein ser/thr kinase that plays diverse roles in cell proliferation and apoptosis. We have previously shown that overexpression of CK2 suppresses apoptosis induced by a variety of agents, whereas down-regulation of CK2 sensitizes cells to induction of apoptosis. We therefore investigated whether or not CK2 played a role in resveratrol and EGCG signaling in androgen-sensitive (ALVA-41) and androgen-insensitive (PC-3) prostate cancer cells. Resveratrol- and EGCG-induced apoptosis is associated with a significant down-regulation of CK2 activity and protein expression in both the ALVA-41 and PC-3 cells. Overexpression of CK2alpha protected prostatic cancer cells against resveratrol- and EGCG-induced apoptosis. Relatively low doses (10 mumol/L) of resveratrol and EGCG induced a modest proliferative response in cancer cells that could be switched to cell death by moderate inhibition of CK2. These findings characterize, for the first time, the effects of polyphenolic compounds on CK2 signaling in androgen-sensitive and androgen-insensitive prostatic carcinoma cells and suggest that resveratrol and EGCG may mediate their cellular activity, at least in part, via their targeting of CK2. Further, the data hint at the potential of using these polyphenols alongside CK2 inhibitors in combination chemotherapy.
Over the past year, new 1m×1m neutron detectors have been installed at both the General Purpose SANS (GP-SANS) and the Bio-SANS instruments at HFIR, each intended as an upgrade to provide improved ...high rate capability. This paper presents the results of characterization studies performed in the detector test laboratory, including position resolution, linearity and background, as well as a preliminary look at high count rate performance.
Reduced partial pressure of oxygen impairs exercise performance at altitude. Acute nitrate supplementation, at sea level, may reduce oxygen cost during submaximal exercise in hypobaric hypoxia. ...Therefore, we investigated the metabolic response during exercise at altitude following acute nitrate consumption. Ten well-trained (61.0 ± 7.4 ml/kg/min) males (age 28 ± 7 yr) completed 3 experimental trials (T1, T2, T3). T1 included baseline demographics, a maximal aerobic capacity test (VO2max) and five submaximal intensity cycling determination bouts at an elevation of 1600 m. A 4-day dietary washout, minimizing consumption of nitrate-rich foods, preceded T2 and T3. In a randomized, double-blind, placebo-controlled, crossover fashion, subjects consumed either a nitrate-depleted beetroot juice (PL) or ~12.8 mmol nitrate rich (NR) beverage 2.5 hr before T2 and T3. Exercise at 3500 m (T2 and T3) via hypobaric hypoxia consisted of a 5-min warm-up (25% of normobaric VO2max) and four 5-min cycling bouts (40, 50, 60, 70% of normobaric VO2max) each separated by a 4-min rest period. Cycling RPM and watts for each submaximal bout during T2 and T3 were determined during T1. Preexercise plasma nitrite was elevated following NR consumption compared with PL (1.4 ± 1.2 and 0.7 ± 0.3 uM respectively; p < .05). There was no difference in oxygen consumption (-0.5 ± 1.8, 0.1 ± 1.7, 0.7 ± 2.1, and 1.0 ± 3.0 ml/kg/min) at any intensity (40, 50, 60, 70% of VO2max, respectively) between NR and PL. Further, respiratory exchange ratio, oxygen saturation, heart rate and rating of perceived exertion were not different at any submaximal intensity between NR and PL either. Blood lactate, however, was reduced following NR consumption compared with PL at 40 and 60% of VO2max (p < .0.05). Our findings suggest that acute nitrate supplementation before exercise at 3500 m does not reduce oxygen cost but may reduce blood lactate accumulation at lower intensity workloads.
We describe a theoretical analysis of the structures of self-organizing nanoparticles formed by Pt and Ru−Pt on carbon support. The calculations provide insights into the nature of these metal ...particle systemsones of current interest for use as the electrocatalytic materials of direct oxidation fuel cellsand clarify complex behaviors noted in earlier experimental studies. With clusters deposited via metallo-organic Pt or PtRu5 complexes, previous experiments Nashner et al. J. Am. Chem. Soc. 1997, 119, 7760; Nashner et al. J. Am. Chem. Soc. 1998, 120, 8093; Frenkel et al. J. Phys. Chem. B 2001, 105, 12689 showed that the Pt and Pt−Ru based clusters are formed with fcc(111)-stacked cuboctahedral geometry and essentially bulklike metal−metal bond lengths, even for the smallest (few atom) nanoparticles for which the average coordination number is much smaller than that in the bulk, and that Pt in bimetallic PtRu5 clusters segregates to the ambient surface of the supported nanoparticles. We explain these observations and characterize the cluster structures and bond length distributions using density functional theory calculations with graphite as a model for the support. The present study reveals the origin of the observed metal−metal bond length disorder, distinctively different for each system, and demonstrates the profound consequences that result from the cluster/carbon-support interactions and their key role in the structure and electronic properties of supported metallic nanoparticles.
Burkholderia pseudomallei and mallei are biological agents of military significance. There has been significant research in recent years to develop medical countermeasures for these organisms. This ...review summarizes work which details aspects of the pathogenesis of B. pseudomallei and mallei and discusses key scientific questions and directions for future research.
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