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Background The COVID-19 pandemic is a widespread source of stress with adverse mental health impacts. Meaning in life, both as a trait and as momentary awareness of what is personally meaningful (meaning salience), is associated with positive health outcomes and may buffer against the deleterious effects of stress. Purpose This project examines prospective associations between baseline meaning salience (daily, post-laboratory stressor) and meaning in life with perceived stress during COVID-19. Methods A community sample of healthy adults (n = 147) completed a laboratory stress protocol in 2018–2019, where perceived stress, meaning in life, and meaning salience (daily, post-stressor) were assessed. During April and July 2020 (n = 95, and 97, respectively), participants were re-contacted and reported perceived stress. General linear mixed-effects models accounting for repeated measures of stress during COVID-19 were conducted. Results Partial correlations holding constant baseline perceived stress showed that COVID-19 perceived stress was correlated with daily meaning salience (r = –.28), post-stressor meaning salience (r = –.20), and meaning in life (r = –.22). In mixed-effects models, daily and post-stressor meaning salience and higher meaning in life, respectively, predicted lower perceived stress during COVID-19, controlling for age, gender, and baseline perceived stress. Conclusions Individuals more capable of accessing meaning when exposed to laboratory stress reported lower perceived stress during a global health crisis. Despite study limitations concerning generalizability, results support meaning in life and meaning salience as important aspects of psychological functioning that may promote well-being by affecting stress appraisals and available resources for coping.

U.S.-Mexico border residents experience pervasive social and ecological stressors that contribute to a high burden of chronic disease. However, the border region is primarily composed of high-density Mexican-origin neighborhoods, a characteristic that is most commonly health-promoting. Understanding factors that contribute to border stress and resilience is essential to informing the effective design of community-level health promotion strategies. La Vida en La Frontera is a mixed-methods, participatory study designed to understand factors that may contribute to border resilience in San Luis, Arizona. The study’s initial qualitative phase included interviews with 30 Mexican-origin adults exploring community perceptions of the border environment, cross-border ties, and health-related concepts. Border residents described the border as a Mexican enclave characterized by individuals with a common language and shared cultural values and perspectives. Positive characteristics related to living in proximity to Mexico included close extended family relationships, access to Mexican food and products, and access to more affordable health care and other services. Based on these findings, we co-designed the 9-item Border Resilience Scale that measures agreement with the psychosocial benefits of these border attributes. Pilot data with 60 residents suggest there are positive sociocultural attributes associated with living in border communities. Further research should test if they mitigate environmental stressors and contribute to a health-promoting environment for residents.

Purpose: Polysaccharide krestin (PSK) is a mushroom extract that has been long used in Asia and recently in Western countries as a treatment for cancer due to its presumed immune potentiating effects. Although there have been reports of clinical responses after patients have ingested PSK, the mechanism of action of the agent remains undefined. The current study was undertaken to investigate the mechanism of the antitumor actions of PSK.Experimental Design: The immunostimulatory effect of PSK was first evaluated in vitro using splenocytes from neu transgenic mice and Toll-like receptor (TLR) 2 knockout (TLR2−/−) mice. Then the immunostimualtory and antitumor effect of PSK was determined using tumor-bearing neu transgenic mice, TLR2−/−, and wild-type C57BL/6 mice.Results: We demonstrate that PSK is a selective TLR2 agonist, and the activation of dendritic cells (DC) and T cells by PSK is dependent on TLR2. Oral administration of PSK in neu transgenic mice significantly inhibits breast cancer growth. Selective depletion of specific cell populations suggests that the antitumor effect of PSK is dependent on both CD8+ T cell and NK cells, but not CD4+ T cells. PSK does not inhibit tumor growth in TLR2−/− mice suggesting that the antitumor effect is mediated by TLR2.Conclusion: These results demonstrate that PSK, a natural product commonly used for the treatment of cancer, is a specific TLR2 agonist and has potent antitumor effects via stimulation of both innate and adaptive immune pathways. Clin Cancer Res; 17(1); 67–76. ©2010 AACR.

Supplementary Figures S1-S2.

This study sought to compare the brachial and carotid hemodynamic response to hot water immersion (HWI) between healthy young men and women. Ten women (W) and 11 men (M) (24 ± 4 yr) completed a 60-min HWI session immersed to the level of the sternum in 40°C water. Brachial and carotid artery hemodynamics (Doppler ultrasound) were measured at baseline (seated rest) and every 15 min throughout HWI. Within the brachial artery, total shear rate was elevated to a greater extent in women [+479 (+364, +594) s−1] than in men [+292 (+222, +361) s−1] during HWI ( P = 0.005). As shear rate is inversely proportional to blood vessel diameter and directly proportional to blood flow velocity, the sex difference in brachial shear response to HWI was the result of a smaller brachial diameter among women at baseline ( P < 0.0001) and throughout HWI (main effect of sex, P < 0.0001) and a greater increase in brachial velocity seen in women [+48 (+36, +61) cm/s] compared with men [+35 (+27, +43) cm/s] with HWI ( P = 0.047) which allowed for a similar increase in brachial blood flow between sexes [M: +369 (+287, +451) mL/min, W: +364 (+243, +486) mL/min, P = 0.943]. In contrast, no differences were seen between sexes in carotid total shear rate, flow, velocity, or diameter at baseline or throughout HWI. These data indicate the presence of an artery-specific sex difference in the hemodynamic response to a single bout of HWI.

BACKGROUND The COVID-19 pandemic yielded extraordinary stressors and well-being challenges for physicians. OBJECTIVE We sent light-touch SMS messages to improve well-being in Ontario physicians and sought to determine which types of messages were most effective. METHODS We conducted a randomized longitudinal study with three trial arms for comparison of changes. All residents and practicing physician members of the Ontario Medical Association with available mobile numbers were randomly assigned to a trial arm: messages with well-being resources, stories from fellow Ontario physicians, or combined resources and stories. Baseline and endline data were collected through online surveys primarily using the short Warwick-Edinburgh Mental Wellbeing Scale, with single-item ‘pulse surveys’ delivered via SMS weekly through the intervention. RESULTS 3,356 and 1,230 participants completed the baseline and endline surveys, respectively. Of these, 614 participants also completed the endline survey and were included in our analyses. There were no significant differences in well-being, happiness, anxiety, life satisfaction, or worthwhileness across treatment groups, nor in how helpful participants found the messages. Participants in the resources-only trial arm were more likely (p=0.036) to report reading the messages compared to members in other groups. CONCLUSIONS Texts with stories from peer physicians and referral to well-being resources alone or in combination were not superior to each other in improving physicians’ well-being. Our findings support the notion that interventions focused on individual physicians alone are unlikely to address poor well-being and burnout among physicians. Further research is needed on the use of digital-based interventions in relation to well-being and burnout, particularly as health human resource well-being and sustainability are key to post-pandemic recovery efforts. CLINICALTRIAL ClinicalTrials.gov NCT04803812

Whether coevolution determines distribution patterns of facultative symbionts among individuals of a host species is an open question. We used theDictyostelium discoideum-Paraburkholderiasystem to investigate the role of host fitness and symbiont transmission in co-occurrence patterns of naturally occurring (native) host-symbiont strain pairs.P. bonnieais able to persistently infectD. discoideumin the lab, yet few wildD. discoideumisolates natively host this symbiont. If native host-symbiont combinations lead to higher fitness for host and symbiont compared to nonnative combinations, we assumed a stronger chance that coevolution had led to their co-occurrence. We approached the factors that influence the fitness consequences of host-symbiont interactions in terms of host defense mechanisms and symbiont virulence mechanisms. Given a specific combination of host and symbiont, variable host resistance and symbiont proliferation lead to variation in symbiont density, while variable host tolerance and symbiont benevolence lead to variation in host fitness relative to symbiont density. We used both vegetative and social stages of the host life cycle to approximate interactions betweenD. discoideumandP. bonniea, when hosts form social groups and symbiont horizontal transmission is facilitated by these social groups. We found no difference in host defense mechanisms between native and nonnative hosts ofP. bonniea, butP. bonnieapossesses variable phenotypes in proliferation and benevolence. More importantly, variation in symbiont benevolence led to increased horizontal transmission of benevolent strains compared to malevolent strains during the social stage of the host life cycle.ImportanceHosts and symbionts in a facultative symbiosis do not depend on each other for survival. Perhaps due to this labile relationship, we lack a solid understanding of why only some individual hosts carry facultative symbionts rather than all. We used the social amoebaDictyostelium discoideumand its bacterial symbiontParaburkholderia bonnieato test whether naturally occurring (native) host-symbiont strain pairs are the result of coevolution. We find that native combinations of hosts and symbionts do not enjoy improved fitness compared to nonnative combinations. Instead, both host and symbiont fitness depend on symbiont identity, asP. bonnieastrains varied in their ability to proliferate within groups of hosts and in the degree of fitness loss they caused given a similar infection prevalence. More importantly, variation in the latter property, known as benevolence, led to increased horizontal transmission of benevolent strains compared to malevolent strains during the social stage of the host life cycle.

Aerobic exercise induces mast cell degranulation and increases histamine formation by histidine decarboxylase, resulting in an ∼150% increase in intramuscular histamine. The purpose of this study was to determine if the increase in skeletal muscle temperature associated with exercise is sufficient to explain this histamine response. Specifically, we hypothesized that local passive heating that mimics the magnitude and time course of changes in skeletal muscle temperature observed during exercise would result in increased intramuscular histamine concentrations comparable to exercising values. Seven subjects participated in the main study in which pulsed short-wave diathermy was used to passively raise the temperature of the vastus lateralis over 60 min. Heating increased intramuscular temperature from 32.6°C [95% confidence interval (CI) 32.0°C to 33.2°C] to 38.9°C (38.7°C to 39.2°C) (P < 0.05) and increased intramuscular histamine concentration from 2.14 ng/mL (1.92 to 2.36 ng/mL) to 2.97 ng/mL (2.57 to 3.36 ng/mL) (P < 0.05), an increase of 41%. In a follow-up in vitro experiment using human-derived cultured mast cells, heating to comparable temperatures did not activate mast cell degranulation. Therefore, it appears that exercise-associated changes in skeletal muscle temperature are sufficient to generate elevations in intramuscular histamine concentration. However, this thermal effect is most likely due to changes in de novo histamine formation via histidine decarboxylase and not due to degranulation of mast cells. In conclusion, physiologically relevant increases in skeletal muscle temperature explain part, but not all, of the histamine response to aerobic exercise. This thermal effect may be important in generating positive adaptations to exercise training. NEW & NOTEWORTHY The “exercise signal” that triggers histamine release within active skeletal muscle during aerobic exercise is unknown. By mimicking the magnitude and time course of increasing skeletal muscle temperature observed during aerobic exercise, we demonstrate that part of the exercise-induced rise in histamine is explained by a thermal effect, with in vitro experiments suggesting this is most likely via de novo histamine formation. This thermal effect may be important in generating positive adaptations to exercise training.

Osteopenia and osteoporosis have increasingly become a recognized morbidity in those persons with hemophilia (PwH) receiving inadequate prophylactic clotting factor replacement. Animal models can control or eliminate genetic and environmental factors and allow for invasive testing not clinically permissible. Here, we describe the skeletal phenotype of juvenile and adult male mice with a genetically engineered deficiency in coagulation factor IX (FIX KO). Although the somatic growth of FIX KO mice matched that of their wild-type (WT) littermates at 10 and 20 weeks of age, the FIX KO mice displayed reduced bone mineral density (BMD), reduced cortical and cancellous bone mass, and diminished whole bone fracture resistance. These findings coupled with parallel observations in a murine model of hemophilia A (FVIII deficiency) point to an effector downstream of the coagulation cascade that is necessary for normal skeletal development. Further study of potential mechanisms underlying the bone disease observed in rare clotting factor deficiency syndromes may lead to new diagnostic and therapeutic insights for metabolic bone diseases in general.

This study sought to compare the hemodynamics of the recovery periods following exercise versus hot water immersion. Twelve subjects (6 women, 22.7 ± 0.8 yr; body mass index: 21.8 ± 2.1 kg/m(2)) exercised for 60 min at 60% V̇o(2) peak or were immersed in 40.5°C water for 60 min on separate days, in random order. Measurements were made before, during, and for 60-min postintervention (i.e., recovery) and included heart rate, arterial pressure, core temperature, and subjective measures. Brachial and superficial femoral artery blood flows were assessed using Doppler ultrasonography and cardiac output was measured using the acetylene wash-in method. Internal temperature increased to a similar extent during exercise and hot water immersion. Cardiac output and mean arterial pressure were greater during exercise than during hot water immersion (both P < 0.01). Sustained reductions in mean arterial pressure compared with baseline were observed under both conditions during recovery (P < 0.001 vs. before each intervention). Cardiac output was similar during recovery between the interventions. Stroke volume was reduced throughout recovery following exercise, but not following hot water immersion (P < 0.01). Brachial artery retrograde shear was reduced following hot water immersion, but not following exercise (interaction; P = 0.035). Antegrade shear in the superficial femoral artery was elevated compared with baseline (P = 0.027) for 60 min following exercise, whereas it returned near baseline values (P = 0.564) by 40 min following hot water immersion. Many of the changes observed during the postexercise recovery period that are thought to contribute to long-term beneficial cardiovascular adaptations were also observed during the post hot water immersion recovery period. NEW & NOTEWORTHY Hot water immersion resulted in a postintervention hypotension similar to that observed following exercise matched for time and core temperature rise, but with greater reductions in brachial retrograde shear. Heating was associated with lower heart rate, cardiac output, and mean arterial pressure than exercise. Thus, acute hot water immersion may provide similar or greater vascular changes during the hour following the intervention compared with acute exercise, but with a less taxing cardiac workload during the intervention.

Critical power (CP) delineates the heavy and severe exercise intensity domains, and sustained work rates above CP result in an inexorable progression of oxygen uptake to a maximal value and, subsequently, the limit of exercise tolerance. The finite work capacity above CP, W′, is defined by the curvature constant of the power-duration relationship. Heavy or severe exercise in a hot environment generates additional challenges related to the rise in body core temperature (T(c)) that may impact CP and W′. The purpose of this study was to determine the effect of elevated T(c) on CP and W′. CP and W′ were estimated by end-test power (EP; mean of final 30 s) and work above end-test power (WEP), respectively, from 3-min “all-out” tests performed on a cycle ergometer. Volunteers (n = 8, 4 female) performed the 3-min tests during a familiarization visit and two experimental visits (thermoneutral vs. hot, randomized crossover design). Before experimental 3-min tests, the subjects were immersed in water (thermoneutral: 36°C for 30 min; hot: 40.5°C until T(c) was ≥38.5°C). Mean T(c) was significantly greater in the hot condition than in the thermoneutral condition (38.5 ± 0.0°C vs. 37.4 ± 0.2°C; means ± SD, P < 0.01). All 3-min tests were performed in an environmental chamber [thermoneutral: 18°C, 45% relative humidity (RH); hot: 38 °C, 40% RH]. EP was similar between thermoneutral (239 ± 57 W) and hot (234 ± 66 W; P = 0.55) conditions. WEP was similar between thermoneutral (10.9 ± 3.0 kJ) and hot conditions (9.3 ± 3.6; P = 0.19). These results suggest that elevated T(c) has no significant impact on EP or WEP. NEW & NOTEWORTHY The parameters of the power-duration relationship (critical power and W′) estimated by a 3-min all-out test were not altered by elevated body core temperature as compared with a thermoneutral condition.

The physical presence of roots and the compounds they release affect the cohesion between roots and their environment. However, the plant traits that are important for these interactions are unknown and most methods that quantify the contributions of these traits are time-intensive and require specialist equipment and complex substrates. Our lab developed an inexpensive, high-throughput phenotyping assay that quantifies root-substrate adhesion in Arabidopsis thaliana. We now report that this method has high sensitivity and versatility for identifying different types of traits affecting root-substrate adhesion including root hair morphology, vesicle trafficking pathways, and root exudate composition. We describe a practical protocol for conducting this assay and introduce its use in a forward genetic screen to identify novel genes affecting root-substrate interactions. This assay is a powerful tool for identifying and quantifying genetic contributions to cohesion between roots and their environment.

The physical presence of roots and the compounds they release affect the cohesion between roots and their environment. However, the plant traits that are important for these interactions are unknown and most methods that quantify the contributions of these traits are time-intensive and require specialist equipment and complex substrates. Our lab developed an inexpensive, high-throughput phenotyping assay that quantifies root-substrate adhesion in Arabidopsis thaliana. We now report that this method has high sensitivity and versatility for identifying different types of traits affecting root-substrate adhesion including root hair morphology, vesicle trafficking pathways, and root exudate composition. We describe a practical protocol for conducting this assay and introduce its use in a forward genetic screen to identify novel genes affecting root-substrate interactions. This assay is a powerful tool for identifying and quantifying genetic contributions to cohesion between roots and their environment.

Vesicle exocytosis underpins signaling and development in plants and is vital for cell expansion. Vesicle tethering and fusion are thought to occur sequentially, with tethering mediated by the exocyst and fusion driven by assembly of soluble NSF attachment protein receptor (SNARE) proteins from the vesicle membrane (R-SNAREs or vesicle-associated membrane proteins [VAMPs]) and the target membrane (Q-SNAREs). Interactions between exocyst and SNARE protein complexes are known, but their functional consequences remain largely unexplored. We now identify a hierarchy of interactions leading to secretion in Arabidopsis (Arabidopsis thaliana). Mating-based split-ubiquitin screens and in vivo Förster resonance energy transfer analyses showed that exocyst EXO70 subunits bind preferentially to cognate plasma membrane SNAREs, notably SYP121 and VAMP721. The exo70A1 mutant affected SNARE distribution and suppressed vesicle traffic similarly to the dominant-negative truncated protein SYP121(ΔC), which blocks secretion at the plasma membrane. These phenotypes are consistent with the epistasis of exo70A1 in the exo70A1 syp121 double mutant, which shows decreased growth similar to exo70A1 single mutants. However, the exo70A1 vamp721 mutant showed a strong, synergy, suppressing growth and cell expansion beyond the phenotypic sum of the two single mutants. These data are best explained by a hierarchy of SNARE recruitment to the exocyst at the plasma membrane, dominated by the R-SNARE and plausibly with the VAMP721 longin domain as a nexus for binding.

The physical presence of roots and the compounds they release affect the cohesion between roots and their environment. However, the plant traits that are important for these interactions are unknown and most methods that quantify the contributions of these traits are time-intensive and require specialist equipment and complex substrates. Our lab developed an inexpensive, high-throughput phenotyping assay that quantifies root-substrate adhesion inArabidopsis thaliana. We now report that this method has high sensitivity and versatility for identifying different types of traits affecting root-substrate adhesion including root hair morphology, vesicle trafficking pathways and root exudate composition. We describe a practical protocol for conducting this assay and introduce its use in a forward genetic screen to identify novel genes affecting root-substrate interactions. This assay is a powerful tool for identifying and quantifying genetic contributions to cohesion between roots and their environment.

Histamine is released within skeletal muscle during exercise. In humans, antihistamines have no effect on speed, power output, or time-to-completion of short-duration high-intensity exercise. In mice, blocking histamine’s actions decreases speed and duration of endurance tasks. It is unknown if these opposing outcomes are the result of differences in histamine’s actions between species or are related to duration and/or intensity of exercise, as blocking histamine during endurance exercise has not been examined in humans. PURPOSE: Determine the effects of histamine-receptor antagonism on cycling time-trial performance in humans, with and without a preceding bout of sustained steady-state exercise. METHODS: Eleven (3F) competitive cyclists performed six 10-km time-trials on separate days. The first two time-trials served as familiarization. The next four time-trials were performed in randomized-block order, where two were preceded by 120 min of seated rest (Rest) and two by 120 min of cycling exercise (Exercise) at 50% VO(2peak). Within each block, subjects consumed either combined histamine H(1) and H(2) receptor antagonists (Blockade) or Placebo, prior to the start of the 120-min Rest/Exercise. RESULTS: Blockade had no discernible effects on hemodynamic or metabolic variables during Rest or Exercise. However, Blockade increased time-to-completion of the 10-km time-trial compared to Placebo (+10.5 ± 3.7 s, P < 0.05). Slowing from Placebo to Blockade was not different between Rest (+8.7 ± 5.2 s) and Exercise (+12.3 ± 5.8 s, P = 0.716). CONCLUSION: Exercise-related histaminergic signaling appears inherent to endurance exercise and may play a role in facilitating optimal function during high-intensity endurance exercise.

Soil is essential for sustaining life on land. Plant roots play a crucial role in stabilising soil and minimising erosion, although these mechanisms are still not completely understood. Consequently, identifying and breeding for plant traits to enhance erosion resistance is challenging. Root hair mutants in Arabidopsis thaliana were studied using three different quantitative methods to isolate their effect on root-soil cohesion. We present compelling evidence that micro-scale interactions of root hairs with surrounding soil increase soil cohesion and reduce erosion. Arabidopsis seedlings with root hairs were more difficult to detach from soil, compost and sterile gel media than those with hairless roots, and it was 10-times harder to erode soil from roots with than without hairs. We also developed a model that can consistently predict the impact root hairs make to soil erosion resistance. Our study thus provides new insight into the mechanisms by which roots maintain soil stability., Sarah De Baets et al. investigate the effect of root hair abundance on root-substrate cohesion and experimental soil erosion in Arabidopsis. They find that plants with root hairs are more difficult to detach from soil and are better able to prevent soil erosion than root hairless plants and present a model to predict the impact of root hairs on soil erosion resistance.

Releases of Perfluoroalkyl and Polyfluoroalkyl Substances (PFASs) associated with Aqueous Film Forming Foams (AFFFs) have the potential to impact on-site and downgradient aquatic habitats. Dietary exposures of aquatic-dependent birds were modeled for seven PFASs (PFHxA, PFOA, PFNA, PFDA, PFHxS, PFOS, and PFDS) using five different scenarios based on measurements of PFASs obtained from five investigations of sites historically-impacted by AFFF. Exposure modeling was conducted for four avian receptors representing various avian feeding guilds: lesser scaup (Aythya affinis), spotted sandpiper (Actitis macularia), great blue heron (Ardea herodias), and osprey (Pandion haliaetus). For the receptor predicted to receive the highest PFAS exposure (spotted sandpiper), model-predicted exposure to PFOS exceeded a laboratory-based, No Observed Adverse Effect Level exposure benchmark in three of the five model scenarios, confirming that risks to aquatic-dependent avian wildlife should be considered for investigations of historic AFFF releases. Perfluoroalkyl sulfonic acids (PFHxS, PFOS, and PFDS) represented 94% (on average) of total PFAS exposures due to their prevalence in historical AFFF formulations, and increased bioaccumulation in aquatic prey items and partitioning to aquatic sediment relative to perfluoroalkyl carboxylic acids. Sediment-associated PFASs (rather than water-associated PFASs) were the source of the highest predicted PFAS exposures, and are likely to be very important for understanding and managing AFFF site-specific ecological risks. Additional considerations for research needs and site-specific ecological risk assessments are discussed with the goal of optimizing ecological risk-based decision making at AFFF sites and prioritizing research needs.

To reach the female gametophyte, growing pollen tubes must penetrate different tissues within the pistil, the female reproductive organ of a flower. Past research has identified various chemotropic cues that guide pollen tubes through the transmitting tract of the pistil, which represents the longest segment of its growth path. In addition, physical mechanisms also play a role in pollen tube guidance; however, these processes remain poorly understood. Here we show that pollen tubes from plants with solid transmitting tracts actively respond to the stiffness of the environment. We found that pollen tubes from Nicotiana tabacum and other plant species with a solid or semisolid transmitting tract increase their growth rate in response to an increasing matrix stiffness. By contrast, pollen tubes from Lilium longiflorum and other plant species with a hollow transmitting tract decrease their growth rate with increasing matrix stiffness, even though the forces needed to maintain a constant growth rate remain far below the maximum penetration force these pollen tubes are able to generate. Moreover, when confronted with a transition from a softer to a stiffer matrix, pollen tubes from N. tabacum display a greater ability to penetrate into a stiffer matrix compared with pollen tubes from L. longiflorum, even though the maximum force generated by pollen tubes from N. tabacum (11 µN) is smaller than the maximum force generated by pollen tubes from L. longiflorum (36 µN). These findings demonstrate a mechano-sensitive growth behavior, termed here durotropic growth, that is only expressed in pollen tubes from plants with a solid or semisolid transmitting tract and thus may contribute to an effective pollen tube guidance within the pistil.

Polycystic ovary syndrome (PCOS) affects up to 15% of women and is associated with increased risk of obesity and cardiovascular disease. Repeated passive heat exposure [termed “heat therapy” (HT)] is a lifestyle intervention with the potential to reduce cardiovascular risk in obesity and PCOS. Women with obesity ( n = 18) with PCOS [age 27 ± 4 yr, body mass index (BMI) 41.3 ± 4.7 kg/m2] were matched for age and BMI, then assigned to HT ( n = 9) or time control (CON; n = 9). HT subjects underwent 30 one-hour hot tub sessions over 8–10 wk, whereas CON subjects did not undergo HT. Muscle sympathetic nerve activity (MSNA), blood pressure, cholesterol, C-reactive protein, and markers of vascular function were assessed at the start (Pre) and end (Post) of 8–10 wk. These measures included carotid and femoral artery wall thickness and flow-mediated dilation (FMD), measured both before and after 20 min of ischemia-20 min of reperfusion (I/R) stress. HT subjects exhibited reduced MSNA burst frequency (Pre: 20 ± 8 bursts/min, Post: 13 ± 5 bursts/min, P = 0.012), systolic (Pre: 124 ± 5 mmHg, Post: 114 ± 6 mmHg; P < 0.001) and diastolic blood pressure (Pre: 77 ± 6 mmHg, Post: 68 ± 3 mmHg; P < 0.001), C-reactive protein (Pre: 19.4 ± 13.7 nmol/L, Post: 15.2 ± 12.3 nmol/L; P = 0.018), total cholesterol (Pre: 5.4 ± 1.1 mmol/L, Post: 5.0 ± 0.8 mmol/L; P = 0.028), carotid wall thickness (Pre: 0.054 ± 0.005 cm, Post: 0.044 ± 0.005 cm; P = 0.010), and femoral wall thickness (Pre: 0.056 ± 0.009 cm, Post: 0.042 ± 0.005 cm; P = 0.003). FMD significantly improved in HT subjects over time following I/R (Pre: 5.6 ± 2.5%, Post: 9.5 ± 1.7%; P < 0.001). No parameters changed over time in CON, and BMI did not change in either group. These findings indicate that HT reduces sympathetic nerve activity, provides protection from I/R stress, and substantially improves cardiovascular risk profiles in women who are obese with PCOS.

Targeted protein degradation is an important and pervasive regulatory mechanism in plants, required for perception and response to the environment as well as developmental signaling. Despite the significance of this process, relatively few studies have assessed plant protein turnover in a quantitative fashion. Tandem fluorescent protein timers (tFTs) offer a powerful approach for the assessment of in vivo protein turnover in distinct subcellular compartments of single or multiple cells. A tFT is a fusion of two different fluorescent proteins with distinct fluorophore maturation kinetics, which enable protein age to be estimated from the ratio of fluorescence intensities of the two fluorescent proteins. Here, we used short-lived auxin signaling proteins and model N-end rule (N-recognin) pathway reporters to demonstrate the utility of tFTs for studying protein turnover in living plant cells of Arabidopsis (Arabidopsis thaliana) and Nicotiana benthamiana. We present transient expression of tFTs as an efficient screen for relative protein lifetime, useful for testing the effects of mutations and different genetic backgrounds on protein stability. This work demonstrates the potential for using stably expressed tFTs to study native protein dynamics with high temporal resolution in response to exogenous or endogenous stimuli.

IntroductionPrevious studies observed diurnal variation in hemodynamic responses during recovery from whole-body exercise, with vasodilation appearing greater after evening versus morning sessions. It is unclear what mechanism(s) underlie this response. Since small muscle-mass exercise can isolate peripheral effects related to postexercise vasodilation, it may provide insight into possible mechanisms behind this diurnal variation.MethodsThe study was conducted in ten healthy (5F, 5M) young individuals, following single-leg dynamic knee-extension exercise performed in the Morning (7:30–11:30 am) or the Evening (5–9 pm) on two different days, in random order. Arterial pressure (automated auscultation) and leg blood flow (femoral artery Doppler ultrasound) were measured pre-exercise and during 120 min postexercise. Net effect for each session was calculated as percent change in blood flow (or vascular conductance) between the Active Leg and the Inactive Leg.ResultsFollowing Morning exercise, blood flow was 34.9 ± 8.9% higher in the Active Leg versus the Inactive Leg (p < 0.05) across recovery. Following Evening exercise, blood flow was 35.0 ± 8.8% higher in the Active Leg versus the Inactive Leg (p < 0.05). Likewise, vascular conductance was higher in the Active Leg versus the Inactive Leg (Morning: +35.1 ± 9.0%, p < 0.05; Evening: +33.2 ± 8.2%, p < 0.05). Morning and Evening blood flow (p = 0.66) and vascular conductance (p = 0.64) did not differ.ConclusionThese data suggest previous studies which identified diurnal variations in postexercise vasodilation responses are likely reflecting central rather than peripheral modulation of cardiovascular responses.

Efforts to understand the genetic and environmental conditioning of plant morphology are hindered by the lack of flexible and effective tools for quantifying morphology. Here, we demonstrate that persistent-homology-based topological methods can improve measurement of variation in leaf shape, serrations, and root architecture. We apply these methods to 2D images of leaves and root systems in field-grown plants of a domesticated introgression line population of tomato (