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The sarcomere is the functional unit of cardiac muscle, essential for normal heart function. To date, it has not been possible to study, in real time, thin filament-based activation dynamics in live cardiac muscle. We report here results from a cardiac troponin C (TnC) FRET-based biosensor integrated into the cardiac sarcomere via stoichiometric replacement of endogenous TnC. The TnC biosensor provides, for the first time, evidence of multiple thin filament activating ligands, including troponin I interfacing with TnC and cycling myosin, during a cardiac twitch. Results show that the TnC FRET biosensor transient significantly precedes that of peak twitch force. Using small molecules and genetic modifiers known to alter sarcomere activation, independently of the intracellular Ca(2+) transient, the data show that the TnC biosensor detects significant effects of the troponin I switch domain as a sarcomere-activating ligand. Interestingly, the TnC biosensor also detected the effects of load-dependent altered myosin cycling, as shown by a significant delay in TnC biosensor transient inactivation during the isometric twitch. In addition, the TnC biosensor detected the effects of myosin as an activating ligand during the twitch by using a small molecule that directly alters cross-bridge cycling, independently of the intracellular Ca(2+) transient. Collectively, these results aid in illuminating the basis of cardiac muscle contractile activation with implications for gene, protein, and small molecule-based strategies designed to target the sarcomere in regulating beat-to-beat heart performance in health and disease.

Women continue to be underrepresented in STEM (science, technology, engineering, math) fields. As such, there has been an increased interest in interventions to reduce bias against, and increase inclusion of, women in STEM. In this paper, we compare and contrast two commonly used strategies: awareness and blindness. We demonstrate that gender-blindness—a diversity ideology that advocates for downplaying gender differences, rather than embracing them—has the potential to diminish stereotyping of women in STEM fields. In six total studies, we show that men who believe, or are primed with, gender-blindness (compared to gender-awareness) are less likely to endorse gender stereotypes around women's STEM competencies. By measuring (Study 1) and manipulating ( Studies 2 –5) gender-blindness, we show that gender-blindness (compared to awareness) minimizes the gender gap on explicit stereotyping measures, as well as diminishes STEM stereotyping in target evaluations. Across six studies, we show the influence of diversity ideologies on stereotyping of women in STEM.

Nicotinic acetylcholine receptors (nAChR) are present in many excitable tissues and are found both pre and post-synaptically. Through their non-specific cationic permeability, these nAChRs have excitatory roles in neurotransmission, neuromodulation, synaptic plasticity, and neuroprotection. Thus, nAChR mislocalization or functional deficits are associated with many neurological disease states. Therefore identifying the mechanisms that regulate nAChR expression and function will inform our understanding of normal as well as pathological physiological conditions and offer avenues for potential therapeutic advances. Taking advantage of the genetic tractability of the soil nematode Caenorhabditis elegans, a forward genetic screen was performed to isolate regulators of the vertebrate α7 nAChR homologue ACR-16. From this screen a novel regulator of the ACR-16 receptor was identified, the sarco(endo)plasmic reticulum calcium ATPase sca-1. The sca-1 mutant affects ACR-16 receptor level at the NMJ, receptor functionality, and synaptic transmission. Responses to pressure-ejected nicotine in sca-1 mutants are indistinguishable from wild type, which implies the ACR-16 receptors are mislocalized at the NMJ. Changes in cytosolic baseline calcium levels in sca-1 and other mutants indicates a calcium-driven regulation mechanism of the α7-like NAChR ACR-16.

Despite a substantial amount of animal data linking deficits in memory inhibition to the development of overeating and obesity, few studies have investigated the relevance of memory inhibition to uncontrolled eating in humans. Further, although memory for recent eating has been implicated as an important contributor to satiety and energy intake, the possibility that variations in episodic memory relate to individual differences in food intake control has been largely neglected. To examine these relationships, we recruited ninety-three adult subjects to attend a single lab session where we assessed body composition, dietary intake, memory performance, and eating behaviors (Three Factor Eating Questionnaire). Episodic recall and memory inhibition were assessed using a well-established measure of memory interference (Retrieval Practice Paradigm). Hierarchical regression analyses indicated that memory inhibition was largely unrelated to participants' eating behaviors; however, episodic recall was reliably predicted by restrained vs. uncontrolled eating: recall was positively associated with strategic dieting (β = 2.45, p = 0.02), avoidance of fatty foods (β = 3.41, p = 0.004), and cognitive restraint (β = 1.55, p = 0.04). In contrast, recall was negatively associated with uncontrolled eating (β = −1.15, p = 0.03) and emotional eating (β = −2.46, p = 0.04). These findings suggest that episodic memory processing is related to uncontrolled eating in humans. The possibility that deficits in episodic memory may contribute to uncontrolled eating by disrupting memory for recent eating is discussed.

Ascribing and denying humanity has profound consequences, often leading to devastating outcomes (e.g., violence, genocide). As such, understanding what, exactly, makes “someone human” becomes imperative. In this paper, we leverage the ubiquitous Big Two dimensions of social perception (agency and communality) to examine the process of humanization. In five studies (N = 1900), we find that the “Big Two” dimensions—agency (assertiveness, competence) and communality (warmth, kindness)—predict humanization, and critically, we show the primacy of communality in this process. We find that communality takes primacy in humanization when anthropomorphizing, describing an alien species, or ascribing humanness to real-world social targets (Studies 1–3); it is only for contexts where, or targets for whom, agency is particularly relevant that agency predicts humanization (Studies 4–5). We conclude with implications for research on (de)humanization, mind-perception, and social-perception.

The ways in which we discuss gender (embracing vs. downplaying difference) has implications for women’s workplace confidence and behavior, especially in male-dominated environments and positions of power. In five total studies (N = 1453), across a variety of samples, we found that gender-blindness—the belief that gender differences should be downplayed—is a more adaptive strategy for increasing female workplace confidence than gender-awareness—the belief that gender differences should be celebrated. In addition to increasing confidence, gender-blindness was related to actions necessary for reducing gender disparities (e.g., risk-taking, negotiation). We found that perceived gender differences in agency (i.e., assertiveness, independence) accounts for gender differences in workplace confidence, especially in male-dominated environments (e.g., business school) and positions of power (managerial positions). Finally, we found that gender-blindness either lessened or had no effect on men’s confidence, demonstrating the unique positive effect of gender-blindness on women’s confidence. Together, this research highlights the potential for downplaying differences, instead of emphasizing them, to combat the confidence gap.

Crotalidae envenomation has been managed successfully in emergency departments across the world with antivenom. Over the years, antivenom has evolved and newer agents have been studied with the possibility of eliminating maintenance antivenom therapy. Here we report a patient who had worsening platelet and fibrinogen concentrations, as well as complaints of swelling and pain at the site of a rattlesnake envenomation following an initial dose of F(ab')2AV (Crotalidae immune F(ab')2 (equine) [ANAVIP®]) Crotalidae antivenom. The patient was subsequently transferred to a tertiary children's hospital for a higher level of care and received FabAV (Crotalidae polyvalent immune Fab (ovine) [CroFab®]) Crotalidae antivenom. The details of this patient's treatment course highlight the possibility that patients who receive F(ab')2AV, may require additional antivenom treatment. Furthermore, it appears that based on our single patient experience, giving FabAV after F(ab')2AV is safe and effective.

There is a lack of knowledge regarding in-vehicle concentrations of nitrogen dioxide (NO2) during transit through road tunnels in urban environments. Furthermore, previous studies have tended to involve a single vehicle and the range of in-vehicle NO2 concentrations that vehicle occupants may be exposed to is not well defined. This study describes simultaneous measurements of in-vehicle and outside-vehicle NO2 concentrations on a route through Sydney, Australia that included several major tunnels, minor tunnels and busy surface roads. Tests were conducted on nine passenger vehicles to assess how vehicle characteristics and ventilation settings affected in-vehicle NO2 concentrations and the in-vehicle-to-outside vehicle (I/O) concentration ratio. NO2 was measured directly using a cavity attenuated phase shift (CAPS) technique that gave a high temporal and spatial resolution. In the major tunnels, transit-average in-vehicle NO2 concentrations were lower than outside-vehicle concentrations for all vehicles with cabin air recirculation either on or off. However, markedly lower I/O ratios were obtained with recirculation on (0.08–0.36), suggesting that vehicle occupants can significantly lower their exposure to NO2 in tunnels by switching recirculation on. The highest mean I/O ratios for NO2 were measured in older vehicles (0.35–0.36), which is attributed to older vehicles having higher air exchange rates. The results from this study can be used to inform the design and operation of future road tunnels and modelling of personal exposure to NO2.

We explored medication use by children born preterm at 5-8 years of age. Compared with children born at full term, children born preterm had higher medication use that included most therapeutic classifications. Although asthma and chronic lung disease influenced use, prematurity remained an independent risk factor.

In western and westernized societies, large portions of the population live in what are considered to be “obesogenic” environments. Among other things, obesogenic environments are characterized by a high prevalence of external cues that are associated with highly palatable, energy-dense foods. One prominent hypothesis suggests that these external cues become such powerful conditioned elicitors of appetitive and eating behavior that they overwhelm the internal, physiological mechanisms that serve to maintain energy balance. The present research investigated a learning mechanism that may underlie this loss of internal relative to external control. In Experiment 1, rats were provided with both auditory cues (external stimuli) and varying levels of food deprivation (internal stimuli) that they could use to solve a simple discrimination task. Despite having access to clearly discriminable external cues, we found that the deprivation cues gained substantial discriminative control over conditioned responding. Experiment 2 found that, compared to standard chow, maintenance on a “western-style” diet high in saturated fat and sugar weakened discriminative control by food deprivation cues, but did not impair learning when external cues were also trained as relevant discriminative signals for sucrose. Thus, eating a western-style diet contributed to a loss of internal control over appetitive behavior relative to external cues. We discuss how this relative loss of control by food deprivation signals may result from interference with hippocampal-dependent learning and memory processes, forming the basis of a vicious-cycle of excessive intake, body weight gain, and progressive cognitive decline that may begin very early in life.

Driving in fog is a potentially dangerous activity that has been investigated in a number of different ways; however, most have focused on identifying the underlying perceptual changes that result in an inability to perceive speed of vehicle motion. Although the previous research has identified the perceptual changes associated with driving in fog and shows that people are highly likely to perceive their speed to be higher than it actually is, these research studies have not investigated driving behavior when drivers are allowed to maintain speed as they feel appropriate and make use of the vehicle's speedometer. In addition, much of the existing research focuses on speed perception and presents a limited view of other driving performance metrics in terms of lane keeping and event detection. The current study addresses these issues utilizing a driving simulator-based method where fog is simulated as a distance dependent contrast reduction while having participants drive at speeds they feel are appropriate. A number of different instructions and speed feedback mechanisms were tested in order to determine how drivers react when driving in varying levels of fog. Results also include lane keeping measures in order to assess whether drivers are willing to drive at speeds where their lane keeping performance is degraded due to the reduced visibility. Results indicate that, in general, drivers do not tend to slow down significantly until visibility distance is drastically reduced by fog; however, lane keeping ability is maintained throughout most of the range of visibility distances. Lane keeping ability was reduced only when fog results in visibility distances

Previous studies show that high-intensity sweeteners can stimulate weight gain in rats. The present studies examined whether caffeine, a stimulant commonly added to beverages consumed by humans, influences intake of saccharin- or glucose-sweetened solutions or body weight gain in rats and whether the nature of the maintenance diet influences the effects of caffeine. In two experiments, rats received glucose or saccharin solution mixed with 0.125 mg/g caffeine or no caffeine. Rats consumed significantly more caffeinated than noncaffeinated solutions when they were maintained on a low-fat chow diet (Experiment 1) and when maintained on a sweet, high-fat, high calorie chow diet (Experiment 2). Consumption of saccharin resulted in higher body weight gain in both experiments. Caffeine reversed this effect in Experiment 1 (low-fat diet) but not Experiment 2 (sweet, high-fat diet). The findings extend what is known about the conditions under which consumption of high intensity sweeteners promote energy dysregulation.

Recent epidemiological evidence points to a link between a variety of negative health outcomes (e.g. metabolic syndrome, diabetes and cardiovascular disease) and the consumption of both calorically sweetened beverages and beverages sweetened with high-intensity, non-caloric sweeteners. Research on the possibility that non-nutritive sweeteners promote food intake, body weight gain, and metabolic disorders has been hindered by the lack of a physiologically-relevant model that describes the mechanistic basis for these outcomes. We have suggested that based on Pavlovian conditioning principles, consumption of non-nutritive sweeteners could result in sweet tastes no longer serving as consistent predictors of nutritive postingestive consequences. This dissociation between the sweet taste cues and the caloric consequences could lead to a decrease in the ability of sweet tastes to evoke physiological responses that serve to regulate energy balance. Using a rodent model, we have found that intake of foods or fluids containing non-nutritive sweeteners was accompanied by increased food intake, body weight gain, accumulation of body fat, and weaker caloric compensation, compared to consumption of foods and fluids containing glucose. Our research also provided evidence consistent with the hypothesis that these effects of consuming saccharin may be associated with a decrement in the ability of sweet taste to evoke thermic responses, and perhaps other physiological, cephalic phase, reflexes that are thought to help maintain energy balance.

Conjugation of the phenol derived from rivastigmine with amphetamines gave access to novel carbamate cholinesterase inhibitors. All compounds possessed increased affinity and selectivity for AChE compared to rivastigmine and were orally bioavailable. Compound 4a, incorporating d-amphetamine, caused significant inhibition of cholinesterase in vivo at doses that were well tolerated. Release of amphetamine from 4a was demonstrated following in vitro and in vivo inhibition of cholinesterase. Compound 4a was also effective in alleviating scopolamine induced amnesia in a rat passive avoidance model.