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Conjugated molecules and polymers have the ability to be transformative semiconducting materials; however, to reach their full potential a detailed understanding of the factors governing the molecular structure is crucial for establishing design principles for improved materials. Creating planar or "locking" structures is of particular interest for tuning electronic properties. While noncovalent locks are an effective strategy for increasing planarity, the precise interactions leading to these planar structures are often unknown or mischaracterized. In this study, we demonstrate that aromaticity can be used to investigate, interpret, and modify the complex physical interactions which lead to planarity. Furthermore, we clearly illustrate the important role aromaticity has in determining the structure through torsional preferences and find that modern noncovalent locks utilize hyperconjugation to alter aromaticity and increase planarity. We envision that our approach and our explanation of prevalent noncovalent locks will assist in the design of improved materials for organic electronics.

Hunter-gatherer populations are remarkable for their excellent metabolic and cardiovascular health and thus are often used as models in public health, in an effort to understand the root, evolutionary causes of non-communicable diseases. Here, we review recent work on health, activity, energetics and diet among hunter-gatherers and other small-scale societies (e.g. subsistence farmers, horticulturalists and pastoralists), as well as recent fossil and archaeological discoveries, to provide a more comprehensive perspective on lifestyle and health in these populations. We supplement these analyses with new data from the Hadza, a hunter-gatherer population in northern Tanzania. Longevity among small-scale populations approaches that of industrialized populations, and metabolic and cardiovascular disease are rare. Obesity prevalence is very low (

Through the use of genetic, enzymatic, metabolomic, and structural analyses, we have discovered the catabolic pathway for proline betaine, an osmoprotectant, in Paracoccus denitrificans and Rhodobacter sphaeroides. Genetic and enzymatic analyses showed tha

Assigning valid functions to proteins identified in genome projects is challenging: overprediction and database annotation errors are the principal concerns. We and others are developing computation-guided strategies for functional discovery with 'metaboli

Human evolutionary ecology stands to benefit by integrating theory and methods developed in movement ecology, and in turn, to make contributions to the broader field of movement ecology by leveraging our species' distinct attributes. In this paper, we review data and evolutionary models suggesting that major changes in socio-spatial behaviour accompanied the evolution of language. To illustrate and explore these issues, we present a comparison of GPS measures of the socio-spatial behaviour of Hadza hunter-gatherers of northern Tanzania to those of olive baboons ( Papio anubis ), a comparatively small-brained primate that is also savanna-adapted. While standard spatial metrics show modest differences, measures of spatial diversity, landscape exploration and spatiotemporal displacement between individuals differ markedly. Groups of Hadza foragers rapidly accumulate a vast, diverse knowledge pool about places and things over the horizon, contrasting with the baboon's narrower and more homogeneous pool of ecological information. The larger and more complex socio-spatial world illustrated by the Hadza is one where heightened cognitive abilities for spatial and episodic memory, navigation, perspective taking and communication about things beyond the here and now all have clear value.This article is part of the theme issue 'The spatial-social interface: a theoretical and empirical integration'.

We present the first published ethnographic description of landscape burning by Hadza hunter-gatherers of northern Tanzania and identify environmental, social, and cultural influences on Hadza landscape burning, thereby broadening the ethnographic record of anthropogenic burning practices described for hunter-gatherer communities. We report interview data collected in 2022 and 2023, describing their practices and attitudes regarding the causes and consequences of burning. We provide context by comparing our observations with those recorded for hunting and gathering populations in Africa, Australia, and North America. Hadza landscape burning is generally a solitary and male-dominated activity, contrary to ethnographic accounts of Indigenous landscape burning from North America and Australia. The primary goals stated by Hadza for landscape burning were improved hunting, reduced hazards from dangerous animals, and to reduce the density of livestock. Firsthand observations suggest that landscape burning has decreased over the past 20 years, and this historical trend is supported by interviews. Satellite imagery also suggests an overall decrease in burning activity in the region from 2001 to 2022. Among the Hadza, landscape burning is a culturally influenced and strongly gender-biased activity that is rapidly disappearing. Because burning can radically transform landscapes, these practices often generate or amplify conflicts of interest between groups with different land use strategies. Hadza report serious social conflict with pastoralists over landscape burning, and our study suggests this tension has constrained the practice in the past two decades., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Racial concentration of neighborhoods is often associated with the risk of preterm birth (PTB) for women. This study examined differences between racially diverse and racially concentrated neighborhoods when examining preterm birth. Individual-level data were obtained from Texas natality files for 2009-2011, and neighborhood-level (i.e., census tract) data were obtained from the decennial census in 2010 and the American Community Survey 2005-2009. We used multilevel modeling to assess the association between neighborhood racial diversity and odds of PTB, after controlling for individual characteristics, neighborhood poverty, and population density. We found that neighborhood racial diversity and concentration matter for PTB. Results suggest that systemic racism is still key to understanding PTB. Furthermore, findings support policies that prevent displacement from gentrification of diverse neighborhoods and promote equal access to health-related resources for women in predominantly Black, Hispanic, and/or immigrant neighborhoods., (© 2024. The Author(s).)

This article underscores the critical role of social workers in harnessing the potential therapeutic benefits of psilocybin for treating major depressive disorder (MDD) and substance use disorder (SUD). Contemporary treatments for MDD often have side effects, and the success rate for SUD treatments remains low. The pervasiveness of MDD, combined with the challenges in treating SUD, highlights a need for innovative treatments. This article provides an overview of the resurgence of literature over the past two decades that illuminates the therapeutic promise of psilocybin for mental health treatment; clinical trials elucidate the efficacy of psilocybin-assisted therapy in mitigating MDD and demonstrate great promise in reducing SUD symptoms. The long-lasting posttreatment effect emphasizes its potential as a novel treatment modality. Furthermore, psilocybin's recognition as a "breakthrough therapy" by the U.S. Food and Drug Administration (FDA) and the accelerating pace of psychedelic reform bills indicate growing acceptance and interest in its therapeutic capacities. Psilocybin-assisted therapy emerges as a potent treatment option, showcasing remarkable effectiveness even after a single dose. Recommendations and pathways for social workers to be involved in psilocybin-assisted therapy investigation, advocacy, and implementation are provided., (© 2024 National Association of Social Workers.)

Species interactions that vary across environments can create geographical mosaics of genetic coevolution. However, traits mediating species interactions are sometimes culturally inherited. Here we show that traditions of interspecies communication between people and wild birds vary in a culturally determined geographical mosaic. Honey hunters in different parts of Africa use different calls to communicate with greater honeyguides ( Indicator indicator ) that lead them to bees' nests. We show experimentally that honeyguides in Tanzania and Mozambique discriminate among honey hunters' calls, responding more readily to local than to foreign calls. This was not explained by variation in sound transmission and instead suggests that honeyguides learn local human signals. We discuss the forces stabilizing and diversifying interspecies communication traditions, and the potential for cultural coevolution between species.

Objectives: Physically active lifestyles are associated with several health benefits. Physical activity (PA) levels are low in post-industrial populations, but generally high throughout life in subsistence populations. The Hadza are a subsistence-oriented foraging population in Tanzania known for being physically active, but it is unknown how recent increases in market integration may have altered their PA patterns. In this study, we examine PA patterns for Hadza women and men who engage in different amounts of traditional foraging., Materials and Methods: One hundred and seventy seven Hadza participants (51% female, 19-87 years) wore an Axivity accelerometer (dominant wrist) for ~6 days during dry season months. We evaluated the effects of age, sex, and lifestyle measures on four PA measures that capture different aspects of the PA profile., Results: Participants engaged in high levels of both moderate-intensity PA and inactivity. Although PA levels were negatively associated with age, older participants were still highly active. We found no differences in PA between participants living in more traditional "bush" camps and those living in more settled "village" camps. Mobility was positively associated with step counts for female participants, and schooling was positively associated with inactive time for male participants., Conclusions: The similarity in PA patterns between Hadza participants in different camp types suggests that high PA levels characterize subsistence lifestyles generally. The sex-based difference in the effects of mobility and schooling on PA could be a reflection of the Hadza's gender-based division of labor, or indicate that changes to subsistence-oriented lifestyles impact women and men in different ways., (© 2023 The Authors. American Journal of Biological Anthropology published by Wiley Periodicals LLC.)

Among mammals, post-reproductive life spans are currently documented only in humans and a few species of toothed whales. Here we show that a post-reproductive life span exists among wild chimpanzees in the Ngogo community of Kibale National Park, Uganda. Post-reproductive representation was 0.195, indicating that a female who reached adulthood could expect to live about one-fifth of her adult life in a post-reproductive state, around half as long as human hunter-gatherers. Post-reproductive females exhibited hormonal signatures of menopause, including sharply increasing gonadotropins after age 50. We discuss whether post-reproductive life spans in wild chimpanzees occur only rarely, as a short-term response to favorable ecological conditions, or instead are an evolved species-typical trait as well as the implications of these alternatives for our understanding of the evolution of post-reproductive life spans.

Neighborhoods, as built and social environments, have significant implications for mental health. Children raised in high-poverty neighborhoods, who are disproportionately Black, Indigenous, and people of color, have a greater risk of adverse life outcomes. Neighborhood gentrification is also salient when examining mental health outcomes as neighborhood economic contexts shift around a child. This review scopes, describes, synthesizes, and critiques the existing literature on the relationship between neighborhood poverty/gentrification and mood disorder symptoms among children ages 3-17 in the United States (U.S.). Given the history of structural racism in the creation of U.S. neighborhoods, inclusion criteria required that study samples be racially diverse. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for scoping reviews, seven databases and grey literature were searched; 17 studies were included (total n = 122,089). Fourteen studies found significant associations between neighborhood poverty/gentrification and child depression. Three longitudinal studies found significant results suggesting that childhood neighborhood poverty/gentrification may have a lagged effect, with depression emerging later in life. Neighborhood poverty and gentrification require further examination as social determinants of mental health. Researchers should examine neighborhood poverty and gentrification as social determinants of mental health. Policies that reduce neighborhood economic disparities are needed across the U.S.

Racial/ethnic minority adolescents are at greater risk of attempting suicide compared to their White counterparts. Yet, racial/ethnic minority adolescents are more likely to not respond to questions on suicidal behaviors. The objective of this study was to investigate the association between race/ethnicity and missing response to suicide attempt among adolescents in the United States. Data for this study were obtained the 2015-2019 national Youth Risk Behavior Survey (n = 40,360). The outcome variable investigated in this study was missing response to suicide attempt and the main explanatory variable was race/ethnicity. Two hierarchical binary logistic regression models were fitted to examine the association between race/ethnicity and missing response to suicide attempt. Of the 40,036 adolescents, 13.4% had missing response to suicide attempt. Controlling for the effects of demographic factors and symptoms of depression, adolescents who self-identified as non-Hispanic Black had more than threefold higher odds of having missing response to suicide attempt when compared to their non-Hispanic White counterparts (AOR = 3.62, p < .001, 95% CI = 2.45-5.34). Adolescent males and adolescents questioning their sexual identity had higher odds of having missing response to suicide attempt. Adolescents with depressive symptoms had lower odds of having missing response to suicide attempt. Missing response to suicide attempt among adolescents continues to differ by race/ethnicity and other demographic factors. The use of a single item in assessing suicide attempt history may be inadequate in capturing national estimates of adolescent suicide metrics., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interests with respect to the authorship and/or the publication of this manuscript., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Diminished immune defense plays an important role in cancer development. Cancer risk in immunocompromised patients may differ. Identifying individuals with elevated cancer risk can inform strategies for routine cancer screening. This study aimed to understand and compare cancer incidence and risk in three patient groups: recipients of solid organ transplant (SOT) or hematopoietic stem cell transplant (HSCT); diagnosis of primary or secondary immunodeficiency disorder (PID/SID); and recipients of tumor necrosis factor inhibitor (TNF-i) therapy., Methods: This retrospective cohort study used the University of Utah Health System database and Huntsman Cancer Institute tumor registry. Patients aged ≥18 years with SOT/HSCT, PID/SID or ≥ 3 months of TNF-i therapy were included. The date of transplant, diagnosis of PID/SID, or 1st TNF-i medication order date was defined as the index date. We calculated cumulative cancer incidence by Kaplan-Meier method. A Cox-proportional hazard regression model with a stepwise variable selection process was used to identify independent risk factors associated with the time to onset of a new primary cancer., Results: In total, 13,887 patients were included which comprised of 2982 (21%) SOT/HSCT, 7542 (54%) PID/SID and 3363 (24%) patients receiving TNF-i. The mean (SD) age ranged from 46.8 (15) years - 50.4 (18.2) years. The proportion of white patients ranged from 72.3-84.8%. The estimated cumulative cancer incidence was 11.5% in the SOT/HSCT cohort, 14.3% in the PID/SID cohort, and 8.8% in the TNF-i cohort. The multivariable model adjusted for age, benign in-situ disease, Charlson Comorbidity Index, hypertension/cardiovascular disease/end stage renal disease, gender, race/ethnicity, and renal cyst as significant risk factors. The adjusted hazard ratios for cancer development in SOT/HSCT and PID/SID cohorts compared to the TNF-i cohort over the full follow-up period were 1.57 (95% CI: 1.16-2.13) and 2.14 (95% CI: 1.65-2.77), respectively., Conclusion: A significantly increased risk of cancer was observed in PID/SID patients and SOT/HSCT patients compared to TNF-i patients. Age ≥ 50 years, male gender, and clinical comorbidities were additional factors impacting cancer risk. PID/SID and SOT/HSCT patients may benefit from more intensive cancer screening., (© 2023. The Author(s).)

Water is essential for survival, but one in three individuals worldwide (2.2 billion people) lacks access to safe drinking water. Water intake requirements largely reflect water turnover (WT), the water used by the body each day. We investigated the determinants of human WT in 5604 people from the ages of 8 days to 96 years from 23 countries using isotope-tracking ( 2 H) methods. Age, body size, and composition were significantly associated with WT, as were physical activity, athletic status, pregnancy, socioeconomic status, and environmental characteristics (latitude, altitude, air temperature, and humidity). People who lived in countries with a low human development index (HDI) had higher WT than people in high-HDI countries. On the basis of this extensive dataset, we provide equations to predict human WT in relation to anthropometric, economic, and environmental factors.

When interacting with infants, humans often alter their speech and song in ways thought to support communication. Theories of human child-rearing, informed by data on vocal signalling across species, predict that such alterations should appear globally. Here, we show acoustic differences between infant-directed and adult-directed vocalizations across cultures. We collected 1,615 recordings of infant- and adult-directed speech and song produced by 410 people in 21 urban, rural and small-scale societies. Infant-directedness was reliably classified from acoustic features only, with acoustic profiles of infant-directedness differing across language and music but in consistent fashions. We then studied listener sensitivity to these acoustic features. We played the recordings to 51,065 people from 187 countries, recruited via an English-language website, who guessed whether each vocalization was infant-directed. Their intuitions were more accurate than chance, predictable in part by common sets of acoustic features and robust to the effects of linguistic relatedness between vocalizer and listener. These findings inform hypotheses of the psychological functions and evolution of human communication., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

In mammals, trait variation is often reported to be greater among males than females. However, to date, mainly only morphological traits have been studied. Energy expenditure represents the metabolic costs of multiple physical, physiological, and behavioral traits. Energy expenditure could exhibit particularly high greater male variation through a cumulative effect if those traits mostly exhibit greater male variation, or a lack of greater male variation if many of them do not. Sex differences in energy expenditure variation have been little explored. We analyzed a large database on energy expenditure in adult humans (1494 males and 3108 females) to investigate whether humans have evolved sex differences in the degree of interindividual variation in energy expenditure. We found that, even when statistically comparing males and females of the same age, height, and body composition, there is much more variation in total, activity, and basal energy expenditure among males. However, with aging, variation in total energy expenditure decreases, and because this happens more rapidly in males, the magnitude of greater male variation, though still large, is attenuated in older age groups. Considerably greater male variation in both total and activity energy expenditure could be explained by greater male variation in levels of daily activity. The considerably greater male variation in basal energy expenditure is remarkable and may be explained, at least in part, by greater male variation in the size of energy-demanding organs. If energy expenditure is a trait that is of indirect interest to females when choosing a sexual partner, this would suggest that energy expenditure is under sexual selection. However, we present a novel energetics model demonstrating that it is also possible that females have been under stabilizing selection pressure for an intermediate basal energy expenditure to maximize energy available for reproduction., Competing Interests: Conflicts of interest The authors have no conflicts of interest to declare., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Human-wildlife cooperation occurs when humans and free-living wild animals actively coordinate their behavior to achieve a mutually beneficial outcome. These interactions provide important benefits to both the human and wildlife communities involved, have wider impacts on the local ecosystem, and represent a unique intersection of human and animal cultures. The remaining active forms are human-honeyguide and human-dolphin cooperation, but these are at risk of joining several inactive forms (including human-wolf and human-orca cooperation). Human-wildlife cooperation faces a unique set of conservation challenges, as it requires multiple components-a motivated human and wildlife partner, a suitable environment, and compatible interspecies knowledge-which face threats from ecological and cultural changes. To safeguard human-wildlife cooperation, we recommend: (i) establishing ethically sound conservation strategies together with the participating human communities; (ii) conserving opportunities for human and wildlife participation; (iii) protecting suitable environments; (iv) facilitating cultural transmission of traditional knowledge; (v) accessibly archiving Indigenous and scientific knowledge; and (vi) conducting long-term empirical studies to better understand these interactions and identify threats. Tailored safeguarding plans are therefore necessary to protect these diverse and irreplaceable interactions. Broadly, our review highlights that efforts to conserve biological and cultural diversity should carefully consider interactions between human and animal cultures. Please see AfricanHoneyguides.com/abstract-translations for Kiswahili and Portuguese translations of the abstract., Competing Interests: The authors declare no conflict of interest., (© 2022 The Authors. Conservation Letters published by Wiley Periodicals LLC.)

Lower ambient temperature (T a ) requires greater energy expenditure to sustain body temperature. However, effects of T a on human energetics may be buffered by environmental modification and behavioral compensation. We used the IAEA DLW database for adults in the USA (n = 3213) to determine the effect of T a (-10 to +30°C) on TEE, basal (BEE) and activity energy expenditure (AEE) and physical activity level (PAL). There were no significant relationships (p > 0.05) between maximum, minimum and average T a and TEE, BEE, AEE and PAL. After adjustment for fat-free mass, fat mass and age, statistically significant (p < 0.01) relationships between TEE, BEE and T a emerged in females but the effect sizes were not biologically meaningful. Temperatures inside buildings are regulated at 18-25°C independent of latitude. Hence, adults in the US modify their environments to keep TEE constant across a wide range of external ambient temperatures., Competing Interests: The authors declare no conflicts of interest., (© 2022 The Authors.)

The purpose of this study was to determine whether housing age in combination with neighborhood poverty, as a proxy for fetal exposure to heavy metal lead, is associated with adverse birth outcomes. We linked population-level birth certificate data for Black, Hispanic, White and Other women, stratified by nativity, from 2009-2011 in Texas ( n = 1,040,642) to census the tract-level median housing age/poverty level from the American Community Survey, 2007-2011. Tracts with median housing age values before 1975 with a poverty level of 20% or more were considered to be neighborhoods with a high risk of exposure to deteriorating lead-based paint. We estimated multilevel models to examine the relationship between neighborhood housing age/poverty level and each dependent variable (preterm birth, low birth weight, small-for-gestational age). The odds of adverse birth outcomes were significantly higher for mothers living in high-poverty neighborhoods with median housing built before the lead-based paint ban. Increased awareness of-and improved methods of alleviating- ubiquitous lead-based paint exposure in Texas may be necessary interventions for positive developmental trajectories of children. Allocating federal funds for place-based interventions, including universal lead paint mitigation, in older, high-poverty neighborhoods may reduce the disproportionate risk of adverse birth outcomes.

Low total energy expenditure (TEE, MJ/d) has been a hypothesized risk factor for weight gain, but repeatability of TEE, a critical variable in longitudinal studies of energy balance, is understudied. We examine repeated doubly labeled water (DLW) measurements of TEE in 348 adults and 47 children from the IAEA DLW Database (mean ± SD time interval: 1.9 ± 2.9 y) to assess repeatability of TEE, and to examine if TEE adjusted for age, sex, fat-free mass, and fat mass is associated with changes in weight or body composition. Here, we report that repeatability of TEE is high for adults, but not children. Bivariate Bayesian mixed models show no among or within-individual correlation between body composition (fat mass or percentage) and unadjusted TEE in adults. For adults aged 20-60 y (N = 267; time interval: 7.4 ± 12.2 weeks), increases in adjusted TEE are associated with weight gain but not with changes in body composition; results are similar for subjects with intervals >4 weeks (N = 53; 29.1 ± 12.8 weeks). This suggests low TEE is not a risk factor for, and high TEE is not protective against, weight or body fat gain over the time intervals tested., (© 2022. The Author(s).)

Background: Physical activity may be a way to increase and maintain fat-free mass (FFM) in later life, similar to the prevention of fractures by increasing peak bone mass., Objectives: A study is presented of the association between FFM and physical activity in relation to age., Methods: In a cross-sectional study, FFM was analyzed in relation to physical activity in a large participant group as compiled in the International Atomic Energy Agency Doubly Labeled Water database. The database included 2000 participants, age 3-96 y, with measurements of total energy expenditure (TEE) and resting energy expenditure (REE) to allow calculation of physical activity level (PAL = TEE/REE), and calculation of FFM from isotope dilution., Results: PAL was a main determinant of body composition at all ages. Models with age, fat mass (FM), and PAL explained 76% and 85% of the variation in FFM in females and males < 18 y old, and 32% and 47% of the variation in FFM in females and males ≥ 18 y old, respectively. In participants < 18 y old, mean FM-adjusted FFM was 1.7 kg (95% CI: 0.1, 3.2 kg) and 3.4 kg (95% CI: 1.0, 5.6 kg) higher in a very active participant with PAL = 2.0 than in a sedentary participant with PAL = 1.5, for females and males, respectively. At age 18 y, height and FM-adjusted FFM was 3.6 kg (95% CI: 2.8, 4.4 kg) and 4.4 kg (95% CI: 3.2, 5.7 kg) higher, and at age 80 y 0.7 kg (95% CI: -0.2, 1.7 kg) and 1.0 kg (95% CI: -0.1, 2.1 kg) higher, in a participant with PAL = 2.0 than in a participant with PAL = 1.5, for females and males, respectively., Conclusions: If these associations are causal, they suggest physical activity is a major determinant of body composition as reflected in peak FFM, and that a physically active lifestyle can only partly protect against loss of FFM in aging adults., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Understanding the impacts of activity on energy balance is crucial. Increasing levels of activity may bring diminishing returns in energy expenditure because of compensatory responses in non-activity energy expenditures. 1-3 This suggestion has profound implications for both the evolution of metabolism and human health. It implies that a long-term increase in activity does not directly translate into an increase in total energy expenditure (TEE) because other components of TEE may decrease in response-energy compensation. We used the largest dataset compiled on adult TEE and basal energy expenditure (BEE) (n = 1,754) of people living normal lives to find that energy compensation by a typical human averages 28% due to reduced BEE; this suggests that only 72% of the extra calories we burn from additional activity translates into extra calories burned that day. Moreover, the degree of energy compensation varied considerably between people of different body compositions. This association between compensation and adiposity could be due to among-individual differences in compensation: people who compensate more may be more likely to accumulate body fat. Alternatively, the process might occur within individuals: as we get fatter, our body might compensate more strongly for the calories burned during activity, making losing fat progressively more difficult. Determining the causality of the relationship between energy compensation and adiposity will be key to improving public health strategies regarding obesity., Competing Interests: Declaration of interests The authors have no conflicts of interest to declare., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

We review the evolutionary origins of the human diet and the effects of ecology economy on the dietary proportion of plants and animals. Humans eat more meat than other apes, a consequence of hunting and gathering, which arose ∼2.5 Mya with the genus Homo . Paleolithic diets likely included a balance of plant and animal foods and would have been remarkably variable across time and space. A plant/animal food balance of 50/50% prevails among contemporary warm-climate hunter-gatherers, but these proportions vary widely. Societies in cold climates, and those that depend more on fishing or pastoralism, tend to eat more meat. Warm-climate foragers, and groups that engage in some farming, tend to eat more plants. We present a case study of the wild food diet of the Hadza, a community of hunter-gatherers in northern Tanzania, whose diet is high in fiber, adequate in protein, and remarkably variable over monthly timescales.

Purpose: To document gender-specific racial-ethnic disparities in cardiovascular (CV) conditions and risk factors net of socioeconomic status (SES) across the lifespan., Methods: Using pooled data from the 1999 to 2016 U.S. National Health and Nutrition Examination Survey, we document gender-specific proportions of non-Hispanic Whites, non-Hispanic Blacks, and Hispanics ages 12-69 years with various socioeconomic characteristics and CV conditions. We then further disaggregate into 10-year age groups and present unadjusted and SES-adjusted prevalence of each CV condition for each gender/racial-ethnic/age group., Results: Racial-ethnic differences in the prevalence of CV conditions are large for some conditions, emerge early in adulthood, and remain relatively constant though age 69. Only small proportions of the differences can be attributed to differences in SES across groups; attenuation after adjusting for income, education, and available measures of wealth ranged from 0 to 2.3 percentage points. Black-White differences in prevalence of CV conditions differ substantially and systematically by gender; White females have larger advantages or smaller disadvantages (depending on indicator) relative to Black females than White males do relative to Black males., Conclusions: Racial-ethnic disparities in CV conditions are rooted early in the life course, do not mirror socioeconomic disparities, and vary considerably by gender. Explanations likely involve early life experiences such as racial discrimination and entrenched inequality., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Total daily energy expenditure ("total expenditure") reflects daily energy needs and is a critical variable in human health and physiology, but its trajectory over the life course is poorly studied. We analyzed a large, diverse database of total expenditure measured by the doubly labeled water method for males and females aged 8 days to 95 years. Total expenditure increased with fat-free mass in a power-law manner, with four distinct life stages. Fat-free mass-adjusted expenditure accelerates rapidly in neonates to ~50% above adult values at ~1 year; declines slowly to adult levels by ~20 years; remains stable in adulthood (20 to 60 years), even during pregnancy; then declines in older adults. These changes shed light on human development and aging and should help shape nutrition and health strategies across the life span., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Morphogen signaling proteins disperse across tissues to activate signal transduction in target cells. We investigated dispersion of Hedgehog (Hh), Wnt homolog Wingless (Wg), and Bone morphogenic protein homolog Decapentaplegic (Dpp) in the Drosophila wing imaginal disc. We discovered that delivery of Hh, Wg, and Dpp to their respective targets is regulated. We found that <5% of Hh and <25% of Wg are taken up by disc cells and activate signaling. The amount of morphogen that is taken up and initiates signaling did not change when the level of morphogen expression was varied between 50 and 200% (Hh) or 50 and 350% (Wg). Similar properties were observed for Dpp. We analyzed an area of 150 μm×150 μm that includes Hh-responding cells of the disc as well as overlying tracheal cells and myoblasts that are also activated by disc-produced Hh. We found that the extent of signaling in the disc was unaffected by the presence or absence of the tracheal and myoblast cells, suggesting that the mechanism that disperses Hh specifies its destinations to particular cells, and that target cells do not take up Hh from a common pool., Competing Interests: RH, BW, GO, TK No competing interests declared, (© 2021, Hatori et al.)

In many regions of sub Saharan Africa large mammals occur in human-dominated areas, yet their community composition and abundance have rarely been described in areas occupied by traditional hunter-gatherers and pastoralists. Surveys of mammal populations in such areas provide important measures of biodiversity and provide ecological context for understanding hunting practices. Using a sampling grid centered on a Hadza hunter-gatherer camp and covering 36 km2 of semi-arid savannah in northern Tanzania, we assessed mammals using camera traps (n = 19 stations) for c. 5 months (2,182 trap nights). In the study area (Tli'ika in the Hadza language), we recorded 36 wild mammal species. Rarefaction curves suggest that sampling effort was sufficient to capture mammal species richness, yet some species known to occur at low densities in the wider area (e.g. African lions, wildebeest) were not detected. Relative abundance indices of wildlife species varied by c. three orders of magnitude, from a mean of 0.04 (African wild dog) to 20.34 capture events per 100 trap-nights (Kirk's dik dik). To contextualize the relative abundance of wildlife in the study area, we compared our study's data to comparable camera trap data collected in a fully protected area of northern Tanzania with similar rainfall (Lake Manyara National Park). Raw data and negative binomial regression analyses show that wild herbivores and wild carnivores were generally detected in the national park at higher rates than in the Hadza-occupied region. Livestock were notably absent from the national park, but were detected at high levels in Tli'ika, and cattle was the second most frequently detected species in the Hadza-used area. We discuss how these data inform current conservation efforts, studies of Hadza hunting, and models of hunter-gatherer foraging ecology and diet., Competing Interests: The authors have declared that no competing interests exist.

Cytonemes are specialized filopodia that mediate paracrine signaling in Drosophila and other animals. Studies using fluorescence confocal microscopy (CM) established their general paths, cell targets, and essential roles in signaling. To investigate details unresolvable by CM, we used high-pressure freezing and EM to visualize cytoneme structures, paths, contents, and contacts. We observed cytonemes previously seen by CM in the Drosophila wing imaginal disc system, including disc, tracheal air sac primordium (ASP), and myoblast cytonemes, and identified cytonemes extending into invaginations of target cells, and cytonemes connecting ASP cells and connecting myoblasts. Diameters of cytoneme shafts vary between repeating wide (206 ± 51.8 nm) and thin (55.9 ± 16.2 nm) segments. Actin, ribosomes, and membranous compartments are present throughout; rough ER and mitochondria are in wider proximal sections. These results reveal novel structural features of filopodia and provide a basis for understanding cytoneme cell biology and function., (© 2021 Wood et al.)

To sustain life, humans and other terrestrial animals must maintain a tight balance of water gain and water loss each day. 1-3 However, the evolution of human water balance physiology is poorly understood due to the absence of comparative measures from other hominoids. While humans drink daily to maintain water balance, rainforest-living great apes typically obtain adequate water from their food and can go days or weeks without drinking 4-6 . Here, we compare isotope-depletion measures of water turnover (L/d) in zoo- and rainforest-sanctuary-housed apes (chimpanzees, bonobos, gorillas, and orangutans) with 5 diverse human populations, including a hunter-gatherer community in a semi-arid savannah. Across the entire sample, water turnover was strongly related to total energy expenditure (TEE, kcal/d), physical activity, climate (ambient temperature and humidity), and fat free mass. In analyses controlling for those factors, water turnover was 30% to 50% lower in humans than in other apes despite humans' greater sweating capacity. Water turnover in zoo and sanctuary apes was similar to estimated turnover in wild populations, as was the ratio of water intake to dietary energy intake (∼2.8 mL/kcal). However, zoo and sanctuary apes ingested a greater ratio of water to dry matter of food, which might contribute to digestive problems in captivity. Compared to apes, humans appear to target a lower ratio of water/energy intake (∼1.5 mL/kcal). Water stress due to changes in climate, diet, and behavior apparently led to previously unknown water conservation adaptations in hominin physiology., Competing Interests: Declaration of interests The authors declare no competing financial interests., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Humans occupy a wider range of environments, process more energy, and have greater biomass than any other species because we are able to culturally evolve complex, locally adaptive technologies. 1 Competing models make different predictions about the role of causal knowledge in this process. Some argue that innovation and transmission cannot occur without causal understanding, 2-5 while others posit that complex technologies can evolve without causal understanding. 1 , 6-10 Prior research on this topic has been restricted to theoretical work and experimental studies with student participants. 11-13 The Hadza are foragers who rely on bows for subsistence. 14-16 We interviewed skilled Hadza bowyers (bow-makers) and compared their beliefs regarding the tradeoffs in bow construction to those revealed by experimental and engineering research. If bowyers understand the tradeoffs, it is plausible that cultural evolution is rooted in causal understanding, while if they do not, the cultural accumulation of knowledge is likely more important in the process. We show that Hadza bowyers understand some mechanical trade-offs but not others, and therefore the evolution of a complex, highly adaptive technology is possible with incomplete causal knowledge regarding key mechanical trade-offs. Instead, some important design choices made by subjects seem to reflect cultural norms. Although previously published reports have suggested that some individuals are recognized by the Hadza as being especially skilled or knowledgeable, 14 , 17 our results do not indicate that some individuals are significantly more knowledgeable about bow-making than others, nor is there statistical evidence that causal knowledge increases with age., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Understanding how gendered economic roles structure space use is critical to evolutionary models of foraging behaviour, social organization and cognition. Here, we examine hunter-gatherer spatial behaviour on a very large scale, using GPS devices worn by Hadza foragers to record 2,078 person-days of movement. Theory in movement ecology suggests that the density and mobility of targeted foods should predict spatial behaviour and that strong gender differences should arise in a hunter-gatherer context. As predicted, we find that men walked further per day, explored more land, followed more sinuous paths and were more likely to be alone. These data are consistent with the ecology of male- and female-targeted foods and suggest that male landscape use is more navigationally challenging in this hunter-gatherer context. Comparisons of Hadza space use with space use data available for non-human primates suggest that the sexual division of labour likely co-evolved with increased sex differences in spatial behaviour and landscape use.

The doubly labeled water (DLW) method measures total energy expenditure (TEE) in free-living subjects. Several equations are used to convert isotopic data into TEE. Using the International Atomic Energy Agency (IAEA) DLW database (5,756 measurements of adults and children), we show considerable variability is introduced by different equations. The estimated rCO 2 is sensitive to the dilution space ratio (DSR) of the two isotopes. Based on performance in validation studies, we propose a new equation based on a new estimate of the mean DSR. The DSR is lower at low body masses (<10 kg). Using data for 1,021 babies and infants, we show that the DSR varies non-linearly with body mass between 0 and 10 kg. Using this relationship to predict DSR from weight provides an equation for rCO 2 over this size range that agrees well with indirect calorimetry (average difference 0.64%; SD = 12.2%). We propose adoption of these equations in future studies., Competing Interests: The authors declare no competing interests., (© 2021 The Authors.)

Nuclear histone deacetylase 4 (HDAC4) represses MEF2-mediated transcription, implicated in the development of heart failure. CaMKII-dependent phosphorylation drives nucleus-to-cytoplasm HDAC4 shuttling, but protein kinase A (PKA) is also linked to HDAC4 translocation. However, the interplay of CaMKII and PKA in regulating adult cardiomyocyte HDAC4 translocation is unclear. Here we sought to determine the interplay of PKA- and CaMKII-dependent HDAC4 phosphorylation and translocation in adult mouse, rabbit and human ventricular myocytes. Confocal imaging and protein analyses revealed that inhibition of CaMKII-but not PKA, PKC or PKD-raised nucleo-to-cytoplasmic HDAC4 fluorescence ratio (F Nuc /F Cyto ) by ~ 50%, indicating baseline CaMKII activity that limits HDAC4 nuclear localization. Further CaMKII activation (via increased extracellular [Ca 2+ ], high pacing frequencies, angiotensin II or overexpression of CaM or CaMKIIδC) led to significant HDAC4 nuclear export. In contrast, PKA activation by isoproterenol or forskolin drove HDAC4 into the nucleus (raising F Nuc /F Cyto by > 60%). These PKA-mediated effects were abolished in cells pretreated with PKA inhibitors and in cells expressing mutant HDAC4 in S265/266A mutant. In physiological conditions where both kinases are active, PKA-dependent nuclear accumulation of HDAC4 was predominant in the very early response, while CaMKII-dependent HDAC4 export prevailed upon prolonged stimuli. This orchestrated co-regulation was shifted in failing cardiomyocytes, where CaMKII-dependent effects predominated over PKA-dependent response. Importantly, human cardiomyocytes showed similar CaMKII- and PKA-dependent HDAC4 shifts. Collectively, CaMKII limits nuclear localization of HDAC4, while PKA favors HDAC4 nuclear retention and S265/266 is essential for PKA-mediated regulation. These pathways thus compete in HDAC4 nuclear localization and transcriptional regulation in cardiac signaling.

Human lifespans are exceptionally long compared with those of other primates. A key element in exploring the evolution of human longevity is understanding how modern humans grow older. Our current understanding of common age-related changes in human health and function stems mostly from studies in industrialized societies, where older adulthood is often associated with an increased incidence of chronic diseases. However, individuals who engage in different lifestyles across industrialized and non-industrialized contexts may display variance in age-related changes in health and function. Here, we explore aspects of physical function in a non-industrialized context using three objective measures of physical function. We assessed physical activity levels, walking endurance and muscle strength in two East African populations: Hadza hunter-gatherers in Tanzania and Pokot pastoralists in Kenya. Both Hadza and Pokot participants displayed significant age-related differences in most, but not all, functional measures. Our results suggest that some age-related differences in physical function seen in industrialized contexts could be consistently experienced by most humans, while other age-related differences may vary across populations. Studies of ageing should expand to include a broad range of populations so we can create a more comprehensive understanding of how senescence varies across different lifestyle contexts. This article is part of the theme issue 'Evolution of the primate ageing process'.

Rationale: CaMKII (Ca 2+ -Calmodulin dependent protein kinase) δC activation is implicated in pathological progression of heart failure (HF) and CaMKIIδC transgenic mice rapidly develop HF and arrhythmias. However, little is known about early spatio-temporal Ca 2+ handling and CaMKII activation in hypertrophy and HF., Objective: To measure time- and location-dependent activation of CaMKIIδC signaling in adult ventricular cardiomyocytes, during transaortic constriction (TAC) and in CaMKIIδC transgenic mice., Methods and Results: We used human tissue from nonfailing and HF hearts, 4 mouse lines: wild-type, KO (CaMKIIδ-knockout), CaMKIIδC transgenic in wild-type (TG), or KO background, and wild-type mice exposed to TAC. Confocal imaging and biochemistry revealed disproportional CaMKIIδC activation and accumulation in nuclear and perinuclear versus cytosolic regions at 5 days post-TAC. This CaMKIIδ activation caused a compensatory increase in sarcoplasmic reticulum Ca 2+ content, Ca 2+ transient amplitude, and [Ca 2+ ] decline rates, with reduced phospholamban expression, all of which were most prominent near and in the nucleus. These early adaptive effects in TAC were entirely mimicked in young CaMKIIδ TG mice (6-8 weeks) where no overt cardiac dysfunction was present. The (peri)nuclear CaMKII accumulation also correlated with enhanced HDAC4 (histone deacetylase) nuclear export, creating a microdomain for transcriptional regulation. At longer times both TAC and TG mice progressed to overt HF (at 45 days and 11-13 weeks, respectively), during which time the compensatory Ca 2+ transient effects reversed, but further increases in nuclear and time-averaged [Ca 2+ ] and CaMKII activation occurred. CaMKIIδ TG mice lacking δB exhibited more severe HF, eccentric myocyte growth, and nuclear changes. Patient HF samples also showed greatly increased CaMKIIδ expression, especially for CaMKIIδC in nuclear fractions., Conclusions: We conclude that in early TAC perinuclear CaMKIIδC activation promotes adaptive increases in myocyte Ca 2+ transients and nuclear transcriptional responses but that chronic progression of this nuclear Ca 2+ -CaMKIIδC axis contributes to eccentric hypertrophy and HF.

The opportunistic pathogen Staphylococcus aureus is protected by a cell envelope that is crucial for viability. In addition to peptidoglycan, lipoteichoic acid (LTA) is an especially important component of the S. aureus cell envelope. LTA is an anionic polymer anchored to a glycolipid in the outer leaflet of the cell membrane. It was known that deleting the gene for UgtP, the enzyme that makes this glycolipid anchor, causes cell growth and division defects. In Bacillus subtilis , growth abnormalities from the loss of ugtP have been attributed to both the absence of the encoded protein and to the loss of its products. Here, we show that growth defects in S. aureus ugtP deletion mutants are due to the long, abnormal LTA polymer that is produced when the glycolipid anchor is missing from the outer leaflet of the membrane. Dysregulated cell growth leads to defective cell division, and these phenotypes are corrected by mutations in the LTA polymerase, ltaS , that reduce polymer length. We also show that S. aureus mutants with long LTA are sensitized to cell wall hydrolases, beta-lactam antibiotics, and compounds that target other cell envelope pathways. We conclude that control of LTA polymer length is important for S. aureus physiology and promotes survival under stressful conditions, including antibiotic stress. IMPORTANCE Methicillin-resistant Staphylococcus aureus (MRSA) is a common cause of community- and hospital-acquired infections and is responsible for a large fraction of deaths caused by antibiotic-resistant bacteria. S. aureus is surrounded by a complex cell envelope that protects it from antimicrobial compounds and other stresses. Here we show that controlling the length of an essential cell envelope polymer, lipoteichoic acid, is critical for controlling S. aureus cell size and cell envelope integrity. We also show that genes involved in LTA length regulation are required for resistance to beta-lactam antibiotics in MRSA. The proteins encoded by these genes may be targets for combination therapy with an appropriate beta-lactam., (Copyright © 2020 American Society for Microbiology.)

Recent work suggests human physiology is not well adapted to prolonged periods of inactivity, with time spent sitting increasing cardiovascular disease and mortality risk. Health risks from sitting are generally linked with reduced levels of muscle contractions in chair-sitting postures and associated reductions in muscle metabolism. These inactivity-associated health risks are somewhat paradoxical, since evolutionary pressures tend to favor energy-minimizing strategies, including rest. Here, we examined inactivity in a hunter-gatherer population (the Hadza of Tanzania) to understand how sedentary behaviors occur in a nonindustrial economic context more typical of humans' evolutionary history. We tested the hypothesis that nonambulatory rest in hunter-gatherers involves increased muscle activity that is different from chair-sitting sedentary postures used in industrialized populations. Using a combination of objectively measured inactivity from thigh-worn accelerometers, observational data, and electromygraphic data, we show that hunter-gatherers have high levels of total nonambulatory time (mean ± SD = 9.90 ± 2.36 h/d), similar to those found in industrialized populations. However, nonambulatory time in Hadza adults often occurs in postures like squatting, and we show that these "active rest" postures require higher levels of lower limb muscle activity than chair sitting. Based on our results, we introduce the Inactivity Mismatch Hypothesis and propose that human physiology is likely adapted to more consistently active muscles derived from both physical activity and from nonambulatory postures with higher levels of muscle contraction. Interventions built on this model may help reduce the negative health impacts of inactivity in industrialized populations., Competing Interests: The authors declare no competing interest.

Control of equilibrium and non-equilibrium thermomechanical behavior of poly(diketoenamine) vitrimers is shown by incorporating linear polymer segments varying in molecular weight (MW) and conformational degrees of freedom into the dynamic covalent network. While increasing MW of linear segments yields a lower storage modulus at the rubbery plateau after softening above the glass transition (T g ), both T g and the characteristic time of stress relaxation are independently governed by the conformational entropy of the embodied linear segments. Activation energies for bond exchange in the solid state are lower for networks incorporating flexible chains; the network topology freezing temperature decreases with increasing MW of flexible linear segments but increases with increasing MW of stiff segments. Vitrimer reconfigurability is therefore influenced not only by the energetics of bond exchange for a given network density, but also the entropy of polymer chains within the network., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Veteran suicide is a serious public health problem. Some data suggest that veteran suicide risk profiles differ from those of nonveterans. Records for veteran (n = 21,692) and nonveteran (n = 83,430) men who died by suicide were examined from 17 U.S. states using the National Violent Death Reporting System data. Seventeen precipitating factors were examined and combined through meta-analysis of proportions. Many precipitating factors were found to be less frequent for veterans. A smaller number of factors were found to be higher in the veteran population, including physical health problems. A sizable cumulative effect size (1.02) was observed, suggesting that veteran and nonveteran men show meaningful and substantive differences in their risk profiles-differences that should be considered when planning and implementing suicide prevention and intervention efforts. The conspicuous role of physical health problems among veterans who die by suicide is discussed. The article concludes with specific practice recommendations for social workers., (© 2020 National Association of Social Workers.)

Nonaqueous polyelectrolyte solutions have been recently proposed as high Li + transference number electrolytes for lithium ion batteries. However, the atomistic phenomena governing ion diffusion and migration in polyelectrolytes are poorly understood, particularly in nonaqueous solvents. Here, the structural and transport properties of a model polyelectrolyte solution, poly(allyl glycidyl ether-lithium sulfonate) in dimethyl sulfoxide, are studied using all-atom molecular dynamics simulations. We find that the static structural analysis of Li + ion pairing is insufficient to fully explain the overall conductivity trend, necessitating a dynamic analysis of the diffusion mechanism, in which we observe a shift from largely vehicular transport to more structural diffusion as the Li + concentration increases. Furthermore, we demonstrate that despite the significantly higher diffusion coefficient of the lithium ion, the negatively charged polyion is responsible for the majority of the solution conductivity at all concentrations, corresponding to Li + transference numbers much lower than previously estimated experimentally. We quantify the ion-ion correlations unique to polyelectrolyte systems that are responsible for this surprising behavior. These results highlight the need to reconsider the approximations typically made for transport in polyelectrolyte solutions., Competing Interests: The authors declare no competing financial interest.

Objectives: Evidence from industrialized populations suggests that urine concentrating ability declines with age. However, lifestyle factors including episodic protein intake and low hypertension may help explain differences between populations. Whether this age-related decline occurs among small-scale populations with active lifestyles and non-Western diets is unknown. We test the universality of age-related urine concentration decline., Materials and Methods: We used urine specific gravity (Usg) and urine osmolality (Uosm) data from 15,055 U.S. nonpregnant adults without kidney failure aged 18-80 in 2007-2012 participating in the National Health and Nutrition Examination Survey (NHANES). We tested the relationship of age on urine concentration biomarkers with multiple linear regressions using survey commands. We compared results to longitudinal data on Usg from 116 Tsimane' forager-horticulturalists (266 observations) adults aged 18-83 in 2013-2014 from Lowland Bolivia, and to 38 Hadza hunter-gatherers (156 observations) aged 18-75 in 2010-2015 from Tanzania using random-effects panel linear regressions., Results: Among U.S. adults, age was significantly negatively associated with Usg (Adjusted beta [B] = -0.0009 g/mL/10 years; SE = 0.0001; p < 0.001) and Uosm (B = -28.1 mOsm/kg/10 yr; SE = 2.4; p < 0.001). In contrast, among Tsimane' (B = 0.0003 g/mL/10 yr; SE = 0.0002; p = 0.16) and Hadza (B = -0.0004 g/mL/10 yr; SE = 0.0004; p = 0.29) age was not associated with Usg. Older Tsimane' and Hadza exhibited similar within-individual variability in Usg equivalent to younger adults., Discussion: While U.S. adults exhibited age-related declines in urine concentration, Tsimane' and Hadza adults did not exhibit the same statistical decline in Usg. Mismatches between evolved physiology and modern environments in lifestyle may affect kidney physiology and disease risk., (© 2019 Wiley Periodicals, Inc.)

New antibiotics are needed to combat the growing problem of resistant bacterial infections. An attractive avenue toward the discovery of such next-generation therapies is to identify novel inhibitors of clinically validated targets, like cell wall biogenesis. We have therefore developed a pathway-directed whole-cell screen for small molecules that block the activity of the Rod system of Escherichia coli This conserved multiprotein complex is required for cell elongation and the morphogenesis of rod-shaped bacteria. It is composed of cell wall synthases and membrane proteins of unknown function that are organized by filaments of the actin-like MreB protein. Our screen takes advantage of the conditional essentiality of the Rod system and the ability of the beta-lactam mecillinam (also known as amdinocillin) to cause a toxic malfunctioning of the machinery. Rod system inhibitors can therefore be identified as molecules that promote growth in the presence of mecillinam under conditions permissive for the growth of Rod - cells. A screen of ∼690,000 compounds identified 1,300 compounds that were active against E. coli Pathway-directed screening of a majority of this subset of compounds for Rod inhibitors successfully identified eight analogs of the MreB antagonist A22. Further characterization of the A22 analogs identified showed that their antibiotic activity under conditions where the Rod system is essential was strongly correlated with their ability to suppress mecillinam toxicity. This result combined with those from additional biological studies reinforce the notion that A22-like molecules are relatively specific for MreB and suggest that the lipoprotein transport factor LolA is unlikely to be a physiologically relevant target as previously proposed., (Copyright © 2018 American Society for Microbiology.)

Calcium-calmodulin dependent protein kinase IIδ (CaMKIIδ) is an important regulator of cardiac electrophysiology, calcium (Ca) balance, contraction, transcription, arrhythmias and progression to heart failure. CaMKII is readily activated at mouths of dyadic cleft Ca channels, but because of its low Ca-calmodulin affinity and presumed immobility it is less clear how CaMKII gets activated near other known, extra-dyad targets. CaMKII is typically considered to be anchored in cardiomyocytes, but while untested, mobility of active CaMKII could provide a mechanism for broader target phosphorylation in cardiomyocytes. We therefore tested CaMKII mobility and how this is affected by kinase activation in adult rabbit cardiomyocytes. We measured translocation of both endogenous and fluorescence-tagged CaMKII using immunocytochemistry, fluorescence recovery after photobleach (FRAP) and photoactivation of fluorescence. In contrast to the prevailing view that CaMKII is anchored near its myocyte targets, we found CaMKII to be highly mobile in resting myocytes, which was slowed by Ca chelation and accelerated by pacing. At low [Ca], CaMKII was concentrated at Z-lines near the dyad but spread throughout the sarcomere upon pacing. Nuclear exchange of CaMKII was also enhanced upon pacing- and heart failure-induced chronic activation. This mobilization of active CaMKII and its intrinsic memory may allow CaMKII to be activated in high [Ca] regions and then move towards more distant myocyte target sites., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Hunter-gatherer populations are remarkable for their excellent metabolic and cardiovascular health and thus are often used as models in public health, in an effort to understand the root, evolutionary causes of non-communicable diseases. Here, we review recent work on health, activity, energetics and diet among hunter-gatherers and other small-scale societies (e.g. subsistence farmers, horticulturalists and pastoralists), as well as recent fossil and archaeological discoveries, to provide a more comprehensive perspective on lifestyle and health in these populations. We supplement these analyses with new data from the Hadza, a hunter-gatherer population in northern Tanzania. Longevity among small-scale populations approaches that of industrialized populations, and metabolic and cardiovascular disease are rare. Obesity prevalence is very low (<5%), and mean body fat percentage is modest (women: 24-28%, men: 9-18%). Activity levels are high, exceeding 100 min d -1 of moderate and vigorous physical activity, but daily energy expenditures are similar to industrialized populations. Diets in hunter-gatherer and other small-scale societies tend to be less energy dense and richer in fibre and micronutrients than modern diets but are not invariably low carbohydrate as sometimes argued. A more integrative understanding of hunter-gatherer health and lifestyle, including elements beyond diet and activity, will improve public health efforts in industrialized populations., (© 2018 World Obesity Federation.)

Modifications to the Gram-positive bacterial cell wall play important roles in antibiotic resistance and pathogenesis, but the pathway for the d-alanylation of teichoic acids (DLT pathway), a ubiquitous modification, is poorly understood. The d-alanylation machinery includes two membrane proteins of unclear function, DltB and DltD, which are somehow involved in transfer of d-alanine from a carrier protein inside the cell to teichoic acids on the cell surface. Here, we probed the role of DltD in the human pathogen Staphylococcus aureus using both cell-based and biochemical assays. We first exploited a known synthetic lethal interaction to establish the essentiality of each gene in the DLT pathway for d-alanylation of lipoteichoic acid (LTA) and confirmed this by directly detecting radiolabeled d-Ala-LTA both in cells and in vesicles prepared from mutant strains of S. aureus We developed a partial reconstitution of the pathway by using cell-derived vesicles containing DltB, but no other components of the d-alanylation pathway, and showed that d-alanylation of previously formed lipoteichoic acid in the DltB vesicles requires the presence of purified and reconstituted DltA, DltC, and DltD, but not of the LTA synthase LtaS. Finally, based on the activity of DltD mutants in cells and in our reconstituted system, we determined that Ser-70 and His-361 are essential for d-alanylation activity, and we propose that DltD uses a catalytic dyad to transfer d-alanine to LTA. In summary, we have developed a suite of assays for investigating the bacterial DLT pathway and uncovered a role for DltD in LTA d-alanylation., (© 2018 Wood et al.)