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The biological rhythms generated by the endogenous circadian clocks across the tree of life regulate numerous behavioural, metabolic and physiological processes. Although evidence from various studies in Drosophila melanogaster indicates the importance of the core circadian clock genes in the intricate interplay between the circadian clock and metabolism, little is known about the contribution of the circadian photoreceptor/s in this process. The deep brain circadian photoreceptor CRYPTOCHROME (CRY) is essential for resetting the clock in response to light and is also highly expressed in metabolically active tissues in Drosophila. In this study, we sought to explore the possible roles played by CRY in triglyceride metabolism. We observed that the cry mutant (cry01) flies exhibited increased starvation resistance and triglyceride levels under both 12-hour (h) light:12 h dark cycle (LD) and under constant light (LL) compared to the control w1118 flies. We also observed that cry01 flies had significantly increased food intake, glycogen concentrations and life span under LD. In addition, cryptochrome seemed to affect triglyceride levels in adult flies in response to calorie-restricted and high-fat diets. These results suggest a role for the circadian photoreceptor CRY in triglyceride metabolism in Drosophila.

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Beyond the specific cognitive capacities like numerical or verbal intelligence and cognitive speed, the so-called soft skills, namely, psychological capacities, have become highly important in modern life. This is the first representative study on the distribution of work-relevant psychological capacities in the general population. We investigate capacities in different age groups, gender, and their relation with basic sociodemographics. A representative sample of 2531 people aged 14-95 years was investigated concerning work-relevant psychological capacities with the mini self-rating for psychological activities and participation (Mini-ICF-APP-S). The strongest capacities in young people were mobility, flexibility, proactivity, contact to thirds, and group interaction. Other capacities were stronger in midlife (30-59 years), such as adjustment to rules and routines, planning and structuring, decision making and judgement, application of competence and knowledge, assertiveness, dyadic relationships, endurance, and self-care. Women reported better dyadic relationship capacities, and men felt more assertive. The study provides, for the first time, representative data on a broad range of psychological capacities according to an internationally validated capacity concept. Good psychological capacities occur not primarily in youth, but especially in midlife and older age. Regarding demographic change, this implies older people are highly competent in the working world.

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INTRODUCTION: Aspartame, invented in 1965 by GD-Searle, is an intense artificial sweetener taste approximately 200 times as sweet as sucrose and used as an additive in more than 6,000 products. Aspartame (APM) was submitted for pre-marketing safety evaluation in early 1980. The studies, performed by GD-Searle, produced controversial results. AREAS COVERED: Because of the great commercial diffusion of aspartame, in 1997 the Ramazzini Institute (RI) started a large experimental project on rodents to test the carcinogenic effects of aspartame following an experimental model with more sensitive characteristics, namely a large number of rat and mice, starting treatment from prenatal life, observation until spontaneous death. Overall, the project included studying 2270 rats and 852 mice. These studies have shown that aspartame is a carcinogenic agent in experimental animals, inducing a significant dose-related increased incidence of several types of malignant tumors and, among them, hematological neoplasia, and liver cancer. EXPERT OPINION: The results of these studies on aspartame by the Ramazzini Institute opened a real front on the evaluation of artificial sweeteners and their possible health risks. Adequate long-term carcinogenicity bioassays on other diffuse artificial sweeteners such as acesulfame-k, sucralose, saccharin, including their blends, are likewise important for public health.

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Serine proteases are important regulators of airway epithelial homeostasis. Altered serum or cellular levels of two serpins, Scca1 and Spink5, have been described for airway diseases but their function beyond antiproteolytic activity is insufficiently understood. To close this gap, we generated fly lines with overexpression or knockdown for each gene in the airways. Overexpression of both fly homologues of Scca1 and Spink5 induced the growth of additional airway branches, with more variable results for the respective knockdowns. Dysregulation of Scca1 resulted in a general delay in fruit fly development, with increases in larval and pupal mortality following overexpression of this gene. In addition, the morphological changes in the airways were concomitant with lower tolerance to hypoxia. In conclusion, the observed structural changes of the airways evidently had a strong impact on the airway function in our model as they manifested in a lower physical fitness of the animals. We assume that this is due to insufficient tissue oxygenation. Future work will be directed at the identification of key molecular regulators following the airway-specific dysregulation of Scca1 and Spink5 expression.

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As an introduction to this special issue on geroscience, the present work focuses on the complexity of disentangling biomolecular mechanisms of aging from biopsychosocial causes of accelerated aging. Due to this complexity, the biomolecular aging hallmarks of frailty and multimorbidity as predominant aging phenotypes in geriatrics reflect single aspects of the aging process. A possible approach to facilitate the integration of geroscience into healthcare might be to consider aging as the dynamic ratio between damage accumulation at the molecular and cellular level and resilience as strategies that prevent or repair such damage. There is a large body of evidence to show that geroscience has the potential to change healthcare; however, reaching a consensus and translating the best tool to measure aging needs more research on 1) the sensitivity of biomarkers to interventions and 2) the relationship between changes in biomarkers and changes in health trajectories.

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Emerging theories emphasize the crucial role of allostasis (anticipatory and adaptive regulation of the body's biological processes) and interoception (integration, anticipation, and regulation of internal bodily states) in adjusting physiological responses to environmental and bodily demands. In this review, we explore the disruptions in integrated allostatic interoceptive mechanisms in psychiatric and neurological disorders, including anxiety, depression, Alzheimer's disease, and frontotemporal dementia. We assess the biological mechanisms associated with allostatic interoception, including whole-body cascades, brain structure and function of the allostatic interoceptive network, heart-brain interactions, respiratory-brain interactions, the gut-brain-microbiota axis, peripheral biological processes (inflammatory, immune), and epigenetic pathways. These processes span psychiatric and neurological conditions and call for developing dimensional and transnosological frameworks. We synthesize new pathways to understand how allostatic interoceptive processes modulate interactions between environmental demands and biological functions in brain disorders. We discuss current limitations of the framework and future transdisciplinary developments. This review opens a new research agenda for understanding how allostatic interoception involves brain predictive coding in psychiatry and neurology, allowing for better clinical application and the development of new therapeutic interventions.

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BACKGROUND: Work-life balance is associated with many positive effects at multiple levels and demands increased research attention. In the international literature on work-life balance, the term "gendered life-course" has been used to describe the differences between men and women in work biographies. However, whether this term applies to the Nordic work context remains underexplored. OBJECTIVE: This study examined Finnish men's and women's subjective experience of the association between work-life balance and the psychosocial work environment (work demands and social support at work) across the life course, devoting special attention to family life stages encompassing the care of (young) children. METHODS: Data from the Quality of Work Life Survey 2018 were utilized to conduct binary logistic regression analyses (N = 3790). Separate analyses were conducted for men and women. RESULTS: A significant association between family life stage and high work-life balance was found for women but not for men in the Finnish working life. Women in family life stages involving the care of young, dependent children reported the lowest odds of high work-life balance. For both men and women, a positive association between social support at work and high work-life balance was found, while a negative association was found between work demands and high work-life balance. CONCLUSIONS: These findings highlight the importance of psychosocial factors in both the work and family settings for work-life balance. Further, the findings call for an expanded focus on gender equality, also including issues in unpaid work in addition to issues in paid work.

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Bismuth oxide (Bi2O3) materials are considered as great promising anodes for aqueous batteries on account of the high capacity as well as wide potential plateau. Nevertheless, the low conductivity and severe volumetric change of Bi2O3 in the course of cycling are the main limiting factors for their application in energy-storage systems. Herein, we propose and design unique hierarchical heterostructures constructed by Bi2O3 and Bi2S3 nanosheets (NSs) manufactured immediately on the surface of carbon nanotube fibers (CNTFs). The Bi2O3-Bi2S3 (BO-BS) exhibits enhanced conductivity and increased stability in comparison with pure Bi2O3 and Bi2S3. The BO-BS NSs/CNTF electrode indicates exceptional rate capability and cycling stability, while creating a high reversible capacity of 0.68 mAh cm-2 at 4 mA cm-2, as anticipated. Additionally, the quasi-solid-state fibrous aqueous Ni//Bi battery that was built with the BO-BS NSs/CNTF anode delivers an exceptional cycling stability of 52.7% capacity retention after 4000 cycles at 80 mA cm-2, an ultrahigh capacity of 0.35 mAh cm-2 at 4 mA cm-2, and a high energy density of 340.1 mWh cm-3 at 880 mW cm-3. This work demonstrates the potential of constructing hierarchical heterostructures of bismuth-based materials for high-performance aqueous Ni//Bi batteries and other energy-storage devices.

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Although epigenetic age acceleration (EAA) might serve as a molecular signature of childhood cardiovascular disease (CVD) risk factors and further promote midlife subclinical CVD, few studies have comprehensively examined these life course associations. This study sought to test whether childhood CVD risk factors predict EAA in adulthood and whether EAA mediates the association between childhood CVD risks and midlife subclinical disease. Among 1,580 Bogalusa Heart Study participants, we estimated extrinsic EAA, intrinsic EAA, PhenoAge acceleration (PhenoAgeAccel), and GrimAge acceleration (GrimAgeAccel) during adulthood. We tested prospective associations of longitudinal childhood body mass index (BMI), blood pressure, lipids, and glucose with EAAs using linear mixed effects models. After confirming EAAs with midlife carotid intima-media thickness and carotid plaque, structural equation models examined mediating effects of EAAs on associations of childhood CVD risk factors with subclinical CVD measures. After stringent multiple testing corrections, each SD increase in childhood BMI was significantly associated with 0.6-, 0.9-, and 0.5-year increases in extrinsic EAA, PhenoAgeAccel, and GrimAgeAccel, respectively (P < 0.001 for all 3 associations). Likewise, each SD increase in childhood log-triglycerides was associated with 0.5- and 0.4-year increases in PhenoAgeAccel and GrimAgeAccel (P < 0.001 for both), respectively, whereas each SD increase in childhood high-density lipoprotein cholesterol was associated with a 0.3-year decrease in GrimAgeAccel (P = 0.002). Our findings indicate that PhenoAgeAccel mediates an estimated 27.4% of the association between childhood log-triglycerides and midlife carotid intima-media thickness (P = 0.022). Our data demonstrate that early life CVD risk factors may accelerate biological aging and promote subclinical atherosclerosis.

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Congenital heart diseases (or congenital heart defects/disorders; CHDs) are structural abnormalities of the heart and/or great vessels that are present at birth. CHDs include an extensive range of defects that may be minor and require no intervention or may be life-limiting and require complex surgery shortly after birth. This chapter reviews the current knowledge on the genetic causes of CHD.

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Individuals constantly exert inhibitory control over their thoughts and behaviors to plan actions that compete with habits and impulses. Cognitive inhibition enhances the selection of task-relevant stimuli and is closely related to neural changes that occur across the lifespan. Since few studies have focused on the entire lifespan, this study aimed to assess cognitive inhibition abilities in a sample of 425 healthy participants (age range: 7-88 years) using the Stroop task. The participants were grouped according to age into children, adolescents, young adults, adults, middle-aged adults, and older adults. A series of ANOVAs considered Group as the independent variable and Performance indices as the dependent variables. The children did not show an interference effect (Stroop effect), likely due to the lack of an automated reading process as a consequence of ongoing brain maturation. Adolescents and young adults performed significantly faster than older adults did. The results indicate that response speed reaches its peak during adolescence and young adulthood and then slightly decreases until older age. Nevertheless, when compared with the other groups, only older adults showed significant differences in the Stroop effect, suggesting that inhibitory abilities remain relatively consistent throughout adulthood but rapidly worsen in recent years due to the physiological decline in cognitive and brain functioning associated with aging.

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OBJECTIVES: Numerous theories exist regarding age differences in risk preference and related constructs, yet many of them offer conflicting predictions and fail to consider convergence between measurement modalities or constructs. To pave the way for conceptual clarification and theoretical refinement, in this preregistered study we aimed to comprehensively examine age effects on risk preference, impulsivity, and self-control using different measurement modalities, and to assess their convergence. METHODS: We collected a large battery of self-report, informant report, behavioral, hormone, and neuroimaging measures from a cross-sectional sample of 148 (55% female) healthy human participants between 16 and 81 years (mean age = 46 years, standard deviation [SD] = 19). We used an extended sample of 182 participants (54% female, mean age = 46 years, SD = 19) for robustness checks concerning the results from self-reports, informant reports, and behavioral measures. For our main analysis, we performed specification curve analyses to visualize and estimate the convergence between the different modalities and constructs. RESULTS: Our multiverse analysis approach revealed convergent results for risk preference, impulsivity, and self-control from self- and informant reports, suggesting a negative effect of age. For behavioral, hormonal, and neuroimaging outcomes, age effects were mostly absent. DISCUSSION: Our findings call for conceptual clarification and improved operationalization to capture the putative mechanisms underlying age-related differences in risk preference and related constructs.

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The Office of Research on Women's Health (ORWH)'s whole health paradigm expands the scope of women's health research, incorporating a life-course perspective that recognizes the profound influences of sex and gender on health. From childhood through adulthood, external and societal factors along with internal factors and biology shape women's health and influence access to quality healthcare. This comprehensive approach integrates data-driven sex- and gender-aware strategies to prevent, diagnose, and treat disease, focusing on the unique needs of women. Acknowledging the historical lack of timely research and data on women's health, an initiative led by First Lady Dr. Jill Biden and the White House Gender Policy Council, ushers in a new era of women's health research that offers unprecedented opportunities to enhance the health of women through biomedical and behavioral research. The initiative fosters interdisciplinary collaboration, supporting research on autoimmune diseases, menopause, oral health, and chronic pain conditions. ORWH serves as the focal point for National Institutes of Health (NIH) women's health research. With a commitment to advancing holistic outcomes, ORWH engages in partnerships, outreach, and educational initiatives to disseminate critical research findings and support women's health researchers. Here we describe the convergence of this initiative with the National Institute of Dental and Craniofacial Research's work to advance the understanding of sex as a biological variable for conditions such as Sjogren's disease and temporomandibular disorder. This transformative approach to women's health research propels the United States toward innovative solutions, ensuring that science works for the health and well-being of every woman.

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BACKGROUND AND AIMS: There is ample theoretical and experimental evidence that angiosperms harbouring self-incompatibility (SI) systems are likely to respond to global changes in unique ways relative to taxa with other mating systems. In this paper, we present an updated database on the prevalence of SI systems across angiosperms and examine the relationship between the presence of SI and latitude, biomes, life-history traits and management conditions to evaluate the potential vulnerability of SI taxa to climate change and habitat disturbance. METHODS: We performed literature searches to identify studies that employed controlled crosses, microscopic analyses and/or genetic data to classify taxa as having SI, self-compatibility (SC), partial self-compatibility (PSC) or self-sterility (SS). Where described, the site of the SI reaction and the presence of dimorphic versus monomorphic flowers were also recorded. We then combined this database on the distribution of mating systems with information about the life span, growth habit, management conditions and geographic distribution of taxa. Information about the geographic distribution of taxa was obtained from a manually curated version of the Global Biodiversity Information Facility database, and from vegetation surveys encompassing 9 biomes. We employed multinomial logit regression to assess the relationship between mating system and life-history traits, management condition, latitude and latitude-squared using self-compatible taxa as the baseline. Additionally, we employed LOESS regression to examine the relationship between the probability of SI and latitude. Finally, by summarizing information at the family level, we plotted the distribution of SI systems across angiosperms including information about the presence of SI or dioecy, the inferred reaction site of the SI system when known, as well as the proportion of taxa in a family for which information is available. KEY RESULTS: We obtained information about the SI status of 5686 hermaphroditic taxa, of which 55% exhibited SC, and the remaining 45% harbour SI, self-sterility (SS), or PSC. Highlights of the multinomial logit regression include that taxa with PSC have a greater odds of being short- (OR=1.3) or long- (OR=1.57) lived perennials relative to SC ones, and that SS/SI taxa (pooled) are less likely to be annuals (OR=0.64) and more likely to be long-lived perennials (OR=1.32). SS/SI taxa had a greater odds of being succulent (OR=2.4) or a tree (OR=2.05), and were less likely to be weeds (OR=0.34). Further, we find a quadratic relationship between the probability of being SI with latitude: SI taxa were more common in the tropics, a finding that was further supported by the vegetation surveys which showed fewer species with SS/SI in temperate and northern latitudes compared to mediterranean and tropical biomes. CONCLUSIONS: We conclude that in the short-term habitat fragmentation, pollinator loss and temperature increases may negatively impact plants with SI systems, particularly long-lived perennial and woody species dominant in tropical forests. In the longer term, these and other global changes are likely to select for self-compatible or partially self-compatible taxa which, due to the apparent importance of SI as a driver of plant diversification across the angiosperm tree of life, may globally influence plant species richness.

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What develops in adulthood? More specifically, what develops in adult analysis, not just in terms of thwarted childhood capacities, not just through accrued experience, but even more fundamentally in terms of abilities or structures not possible until the present moment? In this paper, I posit narrative capacity-the capacity to organize conflictual aspects of self and other in a temporary causal-motivational sequence-as a core feature of what develops in the clinical encounter between the analyst and adult patient. It develops, as I demonstrate, through play with narrative fragments, contrasts, and integrations in the analytic field. I present a clinical process note to show how these elements texture and problematize one another. A successful analysis leads not to any one life story but to the more basic ability to weave and unweave our stories.

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Neural variability is thought to facilitate survival through flexible adaptation to changing environmental demands. In humans, such capacity for flexible adaptation may manifest as fluid reasoning, inhibition of automatic responses, and mental set-switching-skills falling under the broad domain of executive functions that fluctuate over the life span. Neural variability can be quantified via the BOLD signal in resting-state fMRI. Variability of large-scale brain networks is posited to underpin complex cognitive activities requiring interactions between multiple brain regions. Few studies have examined the extent to which network-level brain signal variability across the life span maps onto high-level processes under the umbrella of executive functions. The present study leveraged a large publicly available neuroimaging dataset to investigate the relationship between signal variability and executive functions across the life span. Associations between brain signal variability and executive functions shifted as a function of age. Limbic-specific variability was consistently associated with greater performance across subcomponents of executive functions. Associations between executive function subcomponents and network-level variability of the default mode and central executive networks, as well as whole-brain variability, varied across the life span. Findings suggest that brain signal variability may help to explain to age-related differences in executive functions across the life span.

Traditionally, regional variability in brain signals has been viewed as a source of noise in human neuroimaging research. Our study demonstrates that brain signal variability may contain meaningful information related to psychological processes. We demonstrate that brain signal variability, particularly whole-brain variability, may serve as a reliable indicator of cognitive functions across the life span. Global variability and network-level variability play differing roles in supporting executive functions. Findings suggest that brain signal variability serves as a meaningful indicator of development and cognitive aging.

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The large conductance, calcium, and voltage-active potassium channels (BKCa) were originally discovered in Drosophila melanogaster as slowpoke (slo). They are extensively characterized in fly models as ion channels for their roles in neurological and muscular function, as well as aging. BKCa is known to modulate cardiac rhythm and is localized to the mitochondria. Activation of mitochondrial BKCa causes cardioprotection from ischemia-reperfusion injury, possibly via modulating mitochondrial function in adult animal models. However, the role of BKCa in cardiac function is not well-characterized, partially due to its localization to the plasma membrane as well as intracellular membranes and the wide array of cells present in mammalian hearts. Here we demonstrate for the first time a direct role for BKCa in cardiac function and cardioprotection from IR injury using the Drosophila model system. We have also discovered that the BKCa channel plays a role in the functioning of aging hearts. Our study establishes the presence of BKCa in the fly heart and ascertains its role in aging heart function.

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OBJECTIVE: To examine the association between changes in self-reported neighborhood stressors and sleep quality and determine whether this varied by sociocultural context among Puerto Rican young adults. METHODS: Data come from the Boricua Youth Study Health Assessment, a sample of Puerto Rican young adults from San Juan, Puerto Rico, and South Bronx, New York (n = 818; mean age=22.9years). Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). Neighborhood social stressors (disorder, social cohesion, and safety) were parent-reported in childhood and self-reported in young adulthood and categorized into: low in childhood/young adulthood (reference group), high in childhood/low in young adulthood, low in childhood/high in young adulthood, and high in childhood/young adulthood. Sociocultural context was based on participant residence during childhood (San Juan vs. South Bronx). RESULTS: Adjusting for sociodemographic factors, living with high neighborhood stressors in both childhood and young adulthood (prevalence ratios=1.30, 95% CI: 1.01, 1.66) was associated with overall poor sleep (PSQI score >5). Among PSQI components, living with high neighborhood stressors in young adulthood only or in both time periods was associated with worse subjective sleep quality and daytime dysfunction. Additionally, there were various associations between the neighborhood stressor measures and PSQI components. Results did not differ by sociocultural context. CONCLUSION: Findings suggest that living with high levels of neighborhood stressors during childhood and young adulthood may have a cumulative adverse impact on sleep quality in young adulthood.

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Macrophage niches are the anatomical locations within organs or tissues consisting of various cells, intercellular and extracellular matrix, transcription factors, and signaling molecules that interact to influence macrophage self-maintenance, phenotype, and behavior. The niche, besides physically supporting macrophages, imposes a tissue- and organ-specific identity on the residing and infiltrating monocytes and macrophages. In this review, we give examples of macrophage niches and the modes of communication between macrophages and surrounding cells. We also describe how macrophages, acting against their immune defensive nature, can create a hospitable niche for pathogens and cancer cells.

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The development of mathematical models capable of predicting the lifespan of animals is growing. However, there are no studies that compare the predictive power of different sets of parameters depending on the age of the animals. The aim of the present study is to test whether mathematical models for life span prediction developed in adult female mice based on immune, redox, and behavioral parameters can predict life span in old animals and to develop new models in old mice. For this purpose, 29 variables, including parameters of immune function, redox state, and behavioral ones, were evaluated in old female Swiss mice (80 ± 4 weeks). Life span was registered when they died naturally. Firstly, we observed that the models developed in adults were not able to accurately predict the life span of old mice. Therefore, the immunity (adjusted R2 = 73.6%), redox (adjusted R2 = 46.5%), immunity-redox (adjusted R2 = 96.4%), and behavioral (adjusted R2 = 67.9%) models were developed in old age. Finally, the models were validated in another batch of mice. The developed models in old mice show certain similarities to those in adults but include different immune, redox, and behavioral markers, which highlights the importance of age in the prediction of life span.

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