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As the demographics of the modern world skew older, understanding and mitigating the effects of aging is increasingly important within biomedical research. Recent studies in model organisms demonstrate that the aging process is frequently modified by an organism’s ability to perceive and respond to changes in its environment. Many well-studied pathways that influence aging involve sensory cells, frequently neurons, that signal to peripheral tissues and promote survival during the presence of stress. Importantly, this activation of stress response pathways is often sufficient to improve health and longevity even in the absence of stress. Here, we review the current landscape of research highlighting the importance of cell non-autonomous signaling in modulating aging from C. elegans to mammals. We also discuss emerging concepts including retrograde signaling, approaches to mapping these networks, and development of potential therapeutics.

An organism’s ability to perceive and respond to changes in its environment is crucial for its health and survival. Here we reveal how the most well-studied longevity intervention, dietary restriction, acts in-part through a cell non-autonomous signaling pathway that is inhibited by the presence of attractive smells. Using an intestinal reporter for a key gene induced by dietary restriction but suppressed by attractive smells, we identify three compounds that block food odor effects in C. elegans , thereby increasing longevity as dietary restriction mimetics. These compounds clearly implicate serotonin and dopamine in limiting lifespan in response to food odor. We further identify a chemosensory neuron that likely perceives food odor, an enteric neuron that signals through the serotonin receptor 5-HT1A/SER-4, and a dopaminergic neuron that signals through the dopamine receptor DRD2/DOP-3. Aspects of this pathway are conserved in D. melanogaster . Thus, blocking food odor signaling through antagonism of serotonin or dopamine receptors is a plausible approach to mimic the benefits of dietary restriction. This report finds that dietary restriction, the most extensively studied anti-aging intervention, can be mimicked by blocking food odour signaling and identifies a neural network of food perception that functions through serotonin and dopamine.

Flavin containing monooxygenases (FMOs) are promiscuous enzymes known for metabolizing a wide range of exogenous compounds. In C. elegans , fmo-2 expression increases lifespan and healthspan downstream of multiple longevity-promoting pathways through an unknown mechanism. Here, we report that, beyond its classification as a xenobiotic enzyme, fmo-2 expression leads to rewiring of endogenous metabolism principally through changes in one carbon metabolism (OCM). These changes are likely relevant, as we find that genetically modifying OCM enzyme expression leads to alterations in longevity that interact with fmo-2 expression. Using computer modeling, we identify decreased methylation as the major OCM flux modified by FMO-2 that is sufficient to recapitulate its longevity benefits. We further find that tryptophan is decreased in multiple mammalian FMO overexpression models and is a validated substrate for FMO-2. Our resulting model connects a single enzyme to two previously unconnected key metabolic pathways and provides a framework for the metabolic interconnectivity of longevity-promoting pathways such as dietary restriction. FMOs are well-conserved enzymes that are also induced by lifespan-extending interventions in mice, supporting a conserved and important role in promoting health and longevity through metabolic remodeling. Flavin containing monooxygenase 2 (FMO-2) is known to increase lifespan under dietary restriction through incompletely understood mechanisms. Here the authors report that FMO-2 modifies tryptophan and methionine metabolic pathways to enhance stress resistance and slow aging in C. elegans .

Stabilization of the hypoxia-inducible factor 1 (HIF-1) increases life span and health span in nematodes through an unknown mechanism. We report that neuronal stabilization of HIF-1 mediates these effects in Caenorhabditis elegans through a cell nonautonomous signal to the intestine, which results in activation of the xenobiotic detoxification enzyme flavincontaining monooxygenase-2 (FMO-2). This prolongevity signal requires the serotonin biosynthetic enzyme TPH-1 in neurons and the serotonin receptor SER-7 in the intestine. Intestinal FMO-2 is also activated by dietary restriction (DR) and is necessary for DR-mediated life-span extension, which suggests that this enzyme represents a point of convergence for two distinct longevity pathways. FMOs are conserved in eukaryotes and induced by multiple life span–extending interventions in mice, which suggests that these enzymes may play a critical role in promoting health and longevity across phyla.

Caenorhabditis elegans is an instrumental research model used to advance our knowledge in areas including development, metabolism, and aging. However, research on metabolism and/or other measures of health/aging are confounded by the nematode’s food source in the lab, live E. coli bacteria. Commonly used treatments, including ultraviolet irradiation and antibiotics, are successful in preventing bacterial replication, but the bacteria can remain metabolically active. The purpose of this study is to develop a metabolically inactive food source for the worms that will allow us to minimize the confounding effects of bacterial metabolism on worm metabolism and aging. Our strategy is to use a paraformaldehyde (PFA) treated E. coli food source and to determine its effects on worm health, metabolism and longevity. We initially determine the lowest possible concentrations of PFA necessary to rapidly and reproducibly kill bacteria. We then measure various aspects of worm behavior, healthspan and longevity, including growth rate, food attraction, brood size, lifespan and metabolic assessments, such as oxygen consumption and metabolomics. Our resulting data show that worms eat and grow well on these bacteria and support the use of 0.5% PFA-killed bacteria as a nematode food source for metabolic, drug, and longevity experiments.Beydoun, Choi et al. develop a metabolically inactive food source for C. elegans worms that minimizes the confounding effects of bacterial metabolism on worm metabolism and aging. They find that worms eat and grow well on a paraformaldehyde (PFA)-treated E. coli food source, recommending the use of 0.5% PFA-killed bacteria as a nematode food source for metabolic experiments.

IntroductionOpioid use disorder affects 2.1 million individuals in the USA, causing more than 100 000 overdose-related deaths annually. While the neurobiological model of addiction is well described and accepted, there is a lack of morbidity and mortality prognosticators for patients struggling with opioid use disorder. Allostatic load index is a promising candidate for the basis of a prognostication tool. Previous studies show that allostatic load predicts both morbidity and mortality in a variety of cohorts. This scoping review protocol provides the rationale and steps for summarising and presenting existing evidence surrounding allostatic load in the context of opioid use disorder. Identification of current knowledge gaps will pave the way for subsequent prospective studies.Methods and analysisThis scoping review protocol will follow the five-step method designed by Arksey and O’Malley. All studies written in English on allostatic load in the context of opioid use disorder, as defined in our inclusion criteria, will be included. There will be no limit on the year of publication. We will search PubMed, Embase, CINAHL, PsycINFO and Google Scholar. We will hand-review reference lists of included articles, and we will hand search grey literature. We will then group, analyse and present the data in narrative, tabular and diagrammatic format according to themes identified in the scoping review.Ethics and disseminationEthics approval is not necessary, as data are gathered from publicly accessible sources. The results will be disseminated through a peer-reviewed journal and reported at conferences related to addiction medicine.Trial registration number10.17605/OSF.IO/4J6DQ.

Background Angelman syndrome (AS) is a neurodevelopmental disorder associated with severe global developmental delay. However, the ages at which different developmental skills are achieved in these individuals remain unclear. We seek to determine the probability and the age of acquisition of specific developmental milestones and daily living skills in individuals with AS across the different molecular subtypes, viz. class I deletion, class II deletion, uniparental disomy, imprinting defect, and UBE3A variants. Methods Caregivers participating in a longitudinal multicenter Angelman Syndrome Natural History Study completed a questionnaire regarding the age at which their children achieved specific developmental milestones and daily living skills. The Cox Proportional Hazard model was applied to analyze differences in the probability of achievement of skills at various ages among five molecular subtypes of AS. Results Almost all individuals, regardless of molecular subtype, were able to walk with support by five years of age. By age 15, those with a deletion had at least a 50% probability of acquiring 17 out of 30 skills compared to 25 out of 30 skills among those without a deletion. Overall, fine and gross motor skills such as holding and reaching for small objects, sitting, and walking with support were achieved within a fairly narrow range of ages, while toileting, feeding, and hygiene skills tend to have greater variability in the ages at which these skills were achieved. Those without a deletion had a higher probability (25–92%) of achieving daily living skills such as independently toileting and dressing compared to those with a deletion (0–13%). Across all molecular subtypes, there was a low probability of achieving independence in bathing and brushing teeth. Conclusion Individuals with AS without a deletion are more likely to achieve developmental milestones and daily living skills at an earlier age than those with a deletion. Many individuals with AS are unable to achieve daily living skills necessary for independent self-care.

Since its founding in 1980, the WOOSTER GROUP has developed practices that heighten theatrical contrasts; they are known for experimental pieces that juxtapose historical reenactments with surprising texts and technologically mediated relations between performers on stage. The Wooster Group's métier offers a symbiotic platform for Johnston's contradictions and ambivalences in the 1970s—a crucial decade for the development of feminist/queer activism and thought as well as the postmodern avant-garde on stage.14 The Town Hall Affair addresses these two currents simultaneously; Johnston's presence on the stage of Mailer's event and within the feminist movement doubles as an encounter in the present with the Wooster Group's own practices and influences. José Esteban Muñoz considers Johnston a model \"of queer presence in the public sphere that preceded current models\" of political pragmatism; Sally Banes marvels at Johnston's dance criticism for its attention to the \"chaotic, messy, raw vitality of movement and materials\"; Sara Warner theorizes Johnston's performance protests as queer \"joker citizenship\".15 Dance scholar Clare Croft builds on these foundations; she writes of Johnston's \"lesbian dancing body as a form of public disruption\" and her resonance in the lesbian archive.16 Art historian Jennifer Sichel focuses on the intertwined careers of Johnston, Gene Swendon, and Andy Warhol.17 Much of this work is motivated by a desire to address the caricaturing of Johnston's contributions as reducible to the (often misunderstood) ideology of lesbian separatism. The same impetus has led artists and curators to also mount their own performative returns to Johnston, frequently relying on archival materials to communicate the elided political and aesthetic phases of her biography and career.18 This attention has contributed nuance and precision to understandings of Johnston in feminist and art history; the Johnston at the center of her autobiographical writings—Valk's Johnston—remains a restless subject who insistently resists categorization.

INTRODUCTION There is a growing body of accepted author manuscripts (AAMs) in national, professional, and institutional repositories. This study seeks to explore librarian attitudes about AAMs and in what contexts they should be recommended. Particular attention is paid to differences between the attitudes of librarians whose primary job responsibilities are within the field of scholarly communications as opposed to the rest of the profession. METHODS An Internet survey was sent to nine different professional listservs, asking for voluntary anonymous participation. RESULTS This study finds that AAMs are considered an acceptable source by many librarians, with scholarly communications librarians more willing to recommend AAMs in higher-stakes contexts such as health care and dissertation research. DISCUSSION Librarian AAM attitudes are discussed, with suggestions for future research and implications for librarians.