Calorie restriction (CR) extends life span in diverse species. Mitochondria play a key role in CR adaptation; however, the molecular details remain elusive. We developed and applied a quantitative ...mass spectrometry method to probe the liver mitochondrial acetyl-proteome during CR versus control diet in mice that were wild-type or lacked the protein deacetylase SIRT3. Quantification of 3,285 acetylation sites—2,193 from mitochondrial proteins—rendered a comprehensive atlas of the acetyl-proteome and enabled global site-specific, relative acetyl occupancy measurements between all four experimental conditions. Bioinformatic and biochemical analyses provided additional support for the effects of specific acetylation on mitochondrial protein function. Our results (1) reveal widespread reprogramming of mitochondrial protein acetylation in response to CR and SIRT3, (2) identify three biochemically distinct classes of acetylation sites, and (3) provide evidence that SIRT3 is a prominent regulator in CR adaptation by coordinately deacetylating proteins involved in diverse pathways of metabolism and mitochondrial maintenance.
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► MS quantifies 1,578 mitochondrial acetyl sites altered during CR and loss of SIRT3 ► SIRT3 functions as a prominent regulator in CR adaptation ► CR and SIRT3 regulate previously unrecognized processes in mitochondria ► We provide an acetylation atlas for understanding mitochondrial regulation in CR
The social gradient for cardiovascular disease (CVD) onset and outcomes is well established. The American Heart Association’s Social Determinants of Risk and Outcomes of Cardiovascular Disease ...Scientific Statement advocates looking beyond breakthroughs in biological science toward a social determinants approach that focuses on socioeconomic position, race and ethnicity, social support, culture and access to medical care, and residential environments to curb the burden of CVD going forward. Indeed, the benefits of this approach are likely to be far reaching, enhancing the positive effects of advances in CVD related to prevention and treatment while reducing health inequities that contribute to CVD onset and outcomes. It is disappointing that the role of gender has been largely neglected despite being a critical determinant of cardiovascular health. It is clear that trajectories and outcomes of CVD differ by biological sex, yet the tendency for sex and gender to be conflated has contributed to the idea that both are constant or fixed with little room for intervention. Rather, as distinct from biological sex, gender is socially produced. Overlaid on biological sex, gender is a broad term that shapes and interacts with one’s cognition to guide norms, roles, behaviors, and social relations. It is a fluid construct that varies across time, place, and life stage. Gender can interact with biological sex and, indeed, other social determinants, such as ethnicity and socioeconomic position, to shape cardiovascular health from conception, through early life when health behaviors and risk factors are shaped, into adolescence and adulthood. This article will illustrate how gender shapes the early adoption of health behaviors in childhood, adolescence, and young adulthood by focusing on physical activity, drinking, and smoking behaviors (including the influence of role modeling). We will also discuss the role of gender in psychosocial stress with a focus on trauma from life events (childhood assault and intimate partner violence) and work, home, and financial stresses. We conclude by exploring potential biological pathways, with a focus on autonomic functioning, which may underpin gender as a social determinant of cardiovascular health. Finally, we discuss implications for cardiovascular treatment and awareness campaigns and consider whether gender equality strategies could reduce the burden of CVD for men and women at the population level.
E-cigarette use is increasing among adolescents, despite potential harms. Social media messages are a promising way to educate youth about e-cigarettes, yet little is known about what message topics ...and formats will have beneficial impacts for message reception, reach, e-cigarette knowledge, and beliefs about harms.
A national convenience sample of adolescents (n = 928, aged 15–18 years) in high school was recruited for an online experiment. In October 2019, participants were randomized to view one of three social media formats (visual based, quiz, and text only) or a no-message control. Participants in format conditions viewed six unique topics in a random order. Outcomes were e-cigarette knowledge and beliefs. Message reactions and sharing preferences were also assessed among youth who saw social media messages.
Social media messages led to greater knowledge (Cohen's f = .19; p < .001) and beliefs (f = .16; p < .001) about harms of e-cigarettes compared with the control, regardless of format. Almost four in five adolescents (79%) reported they would share the social media messages, most likely in person (49%) and with friends (52%). Message topics for missing out because of lung damage, having uncontrolled moods, and ingesting specific harmful chemicals elicited higher intended message reactions.
Social media messages can educate about e-cigarette harms. Social media campaigns are a promising e-cigarette education strategy to reach youth, directly and potentially through peer-to-peer sharing.
Aim
To summarize developmental delay among infants and toddlers with sickle cell disease (SCD).
Method
This systematic review included studies that reported developmental outcomes of children with ...SCD between 0 months and 48 months of age and followed standards set forth by the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines.
Results
Ten studies were included, describing 596 unique developmental assessments. The rate of developmental delay ranged from 17.5% to 50% and increased with age. Cognition was the only domain included in all studies and the most frequently identified delay. One study reported that more severe SCD genotypes predicted worse development, while five studies reported no difference in rates of developmental delay across genotypes.
Interpretation
These findings emphasize the need for standardized screening to identify children with SCD at risk of delay at a young age to facilitate appropriate referrals for therapeutic intervention. Frequent and comprehensive developmental screening is necessary among all SCD genotypes.
The use of mesenchymal stem cells (MSC) for the treatment of cutaneous wounds is currently of enormous interest. However, the broad translation of cell therapies into clinical use is hampered by ...their efficacy, safety, manufacturing and cost. MSCs release a broad repertoire of trophic factors and immunomodulatory cytokines, referred to as the MSC secretome, that has considerable potential for the treatment of cutaneous wounds as a cell-free therapy. In this review, we outline the current status of MSCs as a treatment for cutaneous wounds and introduce the potential of the MSC secretome as a cell-free alternative for wound repair. We discuss the challenges and provide insights and perspectives for the future development of the MSC secretome as well as identify its potential clinical translation into a therapeutic treatment.
Objective
Following a cancer diagnosis, restricted participation in daily life is common. Restricted participation can be temporary or long lasting. The aim of this study was to characterize how ...daily life participation is impacted following a cancer diagnosis.
Methods
Eligible individuals included adults (>18 years) with any stage/grade brain, breast, colorectal, or lung cancer in any phase of treatment or post‐treatment. Participants completed a semi‐structured interview about how their life participation was impacted following their cancer diagnosis. Data were analyzed through team‐based thematic analysis.
Results
Forty adults, 10 per disease category, participated. Four themes were identified that supported or hindered daily life participation: (1) self‐expectations, (2) expectations of others, (3) awareness of mortality, and (4) symptoms and side effects of cancer. Participants discussed how their cancer experience resulted in a reprioritization of what they valued doing in their life. However, many survivors struggled to adapt and described a tension between their need to adapt to their current life circumstances and their contrasting desire to stay connected with their pre‐cancer selves through daily life participation. The mental health challenges associated with decreased participation were also outlined by participants.
Conclusions
Cancer survivors' daily life participation is influenced by expectations from themselves and others, awareness of mortality, and disease symptoms/side effects. Future interventions can target these domains to supports survivors' life participation.
The rationalization of human life in work, feeling, and relationships is amplified by artificial intelligence (AI), apps and automation, challenging interpersonal workers not only in how and whether ...they do their work, but also how they understand themselves as human. Given these trends, how do interpersonal workers interpret the humanness of their work? To answer this question, I focus on the interactive service work I call “connective labor,” relying on 80+ in-depth interviews and 300+ hours of ethnographic observations with teachers, therapists and primary care physicians in the San Francisco Bay Area and mid-Atlantic United States, as well as with less advantaged practitioners such as sex workers, hairdressers, and home health care aides. I found that these interpersonal workers differentiated themselves from AI, automated agents, and robots in three ways: (1) by describing and defending their work as not rote, (2) taking pains to prove that they were not robots, and (3) justifying their judgments as safe, unique, and worthwhile. Much of their case rested on the unpredictability of humans, in terms of feelings, secrets, and mistakes. These findings have implications for race, class, and gender inequality, as advantage shaped how people were able to demand, perform, or experience their humanness in the ways that the proliferation of algorithmic technologies made salient.
The receptor binding domain (RBD) of the SARS-CoV-2 spike glycoprotein mediates viral attachment to ACE2 receptor and is a major determinant of host range and a dominant target of neutralizing ...antibodies. Here, we experimentally measure how all amino acid mutations to the RBD affect expression of folded protein and its affinity for ACE2. Most mutations are deleterious for RBD expression and ACE2 binding, and we identify constrained regions on the RBD’s surface that may be desirable targets for vaccines and antibody-based therapeutics. But a substantial number of mutations are well tolerated or even enhance ACE2 binding, including at ACE2 interface residues that vary across SARS-related coronaviruses. However, we find no evidence that these ACE2-affinity-enhancing mutations have been selected in current SARS-CoV-2 pandemic isolates. We present an interactive visualization and open analysis pipeline to facilitate use of our dataset for vaccine design and functional annotation of mutations observed during viral surveillance.
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•Measured effects on folding and ACE2 binding of all mutations to the SARS-CoV-2 RBD•Provide open data and interactive visualization for vaccine design and surveillance•Identify constrained surfaces as ideal targets for vaccines and antibody therapeutics•Mutations that enhance ACE2 affinity exist but are not selected in pandemic isolates
Starr et al. systematically change every amino acid in the receptor binding domain (RBD) of the SARS-CoV-2 spike protein and determine the effects of the substitutions on RBD expression, folding, and ACE2 binding. The work identifies structurally constrained regions of the spike RBD that would be ideal targets for COVID-19 countermeasures and demonstrates that mutations in the virus that enhance ACE2 affinity can be engineered but have not, to date, been naturally selected during the pandemic.
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