Aging gracefully: social engagement joins exercise and enrichment as a key lifestyle factor in resistance to age-related cognitive decline

Cognitive impairment is a consequence of the normal aging process that effects many species, including humans and rodent models. Decline in hippocampal memory function is especially prominent with age and often reduces quality of life. As the aging population expands, the need for interventional strategies to prevent cognitive decline has become more pressing. Fortunately, several major lifestyle factors have proven effective at combating hippocampal aging, the most well-known of which are environmental enrichment and exercise. While the evidence supporting the beneficial nature of these factors is substantial, a less well-understood factor may also contribute to healthy cognitive aging: social engagement. We review the evidence supporting the role of social engagement in preserving hippocampal function in old age. In elderly humans, high levels of social engagement correlate with better hippocampal function, yet there is a dearth of work to indicate a causative role. Existing rodent literature is also limited but has begun to provide causative evidence and establish candidate mechanisms. Summed together, while many unanswered questions remain, it is clear that social engagement is a viable lifestyle factor for preserving cognitive function in old age. Social integration across the lifespan warrants more investigation and more appreciation when designing living circumstances for the elderly

Myogenic Progenitor Cells Control Extracellular Matrix Production by Fibroblasts during Skeletal Muscle Hypertrophy

Satellite cells, the predominant stem cell population in adult skeletal muscle, are activated in response to hypertrophic stimuli and give rise to myogenic progenitor cells (MPCs) within the extracellular matrix (ECM) that surrounds myofibers. This ECM is composed largely of collagens secreted by interstitial fibrogenic cells, which influence satellite cell activity and muscle repair during hypertrophy and aging. Here we show that MPCs interact with interstitial fibrogenic cells to ensure proper ECM deposition and optimal muscle remodeling in response to hypertrophic stimuli. MPC-dependent ECM remodeling during the first week of a growth stimulus is sufficient to ensure long-term myofiber hypertrophy. MPCs secrete exosomes containing miR-206, which represses Rrbp1, a master regulator of collagen biosynthesis, in fibrogenic cells to prevent excessive ECM deposition. These findings provide insights into how skeletal stem and progenitor cells interact with other cell types to actively regulate their extracellular environments for tissue maintenance and adaptation

Myonuclear Transcription is Responsive to Mechanical Load and DNA Content but Uncoupled from Cell Size During Hypertrophy

Myofibers increase size and DNA content in response to a hypertrophic stimulus, thus providing a physiological model with which to study how these factors affect global transcription. Using 5-ethynyl uridine (EU) to metabolically label nascent RNA, we measured a sevenfold increase in myofiber transcription during early hypertrophy before a change in cell size and DNA content. The typical increase in myofiber DNA content observed at the later stage of hypertrophy was associated with a significant decrease in the percentage of EU-positive myonuclei; however, when DNA content was held constant by preventing myonuclear accretion via satellite cell depletion, both the number of transcriptionally active myonuclei and the amount of RNA generated by each myonucleus increased. During late hypertrophy, transcription did not scale with cell size, as smaller myofibers (\u3c 1000 μm2) demonstrated the highest transcriptional activity. Finally, transcription was primarily responsible for changes in the expression of genes known to regulate myofiber size. These findings show that resident myonuclei possess a significant reserve capacity to up-regulate transcription during hypertrophy and that myofiber transcription is responsive to DNA content but uncoupled from cell size during hypertrophy

Reduced Voluntary Running Performance is Associated with Impaired Coordination as a Result of Muscle Satellite Cell Depletion in Adult Mice

BACKGROUND: Satellite cells, or muscle stem cells, have been thought to be responsible for all muscle plasticity, but recent studies using genetically modified mouse models that allow for the conditional ablation of satellite cells have challenged this dogma. Results have confirmed the absolute requirement of satellite cells for muscle regeneration but surprisingly also showed that they are not required for adult muscle growth. While the function of satellite cells in muscle growth and regeneration is becoming better defined, their role in the response to aerobic activity remains largely unexplored. The purpose of the current study was to assess the involvement of satellite cells in response to aerobic exercise by evaluating the effect of satellite cell depletion on wheel running performance. RESULTS: Four-month-old female Pax7/DTA mice (n = 8-12 per group) were satellite cell depleted via tamoxifen administration; at 6 months of age, mice either remained sedentary or were provided with running wheels for 8 weeks. Plantaris muscles were significantly depleted of Pax7+cells (≥90 % depleted), and 8 weeks of wheel running did not result in an increase in Pax7+ cells, or in myonuclear accretion. Interestingly, satellite cell-depleted animals ran ~27 % less distance and were 23 % slower than non-depleted animals. Wheel running was associated with elevated succinate dehydrogenase activity, muscle vascularization, lipid accumulation, and a significant shift toward more oxidative myosin heavy chain isoforms, as well as an increase in voltage dependent anion channel abundance, a marker of mitochondrial density. Importantly, these changes were independent of satellite cell content. Interestingly, depletion of Pax7+ cells from intra- as well as extrafusal muscle fibers resulted in atrophy of intrafusal fibers, thickening of muscle spindle-associated extracellular matrix, and a marked reduction of functional outcomes including grip strength, gait fluidity, and balance, which likely contributed to the impaired running performance. CONCLUSIONS: Depletion of Pax7-expressing cells in muscle resulted in reduced voluntary wheel running performance, without affecting markers of aerobic adaptation; however, their absence may perturb proprioception via disruption of muscle spindle fibers resulting in loss of gross motor coordination, indicating that satellite cells have a yet unexplored role in muscle function

Insidious procedures: diversity awards legitimize unfair organizational practices

This is the author's version of an article subsequently published in Social Justice Research in final format. The final publication is available at Springer via http://dx.doi.org/10.1007/s11211-015-0240-zDoes the presence (versus absence) of an organizational diversity award increase the perceived fairness of biased personnel procedures? Participants examined fair or unfair personnel procedures at a company that had received a diversity award or an award unrelated to diversity. When the company had received a diversity award (versus a control award), participants perceived the unfair personnel procedure as fairer for minorities, and White participants were more supportive of enacting the biased procedure. These findings suggest that organizations perceived as successfully supporting diversity might be afforded particular legitimacy to enact policies and procedures that disadvantage the very groups they are perceived as valuing.National Science Foundatio

Inducible Depletion of Satellite Cells in Adult, Sedentary Mice Impairs Muscle Regenerative Capacity without Affecting Sarcopenia

A key determinant of geriatric frailty is sarcopenia, the age-associated loss of skeletal muscle mass and strength. Although the etiology of sarcopenia is unknown, the correlation during aging between the loss of activity of satellite cells, which are endogenous muscle stem cells, and impaired muscle regenerative capacity has led to the hypothesis that the loss of satellite cell activity is also a cause of sarcopenia. We tested this hypothesis in male sedentary mice by experimentally depleting satellite cells in young adult animals to a degree sufficient to impair regeneration throughout the rest of their lives. A detailed analysis of multiple muscles harvested at various time points during aging in different cohorts of these mice showed that the muscles were of normal size, despite low regenerative capacity, but did have increased fibrosis. These results suggest that lifelong reduction of satellite cells neither accelerated nor exacerbated sarcopenia and that satellite cells did not contribute to the maintenance of muscle size or fiber type composition during aging, but that their loss may contribute to age-related muscle fibrosis

Use of the second-generation antipsychotic, risperidone and secondary weight gain are associated with an altered gut microbiota in children

The atypical antipsychotic risperidone (RSP) is often associated with weight gain and cardiometabolic side effects. The mechanisms for these adverse events are poorly understood and, undoubtedly, multifactorial in etiology. In light of growing evidence implicating the gut microbiome in the host's energy regulation and in xenobiotic metabolism, we hypothesized that RSP treatment would be associated with changes in the gut microbiome in children and adolescents. Thus, the impact of chronic (>12 months) and short-term use of RSP on the gut microbiome of pediatric psychiatrically ill male participants was examined in a cross-sectional and prospective (up to 10 months) design, respectively. Chronic treatment with RSP was associated with an increase in body mass index (BMI) and a significantly lower ratio of Bacteroidetes:Firmicutes as compared with antipsychotic-naïve psychiatric controls (ratio=0.15 vs 1.24, respectively; P<0.05). Furthermore, a longitudinal observation, beginning shortly after onset of RSP treatment, revealed a gradual decrease in the Bacteroidetes:Firmicutes ratio over the ensuing months of treatment, in association with BMI gain. Lastly, metagenomic analyses were performed based on extrapolation from 16S ribosomal RNA data using the software package, Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt). Those data indicate that gut microbiota dominating the RSP-treated participants are enriched for pathways that have been implicated in weight gain, such as short-chain fatty acid production

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London