Sex-specific preservation of neuromuscular function and metabolism following systemic transplantation of multipotent adult stem cells in a murine model of progeria.

Onset and rates of sarcopenia, a disease characterized by a loss of muscle mass and function with age, vary greatly between sexes. Currently, no clinical interventions successfully arrest age-related muscle impairments since the decline is frequently multifactorial. Previously, we found that systemic transplantation of our unique adult multipotent muscle-derived stem/progenitor cells (MDSPCs) isolated from young mice-but not old-extends the health-span in DNA damage mouse models of progeria, a disease of accelerated aging. Additionally, induced neovascularization in the muscles and brain-where no transplanted cells were detected-strongly suggests a systemic therapeutic mechanism, possibly activated through circulating secreted factors. Herein, we used ZMPSTE24-deficient mice, a lamin A defect progeria model, to investigate the ability of young MDSPCs to preserve neuromuscular tissue structure and function. We show that progeroid ZMPST24-deficient mice faithfully exhibit sarcopenia and age-related metabolic dysfunction. However, systemic transplantation of young MDSPCs into ZMPSTE24-deficient progeroid mice sustained healthy function and histopathology of muscular tissues throughout their 6-month life span in a sex-specific manner. Indeed, female-but not male-mice systemically transplanted with young MDSPCs demonstrated significant preservation of muscle endurance, muscle fiber size, mitochondrial respirometry, and neuromuscular junction morphometrics. These novel findings strongly suggest that young MDSPCs modulate the systemic environment of aged animals by secreted rejuvenating factors to maintain a healthy homeostasis in a sex-specific manner and that the female muscle microenvironment remains responsive to exogenous regenerative cues in older age. This work highlights the age- and sex-related differences in neuromuscular tissue degeneration and the future prospect of preserving health in older adults with systemic regenerative treatments.

Adolescent boys and girls learning, reproducing, and resisting gender norms in Colombia and Uganda: a qualitative comparative study.

There is growing interest in studying inequitable gender norms and their impact on health and wellbeing, particularly among adolescents. Studies have shown that discriminatory gender norms limit girls' access to power within their families and communities, reduce their educational and economic opportunities, and alter their own aspiration and ambitions for their lives. This comparative qualitative study sought to understand how gender norms manifest themselves in the lives of adolescents in two distinct settings: Uganda and Colombia. A total of 133 young people aged 13-21 years from Colombia and 109 from Uganda participated in either focus group discussions or individual semi-structured interviews in May 2017. Results reveal similarities and differences in how norms are learned, reinforced and resisted and how intersecting social factors affect the ability of adolescents to facilitate norm change. A key similarity was the primacy of parents and peers in the transmission and reinforcement of gender norms. However, setting-specific material and structural factors shaped the manifestation of power and policing of gender norms as well as the ability of young people to contest them. Lessons are identified for the future design of effective gender transformative interventions with adolescents.

Liquid Crystal Emulsions That Intercept and Report on Bacterial Quorum Sensing.

We report aqueous emulsions of thermotropic liquid crystals (LCs) that can intercept and report on the presence of N-acyl-l-homoserine lactones (AHLs), a class of amphiphiles used by pathogenic bacteria to regulate quorum sensing (QS), monitor population densities, and initiate group activities, including biofilm formation and virulence factor production. The concentration of AHL required to promote "bipolar" to "radial" transitions in micrometer-scale droplets of the nematic LC 4'-pentyl-cyanobiphenyl (5CB) decreases with increasing carbon number in the acyl tail, reaching a threshold concentration of 7.1 µM for 3-oxo-C12-AHL, a native QS signal in the pathogen Pseudomonas aeruginosa. The LC droplets in these emulsions also respond to biologically relevant concentrations of the biosurfactant rhamnolipid, a virulence factor produced by communities of P. aeruginosa under the control of QS. Systematic studies using bacterial mutants support the conclusion that these emulsions respond selectively to the production of rhamnolipid and AHLs and not to other products produced by bacteria at lower (subquorate) population densities. Finally, these emulsions remain configurationally stable in growth media, enabling them to be deployed either in bacterial supernatants or in situ in bacterial cultures to eavesdrop on QS and report on changes in bacterial group behavior that can be detected in real time using polarized light. Our results provide new tools to detect and report on bacterial QS and virulence and a materials platform for the rapid and in situ monitoring of bacterial communication and resulting group behaviors in bacterial communities.

Genetic determinants of gut microbiota composition and bile acid profiles in mice.

The microbial communities that inhabit the distal gut of humans and other mammals exhibit large inter-individual variation. While host genetics is a known factor that influences gut microbiota composition, the mechanisms underlying this variation remain largely unknown. Bile acids (BAs) are hormones that are produced by the host and chemically modified by gut bacteria. BAs serve as environmental cues and nutrients to microbes, but they can also have antibacterial effects. We hypothesized that host genetic variation in BA metabolism and homeostasis influence gut microbiota composition. To address this, we used the Diversity Outbred (DO) stock, a population of genetically distinct mice derived from eight founder strains. We characterized the fecal microbiota composition and plasma and cecal BA profiles from 400 DO mice maintained on a high-fat high-sucrose diet for ~22 weeks. Using quantitative trait locus (QTL) analysis, we identified several genomic regions associated with variations in both bacterial and BA profiles. Notably, we found overlapping QTL for Turicibacter sp. and plasma cholic acid, which mapped to a locus containing the gene for the ileal bile acid transporter, Slc10a2. Mediation analysis and subsequent follow-up validation experiments suggest that differences in Slc10a2 gene expression associated with the different strains influences levels of both traits and revealed novel interactions between Turicibacter and BAs. This work illustrates how systems genetics can be utilized to generate testable hypotheses and provide insight into host-microbe interactions.

Feasibility of utilizing the SD BIOLINE Onchocerciasis IgG4 rapid test in onchocerciasis surveillance in Senegal.

As effective onchocerciasis control efforts in Africa transition to elimination efforts, different diagnostic tools are required to support country programs. Senegal, with its long standing, successful control program, is transitioning to using the SD BIOLINE Onchocerciasis IgG4 (Ov16) rapid test over traditional skin snip microscopy. The aim of this study is to demonstrate the feasibility of integrating the Ov16 rapid test into onchocerciasis surveillance activities in Senegal, based on the following attributes of acceptability, usability, and cost. A cross-sectional study was conducted in 13 villages in southeastern Senegal in May 2016. Individuals 5 years and older were invited to participate in a demographic questionnaire, an Ov16 rapid test, a skin snip biopsy, and an acceptability interview. Rapid test technicians were interviewed and a costing analysis was conducted. Of 1,173 participants, 1,169 (99.7%) agreed to the rapid test while 383 (32.7%) agreed to skin snip microscopy. The sero-positivity rate of the rapid test among those tested was 2.6% with zero positives 10 years and younger. None of the 383 skin snips were positive for Ov microfilaria. Community members appreciated that the rapid test was performed quickly, was not painful, and provided reliable results. The total costs for this surveillance activity was $22,272.83, with a cost per test conducted at $3.14 for rapid test, $7.58 for skin snip microscopy, and $13.43 for shared costs. If no participants had refused skin snip microscopy, the total cost per method with shared costs would have been around $16 per person tested. In this area with low onchocerciasis sero-positivity, there was high acceptability and perceived value of the rapid test by community members and technicians. This study provides evidence of the feasibility of implementing the Ov16 rapid test in Senegal and may be informative to other country programs transitioning to Ov16 serologic tools.