Post-translational control of beige fat biogenesis by PRDM16 stabilization.

Compelling evidence shows that brown and beige adipose tissue are protective against metabolic diseases1,2. PR domain-containing 16 (PRDM16) is a dominant activator of the biogenesis of beige adipocytes by forming a complex with transcriptional and epigenetic factors and is therefore an attractive target for improving metabolic health3-8. However, a lack of knowledge surrounding the regulation of PRDM16 protein expression hampered us from selectively targeting this transcriptional pathway. Here we identify CUL2-APPBP2 as the ubiquitin E3 ligase that determines PRDM16 protein stability by catalysing its polyubiquitination. Inhibition of CUL2-APPBP2 sufficiently extended the half-life of PRDM16 protein and promoted beige adipocyte biogenesis. By contrast, elevated CUL2-APPBP2 expression was found in aged adipose tissues and repressed adipocyte thermogenesis by degrading PRDM16 protein. Importantly, extended PRDM16 protein stability by adipocyte-specific deletion of CUL2-APPBP2 counteracted diet-induced obesity, glucose intolerance, insulin resistance and dyslipidaemia in mice. These results offer a cell-autonomous route to selectively activate the PRDM16 pathway in adipose tissues.

Size Distributions of Gold Nanoparticles in Solution Measured by Single-Particle Mass Photometry.

Specialized applications of nanoparticles often call for particular, well-characterized particle size distributions in solution, but this property can prove difficult to measure. High-throughput methods, such as dynamic light scattering, detect nanoparticles in solution with an efficiency that scales with diameter to the sixth power. This diminishes the accuracy of any determination that must span a range of particle sizes. The accurate classification of broadly distributed systems thus requires very large numbers of measurements. Mass-filtered particle-sensing techniques offer a better dynamic range but are labor-intensive and so have low throughput. Progress in many areas of nanotechnology requires a faster, lower-cost, and more accurate measure of particle size distributions, particularly for diameters smaller than 20 nm. Here, we present a tailored interferometric microscope system, combined with a high-speed image-processing strategy, optimized for real-time particle tracking that determines accurate size distributions in nominal 5, 10, and 15 nm colloidal gold nanoparticle systems by automatically sensing and classifying thousands of single particles sampled from solution at rates as high as 4000 particles per minute. We demonstrate this method by sensing the irreversible binding of gold nanoparticles to poly-d-lysine functionalized coverslips. Variations in the single-particle signal as a function of time and mass, calibrated by TEM, show clear evidence for the presence of diffusion-limited transport that most affects larger particles in solution.

Examining Health Care Access for Refugee Children and Families in the North Carolina Triangle Area.

BACKGROUND Resettled refugees are at increased risk of poor health outcomes due to acculturation challenges, logistical barriers, experiences of trauma, and other barriers to care that are poorly understood. Refugee children may be particularly vulnerable due to disruptions in health, well-being, education, and nutrition during the resettlement process.METHOD To describe the health care barriers facing refugees in the North Carolina Triangle area (comprised of Durham, Chapel Hill, Raleigh, and their surrounding areas), we conducted three focus group interviews (in Arabic, French, and Swahili) with 25 refugee parents from Syria, Iraq, Central African Republic, the Democratic Republic of the Congo, and Chad. We also administered a survey to nine organizations that provide services for refugees.RESULTS Focus group responses highlighted the multidimensional nature of health care barriers for refugee families and children, encompassing challenges with acculturation, communication, transportation, finances, and health literacy. Organizations emphasized similar challenges and described their efforts to improve access to services through increased communication, coordination, and seeking new financial support for programs.LIMITATIONS Given the geographic focus of the study, results may not be generalizable to other populations and settings. Men spoke more than women in some focus groups, and participants may have been influenced by more vocal contributors. Furthermore, this study is limited by a lack of health outcomes data.CONCLUSIONS This study suggests that the health care needs of refugees living in the North Carolina Triangle area can be better met by providing comprehensive, coordinated, and culturally relevant care. This could include minimizing the number of visits by integrating multiple services under one roof, providing trauma-informed interpreters, and offering accessible transportation services.