Impact of Human Management on the Genetic Variation of Wild Pepper, Capsicum annuum var. glabriusculum

Management of wild peppers in Mexico has occurred for a long time without clear phenotypic signs of domestication. However, pre-domestication management could have implications for the population's genetic richness. To test this hypothesis we analysed 27 wild (W), let standing (LS) and cultivated (C) populations, plus 7 samples from local markets (LM), with nine polymorphic microsatellite markers. Two hundred and fifty two alleles were identified, averaging 28 per locus. Allele number was higher in W, and 15 and 40% less in LS and C populations, respectively. Genetic variation had a significant population structure. In W populations, structure was associated with ecological and geographic areas according to isolation by distance. When LM and C populations where included in the analysis, differentiation was no longer apparent. Most LM were related to distant populations from Sierra Madre Oriental, which represents their probable origin. Historical demography shows a recent decline in all W populations. Thus, pre-domestication human management is associated with a significant reduction of genetic diversity and with a loss of differentiation suggesting movement among regions by man. Measures to conserve wild and managed populations should be implemented to maintain the source and the architecture of genetic variation in this important crop relative

Extracellular vesicles from pluripotent stem cell-derived mesenchymal stem cells acquire a stromal modulatory proteomic pattern during differentiation

Mesenchymal stem/stromal cells (MSCs) obtained from pluripotent stem cells (PSCs) constitute an interesting alternative to classical MSCs in regenerative medicine. Among their many mechanisms of action, MSC extracellular vesicles (EVs) are a potential suitable substitute for MSCs in future cell-free-based therapeutic approaches. Unlike cells, EVs do not elicit acute immune rejection, and they can be produced in large quantities and stored until ready to use. Although the therapeutic potential of MSC EVs has already been proven, a thorough characterization of MSC EVs is lacking. In this work, we used a label-free liquid chromatography tandem mass spectrometry proteomic approach to identify the most abundant proteins in EVs that are secreted from MSCs derived from PSCs (PD-MSCs) and from their parental induced PSCs (iPSCs). Next, we compared both datasets and found that while iPSC EVs enclose proteins that modulate RNA and microRNA stability and protein sorting, PD-MSC EVs are rich in proteins that organize extracellular matrix, regulate locomotion, and influence cell–substrate adhesion. Moreover, compared to their respective cells, iPSCs and iPSC EVs share a greater proportion of proteins, while the PD-MSC proteome appears to be more specific. Correlation and principal component analysis consistently aggregate iPSCs and iPSC EVs but segregate PD-MSC and their EVs. Altogether, these findings suggest that during differentiation, compared with their parental iPSC EVs, PD-MSC EVs acquire a more specific set of proteins; arguably, this difference might confer their therapeutic properties.Fil: la Greca, Alejandro Damián. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Solari, Claudia María. Ministerio de Ciencia. Tecnología e Innovación Productiva. Agencia Nacional de Promoción Científica y Tecnológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Furmento, Verónica Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Lombardi, Antonella. Universidad de Buenos Aires; ArgentinaFil: Biani, María Celeste. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Aban, Cyntia Estefania. Ministerio de Ciencia. Tecnología e Innovación Productiva. Agencia Nacional de Promoción Científica y Tecnológica; ArgentinaFil: Moro, Lucía Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: García, Marcela. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Guberman, Alejandra Sonia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Sevlever, Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Miriuka, Santiago Gabriel. Universidad Nacional de La Plata; ArgentinaFil: Luzzani, Carlos Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Osteoprotegerin in Exosome-Like Vesicles from Human Cultured Tubular Cells and Urine

Urinary exosomes have been proposed as potential diagnostic tools. TNF superfamily cytokines and receptors may be present in exosomes and are expressed by proximal tubular cells. We have now studied the expression of selected TNF superfamily proteins in exosome-like vesicles from cultured human proximal tubular cells and human urine and have identified additional proteins in these vesicles by LC-MS/MS proteomics. Human proximal tubular cells constitutively released exosome-like vesicles that did not contain the TNF superfamily cytokines TRAIL or TWEAK. However, exosome-like vesicles contained osteoprotegerin (OPG), a TNF receptor superfamily protein, as assessed by Western blot, ELISA or selected reaction monitoring by nLC-(QQQ)MS/MS. Twenty-one additional proteins were identified in tubular cell exosomelike vesicles, including one (vitamin D binding protein) that had not been previously reported in exosome-like vesicles. Twelve were extracellular matrix proteins, including the basement membrane proteins type IV collagen, nidogen-1, agrin and fibulin-1. Urine from chronic kidney disease patients contained a higher amount of exosomal protein and exosomal OPG than urine from healthy volunteers. Specifically OPG was increased in autosomal dominant polycystic kidney disease urinary exosome-like vesicles and expressed by cystic epithelium in vivo. In conclusion, OPG is present in exosome-like vesicles secreted by proximal tubular epithelial cells and isolated from Chronic Kidney Disease urine.This work was supported by grants from the Instituto de Salud Carlos III (ISCIIIRETIC REDINREN RD06/0016, RD12/0021, PI11/01854, PI10/00072 PI09/ 00641 and PS09/00447); Comunidad de Madrid (Fibroteam S2010/BMD-2321, S2010/BMD-2378); Sociedad Española de NefrologÍa; European Network (HEALTH F2-2008-200647); DIALOK European project LSHB-CT-2007-036644; Fundacion Lilly and IRSIN/FRIAT to JE; Programa Intensificación Actividad Investigadora (ISCIII/ Agencia Laín-Entralgo/CM) to AO; Instituto de Salud Carlos III (FIS PI11/01401, CP09/00229); and Fundación Conchita Rábago de Jiménez DÍaz to GAL. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscrip

Five insights from the Global Burden of Disease Study 2019

The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 provides a rules-based synthesis of the available evidence on levels and trends in health outcomes, a diverse set of risk factors, and health system responses. GBD 2019 covered 204 countries and territories, as well as first administrative level disaggregations for 22 countries, from 1990 to 2019. Because GBD is highly standardised and comprehensive, spanning both fatal and non-fatal outcomes, and uses a mutually exclusive and collectively exhaustive list of hierarchical disease and injury causes, the study provides a powerful basis for detailed and broad insights on global health trends and emerging challenges. GBD 2019 incorporates data from 281 586 sources and provides more than 3.5 billion estimates of health outcome and health system measures of interest for global, national, and subnational policy dialogue. All GBD estimates are publicly available and adhere to the Guidelines on Accurate and Transparent Health Estimate Reporting. From this vast amount of information, five key insights that are important for health, social, and economic development strategies have been distilled. These insights are subject to the many limitations outlined in each of the component GBD capstone papers.Peer reviewe

North American Wild Relatives of Grain Crops

The wild-growing relatives of the grain crops are useful for long-term worldwide crop improvement research. There are neglected examples that should be accessioned as living seeds in gene banks. Some of the grain crops, amaranth, barnyard millet, proso millet, quinoa, and foxtail millet, have understudied unique and potentially useful crop wild relatives in North America. Other grain crops, barley, buckwheat, and oats, have fewer relatives in North America that are mostly weeds from other continents with more diverse crop wild relatives. The expanding abilities of genomic science are a reason to accession the wild species since there are improved ways to study evolution within genera and make use of wide gene pools. Rare wild species, especially quinoa relatives in North American, should be acquired by gene banks in cooperation with biologists that already study and conserve at-risk plant populations. Many of the grain crop wild relatives are weeds that have evolved herbicide resistance that could be used in breeding new herbicide-resistant cultivars, so well-documented examples should be accessioned and also vouchered in gene banks

Measuring universal health coverage based on an index of effective coverage of health services in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Background Achieving universal health coverage (UHC) involves all people receiving the health services they need, of high quality, without experiencing financial hardship. Making progress towards UHC is a policy priority for both countries and global institutions, as highlighted by the agenda of the UN Sustainable Development Goals (SDGs) and WHO's Thirteenth General Programme of Work (GPW13). Measuring effective coverage at the health-system level is important for understanding whether health services are aligned with countries' health profiles and are of sufficient quality to produce health gains for populations of all ages. Methods Based on the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, we assessed UHC effective coverage for 204 countries and territories from 1990 to 2019. Drawing from a measurement framework developed through WHO's GPW13 consultation, we mapped 23 effective coverage indicators to a matrix representing health service types (eg, promotion, prevention, and treatment) and five population-age groups spanning from reproductive and newborn to older adults (≥65 years). Effective coverage indicators were based on intervention coverage or outcome-based measures such as mortality-to-incidence ratios to approximate access to quality care; outcome-based measures were transformed to values on a scale of 0–100 based on the 2·5th and 97·5th percentile of location-year values. We constructed the UHC effective coverage index by weighting each effective coverage indicator relative to its associated potential health gains, as measured by disability-adjusted life-years for each location-year and population-age group. For three tests of validity (content, known-groups, and convergent), UHC effective coverage index performance was generally better than that of other UHC service coverage indices from WHO (ie, the current metric for SDG indicator 3.8.1 on UHC service coverage), the World Bank, and GBD 2017. We quantified frontiers of UHC effective coverage performance on the basis of pooled health spending per capita, representing UHC effective coverage index levels achieved in 2019 relative to country-level government health spending, prepaid private expenditures, and development assistance for health. To assess current trajectories towards the GPW13 UHC billion target—1 billion more people benefiting from UHC by 2023—we estimated additional population equivalents with UHC effective coverage from 2018 to 2023. Findings Globally, performance on the UHC effective coverage index improved from 45·8 (95% uncertainty interval 44·2–47·5) in 1990 to 60·3 (58·7–61·9) in 2019, yet country-level UHC effective coverage in 2019 still spanned from 95 or higher in Japan and Iceland to lower than 25 in Somalia and the Central African Republic. Since 2010, sub-Saharan Africa showed accelerated gains on the UHC effective coverage index (at an average increase of 2·6% [1·9–3·3] per year up to 2019); by contrast, most other GBD super-regions had slowed rates of progress in 2010–2019 relative to 1990–2010. Many countries showed lagging performance on effective coverage indicators for non-communicable diseases relative to those for communicable diseases and maternal and child health, despite non-communicable diseases accounting for a greater proportion of potential health gains in 2019, suggesting that many health systems are not keeping pace with the rising non-communicable disease burden and associated population health needs. In 2019, the UHC effective coverage index was associated with pooled health spending per capita (r=0·79), although countries across the development spectrum had much lower UHC effective coverage than is potentially achievable relative to their health spending. Under maximum efficiency of translating health spending into UHC effective coverage performance, countries would need to reach $1398 pooled health spending per capita (US$ adjusted for purchasing power parity) in order to achieve 80 on the UHC effective coverage index. From 2018 to 2023, an estimated 388·9 million (358·6–421·3) more population equivalents would have UHC effective coverage, falling well short of the GPW13 target of 1 billion more people benefiting from UHC during this time. Current projections point to an estimated 3·1 billion (3·0–3·2) population equivalents still lacking UHC effective coverage in 2023, with nearly a third (968·1 million [903·5–1040·3]) residing in south Asia. Interpretation The present study demonstrates the utility of measuring effective coverage and its role in supporting improved health outcomes for all people—the ultimate goal of UHC and its achievement. Global ambitions to accelerate progress on UHC service coverage are increasingly unlikely unless concerted action on non-communicable diseases occurs and countries can better translate health spending into improved performance. Focusing on effective coverage and accounting for the world's evolving health needs lays the groundwork for better understanding how close—or how far—all populations are in benefiting from UHC. Funding Bill & Melinda Gates Foundation