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27,198 result(s) for "David Gonzalez"
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Social Entrepreneurship in Non-Profit and Profit Sectors : Theoretical and Empirical Perspectives
This volume examines the theoretical and empirical landscape of social entrepreneurship in both non-profit and profit sectors. It extends the traditional view of social entrepreneurship to include the environmental and institutional factors that affect the emergence of social entrepreneurship activities, such as formal laws, regulations, procedures and informal institutions. The editors aim to provide evidence and increased understanding of this growing phenomenon. Social Entrepreneurship is gaining recognition as a key element of economic and social development. It embraces a wide set of situations with a broad scope of activities in for-profit and non-profit organizations interested in social performance and/or in economically profitable performance, with an emphasis on achieving social aim. In the strict sense, social entrepreneurship corresponds to entrepreneurs whose main concern is to achieve social objectives rather than to obtain personal financial profits. However, there is still much to be learned about the dynamics and processes of social entrepreneurship. The current literature in the field has tended to focus on psychological experiences and personal characteristics, or on organizational perspectives such as resources, capabilities and leadership. This book intends to provide theoretical frameworks and empirical studies to this very new and broad field. Specifically, this book provides a collection of contemporary research in the following topics: How to create opportunity through social innovation How to detect entrepreneurial opportunity to meet social needs How to develop social entrepreneurship, while still seeking profits How to discover opportunities for different forms of social entrepreneurship Featuring contributions from around the world, this book is a valuable source for students, academics, researchers, policy makers, and professionals in the area of social entrepreneurship.
Racial Disparities in Climate Change-Related Health Effects in the United States
Purpose of Review Climate change is causing warming over most parts of the USA and more extreme weather events. The health impacts of these changes are not experienced equally. We synthesize the recent evidence that climatic changes linked to global warming are having a disparate impact on the health of people of color, including children. Recent Findings Multiple studies of heat, extreme cold, hurricanes, flooding, and wildfires find evidence that people of color, including Black, Latinx, Native American, Pacific Islander, and Asian communities are at higher risk of climate-related health impacts than Whites, although this is not always the case. Studies of adults have found evidence of racial disparities related to climatic changes with respect to mortality, respiratory and cardiovascular disease, mental health, and heat-related illness. Children are particularly vulnerable to the health impacts of climate change, and infants and children of color have experienced adverse perinatal outcomes, occupational heat stress, and increases in emergency department visits associated with extreme weather. Summary The evidence strongly suggests climate change is an environmental injustice that is likely to exacerbate existing racial disparities across a broad range of health outcomes.
Microalgae for bioremediation: advances, challenges, and public perception on genetic engineering
The increase in the global population and industrial activities has led to an extensive use of water, the release of wastewater, and overall contamination of the environment. To address these issues, efficient treatment methods have been developed to decrease wastewater nutrient content and contaminants. Microalgae are a promising tool as a sustainable alternative to traditional wastewater treatment. Furthermore, the biomass obtained from the wastewater treatment can be used in different applications, having a positive economic impact. This review describes the potential of microalgae as a biological wastewater remediation tool, including the use of genetically engineered strains. Their current industrial utilization and their untapped commercial potential in terms of bioremediation are also examined. Finally, this work discusses how microalgal biotechnology is perceived by the public and governments, analyses the potential risks of microalgae to the environment, and examines standard procedures that can be implemented for the safe biocontainment of large-scale microalgae cultures.
Historic redlining and the siting of oil and gas wells in the United States
BackgroundThe presence of active or inactive (i.e., postproduction) oil and gas wells in neighborhoods may contribute to ongoing pollution. Racially discriminatory neighborhood security maps developed by the Home-Owners Loan Corporation (HOLC) in the 1930s may contribute to environmental exposure disparities.ObjectiveTo determine whether receiving worse HOLC grades was associated with exposure to more oil and gas wells.MethodsWe assessed exposure to oil and gas wells among HOLC-graded neighborhoods in 33 cities from 13 states where urban oil and gas wells were drilled and operated. Among the 17 cities for which 1940 census data were available, we used propensity score restriction and matching to compare well exposure neighborhoods that were similar on observed 1940 sociodemographic characteristics but that received different grades.ResultsAcross all included cities, redlined D-graded neighborhoods had 12.2 ± 27.2 wells km−2, nearly twice the density in neighborhoods graded A (6.8 ± 8.9 wells km−2). In propensity score restricted and matched analyses, redlined neighborhoods had 2.0 (1.3, 2.7) more wells than comparable neighborhoods with a better grade.SignificanceOur study adds to the evidence that structural racism in federal policy is associated with the disproportionate siting of oil and gas wells in marginalized neighborhoods.
Quality of life and mortality in the general population: a systematic review and meta-analysis
Background Quality of life (QoL) is multi-dimensional concept of an individual’ general well-being status in relation to their value, environment, cultural and social context in which they live. This study aimed to quantitatively synthesise available evidence on the association between QoL and mortality in the general population. Methods An electronic search was conducted using three bibliographic databases, MEDLINE, EMBASE and PsycINFO. Inclusion criteria were studies that assessed QoL using standardized tools and examined mortality risk in a non-patient population. Qualitative data synthesis and meta-analyses using a random-effects model were performed. Results Of 4184 articles identified, 47 were eligible for inclusion, involving approximately 1,200,000 participants. Studies were highly heterogeneous in terms of QoL measures, population characteristics and data analysis. In total, 43 studies (91.5%) reported that better QoL was associated with lower mortality risk. The results of four meta-analyses indicated that higher health-related QoL (HRQoL) is associated with lower mortality risk, which was consistent for overall HRQoL (HR 0.633, 95% CI: 0.514 to 0.780), physical function (HR 0.987, 95% CI: 0.982 to 0.992), physical component score (OR 0.950, 95% CI: 0.935 to 0.965), and mental component score (OR 0.980, 95% CI: 0.969 to 0.992). Conclusion These findings provide evidence that better QoL/HRQoL was associated with lower mortality risk. The utility of these measures in predicting mortality risk indicates that they should be considered further as potential screening tools in general clinical practice, beyond the traditional objective measures such as body mass index and the results of laboratory tests.
Niche-induced cell death and epithelial phagocytosis regulate hair follicle stem cell pool
Mouse hair follicles in the skin cycle between growth and regression, while maintaining a pool of stem cells for continued regeneration; here, live imaging is used to show that a combination of niche-induced stem cell apoptosis and epithelial phagocytosis underlies regression, regulating the stem cell pool. Mechanisms of tissue regression Mouse hair follicles in the skin cycle between growth and regression, while maintaining a pool of stem cells for regeneration. Valentina Greco and colleagues used imaging in live mice to show that regression involves a combination of niche-induced stem cell apoptosis and epithelial phagocytosis. Dead cells are removed from the follicle by their neighbouring epithelial cells through phagocytosis. The authors also show that regression is essential for the reduction of the overall stem cell pool as part of tissue homeostasis. Tissue homeostasis is achieved through a balance of cell production (growth) and elimination (regression) 1 , 2 . In contrast to tissue growth, the cells and molecular signals required for tissue regression remain unknown. To investigate physiological tissue regression, we use the mouse hair follicle, which cycles stereotypically between phases of growth and regression while maintaining a pool of stem cells to perpetuate tissue regeneration 3 . Here we show by intravital microscopy in live mice 4 , 5 , 6 that the regression phase eliminates the majority of the epithelial cells by two distinct mechanisms: terminal differentiation of suprabasal cells and a spatial gradient of apoptosis of basal cells. Furthermore, we demonstrate that basal epithelial cells collectively act as phagocytes to clear dying epithelial neighbours. Through cellular and genetic ablation we show that epithelial cell death is extrinsically induced through transforming growth factor (TGF)-β activation and mesenchymal crosstalk. Strikingly, our data show that regression acts to reduce the stem cell pool, as inhibition of regression results in excess basal epithelial cells with regenerative abilities. This study identifies the cellular behaviours and molecular mechanisms of regression that counterbalance growth to maintain tissue homeostasis.
Direct cloning and refactoring of a silent lipopeptide biosynthetic gene cluster yields the antibiotic taromycin A
Recent developments in next-generation sequencing technologies have brought recognition of microbial genomes as a rich resource for novel natural product discovery. However, owing to the scarcity of efficient procedures to connect genes to molecules, only a small fraction of secondary metabolomes have been investigated to date. Transformation-associated recombination (TAR) cloning takes advantage of the natural in vivo homologous recombination of Saccharomyces cerevisiae to directly capture large genomic loci. Here we report a TAR-based genetic platform that allows us to directly clone, refactor, and heterologously express a silent biosynthetic pathway to yield a new antibiotic. With this method, which involves regulatory gene remodeling, we successfully expressed a 67-kb nonribosomal peptide synthetase biosynthetic gene cluster from the marine actinomycete Saccharomonospora sp. CNQ-490 and produced the dichlorinated lipopeptide antibiotic taromycin A in the model expression host Streptomyces coelicolor. The taromycin gene cluster (tar) is highly similar to the clinically approved antibiotic daptomycin from Streptomyces roseosporus, but has notable structural differences in three amino acid residues and the lipid side chain. With the activation of the tar gene cluster and production of taromycin A, this study highlights a unique \"plug-and-play\" approach to efficiently gaining access to orphan pathways that may open avenues for novel natural product discoveries and drug development.
Kinetic profiling of metabolic specialists demonstrates stability and consistency of in vivo enzyme turnover numbers
Enzyme turnover numbers (k cats) are essential for a quantitative understanding of cells. Because k cats are traditionally measured in low-throughput assays, they can be inconsistent, labor-intensive to obtain, and can miss in vivo effects. We use a data-driven approach to estimate in vivo k cats using metabolic specialist Escherichia coli strains that resulted from gene knockouts in central metabolism followed by metabolic optimization via laboratory evolution. By combining absolute proteomics with fluxomics data, we find that in vivo k cats are robust against genetic perturbations, suggesting that metabolic adaptation to gene loss is mostly achieved through other mechanisms, like gene-regulatory changes. Combining machine learning and genome-scale metabolic models, we show that the obtained in vivo k cats predict unseen proteomics data with much higher precision than in vitro k cats. The results demonstrate that in vivo k cats can solve the problem of inconsistent and low-coverage parameterizations of genome-scale cellular models.
Gradual differentiation uncoupled from cell cycle exit generates heterogeneity in the epidermal stem cell layer
Highly regenerative tissues continuously produce terminally differentiated cells to replace those that are lost. How they orchestrate the complex transition from undifferentiated stem cells towards post-mitotic, molecularly distinct and often spatially segregated differentiated populations is not well understood. In the adult skin epidermis, the stem cell compartment contains molecularly heterogeneous subpopulations 1 – 4 whose relationship to the complete trajectory of differentiation remains unknown. Here we show that differentiation, from commitment to exit from the stem cell layer, is a multi-day process wherein cells transit through a continuum of transcriptional changes with upregulation of differentiation genes preceding downregulation of typical stemness genes. Differentiation-committed cells remain capable of dividing to produce daughter cells fated to further differentiate, demonstrating that differentiation is uncoupled from cell cycle exit. These cell divisions are not required as part of an obligate transit-amplifying programme but help to buffer the differentiating cell pool during heightened demand. Thus, instead of distinct contributions from multiple progenitors, a continuous gradual differentiation process fuels homeostatic epidermal turnover. Cockburn et al. report that epidermal differentiation is a multi-day process through which cells undergo a continuum of transcriptional alterations initiated independently of cell cycle exit.
mspms: an R package and GUI for multiplex substrate profiling by mass spectrometry
Background Multiplex Substrate Profiling by Mass Spectrometry (MSP-MS) is a powerful method for determining the substrate specificity of proteolytic enzymes, which is essential for developing protease inhibitors, diagnostics, and protease-activated therapeutics. However, the complex datasets generated by MSP-MS pose significant analytical challenges and have limited accessibility for non-specialist users. Results We developed mspms , a Bioconductor R package with an accompanying graphical interface, to streamline the analysis of MSP-MS data. Mspms standardizes workflows for data preparation, processing, statistical analysis, and visualization. The tool is designed for accessibility, serving advanced users through the R package and broader audiences through a web-based interface. We validated mspms using data from four well-characterized cathepsins (A–D), demonstrating that it reliably captures expected substrate specificities. Conclusions mspms is the first publicly available, comprehensive platform for MSP-MS data analysis downstream of peptide identification and quantification. It integrates preprocessing, normalization, statistical testing, and visualization into a single, transparent, and user-friendly framework, making it a valuable resource for the protease research community. The package is distributed via Bioconductor, and a graphical interface is available online for interactive use.