Advancing Health Equity through 15-min Cities and Chrono-urbanism.

Implementing the 15-min city and chrono-urbanism aims to improve sustainability and quality of life by ensuring residents' proximity to essential services. The 15-min city model is gaining global traction, with localized adaptations to suit communities' needs. Beyond environmental motivations, 15-min cities can benefit public health through enhanced walkability, social cohesion, and universal accessibility. However, research examining the intersection of health and equity among chrono-urbanism and the 15-min city remains limited. This study aims to develop a framework to integrate health and equity into chrono-urbanism and 15-min city plans. We describe the potential benefits and risks of the 15-min approach for urban planning, daily behaviors, and health outcomes. Potential benefits of 15-min cities for health equity include proximity to destinations, increased physical activity, strengthened social capital, reduced emissions, and traffic calming. Risks that must be mitigated include gentrification, variable proximity definitions, infrastructure upgrades, and inadequate cultural sensitivity. Recommendations to integrate 15-min cities into planning activities include conducting comprehensive baseline assessments, aligning goals with sustainability, economic development, flexible zoning, inclusive public spaces, and diverse community engagement tactics. We recommend interventions targeting marginalized communities and developing standardized measurement tools for comparison, monitoring, and evaluation. A nuanced, equitable approach to implementing 15-min cities can help urban plans support health equity across diverse populations.

The 2023 Latin America report of the Lancet Countdown on health and climate change: the imperative for health-centred climate-resilient development.

In 2023, a series of climatological and political events unfolded, partly driving forward the global climate and health agenda while simultaneously exposing important disparities and vulnerabilities to climate-related events. On the policy front, a significant step forward was marked by the inaugural Health Day at COP28, acknowledging the profound impacts of climate change on health. However, the first-ever Global Stocktake showed an important gap between the current progress and the targets outlined in the Paris Agreement, underscoring the urgent need for further and decisive action. From a Latin American perspective, some questions arise: How do we achieve the change that is needed? How to address the vulnerabilities to climate change in a region with long-standing social inequities? How do we promote intersectoral collaboration to face a complex problem such as climate change? The debate is still ongoing, and in many instances, it is just starting. The renamed regional centre Lancet Countdown Latin America (previously named Lancet Countdown South America) expanded its geographical scope adding Mexico and five Central American countries: Costa Rica, El Salvador, Guatemala, Honduras, and Panama, as a response to the need for stronger collaboration in a region with significant social disparities, including research capacities and funding. The centre is an independent and multidisciplinary collaboration that tracks the links between health and climate change in Latin America, following the global Lancet Countdown's methodologies and five domains. The Lancet Countdown Latin America work hinges on the commitment of 23 regional academic institutions, United Nations agencies, and 34 researchers who generously contribute their time and expertise. Building from the first report, the 2023 report of the Lancet Countdown Latin America, presents 34 indicators that track the relationship between health and climate change up to 2022, aiming at providing evidence to public decision-making with the purpose of improving the health and wellbeing of Latin American populations and reducing social inequities through climate actions focusing on health. This report shows that Latin American populations continue to observe a growing exposure to changing climatic conditions. A warming trend has been observed across all countries in Latin America, with severe direct impacts. In 2022, people were exposed to ambient temperatures, on average, 0.38 °C higher than in 1986-2005, with Paraguay experiencing the highest anomaly (+1.9 °C), followed by Argentina (+1.2 °C) and Uruguay (+0.9 °C) (indicator 1.1.1). In 2013-2022, infants were exposed to 248% more heatwave days and people over 65 years old were exposed to 271% more heatwave days than in 1986-2005 (indicator 1.1.2). Also, compared to 1991-2000, in 2013-2022, there were 256 and 189 additional annual hours per person, during which ambient heat posed at least moderate and high risk of heat stress during light outdoor physical activity in Latin America, respectively (indicator 1.1.3). Finally, the region had a 140% increase in heat-related mortality from 2000-2009 to 2013-2022 (indicator 1.1.4). Changes in ecosystems have led to an increased risk of wildfires, exposing individuals to very or extremely high fire danger for more extended periods (indicator 1.2.1). Additionally, the transmission potential for dengue by Aedes aegypti mosquitoes has risen by 54% from 1951-1960 to 2013-2022 (indicator 1.3), which aligns with the recent outbreaks and increasing dengue cases observed across Latin America in recent months. Based on the 2023 report of the Lancet Countdown Latin America, there are three key messages that Latin America needs to further explore and advance for a health-centred climate-resilient development. Latin American countries require intersectoral public policies that simultaneously increase climate resilience, reduce social inequities, improve population health, and reduce greenhouse gas (GHG) emissions. The findings show that adaptation policies in Latin America remain weak, with a pressing need for robust vulnerability and adaptation (V&A) assessments to address climate risks effectively. Unfortunately, such assessments are scarce. Up to 2021, Brazil is the only country that has completed and officially reported a V&A to the 2021 Global Survey conducted by the World Health Organization (WHO). Argentina, Guatemala, and Panama have also conducted them, but they have not been reported (indicator 2.1.1). Similarly, efforts in developing and implementing Health National Adaptation Plans (HNAPs) are varied and limited in scope. Brazil, Chile, and Uruguay are the only countries that have an HNAP (indicator 2.1.2). Moreover, self-reported city-level climate change risk assessments are very limited in the region (indicator 2.1.3). The collaboration between meteorological and health sectors remains insufficient, with only Argentina, Brazil, Colombia, and Guatemala self-reporting some level of integration (indicator 2.2.1), hindering comprehensive responses to climate-related health risks in the region. Additionally, despite the urgent need for action, there has been minimal progress in increasing urban greenspaces across the region since 2015, with only Colombia, Nicaragua, and Venezuela showing slight improvements (indicator 2.2.2). Compounding these challenges is the decrease in funding for climate change adaptation projects in Latin America, as evidenced by the 16% drop in funds allocated by the Green Climate Fund (GCF) in 2022 compared to 2021. Alarmingly, none of the funds approved in 2022 were directed toward climate change and health projects, highlighting a critical gap in addressing health-related climate risks (indicator 2.2.3). From a vulnerability perspective, the Mosquito Risk Index (MoRI) indicates an overall decrease in severe mosquito-borne disease risk in the region due to improvements in water, sanitation, and hygiene (WASH) (indicator 2.3.1). Brazil and Paraguay were the only countries that showed an increase in this indicator. It is worth noting that significant temporal variation within and between countries still persists, suggesting inadequate preparedness for climate-related changes. Overall, population health is not solely determined by the health sector, nor are climate policies a sole responsibility of the environmental sector. More and stronger intersectoral collaboration is needed to pave development pathways that consider solid adaptation to climate change, greater reductions of GHG emissions, and that increase social equity and population health. These policies involve sectors such as finance, transport, energy, housing, health, and agriculture, requiring institutional structures and policy instruments that allow long-term intersectoral collaboration. Latin American countries need to accelerate an energy transition that prioritises people's health and wellbeing, reduces energy poverty and air pollution, and maximises health and economic gains. In Latin America, there is a notable disparity in energy transition, with electricity generation from coal increasing by an average of 2.6% from 1991-2000 to 2011-2020, posing a challenge to efforts aimed at phasing out coal (indicator 3.1.1). However, this percentage increase is conservative as it may not include all the fossil fuels for thermoelectric electricity generation, especially during climate-related events and when hydropower is affected (Panel 4). Yet, renewable energy sources have been growing, increasing by an average of 5.7% during the same period. Access to clean fuels for cooking remains a concern, with 46.3% of the rural population in Central America and 23.3% in South America lacking access to clean fuels in 2022 (indicator 3.1.2). It is crucial to highlight the concerning overreliance on fossil fuels, particularly liquefied petroleum gas (LPG), as a primary cooking fuel. A significant majority of Latin American populations, approximately 74.6%, rely on LPG for cooking. Transitioning to cleaner heating and cooking alternatives could also have a health benefit by reducing household air pollution-related mortality. Fossil fuels continue to dominate road transport energy in Latin America, accounting for 96%, although some South American countries are increasing the use of biofuels (indicator 3.1.3). Premature mortality attributable to fossil-fuel-derived PM2.5 has shown varied trends across countries, increasing by 3.9% from 2005 to 2020 across Latin America, which corresponds to 123.5 premature deaths per million people (indicator 3.2.1). The Latin American countries with the highest premature mortality rate attributable to PM2.5 in 2020 were Chile, Peru, Brazil, Colombia, Mexico, and Paraguay. Of the total premature deaths attributable to PM2.5 in 2020, 19.1% was from transport, 12.3% from households, 11.6% from industry, and 11% from agriculture. From emission and capture of GHG perspective, commodity-driven deforestation and expansion of agricultural land remain major contributors to tree cover loss in the region, accounting for around 80% of the total loss (indicator 3.3). Additionally, animal-based food production in Latin America contributes 85% to agricultural CO2 equivalent emissions, with Argentina, Brazil, Panama, Paraguay, and Uruguay ranking highest in per capita emissions (indicator 3.4.1). From a health perspective, in 2020, approximately 870,000 deaths were associated with imbalanced diets, of which 155,000 (18%) were linked to high intake of red and processed meat and dairy products (indicator 3.4.2). Energy transition in Latin America is still in its infancy, and as a result, millions of people are currently exposed to dangerous levels of air pollution and energy poverty (i.e., lack of access to essential energy sources or services). As shown in this report, the levels of air pollution, outdoors and indoors, are a significant problem in the wholeregion, with marked disparities between urban and rural areas. In 2022, Peru, Chile, Mexico, Guatemala, Colombia, El Salvador, Brazil, Uruguay, Honduras, Panama, and Nicaragua were in the top 100 most polluted countries globally. Transitioning to cleaner sources of energy, phasing out fossil fuels, and promoting better energy efficiency in the industrial and housing sectors are not only climate mitigation measures but also huge health and economic opportunities for more prosperous and healthy societies. Latin American countries need to increase climate finance through permanent fiscal commitments and multilateral development banks to pave climate-resilient development pathways. Climate change poses significant economic costs, with investments in mitigation and adaptation measures progressing slowly. In 2022, economic losses due to weather-related extreme events in Latin America were US$15.6 billion -an amount mainly driven by floods and landslides in Brazil-representing 0.28% of Latin America's Gross Domestic Product (GDP) (indicator 4.1.1). In contrast to high-income countries, most of these losses lack insurance coverage, imposing a substantial financial strain on affected families and governments. Heat-related mortality among individuals aged 65 and older in Latin America reached alarming levels, with losses exceeding the equivalent of the average income of 451,000 people annually (indicator 4.1.2). Moreover, the total potential income loss due to heat-related labour capacity reduction amounted to 1.34% of regional GDP, disproportionately affecting the agriculture and construction sectors (indicator 4.1.3). Additionally, the economic toll of premature mortality from air pollution was substantial, equivalent to a significant portion of regional GDP (0.61%) (indicator 4.1.4). On a positive note, clean energy investments in the region increased in 2022, surpassing fossil fuel investments. However, in 2020, all countries reviewed continued to offer net-negative carbon prices, revealing fossil fuel subsidies totalling US$23 billion. Venezuela had the highest net subsidies relative to current health expenditure (123%), followed by Argentina (10.5%), Bolivia (10.3%), Ecuador (8.3%), and Chile (5.6%) (indicator 4.2.1). Fossil fuel-based energy is today more expensive than renewable energy. Fossil fuel burning drives climate change and damages the environment on which people depend, and air pollution derived from the burning of fossil fuels causes seven million premature deaths each year worldwide, along with a substantial burden of disease. Transitioning to sustainable, zero-emission energy sources, fostering healthier food systems, and expediting adaptation efforts promise not only environmental benefits but also significant economic gains. However, to implement mitigation and adaptation policies that also improve social wellbeing and prosperity, stronger and solid financial systems are needed. Climate finance in Latin American countries is scarce and strongly depends on political cycles, which threatens adequate responses to the current and future challenges. Progress on the climate agenda is lagging behind the urgent pace required. While engagement with the intersection of health and climate change is increasing, government involvement remains inadequate. Newspaper coverage of health and climate change has been on the rise, peaking in 2022, yet the proportion of climate change articles discussing health has declined over time (indicator 5.1). Although there has been significant growth in the number of scientific papers focusing on Latin America, it still represents less than 4% of global publications on the subject (indicator 5.3). And, while health was mentioned by most Latin American countries at the UN General Debate in 2022, only a few addressed the intersection of health and climate change, indicating a lack of awareness at the governmental level (indicator 5.4). The 2023 Lancet Countdown Latin America report underscores the cascading and compounding health impacts of anthropogenic climate change, marked by increased exposure to heatwaves, wildfires, and vector-borne diseases. Specifically, for Latin America, the report emphasises three critical messages: the urgent action to implement intersectoral public policies that enhance climate resilience across the region; the pressing need to prioritise an energy transition that focuses on health co-benefits and wellbeing, and lastly, that need for increasing climate finance by committing to sustained fiscal efforts and engaging with multilateral development banks. By understanding the problems, addressing the gaps, and taking decisive action, Latin America can navigate the challenges of climate change, fostering a more sustainable and resilient future for its population. Spanish and Portuguese translated versions of this Summary can be found in Appendix B and C, respectively. The full translated report in Spanish is available in Appendix D.

Post-traumatic stress disorder, food insecurity, and social capital after the 2017 coastal El Niño flooding among mothers from Piura, Peru: A mixed method study.

In order to understand the impacts in the post-disaster scenario of the 2017 El Niño events in the Piura region-Peru, we examined post-traumatic stress disorder (PTSD), food insecurity (FI), and social capital (SC) across three-time points in mothers in highly affected areas. In the Piura, Castilla, and Catacaos districts, we studied mothers combining mixed-method assessments at three (June-July 2017), eight and 12 months after the flooding. Each outcome was measured with the PTSD-Checklist-Civilian (PCL-C), the Household-Food-Insecurity-Access-Scale (HFIAS), the Adapted-Social-Capital-Assessment-Tool (SASCAT) surveys. In-depth interviews at the first evaluation were also conducted. At the first evaluation, 38.1% (n = 21) of 179 mothers reported PTSD; eight months and one year after the flooding, it dropped to 1.9% and virtually zero, respectively. Severe FI also declined over time, from 90.0% three months after the flooding to 31.8% eight months after, to 13.1% one year after. Conversely, high-cognitive SC was increased three months after the flooding (42.1%) and much greater levels at eight and 12 months after (86.7% and 77.7%, respectively). High levels of PTSD and severe FI three months after the flooding consistently decreased to nearly zero one-year post-disaster. High levels of high-cognitive SC may have helped mothers to recover from PTSD and FI in Piura.

Addressing Health Equity in the Context of Carbon Capture, Utilization, and Sequestration Technologies.

PURPOSE OF REVIEW: To describe the role of health equity in the context of carbon capture, utilization, and sequestration (CCUS) technologies. RECENT FINDINGS: CCUS technologies have the potential to both improve and worsen health equity. They could help reduce greenhouse gas emissions, a major contributor to climate change, but they could also have negative health impacts like air and noise pollution. More research is needed to fully understand the health equity implications of CCUS technologies. CCUS technologies have both health equity risks and benefits. Implementing misguided CCUS projects in vulnerable communities could exacerbate environmental injustice and health disparities and have the potential to increase carbon emissions. However, well-conceived projects could benefit communities through economic development. Governments, industry, and society should prioritize and expedite the reduction of CO2 emissions before considering carbon reductions via CCUS. Furthermore, CCUS projects must be thoroughly evaluated and should only proceed if they have demonstrated a net reduction in CO2 emissions and provide more benefits than risks to local communities. This underscores the importance of prioritizing health equity in the planning of CCUS projects.

Tracking Progress Toward Urban Nature Targets Using Landcover and Vegetation Indices: A Global Study for the 96 C40 Cities.

Access to urban natural space, including blue and greenspace, is associated with improved health. In 2021, the C40 Cities Climate Leadership Group set 2030 Urban Nature Declaration (UND) targets: "Quality Total Cover" (30% green area within each city) and "Equitable Spatial Distribution" (70% of the population living close to natural space). We evaluate progress toward these targets in the 96 C40 cities using globally available, high-resolution data sets for landcover and normalized difference vegetation index (NDVI). We use the European Space Agency (ESA)'s WorldCover data set to define greenspace with discrete landcover categories and ESA's Sentinel-2A to calculate NDVI, adding the "open water" landcover category to characterize total natural space. We compare 2020 levels of urban green and natural space to the two UND targets and predict the city-specific NDVI level consistent with the UND targets using linear regressions. The 96-city mean NDVI was 0.538 (range: 0.148, 0.739). Most (80%) cities meet the Quality Total Cover target, and nearly half (47%) meet the Equitable Spatial Distribution target. Landcover-measured greenspace and total natural space were strong (mean R 2 = 0.826) and moderate (mean R 2 = 0.597) predictors of NDVI and our NDVI-based natural space proximity measure, respectively. The 96-city mean predicted NDVI value of meeting the UND targets was 0.478 (range: 0.352-0.565) for Quality Total Cover and 0.660 (range: 0.498-0.767) for Equitable Spatial Distribution. Our translation of the area- and access-based metrics common in urban natural space targets into the NDVI metric used in epidemiology allows for quantifying the health benefits of achieving such targets.

Health implications of urban tree canopy policy scenarios in Denver and Phoenix: A quantitative health impact assessment.

BACKGROUND: Urban tree canopy (UTC) goals are a popular policy to increase urban vegetation, support climate strategies, and encourage a healthy environment. Health studies related to UTC are needed across cities to support evidence-based decision-making. METHODS: We used a quantitative Health Impact Assessment (HIA) to model the annual number of premature deaths prevented, and the number of stroke and dementia cases, under UTC goals in Denver, Colorado, and Phoenix, Arizona, USA, using standing policy goals (20% and 25% UTC, respectively) and 50% ("half-way") attainment scenarios from current levels (16.5% and 13% UTC, respectively), using publicly accessible national datasets, and a proportional representation of UTC change to standardize across methodologies. We estimated UTC health impacts by relating UTC with scenario-based changes in the Normalized Difference Vegetation Index (NDVI) and considered health equity in UTC distributions and benefits. RESULTS: We projected that at 2020 populations, uniform 20% UTC attainment across Denver block groups would avert 200 (95% uncertainty interval: (UI) 100, 306) annual premature deaths among adults 18 and older, along with 4.1 (95% UI: 2.2, 6.7) annual cases of stroke (adults ≥35), and 2.6 (95% UI: 1.5, 4.1) cases of dementia (adults ≥65), with "halfway" attainment from current levels (16.5% UTC) capturing ∼64% of these benefits. In Phoenix, uniform 25% UTC would annually prevent 368 (95% UI: 181, 558) premature deaths, 8.7 (95% UI: 4.7, 13.9) cases of stroke, and 5,1 (95% UI: 2.9, 8.0) of dementia, with the "halfway" scenario (17% UTC) achieving ∼44% of these results. Both cities saw significantly different greenspace exposures and health outcomes by socioeconomic vulnerability. Denver had more spatially and socioeconomically heterogeneous projected health benefits than Phoenix. CONCLUSIONS: Implementing UTC goals can prevent excess mortality and chronic diseases among urban residents. UTC goals can be used as a health promotion and prevention tool.

Sustainability and Equity in Urban Development (S&EUD): A Content Analysis of "Bright Spots" from the Accelerating City Equity (ACE) Project.

Sustainable and equitable urban development (S&EUD) is vital to promote healthy lives and well-being for all ages. Recognizing equity as core to urban development is essential to ensure that cities are inclusive, safe, resilient, and sustainable. The aim of this study was to identify and assess the elements of equity and sustainability in exemplary bright spots using the ACE Framework and the United Nations' 5 Ps of Sustainable Development. A content analysis process was performed to identify initial case studies, obtain bright spot information, and select final case studies. The exemplary bright spots selected were assessed for drivers of equity and the five pillars of sustainability. Results showed that equity and sustainability have become key considerations in urban development work. Numerous effective strategies and outcomes identified in the exemplary bright spots could be replicated in other contexts.

Genetic screening for anticancer genes highlights FBLN5 as a synthetic lethal partner of MYC.

BACKGROUND: When ectopically overexpressed, anticancer genes, such as TRAIL, PAR4 and ORCTL3, specifically destroy tumour cells without harming untransformed cells. Anticancer genes can not only serve as powerful tumour specific therapy tools but studying their mode of action can reveal mechanisms underlying the neoplastic transformation, sustenance and spread. METHODS: Anticancer gene discovery is normally accidental. Here we describe a systematic, gain of function, forward genetic screen in mammalian cells to isolate novel anticancer genes of human origin. Continuing with over 30,000 transcripts from our previous study, 377 cell death inducing genes were subjected to screening. FBLN5 was chosen, as a proof of principle, for mechanistic gene expression profiling, comparison pathways analyses and functional studies. RESULTS: Sixteen novel anticancer genes were isolated; these included non-coding RNAs, protein-coding genes and novel transcripts, such as ZNF436-AS1, SMLR1, TMEFF2, LINC01529, HYAL2, NEIL2, FBLN5, YPEL4 and PHKA2-processed transcript. FBLN5 selectively caused inhibition of MYC in COS-7 (transformed) cells but not in CV-1 (normal) cells. MYC was identified as synthetic lethality partner of FBLN5 where MYC transformed CV-1 cells experienced cell death upon FBLN5 transfection, whereas FBLN5 lost cell death induction in MCF-7 cells upon MYC knockdown. CONCLUSIONS: Sixteen novel anticancer genes are present in human genome including FBLN5. MYC is a synthetic lethality partner of FBLN5. Video Abstract.

A scoping review of the health co-benefits of climate mitigation strategies in South America.

The accelerated production of greenhouse gases (GHG) due to human activity has led to unprecedented global warming, making climate mitigation strategies crucial for minimizing its impacts. South America, a region highly vulnerable to climate change, stands to benefit from implementing such strategies to reduce future risks and generate health co-benefits. This scoping review, aimed to assess the existing evidence on the health benefits of climate mitigation strategies in South American countries. PubMed, Web of Science, and LILACS databases were searched until June 15, 2023. Nine studies published between 2001 and 2021 were analyzed, focusing on Brazil, Chile, and Bolivia. All the studies identified in this review used scenario modeling. They evaluated various GHG emission mitigation strategies, including land management, reducing livestock production, biofuel production, increased active transportation, renewable energy, and waste reduction. Only one study looked at GHG capture and sequestration through afforestation. Given the limited information available, there is a pressing need for more research on the region's potential health, environmental, and economic co-benefits. This review serves as a starting point and suggests that climate mitigation can offer a range of positive co-benefits, such as improved air quality and increased resilience to climate impacts, thereby advancing public health initiatives. Funding: MYG was supported by the Wellcome Trust (grant number 209734/Z/17/Z). The other authors did not receive financial support for their research or authorship. The publication of this article was financially supported by Universidad Peruana Cayetano Heredia.

The Lancet Countdown South America: increasing health opportunities by identifying the gaps in health and climate change research.

South America is experiencing the effects of climate change, including extreme weather events and changes in temperature and precipitation patterns. These effects interact with existing social vulnerabilities, exacerbating their impact on the health and wellbeing of populations. This viewpoint highlights four main messages from the series, which presented key gaps from five different perspectives of health and climate. First, there is an overall need for local analyses of priority topics to inform public policy, which include national and sub-national evidence to adequately strengthen responses and preparedness for climate change hazards and address relevant social vulnerabilities in South American countries. Second, research in health and climate is done in silos and the intersection is not clear in terms of responsibility and leadership; therefore, transdisciplinary research and action are key. Third, climate research, policies, and action need to be reflected in effective funding schemes, which until now are very limited. For adaptation and mitigation policies to be effective, they need a robust and long-term funding scheme. Finally, climate action is a big opportunity for healthier and more prosperous societies in South America, taking the advantage of strategic climate policies to face the challenges of climate change and tackle existing social inequities.

Negative DNA supercoiling induces genome-wide Cas9 off-target activity.

CRISPR-Cas9 is a powerful gene-editing technology; however, off-target activity remains an important consideration for therapeutic applications. We have previously shown that force-stretching DNA induces off-target activity and hypothesized that distortions of the DNA topology in vivo, such as negative DNA supercoiling, could reduce Cas9 specificity. Using single-molecule optical-tweezers, we demonstrate that negative supercoiling λ-DNA induces sequence-specific Cas9 off-target binding at multiple sites, even at low forces. Using an adapted CIRCLE-seq approach, we detect over 10,000 negative-supercoiling-induced Cas9 off-target double-strand breaks genome-wide caused by increased mismatch tolerance. We further demonstrate in vivo that directed local DNA distortion increases off-target activity in cells and that induced off-target events can be detected during Cas9 genome editing. These data demonstrate that Cas9 off-target activity is regulated by DNA topology in vitro and in vivo, suggesting that cellular processes, such as transcription and replication, could induce off-target activity at previously overlooked sites.

A new twist on PIFE: photoisomerisation-related fluorescence enhancement.

PIFE was first used as an acronym for protein-induced fluorescence enhancement, which refers to the increase in fluorescence observed upon the interaction of a fluorophore, such as a cyanine, with a protein. This fluorescence enhancement is due to changes in the rate ofcis/transphotoisomerisation. It is clear now that this mechanism is generally applicable to interactions with any biomolecule. In this review, we propose that PIFE is thereby renamed according to its fundamental working principle as photoisomerisation-related fluorescence enhancement, keeping the PIFE acronym intact. We discuss the photochemistry of cyanine fluorophores, the mechanism of PIFE, its advantages and limitations, and recent approaches to turning PIFE into a quantitative assay. We provide an overview of its current applications to different biomolecules and discuss potential future uses, including the study of protein-protein interactions, protein-ligand interactions and conformational changes in biomolecules.

DNA-directed termination of RNA polymerase II transcription.

RNA polymerase II (RNAPII) transcription involves initiation from a promoter, transcriptional elongation through the gene, and termination in the terminator region. In bacteria, terminators often contain specific DNA elements provoking polymerase dissociation, but RNAPII transcription termination is thought to be driven entirely by protein co-factors. We used biochemical reconstitution, single-molecule studies, and genome-wide analysis in yeast to study RNAPII termination. Transcription into natural terminators by pure RNAPII results in spontaneous termination at specific sequences containing T-tracts. Single-molecule analysis indicates that termination involves pausing without backtracking. The "torpedo" Rat1-Rai1 exonuclease (XRN2 in humans) greatly stimulates spontaneous termination but is ineffectual on other paused RNAPIIs. By contrast, elongation factor Spt4-Spt5 (DSIF) suppresses termination. Genome-wide analysis further indicates that termination occurs by transcript cleavage at the poly(A) site exposing a new 5' RNA-end that allows Rat1-Rai1 loading, which then catches up with destabilized RNAPII at specific termination sites to end transcription.

Impact of native-plants policy scenarios on premature mortality in Denver: A quantitative health impact assessment.

BACKGROUND: Cities often use non-native plants such as turf grass to expand green space. Native plants, however, may require less water and maintenance and have co-benefits for local biodiversity, including pollinators. Previous studies estimating mortality averted by adding green space have not considered the provision of native plants as part of the greening policies. AIM: We aim to estimate premature deaths that would be prevented by the implementation of native-plants policy scenarios in the City of Denver, Colorado, USA. METHODS: After conducting interviews with local expert stakeholders, we designed four native-plants policy scenarios: (1) greening 30% of all city census-block groups to the greenness level of native plants, (2) adding 200-foot native-plants buffers around riparian areas, (3) constructing large water retention ponds landscaped with native plants, and (4) greening parking lots. We defined the normalized difference vegetation index (NDVI) corresponding to native plants by measuring the NDVI at locations with known native or highly diverse vegetation. Using a quantitative health-impact assessment approach, we estimated premature mortality averted under each scenario, comparing alternative NDVI with the baseline value. RESULTS: In the most ambitious scenario, we estimated that 88 (95% uncertainty interval (UI): 20, 128) annual premature deaths would be prevented by greening 30% of the area of census block groups with native plants. We estimated that greening 30% of parking-lot surface with native plants would prevent 14 annual deaths (95% UI: 7, 18), adding the native buffers around riparian areas would prevent 13 annual deaths (95% UI: 2, 20), and adding the proposed stormwater retention ponds would prevent no annual deaths (95% UI: 0, 1). CONCLUSION: Using native plants to increase green spaces has the potential to prevent premature deaths in the City of Denver, but results were sensitive to the definition of native plants and the policy scenario.

Health benefits of Open Streets programmes in Latin America: a quantitative health impact assessment.

BACKGROUND: To improve physical activity in Latin American cities, several interventions have been promoted, such as Open Streets programmes. Our study aims to quantify the health and economic effects of Open Streets-related physical activity in 15 Latin American cities. METHODS: We used a quantitative health impact assessment approach to estimate annual premature deaths and disease incidence (ischaemic heart disease, ischaemic stroke, type 2 diabetes, colon cancer, breast cancer, and dementia) avoided, the disability-adjusted life-years (DALYs) gained, and the cost saving (from reduced premature mortality) related to increased physical activity from Open Streets programmes in 15 Latin American cities. Input data were obtained from scientific publications, reports, and open street city surveys spanning 2017 to 2019. Physical activity data were converted to metabolic equivalent of the task. Exposure-response relationship functions were applied to estimate relative risk and population-attributable fraction, enabling the assessment of premature deaths and disease incidence. FINDINGS: The percentage of male users of the Open Streets programmes ranged from 55% (27 500 of 50 000 in Guatemala) to 75% (2250 of 3000 in El Alto, Bolivia), and female users ranged from 25% (750; El Alto) to 45% (22 500; Guatemala). We estimated that the current Open Streets programmes in the 15 Latin American cities studied could prevent 363 (95% CI 271-494) annual premature deaths due to increased physical activity, with an annual economic impact of US$194·1 million (144·9 million-263·9 million) saved and an annual reduction of 1036·7 DALYs (346·7-1778·3). If one Open Streets event is added per week in each of those cities, the potential benefit could increase to 496 (370 to 677) premature deaths prevented each year. INTERPRETATION: Open Streets programmes in Latin America can provide health and economic benefits related to increased physical activity and can be used as a health promotion and disease prevention tool. FUNDING: EU's Horizon 2020 research and innovation programme.

The transcriptome of HTLV-1-infected primary cells following reactivation reveals changes to host gene expression central to the proviral life cycle.

Infections by Human T cell Leukaemia Virus type 1 (HTLV-1) persist for the lifetime of the host by integrating into the genome of CD4+ T cells. Proviral gene expression is essential for proviral survival and the maintenance of the proviral load, through the pro-proliferative changes it induces in infected cells. Despite their role in HTLV-1 infection and a persistent cytotoxic T lymphocyte response raised against the virus, proviral transcripts from the sense-strand are rarely detected in fresh cells extracted from the peripheral blood, and have recently been found to be expressed intermittently by a small subset of cells at a given time. Ex vivo culture of infected cells prompts synchronised proviral expression in infected cells from peripheral blood, allowing the study of factors involved in reactivation in primary cells. Here, we used bulk RNA-seq to examine the host transcriptome over six days in vitro, following proviral reactivation in primary peripheral CD4+ T cells isolated from subjects with non-malignant HTLV-1 infection. Infected cells displayed a conserved response to reactivation, characterised by discrete stages of gene expression, cell division and subsequently horizontal transmission of the virus. We observed widespread changes in Polycomb gene expression following reactivation, including an increase in PRC2 transcript levels and diverse changes in the expression of PRC1 components. We hypothesize that these transcriptional changes constitute a negative feedback loop that maintains proviral latency by re-deposition of H2AK119ub1 following the end of proviral expression. Using RNAi, we found that certain deubiquitinases, BAP1, USP14 and OTUD5 each promote proviral transcription. These data demonstrate the detailed trajectory of HTLV-1 proviral reactivation in primary HTLV-1-carrier lymphocytes and the impact on the host cell.

Visualization of direct and diffusion-assisted RAD51 nucleation by full-length human BRCA2 protein.

Homologous recombination (HR) is essential for error-free repair of DNA double-strand breaks, perturbed replication forks (RFs), and post-replicative single-stranded DNA (ssDNA) gaps. To initiate HR, the recombination mediator and tumor suppressor protein BRCA2 facilitates nucleation of RAD51 on ssDNA prior to stimulation of RAD51 filament growth by RAD51 paralogs. Although ssDNA binding by BRCA2 has been implicated in RAD51 nucleation, the function of double-stranded DNA (dsDNA) binding by BRCA2 remains unclear. Here, we exploit single-molecule (SM) imaging to visualize BRCA2-mediated RAD51 nucleation in real time using purified proteins. We report that BRCA2 nucleates and stabilizes RAD51 on ssDNA either directly or through an unappreciated diffusion-assisted delivery mechanism involving binding to and sliding along dsDNA, which requires the cooperative action of multiple dsDNA-binding modules in BRCA2. Collectively, our work reveals two distinct mechanisms of BRCA2-dependent RAD51 loading onto ssDNA, which we propose are critical for its diverse functions in maintaining genome stability and cancer suppression.

Who benefits from green spaces? Surrounding greenness and incidence of cardiovascular disease in a population-based electronic medical records cohort in Madrid.

The objective was to study the association between surrounding greenness and the incidence of cardiovascular diseases (CVD) with a four years follow-up in almost half a million high CVD-risk women and men, as well as its differential effect by area-level deprivation in Madrid. We analyzed 2015-2018 primary healthcare electronic medical records for 437,513 high CVD risk individuals representing more than 95% of the population of that age range residing in Madrid. The outcome variable was any cardiovascular event. We measured surrounding residence greenness at 200 m, 300 m, 500 m, and 1000 m through the Normalized Difference Vegetation Index (NDVI). We assessed socioeconomic deprivation through a census-based deprivation index. We estimated the 4-year relative risk of CVD by an increase in 0.1 units of NDVI and then stratified the models by quintiles of deprivation (Q5 the most deprived). We found that for every increase in 0.1 units of NDVI at 1000 m there was a 16% decrease in CVD risk (RR = 0.84 95% CI 0.75-0.94). CVD risk for the remaining distance exposures (at 200 m, 300 m, and 500 m) were none statistically significant. In general, the protective effect of green spaces was present in medium-deprivation areas and males, but the associations were inconsistent across deprivation levels. This study highlights the relevance of evaluating the interaction between physical and social urban components to further understand possible population prevention approaches for cardiovascular diseases. Future studies should focus on the mechanisms of context-specific interactions between social inequalities and green spaces' effects on health.

Green space exposure and type 2 diabetes mellitus incidence: A systematic review.

INTRODUCTION: Epidemiological studies have suggested that exposure to green spaces is associated with a lower prevalence of diabetes. The aim of this systematic review was to summarize the evidence on green spaces and diabetes mellitus II (T2DM) in longitudinal studies. METHODS: We searched PubMed, SCOPUS, Web of Science (WoS)/Core Collection, WoS/MEDLINE, and EMBASE until February 2023. We included cohort studies that assessed the incidence of T2DM according to the level of exposure to green spaces. Two authors independently performed study selection, data extraction, and analysis of risk of bias. No meta-analysis was performed due to clinical heterogeneity between studies. RESULTS: We included 13 cohort studies with a sample size ranging from 1700 to 1 922 545 participants. Studies presented different ways of defining (quartiles, percentages) and measuring (tools, buffers) green spaces. Similarly, the definition of T2DM was heterogeneous (self-reports, medical records, clinical criteria). Twelve studies showed that individuals with higher exposure to green spaces had a decreased incidence of T2DM. Out of these 12 studies, 10 revealed statistically significant differences. All studies were of high methodological quality, except for one. CONCLUSION: Our findings suggest that exposure to green space could be a protective factor for the development of T2DM. Promoting policies to preserve and increase green space could help to reduce T2DM at the community level. More standardization of green space exposure definition is needed in studies on green space and T2DM.