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The splenic marginal zone is a unique microenvironment where resident immune cells are exposed to the open blood circulation. Even though it has an important role in responses against blood-borne antigens, lymphocyte migration in the marginal zone has not

Recent studies project that temperature-related mortality will be the largest source of damage from climate change, with particular concern for the elderly whom it is believed bear the largest heat-related mortality risk. We study heat and mortality in Mexico, a country that exhibits a unique combination of universal mortality microdata and among the most extreme levels of humid heat. Combining detailed measurements of wet-bulb temperature with age-specific mortality data, we find that younger people who are particularly vulnerable to heat: People under 35 years old account for 75% of recent heat-related deaths and 87% of heat-related lost life years, while those 50 and older account for 96% of cold-related deaths and 80% of cold-related lost life years. We develop high-resolution projections of humid heat and associated mortality and find that under the end-of-century SSP 3-7.0 emissions scenario, temperature-related deaths shift from older to younger people. Deaths among under-35-year-olds increase 32% while decreasing by 33% among other age groups.

Simultaneous harvest failures across major crop-producing regions are a threat to global food security. Concurrent weather extremes driven by a strongly meandering jet stream could trigger such events, but so far this has not been quantified. Specifically, the ability of state-of-the art crop and climate models to adequately reproduce such high impact events is a crucial component for estimating risks to global food security. Here we find an increased likelihood of concurrent low yields during summers featuring meandering jets in observations and models. While climate models accurately simulate atmospheric patterns, associated surface weather anomalies and negative effects on crop responses are mostly underestimated in bias-adjusted simulations. Given the identified model biases, future assessments of regional and concurrent crop losses from meandering jet states remain highly uncertain. Our results suggest that model-blind spots for such high-impact but deeply-uncertain hazards have to be anticipated and accounted for in meaningful climate risk assessments., (© 2023. The Author(s).)

The impact of extreme heat on crop yields is an increasingly pressing issue given anthropogenic climate warming. However, some of the physical mechanisms involved in these impacts remain unclear, impeding adaptation-relevant insight and reliable projections of future climate impacts on crops. Here, using a multiple regression model based on observational data, we show that while extreme dry heat steeply reduced U.S. corn and soy yields, humid heat extremes had insignificant impacts and even boosted yields in some areas, despite having comparably high dry-bulb temperatures as their dry heat counterparts. This result suggests that conflating dry and humid heat extremes may lead to underestimated crop yield sensitivities to extreme dry heat. Rainfall tends to precede humid but not dry heat extremes, suggesting that multivariate weather sequences play a role in these crop responses. Our results provide evidence that extreme heat in recent years primarily affected yields by inducing moisture stress, and that the conflation of humid and dry heat extremes may lead to inaccuracy in projecting crop yield responses to warming and changing humidity., (© 2023. The Author(s).)

Climate change necessitates a global effort to reduce greenhouse gas emissions while adapting to increased climate risks. This broader climate transition will involve large-scale global interventions including renewable energy deployment, coastal protection and retreat, and enhanced space cooling, all of which will result in CO 2 emissions from energy and materials use. Yet, the magnitude of the emissions embedded in these interventions remains unconstrained, opening the potential for underaccounting of emissions and conflicts or synergies between mitigation and adaptation goals. Here, we use a suite of models to estimate the CO 2 emissions embedded in the broader climate transition. For a gradual decarbonization pathway limiting warming to 2 °C, selected adaptation-related interventions will emit ∼1.3 GtCO 2 through 2100, while emissions from energy used to deploy renewable capacity are much larger at ∼95 GtCO 2 . Together, these emissions are equivalent to over 2 y of current global emissions and 8.3% of the remaining carbon budget for 2 °C. Total embedded transition emissions are reduced by ∼80% to 21.2 GtCO 2 under a rapid pathway limiting warming to 1.5 °C. However, they roughly double to 185 GtCO 2 under a delayed pathway consistent with current policies (2.7 °C warming by 2100), mainly because a slower transition relies more on fossil fuel energy. Our results provide a holistic assessment of carbon emissions from the transition itself and suggest that these emissions can be minimized through more ambitious energy decarbonization. We argue that the emissions from mitigation, but likely much less so from adaptation, are of sufficient magnitude to merit greater consideration in climate science and policy.

Arctic sea ice has decreased substantially and is projected to reach a seasonally ice-free state in the coming decades. Little is known about whether dwindling Arctic sea ice is capable of influencing the occurrence of strong El Niño, a prominent mode of climate variability with global impacts. Based on time slice coupled model experiments, here we show that no significant change in the occurrence of strong El Niño is found in response to moderate Arctic sea-ice loss that is consistent with satellite observations to date. However, as the ice loss continues and the Arctic becomes seasonally ice-free, the frequency of strong El Niño events increases by more than one third, as defined by gradient-based indices that remove mean tropical Pacific warming induced by the seasonally ice-free Arctic. By comparing our time slice experiments with greenhouse warming experiments, we conclude that at least 37-48% of the increase of strong El Niño near the end of the 21st century is associated specifically with Arctic sea-ice loss. Further separation of Arctic sea-ice loss and greenhouse gas forcing only experiments implies that the seasonally ice-free Arctic might play a key role in driving significantly more frequent strong El Niño events., (© 2022. The Author(s).)

Humans' ability to efficiently shed heat has enabled us to range over every continent, but a wet-bulb temperature (TW) of 35°C marks our upper physiological limit, and much lower values have serious health and productivity impacts. Climate models project the first 35°C TW occurrences by the mid-21st century. However, a comprehensive evaluation of weather station data shows that some coastal subtropical locations have already reported a TW of 35°C and that extreme humid heat overall has more than doubled in frequency since 1979. Recent exceedances of 35°C in global maximum sea surface temperature provide further support for the validity of these dangerously high TW values. We find the most extreme humid heat is highly localized in both space and time and is correspondingly substantially underestimated in reanalysis products. Our findings thus underscore the serious challenge posed by humid heat that is more intense than previously reported and increasingly severe., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

The National Coastal Property Model (NCPM) simulates flood damages resulting from sea level rise and storm surge along the contiguous U.S. coastline. The model also projects local-level investments in a set of adaptation measures under the assumption that these measures will be adopted when benefits exceed the costs over a 30-year period. However, it has been observed that individuals and communities often underinvest in adaptive measures relative to standard cost-benefit assumptions due to financial, psychological, sociopolitical, and technological factors. This study applies an updated version of the NCPM to incorporate improved cost-benefit tests and to approximate observed sub-optimal flood risk reduction behavior. The updated NCPM is tested for two multi-county sites: Virginia Beach, VA and Tampa, FL. Sub-optimal adaptation approaches slow the implementation of adaptation measures throughout the 100-year simulation and they increase the amount of flood damages, especially early in the simulation. The net effect is an increase in total present value cost of $1.1 to $1.3 billion (2015 USD), representing about a 10% increase compared to optimal adaptation approaches. Future calibrations against historical data and incorporation of non-economic factors driving adaptation decisions could prove useful in better understanding the impacts of continued sub-optimal behavior., Competing Interests: Declaration of Competing Interest The authors declare no competing interests.

The health effects of climatic changes constitute an important research area, yet few researchers have reported city- or region-specific projections of temperature-related deaths based on assumptions about mitigation and adaptation. Herein, we provide quantitative projections for the number of additional deaths expected in the future, owing to the cold and heat in the city of Nanjing, China, based on 31 global circulation models (GCMs), two representative concentration pathways (RCPs) (RCP4.5 and RCP8.5), and three population scenarios [a constant scenario and two shared socioeconomic pathways (SSPs) (SSP2 and SSP5)], for the periods of 2010-2039, 2040-2069, and 2070-2099. The results show that for the period 2070-2099, the net number of temperature-related deaths can be comparable in the cases of RCP4.5/SSP2 and RCP8.5/SSP5 owing to the offsetting effects attributed to the increase of heat related deaths and the decrease of cold-related deaths. In consideration of this adaptation, we suggest that RCP4.5/SSP2 is a better future development pathway/scenario., (Copyright © 2019 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)

Sea-level rise (SLR) is not just a future trend; it is occurring now in most coastal regions across the globe. It thus impacts not only long-range planning in coastal environments, but also emergency preparedness. Its inevitability and irreversibility on long time scales, in addition to its spatial non-uniformity, uncertain magnitude and timing, and capacity to drive non-stationarity in coastal flooding on planning and engineering timescales, create unique challenges for coastal risk-management decision processes. This review assesses past United States federal efforts to synthesize evolving SLR science in support of coastal risk management. In particular, it outlines the: (1) evolution in global SLR scenarios to those using a risk-based perspective that also considers low-probability but high-consequence outcomes, (2) regionalization of the global scenarios, and (3) use of probabilistic approaches. It also describes efforts to further contextualize regional scenarios by combining local mean sea-level changes with extreme water level projections. Finally, it offers perspectives on key issues relevant to the future uptake, interpretation, and application of sea-level change scenarios in decision-making. These perspectives have utility for efforts to craft standards and guidance for preparedness and resilience measures to reduce the risk of coastal flooding and other impacts related to SLR., Competing Interests: Disclosure statement No potential conflict of interest was reported by the authors.

Background: Changing climates have been causing variations in the number of global ischemic heart disease and stroke incidences, and will continue to affect disease occurrence in the future., Objectives: To project temperature-related mortality for acute ischemic heart disease, and ischemic and hemorrhagic stroke with concomitant climate warming., Methods: We estimated the exposure-response relationship between daily cause-specific mortality and daily mean temperature in Beijing. We utilized outputs from 31 downscaled climate models and two representative concentration pathways (RCPs) for the 2020s, 2050s, and 2080s. This strategy was used to estimate future net temperature along with heat- and cold-related deaths. The results for predicted temperature-related deaths were subsequently contrasted with the baseline period., Results: In the 2080s, using the RCP8.5 and no population variation scenarios, the net total number of annual temperature-related deaths exhibited a median value of 637 (with a range across models of 434-874) for ischemic stroke; this is an increase of approximately 100% compared with the 1980s. The median number of projected annual temperature-related deaths was 660 (with a range across models of 580-745) for hemorrhagic stroke (virtually no change compared with the 1980s), and 1683 (with a range across models of 1351-2002) for acute ischemic heart disease (a slight increase of approximately 20% compared with the 1980s). In the 2080s, the monthly death projection for hemorrhagic stroke and acute ischemic heart disease showed that the largest absolute changes occurred in summer and winter while the largest absolute changes for ischemic stroke occurred in summer., Conclusions: We projected that the temperature-related mortality associated with ischemic stroke will increase dramatically due to climate warming. However, projected temperature-related mortality pertaining to acute ischemic heart disease and hemorrhagic stroke should remain relatively stable over time., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

As a result of global increases in both temperature and specific humidity, heat stress is projected to intensify throughout the 21 st century. Some of the regions most susceptible to dangerous heat and humidity combinations are also among the most densely populated. Consequently, there is the potential for widespread exposure to wet bulb temperatures that approach and in some cases exceed postulated theoretical limits of human tolerance by mid- to late-century. We project that by 2080 the relative frequency of present-day extreme wet bulb temperature events could rise by a factor of 100 - 250 (approximately double the frequency change projected for temperature alone) in the tropics and parts of the mid-latitudes, areas which are projected to contain approximately half the world's population. In addition, population exposure to wet bulb temperatures that exceed recent deadly heat waves may increase by a factor of five to ten, with 150 - 750 million person-days of exposure to wet bulb temperatures above those seen in today's most severe heat waves by 2070 - 2080. Under RCP 8.5, exposure to wet bulb temperatures above 35°C - the theoretical limit for human tolerance - could exceed a million person-days per year by 2080. Limiting emissions to follow RCP 4.5 entirely eliminates exposure to that extreme threshold. Some of the most affected regions, especially Northeast India and coastal West Africa, currently have scarce cooling infrastructure, relatively low adaptive capacity, and rapidly growing populations. In the coming decades heat stress may prove to be one of the most widely experienced and directly dangerous aspects of climate change, posing a severe threat to human health, energy infrastructure, and outdoor activities ranging from agricultural production to military training.

The Northeastern United States has experienced a large increase in precipitation over recent decades. Annual and seasonal changes of total and extreme precipitation from station observations in the Northeast are assessed over multiple time periods spanning 1901-2014. Spatially averaged, both annual total and extreme precipitation across the Northeast have increased significantly since 1901, with changepoints occurring in 2002 and 1996, respectively. Annual extreme precipitation has experienced a larger increase than total precipitation; extreme precipitation from 1996-2014 was 53% higher than from 1901-1995. Spatially, coastal areas received more total and extreme precipitation on average, but increases across the changepoints are distributed fairly uniformly across the domain. Increases in annual total precipitation across the 2002 changepoint have been driven by significant total precipitation increases in fall and summer, while increases in annual extreme precipitation across the 1996 changepoint have been driven by significant extreme precipitation increases in fall and spring. The ability of gridded observed and reanalysis precipitation data to reproduce station observations was also evaluated. Gridded observations perform well in reproducing averages and trends of annual and seasonal total precipitation, but extreme precipitation trends show significantly different spatial and domain-averaged trends than station data. North American Regional Reanalysis generally underestimates annual and seasonal total and extreme precipitation means and trends relative to station observations, and also shows substantial differences in the spatial pattern of total and extreme precipitation trends within the Northeast.

A warming climate is anticipated to increase the future heat-related total mortality in urban areas. However, little evidence has been reported for cause-specific mortality or nonurban areas. Here we assessed the impact of climate change on heat-related total and cause-specific mortality in both urban and rural counties of Jiangsu Province, China, in the next five decades. To address the potential uncertainty in projecting future heat-related mortality, we applied localized urban- and nonurban-specific exposure response functions, six population projections including a no population change scenario and five Shared Socioeconomic Pathways (SSPs), and 42 temperature projections from 21 global-scale general circulation models and two Representative Concentration Pathways (RCPs). Results showed that projected warmer temperatures in 2016-2040 and 2041-2065 will lead to higher heat-related mortality for total non-accidental, cardiovascular, respiratory, stroke, ischemic heart disease (IHD), and chronic obstructive pulmonary disease (COPD) causes occurring annually during May to September in Jiangsu Province, China. Nonurban residents in Jiangsu will suffer from more excess heat-related cause-specific mortality in 2016-2065 than urban residents. Variations across climate models and RCPs dominated the uncertainty of heat-related mortality estimation whereas population size change only had limited influence. Our findings suggest that targeted climate change mitigation and adaptation measures should be taken in both urban and nonurban areas of Jiangsu Province. Specific public health interventions should be focused on the leading causes of death (stroke, IHD, and COPD), whose health burden will be amplified by a warming climate., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Future freshwater supply, human water demand, and people's exposure to water stress are subject to multiple sources of uncertainty, including unknown future pathways of fossil fuel and water consumption, and 'irreducible' uncertainty arising from internal climate system variability. Such internal variability can conceal forced hydroclimatic changes on multi-decadal timescales and near-continental spatial-scales. Using three projections of population growth, a large ensemble from a single Earth system model, and assuming stationary per capita water consumption, we quantify the likelihoods of future population exposure to increased hydroclimatic deficits, which we define as the average duration and magnitude by which evapotranspiration exceeds precipitation in a basin. We calculate that by 2060, ~31%-35% of the global population will be exposed to >50% probability of hydroclimatic deficit increases that exceed existing hydrological storage, with up to 9% of people exposed to >90% probability. However, internal variability, which is an irreducible uncertainty in climate model predictions that is under-sampled in water resource projections, creates substantial uncertainty in predicted exposure: ~86%-91% of people will reside where irreducible uncertainty spans the potential for both increases and decreases in sub-annual water deficits. In one population scenario, changes in exposure to large hydroclimate deficits vary from -3% to +6% of global population, a range arising entirely from internal variability. The uncertainty in risk arising from irreducible uncertainty in the precise pattern of hydroclimatic change, which is typically conflated with other uncertainties in projections, is critical for climate risk management that seeks to optimize adaptations that are robust to the full set of potential real-world outcomes., Competing Interests: Competing financial interests The authors declare no competing financial interests.

Background: High temperatures have substantial impacts on mortality and, with growing concerns about climate change, numerous studies have developed projections of future heat-related deaths around the world. Projections of temperature-related mortality are often limited by insufficient information to formulate hypotheses about population sensitivity to high temperatures and future demographics., Objectives: The present study derived projections of temperature-related mortality in New York City by taking into account future patterns of adaptation or demographic change, both of which can have profound influences on future health burdens., Methods: We adopted a novel approach to modeling heat adaptation by incorporating an analysis of the observed population response to heat in New York City over the course of eight decades. This approach projected heat-related mortality until the end of the 21st century based on observed trends in adaptation over a substantial portion of the 20th century. In addition, we incorporated a range of new scenarios for population change until the end of the 21st century. We then estimated future heat-related deaths in New York City by combining the changing temperature-mortality relationship and population scenarios with downscaled temperature projections from the 33 global climate models (GCMs) and two Representative Concentration Pathways (RCPs)., Results: The median number of projected annual heat-related deaths across the 33 GCMs varied greatly by RCP and adaptation and population change scenario, ranging from 167 to 3,331 in the 2080s compared with 638 heat-related deaths annually between 2000 and 2006., Conclusions: These findings provide a more complete picture of the range of potential future heat-related mortality risks across the 21st century in New York City, and they highlight the importance of both demographic change and adaptation responses in modifying future risks. Citation: Petkova EP, Vink JK, Horton RM, Gasparrini A, Bader DA, Francis JD, Kinney PL. 2017. Towards more comprehensive projections of urban heat-related mortality: estimates for New York City under multiple population, adaptation, and climate scenarios. Environ Health Perspect 125:47-55; http://dx.doi.org/10.1289/EHP166., Competing Interests: The authors declare they have no actual or potential competing financial interests.

An aging population could substantially enhance the burden of heat-related health risks in a warming climate because of their higher susceptibility to extreme heat health effects. Here, we project heat-related mortality for adults 65 years and older in Beijing China across 31 downscaled climate models and 2 representative concentration pathways (RCPs) in the 2020s, 2050s, and 2080s. Under a scenario of medium population and RCP8.5, by the 2080s, Beijing is projected to experience 14,401 heat-related deaths per year for elderly individuals, which is a 264.9% increase compared with the 1980s. These impacts could be moderated through adaptation. In the 2080s, even with the 30% and 50% adaptation rate assumed in our study, the increase in heat-related death is approximately 7.4 times and 1.3 times larger than in the 1980s respectively under a scenario of high population and RCP8.5. These findings could assist countries in establishing public health intervention policies for the dual problems of climate change and aging population. Examples could include ensuring facilities with large elderly populations are protected from extreme heat (for example through back-up power supplies and/or passive cooling) and using databases and community networks to ensure the home-bound elderly are safe during extreme heat events.

Background: Climate change is projected to increase the frequency, intensity, and duration of heat waves while reducing cold extremes, yet few studies have examined the relationship between temperature and fetal health., Objectives: We estimate the impacts of extreme temperatures on birth weight and gestational age in Manhattan, a borough in New York City, and explore differences by socioeconomic status (SES)., Methods: We combine average daily temperature from 1985 to 2010 with birth certificate data in Manhattan for the same time period. We then generate 33 downscaled climate model time series to project impacts on fetal health., Results: We find exposure to an extra day where average temperature <25 °F and >85 °F during pregnancy is associated with a 1.8 and 1.7 g (respectively) reduction in birth weight, but the impact varies by SES, particularly for extreme heat, where teen mothers seem most vulnerable. We find no meaningful, significant effect on gestational age. Using projections of temperature from these climate models, we project average net reductions in birth weight in the 2070-2099 period of 4.6g in the business-as-usual scenario., Conclusions: Results suggest that increasing heat events from climate change could adversely impact birth weight and vary by SES., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: A warming climate will affect future temperature-attributable premature deaths. This analysis is the first to project these deaths at a near national scale for the United States using city and month-specific temperature-mortality relationships., Methods: We used Poisson regressions to model temperature-attributable premature mortality as a function of daily average temperature in 209 U.S. cities by month. We used climate data to group cities into clusters and applied an Empirical Bayes adjustment to improve model stability and calculate cluster-based month-specific temperature-mortality functions. Using data from two climate models, we calculated future daily average temperatures in each city under Representative Concentration Pathway 6.0. Holding population constant at 2010 levels, we combined the temperature data and cluster-based temperature-mortality functions to project city-specific temperature-attributable premature deaths for multiple future years which correspond to a single reporting year. Results within the reporting periods are then averaged to account for potential climate variability and reported as a change from a 1990 baseline in the future reporting years of 2030, 2050 and 2100., Results: We found temperature-mortality relationships that vary by location and time of year. In general, the largest mortality response during hotter months (April - September) was in July in cities with cooler average conditions. The largest mortality response during colder months (October-March) was at the beginning (October) and end (March) of the period. Using data from two global climate models, we projected a net increase in premature deaths, aggregated across all 209 cities, in all future periods compared to 1990. However, the magnitude and sign of the change varied by cluster and city., Conclusions: We found increasing future premature deaths across the 209 modeled U.S. cities using two climate model projections, based on constant temperature-mortality relationships from 1997 to 2006 without any future adaptation. However, results varied by location, with some locations showing net reductions in premature temperature-attributable deaths with climate change.

Because heat-related health effects tend to become more serious at higher temperatures, there is an urgent need to determine the mortality projection of specific heat-sensitive diseases to provide more detailed information regarding the variation of the sensitivity of such diseases. In this study, the specific mortality of cardiovascular and respiratory disease in Beijing was initially projected under five different global-scale General Circulation Models (GCMs) and two Representative Concentration Pathways scenarios (RCPs) in the 2020s, 2050s, and 2080s compared to the 1980s. Multi-model ensembles indicated cardiovascular mortality could increase by an average percentage of 18.4%, 47.8%, and 69.0% in the 2020s, 2050s, and 2080s under RCP 4.5, respectively, and by 16.6%,73.8% and 134% in different decades respectively, under RCP 8.5 compared to the baseline range. The same increasing pattern was also observed in respiratory mortality. The heat-related deaths under the RCP8.5 scenario were found to reach a higher number and to increase more rapidly during the 21(st) century compared to the RCP4.5 scenario, especially in the 2050s and the 2080s. The projection results show potential trends in cause-specific mortality in the context of climate change, and provide support for public health interventions tailored to specific climate-related future health risks.

Heat is among the deadliest weather-related phenomena in the United States, and the number of heat-related deaths may increase under a changing climate, particularly in urban areas. Regional adaptation planning is unfortunately often limited by the lack of quantitative information on potential future health responses. This study presents an assessment of the future impacts of climate change on heat-related mortality in 12 cities using 16 global climate models, driven by two scenarios of greenhouse gas emissions. Although the magnitude of the projected heat effects was found to differ across time, cities, climate models and greenhouse pollution emissions scenarios, climate change was projected to result in increases in heat-related fatalities over time throughout the 21st century in all of the 12 cities included in this study. The increase was more substantial under the high emission pathway, highlighting the potential benefits to public health of reducing greenhouse gas emissions. Nearly 200,000 heat-related deaths are projected to occur in the 12 cities by the end of the century due to climate warming, over 22,000 of which could be avoided if we follow a low GHG emission pathway. The presented estimates can be of value to local decision makers and stakeholders interested in developing strategies to reduce these impacts and building climate change resilience.

The generation of naïve T lymphocytes is critical for immune function yet the mechanisms governing their maturation remain incompletely understood. We have identified a mouse mutant, bloto, that harbors a hypomorphic mutation in the zinc finger protein Zfp335. Zfp335(bloto/bloto) mice exhibit a naïve T cell deficiency due to an intrinsic developmental defect that begins to manifest in the thymus and continues into the periphery, affecting T cells that have recently undergone thymic egress. The effects of Zfp335(bloto) are multigenic and cannot be attributed to altered thymic selection, proliferation or Bcl2-dependent survival. Zfp335 binds to promoter regions via a consensus motif, and its target genes are enriched in categories related to protein metabolism, mitochondrial function, and transcriptional regulation. Restoring the expression of one target, Ankle2, partially rescues T cell maturation. These findings identify Zfp335 as a transcription factor and essential regulator of late-stage intrathymic and post-thymic T cell maturation.

Increased heat-related mortality is projected to be among the major impacts of climate change on human health, and the United States urban Northeast region is likely to be particularly vulnerable. In support of regional adaptation planning, quantitative information is needed on potential future health responses at the urban and regional scales. Here, we present future projections of heat-related mortality in Boston, New York and Philadelphia utilizing downscaled next-generation climate models and Representative Concentration Pathways (RCPs) developed in support of the Intergovernmental Panel on Climate Change (IPCC)'s Fifth Assessment Report (AR5). Our analyses reveal that heat-related mortality rates per 100,000 of population during the baseline period between 1985 and 2006 were highest in Philadelphia followed by New York City and Boston. However, projected heat-related mortality rates in the 2020s, 2050s and 2080s were highest in New York City followed by Philadelphia and Boston. This study may be of value in developing strategies for reducing the future impacts of heat and building climate change resilience in the urban Northeast region.

Germinal center (GC) B cells cycle between the dark zone (DZ) and light zone (LZ) during antibody affinity maturation. Whether this movement is necessary for GC function has not been tested. Here we show that CXCR4-deficient GC B cells, which are restricted to the LZ, are gradually outcompeted by WT cells indicating an essential role for DZ access. Remarkably, the transition between DZ centroblast and LZ centrocyte phenotypes occurred independently of positioning. However, CXCR4-deficient cells carried fewer mutations and were overrepresented in the CD73(+) memory compartment. These findings are consistent with a model where GC B cells change from DZ to LZ phenotype according to a timed cellular program but suggest that spatial separation of DZ cells facilitates more effective rounds of mutation and selection. Finally, we identify a network of DZ CXCL12-expressing reticular cells that likely support DZ functions., (Copyright © 2013 Elsevier Inc. All rights reserved.)

A methodology for calculating the contribution of charged defects to the configurational free energy of an ionic crystal is introduced. The temperature-independent Wang-Landau Monte Carlo technique is applied to a simple model of a solid electrolyte, consisting of charged positive and negative defects on a lattice. The electrostatic energy is computed on lattices with periodic boundary conditions, and used to calculate the density of states and statistical-thermodynamic potentials of this system. The free energy as a function of defect concentration and temperature is accurately described by a regular solution model up to concentrations of 10% of defects, well beyond the range described by the ideal solution theory. The approach, supplemented by short-ranged terms in the energy, is proposed as an alternative to free energy methods that require a number of simulations to be carried out over a range of temperatures.

Global average temperatures have been rising for the past half-century, and the warming trend has accelerated in recent decades 1 . Further warming is expected over the next few decades, with significant regional variations. These warming trends will likely result in more frequent, intense and persistent periods of hot temperatures in summer, and generally higher temperatures in winter. Daily death counts in cities increase markedly when temperatures reach levels that are very high relative to what is normal in a given location 2-4 . Relatively cold temperatures also appear to carry risk 2,4 . Rising temperatures may result in more heat-related mortality but may also reduce cold-related mortality, and the net impact on annual mortality remains uncertain. Here we use 16 downscaled global climate models and two emissions scenarios to estimate current and future seasonal patterns in temperature-related mortality in Manhattan, New York. All 32 projections yielded warm season increases and cold season decreases in temperature-related mortality, with positive net annual temperature-related deaths in all cases. Monthly analyses showed that the largest percentage increases may occur in May and September. These results suggest that, over a range of models and scenarios of future greenhouse gas emissions, increases in heat-related mortality could outweigh reductions in cold-related mortality, with shifting seasonal patterns.

This paper addresses the specter of a September ice-free Arctic in the 21st century using newly available simulations from the Coupled Model Intercomparison Project Phase 5 (CMIP5). We find that large spread in the projected timing of the September ice-free Arctic in 30 CMIP5 models is associated at least as much with different atmospheric model components as with initial conditions. Here we reduce the spread in the timing of an ice-free state using two different approaches for the 30 CMIP5 models: (i) model selection based on the ability to reproduce the observed sea ice climatology and variability since 1979 and (ii) constrained estimation based on the strong and persistent relationship between present and future sea ice conditions. Results from the two approaches show good agreement. Under a high-emission scenario both approaches project that September ice extent will drop to ∼1.7 million km(2) in the mid 2040s and reach the ice-free state (defined as 1 million km(2)) in 2054-2058. Under a medium-mitigation scenario, both approaches project a decrease to ∼1.7 million km(2) in the early 2060s, followed by a leveling off in the ice extent.

The splenic marginal zone is a unique microenvironment where resident immune cells are exposed to the open blood circulation. Even though it has an important role in responses against blood-borne antigens, lymphocyte migration in the marginal zone has not been intravitally visualized due to challenges associated with achieving adequate imaging depth in this abdominal organ. Here we develop a two-photon microscopy procedure to study marginal zone and follicular B-cell movement in the live mouse spleen. We show that marginal zone B cells are highly motile and exhibit long membrane extensions. Marginal zone B cells shuttle between the marginal zone and follicles with at least one-fifth of the cells exchanging between compartments per hour, a behaviour that explains their ability to deliver antigens rapidly from the open blood circulation to the secluded follicles. Follicular B cells also transit from follicles to the marginal zone, but unlike marginal zone B cells, they fail to undergo integrin-mediated adhesion, become caught in fluid flow and are carried into the red pulp. Follicular B-cell egress via the marginal zone is sphingosine-1-phosphate receptor-1 (S1PR1)-dependent. This study shows that marginal zone B cells migrate continually between marginal zone and follicles and establishes the marginal zone as a site of S1PR1-dependent B-cell exit from follicles. The results also show how adhesive differences of similar cells critically influence their behaviour in the same microenvironment.

While the Arctic region has been warming strongly in recent decades, anomalously large snowfall in recent winters has affected large parts of North America, Europe, and east Asia. Here we demonstrate that the decrease in autumn Arctic sea ice area is linked to changes in the winter Northern Hemisphere atmospheric circulation that have some resemblance to the negative phase of the winter Arctic oscillation. However, the atmospheric circulation change linked to the reduction of sea ice shows much broader meridional meanders in midlatitudes and clearly different interannual variability than the classical Arctic oscillation. This circulation change results in more frequent episodes of blocking patterns that lead to increased cold surges over large parts of northern continents. Moreover, the increase in atmospheric water vapor content in the Arctic region during late autumn and winter driven locally by the reduction of sea ice provides enhanced moisture sources, supporting increased heavy snowfall in Europe during early winter and the northeastern and midwestern United States during winter. We conclude that the recent decline of Arctic sea ice has played a critical role in recent cold and snowy winters.

We demonstrated previously that human skin keratinocytes express acetylcholine receptors (AChRs) sensitive to acetylcholine and nicotine, which regulate cell adhesion and motility. We demonstrate here that human and rodent bronchial epithelial cells (BECs) express AChRs similar to those expressed by keratinocytes and by some neurons. Patch-clamp experiments demonstrated that the BEC AChRs are functional, and they are activated by acetylcholine and nicotine. They are blocked by kappa-bungarotoxin, a specific antagonist of the AChR isotypes expressed by neurons in ganglia. Their ion-gating properties are consistent with those of AChR isotypes expressed in ganglia, formed by alpha3, alpha5, and beta2 or beta4 subunits. Reverse transcription-polymerase chain reaction and in situ hybridization experiments demonstrated the presence in BECs of mRNA transcripts for all those AChR subunits, both in cell cultures and in tissue sections, whereas we could not detect transcripts for the alpha2, alpha4, alpha6, and beta3 AChR subunits. The expression of alpha3 and alpha5 proteins in BEC in vivo was verified by the binding of subunit-specific antibodies to sections of trachea. Mecamylamine and kappa-bungarotoxin, which are cholinergic antagonists able to block the ganglionic alpha3 AChRs, caused a reversible change of the cell shape of cultured, confluent human BECs. This resulted in a reduction of the area covered by the cell and in cell/cell detachment. The presence of AChRs sensitive to nicotine on the lining of the airways raises the possibility that the high concentrations of nicotine resulting from tobacco smoking will cause an abnormal activation, a desensitization, or both of the bronchial AChRs. This may mediate or facilitate some of the toxic effects of cigarette smoking in the respiratory system.

In myasthenia gravis the muscle acetylcholine receptor (AChR) is the target of an autoimmune response. AChR epitopes recognized by CD4+ T cells in myasthenic patients have been identified. AChR-specific CD4+ cell lines can be propagated by stimulation of blood lymphocytes with synthetic or biosynthetic AChR sequences. We analysed, using a semi-quantitative PCR assay, the T cell receptor (TCR) V beta usage of 16 anti-AChR polyclonal CD4+ T cell lines of known epitope specificity, propagated from myasthenic patients using pools of overlapping peptides corresponding to the sequence of an AChR subunit, or individual synthetic AChR sequences. Twelve lines had been propagated for less than 2 months, four lines for 3.5-5 months. Most lines had limited V beta usage, but in most cases different V beta regions were used for different epitopes in the same patient, and for the same epitope in different patients. In a few patients, the same V beta regions were used for recognition of different epitopes. The V beta 4 and V beta 6 regions were used most frequently. These findings suggest that the potentially autoimmune T cells that survive clonal deletion have a limited TCR repertoire. Although the present data do allow conclusions on the role of a superantigen in triggering the anti-AChR autoimmune response, the finding that different V beta regions were used in different patients does not support an important role of a superantigen in the maintenance of the CD4+ response in myasthenia gravis.