Correction: Kinesin-2 transports Orco into the olfactory cilium of Drosophila melanogaster at specific developmental stages.

[This corrects the article DOI: 10.1371/journal.pgen.1009752.].

Kinesin-2 transports Orco into the olfactory cilium of Drosophila melanogaster at specific developmental stages.

The cilium, the sensing centre for the cell, displays an extensive repertoire of receptors for various cell signalling processes. The dynamic nature of ciliary signalling indicates that the ciliary entry of receptors and associated proteins must be regulated and conditional. To understand this process, we studied the ciliary localisation of the odour-receptor coreceptor (Orco), a seven-pass transmembrane protein essential for insect olfaction. Little is known about when and how Orco gets into the cilia. Here, using Drosophila melanogaster, we show that the bulk of Orco selectively enters the cilia on adult olfactory sensory neurons in two discrete, one-hour intervals after eclosion. A conditional loss of heterotrimeric kinesin-2 during this period reduces the electrophysiological response to odours and affects olfactory behaviour. We further show that Orco binds to the C-terminal tail fragments of the heterotrimeric kinesin-2 motor, which is required to transfer Orco from the ciliary base to the outer segment and maintain within an approximately four-micron stretch at the distal portion of the ciliary outer-segment. The Orco transport was not affected by the loss of critical intraflagellar transport components, IFT172/Oseg2 and IFT88/NompB, respectively, during the adult stage. These results highlight a novel developmental regulation of seven-pass transmembrane receptor transport into the cilia and indicate that ciliary signalling is both developmentally and temporally regulated.

Ciliary membrane, localised lipid modification and cilia function.

Cilium, a tiny microtubule-based cellular appendage critical for cell signalling and physiology, displays a large variety of receptors. The composition and turnover of ciliary lipids and receptors determine cell behaviour. Due to the exclusion of ribosomal machinery and limited membrane area, a cilium needs adaptive logistics to actively reconstitute the lipid and receptor compositions during development and differentiation. How is this dynamicity generated? Here, we examine whether, along with the Intraflagellar-Transport, targeted changes in sector-wise lipid composition could control the receptor localisation and functions in the cilia. We discuss how an interplay between ciliary lipid composition, localised lipid modification, and receptor function could contribute to cilia growth and signalling. We argue that lipid modification at the cell-cilium interface could generate an added thrust for a selective exchange of membrane lipids and the transmembrane and membrane-associated proteins.

Air quality and health co-benefits of climate change mitigation and adaptation actions by 2030: an interdisciplinary modeling study in Ahmedabad, India.

Climate change-driven temperature increases worsen air quality in places where coal combustion powers electricity for air conditioning. Climate solutions that substitute clean and renewable energy in place of polluting coal and promote adaptation to warming through reflective cool roofs can reduce cooling energy demand in buildings, lower power sector carbon emissions, and improve air quality and health. We investigate the air quality and health co-benefits of climate solutions in Ahmedabad, India-a city where air pollution levels exceed national health-based standards-through an interdisciplinary modeling approach. Using a 2018 baseline, we quantify changes in fine particulate matter (PM2.5) air pollution and all-cause mortality in 2030 from increasing renewable energy use (mitigation) and expanding Ahmedabad's cool roofs heat resilience program (adaptation). We apply local demographic and health data and compare a 2030 mitigation and adaptation (M&A) scenario to a 2030 business-as-usual (BAU) scenario (without climate change response actions), each relative to 2018 pollution levels. We estimate that the 2030 BAU scenario results in an increase of PM2.5 air pollution of 4.13 µg m-3 from 2018 compared to a 0.11 µg m-3 decline from 2018 under the 2030 M&A scenario. Reduced PM2.5 air pollution under 2030 M&A results in 1216-1414 fewer premature all-cause deaths annually compared to 2030 BAU. Achievement of National Clean Air Programme, National Ambient Air Quality Standards, or World Health Organization annual PM2.5 Air Quality Guideline targets in 2030 results in up to 6510, 9047, or 17 369 fewer annual deaths, respectively, relative to 2030 BAU. This comprehensive modeling method is adaptable to estimate local air quality and health co-benefits in other settings by integrating climate, energy, cooling, land cover, air pollution, and health data. Our findings demonstrate that city-level climate change response policies can achieve substantial air quality and health co-benefits. Such work can inform public discourse on the near-term health benefits of mitigation and adaptation.

Climate Change Adaptation: Prehospital Data Facilitate the Detection of Acute Heat Illness in India.

INTRODUCTION: Extreme heat is a significant cause of morbidity and mortality, and the incidence of acute heat illness (AHI) will likely increase secondary to anthropogenic climate change. Prompt diagnosis and treatment of AHI are critical; however, relevant diagnostic and surveillance tools have received little attention. In this exploratory cross-sectional and diagnostic accuracy study, we evaluated three tools for use in the prehospital setting: 1) case definitions; 2) portable loggers to measure on-scene heat exposure; and 3) prevalence data for potential AHI risk factors. METHODS: We enrolled 480 patients who presented to emergency medical services with chief complaints consistent with AHI in Ahmedabad, India, from April-June 2016 in a cross-sectional study. We evaluated AHI case definition test characteristics in reference to trained prehospital provider impressions, compared on-scene heat index measured by portable loggers to weather station measurements, and identified AHI behavioral and environmental risk factors using logistic regression. RESULTS: The case definition for heat exhaustion was 23.8% (12.1-39.5%) sensitive and 93.6% (90.9-95.7%) specific. The positive and negative predictive values were 33.5% (20.8-49.0%) and 90.1% (88.5-91.5%), respectively. Mean scene heat index was 6.7°C higher than the mean station heat index (P < 0.001), and station data systematically underestimated heat exposure, particularly for AHI cases. Heat exhaustion cases were associated with on-scene heat index ≥ 49°C (odds ratio [OR] 2.66 [1.13-6.25], P = 0.025) and a history of recent exertion (OR 3.66 [1.30-10.29], P = 0.014), while on-scene air conditioning was protective (OR 0.29 [0.10-0.85], P = 0.024). CONCLUSION: Systematic collection of prehospital data including recent activity history and presence of air conditioning can facilitate early AHI detection, timely intervention, and surveillance. Scene temperature data can be reliably collected and improve heat exposure and AHI risk assessment. Such data may be important elements of surveillance, clinical practice, and climate change adaptation.

Extreme Heat Kills Even in Very Hot Cities: Evidence from Nagpur, India.

BACKGROUND: Although many studies have provided evidence for all-cause mortality attributed to extreme temperature across India, few studies have provided a systematic analysis of the association between all-cause mortality and temperature. OBJECTIVE: To estimate the risk associated with heat waves during two major heat waves of Nagpur occurred in 2010 and 2014. METHODS: The association between temperature and mortality was measured using a distributed lag non-linear model (DLNM) and the attributable deaths associated with the heat waves with forward perspective in the DLNM framework. RESULTS: From the ecological analysis, we found 580 and 306 additional deaths in 2010 and 2014, respectively. Moving average results also gave similar findings. DLNM results showed that the relative risk was 1.5 for the temperature above 45 °C; forward perspective analysis revealed that the attributable deaths during 2010 and 2014 were 505 and 376, respectively. Results from different methods showed that heat waves in different years had variable impacts for various reasons. However, all the results were consistent during 2010 and 2014; there were 30% and 14% extra-mortalities due to heat comparing to non-heat wave years. CONCLUSION: We strongly recommend the city Government to implement the action plans based on this research outcome to reduce the risk from the heat wave in future.

Combating Climate Change-induced Heat Stress: Assessing Cool Roofs and Its Impact on the Indoor Ambient Temperature of the Households in the Urban Slums of Ahmedabad.

BACKGROUND: The rising global temperature and frequent heatwaves are the adverse effects of climate change. The causalities and ill impacts of the heat stress were higher among the slum dwellers because of the vulnerable household structures, which were made by heat-trapping materials like tin sheets, cement sheet (asbestos), plastic, and tarpaulin. The houses are not only dwellings but also a source of livelihood for many slum dwellers as they are involved in home-based work. The increase in the temperature of more than 40°C severely affects health and increases energy expenditures. OBJECTIVE: The present study conducted to identify the efficient cool roof technologies that reduce indoor temperature of the households and improve the heat resilience of dwellings located in the urban slums of Ahmedabad. METHODOLOGY: The performances of cool roof interventions were compared with the nonintervention - roof types, namely, tin, asbestos/cement sheet, and concrete. Relative humidity/temperature data loggers (Lascar EL-USB-2-LCD, Sweden) were used to measure the indoor ambient temperature and humidity. The questionnaire-based survey also has been conducted to understand the socioeconomic status and the perceptions related to roofing and health. RESULTS: The results revealed that selected cool roof technologies including Thermocol insulation, solar reflective white paint on the outer surface of the roof, and Modroof are effectively reducing the indoor temperature as compared to the nonintervention roofing. CONCLUSION: Cool roof technologies have a wider scope as number of informal settlements are increasing across the cities in India and other developing countries. The governments may not able to provide proper housing to all these inhabitants due to various reasons including the land tenure of the habitats. Validated cool roof technologies can be promoted as these structures are not requires legal sanctions and easily dismantled and installed in multiple places and safeguards the investment of urban poor.

Site of Azido Substitution in the Sugar Moiety of Azidopyrimidine Nucleosides Influences the Reactivity of Aminyl Radicals Formed by Dissociative Electron Attachment.

In this work, electron-induced site-specific formation of neutral π-type aminyl radicals (RNH·) and their reactions with pyrimidine nucleoside analogs azidolabeled at various positions in the sugar moiety, e.g., at 2'-, 3'-, 4'-, and 5'- sites along with a model compound 3-azido-1-propanol (3AZPrOH), were investigated. Electron paramagnetic resonance (EPR) studies confirmed the site and mechanism of RNH· formation via dissociative electron attachment-mediated loss of N2 and subsequent facile protonation from the solvent employing the 15N-labeled azido group, deuterations at specific sites in the sugar and base, and changing the solvent from H2O to D2O. Reactions of RNH· were investigated employing EPR by warming these samples from 77 K to ca. 170 K. RNH· at a primary carbon site (5'-azido-2',5'-dideoxyuridine, 3AZPrOH) facilely converted to a σ-type iminyl radical (R═N·) via a bimolecular H-atom abstraction forming an α-azidoalkyl radical. RNH· when at a secondary carbon site (e.g., 2'-azido-2'-deoxyuridine) underwent bimolecular electrophilic addition to the C5═C6 double bond of a proximate pyrimidine base. Finally, RNH· at tertiary alkyl carbon (4'-azidocytidine) underwent little reaction. These results show the influence of the stereochemical and electronic environment on RNH· reactivity and allow the selection of those azidonucleosides that would be most effective in augmenting cellular radiation damage.

Effects of Occupational Heat Exposure on Traffic Police Workers in Ahmedabad, Gujarat.

One of the most concerning environmental effects of climate change is rising levels of extreme heat, which already poses serious risks in many parts of the world. In June and July 2015, we collected weekly heat exposure data using area and personal temperature monitoring in Ahmedabad, Gujarat. The study was conducted at four different traffic junctions with a cohort of 16 traffic police. For information on health effects, we administered a baseline survey at the start of the study and prospectively followed up with the officers on prevalence of heat-related symptoms. Wet bulb globe temperature (WBGT) levels ranged from 28.2°C to 36.1°C during the study period. Traffic police workers who participated in this study were exposed to WBGT levels higher than the recommended threshold limit value as per American Conference of Governmental Industrial Hygienists guidelines even beyond the hottest months of the season. Our findings suggest that airport measurements by the Indian Meteorological Department may not accurately capture heat exposures among individuals who work in and alongside high-density traffic junctions. Based on our temperature estimates, traffic police are at risk for heat stress. India is likely to experience warmer temperatures and increased heat waves in the coming decades, fueled by climate change. Therefore, it is important to reduce current and future heat-related risks for traffic police workers and similar occupational risk groups by establishing protection strategies. The protocol established in this study for occupational heat exposure assessment could be applied to a larger cohort.

Building Resilience to Climate Change: Pilot Evaluation of the Impact of India's First Heat Action Plan on All-Cause Mortality.

Background: Ahmedabad implemented South Asia's first heat action plan (HAP) after a 2010 heatwave. This study evaluates the HAP's impact on all-cause mortality in 2014-2015 relative to a 2007-2010 baseline. Methods: We analyzed daily maximum temperature (T max)-mortality relationships before and after HAP. We estimated rate ratios (RRs) for daily mortality using distributed lag nonlinear models and mortality incidence rates (IRs) for HAP warning days, comparing pre- and post-HAP periods, and calculated incidence rate ratios (IRRs). We estimated the number of deaths avoided after HAP implementation using pre- and post-HAP IRs. Results: The maximum pre-HAP RR was 2.34 (95%CI 1.98-2.76) at 47°C (lag 0), and the maximum post-HAP RR was 1.25 (1.02-1.53) estimated at 47°C (lag 0). Post-to-pre-HAP nonlagged mortality IRR for T max over 40°C was 0.95 (0.73-1.22) and 0.73 (0.29-1.81) for T max over 45°C. An estimated 1,190 (95%CI 162-2,218) average annualized deaths were avoided in the post-HAP period. Conclusion: Extreme heat and HAP warnings after implementation were associated with decreased summertime all-cause mortality rates, with largest declines at highest temperatures. Ahmedabad's plan can serve as a guide for other cities attempting to increase resilience to extreme heat.

Development of Ahmedabad's Air Information and Response (AIR) Plan to Protect Public Health.

Indian cities struggle with some of the highest ambient air pollution levels in the world. While national efforts are building momentum towards concerted action to reduce air pollution, individual cities are taking action on this challenge to protect communities from the many health problems caused by this harmful environmental exposure. In 2017, the city of Ahmedabad launched a regional air pollution monitoring and risk communication project, the Air Information and Response (AIR) Plan. The centerpiece of the plan is an air quality index developed by the Indian Institute of Tropical Meteorology’s System for Air Quality and Weather Forecasting and Research program that summarizes information from 10 new continuous air pollution monitoring stations in the region, each reporting data that can help people avoid harmful exposures and inform policy strategies to achieve cleaner air. This paper focuses on the motivation, development, and implementation of Ahmedabad’s AIR Plan. The project is discussed in terms of its collaborative roots, public health purpose in addressing the grave threat of air pollution (particularly to vulnerable groups), technical aspects in deploying air monitoring technology, and broader goals for the dissemination of an air quality index linked to specific health messages and suggested actions to reduce harmful exposures. The city of Ahmedabad is among the first cities in India where city leaders, state government, and civil society are proactively working together to address the country’s air pollution challenge with a focus on public health. The lessons learned from the development of the AIR Plan serve as a template for other cities aiming to address the heavy burden of air pollution on public health. Effective working relationships are vital since they form the foundation for long-term success and useful knowledge sharing beyond a single city.

Harvesting clues from genome wide transcriptome analysis for exploring thalidomide mediated anomalies in eye development of chick embryo: Nitric oxide rectifies the thalidomide mediated anomalies by swinging back the system to normal transcriptome pattern.

Thalidomide, the notorious teratogen is known to cause various developmental abnormalities, among which a range of eye deformations are very common. From the clinical point of view, it is necessary to pinpoint the mechanisms of teratogens that tune the gene expression. However, to our knowledge, the molecular basis of eye deformities under thalidomide treatmenthas not been reported so far. Present study focuses on the possible mechanism by which thalidomide affects eye development and the role of Nitric Oxide in recovering thalidomide-mediated anomalies of eye development using chick embryo and zebrafish models with transcriptome analysis. Transcriptome analysis showed that 403 genes were up-regulated and 223 genes were down-regulated significantly in thalidomide pre-treated embryos. 8% of the significantly modulated genes have been implicated in eye development including Pax6, OTX2, Dkk1 and Shh. A wide range of biological process and molecular function was affected by thalidomide exposure. Biological Processes including structural constituent of eye lens and Molecular functions such as visual perception and retinal metabolic process formed strong annotation clustersindicating the adverse effects of thalidomide on eye development and function. Here, we have discussed the whole embryo transcriptome with the expression of PAX6, SOX2, and CRYAAgenes from developing eyes. Our experimental data showing structural and functional aspects includingeye size, lens transparency and optic nerve activity and bioinformatics analyses of transcriptome suggest that NO could partially protect thalidomide treated embryos from its devastating effects on eye development and function.

Antimicrobial susceptibility pattern of blood isolates from a teaching hospital in north India.

Bloodstream infections are associated with significant patient morbidity and mortality worldwide. In this study, we examined antimicrobial susceptibility patterns by reviewing the data on 5,704 blood samples that were collected from patients with fever/sepsis admitted to Government Medical College and Hospital, Chandigarh, India, over a period of 1 year from August 2003 to July 2004. Among the 567 qualifying samples, Pseudomonas aeruginosa (19.75%), Escherichia coli (15.17%), Klebsiella pneumoniae (14.99%), and Salmonella enterica serovar Typhi (12.87%) were the most frequently isolated Gram-negative bacteria other than Citrobacter, Acinetobacter, Proteus, and Enterobacter spp. collectively accounting for 80.96% of the isolates. Staphylococus aureus (13.86%) and Enterococcus feacalis (2.35%) were most frequently isolated Gram-positive bacteria other than other Streptococcus and Staphylococcus spp. collectively accounting for 18% of the isolates. Among the antibiotics used for susceptibility testing of Gram-negative isolates, amikacin showed higher activity (76.61%) against Enterobacteriaceae and ciprofloxacin (65.17%) against non-fermenters. However, cefoperazone + sulbactum showed the highest activity (82.66%) among all Gram-negative isolates. For Gram-positive isolates, vancomycin (100%), ciprofloxacin (89.74%) showed the highest activity against Staphylococcus spp. Combinations of antibiotics are often prescribed as emperic therapy for bacteremia, especially for Gram-negative pathogens. Hence the antibiotic susceptibility patterns of blood isolates reported here may be a useful guide for physicians initiating emperic therapy with antibiotics.

Perceived heat stress and health effects on construction workers.

INTRODUCTION: Increasing heat waves-particularly in urban areas where construction is most prevalent, highlight a need for heat exposure assessment of construction workers. This study aims to characterize the effects of heat on construction workers from a site in Gandhinagar. MATERIALS AND METHODS: This study involved a mixed methods approach consisting of a cross sectional survey with anthropometric measurements (n = 219) and four focus groups with construction workers, as well as environmental measurements of heat stress exposure at a construction site. Survey data was collected in two seasons i.e., summer and winter months, and heat illness and symptoms were compared between the two time periods. Thematic coding of focus group data was used to identify vulnerability factors and coping mechanisms of the workers. Heat stress, recorded using a wet bulb globe temperature monitor, was compared to international safety standards. RESULTS: The survey findings suggest that heat-related symptoms increased in summer; 59% of all reports in summer were positive for symptoms (from Mild to Severe) as compared to 41% in winter. Focus groups revealed four dominant themes: (1) Non-occupational stressors compound work stressors; (2) workers were particularly attuned to the impact of heat on their health; (3) workers were aware of heat-related preventive measures; and (4) few resources were currently available to protect workers from heat stress. Working conditions often exceed international heat stress safety thresholds. Female workers and new employees might be at increased risk of illness or injury. CONCLUSION: This study suggests significant health impacts on construction workers from heat stress exposure in the workplace, showed that heat stress levels were higher than those prescribed by international standards and highlights the need for revision of work practices, increased protective measures, and possible development of indigenous work safety standards for heat exposure.

Heat-related mortality in India: excess all-cause mortality associated with the 2010 Ahmedabad heat wave.

INTRODUCTION: In the recent past, spells of extreme heat associated with appreciable mortality have been documented in developed countries, including North America and Europe. However, far fewer research reports are available from developing countries or specific cities in South Asia. In May 2010, Ahmedabad, India, faced a heat wave where the temperatures reached a high of 46.8 °C with an apparent increase in mortality. The purpose of this study is to characterize the heat wave impact and assess the associated excess mortality. METHODS: We conducted an analysis of all-cause mortality associated with a May 2010 heat wave in Ahmedabad, Gujarat, India, to determine whether extreme heat leads to excess mortality. Counts of all-cause deaths from May 1-31, 2010 were compared with the mean of counts from temporally matched periods in May 2009 and 2011 to calculate excess mortality. Other analyses included a 7-day moving average, mortality rate ratio analysis, and relationship between daily maximum temperature and daily all-cause death counts over the entire year of 2010, using month-wise correlations. RESULTS: The May 2010 heat wave was associated with significant excess all-cause mortality. 4,462 all-cause deaths occurred, comprising an excess of 1,344 all-cause deaths, an estimated 43.1% increase when compared to the reference period (3,118 deaths). In monthly pair-wise comparisons for 2010, we found high correlations between mortality and daily maximum temperature during the locally hottest "summer" months of April (r = 0.69, p<0.001), May (r = 0.77, p<0.001), and June (r = 0.39, p<0.05). During a period of more intense heat (May 19-25, 2010), mortality rate ratios were 1.76 [95% CI 1.67-1.83, p<0.001] and 2.12 [95% CI 2.03-2.21] applying reference periods (May 12-18, 2010) from various years. CONCLUSION: The May 2010 heat wave in Ahmedabad, Gujarat, India had a substantial effect on all-cause excess mortality, even in this city where hot temperatures prevail through much of April-June.

Development and implementation of South Asia's first heat-health action plan in Ahmedabad (Gujarat, India).

Recurrent heat waves, already a concern in rapidly growing and urbanizing South Asia, will very likely worsen in a warming world. Coordinated adaptation efforts can reduce heat's adverse health impacts, however. To address this concern in Ahmedabad (Gujarat, India), a coalition has been formed to develop an evidence-based heat preparedness plan and early warning system. This paper describes the group and initial steps in the plan's development and implementation. Evidence accumulation included extensive literature review, analysis of local temperature and mortality data, surveys with heat-vulnerable populations, focus groups with health care professionals, and expert consultation. The findings and recommendations were encapsulated in policy briefs for key government agencies, health care professionals, outdoor workers, and slum communities, and synthesized in the heat preparedness plan. A 7-day probabilistic weather forecast was also developed and is used to trigger the plan in advance of dangerous heat waves. The pilot plan was implemented in 2013, and public outreach was done through training workshops, hoardings/billboards, pamphlets, and print advertisements. Evaluation activities and continuous improvement efforts are ongoing, along with plans to explore the program's scalability to other Indian cities, as Ahmedabad is the first South Asian city to address heat-health threats comprehensively.

Critical body temperature profile as indicator of heat stress vulnerability.

Extreme climatic heat is a major health concern among workers in different occupational pursuits. People in the regions of western India confront frequent heat emergencies, with great risk of mortality and morbidity. Taking account of informal occupational groups (foundry and sheet metal, FSM, N=587; ceramic and pottery, CP, N=426; stone quarry, SQ, N=934) in different seasons, the study examined the body temperature profiling as indicator of vulnerability to environmental warmth. About 3/4th of 1947 workers had habitual exposure at 30.1-35.5°C WBGT and ~10% of them were exposed to 38.2-41.6°C WBGT. The responses of FSM, CP and SQ workers indicated prevailing high heat load during summer and post-monsoon months. Local skin temperatures (T(sk)) varied significantly in different seasons, with consistently high level in summer, followed by post-monsoon and winter months. The mean difference of T(cr) and T(sk) was ~5.2°C up to 26.7°C WBGT, and ~2.5°C beyond 30°C WBGT. Nearly 90% of the workers had T(cr) within 38°C, suggesting their self-adjustment strategy in pacing work and regulating T(cr). In extreme heat, the limit of peripheral adjustability (35-36°C T(sk)) and the narrowing down of the difference between T(cr) and T(sk) might indicate the limit of one's ability to withstand heat exposure.