Seven centuries of reconstructed Brahmaputra River discharge demonstrate underestimated high discharge and flood hazard frequency.

The lower Brahmaputra River in Bangladesh and Northeast India often floods during the monsoon season, with catastrophic consequences for people throughout the region. While most climate models predict an intensified monsoon and increase in flood risk with warming, robust baseline estimates of natural climate variability in the basin are limited by the short observational record. Here we use a new seven-century (1309-2004 C.E) tree-ring reconstruction of monsoon season Brahmaputra discharge to demonstrate that the early instrumental period (1956-1986 C.E.) ranks amongst the driest of the past seven centuries (13th percentile). Further, flood hazard inferred from the recurrence frequency of high discharge years is severely underestimated by 24-38% in the instrumental record compared to previous centuries and climate model projections. A focus on only recent observations will therefore be insufficient to accurately characterise flood hazard risk in the region, both in the context of natural variability and climate change.

Piezo1 channels sense whole body physical activity to reset cardiovascular homeostasis and enhance performance.

Mammalian biology adapts to physical activity but the molecular mechanisms sensing the activity remain enigmatic. Recent studies have revealed how Piezo1 protein senses mechanical force to enable vascular development. Here, we address Piezo1 in adult endothelium, the major control site in physical activity. Mice without endothelial Piezo1 lack obvious phenotype but close inspection reveals a specific effect on endothelium-dependent relaxation in mesenteric resistance artery. Strikingly, the Piezo1 is required for elevated blood pressure during whole body physical activity but not blood pressure during inactivity. Piezo1 is responsible for flow-sensitive non-inactivating non-selective cationic channels which depolarize the membrane potential. As fluid flow increases, depolarization increases to activate voltage-gated Ca2+ channels in the adjacent vascular smooth muscle cells, causing vasoconstriction. Physical performance is compromised in mice which lack endothelial Piezo1 and there is weight loss after sustained activity. The data suggest that Piezo1 channels sense physical activity to advantageously reset vascular control.The mechanisms that regulate the body's response to exercise are poorly understood. Here, Rode et al. show that the mechanically activated cation channel Piezo1 is a molecular sensor of physical exercise in the endothelium that triggers endothelial communication to mesenteric vessel muscle cells, leading to vasoconstriction.

Upregulated WEE1 protects endothelial cells of colorectal cancer liver metastases.

Surgical resection of colorectal cancer liver metastases (CLM) can be curative, yet 80% of patients are unsuitable for this treatment. As angiogenesis is a determinant of CLM progression we isolated endothelial cells from CLM and sought a mechanism which is upregulated, essential for angiogenic properties of these cells and relevant to emerging therapeutic options. Matched CLM endothelial cells (CLMECs) and endothelial cells of normal adjacent liver (LiECs) were superficially similar but transcriptome sequencing revealed molecular differences, one of which was unexpected upregulation and functional significance of the checkpoint kinase WEE1. Western blotting confirmed that WEE1 protein was upregulated in CLMECs. Knockdown of WEE1 by targeted short interfering RNA or the WEE1 inhibitor AZD1775 suppressed proliferation and migration of CLMECs. Investigation of the underlying mechanism suggested induction of double-stranded DNA breaks due to nucleotide shortage which then led to caspase 3-dependent apoptosis. The implication for CLMEC tube formation was striking with AZD1775 inhibiting tube branch points by 83%. WEE1 inhibitors might therefore be a therapeutic option for CLM and could be considered more broadly as anti-angiogenic agents in cancer treatment.

Orai3 Surface Accumulation and Calcium Entry Evoked by Vascular Endothelial Growth Factor.

OBJECTIVE: Vascular endothelial growth factor (VEGF) acts, in part, by triggering calcium ion (Ca(2+)) entry. Here, we sought understanding of a Synta66-resistant Ca(2+) entry pathway activated by VEGF. APPROACH AND RESULTS: Measurement of intracellular Ca(2+) in human umbilical vein endothelial cells detected a Synta66-resistant component of VEGF-activated Ca(2+) entry that occurred within 2 minutes after VEGF exposure. Knockdown of the channel-forming protein Orai3 suppressed this Ca(2+) entry. Similar effects occurred in 3 further types of human endothelial cell. Orai3 knockdown was inhibitory for VEGF-dependent endothelial tube formation in Matrigel in vitro and in vivo in the mouse. Unexpectedly, immunofluorescence and biotinylation experiments showed that Orai3 was not at the surface membrane unless VEGF was applied, after which it accumulated in the membrane within 2 minutes. The signaling pathway coupling VEGF to the effect on Orai3 involved activation of phospholipase Cγ1, Ca(2+) release, cytosolic group IV phospholipase A2α, arachidonic acid production, and, in part, microsomal glutathione S-transferase 2, an enzyme which catalyses the formation of leukotriene C4 from arachidonic acid. Shear stress reduced microsomal glutathione S-transferase 2 expression while inducing expression of leukotriene C4 synthase, suggesting reciprocal regulation of leukotriene C4-synthesizing enzymes and greater role of microsomal glutathione S-transferase 2 in low shear stress. CONCLUSIONS: VEGF signaling via arachidonic acid and arachidonic acid metabolism causes Orai3 to accumulate at the cell surface to mediate Ca(2+) entry and downstream endothelial cell remodeling.

Rethinking Indian monsoon rainfall prediction in the context of recent global warming.

Prediction of Indian summer monsoon rainfall (ISMR) is at the heart of tropical climate prediction. Despite enormous progress having been made in predicting ISMR since 1886, the operational forecasts during recent decades (1989-2012) have little skill. Here we show, with both dynamical and physical-empirical models, that this recent failure is largely due to the models' inability to capture new predictability sources emerging during recent global warming, that is, the development of the central-Pacific El Nino-Southern Oscillation (CP-ENSO), the rapid deepening of the Asian Low and the strengthening of North and South Pacific Highs during boreal spring. A physical-empirical model that captures these new predictors can produce an independent forecast skill of 0.51 for 1989-2012 and a 92-year retrospective forecast skill of 0.64 for 1921-2012. The recent low skills of the dynamical models are attributed to deficiencies in capturing the developing CP-ENSO and anomalous Asian Low. The results reveal a considerable gap between ISMR prediction skill and predictability.

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.

Northern Hemisphere summer monsoon intensified by mega-El Nino/southern oscillation and Atlantic multidecadal oscillation.

Prediction of monsoon changes in the coming decades is important for infrastructure planning and sustainable economic development. The decadal prediction involves both natural decadal variability and anthropogenic forcing. Hitherto, the causes of the decadal variability of Northern Hemisphere summer monsoon (NHSM) are largely unknown because the monsoons over Asia, West Africa, and North America have been studied primarily on a regional basis, which is unable to identify coherent decadal changes and the overriding controls on planetary scales. Here, we show that, during the recent global warming of about 0.4 °C since the late 1970s, a coherent decadal change of precipitation and circulation emerges in the entirety of the NHSM system. Surprisingly, the NHSM as well as the Hadley and Walker circulations have all shown substantial intensification, with a striking increase of NHSM rainfall by 9.5% per degree of global warming. This is unexpected from recent theoretical prediction and model projections of the 21st century. The intensification is primarily attributed to a mega-El Niño/Southern Oscillation (a leading mode of interannual-to-interdecadal variation of global sea surface temperature) and the Atlantic Multidecadal Oscillation, and further influenced by hemispherical asymmetric global warming. These factors driving the present changes of the NHSM system are instrumental for understanding and predicting future decadal changes and determining the proportions of climate change that are attributable to anthropogenic effects and long-term internal variability in the complex climate system.

Environmental prediction, risk assessment and extreme events: adaptation strategies for the developing world.

The uncertainty associated with predicting extreme weather events has serious implications for the developing world, owing to the greater societal vulnerability to such events. Continual exposure to unanticipated extreme events is a contributing factor for the descent into perpetual and structural rural poverty. We provide two examples of how probabilistic environmental prediction of extreme weather events can support dynamic adaptation. In the current climate era, we describe how short-term flood forecasts have been developed and implemented in Bangladesh. Forecasts of impending floods with horizons of 10 days are used to change agricultural practices and planning, store food and household items and evacuate those in peril. For the first time in Bangladesh, floods were anticipated in 2007 and 2008, with broad actions taking place in advance of the floods, grossing agricultural and household savings measured in units of annual income. We argue that probabilistic environmental forecasts disseminated to an informed user community can reduce poverty caused by exposure to unanticipated extreme events. Second, it is also realized that not all decisions in the future can be made at the village level and that grand plans for water resource management require extensive planning and funding. Based on imperfect models and scenarios of economic and population growth, we further suggest that flood frequency and intensity will increase in the Ganges, Brahmaputra and Yangtze catchments as greenhouse-gas concentrations increase. However, irrespective of the climate-change scenario chosen, the availability of fresh water in the latter half of the twenty-first century seems to be dominated by population increases that far outweigh climate-change effects. Paradoxically, fresh water availability may become more critical if there is no climate change.

Impact of shifting patterns of Pacific Ocean warming on North Atlantic tropical cyclones.

Two distinctly different forms of tropical Pacific Ocean warming are shown to have substantially different impacts on the frequency and tracks of North Atlantic tropical cyclones. The eastern Pacific warming (EPW) is identical to that of the conventional El Niño, whereas the central Pacific warming (CPW) has maximum temperature anomalies located near the dateline. In contrast to EPW events, CPW episodes are associated with a greater-than-average frequency and increasing landfall potential along the Gulf of Mexico coast and Central America. Differences are shown to be associated with the modulation of vertical wind shear in the main development region forced by differential teleconnection patterns emanating from the Pacific. The CPW is more predictable than the EPW, potentially increasing the predictability of cyclones on seasonal time scales.

Heightened tropical cyclone activity in the North Atlantic: natural variability or climate trend?

We find that long-period variations in tropical cyclone and hurricane frequency over the past century in the North Atlantic Ocean have occurred as three relatively stable regimes separated by sharp transitions. Each regime has seen 50% more cyclones and hurricanes than the previous regime and is associated with a distinct range of sea surface temperatures (SSTs) in the eastern Atlantic Ocean. Overall, there appears to have been a substantial 100-year trend leading to related increases of over 0.7 degrees C in SST and over 100% in tropical cyclone and hurricane numbers. It is concluded that the overall trend in SSTs, and tropical cyclone and hurricane numbers is substantially influenced by greenhouse warming. Superimposed on the evolving tropical cyclone and hurricane climatology is a completely independent oscillation manifested in the proportions of tropical cyclones that become major and minor hurricanes. This characteristic has no distinguishable net trend and appears to be associated with concomitant variations in the proportion of equatorial and higher latitude hurricane developments, perhaps arising from internal oscillations of the climate system. The period of enhanced major hurricane activity during 1945-1964 is consistent with a peak period in major hurricane proportions.