NEWS
BUSINESS Weather warning for chemicals MARIA BURKE
More research and better regulation are needed to guard against risks from chemical facilities at danger from extreme weather events, according to a new US study. These risks are already acute and are growing due to the effects of climate change. Many chemical facilities are located
in low-lying coastal areas and vulnerable to damage from hurricanes, flooding and erosion, all of which are increasing with climate change, say Susan Anenberg and Casey Kalman of George Washington University Milken Institute School of Public Health (GeoHealth, doi: 10.1029/2019GH000197). Extreme weather can trigger industrial disasters, including explosions, fires and major chemical releases, as well as chronic chemical leakage into air, water and soil. A recent example occurred at the Arkema facility in Crosby, Texas, during Hurricane Harvey in 2017. Officials evacuated 200 people living around the plant after flooding shut down the plant’s refrigeration system, causing organic
MEDICINE Quenching inflammation MARIA BURKE
Treatments for chronic inflammatory diseases may be one step closer, thanks to two independent teams of researchers. Their findings give new insight into how to stop inflammation at the molecular level. Inflammasomes are part of the immune
system that help regulate inflammation. When these protein complexes ‘sense’ danger, they produce and control a family of cytokines involved in inflammation. Inflammasomes are important in protecting against infection, but they are also a key driver of unhealthy inflammation. When the inflammasome is not switched off, inflammation becomes damaging. Uncontrolled inflammation results in chronic diseases, such as Parkinson’s and Alzheimer’s, and respiratory diseases such as asthma. Whereas some inflammasomes
are triggered by pathogens, the NLRP3 inflammasome responds mainly to ‘signals’ from the environment, or from the host, and has been linked to various inflammatory diseases. Finding molecules that inhibit its
activity is a promising strategy for developing new treatments. University of Queensland (UQ)
researchers Kate Schroder, Rebecca Coll, now at Queen’s University Belfast, and Avril Robertson have previously identified a small molecule, MCC950, that inhibits the NRLP3 inflammasome but they did not understand how it worked. Now they have discovered that MCC950 binds to and inactivates the inflammasome at specific sites, turning off inflammation (Nature Chemical Biology, 2019, 15, 556).
In the paper, the team reports that MCC950 specifically and reversibly binds to NLRP3, blocking its ability to hydrolyse adenosine triphosphate (ATP), a nucleotide that is the primary source of energy in all living cells. By binding to NLRP3, MCC950 prevents it tak- ing on its active, open conformation, and so blocks its role in inflammation. They say their data confirm the critical role of ATP binding and hydrolysis in the function of NLRP3. The finding could unlock the potential of inflammasome inhibitors as anti-
inflammatory drugs. UQ start-up Inflazome, which is developing targeted therapies for inflammatory diseases, has announced plans to start clinical trials of these inflammasome inhibitors in 2019. Another paper from Pablo Perregrin’s
group at the Murcia BioHealth Research Institute in Spain confirms the molecular mechanism involved in NLRP3 binding (Nature Chemical Biology, 2019, 15, 560). The Schroder and Pellegrin laboratories
now independently provide compelling evidence for direct inhibition of NLRP3, write Oliver Gorka, Emilia Neuwirt and Olaf Groß of the University of Freiburg, Germany, in an accompanying commentary (Nature Chemical Biology, 2019, 15, 552). These studies suggest the ATP-binding domain of NLRP3 is ‘the primary druggable site’ for modulating inflammasome activity. ‘These insights provide a basis for the rational development of new, superior NLRP3-inhibiting compounds to target this inflammasome in conditions of acute and chronic inflammation and connected pathologies.’
peroxides on site to explode. This study finds that there
are almost 900 industrial chemical facilities within 50 miles of the Gulf Coast in the US, a region particularly
prone to hurricanes. More than 4.3m people live within 1.5 miles of the Gulf Coast facilities, and 1717 schools and 98 medical facilities fall within the same area. In an analysis of data from the US Chemical Safety Board (CSB), the authors found that an incident, such as an explosion, fire or chemical release, occurred on average 1.5 times a day at facilities in the US. There were 9406 incidents between 2001 and 2018; and about 40% of them resulted in injuries or fatalities. Twenty per cent of the incidents occurred in the Gulf Coast states of Texas, Florida, Louisiana, Mississippi and Alabama; 10% in Texas alone. However, there are few data on the involvement of natural hazards in triggering these industrial disasters, the
authors note. Anenberg
and Kalman are concerned that the US Environmental Protection Agency and Occupational Safety and Health Administration ‘do not adequately require’ industrial facilities to specifically address the risks posed by extreme events. Natural events are not adequately regulated at the federal, state or local level, they warn, yet on the Gulf Coast, sea levels are rising, and the frequency and intensity of storms are expected to increase. However, they note that US industry has spent $12bn on a 60- mile sea-wall along the Gulf Coast to protect refineries against rising sea levels. ‘Co-location of extreme weather, chemical facilities and vulnerable communities is a potentially disastrous combination that is likely to
worsen with climate change,’ the authors conclude. ‘When the next hurricane hits, will we be prepared?’
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