EGCG inactivates a pore-forming toxin by promoting its oligomerization and decreasing its solvent-exposed hydrophobicity.

Natural proteinaceous pore-forming agents can bind and permeabilize cell membranes, leading to ion dyshomeostasis and cell death. In the search for antidotes that can protect cells from peptide toxins, we discovered that the polyphenol epigallocatechin gallate (EGCG) interacts directly with melittin from honeybee venom, resulting in the elimination of its binding to the cell membrane and toxicity by markedly lowering the extent of its solvent-exposed hydrophobicity and promoting its oligomerization into larger species. These physicochemical parameters have also been shown to play a key role in the binding to cells of misfolded protein oligomers in a host of neurodegenerative diseases, where oligomer-membrane binding and associated toxicity have been shown to correlate negatively with oligomer size and positively with solvent-exposed hydrophobicity. For melittin, which is not an amyloid-forming protein and has a very distinct mechanism of toxicity compared to misfolded oligomers, we find that the size-hydrophobicity-toxicity relationship also rationalizes the pharmacological attenuation of melittin toxicity by EGCG. These results highlight the importance of the physicochemical properties of pore forming agents in mediating their interactions with cell membranes and suggest a possible therapeutic approach based on compounds with a similar mechanism of action as EGCG.

Over half of known human pathogenic diseases can be aggravated by climate change.

It is relatively well accepted that climate change can affect human pathogenic diseases; however, the full extent of this risk remains poorly quantified. Here we carried out a systematic search for empirical examples about the impacts of ten climatic hazards sensitive to greenhouse gas (GHG) emissions on each known human pathogenic disease. We found that 58% (that is, 218 out of 375) of infectious diseases confronted by humanity worldwide have been at some point aggravated by climatic hazards; 16% were at times diminished. Empirical cases revealed 1,006 unique pathways in which climatic hazards, via different transmission types, led to pathogenic diseases. The human pathogenic diseases and transmission pathways aggravated by climatic hazards are too numerous for comprehensive societal adaptations, highlighting the urgent need to work at the source of the problem: reducing GHG emissions.

A Brain-Permeable Aminosterol Regulates Cell Membranes to Mitigate the Toxicity of Diverse Pore-Forming Agents.

The molecular composition of the plasma membrane plays a key role in mediating the susceptibility of cells to perturbations induced by toxic molecules. The pharmacological regulation of the properties of the cell membrane has therefore the potential to enhance cellular resilience to a wide variety of chemical and biological compounds. In this study, we investigate the ability of claramine, a blood-brain barrier permeable small molecule in the aminosterol class, to neutralize the toxicity of acute biological threat agents, including melittin from honeybee venom and α-hemolysin from Staphylococcus aureus. Our results show that claramine neutralizes the toxicity of these pore-forming agents by preventing their interactions with cell membranes without perturbing their structures in a detectable manner. We thus demonstrate that the exogenous administration of an aminosterol can tune the properties of lipid membranes and protect cells from diverse biotoxins, including not just misfolded protein oligomers as previously shown but also biological protein-based toxins. Our results indicate that the investigation of regulators of the physicochemical properties of cell membranes offers novel opportunities to develop countermeasures against an extensive set of cytotoxic effects associated with cell membrane disruption.

Traditional and novel time-series approaches reveal submarine groundwater discharge dynamics under baseline and extreme event conditions.

Groundwater is a vital resource for humans and groundwater dependent ecosystems. Coastal aquifers and submarine groundwater discharge (SGD), both influenced by terrestrial and marine forces, are increasingly affected by climate variations and sea-level rise. Despite this, coastal groundwater resources and discharge are frequently poorly constrained, limiting our understanding of aquifer responses to external forces. We apply traditional and novel time-series approaches using an SGD dataset of previously unpublished resolution and duration, to analyze the dependencies between precipitation, groundwater level, and SGD at a model site (Kiholo Bay, Hawai'i). Our objectives include (1) determining the relative contribution of SGD drivers over tidal and seasonal periods, (2) establishing temporal relationships and thresholds of processes influencing SGD, and (3) evaluating the impacts of anomalous events, such as tropical storms, on SGD. This analysis reveals, for example, that precipitation is only a dominant influence during wet periods, and otherwise tides and waves dictate the dynamics of SGD. It also provides time lags between intense storm events and higher SGD rates, as well as thresholds for precipitation, wave height and tides affecting SGD. Overall, we demonstrate an approach for modeling a hydrological system while elucidating coastal aquifer and SGD response in unprecedented detail.

Submarine groundwater discharge: A previously undocumented source of contaminants of emerging concern to the coastal ocean (Sydney, Australia).

Submarine groundwater discharge (SGD) is rarely considered as a pathway for contaminants of emerging concern (CECs). Here, we investigated SGD as a source of CECs in Sydney Harbour, Australia. CEC detection frequencies based on presence/absence of a specific compound were >90% for caffeine, carbamazepine, and dioxins, and overall ranged from 25 to 100% in five studied embayments. SGD rates estimated from radium isotopes explained >80% of observed CEC inventories for one or more compounds (caffeine, carbamazepine, dioxins, sulfamethoxazole, fluoroquinolones and ibuprofen) in four out of the five embayments. Radium-derived residence times imply mixing is also an important process for driving coastal inventories of these persistent chemicals. Two compounds (ibuprofen and dioxins) were in concentrations deemed a high risk to the ecosystem. Overall, we demonstrate that SGD can act as a vector for CECs negatively impacting coastal water quality.

Fukushima-derived radiocesium fallout in Hawaiian soils.

Several reactors at the Fukushima Dai-ichi Nuclear Power Plant suffered damage on March 11, 2011, resulting in the release of radiocesium (134Cs and 137Cs), as well as other radionuclides, into the atmosphere. A week later, these isotopes were detected in aerosols over the state of Hawai'i and in milk samples analyzed on the island of Hawai'i. This study estimated the magnitude of cesium deposition in soil, collected in 2015-2016, resulting from atmospheric fallout. It also examined the patterns of cesium wet deposition with precipitation observed on O'ahu and the island of Hawai'i following the disaster. Fukushima-derived fallout was differentiated from historic nuclear weapons testing fallout by the presence of 134Cs and the assumption that the 134Cs to 137Cs ratio was 1:1. Detectable, Fukushima-derived 134Cs inventories ranged from 30 to 630 Bq m-2 and 137Cs inventories ranged from 20 to 2200 Bq m-2. Fukushima-derived cesium inventories in soils were related to precipitation gradients, particularly in areas where rainfall exceeded 200 mm between March 19 and April 4, 2011. This research confirmed and quantified the presence of Fukushima-derived fallout in the state of Hawai'i in amounts higher than predicted by models and observed in the United States mainland, however the activities detected were an order of magnitude lower than fallout associated with historic sources such as the nuclear weapons testing in the Pacific. In addition, this study showed that areas of highest cesium deposition do not overlap with densely populated or agriculturally used areas.