A team of researchers at UC San Francisco, the California Academy of Sciences and Stanford University have uncovered some intriguing clues in the mystery of how some poison birds and frogs evade their own toxins. The answer may lead to a much-sought-after antidote to paralytic shellfish poisoning (PSP) experienced by people eating shellfish gathered after red tides, such as those that have recently plagued coasts of Florida and the Gulf of Mexico.
Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the SARS-CoV-2 spike protein is an envelope glycoprotein that binds angiotensin converting enzyme 2 as an entry receptor.
photo credit to:
In major cardiovascular diseases, including stroke and heart attack, loss of blood flow causes loss of oxygen (ischemia), leading to tissue damage and cell deaths. A species of ground squirrels from the Arctic can tolerate such ischemic attack, but the underlying biological basis has been unknown. The study from this paper led by Neel Singhal from the Ma lab at CVRI identified an unusual protein variant ATP5G1 from cells of Arctic ground squirrels that contributes to the protection from ischemic stress. This basic science discovery may lay the groundwork to develop potential therapeutic strategies to treat human ischemic disorders.
In a clinical collaboration with Melvin Scheinman from the UCSF Comprehensive Genetic Arrythmia Program, CVRI investigators Rahul Deo and Natalia Jura, along with MD/PhD trainee Erron Titus, set out to explain how mutations in the calcium-storage protein, calsequestrin, cause lethal arrhthymias. The team solved a new X-ray crystal structure of human cardiac calsequestrin, revealing the biochemical basis of calsequestrin’s assembly into filaments. Using the new structure, the team was able to map disease-associated mutations to the filament surfaces and explain how the location of the mutation in the structure determines the severity of disease.
The global burden of diabetes is rapidly increasing, from 451 million people in 2019 to 693 million by 20451. The insidious onset of type 2 diabetes delays diagnosis and increases morbidity2. Given the multifactorial vascular effects of diabetes, we hypothesized that smartphone-based photoplethysmography could provide a widely accessible digital biomarker for diabetes. y 20451.
Beta blockers are among the most widely used drugs for treating heart failure. It has long been thought that these drugs act on proteins, known as adrenergic receptors, that solely reside on cell surfaces. A recent study by scientists at CVRI and the University of Michigan has discovered a previously unknown role for adrenergic receptors within cells. When beta blockers were developed, there were no considerations for their abilities to access internal adrenergic receptors. This new knowledge can potentially lead to the development of drugs that are more effective in the treatment of cardiovascular disease.
As climate change brings more red tides, a protein from the American bullfrog might provide protection from paralytic shellfish poisoning.
As climate change raises ocean temperatures, fisheries and public health agencies closely monitor the waters for harmful algal blooms known as red tides. The algae in these blooms produce a neurotoxin that accumulates in shellfish, rendering them dangerous, or even lethal, for human consumption. Bullfrogs, however, have a natural defense in the form of a protein known as saxiphilin.
There is a weapon that is released by algae around the world and concentrated, invisible, in the flesh of shellfish. An amount the size of a poppy seed is enough to kill a grown person. It’s part of an onslaught from which we’ve defended ourselves for decades, which might be why you’ve never heard of it.
CVRI investigators have uncovered how an American bullfrog protein known as saxiphilin binds to and inhibits the action of saxitoxin. This deadly neurotoxin, which is about one thousand times more potent than cyanide, is made by algal blooms known as ‘red tide’. If ingested from contaminated shellfish, the toxin blocks electrical signaling in nerves and muscles, leading to death. Red tides are becoming more common due to climate change and these findings may lead to new ways to detect and neutralize the toxin.
CVRI investigators decipher the mechanism by which platelets are activated to form clots, a key step in both normal and thrombotic processes. The researchers reveal how interactions between transmembrane helices of key proteins found in the membranes of platelets and many other cells help orchestrate the process. Their work is also informs our understanding of the assembly of many other proteins involved in transmembrane signal transduction.
Rustem I. Litvinov, Marco Mravic, Hua Zhu, John W. Weisel, William F. DeGrado, and Joel S. Bennett