Toxic protein ‘variant’ may be the next target for ALS therapies

Penn State College of Medicine researchers studied whether toxic trimers of the protein SOD1 are an intermediate step in the formation of large insoluble aggregates, or whether the trimers form separately off pathway. Their latest study shows toxic trimers form off pathway from large insoluble aggregates formation.
Credit: Penn State College of Medicine

Scientists have long known that proteins can form harmful clusters in neurodegenerative diseases like Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis (ALS). But a new study by Penn State researchers shows that ‘variant’ complexes of a protein implicated in ALS pathology form in separate pathways, a discovery which may make it easier for drug developers to design therapies to target the more harmful variant.

Superoxide dismutase (SOD1) is an aggregating protein that contributes to ALS development and progression, though it is unclear which biological mechanisms it uses to do this. Mutations in this protein have been implicated in 15-30% of familial ALS cases and 1-2% of spontaneous ALS cases. Normally existing in a two-part dimer, loss of SOD1 copper or zinc ions can cause it to separate into two separate monomers, or units. Monomers can form form a trimer, or three-part form, or aggregate into larger fibrils, which consist of many SOD1 monomers. Previous research showed that the trimer form is toxic to cells. Other research has suggested that the larger aggregate form may actually have a protective function.

Research Shows How Gulf of Mexico Escaped Ancient Mass Extinction

The Mississippi River flowing into the Gulf of Mexico. According to researchers at the University of Texas Institute for Geophysics, river sediments and ocean currents helped simple sea life in the Gulf survive a deep-ocean mass extinction 56 million years ago.
Credit: U.S. Geological Survey

An ancient bout of global warming 56 million years ago that acidified oceans and wiped-out marine life had a milder effect in the Gulf of Mexico, where life was sheltered by the basin’s unique geology – according to research by the University of Texas Institute for Geophysics (UTIG).

Published in the journal Marine and Petroleum Geology, the findings not only shed light on an ancient mass extinction, but could also help scientists determine how current climate change will affect marine life and aid in efforts to find deposits of oil and gas.

And although the Gulf of Mexico is very different today, UTIG geochemist Bob Cunningham, who led the research, said that valuable lessons can be drawn about climate change today from how the Gulf was impacted in the past.

“This event known as the Paleocene-Eocene Thermal Maximum or PETM is very important to understand because it’s pointing towards a very powerful, albeit brief, injection of carbon into the atmosphere that’s akin to what’s happening now,” he said.

Cunningham and his collaborators investigated the ancient period of global warming and its impact on marine life and chemistry by studying a group of mud, sand, and limestone deposits found across the Gulf.

Less air pollution leads to higher crop yields

Usually, increasing agricultural productivity depends on adding something, such as fertilizer or water. A new Stanford University-led study reveals that removing one thing in particular – a common air pollutant – could lead to dramatic gains in crop yields. The analysis, published June 1 in Science Advances, uses satellite images to reveal for the first time how nitrogen oxides – gases found in car exhaust and industrial emissions – affect crop productivity. Its findings have important implications for increasing agricultural output and analyzing climate change mitigation costs and benefits around the world.

“Nitrogen oxides are invisible to humans, but new satellites have been able to map them with incredibly high precision. Since we can also measure crop production from space, this opened up the chance to rapidly improve our knowledge of how these gases affect agriculture in different regions,” said study lead author David Lobell, the Gloria and Richard Kushel Director of Stanford’s Center on Food Security and the Environment.

A NOx-ious problem

Nitrogen oxides, or NOx, are among the most widely emitted pollutants in the world. These gases can directly damage crop cells and indirectly affect them through their role as precursors to formation of ozone, an airborne toxin known to reduce crop yields, and particulate matter aerosols that can absorb and scatter sunlight away from crops.

How Electric Fish Were Able to Evolve Electric Organs

UT Austin researchers confirmed that the genetic control region they discovered only controls the expression of a sodium channel gene in muscle and no other tissues. In this image, a green fluorescent protein lights up only in trunk muscle in a developing zebrafish embryo.
Image credit: Mary Swartz/Johann Eberhart/University of Texas at Austin.

Electric organs help electric fish, such as the electric eel, do all sorts of amazing things: They send and receive signals that are akin to bird songs, helping them to recognize other electric fish by species, sex and even individual. A new study in Science Advances explains how small genetic changes enabled electric fish to evolve electric organs. The finding might also help scientists pinpoint the genetic mutations behind some human diseases.

Evolution took advantage of a quirk of fish genetics to develop electric organs. All fish have duplicate versions of the same gene that produces tiny muscle motors, called sodium channels. To evolve electric organs, electric fish turned off one duplicate of the sodium channel gene in muscles and turned it on in other cells. The tiny motors that typically make muscles contract were repurposed to generate electric signals, and voila! A new organ with some astonishing capabilities was born.

“This is exciting because we can see how a small change in the gene can completely change where it’s expressed,” said Harold Zakon, professor of neuroscience and integrative biology at The University of Texas at Austin and corresponding author of the study.

In the new paper, researchers from UT Austin and Michigan State University describe discovering a short section of this sodium channel gene—about 20 letters long—that controls whether the gene is expressed in any given cell. They confirmed that in electric fish, this control region is either altered or entirely missing. And that’s why one of the two sodium channel genes is turned off in the muscles of electric fish. But the implications go far beyond the evolution of electric fish.

Small, rare crayfish thought extinct is rediscovered

Dr. Matthew L. Niemiller snorkels in Shelta Cave, where a species of crayfish believed to be extinct was rediscovered. 
Credit: Amata Hinkle

A small, rare crayfish thought to be extinct for 30 years has been rediscovered in a cave in the City of Huntsville in northern Alabama by a team led by an assistant professor at The University of Alabama in Huntsville (UAH).

Dr. Matthew L. Niemiller’s team found individuals of the Shelta Cave Crayfish, known scientifically as Orconectes sheltae, in 2019 and 2020 excursions into Shelta Cave – its only home.

Dr. Niemiller, an assistant professor of biological sciences at UAH, a part of the University of Alabama System, is co-author of a paper on the findings in the journal Subterranean Biology. Besides Dr. Niemiller, authors are UAH’s Katherine E. Dooley and K. Denise Kendall Niemiller, and Nathaniel Sturm of the University of Alabama.

The crayfish’s home is a 2,500-foot cave system that’s owned and managed by the National Speleological Society (NSS) and is unobtrusively located beneath the organization’s national headquarters in northwest Huntsville and is surrounded by subdivisions and bustling roadways.

“The crayfish is only a couple of inches long with diminutive pincers that are called chelae,” Dr. Niemiller says. “Interestingly, the crayfish has been known to cave biologists since the early 1960s but was not formally described until 1997 by the late Dr. John Cooper and his wife Martha.”

Evidence of galactic metal shrouded in dust

NASA’s SOFIA airborne observatory enabled a UCI-led team of astronomers to study infrared emissions from five nearby galaxies. The researchers found more metal than expected in the intergalactic medium, a result that would have been difficult to achieve without the power of viewing infrared radiation through thick galactic dust.
Credit: Jim Ross / NASA

A thorough understanding of galaxy evolution depends in part on an accurate measurement of the abundance of metals in the intergalactic medium – the space between stars – but dust can impede observations in optical wavelengths. An international team of astronomers at the University of California, Irvine, Oxford University in England, and other institutions uncovered evidence of heavier elements in local galaxies – found to be deficient in earlier studies – by analyzing infrared data gathered during a multiyear campaign.

For a paper published recently in Nature Astronomy, the researchers examined five galaxies that are dim in visible wavelengths but trillions of times more luminous than the sun in the infrared. Interactions between these galaxies and neighboring star systems cause gas to shift around and collapse, setting up conditions for prodigious star formation.

“Studying the gas content of these galaxies with optical instruments, astronomers were convinced that they were significantly metal-poor when compared with other galaxies of similar mass,” said lead author Nima Chartab, UCI postdoctoral scholar in physics & astronomy. “But when we observed emission lines of these dusty galaxies in infrared wavelengths, we were afforded a clear view of them and found no significant metal deficiency.”

Boeing Teams with Canadian Industry to Offer P-8A Poseidon

The P-8A Poseidon
Credit: Boeing

Boeing [NYSE: BA] and several Canadian industry partners announced today their intent to collaborate to provide the capability and sustainability of the proven P-8A Poseidon for the Canadian Multi-Mission Aircraft (CMMA) requirement.

Team Poseidon, consisting of CAE, GE Aviation Canada, IMP Aerospace & Defense, KF Aerospace, Honeywell Aerospace Canada and Raytheon Canada, forms the cornerstone of a Canadian P-8 industrial footprint. The team builds on 81 Canadian suppliers to the platform and to more than 550 Canadian suppliers across all provinces contributing to Boeing's annual CAD $5.3 billion in economic benefit to Canada, supporting more than 20,000 Canadian jobs.

The Boeing P-8A is a proven military off-the-shelf solution with nearly 150 aircraft delivered to five nations to date. The P-8 will improve Canada’s capability to defend its northern and maritime borders while ensuring interoperability with NORAD and NATO allies. As a leading platform for reducing the environmental impact of military aircraft, the P-8 can operate on a 50% blend of sustainable aviation fuel today with aspirations to move toward 100% with investment in new technology.

No more flu for you? Discovery blocks influenza virus’ replication in cells

Jiayu Liao
Source: University of California, Riverside

It happens every year, especially in winter. A virus saunters into your wide-open respiratory tract, worms its way into lung cells, and, next thing you know, you’re lying-in bed with a fever, aches, and chills—classic symptoms of influenza, or flu.

Research led by UC Riverside bioengineers may help stop that cycle. The team has just found a way to block one strain of the influenza virus from accessing a human protein it needs to replicate in cells. The discovery could lead to highly effective ways to treat the flu and could also apply to other respiratory viruses, such as SARS-CoV-2, which causes Covid-19.

While the flu is miserable but not life-threatening for many, it nonetheless kills tens of thousands of people each year, often the youngest and oldest members of a population. The Centers for Disease Control and Prevention estimates that flu causes 12,000 to 50,000 deaths in U.S. each year. Flu vaccines, which work by teaching the body’s immune system how to recognize and attack the virus when it enters the body, are not always effective for reasons scientists don’t yet fully understand but are likely related to the complexities of the immune system and viral mutations.

The new research, published in the journal Viruses, does not rely on the immune system to stop the virus. 

In order to make a person sick, the influenza virus has to infect cells in the body, where it replicates and infects more cells. Jiayu Liao, an associate professor of bioengineering at UC Riverside, previously discovered that the two most common types of flu virus, Influenza A and Influenza B, require a unique human protein to proliferate in cells and then infect more cells. 

Blocking enzyme could hold the key to preventing, treating severe COVID-19

Amal Amer

The sickest COVID-19 patients develop acute respiratory distress syndrome resulting from the combination of high levels of pro-inflammatory proteins called cytokines, fluid accumulation in air sacs that seeps into lung tissue and blood clots, or thrombosis, caused by damage to cells lining vessel walls. In a series of experiments in infected mice, the research team found that inhibiting caspase 11 reduced the intensity of multiple effects.

Blocking an immune response-related enzyme holds promise in preventing or treating severe COVID-19 symptoms by reducing inflammation, tissue injury and blood clots in the lungs, new research in mice suggests.

Scientists who have long studied this molecule’s functions in bacterial infections traced the development of extensive lung damage in infected mice to heightened levels of the enzyme triggered by the invading SARS-CoV-2 virus.

Versions of this enzyme exist and have similar functions in both mice and humans – they’re called caspase 11 and caspase 4, respectively. After finding that the molecule is an attractive therapeutic target, researchers are exploring compounds that could safely and effectively block its activation.

“The whole idea is if this molecule is not there, the mouse will do better, which means if you target this molecule, then humans should do better,” said co-senior study author Amal Amer, professor of microbial infection and immunity in The Ohio State University College of Medicine.

The research was published online recently in Proceedings of the National Academy of Sciences.

Cuttlefish: Chameleons of the sea

European cuttlefish
Source: City, University of London

Study suggests that European cuttlefish use a more complex strategy than previously thought to camouflage themselves within underwater surroundings.

A new study by City, University of London and others suggests that the European cuttlefish (sepia officinalis) may combine, as necessary, two distinct neural systems that process specific visual features from its local environment, and visual cues relating to its overall background environment to create the body patterns it uses to camouflage itself on the sea floor.

This is in contrast to previous research suggesting that the cognitive (brain) processes involved are much simpler, in that the cuttlefish adopts one of only three major types of body patterns to visually merge with its background. However, that does not explain why the animal possesses about 30 different body pattern components it could use to achieve this.

The study explored whether the cuttlefish uses a cognitive process that is triggered by specific, visual features in its environment and which warrants the number of body pattern components it possesses.

Like their cephalopod relatives the octopus and the squid, cuttlefish are masters at blending in with their environments, which is largely attributable to the way their brains are able to control how pigments in special cells called chromatophores on their skin are displayed across their bodies.