. Scientific Frontline

Friday, June 9, 2023

Zinc Transporter Has Built-in Self-regulating Sensor

Overall structure of a transmembrane ZIP zinc transporter protein determined by cryo-electron microscopy (cryo-EM) (left) and a schematic showing some of the functional features (right). A flexible loop (magenta) facing into the cell binds to zinc and folds to block the entry of more zinc when levels of this micronutrient get too high.
Illustration Credit: Courtesy of Brookhaven National Laboratory

Scientists at the U.S. Department of Energy’s (DOE) Brookhaven National Laboratory have determined the atomic-level structure of a zinc-transporter protein, a molecular machine that regulates levels of this crucial trace metal micronutrient inside cells. As described in a paper just published in Nature Communications, the structure reveals how the cellular membrane protein shifts its shape to move zinc from the environment into a cell, and temporarily blocks this action automatically when zinc levels inside the cell get too high.

“Zinc is important for many biological activities, but too much can be a problem,” said Qun Liu, the Brookhaven Lab biophysicist who led the project. “During evolution, different organisms have evolved in many ways to regulate zinc. But no one has shown that a transporter that controls the uptake of zinc from the environment can regulate its own activity. Our study is the first to show a zinc transporter with such a built-in sensor.”

The research was conducted as part of Brookhaven Lab’s Quantitative Plant Sciences Initiative (QPSI). Using a bacterial version of a zinc transporter that shares essential features with zinc transporters in plants, the scientists gained key insights into how these proteins work. 

“This research is part of our effort to understand how micronutrients like zinc are taken up by plants so we can understand how to design plants that are better able to grow on marginal land for the production of bioenergy,” said Brookhaven Lab Biology Department Chair John Shanklin, a co-author on the paper.  

Alcohol consumption increases the risks of over 60 diseases

Photo Credit: Taylor Friehl

Alcohol consumption increases the risks of over 60 diseases in Chinese men, including many diseases not previously linked to alcohol, according to a new study by researchers from Oxford Population Health and Peking University, published in Nature Medicine.

Alcohol consumption is estimated to be responsible for about 3 million deaths worldwide each year, and it is increasing in many low- and middle-income countries such as China. The harmful effects of heavy drinking for certain diseases (such as liver cirrhosis, stroke and several types of cancer) are well known, but very few studies have systematically assessed the impact of alcohol use on an extensive range of diseases within the same population.

The study shows that alcohol use increases the risks of 61 diseases in men in China, including many non-fatal diseases not known to be alcohol-related due to limited previous evidence. The findings of this study demonstrate the influence that alcohol intake may have on the risk of disease in populations around the world.

The researchers used data from the China Kadoorie Biobank (CKB), a collaborative study of over 512,000 adults recruited during 2004-08 from ten diverse urban and rural areas across China. Study participants were interviewed about their lifestyle and behaviors, including detailed alcohol drinking patterns. About a third of men, but only 2% of women, drank alcohol regularly (ie at least once a week). The researchers comprehensively assessed the health effects of alcohol use on over 200 different diseases in men identified through linkage to hospital records over a period of about 12 years. Importantly, they also undertook a genetic analysis to clarify whether or not alcohol intake was responsible for causing disease.

Study: Ingestion of taurine delays aging

Treating mice with taurine led to increased lifespans and healthspans, a study in Science shows. Henning Wackerhage, Professor of Exercise Biology provided data on human test subjects hinting at similar mechanisms in humans.
Photo Credit: Andreas Heddergott / TUM

Taurine deficiency is one of the driving forces in the aging process of humans and animals. This is one of the results of a study which has now been published in the prestigious journal Science. Treatment with taurine extends the lifespan of mice by 10 percent. Monkeys that receive the treatment remain healthy for longer. It is not known whether these two results apply to humans. However, the study demonstrates a link between some age-related diseases and low taurine levels.

Treating mice with taurine led to increased lifespans and healthspans, a study in Science shows. Henning Wackerhage, Professor of Exercise Biology provided data on human test subjects hinting at similar mechanisms in humans.

Ancient herbivore’s diet weakened teeth leading to eventual starvation

Reconstruction of the rhynchosaur Bentonyx from the Middle Triassic of Devon, about 245 million years ago.
Illustration Credit: Reconstruction artwork by Mark Witton

A team of researchers from the University of Bristol have shed light on the life of the ancient reptile Rhynchosaur, which walked the earth between 250-225 million years ago, before being replaced by the dinosaurs.

Rhynchosaurs are a little-understood group of roughly sheep-sized ancient reptiles that thrived during the Triassic Period, a time of generally warm climates and tough vegetation.  

In the new study, the researchers studied specimens found in Devon and used CT scanning to see how the teeth wore down as they fed, and how new teeth were added at the backs of the tooth rows as the animals grew in size.

The findings, published today in Palaeontology, show that these early herbivores likely eventually starved to death in old age, the vegetation taking its toll on their teeth.

“I first studied the rhynchosaurs years ago,” said team-leader Professor Mike Benton from Bristol’s School of Earth Sciences, “and I was amazed to find that in many cases they dominated their ecosystems. If you found one fossil, you found hundreds.

Key clue to what causes cancer

Photo Credit: PDPics

Australian cancer researchers have made an important new connection between a person’s cancer risk and the functions of circular RNAs, a recently discovered family of genetic fragments present within our cells. 

A new Flinders University-led study published in Cancer Cell, one of the world’s top cancer journals, finds that specific circular RNAs within many of us can stick to the DNA in our cells and cause DNA mutations which result in cancer. 

“While environmental and genetic factors have long been believed the major contributors to cancer, this revolutionary finding – which we call ‘ER3D’ (from ‘endogenous RNA directed DNA damage’) – ushers in an entirely new area of medical and molecular biology research,” says Flinders University Professor Simon Conn, who leads the Circular RNAs in Cancer Laboratory at the Flinders Health and Medical Research Institute. 

“This is the first example of a genetic molecule present within many of us which has the capacity to mutate our very own DNA and drive cancer from inside.  

“This opens the door to use these molecules as new therapeutic targets and markers of disease at a very early stage, when the likelihood of curing cancers is much higher.”  

Study finds the best plants and bee hotels for boosting urban bee numbers

Photo Credit: Dr Kit Prendergast

The presence of more native Australian flowering plants in urban areas can help boost declining bee numbers, with new Curtin University research finding them to be the preferred source of food for both native bees and the introduced European honeybee.

The study focused on 14 sites across the Perth metropolitan area, including bushland remnants and home gardens,

Researcher Dr Kit Prendergast from the Curtin School of Molecular and Life Sciences, said the study found Australian and introduced bees preferred to visit and feed from native flowers and plants rather than exotic species, with the former particularly reliant on native flora.

“With wild bees facing a global decline, largely due to habitat loss through urbanization, it is vital to understand their preferences. Although urban areas often have a diversity of flowers compared to natural habitats, many of these flowers are exotic species,” Dr Prendergast said.

The research also helps homeowners, landscapers, landcare communities and councils with a “top ten” species to plant.

Scientists Discover what Influences Seawater Freezing Rates

Sea ice freezes faster when temperatures fluctuate.
Photo Credit: Cassie Matias

Seawater freezes faster in the presence of wind and underwater currents at temperatures below zero. This was found out by experts from the Laboratories of Multiscale Mathematical Modeling, and Climate and Environmental Physics of the Ural Federal University. They created a mathematical model and calculated the conditions of seawater freezing. The description of the model and its conclusions were published in the European Physical Journal.

"It turns out that at temperatures around zero and below, even a slight breeze affects the rate of ice formation. The fact is that the wind, just like the underwater current, causes fluctuations (jumps) in temperature, and this in turn leads to faster formation of ice crystals. In other words, with wind or underwater currents, ice freezes faster, the ice layer becomes thicker. Yes, it is looser, not as dense, but the rate of formation increases," explains study co-author Evgeniya Makoveeva, Lead Researcher at the Laboratory of Multi-Scale Mathematical Modeling of the Ural Federal University.

This happens at any temperature suitable for crystallization, the scientist adds. The effect of temperature is amplified by external noises - wind and underwater currents - that "bring" different temperatures.

Thursday, June 8, 2023

Some Gut Bacteria Linked to Precancerous Colon Polyps

Scientific Frontline stock graphic

A new study by Harvard Medical School investigators at Massachusetts General Hospital has linked certain types of gut bacteria to the development of precancerous colon polyps. Their results are published in Cell Host & Microbe.

“Researchers have done a lot of work to understand the relationship between the gut microbiome and cancer. But this new study is about understanding the microbiome’s influence on precancerous polyps,” said co-corresponding author Daniel C. Chung, HMS professor of medicine, medical co-director of the Center for Cancer Risk Assessment at Mass General Cancer Center, and a faculty member of the gastroenterology division at Mass General.

“Through the microbiome, we potentially have an opportunity to intervene and prevent colorectal cancer from forming,” he said.

Colorectal cancer is the second-leading cause of cancer-related deaths in the U.S., and rates of colorectal cancer are rising among young adults.

Nearly all colorectal cancers arise from a precancerous polyp. One of the best ways to reduce the incidence of colorectal cancer is to stop the growth at the polyp stage.

New model offers a way to speed up drug discovery

Researchers can screen more than 100 million compounds in a single day — much more than any existing model.
Photo Credit: Myriam Zilles

Huge libraries of drug compounds may hold potential treatments for a variety of diseases, such as cancer or heart disease. Ideally, scientists would like to experimentally test each of these compounds against all possible targets, but doing that kind of screen is prohibitively time-consuming.

In recent years, researchers have begun using computational methods to screen those libraries in hopes of speeding up drug discovery. However, many of those methods also take a long time, as most of them calculate each target protein’s three-dimensional structure from its amino-acid sequence, then use those structures to predict which drug molecules it will interact with.

Researchers at MIT and Tufts University have now devised an alternative computational approach based on a type of artificial intelligence algorithm known as a large language model. These models — one well-known example is ChatGPT — can analyze huge amounts of text and figure out which words (or, in this case, amino acids) are most likely to appear together. The new model, known as ConPLex, can match target proteins with potential drug molecules without having to perform the computationally intensive step of calculating the molecules’ structures.

Researchers warn of future ‘fish wars’ as consequence of climate change

Photo Credit: Sabrina Eickhoff

How climate change could give rise to “fish wars” between nations is the subject of a new research project awarded a £1.1m grant by the US Department of Defense.

The project, entitled “Future Fish Wars: Chasing Ocean Ecosystem Wealth”, is one of 11 to receive a total funding of $18m as part of the US Department of Defense's Minerva Research Initiative, which supports research in social and behavioral sciences on topics relevant to US national security.

The researchers aim to develop new economic theory and approaches to measure the economic value of fisheries in the context of climate change and growing geopolitical ocean conflict.

They say illegal fishing, contested claims to fishing rights and future conflicts are likely outcomes as fish swim for the poles as a result of climate change warming the oceans. 

Over three years, the research team will develop new economic theory for valuing multiple stocks of marine resources, which they will use alongside novel data on conflict and cooperative events to achieve a deeper understanding of future fisheries conflict.

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