How Proteins Control Genes to Prevent our Cells from Maldevelopment

Ole Nørregaard Jensen is a professor and head of research at the Department of Biochemistry and Molecular Biology.
Photo Credit: Stefan Kristensen

Every time a cell in our body prepares to divide, an extremely complex process begins to ensure that the mother cell's DNA is copied into a new daughter cell along with all the correct instructions for which genes on the DNA strand should be turned off and which should be activated.

If errors occur in this process and the new cell is not identical to the mother cell, damage and disease may occur.

Researchers are therefore interested in learning more about these processes and why the copying of DNA and instructions sometimes goes wrong.

Constant DNA replication of the cell

All humans have a unique DNA strand, originating from a single cell: the fertilized egg cell, which has divided and created the billions of cells that make up the whole human being. They all contain a copy of the DNA strand created at fertilization. However, different cells decode the DNA in different ways, allowing for the formation of more than 200 different cell types. Some cell types die quickly and need to be replaced many times during life; for example, skin cells and intestinal cells are renewed every few days. Each time a new cell is created, a copy of the unique DNA strand is made for the new cell.

Shape-shifting ultrasound stickers detect post-surgical complications

Three variations of the soft, flexible ultrasound sticker device displayed on a finger.
Photo Credit: Jiaqi Liu / Northwestern University

Researchers led by Northwestern University and Washington University School of Medicine in St. Louis have developed a new, first-of-its-kind sticker that enables clinicians to monitor the health of patients’ organs and deep tissues with a simple ultrasound device.

When attached to an organ, the soft, tiny sticker changes in shape in response to the body’s changing pH levels, which can serve as an early warning sign for post-surgery complications such as anastomotic leaks. Clinicians then can view these shape changes in real time through ultrasound imaging.

Currently, no existing methods can reliably and non-invasively detect anastomotic leaks — a life-threatening condition that occurs when gastrointestinal fluids escape the digestive system. By revealing the leakage of these fluids with high sensitivity and high specificity, the non-invasive sticker can enable earlier interventions than previously possible. Then, when the patient has fully recovered, the biocompatible, bioresorbable sticker simply dissolves away — bypassing the need for surgical extraction.

The study is published in the journal Science. The paper outlines evaluations across small and large animal models to validate three different types of stickers made of hydrogel materials tailored for the ability to detect anastomotic leaks from the stomach, the small intestine and the pancreas.

Lung cancer cells protected from cigarette smoke damage, researchers find

New research shows how lung cancer cells can survive better and exhibit less cell damage when exposed to cigarette smoke in cell culture experiments compared to non-cancerous lung cells. Image shows non-cancerous lung cells (left) and lung cancer cells (right), subjected to the same concentration of cigarette smoke condensate. Non-cancerous cells have more pronounced protein aggregation granules (shown with an arrow), stained by Proteostat, a type of cell damage that can eventually lead to cell death.
Image Credit: Krasilnikova Lab / Penn State
(CC BY-NC-ND 4.0 DEED)

Lung cancer cells survive better and exhibit less cell damage when exposed to cigarette smoke in cell culture experiments compared to non-cancerous lung cells. New research by a team of undergraduate students led by a Penn State molecular biologist may have revealed how lung cancer cells can persist in smoke. The mechanism could be related to how cancer cells develop resistance to pharmaceutical treatments as well.

The team found that a protein, which is expressed at high levels in some lung cancer cells and acts as a pump to transport molecules across the cell membrane, could potentially be clearing the damaging molecules coming from cigarette smoke. These molecules, if left uncleared inside the cells, can lead to protein aggregation that can damage and eventually kill lung cells.

“Cigarette smoke contains carcinogenic compounds, such as hydrocarbons and reactive oxygen and nitrogen species, that can damage cells in various ways,” said Maria Krasilnikova, associate research professor of biochemistry and molecular biology in the Eberly College of Science at Penn State and the lead author of the paper. “One way these compounds can damage cells is by causing proteins to misfold, which can lead to the formation of protein aggregates.”

When Plants Flower: Scientists ID Genes, Mechanism in Sorghum

Brookhaven Lab biologist Meng Xie and postdoctoral fellow Dimiru Tadesse with sorghum plants like those used in this study. Note that these plants are flowering, unlike those the scientists engineered to delay flowering indefinitely to maximize their accumulation of biomass.
Photo Credit: Kevin Coughlin/Brookhaven National Laboratory

Scientists at the U.S. Department of Energy’s (DOE) Brookhaven National Laboratory and Oklahoma State University have identified key genes and the mechanism by which they control flowering in sorghum, an important bioenergy crop. The findings, just published in the journal New Phytologist, suggest strategies to delay sorghum flowering to maximize plant growth and the amount of biomass available for generating biofuels and bioproducts.

“Our studies elucidate the gene regulatory network controlling sorghum flowering and provide new insights into how these genes could be leveraged to improve sorghum for achieving bioenergy goals,” said Brookhaven Lab biologist Meng Xie, one of the leaders of the research.

Sorghum is particularly well suited for sustainable agriculture because it can grow on marginal lands in semiarid regions and can tolerate relatively high temperatures. Like many plants, its growth and flowering (reproductive) cycles are regulated by the duration of daily sunlight. And once plants start to flower, they stop growing, which has important implications for the accumulation of biomass.

For example, one natural sorghum variety can reach nearly 20 feet in height, only transitioning to the reproductive flowering phase near the end of the summer growing season when the duration of daylight diminishes. Other “day-neutral” lines flower earlier, after reaching about three feet in height, producing less vegetation but more grain.

Researchers develop artificial building blocks of life

Structural comparison of DNA and the artificial TNA, a Xeno nucleic acid with the natural base pairs AT and GC and an additional base pair (XY).
Image Credit: Courtesy of University of Cologne

For the first time, scientists from the University of Cologne (UoC) have developed artificial nucleotides, the building blocks of DNA, with several additional properties in the laboratory. They could be used as artificial nucleic acids for therapeutic applications.

DNA carries the genetic information of all living organisms and consists of only four different building blocks, the nucleotides. Nucleotides are composed of three distinctive parts: a sugar molecule, a phosphate group and one of the four nucleobases adenine, thymine, guanine and cytosine. The nucleotides are lined up millions of times and form the DNA double helix, similar to a spiral staircase. Scientists from the UoC’s Department of Chemistry have now shown that the structure of nucleotides can be modified to a great extent in the laboratory. The researchers developed so-called threofuranosyl nucleic acid (TNA) with a new, additional base pair. These are the first steps on the way to fully artificial nucleic acids with enhanced chemical functionalities. The study ‘Expanding the Horizon of the Xeno Nucleic Acid Space: Threose Nucleic Acids with Increased Information Storage’ was published in the Journal of the American Chemical Society.

How the Body Copes With Airway Closure

Image Credit: Scientific Frontline stock image

There is perhaps no bodily function more essential for humans and other mammals than breathing. With each breath, we suffuse our bodies with oxygen-rich air that keeps our organs and tissues healthy and working properly — and without oxygen, we can survive mere minutes.

But sometimes, our breathing becomes restricted, whether due to infection, allergies, exercise, or some other cause, forcing us to take deep, gasping breaths to quickly draw in more air.

Now, researchers at Harvard Medical School have identified a previously unknown way in which the body counteracts restricted breathing — a new reflex of the vagus nerve that initiates deep breathing. Their work is published in Nature.

The research, conducted in mice, reveals a rare and mysterious cell type in the lungs that detects airway closure and relays the signal to the vagus nerve — the information highway that connects the brain to almost every major organ. After the signal reaches the brain, a gasping reflex is initiated that helps the animal compensate for the lack of air.

Keeping the immune system in check

Image Credit: © Julian Nüchel, Center for Biochemistry Cologne

Researchers from the UoC’s Center for Biochemistry at the Faculty of Medicine and the UoC CECAD Cluster of Excellence in Aging Research have discovered that an excessive immune response can be prevented by the intramembrane protease RHBDL4. In a study now published in Nature Communications under the title ‘RHBDL4-triggered downregulation of COPII adaptor protein TMED7 suppresses TLR4-mediated inflammatory signaling’, a previously unknown regulatory mechanism is described: The cleavage of a cargo receptor by a so-called intramembrane protease reduces the localization of a central immune receptor on the cell surface and thereby the risk of an overreaction of the immune system.

Intramembrane proteases are reactive proteins that reside in the cell membranes. They form a special group of proteases because they cut proteins within cellular membranes. Many of these unusual proteases have not yet been sufficiently characterized and only a few of the molecules they can cleave – the so-called substrates – and thus their functions are known. One of these intramembrane proteases is RHBDL4. It is located in the endoplasmic reticulum, a large intracellular membrane system that is responsible, among other things, for the correct folding of newly synthesized proteins that are fed into the secretory route.

Marine algae implants could boost crop yields

Discovery could lead to more sustainable food supply
Photo Credit: Oktavianus Mulyadi

Scientists have discovered the gene that enables marine algae to make a unique type of chlorophyll. They successfully implanted this gene in a land plant, paving the way for better crop yields on less land. 

Finding the gene solves a long-standing mystery amongst scientists about the molecular pathways that allow the algae to manufacture this chlorophyll and survive. 

“Marine algae produce half of all the oxygen we breathe, even more than plants on land. And they feed huge food webs, fish that get eaten by mammals and humans,” said UC Riverside assistant professor of bioengineering and lead study author Tingting Xiang. “Despite their global significance, we did not understand the genetic basis for the algae’s survival, until now.”

The study, published in Current Biology, also documents another first-of-its-kind achievement: demonstrating that a land plant could produce the marine chlorophyll. Tobacco plants were used for this experiment, but in theory, any land plant may be able to incorporate the marine algae gene, allowing them to absorb a fuller spectrum of light and achieve better growth. 

Unveiling Inaoside A: An Antioxidant Derived from Mushrooms

Discovering a new antioxidant compound, Inaoside A from Laetiporus cremeiporus
Image credit: Atsushi Kawamura from Shinshu University, Japan

Natural products have unique chemical structures and biological activities and can play a pivotal role in advancing pharmaceutical science. In a pioneering study, researchers from Shinshu University discovered Inaoside A, an antioxidant derived from Laetiporus cremeiporus mushrooms. This breakthrough sheds light on the potential of mushrooms as a source of therapeutic bioactive compounds.

The search for novel bioactive compounds from natural sources has gained considerable momentum in recent years due to the need for new therapeutic agents to combat various health challenges. Among a diverse array of natural products, mushrooms have emerged as a rich reservoir of bioactive molecules with potential pharmaceutical and nutraceutical applications. The genus Laetiporus has attracted attention for its extracts exhibiting antimicrobial, antioxidant, and antithrombin bioactivities. The species Laetiporus cremeiporus, spread across East Asia, has also been reported to show antioxidant properties. However, the identification and characterization of specific antioxidant compounds from this species have not been conducted.

In a groundbreakng study, researchers led by Assistant Professor Atsushi Kawamura from the Department of Biomolecular Innovation, Institute for Biomedical Sciences, Interdisciplinary Cluster for Cutting Edge Research, Shinshu University, along with Hidefumi Makabe from the Department of Agriculture, Graduate School of Science and Technology, Shinshu University, and Akiyoshi Yamada from the Department of Mountain Ecosystem, Institute for Mountain Science, Interdisciplinary Cluster for Cutting Edge Research, Shinshu University, recently discovered the antioxidant compound derived from L. cremeiporus.

Gene discovered that can protect against severe muscle disease

The researchers behind the study. Front row from the left: Hanna Nord, Fatima Pedrosa Domellöf, Jingxia Liu. Rear row: Abraha Kahsay, Nils Dennhag, Jonas von Hofsten
Photo Credit: Per Stål

A specific gene may play a key role in new treatments that prevent muscle in the body from breaking down in serious muscle diseases. This is shown in a new study at Umeå University, Sweden. Protein expressed by the gene naturally prevents the muscles around the eye from being affected when other muscles in the body are affected by muscular dystrophies. In the study the gene is expressed in all muscles. The effects were that muscular dystrophy was alleviated throughout the body.

"You could say that the eye muscles function both as an eye-opener for understanding the disease and as a door opener to a treatment for the whole body," says Fatima Pedrosa Domellöf, professor of eye diseases at Umeå University and one of the study's authors.

Muscular dystrophies are a group of congenital genetic diseases that affect muscle tissue and often lead to severe disability and greatly reduced life expectancy. Despite intensive research, there are still no effective treatments for patients suffering from muscular dystrophy.

Earliest-yet Alzheimer’s biomarker found in mouse model could point to new targets

Illinois graduate student Yeeun Yook, left, and professor Nien-Pei Tsai worked with their team to find the earliest marker of Alzheimer’s disease yet reported in the brains of mice. The work could create new targets for early detection or treatment options.
Photo Credit: Fred Zwicky

A surge of a neural-specific protein in the brain is the earliest-yet biomarker for Alzheimer’s disease, report University of Illinois Urbana-Champaign researchers studying a mouse model of the disease. Furthermore, the increased protein activity leads to seizures associated with the earliest stages of neurodegeneration, and inhibiting the protein in the mice slowed the onset and progression of seizure activity. 

The neural-specific protein, PSD-95, could pose a new target for Alzheimer’s research, early diagnosis and treatment, said study leader Nien-Pei Tsai, an Illinois professor of molecular and integrative physiology. 

Tsai’s group studies mice that make more of the proteins that form amyloid-beta, which progressively aggregates in Alzheimer’s disease to form plaques in the brain that hamper neural activity. However, in the new work, the group focused on a time frame much earlier in the mouse lifespan than others have studied – when no other markers or abnormalities have been reported, Tsai said.

An evolutionary mystery 125 million years in the making

A bushel of tomatoes at the CSHL Uplands Farm.
Photo Credit: Courtesy of Cold Spring Harbor Laboratory

Plant genomics has come a long way since Cold Spring Harbor Laboratory (CSHL) helped sequence the first plant genome. But engineering the perfect crop is still, in many ways, a game of chance. Making the same DNA mutation in two different plants doesn’t always give us the crop traits we want. The question is why not? CSHL plant biologists just dug up a reason.

CSHL Professor and HHMI Investigator Zachary Lippman and his team discovered that tomato and Arabidopsis thaliana plants can use very different regulatory systems to control the same exact gene. Incredibly, they linked this behavior to extreme genetic makeovers that occurred over 125 million years of evolution.

Study of slowly evolving ‘living fossils’ reveals key genetic insights

The alligator gar, and other gar species, are “living fossils” that it shows little species diversity or physical differences from ancestors that lived tens of millions of years ago.
Photo Credit: David Solomon

In 1859, Charles Darwin coined the term “living fossils” to describe organisms that show little species diversity or physical differences from their ancestors in the fossil record. In a new study, Yale researchers provide the first evidence of a biological mechanism that explains how living fossils occur in nature.

The study, published in the journal Evolution, shows that gars — an ancient group of ray-finned fishes that fit the definition of a living fossil — have the slowest rate of molecular evolution among all jawed vertebrates, meaning their genome changes more slowly than those of other animals.

By linking this finding to the process of hybridization — when two different species produce viable offspring — of gar species in the wild that last shared common ancestry during the age of the dinosaurs, the researchers demonstrate that slow evolution rate of their genome drives their low species diversity.

“We show that gars’ slow rate of molecular evolution has stymied their rate of speciation,” said Thomas J. Near, professor of Ecology and Evolutionary Biology in Yale’s Faculty of Arts and Sciences and the paper’s senior author. “Fundamentally, this is the first instance where science is showing that a lineage, through an intrinsic aspect of its biology, fits the criteria of living fossils.” 

Low iron levels resulting from infection could be key trigger of long COVID

Photo Credit: Malachi Cowie

Problems with iron levels in the blood and the body’s ability to regulate this important nutrient as a result of SARS-CoV-2 infection could be a key trigger for long COVID, new research has discovered.

"Iron levels, and the way the body regulates iron, were disrupted early on during SARS-CoV-2 infection, and took a very long time to recover, particularly in those people who went on to report long COVID months later"

Aimee Hanson

The discovery not only points to possible ways to prevent or treat the condition, but could help explain why symptoms similar to those of long COVID are also commonly seen in a number of post-viral conditions and chronic inflammation.

Although estimates are highly variable, as many as three in 10 people infected with SARS-CoV-2 could go on to develop long COVID, with symptoms including fatigue, shortness of breath, muscle aches and problems with memory and concentration (‘brain fog’). An estimated 1.9 million people in the UK alone were experiencing self-reported long COVID as of March 2023, according to the Office of National Statistics.

Shortly after the start of the COVID-19 pandemic, researchers at the University of Cambridge began recruiting people who had tested positive for the virus for the COVID-19 cohort of the National Institute for Health and Care Research (NIHR) BioResource. These included asymptomatic healthcare staff identified via routine screening through patients admitted to Cambridge University Hospitals NHS Foundation Trust, and some to its intensive care unit.

Oregon State University researchers are first to see at-risk bat flying over open ocean

Hoary bat at sea.
Photo Credit: Courtesy of Will Kennerley / the MOSAIC Project.

On a research cruise focused on marine mammals and seabirds, Oregon State University scientists earned an unexpected bonus: The first-ever documented sighting of a hoary bat flying over the open ocean.

The bat was seen in the Humboldt Wind Energy Area about 30 miles off the northern California coast; the Humboldt area has been leased for potential offshore energy development, and the hoary bat is the species of bat most frequently found dead at wind power facilities on land.

OSU faculty research assistant Will Kennerley, the first to see the bat, and colleagues documented the sighting with a paper in the Journal of North American Bat Research. The bat was spotted just after 1 p.m. on Oct. 3, 2022, in observing conditions rated as excellent.

“I have spent a lot of time at sea in all oceans of the world, and I’ve seen a lot of amazing things,” said Lisa Ballance, director of OSU’s Marine Mammal Institute. “A hoary bat was a first for all of us. It’s a reminder of the wonder of nature, and of its vulnerability.”

Scientists develop novel RNA- or DNA-based substances to protect plants from viruses

The new active ingredients can be used to protect plants against viruses.
Photo Credit: Uni Halle / Markus Scholz

Individually tailored RNA or DNA-based molecules are able to reliably fight off viral infections in plants, according to a new study by the Martin Luther University Halle-Wittenberg (MLU), which was published in the International Journal of Molecular Sciences. The researchers were able to fend off a common virus using the new active substances in up to 90 per cent of cases. They also developed a method for finding substances tailored specifically to the virus. The team has now patented the method.

During a viral infection, the plant’s cells are hijacked by the virus to multiply itself. Key products of this process are viral RNA molecules that serve as blueprints for the production of proteins. "A virus cannot reproduce without producing its proteins," explains Professor Sven-Erik Behrens from the Institute of Biochemistry and Biotechnology at MLU. For years, his team has been working on ways to disrupt this process and degrade the viral RNA molecules inside the cells. 

In the new study, the researchers describe how this can be achieved using the so-called "antisense" method. It relies on short, synthetically produced DNA molecules known as antisense oligonucleotides (ASOs). In the plant cells, the ASOs direct cellular enzymes acting as scissors towards the foreign RNA so they can degrade it. "For this process to work, it is crucial to identify a suitable target structure in the viral RNA which the enzyme scissors can attach to," explains Behrens. However, finding those accessible sites is really tricky: most potential target RNA molecules have a very complex structure, and they are also masked by other cell components. "This makes it even more difficult to attack them directly," says Behrens. 

A step toward personalized immunotherapy for all

This immunofluorescence image shows CD4+ (green) and CD8+ (yellow) T cells in the microenvironment of a head and neck squamous cell carcinoma.
Image Credit: Allen Lab, NCI/NIH.

Most cancers are thought to evade the immune system. These cancers don’t carry very many mutations, and they aren’t infiltrated by cancer-fighting immune cells. Scientists call these cancers immunologically “cold.”

Now new research suggests such cancers aren’t as “cold” as once thought. Researchers from the La Jolla Institute for Immunology (LJI), UC San Diego Moores Cancer Center, and UC San Diego, have found that patients with “cold” tumors actually do make cancer-fighting T cells.

This discovery opens the door to developing vaccines or therapies to increase T cell numbers and treat many more types of cancer than currently thought possible.

“In virtually every patient we’ve looked at, with every kind of cancer we’ve analyzed, we can detect pre-existing natural immunity against their tumor’s immunogenic subset of mutations known as neoantigens,” says LJI Professor Stephen Schoenberger, Ph.D., who co-led the new study with LJI Professor Bjoern Peters, Ph.D. “Therefore, we think these patients may actually benefit from empowering this response through personalized immunotherapy.”

“Every cancer patient is different,” adds Peters. “But this research is an important step toward finding immune cell targets relevant for individual patient tumors.”

Pancreatic cancer lives on mucus

A cross-section of a mouse’s early-stage pancreatic tumor. CSHL scientists discovered that early pancreatic cancer cells depend on the regulators of mucus production to survive and grow. Green, purple, yellow, cyan, and white denote areas where mucus production is high.
Image Credit: Cold Spring Harbor Laboratory

Knowing exactly what’s inside a tumor can maximize our ability to fight cancer. But that knowledge doesn’t come easy. Tumors are clusters of constantly changing cancer cells. Some become common cancer variants. Others morph into deadlier, drug-resistant varieties. No one truly understands what governs this chaotic behavior.

Now, Cold Spring Harbor Laboratory (CSHL) Professor David Tuveson and his team have uncovered a mechanism involved in pancreatic cancer transformation—mucus. During the disease’s early stage, pancreatic cancer cells produce mucus. Additionally, these cells depend on the body’s regulators of mucus production. This new knowledge could help set the stage for future diagnostic or therapeutic strategies.

The unpredictable, shifting nature of tumors makes it challenging to pinpoint the right treatments for patients. “We need to better understand this concept of cell plasticity and design therapy that takes this into consideration,” says Claudia Tonelli, a research investigator in the Tuveson lab, who led the study.

Walleye struggle with changes to timing of spring thaw

Within a few days of ice-off, when a lakes’ frozen lid has melted away, walleye begin laying eggs and fertilizing them. When lakes thaw earlier than usual, the young walleye that hatch in Midwestern waters may have a more difficult time surviving.
Image Credit: Copilot AI

Walleye are one of the most sought-after species in freshwater sportfishing, a delicacy on Midwestern menus and a critically important part of the culture of many Indigenous communities. They are also struggling to survive in the warming waters of the Midwestern United States and Canada.

According to a new study published in the journal Limnology and Oceanography Letters, part of the problem is that walleye are creatures of habit, and the seasons — especially winter — are changing so fast that this iconic species of freshwater fish can’t keep up.

The timing of walleye spawning — when the fish mate and lay their eggs — has historically been tied to the thawing of frozen lakes each spring, says the study’s lead author, Martha Barta, a research technician at the University of Wisconsin–Madison. Now, due to our changing climate, walleye have been “unable to keep up with increasingly early and more variable ice-off dates,” Barta says.

Within a few days of ice-off, when a lakes’ frozen lid has melted away, walleye begin laying eggs and fertilizing them. In a normal year, that timing sets baby fish up for success once they hatch. But, Barta says, “climate change is interrupting the historical pairing of ice-off and walleye spawning, and that threatens the persistence of walleye populations across the Upper Midwest.”

Immune system meets cancer: Checkpoint identified to fight solid tumor

Immunofluorescence image of the expression of PHGDH (red) and CD3 T cells (green) in cryosectioned AE17 mesothelioma.
Image Credit: Zhengnan Cai

Checkpoint PHDGH in tumor-associated macrophages influences immune response and tumor growth

A study by a scientific team from the University of Vienna and the MedUni Vienna, recently published in the top-class journal Cellular & Molecular Immunology, has a promising result from tumor research: The enzyme phosphoglycerate dehydrogenase (PHDGH) acts as a metabolic checkpoint in the function of tumor-associated macrophages (TAMs) and thus on tumor growth. Targeting PHGDH to modulate the cancer-fighting immune system could be a new starting point in cancer treatment and improve the effectiveness of clinical immunotherapies.

Our immune system constantly fights emerging cancer cells that arise from mutations. This process is controlled, among other things, by different types of macrophages. Tumor-associated macrophages (TAMs) are among the most abundant immune cells in the tumor microenvironment. They come from tissue-resident immune cells circulating in the blood that penetrate the tumor and differentiate there in response to various messenger substances (cytokines) and growth factors. In most solid tumors, TAMs are paradoxically considered to be tumor-promoting ("protumorigenic") overall: they promote tumor growth and metastasis by suppressing the immune response, promoting the vascular supply to the tumor and also increasing resistance to drug therapies – i.e. they generally correlate with a poor prognosis for the affected patients. Previous attempts to influence TAMs proved unsatisfactory because many patients had only a limited response to these therapeutic approaches. This underlines the urgency of finding new active ingredients and strategies.