A Simple and Robust Method to Add Functional Molecules to Peptides

An N-terminal specific three-component [3+2] cycloaddition proceeds without affecting the highly reactive lysine residues. This reaction has been successfully applied to polypeptides of up to 26 residues.
Illustration Credit: ©Kazuya Kanemoto et al.

Peptides are short strands of amino acids that are increasingly used therapeutically, as biomaterials and as chemical and biological probes. The capacity to isolate, manipulate and label peptides and larger proteins is limited, however, by the ability to reliably attach functional molecules, such as fluorescent compounds, to peptides in locations that won't affect the three-dimensional structure and function of the short amino acid strand.

Researchers are most interested in adding functional molecules to the N-terminus, or the end of a peptide with a free amine group (NH2), of an amino acid strand in order to minimize the interference of functional molecules with the structure and function of the bound peptide. Earlier methods of attaching functional molecules to the N-terminus of peptides were insufficient for several reasons: 

1. the functional groups would release from the peptide in human physiological conditions
2. only one functional group could be attached to a peptide at a time 
3. attachment of functional molecules to peptides was not uniform or
4. reactions simply weren't efficient.

To address this issue, researchers from Tohoku University and Chuo University developed a unique chemical reaction to attach two distinct functional molecules to the N-terminus of a peptide with a glycine amino acid at the N-terminus. The researchers published their study in the journal Angewandte Chemie International Edition.

“Molecular Rosetta Stone” Reveals How our Microbiome Talks to Us

Bacteria in the gut convert bile acids produced by the liver into a wide array of new compounds. These molecules are akin to the language of the gut microbiome, allowing them to influence distant organ systems.
Photo Credit: Lakshmiraman Oza

Researchers from Skaggs School of Pharmacy and Pharmaceutical Sciences at the University of California San Diego have uncovered thousands of previously unknown bile acids, a type of molecule used by our gut microbiome to communicate with the rest of the body.

“Bile acids are a key component of the language of the gut microbiome, and finding this many new types radically expands our vocabulary for understanding what our gut microbes do and how they do it,” said senior author Pieter Dorrestein, Ph.D., professor at Skaggs School of Pharmacy and Pharmaceutical Sciences and professor of pharmacology and pediatrics at UC San Diego School of Medicine. “It’s like going from ‘See Spot Run’ to Shakespeare.”

The results, as described by study co-author and bile acids expert Lee Hagey, Ph.D, are akin to a molecular Rosetta stone, providing previously unknown insight into the biochemical language microbes use to influence distant organ systems.

Brain Waves Travel in One Direction When Memories Are Made and the Opposite When Recalled

Traveling wave propagation directions in the memory task reveal how the brain quickly coordinates activity and shares information across multiple regions.
Photo Credit: Hongui Zhang

In the space of just a few seconds, a person walking down a city block might check their phone, yawn, worry about making rent, and adjust their path to avoid a puddle. The smell from a food cart could suddenly conjure a memory from childhood, or they could notice a rat eating a slice of pizza and store the image as a new memory. 

For most people, shifting through behaviors quickly and seamlessly is a mundane part of everyday life. 

For neuroscientists, it’s one of the brain’s most remarkable capabilities. That’s because different activities require the brain to use different combinations of its many regions and billions of neurons. How it manages to do this so rapidly has been an open question for decades. 

The study

In a paper published in Nature Human Behaviour, a team of researchers, led by Joshua Jacobs, associate professor of biomedical engineering at Columbia Engineering, shed new light on this question. By carefully monitoring neural activity of people who were recalling memories or forming new ones, the researchers managed to detect how a newly appreciated type of brainwave — traveling waves — influences the storage and retrieval of memories. 

“Broadly, we found that waves tended to move from the back of the brain to the front while patients were putting something into their memory,” said the paper’s co-author Uma R. Mohan, a postdoctoral researcher at NIH and former postdoctoral researcher in the Electrophysiology, Memory, and Navigation Laboratory at Columbia Engineering. “When patients were later searching to recall the same information, those waves moved in the opposite direction, from the front towards the back of the brain,” she said. 

Halloween toy among plastics swallowed by sea turtles

A rubber witches' finger found inside a dead sea turtle.
Photo Credit: University-of-Exeter

A Halloween toy was among hundreds of plastic items found in the guts of dead sea turtles in the Mediterranean, a new study reveals.

Researchers examined 135 loggerhead turtles either washed up or killed as “bycatch” (accidentally caught) in fishing nets off northern Cyprus.

More than 40% of the turtles contained “macroplastics” (pieces larger than 5mm), including bottle tops and the Halloween toy – a rubber witch’s finger.

The research team, led by the University of Exeter and the North Cyprus Society for the Protection of Turtles (SPOT), say loggerheads are a potential “bioindicator” species that could help them understand the scale and impact of plastic pollution.

“The journey of that Halloween toy – from a child’s costume to the inside of a sea turtle – is a fascinating glimpse into the life cycle of plastic,” said Dr Emily Duncan, from Centre for Ecology and Conservation on Exeter’s Penryn Campus in Cornwall.

“These turtles feed on gelatinous prey such as jellyfish and seabed prey such as crustaceans, and it’s easy to see how this item might have looked like a crab claw.”

Researchers uncover protein responsible for cold sensation

Image Credit: Copilot AI Generated 

University of Michigan researchers have identified the protein that enables mammals to sense cold, filling a long-standing knowledge gap in the field of sensory biology.

The findings, published in Nature Neuroscience, could help unravel how we sense and suffer from cold temperatures in the winter, and why some patients experience cold differently under particular disease conditions.

“The field started uncovering these temperature sensors over 20 years ago, with the discovery of a heat-sensing protein called TRPV1,” said neuroscientist Shawn Xu, a professor at the U-M Life Sciences Institute and a senior author of the new research.

“Various studies have found the proteins that sense hot, warm, even cool temperatures—but we’ve been unable to confirm what senses temperatures below about 60 degrees Fahrenheit.”

In a 2019 study, researchers in Xu’s lab discovered the first cold-sensing receptor protein in Caenorhabditis elegans, a species of millimeter-long worm that the lab studies as a model system for understanding sensory responses.

AI research gives unprecedented insight into heart genetics and structure

Image Credit Copilot AI Generated

A ground-breaking research study has used AI to understand the genetic underpinning of the heart’s left ventricle, using three-dimensional images of the organ. It was led by scientists at the University of Manchester, with collaborators from the University of Leeds (UK), the National Scientific and Technical Research Council (Santa Fe, Argentina), and IBM Research (Almaden, CA).

The highly interdisciplinary team used cutting-edge unsupervised deep learning to analyze over 50,000 three-dimensional Magnetic Resonance images of the heart from UK Biobank, a world-leading biomedical database and research resource.

The study, published in the leading journal Nature Machine Intelligence, focused on uncovering the intricate genetic underpinnings of cardiovascular traits. The research team conducted comprehensive genome-wide association studies (GWAS) and transcriptome-wide association studies (TWAS), resulting in the discovery of 49 novel genetic locations showing an association with morphological cardiac traits with high statistical significance, as well as 25 additional loci with suggestive evidence.  

The study's findings have significant implications for cardiology and precision medicine. By elucidating the genetic basis of cardiovascular traits, the research paves the way for the development of targeted therapies and interventions for individuals at risk of heart disease.

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.

Reconfigurable electronics: More functionality on less chip area

Lukas Wind, Masiar Sistani und Walter Weber (left to right)
Photo Credit: Courtesy of Technische Universität Wien

Even the most complicated data processing on a computer can be broken down into small, simple logical steps: You can add individual bits together, you can reverse logical states, you can use combinations such as "AND" or "OR". Such operations are realized on the computer by very specific sets of transistors. These sets then form larger circuit blocks that carry out more complex data manipulations.

In the future, however, the design of electronic circuits could look completely different: For years, people have been thinking about the possibilities offered by electronic circuits that do not perform a physically fixed task, but can be switched flexibly depending on the task at hand – a new kind of reprogramming that does not take place at the software level, but at the fundamental hardware level: directly on the transistors, the nanoscale building blocks of electronic circuits.

This is exactly what a research team at TU Wien has now achieved: they have developed intelligent, controllable transistors and combined them into circuits that can be reliably and quickly switched back and forth between different tasks. This means that the same functionality as before can be accommodated on less chip space. This does not only save manufacturing costs, but also energy, and it enables higher computing speeds.

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.”

Loss of nature costs more than previously estimated

Photo Credit: Christian Heitz

Researchers propose that governments apply a new method for calculating the benefits that arise from conserving biodiversity and nature for future generations.

The method can be used by governments in cost-benefit analyses for public infrastructure projects, in which the loss of animal and plant species and ‘ecosystem services’ – such as filtering air or water, pollinating crops or the recreational value of a space – are converted into a current monetary value.

This process is designed to make biodiversity loss and the benefits of nature conservation more visible in political decision-making.

However, the international research team says current methods for calculating the values of ecosystem services “fall short” and have devised a new approach, which they believe could easily be deployed in Treasury analysis underpinning future Budget statements.

Their approach, published in the journal Science, takes into consideration the increase in monetary value of nature over time as human income increases, as well as the likely deterioration in biodiversity, making it more of a scarce resource.

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.

What Makes Birds So Smart?

The avian brain is smaller than that of many mammals, but just as capable.
Photo Credit: Kevin Mueller

Researchers at Ruhr University Bochum explain how it is possible for the small brains of pigeons, parrots and corvids to perform equally well as those of mammals, despite their significant differences.

Since the late 19th century, it has been a common belief among researchers that high intelligence requires the high computing capacity of large brains. They also discovered that the cerebral cortex as typical of mammals, is necessary to analyze and link information in great detail. Avian brains, by contrast, are very small and lack any structure resembling a cortex. Nevertheless, scientists showed that parrots and corvids are capable of planning for the future, forging social strategies, recognizing themselves in the mirror and building tools. These and similar aptitudes put them on a par with chimpanzees. Even less gifted birds, such as pigeons, learn orthographic rules that enable them to recognize typos in short words or classify pictures according to categories such as “impressionism”, “water” or “man-made”. How do they do it with such small brains and without a cortex? With their article in Trends in Cognitive Science, Professor Onur Güntürkün, Dr. Roland Pusch and Professor Jonas Rose from Ruhr University Bochum come closer to solving this more than one hundred-year-old puzzle.

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.