Finding Order in the Disorder: New Insights into Seemingly Structureless Regions of Proteins

Protein condensates (shown here in a microscope image) are critical to the process of gene expression in cells, and condensate formation depends on proteins’ intrinsically disordered regions.
Image Credit: Amy Strom, Princeton University

Howard Hughes Medical Institute Investigators Cigall Kadoch and Clifford Brangwynne teamed up to challenge long-held beliefs in the scientific community about how – or even if – structureless, unorganized regions of proteins play specific roles in causing or preventing disease pathogenesis. Their work was published earlier this month in the journal Cell.

To understand the significance of the duo’s findings, it helps to first dive deep into the ways in which cells alter genomic structure through a process known as chromatin remodeling. About two meters – or six and a half feet – of DNA are packed inside each cell’s nucleus, which measures no larger than a pinhead. To fit in that space, DNA winds around proteins, forming a compact structure called chromatin. At the Dana-Farber Cancer Institute, Kadoch and her lab have spent years studying chromatin remodeling complexes – molecular machines made up of multiple proteins that change the physical structure of chromatin and, thus, suppress or enable the activity of genes in a programmatic manner.

In recent years, her lab’s focus has centered on a family of complexes known as mammalian SWI/SNF chromatin remodeling complexes – commonly referred to as BAF complexes – which have garnered significant attention due to their disruption and involvement in human disease. BAF complexes are one of the most frequently mutated cellular entities in human cancer, second only to TP53, a well-studied tumor suppressor gene. Studies have shown that approximately 20 percent of human cancers bear BAF complex mutations and that such disruptions are also among the most common in neurodevelopmental disorders (NDDs) such as autism and intellectual disability.

The encounter between Neanderthals and Sapiens as told by their genomes

analysed the distribution of the portion of DNA inherited from Neanderthals in the genomes of humans (Homo sapiens) over the last 40,000 years.
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Image Credit: © Claudio Quilodrán

About 40,000 years ago, Neanderthals, who had lived for hundreds of thousands of years in the western part of the Eurasian continent, gave way to Homo sapiens, who had arrived from Africa. This replacement was not sudden, and the two species coexisted for a few millennia, resulting in the integration of Neanderthal DNA into the genome of Sapiens. Researchers at the University of Geneva (UNIGE) have analyzed the distribution of the portion of DNA inherited from Neanderthals in the genomes of humans (Homo sapiens) over the last 40,000 years. These statistical analyses revealed subtle variations in time and geographical space. This work, published in the journal Science Advances, helps us to understand the common history of these two species. 

Thanks to genome sequencing and comparative analysis, it is established that Neanderthals and Sapiens interbred and that these encounters were sometimes fruitful, leading to the presence of about 2% of DNA of Neanderthal origin in present-day Eurasians. However, this percentage varies slightly between regions of Eurasia, since DNA from Neanderthals is somewhat more abundant in the genomes of Asian populations than in those of European populations. 

Study Elucidates Evolution of Mosquitoes and Their Hosts

Researchers scoured academic literature and used new genomic techniques to create the mosquito family tree.
Photo Credit: Matt Bertone, NC State University.

Researchers at North Carolina State University and global collaborators have mapped the mosquito’s tree of life, a major step toward understanding important traits, such as how the insects choose their hosts, feed on blood and spread disease. The findings will help researchers make better predictions to model disease transmission and understand what makes some mosquitoes better disease carriers than others.

The research suggests that mosquito evolution over the past 200 million years mirrors the Earth’s history of shifting land masses and changing host organisms, says Dr. Brian Wiegmann, William Neal Reynolds Professor of Entomology at NC State and corresponding author of a paper describing the mosquito family tree, published in Nature Communications.

“This ongoing project builds a big-data resource that mines the academic literature with published observations of the sources of blood mosquitoes drink, from animals as diverse as fish to humans,” Wiegmann said. “It focuses explicitly on data collection to infer aspects of mosquito biology in a contextualized way. That means linking up the family, or phylogenetic, tree with the narrative of life on Earth: geologic history, climate history and organism history.”

Revealing structural secrets of a key cancer protein

Left (a): Three-dimensional structure of active K-Ras protein previously determined by X-ray crystallography with the functionally critical switch regions (red and blue) mostly invisible (dashed lines). Right (b): Two-dimensional NMR spectrum of the same system in solution, with its features annotated to the corresponding amino-acid residues of K-Ras. Tiny features belonging to the switch regions that were previously undetectable are now observable, allowing the detailed characterization of their structure and functional dynamics by solution NMR.
Image Credit: Alexander Hansen et al. (2023)

Scientists have breathed new life into the study of a protein with an outsized link to human cancers because of its dangerous mutations, using advanced research techniques to detect its hidden regions.

The Ras family of proteins are enzymes that set-in motion the growth, division and differentiation of many types of cells, and their genes have been identified as the most frequently mutated cancer-related genes in humans. The subject of this study, the K-Ras protein, is linked to 75% of all Ras-associated cancers.

Researchers at The Ohio State University are the first to detect a section of this protein’s structure that had previously been unobservable by standard lab tools, revealing features and interactions related to the protein’s mutations that put cells into a state of perpetual division – a classic cancer characteristic.  

“We know these mutations are a significant problem: They cause deaths,” said senior study author Rafael Brüschweiler, Ohio Research Scholar and professor of chemistry and biochemistry at Ohio State. “We know that structural biology can provide unique insights into the mechanisms of those mutations and can stimulate the search for potential cures.

From a five-layer graphene sandwich, a rare electronic state emerges

When stacked in five layers in a rhombohedral pattern, graphene takes on a rare “multiferroic” state, in which the material’s electrons (illustrated here as spheres) exhibit two preferred electronic states: an unconventional magnetism (represented as orbits around each electron), and “valley,” or a preference for one of two energy states (depicted in red versus blue). The results could help advance more powerful magnetic memory devices.
Illustration Credits: Sampson Wilcox, RLE
(CC BY-NC-ND 3.0 DEED)

Ordinary pencil lead holds extraordinary properties when shaved down to layers as thin as an atom. A single, atom-thin sheet of graphite, known as graphene, is just a tiny fraction of the width of a human hair. Under a microscope, the material resembles a chicken-wire of carbon atoms linked in a hexagonal lattice. 

Despite its waif-like proportions, scientists have found over the years that graphene is exceptionally strong. And when the material is stacked and twisted in specific contortions, it can take on surprising electronic behavior.

Now, MIT physicists have discovered another surprising property in graphene: When stacked in five layers, in a rhombohedral pattern, graphene takes on a very rare, “multiferroic” state, in which the material exhibits both unconventional magnetism and an exotic type of electronic behavior, which the team has coined ferro-valleytricity. 

“Graphene is a fascinating material,” says team leader Long Ju, assistant professor of physics at MIT. “Every layer you add gives you essentially a new material. And now this is the first time we see ferro-valleytricity, and unconventional magnetism, in five layers of graphene. But we don’t see this property in one, two, three, or four layers.”

No more big needles: scientists develop a skin patch that painlessly delivers drugs into the body

An affordable microneedle skin patch that delivers a controlled dosage of medicine directly into the body, eliminating the need for injections or oral medication, has been developed by a team led by scientists at the University of Bath.

It is hoped that the patches, which are described in the journal Biomaterials Advances, will be ready for use within the next five to 10 years.

What makes the microneedle patches unique is that they are made from a hydrogel (a gel-like substance in which water forms the liquid component), with the active ingredient encapsulated inside the hydrogel microneedle structure rather than in a separate reservoir.

They are also more affordable than other commercially available microneedle patches, as they are produced from 3D printed molds. Molds produced this way are easy to customize, which keeps the costs down.

Scientists discover links between Alzheimer’s disease and gut microbiota

Photo (L-R): Dr Stefanie Grabrucker (a postdoctoral researcher) and Professor Yvonne Nolan, of APC Microbiome Ireland and the Department of Anatomy and Neuroscience.
Photo Credit: Ms Bereniece Riedewald.

Researchers have discovered the link between gut microbiota and Alzheimer’s disease.

For the first time, researchers have found that Alzheimer’s symptoms can be transferred to a healthy young organism via the gut microbiota, confirming its role in the disease.

The research was led by Professor Yvonne Nolan, APC Microbiome Ireland, a world leading SFI funded research center based at University College Cork (UCC), and the Department of Anatomy and Neuroscience, UCC, with Professor Sandrine Thuret at King’s College London and Dr Annamaria Cattaneo IRCCS Fatebenefratelli, Italy. The study supports the emergence of the gut microbiome as a key target for investigation in Alzheimer’s disease due to its particular susceptibility to lifestyle and environmental influences.

Published in Brain, the study shows that memory impairments in people with Alzheimer’s could be transferred to young animals through transplant of gut microbiota. Alzheimer’s patients had a higher abundance of inflammation-promoting bacteria in fecal samples, and these changes were directly associated with their cognitive status.

Warmer climate may impact reliability of solar farms: modeling

Managing weather-induced power fluctuations will be a growing challenge for variable renewables in the future.
Photo Credit: Quang Nguyen Vinh

New research suggests Australia will need to adjust to climate-driven shifts in solar power production.

Australia’s renewable energy transition is well underway, but an impending shift in the reliability of solar due to climate change could impact generation capacity and the management of the electricity grid. 

Modeling conducted by researchers from UNSW Sydney predicts changes in the availability of solar across different regions of Australia under a warmer climate. The findings, published in the journal Solar Energy, have implications for future solar power infrastructure development in Australia, including the world’s largest solar infrastructure energy network.

Australia is a prominent solar hotspot, with several notable large-scale grid-connected solar power systems – or solar photovoltaics (PV) plants – in operation or development. However, the sensitivity of solar power generation to weather-induced variability can limit its ability to deliver a consistent and dependable energy supply.

Managing grid stability due to inherent variability in solar energy generation due to factors like cloud cover, seasonal cycles, and location – all of which will be impacted by future warming – is possible with proper forecasting, power storage and load controls. But, if left unmanaged, it can lead to power deficits that can result in outages or even complete grid failures.

Orchid without bumblebee on island finds wasp, loses self

The relationship between orchids and their pollinators is often highly exclusive because their physical features closely match each other. On mainland Japan, only a specific bumblebee can pollinate Goodyera henryi’s long flower tube with its long mouthparts (top right). Its close relative Goodyera similis has a short flower tube and is pollinated by a wasp with shorter mouthparts (middle right). On a remote island, where only wasps but no bumblebees exist (map, highlighted in red), both flowers are pollinated by the wasp (bottom right). However, for Goodyera henryi this came at the cost of hybridization with Goodyera similis and thus it lost some of its species identity.
Illustration Credit: © ANSAI Shun
(CC BY 4.0 DEED)

Because the bumblebee that an orchid relies on for pollination does not exist on a remote island, the plant gets pollinated by an island wasp. Kobe University researchers found that this came at the cost of being hybridized with another orchid species adapted to being pollinated by the wasp. The finding showcases how plants in ecological relationships adapt to changing circumstances.

Remote islands have been exciting study grounds for biologists since at least the days of Darwin. When studying ecological relationships between different species, the differences between mainland and island can hint at how such relationships evolve and what this means for the participating species. This is what piqued plant scientists’ curiosity when they discovered Goodyera henryi, an orchid which on mainland Japan is pollinated exclusively by a very specific bumblebee, on remote Japanese Kozu Island where the bumblebee doesn’t exist.

For Kobe University Professor SUETSUGU Kenji this fit perfectly into his long-term effort to understand the dynamics of island biology and evolutionary processes. The orchid specialist says: “The combination of our expertise, access to the location, and our interdisciplinary methodology puts us in a special position to study the impact of bumblebee absence on orchid evolution in this context.” With his team he studied the pollination of the orchids both on mainland Japan and on Kozu Island, and also employed genetic analysis to learn about the relationship patterns between the different populations of the plants.

Marine mammals in zoos and aquariums now live 2-3 times longer than in the wild

Photo Credit: Los Muertos Crew

A new study provides compelling evidence that animal care and management practices at zoos and aquariums have significantly improved over time. The study, led by Species360 and University of Southern Denmark Research Scientist Dr. Morgane Tidière in collaboration with 41 co-authors from academic, governmental, and zoological institutions around the world, is the first to examine life expectancy and lifespan equality together as a proxy of population welfare in marine mammal species.

The study also found that marine mammal species live longer in zoological institutions than in the wild as a result of advances in animal care practices centered on animal welfare. The results have been published in Proceedings of the Royal Society B: Biological Sciences.

From SDU the following researchers contributed: Fernando Colchero, Johanna Staerk, Ditte H. Andersen, Kirstin Anderson Hansen and Dalia A. Conde.

The animals in the study
The four species in this study (harbor seal, sea lion, polar bear and bottlenose dolphin) were selected because they represent 63,4% of all marine mammals, registered in the global Species360 Zoological Information Management System (ZIMS).

Critical step made for managing brushtail possums

Researchers say mapping the genetic code of the brushtail possum will benefit those working to both conserve and control the animal.

In a five-year long study, just published in Nature Communications, an international group of researchers led by the University of Otago, has assembled the entire genetic code of the marsupial mammal.

The work also uncovered where and when their genes are expressed, and revealed surprising details about their population diversity, reproduction, and origins.

Study lead Associate Professor Tim Hore, of Otago’s Department of Anatomy, describes possums as “a fascinating animal that is loved in one country and a cause of concern in another”.

“They are hunted in Aotearoa New Zealand for their fur, and controlled for conservation, but treasured and protected in Australia. Having their full genetic code is important for both countries as efforts to manage their respective populations are being held back by the lack of this knowledge,” he says.

UCLA-led team finds a stem-cell derived mechanism that could lead to regenerative therapies for heart damage

Image by rawpixel

A UCLA-led team has identified an essential internal control mechanism that can promote the maturation of human stem cell-derived heart muscle cells, offering a deeper understanding of how heart muscle cells develop from their immature fetal stage to their mature adult form.

The findings, published in the peer-reviewed journal Circulation, could lead to new therapies for heart disease and cardiac damage.

The collaborative effort with Duke-NUS Medical School in Singapore and other institutions identified an RNA splicing regulator named RBFox1, which was considerably more prevalent in adult heart cells than in newborns, based on a preclinical model. The sharp rise in RBFox1 during the maturation of heart cells was also confirmed through analyses of existing single-cell data.

“This is the first piece of evidence suggesting that RNA splicing control plays a vital role in postnatal heart cell maturation,” said study lead Jijun Huang, who conducted this research during his postdoctoral training in anesthesiology at UCLA. “While RBFox1 alone may not be sufficient to push mature fetal heart muscle cells all the way to fully matured adult cells, our findings uncover a new RNA-based internal network that can substantially drive this maturation process beyond other available approaches.”

New patterns in Sun’s layers could help scientists solve solar mystery

In this image, the fine-structure of the quiet Sun is observed at its surface or photosphere.
Image Credit: NSF/AURA/NSO

Astronomers are one step closer to understanding one of the most enduring solar mysteries, having captured unprecedented data from the Sun’s magnetic field.

New research from an international team may explain one of the biggest conundrums in astrophysics – why the outermost layer of the Sun’s atmosphere is hotter than the surface

Groundbreaking data collected from the world's most powerful solar telescopes shows a snake-like pattern in the Sun’s magnetic fields that could contribute to the heating of the Sun’s outermost atmosphere

The project, which includes scientists across a wide range of institutions on both sides of the Atlantic Ocean, has opened new avenues in solar physics

Astronomers are one step closer to understanding one of the most enduring solar mysteries, having captured unprecedented data from the Sun’s magnetic field.

New Research Suggests Why Males and Females Respond Differently to Social Stress

Emily Wright, researcher, in a UC Davis lab.
Photo Credit: Jerry Tsai

Women are nearly twice as likely as men to be diagnosed with an anxiety disorder, but among boys and girls the likelihood is the same. New University of California, Davis, research has identified changes in the brain during puberty that may account for differences in how women and men respond to stress.

A team of psychologists has found that testosterone is the key hormone that drives gender-based differences in responses to social stress. The study encompassed six separate experiments with mice to isolate what changes in the brain drive these differences between males and females. The study was published in the Proceedings of the National Academy of Sciences, or PNAS, today.

“This research shows how the body’s hormones shape the complex interplay between the brain’s circuitry and behavioral responses to stress,” said Brian Trainor, a professor of psychology in the College of Letters and Science at UC Davis and the study’s corresponding author.

Germicidal UV lights could be producing indoor air pollutants

Image Credit: José-Luis Olivares, MIT; iStock
(CC BY-NC-ND 3.0 DEED)

Many efforts to reduce transmission of diseases like Covid-19 and the flu have focused on measures such as masking and isolation, but another useful approach is reducing the load of airborne pathogens through filtration or germicidal ultraviolet light. Conventional UV sources can be harmful to eyes and skin, but newer sources that emit at a different wavelength, 222 nanometers, are considered safe.

However, new research from MIT shows that these UV lights can produce potentially harmful compounds in indoor spaces. While the researchers emphasize that this doesn’t mean the new UV lights should be avoided entirely, they do say the research suggests it is important that the lights have the right strength for a given indoor situation, and that they are used along with appropriate ventilation.

The findings are reported in the journal Environmental Science and Technology, in a paper by recent MIT postdoc Victoria Barber, doctoral student Matthew Goss, Professor Jesse Kroll, and six others at MIT, Aerodyne Research, and Harvard University.

While Kroll and his team usually work on issues of outdoor air pollution, during the pandemic they became increasingly interested in indoor air quality. Usually, little photochemical reactivity happens indoors, unlike outdoors, where the air is constantly exposed to sunlight. But with the use of devices to clean indoor air using chemical methods or UV light, “all of a sudden some of this oxidation is brought indoors,” triggering a potential cascade of reactions, Kroll says.