Gene mutation leads to epileptic encephalopathy symptoms, neuron death in mice

A study led by Illinois postdoctoral researcher Eung Chang Kim and professor Hee Jung Chung found that mice with a genetic mutation associated with epileptic encephalopathy exhibit not only the seizure and behavioral symptoms of the disorder, but also neural degeneration and inflammation in the brain.  Photo by L. Brian Stauffer

Mice with a genetic mutation that’s been observed in patients with epileptic encephalopathy, a severe form of congenital epilepsy, exhibit not only the seizure, developmental and behavioral symptoms of the disorder, but also neural degeneration and inflammation in the brain, University of Illinois Urbana-Champaign researchers found in a new study. The findings highlight the mutation as an important part of the disease’s pathology and a potential target for treatment.

Patients with epileptic encephalopathy begin having seizures when they are born, and display progressive developmental delay, intellectual disability and autismlike behavior, said study leader Hee Jung Chung, a professor of molecular and integrative physiology.

“The dogma regarding epileptic encephalopathy has been that the epileptic seizures are driving the pathogenesis of intellectual disability and developmental delay. But we wanted to answer the question, is it really just the seizures driving the intellectual disability and developmental delay?” Chung said. “This study is the first to show that expressing this human epileptic encephalopathy mutation in mice can cause not only spontaneous seizure and intellectual disability, but also neural degeneration.”

Previous work from Chung’s group found that epileptic encephalopathy is correlated with a mutation in a gene that codes for a potassium channel essential to regulating neuron activity. The mutation prevented the potassium channel from properly embedding in the cell membranes of neurons, causing it to build up inside the neuronal cells instead. Yet, whether and how the mutation played a role in the pathology of epileptic encephalopathy remained unknown.

Room-temperature crystallography aids new study of photosynthetic bacteria

Researchers at SLAC, Stanford University and Washington University
studied a protein that helps transport electrons during bacterial photosynthesis.
Jared Weaver/Stanford University

Chemists have come to a deeper understanding of how photosynthetic bacteria convert light into chemical energy and discovered why one step in the process may be more robust than previously realized, according to a new study published this week in Proceedings of the National Academy of Sciences.

The study focused on proteins called reaction centers in a bacterium called Rhodobacter sphaeroides that help transport electrons in its cell membrane during the first steps of photosynthesis. Although these proteins, which reside in the cell membrane, have been studied for decades, many details of how they work remain unclear. To try to fill in some of those details, Stanford University's Jared Weaver, a graduate student in chemist Steven Boxer's laboratory, worked with fellow Stanford chemist Chi-Yun Lin and Washington University researchers Kaitlyn Fairies, Dewey Holten, and Chris Kirmaier, who have been studying R. sphaeroides reaction centers for over a decade. Their apporach was to replace part of the protein with amino acids – protein building blocks – that do not naturally appear in that part of the protein structure. The results could help researchers better understand how the electron-transporting protein works under normal operation.

As part of those investigations, Weaver teamed up with Irimpan Mathews, a staff scientist at the Stanford Synchrotron Radiation Lightsource (SSRL) at the Department of Energy's SLAC National Accelerator Laboratory. There, the pair worked to crystallize the modified photosynthetic proteins and study them with X-ray macromolecular crystallography at one of SSRL's beamlines.

Engineers and physicists study quantum characteristics of ‘combs’ of light

The silicon carbide microrings developed by the Vučković Lab, as seen through a scanning electron microscope at the Stanford Nano Shared Facilities. 
Image credit: Vučković Lab

Frequency microcombs are specialized light sources that can function as light-based clocks, rulers and sensors to measure time, distance and molecular composition with high precision. New Stanford research presents a novel tool for investigating the quantum characteristics of these sources.

Unlike the jumble of frequencies produced by the light that surrounds us in daily life, each frequency of light in a specialized light source known as a “soliton” frequency comb oscillates in unison, generating solitary pulses with consistent timing.

Each “tooth” of the comb is a different color of light, spaced so precisely that this system is used to measure all manner of phenomena and characteristics. Miniaturized versions of these combs – called microcombs – that are currently in development have the potential to enhance countless technologies, including GPS systems, telecommunications, autonomous vehicles, greenhouse gas tracking, spacecraft autonomy and ultra-precise timekeeping.

Theropod dinosaur jaws became stronger as they evolved

Life reconstruction of the Late Cretaceous Iren Dabasu Formation fauna, showing theropod dinosaurs of various diets
Credit: Gabriel Ugueto

Theropod dinosaurs evolved more robust jaws through time allowing them to consume tougher food, a new study reveals.

Researchers used digital modelling and computer simulation to uncover a common trend of jaw strengthening in theropods - expanding the rear jaw portion in all groups, as well as evolving an upturned jaw in carnivores and a downturned jaw in herbivores.

Publishing their findings today in Current Biology, scientists revealed that biomechanical analysis showed these form changes made jaws mechanically more stable when biting - minimizing the chance of bone fracture.

The international team, led by scientists at the University of Birmingham, created digital models of more than 40 lower jaws from five different theropod dinosaur groups, including typical carnivores like Tyrannosaurus and Velociraptor, and lesser-known herbivores like ornithomimosaurs, therizinosaurs and oviraptorosaurs.

Fion Waisum Ma, PhD researcher at the University of Birmingham, who led the study, said: “Although theropod dinosaurs are always depicted as fearsome predators in popular culture, they are in fact very diverse in terms of diets. It is interesting to observe the jaws becoming structurally stronger over time, in both carnivores and herbivores. This gives them the capacity to exploit a wider range of food items.

Shark antibody-like proteins neutralize COVID-19 virus, help prepare for future coronaviruses

“What we’re doing is preparing an arsenal of shark VNAR therapeutics that could be used down the road for future SARS outbreaks," says researcher Aaron LeBeau.
Photo by: Bryce Richter

Small, unique antibody-like proteins known as VNARs — derived from the immune systems of sharks — can prevent the virus that causes COVID-19, its variants, and related coronaviruses from infecting human cells, according to a new study published Dec. 16.

The new VNARs will not be immediately available as a treatment in people, but they can help prepare for future coronavirus outbreaks. The shark VNARs were able to neutralize WIV1-CoV, a coronavirus that is capable of infecting human cells but currently circulates only in bats, where SARS-CoV-2, the virus that causes COVID-19, likely originated.

Developing treatments for such animal-borne viruses ahead of time can prove useful if those viruses make the jump to people.

“The big issue is there are a number of coronaviruses that are poised for emergence in humans,” says Aaron LeBeau, a University of Wisconsin–Madison professor of pathology who helped lead the study. “What we’re doing is preparing an arsenal of shark VNAR therapeutics that could be used down the road for future SARS outbreaks. It’s a kind of insurance against the future.”

Extreme weather changes predicted by unprecedented model simulations

California fire. (Photo credit: Patrick Perkins via Unsplash)

There is growing public awareness that climate change will impact society not only through changes in mean temperatures and rainfall over the 21st century, but also in the occurrence of more pronounced extreme events, and more generally in natural variability in the Earth system. Such changes could also have large impacts on vulnerable ecosystems in both terrestrial and marine habitats.

A team of researchers including Malte Stuecker from the University of Hawaiʻi at Mānoa School of Ocean and Earth Science and Technology (SOEST), explored projected future changes in climate and ecosystem variability and reported that the impact of climate change is apparent in nearly all aspects of climate variability. The study, led by the IBS Center for Climate Physics (ICCP) at Pusan National University in South Korea and published in Earth System Dynamics, emphasized that the impacts range from temperature and rainfall extremes over land to increased number of fires in California, to changes in bloom amplitude for phytoplankton in the North Atlantic Ocean.

Model simulations over 250 years

The team conducted a set of 100 global Earth system model simulations over 1850–2100, working with a “business-as-usual” scenario for relatively strong emissions of greenhouse gases over the 21st century. The runs were given different initial conditions, and, by virtue of the butterfly effect (a property of chaotic systems by which small changes in initial conditions can lead to large-scale and unpredictable variation in the future state of the system), they were able to represent a broad envelope of possible climate states over 1850-2100, enabling sophisticated analyses of changes in the variability of the Earth system over time.

Darwin’s finches evolve

 Darwin's Finch chick in nest on the Galapagos Islands.
Credit: A Katsis, Flinders University

Spending time with offspring is beneficial to development, but it’s proving lifesaving to Galápagos Islands Darwin’s finches studied by Flinders University experts.

A new study, published in Proceedings of the Royal Society B, has found evidence Darwin’s finch females that spend longer inside the nest can ward off deadly larvae of the introduced avian vampire fly, which otherwise enter and consume the growing chicks.

The maternal buffer is a life-saver, according to the research, especially during the first days after hatching, when chicks are blind, helpless and cannot preen. Although older offspring still have to contend with the larvae, they are better able to preen themselves, and may dislodge and occasionally eat some of them.

“The pair male is also essential for success of the chicks. If he feeds the offspring a lot, the mother can remain inside the nest for longer,” says Flinders University Professor Sonia Kleindorfer, who is also affiliated with the University of Vienna.

“Timing is everything. The female must forgo foraging herself, and her persistence is strongly influenced by good food provisioning of her offspring by the male.”

The unintentionally introduced avian vampire fly, an invasive species on the Galápagos Islands, enters Darwin’s finch nests when attending parents are absent.

The 17 Darwin’s finch species on the Galápagos Islands are a textbook example of a rapid adaptive radiation: each species has a unique beak shape suited to extract resources from a different ecological niche. However, since being first observed in Darwin’s finch nests in 1997, the avian vampire fly has been parasitizing nestlings and changing the beak and behavior of its Darwin’s finch hosts.

New model improves accuracy of machine learning in COVID-19 diagnosis while preserving privacy

The international team, led by the University of Cambridge and the Huazhong University of Science and Technology, used a technique called federated learning to build their model. Using federated learning, an AI model in one hospital or country can be independently trained and verified using a dataset from another hospital or country, without data sharing.

The researchers based their model on more than 9,000 CT scans from approximately 3,300 patients in 23 hospitals in the UK and China. Their results, reported in the journal Nature Machine Intelligence, provide a framework where AI techniques can be made more trustworthy and accurate, especially in areas such as medical diagnosis where privacy is vital.

AI has provided a promising solution for streamlining COVID-19 diagnoses and future public health crises. However, concerns surrounding security and trustworthiness impede the collection of large-scale representative medical data, posing a challenge for training a model that can be used worldwide.

In the early days of the COVID-19 pandemic, many AI researchers worked to develop models that could diagnose the disease. However, many of these models were built using low-quality data, ‘Frankenstein’ datasets, and a lack of input from clinicians. Many of the same researchers from the current study highlighted that these earlier models were not fit for clinical use in the spring of 2021.

“AI has a lot of limitations when it comes to COVID-19 diagnosis, and we need to carefully screen and curate the data so that we end up with a model that works and is trustworthy,” said co-first author Hanchen Wang from Cambridge’s Department of Engineering. “Where earlier models have relied on arbitrary open-sourced data, we worked with a large team of radiologists from the NHS and Wuhan Tongji Hospital Group to select the data, so that we were starting from a strong position.”

Why you drink black coffee: It’s in your genes

People who like to drink their coffee black also prefer dark chocolate, a new Northwestern Medicine study found. The reason is in their genes.

Northwestern scientists have found coffee drinkers who have a genetic variant that reflects a faster metabolism of caffeine prefer bitter, black coffee. And the same genetic variant is found in people who prefer the more bitter dark chocolate over the more mellow milk chocolate.

The reason is not because they love the taste, but rather because they associate the bitter flavor with the boost in mental alertness they expect from caffeine.

“That is interesting because these gene variants are related to faster metabolism of caffeine and are not related to taste,” said lead study author Marilyn Cornelis, associate professor of preventive medicine in nutrition. “These individuals metabolize caffeine faster, so the stimulating effects wear off faster as well. So, they need to drink more.”

“Our interpretation is these people equate caffeine’s natural bitterness with a psycho-stimulation effect,” Cornelis said. “They learn to associate bitterness with caffeine and the boost they feel. We are seeing a learned effect. When they think of caffeine, they think of a bitter taste, so they enjoy dark coffee and, likewise, dark chocolate.”

The paper was published Dec. 13 in Scientific Reports.

The dark chocolate connection also may be related to the fact that dark chocolate contains a small amount of caffeine but predominantly theobromine, a caffeine-related compound, also a psychostimulant.

Meltwater influences ecosystems in the Arctic Ocean

Credit: Alfred Wegener Institute for Polar and Marine Research

In the summer months, sea ice from the Arctic drifts through Fram Strait into the Atlantic. Thanks to meltwater, a stable layer forms around the drifting ice atop the more salty seawater, producing significant effects on biological processes and marine organisms. In turn, this has an effect on when carbon from the atmosphere is absorbed and stored, as a team of researchers led by the Alfred Wegener Institute has now determined with the aid of the FRAM ocean observation system. Their findings have just been published in the journal Nature Communications.

Oceans are one of the largest carbon sinks on our planet, due in part to the biological carbon pump: just below the water’s surface, microorganisms like algae and phytoplankton absorb carbon dioxide from the atmosphere through photosynthesis. When these microorganisms sink to the ocean floor, the carbon they contain can remain isolated from the atmosphere for several thousand years. As experts from the Alfred Wegener Institute, Helmholtz Centre for Polar and Marine Research (AWI), have now discovered, the meltwater from sea-ice floes can delay this process by four months.

From the summer of 2016 to the summer of 2018, the FRAM (Frontiers in Arctic Marine Monitoring) ocean observation system continually gathered data in Fram Strait (between Greenland and Svalbard). Dense clusters of moorings were installed at two sites in the strait in order to monitor as many aspects of the coupled physical-biological processes in the water as possible. Physical, biogeochemical and acoustic sensors throughout the water column and on the ocean floor, as well as devices that gathered water and sediment samples for subsequent laboratory analysis, were used. “For the first time, for two entire years we were able to comprehensively monitor not only the seasonal developments of microalgae and phytoplankton, but also the complete physical, chemical and biological system in which these developments take place,” says Dr. Wilken-Jon von Appen, a climate researcher at the AWI and first author of the study.

Flies Navigate Using Complex Mental Math

Scientists can image the brains of flies to study how they navigate. Here, a fly walks in place inside a visual arena that makes the fly feel as if it is traveling in various directions.
Credit: Maimon Lab

The treadmills in Rachel Wilson’s laboratories at Harvard Medical School aren’t like any you’ll find at a gym. They’re spherical, for one, and encased in bowling ball–sized plastic bubbles. They’re also built for flies.

Inside these bubbles, fruit flies walk in place as they navigate a 360-degree virtual reality environment.

A similar scene unfolds 200 miles away, in Gaby Maimon’s lab at the Rockefeller University, where flies attached to tiny tethers browse their own virtual worlds. By monitoring the flies’ brain signals, researchers in these two labs have discovered a key mechanism behind insect navigation.

These little flies, with brains the size of poppy seeds, navigate the world using mathematics that most of us mere mortals forgot after high school. The feat requires performing calculations with data gleaned from the senses and using geometry to compute the body’s traveling direction. Howard Hughes Medical Institute Investigators Wilson and Maimon and their colleagues report the work in two new studies released together December 15, 2021, in the journal Nature.

Researchers had previously located the fly brain’s compass – a set of neurons arrayed in a donut-shaped structure that keeps track of which direction the fly is facing. But scientists didn’t understand how flies knew which way they were traveling, Maimon says. “Not which way their body is facing, but which way they are moving in the real world.” The new papers identify for the first time which neurons in the brain are tracking both body movement and orientation, and how the signals combine to track a path through the environment.

Research breakthrough could see HIV drugs used to treat low-grade brain tumors

Drugs developed to treat AIDS and HIV could offer hope to patients diagnosed with the most common form of primary brain tumor.

The breakthrough, co-funded by the charity Brain Tumor Research, is significant because, if further research is conclusive, the anti-retroviral drugs could be prescribed for patients diagnosed with meningioma and acoustic neuroma brain tumors (also known as schwannoma).

More effective approaches are urgently needed as there are very few treatment options for these tumor types which frequently return following surgery and radiotherapy.

Meningioma is the most common form of primary brain tumor. Mostly low-grade, it can become cancerous over time, and develops from cells located in the meninges which protect the brain and spinal cord. Acoustic neuroma is a different type of low-grade, or non-cancerous brain tumor, which develops in nerve-protecting cells called Schwann cells. Both tumors may occur spontaneously, usually in adulthood, or in the hereditary disease Neurofibromatosis type 2 (NF2) in childhood/early adolescence.

Researchers at the Brain Tumor Research Centre at the University of Plymouth have shown previously that a tumor suppressor, named Merlin, contributes to the development of meningioma, acoustic neuroma and ependymoma tumors. It can also contribute to neurofibromatosis type 2 (NF2). Tumor suppressor genes play important roles in normal cells by controlling division or repairing errors in DNA. However, when tumor suppressors do not work properly or are absent, cells can grow out of control, leading to cancer.

In this latest study Dr Sylwia Ammoun, Senior Research Fellow, and her collaborator, Dr Robert Belshaw investigated the role that specific sections of our DNA play in tumor development. Named ‘endogenous retrovirus HERV-K’, these sections of DNA are relics of ancient infections that affected our primate ancestors, which have become stable elements of human DNA.

New drone type transports life-saving defibrillator

The prototype of the life-saving drone from TUM Horyzn during the test flight
Image: Andreas Heddergott / TUM

For cardiac arrest victims, minutes can mean the difference between life and death. It’s vital that medical emergency response teams get to them quickly, but in more remote, rural areas this can sometimes be difficult. “HORYZN” is an initiative of students at the Technical University of Munich (TUM) and has developed a remote-controlled, AI-supported rescue drone with a defibrillator on board for just such emergencies.

The fixed-wing drone – nearly 2 meters long with a wingspan of 3 meters – can reach areas that are difficult or even impossible to access with an ambulance. As soon as the aircraft reaches the coordinates received via emergency call, it goes into hover mode and lowers the defibrillator with a winch to the ground, where it can be easily deployed by first-aiders, including non-professionals, at the scene. This rapid deployment considerably increases the survival chances of the heart-attack patient.

With the help of the Bavarian Red Cross and a simulated emergency, the HORYZN team was able to demonstrate the technical capabilities of their prototype with a test flight in Ottobrunn on Wednesday. The demonstration was watched by TUM President, Prof. Thomas F. Hofmann, alongside Bavarian Science Minister Bernd Sibler and other guests.

Common ‘Core’: Using molecular fragments to detect deadly opioids

A photo illustrating 2 milligrams of fentanyl, a lethal dose for most people, compared to a penny. Matthew Moorman, a Sandia National Laboratories researcher, has developed a new method to detect tiny amounts of fentanyl analogs based on their common molecular structures.
Photo courtesy of the Drug Enforcement Administration

Researchers at Sandia National Laboratories have developed a method to detect trace amounts of synthetic opioids. They plan to combine their approach with miniaturized sensors to create a hand-portable instrument easily used by law enforcement agents for efficient detection in the field.

Fentanyl is a fast-acting, opioid-based pain reliever that is 80 to 100 times more potent than morphine. Illegally produced fentanyl often is mixed with other drugs such as cocaine or heroin and minuscule amounts can cause death by overdose. Drug overdose deaths, predominantly due to synthetic opioids such as illicitly manufactured fentanyl and fentanyl analogs, have accelerated during the COVID-19 pandemic, according to the Centers for Disease Control and Prevention.

The chemical structure of fentanyl can be modified to create molecular analogs. These analogs can have different potencies, and it can be difficult for law enforcement agencies to keep up with emerging analogs.

A potential protector against a mild heart attack’s aftereffects on metabolism

Illustration by Kateryna Kon
Science Photo Library
Getty Images

A new study in mice shows transplanted brown fat can reduce type 2 diabetes risk factors after a heart attack, an encouraging finding for scientists who hope to apply the so-called “good” fat’s beneficial properties to drugs that can help prevent health problems.

In the study, transplanting brown fat tissue into the abdomens of obese mice protected the animals from developing glucose intolerance, a hallmark of type 2 diabetes, after a mild heart attack.

Gene activation linked to negative effects after the heart attack was dampened in the transplanted mice, suggesting that brown fat – or adipose – tissue “talks” to other tissue in the body in ways that affect a variety of metabolism-related processes. The research team is continuing to tease out the substances and mechanisms behind that cross talk and how it affects whole-body physiology.

“In this study, the mice transplanted with brown adipose tissue were still obese but more metabolically healthy. The heart attack-induced glucose intolerance was negated by brown adipose tissue. The findings make a pretty powerful statement,” said senior study author Kristin Stanford, associate professor of physiology and cell biology in The Ohio State University College of Medicine.

“We think brown fat is secreting something, and if we can identify what’s being released we can target that as a therapeutic.”

The research is published online in the International Journal of Obesity.

Clinical research has shown that after a mild heart attack, people are more likely to develop insulin resistance and glucose intolerance, and are consequently more susceptible to having a second heart attack. Stanford said that what remains unclear is the cause for those increased risks: Does the first cardiac event itself make people more insulin resistant, or does the condition develop because people tend to be more sedentary after a heart attack?