Newly discovered brain mechanism linked to anxiety, OCD

Distinguished Professor Mario Capecchi, Ph.D. and Naveen Nagajaran, Ph.D.
Photo Credit: Charlie Ehlert/U of U Health

Scientific Frontline: Extended "At a Glance" Summary: Microglia Function in Anxiety and OCSD

The Core Concept: Microglia, which constitute roughly 10 percent of brain cells and were historically viewed merely as cellular waste collectors, act as critical regulators of anxiety and obsessive-compulsive spectrum disorder (OCSD) behaviors.

Key Distinction/Mechanism: Contrary to the conventional dogma that neurons exclusively dictate behavior, specific subpopulations of microglia communicate directly with adjacent neural circuits to function as either an accelerator or a brake for extreme anxiety and fear responses.

Major Frameworks/Components:

• Hoxb8 Microglia: A distinct cellular subpopulation that, when stimulated in specific brain regions, drives extreme anxiety, fear-induced freezing, and uncontrollable grooming.
• Non-Hoxb8 Microglia: A secondary subpopulation that serves as a neurological brake, effectively preventing the onset of OCSD-like behaviors when stimulated simultaneously with Hoxb8 microglia.
• Optogenetics: An experimental technique combining genetic engineering and laser light to selectively activate targeted, living microglia populations in real time.
• Microglia-Neuron Crosstalk: The mechanism by which stimulated microglia induce more robust firing in neighboring neurons, translating immune cell activity directly into physical and psychological behavior.

Scientists closing in on long-lasting swine flu vaccine

 A team led by Eric Weaver, associate professor of biological sciences, has developed a robust vaccine against a strain of swine influenza. Framed by a model of nucleic acid proteins is (from left) Weaver; Matt Pekarek, a graduate student in the Weaver Lab; Cedric Wooledge, a technician with the Institutional Animal Care Program; David Steffen, with the Nebraska Veterinary Diagnostic Center; and Nicholas Jeanjaquet and Erika Petro-Turnquist, both doctoral students in the Weaver Lab. Not pictured is Hiep Vu, assistant professor in the Nebraska Center for Virology and Department of Animal Science.
Photo Credit: Craig Chandler | University Communication and Marketing

A successful long-term experiment with live hogs indicates Nebraska scientists may be another step closer to achieving a safe, long-lasting and potentially universal vaccine against swine flu.

The results are not only important to the pork industry, they hold significant implications for human health. That’s because pigs act as “mixing vessels,” where various swine and bird influenza strains can reconfigure and become transmissible to humans. In fact, the 2009 swine flu pandemic, involving a variant of the H1N1 strain, first emerged in swine before infecting about a fourth of the global population in its first year, causing nearly 12,500 deaths in the United States and perhaps as many as 575,000 worldwide, according to the Centers for Disease Control and Prevention.

“Considering the significant role swine play in the evolution and transmission of potential pandemic strains of influenza and the substantial economic impact of swine flu viruses, it is imperative that efforts be made toward the development of more effective vaccination strategies in vulnerable pig populations,” said Erika Petro-Turnquist, a doctoral student and lead author of the study recently published in Frontiers in Immunology.

Tagged for arrest: “Barcode” determines receptor’s fate

Receptors of the G protein-coupled receptor family contain a specific recognition pattern that determines their fate.
Artwork Credit: Anna Golynski

Receptor proteins serve as the “eyes and ears” of the cell. The largest receptor family is the so-called G protein-coupled receptors. They respond to highly diverse stimuli ranging from photons to hormones and odorants. Researchers at the University of Basel have discovered a unique recognition pattern that works like a barcode and tags the receptor for desensitization. By this mechanism, signaling in cells is rapidly switched off when it is no longer needed.

Odors, light, hormones and a tremendous variety of signaling molecules are recognized by a large family of cell receptors, known as G protein-coupled receptors (GPCRs). They are located on the cell surface and transduce signals into physiological outputs, for example, a rapid heartbeat triggered by fear or inflammation caused by infections. Due to its crucial role in many vital processes, this receptor family is implicated in a wide range of diseases, such as depression, cancer, inflammation, or cardiovascular diseases.

Fine-tuning 3D lab-grown mini tumors to help predict how patients respond to cancer therapies

The improved process allows researchers to use an advanced imaging method to study and analyze individual organoids in great detail.
Image Credit: Soragni Lab.

Scientists from the UCLA Jonsson Comprehensive Cancer Center have developed a new method to bio-print miniature tumor organoids that are designed to mimic the function and architecture of real tumors. The improved process allows researchers to use an advanced imaging method to study and analyze individual organoids in great detail, which can help researchers identify personalized treatments for people with rare or hard-to-treat cancers.

The method is described in the journal Nature Communications.

“Tumor organoids have become fundamental tools to investigate tumor biology and highlight drug sensitivities of individual patients,” said Alice Soragni, PhD, an assistant professor in the department of Orthopedic Surgery at the David Geffen School of Medicine at UCLA and member of the UCLA Jonsson Comprehensive Cancer Center. “However, we still need better ways to anticipate if resistance could be arising in a small population of cells, which we may not detect using conventional screening approaches. This is truly important, particularly as organoid-based drug predictions are starting to be leveraged clinically.”

To Prevent Future Pandemics, Leave Bats Alone

Photo Credit: Clement Kolopp

A new paper in the journal The Lancet Planetary Health makes the case that pandemic prevention requires a global taboo whereby humanity agrees to leave bats alone—to let them have the habitats they need, undisturbed.

Like the SARS coronavirus outbreak of 2003, the COVID-19 pandemic can be traced back to a bat virus. Whether someone handled or ate an infected bat or was exposed to a bat’s bodily fluids in a cave or some other way, or was exposed to another animal that had been infected by a bat, we will quite likely never know. Even a virus released via a lab accident would still have originally come from a bat. But we don’t need to know all of the details in order to act.

Bats are known to be reservoirs for a wide range of viruses that can infect other species, including people. They are a source of rabies, Marburg filoviruses, Hendra and Nipah paramyxoviruses, coronaviruses such as Middle East Respiratory Syndrome (MERS) Coronavirus, and fruit bats are strongly believed to be a source of Ebolaviruses. A new analysis points to the value of a global taboo whereby humanity agrees to leave bats alone—not fear them or try to chase them away or cull them (activities that only serve to disperse them and increase the odds of zoonotic spillover)—but to let them have the habitats they need and live undisturbed.

A lung injury therapy derived from adult skin cells

Natalia Higuita-Castro, seated, with the core team that worked in the lab on this study during the COVID-19 lockdown (L-R): Maria Angelica Rincon-Benavides, a PhD student in the Biophysics Graduate Program, and biomedical engineering postdoctoral fellows Ana Salazar-Puerta and Tatiana Cuellar-Gaviria.
Photo Credit: Matt Schutte

Therapeutic nanocarriers engineered from adult skin cells can curb inflammation and tissue injury in damaged mouse lungs, new research shows, hinting at the promise of a treatment for lungs severely injured by infection or trauma.

Researchers conducted experiments in cell cultures and mice to demonstrate the therapeutic potential of these nanoparticles, which are extracellular vesicles similar to the ones circulating in humans’ bloodstream and biological fluids that carry messages between cells. 

The hope is that a drop of solution containing these nanocarriers, delivered to the lungs via the nose, could treat acute respiratory distress syndrome (ARDS), one of the most frequent causes of respiratory failure that leads to putting patients on a ventilator. In ARDS, inflammation spiraling out of control in the lungs so seriously burdens the immune system that immune cells are unable to tend to the initial cause of the damage. 

Researchers Identify Genetic Makeup of New Strains of West Nile

This study shows the variety of strains in circulation and what mosquitoes may be carrying as we head into summer
Photo Credit: Jimmy Chan

Researchers at Connecticut Veterinary Medical Diagnostic Laboratory (CVMDL) located in UConn’s College of Agriculture, Health and Natural Resources identified the genetic makeup of strains of West Nile virus found in an alpaca and a crow.

These findings were published in Frontiers in Veterinary Science.

In 2021, eight cases of West Nile virus were brought to the CVMDL for diagnosis – seven birds, both domestic and wild – and one alpaca.

“We decided to pursue some research avenues through these diagnostic cases because we had an interesting cohort of West Nile cases that had come through that fall,” says Natalie Tocco ’23 (CAHNR), a resident in anatomic pathology the Department of Pathobiology and Veterinary Science.

Of the eight cases, the alpaca from Massachusetts and a crow from Connecticut had the highest amount of virus in their systems at the time of diagnosis.

Focusing on these two cases, the researchers were interested in seeing if there were genetic differences between the viruses because they occurred in different species in different states.

Organic light-emitting diodes: the blue shines brighter and longer

Thanks to a new type of molecule, blue OLEDs should shine brighter in the future and fade less quickly.
Photo Credit: Markus Breig, KIT

Two-channel intra / intermolecular exciplex emission enables efficient deep blue electroluminescence.

Organic LEDs, or OLEDs for short, are characterized by energy efficiency and flexibility. But one challenge lies in the production of blue OLEDs - these have so far lacked luminance and stability. Researchers at the Karlsruhe Institute of Technology (KIT) and at Shanghai University have now developed a new strategy for producing efficient deep blue OLEDs: A specially produced novel molecule enables two-channel intra / intermolecular exciplex emission with electronic excitation, thereby allowing deep blue electroluminescence. The researchers report in the journal Science Advances.

Organic LEDs are already in many smartphones, tablets and large-scale TVs. They do not require additional backlighting and are therefore energy-efficient, can be produced inexpensively using thin-film technology and also work on flexible substrates, which enables flexible displays and variable room lighting solutions. An OLED (stands for: organic light-emitting diode) consists of two electrodes, at least one of which is transparent. In between are thin layers of organic semiconducting materials. The lighting is created by electroluminescence. When creating an electric field, electrons from the cathode and holes (positive charges) from the anode are injected into the organic materials that act as emitters. Electrons and holes meet there and form electron-hole pairs. These then disintegrate into their initial state and release energy that the organic materials use to emit light. All colors are created by mixing the three colors blue, green and red.

Mechanisms behind aggressive cancer metastases uncovered

A molecular chain reaction gives breast cancer cells the ability to efficiently colonize other organs.
Image Credit: National Cancer Institute

Breast cancer spreading to other organs usually heralds a poorer prognosis. Researchers at the University and University Hospital of Basel have discovered a process that helps breast cancer cells implant themselves in certain places in the body. The results suggest a way of preventing secondary tumors.

For eight years, a team led by Professor Mohamed Bentires-Alj worked to establish the role of a cellular enzyme in breast cancer metastasis. The three lead authors Joana Pinto Couto, Milica Vulin, Charly Jehanno and collaborators discovered a mechanism that appears to support metastasis in a range of aggressive cancers. The team has reported their findings in the Embo Journal.

A cell can be pictured like a social network: in theory, every person is connected to every other person in the world through surprisingly few degrees of separation. Cell factors in molecular networks are connected to each other in an analogous way. If one stops functioning correctly, the system is thrown out of balance. The result is a cascade of effects that can have wide-ranging and unexpected consequences on more distant parts of the network. Deciphering these cascades can contribute to our understanding of how a minor defect in a cell’s system can lead to diseases like cancer. These insights offer ideas for new treatments.

Progesterone could protect against Parkinson's

Lennart Stegemann (left) and Paula Neufeld are working on their doctoral theses and were able to celebrate an early success with the top-class publication.
Photo Credit: © RUB, Marquard

Scientific Frontline: Extended "At a Glance" Summary: Progesterone's Neuroprotective Role in Parkinson's Disease

The Core Concept: Progesterone, a natural steroid hormone, exhibits neuroprotective properties that preserve the viability of nerve cells within the gastrointestinal tract under toxic stress.

Key Distinction/Mechanism: Rather than acting exclusively on the central nervous system, progesterone binds to newly identified receptors in the enteric nervous system (ENS). This localized protection prevents cellular death in the gut, which may interrupt the progression of neurodegenerative signaling to the brain via the gut-brain axis.

Major Frameworks/Components:

• The Enteric Nervous System (ENS): A sophisticated network of approximately 100 million nerve cells autonomously governing the gastrointestinal tract, frequently termed the "second brain."
• The Gut-Brain Axis: A bidirectional communication network connecting the ENS and the central nervous system (CNS), heavily influenced by the intestinal microbiome and the vagus nerve.
• Neurodegeneration Simulation: An experimental model utilizing cellular toxins on ENS cultures to replicate the localized cellular damage characteristic of Parkinson's disease.

Research reveals ants inflict pain with neurotoxins

Bullet ants, along with Australian green ants, inflict pain by targeting nerve cells.
Photo Credit: Hadrien Lalagüe.

University of Queensland researchers have shown for the first time that some of the world’s most painful ant stings target nerves, like snake and scorpion venom.

Dr Sam Robinson and colleagues at UQ’s Institute for Molecular Bioscience discovered the ant neurotoxins while studying the Australian green ant and South American bullet ant which have stings that cause long-lasting pain.

“We have shown that these ant venoms target our nerve cells that send pain signals,” Dr Robinson said.

“Normally, the sodium channels in these sensory neurons open only briefly in response to a stimulus.

“We discovered that the ant toxins bind to the sodium channels and cause them to open more easily and stay open and active, which translates to a long-lasting pain signal.

Physicists discover an exotic material made of bosons

 Two stacked lattices with one slightly offset create a new pattern called a moiré
Photo Credit Matt Perko

Take a lattice — a flat section of a grid of uniform cells, like a window screen or a honeycomb — and lay another, similar lattice above it. But instead of trying to line up the edges or the cells of both lattices, give the top grid a twist so that you can see portions of the lower one through it. This new, third pattern is a moiré, and it’s between this type of overlapping arrangement of lattices of tungsten diselenide and tungsten disulfide where UC Santa Barbara physicists found some interesting material behaviors.

“We discovered a new state of matter — a bosonic correlated insulator,” said Richen Xiong, a graduate student researcher in the group of UCSB condensed matter physicist Chenhao Jin, and the lead author of a paper in the journal Science. According to Xiong, Jin and collaborators from UCSB, Arizona State University and the National Institute for Materials Science in Japan, this is the first time such a material      has been created in a “real” (as opposed to synthetic) matter system. The unique material is a highly ordered crystal of bosonic particles called excitons.

“Conventionally, people have spent most of their efforts to understand what happens when you put many fermions together,” Jin said. “The main thrust of our work is that we basically made a new material out of interacting bosons.”

Imaging agents light up two cancer biomarkers at once to give more complete picture of tumor

Researcher Indrajit Srivastava holds solutions of nanoparticles that can target two cancer biomarkers, giving off two distinct signals when lit by one fluorescent wavelength.  This could give surgeons a more complete picture of a tumor and guide operating-room decisions. In the background is a microscopic scan of a tissue sample. 
Photo Credit: Fred Zwicky

Cancer surgeons may soon have a more complete view of tumors during surgery thanks to new imaging agents that can illuminate multiple biomarkers at once, University of Illinois Urbana-Champaign researchers report. The fluorescent nanoparticles, wrapped in the membranes of red blood cells, target tumors better than current clinically approved dyes and can emit two distinct signals in response to just one beam of surgical light, a feature that could help doctors distinguish tumor borders and identify metastatic cancers. 

The imaging agents can be combined with bioinspired cameras, which the researchers previously developed for real-time diagnosis during surgery, said research group leader Viktor Gruev, an Illinois professor of electrical and computer engineering. In a new study in the journal ACS Nano, the researchers demonstrated their new dual-signal nanoparticles in tumor phantoms – 3D models that mimic the features of tumors and their surroundings – and in live mice. 

“If you want to find all the cancer, imaging one biomarker is not enough. It could miss some tumors. If you introduce a second or a third biomarker, the likelihood of removing all cancer cells increases, and the likelihood of a better outcome for the patients increases.” said Gruev, who also is a professor in the Carle Illinois College of Medicine. “Multiple-targeted drugs and imaging agents are a recent trend, and our group is driving the trend hard because we have the camera technology that can image multiple signals at once.”

Electrical synapses in the neural network of insects found to have unexpected role in controlling flight power

The fruit fly Drosophila melanogaster flaps its wings two hundred times per second to fly forwards.
 Photo Credit: Silvan Hürke

Researchers of Mainz University and Humboldt-Universität zu Berlin revealed previously unknown function of electrical synapses, thus deciphering the neural circuit used to regulate insect wingbeat frequency

A team of experimental neurobiologists at Johannes Gutenberg University Mainz (JGU) and theoretical biologists at Humboldt-Universität zu Berlin has managed to solve a mystery that has been baffling scientists for decades. They have been able to determine the nature of the electrical activity in the nervous system of insects that controls their flight. In a paper recently published in Nature, they report on a previously unknown function of electrical synapses employed by fruit flies during flight.

The fruit fly Drosophila melanogaster beats its wings around 200 times per second in order to move forward. Other small insects manage even 1,000 wingbeats per second. It is this high frequency of wingbeats that generates the annoying high-pitched buzzing sound we commonly associate with mosquitoes. Every insect has to beat its wings at a certain frequency to not get “stuck” in the air, which acts as a viscous medium due to their small body size. For this purpose, they employ a clever strategy that is widely used in the insect world. This involves reciprocal stretch activation of the antagonistic muscles that raise and depress the wings. The system can oscillate at high frequencies, thus producing the high rate of wingbeats required for propulsion. The motor neurons are unable to keep pace with the speed of the wings so that each neuron generates an electrical pulse that controls the wing muscles only about every 20th wingbeat. These pulses are precisely coordinated with the activity of other neurons. Special activity patterns are generated in the motor neurons that regulate the wingbeat frequency. Each neuron fires at a regular rate but not at the same time as the other neurons. There are fixed intervals between which each of them fires. While it has been known since the 1970s that neural activity patterns of this kind occur in the fruit fly, there was no explanation of the underlying controlling mechanism.

Testing for 'zombie cells' could boost number of hearts for transplant

Image Credit: PublicDomainPictures

Scientific Frontline: Extended "At a Glance" Summary: Senescent "Zombie" Cells in Heart Transplants

The Core Concept: Senescent cells, commonly referred to as "zombie" cells, are living but dysfunctional cells that release harmful molecules capable of inducing senescence in neighboring cells, triggering inflammation, and forming scar tissue within the heart muscle.

Key Distinction/Mechanism: Rather than relying exclusively on chronological age to determine organ viability, clinicians can identify the biological signature of senescent cells. These cells secrete elevated levels of specific proteins, such as GDF15, and possess distinct RNA markers like p21, which serve as quantifiable indicators of a heart's true biological age and functional health.

Origin/History: The foundational research identifying this senescent signature was presented in June 2023 at the British Cardiovascular Society conference by scientists from Newcastle University, supported by funding from the British Heart Foundation and the Medical Research Council.