. Scientific Frontline

Tuesday, June 6, 2023

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

In one study, progesterone showed a protective effect on the nerve cells of the intestine. This gives hope for the hormone to be used against Parkinson's.

There is mutual communication between the nerve cells of the gastrointestinal tract and those in the brain and spinal cord. It suggests that the digestive nervous system could affect brain processes that lead to Parkinson's. Paula Neufeld and Lennart Stegemann, who are doing their doctorate in the cytology department of the Medical Faculty of the Ruhr University Bochum, have demonstrated progesterone receptors for the first time in the nerve cells of the gastrointestinal tract and have shown that progesterone protects the cells. Their discovery opens up perspectives for the development of novel neuroprotective therapeutic approaches to counteract diseases such as Parkinson's or Alzheimer's. The study is in the journal Cells.

Monday, June 5, 2023

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.”

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