Chronic Alcohol Use Reshapes the Brain’s Immune Landscape, Driving Anxiety and Addiction (Neuroscience)

In their quest to understand how the immune system is implicated in alcohol use disorder, Scripps Research scientists have found a potential path for treatment.

Deep within the brain, a small almond-shaped region called the amygdala plays a vital role in how we exhibit emotion, behavior and motivation. Understandably, it’s also strongly implicated in alcohol abuse, making it a long-running focus of Marisa Roberto, PhD, professor in Scripps Research’s Department of Molecular Medicine.

In animal studies, prolonged alcohol use led to key changes in a region of the brain called the amygdala, resulting in behaviors that drive addiction. ©Scripps

Now, for the first time, Roberto and her team have identified important changes to anti-inflammatory mechanisms and cellular activity in the amygdala that drive alcohol addiction. By countering this process in mice, they were able to stop excessive alcohol consumption–revealing a potential treatment path for alcohol use disorder. The study is published in Progress in Neurobiology.

“We found that chronic alcohol exposure compromises brain immune cells, which are important for maintaining healthy neurons,” says Reesha Patel, PhD, a postdoctoral fellow in Roberto’s lab and first author of the study. “The resulting damage fuels anxiety and alcohol drinking that may lead to alcohol use disorder.”

Roberto’s study looked specifically at an immune protein called Interleukin 10, or IL-10, which is prevalent in the brain. IL-10 is known to have potent anti-inflammatory properties, which ensures that the immune system doesn’t respond too powerfully to disease threats. In the brain, IL-10 helps to limit inflammation from injury or disease, such as stroke or Alzheimer’s. But it also appears to influence key behaviors associated with chronic alcohol use.

In mice with chronic alcohol use, IL-10 was significantly reduced in the amygdala and didn’t signal properly to neurons, contributing to increased alcohol intake. By boosting IL-10 signaling in the brain, however, the scientists could reverse the aberrant effects. Notably, they observed a stark reduction in anxiety-like behaviors and motivation to drink alcohol.

“We’ve shown that inflammatory immune responses in the brain are very much at play in the development and maintenance of alcohol use disorder,” Roberto says. “But perhaps more importantly, we provided a new framework for therapeutic intervention, pointing to anti-inflammatory mechanisms.”

Alcohol use disorder is widespread, affecting some 15 million people in the United States, and few effective treatments exist. By examining how brain cells change with prolonged exposure to alcohol, Roberto’s lab has uncovered many possible new therapeutic approaches for those with alcohol addiction.

In the latest study, Roberto’s lab collaborated with Silke Paust, PhD, associate professor in the Department of Immunology and Microbiology. Paust and her team determined the precise immune cells throughout the whole brain that are affected by chronic alcohol use. The findings revealed a large shift in the brain immune landscape, with increased levels of immune cells known as microglia and T-regulatory cells, which produce IL-10.

Despite a higher number of IL-10-producing cells in the whole brain of mice with prolonged alcohol use, the amygdala told a different story. In that region, levels of IL-10 were lower and their signaling function was compromised–suggesting that the immune system in the amygdala responds uniquely to chronic alcohol use.

This study complements recent findings by the Roberto lab demonstrating a casual role for microglia in the development of alcohol dependence.

Future studies will build on these findings to identify exactly how and when IL-10 signals to neurons in the amygdala and other addition-related brain circuits to alter behavior.

References: Reesha R. Patel, Marisa Roberto et al., “IL-10 normalizes aberrant amygdala GABA transmission and reverses anxiety-like behavior and dependence-induced escalation of alcohol intake”, Progress in Neurobiology, 2020. https://www.sciencedirect.com/science/article/pii/S0301008220302070 https://doi.org/10.1016/j.pneurobio.2020.101952

Provided by SCRIPPS

New Optical Method Paves Way To Breath Test For Cancer Biomarker (Medicine / Oncology)

Researchers have developed an extremely sensitive, yet simple optical method for detecting formaldehyde in a person’s breath. Because formaldehyde is being studied as a potential biomarker for lung and breast cancer, the new method could one day lead to an inexpensive and fast way to screen for cancer.

Researchers have developed an extremely sensitive, yet simple optical method for detecting formaldehyde. Their approach is based on multipass spectroscopy, which introduces a laser through a small hole in a mirror. The laser light then bounces back and forth between mirrors, creating interaction lengths with the sample that are tens or hundreds of times the length of the cell. ©Mateusz Winkowski, University of Warsaw

“Measuring biomarkers in exhaled breath is noninvasive, painless and fast and could be used to screen for cancer even at very early disease stages, which is crucial for successful treatment,” said research team leader Mateusz Winkowski from the University of Warsaw in Poland. “The optical method we developed could make this type of measurement more practical and inexpensive.”

In The Optical Society (OSA) journal Biomedical Optics Express, Winkowski and Tadeusz Stacewicz show that their new optical sensing method based on multipass spectroscopy can detect the presence of 1 molecule of formaldehyde in a million air particles, or 1 part per million, even in the presence of gasses that can interfere with optical measurements.

“Our dream is to one day build a table-top device that would be inexpensive and could be used for cancer screening in any medical consulting room,” said Winkowski. “During a basic medical examination, the patient could blow into the device, and within a minute the doctor would know if the patient might need additional conventional examinations.”

Boosting sensitivity

Spectroscopy can be used to identify the chemical composition of a substance by measuring the color of light absorbed or emitted from a sample. A spectroscopy approach known as multipass is useful for detecting low concentrations of gas molecules because it increases the extent to which the light interacts with the sample. This setup uses an experimental cell with a mirror on each end. A laser introduced through a small hole in one mirror then bounces back and forth in the cell, creating interaction lengths tens or hundreds of times the length of the cell.

When trying to detect extremely low concentrations, noise can be a problem with multipass spectroscopy. This is because the multiple laser beams create a type of optical interference called fringe interference that decreases sensitivity and makes it impossible to precisely determine the biomarker concentration. To reduce this optical interference, the researchers developed a method called optical fringe quenching.

For the new optical fringe quenching technique, the researchers slightly change, or modulate, the emission of the laser over a range of wavelengths and then average the light emitted from the sample over these wavelengths. This helps eliminate the optical interference enough to allow detection of formaldehyde. The researchers also selected a spectral range and sample pressure that helped reduce interference from other constituents found in breath samples.

Optical sensing of formaldehyde

The researchers tested their new approach using calibrated artificial mixtures of formaldehyde in air. Their results showed that the approach was more than sufficient to detect formaldehyde in breath at levels that might indicate the presence of disease.

“Our optical fringe quenching technique can be used to improve any optical system that uses a multipass cell,” said Winkowski. “It could also be useful for measuring formaldehyde gas emitted from household materials or industrial sources to better understand its effects on human health.”

Next, the researchers plan to test their analysis approach’s ability to measure ethane gas in breath. Study findings have suggested that ethane might also be used as a biomarker for cancer and other diseases.

References: M. Winkowski, T. Stacewicz, “Optical detection of formaldehyde in air in the 3.6 μm range,” Biomed. Opt. Express, volume 11, issue 12, pp. 7019-7031 (2020). https://www.osapublishing.org/boe/fulltext.cfm?uri=boe-11-12-7019&id=442528
DOI: https://doi.org/10.1364/BOE.405384.

Provided by The Optical Society

Computer Scientists Launch Counteroffensive Against Video Game Cheaters (Computer Science)

Cheat detection system could gracefully kick out cheating players.

University of Texas at Dallas computer scientists have devised a new weapon against video game players who cheat.

©Uni. Of Texas

The researchers developed their approach for detecting cheaters using the popular first-person shooter game Counter-Strike. But the mechanism can work for any massively multiplayer online (MMO) game that sends data traffic to a central server.

Their research was published online Aug. 3 in IEEE Transactions on Dependable and Secure Computing.

Counter-Strike is a series of games in which players work in teams to counter terrorists by securing plant locations, defusing bombs and rescuing hostages. Players can earn in-game currency to buy more powerful weapons, which is a key to success. Various software cheats for the game are available online.

“Sometimes when you’re playing against players who use cheats you can tell, but sometimes it may not be evident,” said Md Shihabul Islam, a UT Dallas computer science doctoral student in the Erik Jonsson School of Engineering and Computer Science and lead author of the study, who plays Counter-Strike for fun. “It’s not fair to the other players.”

In addition to fair play, cheating also can have an economic impact when dissatisfied players leave to play other games, Islam said.

Cheating incidents also can have serious consequences in esports, a fast-growing industry with annual revenues close to $1 billion. Cheating can result in sanctions against teams and players, including disqualification, forfeiture of prize money and a ban on future participation, according to the Esports Integrity Commission based in the United Kingdom.

Detecting cheating in MMO games can be challenging because the data that goes from a player’s computer to the game server is encrypted. Previous research has relied on decrypted game logs to detect cheating after the fact. The UT Dallas researchers’ approach eliminates the need for decrypted data and instead analyzes encrypted data traffic to and from the server in real time.

“Players who cheat send traffic in a different way,” said Dr. Latifur Khan, an author of the study, professor of computer science and director of the Big Data Analytics and Management Lab at UT Dallas. “We’re trying to capture those characteristics.”

For the study, 20 students in the UT Dallas class Cyber Security Essentials for Practitioners downloaded Counter-Strike and three software cheats: an aimbot, which automatically targets an opponent; a speed hack, which allows the player to move faster; and a wallhack, which makes walls transparent so players can easily see their opponent. The researchers set up a server dedicated to the project so the students’ activity would not disrupt other online players.

The researchers analyzed game traffic to and from the dedicated server. Data travels in packets, or bundles, of information. The packets can be different sizes, depending on the contents. Researchers analyzed features, including the number of incoming and outgoing packets, their size, the time they were transmitted, their direction and the number of packets in a burst, which is a group of consecutive packets.

By monitoring the data traffic from the student players, researchers identified patterns that indicated cheating. They then used that information to train a machine-learning model, a form of artificial intelligence, to predict cheating based on patterns and features in the game data.

The researchers adjusted their statistical model, based on a small set of gamers, to work for larger populations. Part of the cheat-detection mechanism involves sending the data traffic to a graphics processing unit, which is a parallel server, to make the process faster and take the workload off the main server’s central processing unit.

The researchers plan to extend their work to create an approach for games that do not use a client-server architecture and to make the detection mechanism more secure. Islam said gaming companies could use the UT Dallas technique with their own data to train gaming software to detect cheating. If cheating is detected, the system could take immediate action.

“After detection,” Khan said, “we can give a warning and gracefully kick the player out if they continue with the cheating during a fixed time interval.

“Our aim is to ensure that games like Counter-Strike remain fun and fair for all players.”

References: M. S. Islam, B. Dong, S. Chandra, L. Khan and B. M. Thuraisingham, “GCI: A GPU Based Transfer Learning Approach for Detecting Cheats of Computer Game,” in IEEE Transactions on Dependable and Secure Computing. http://ieeexplore.ieee.org/stamp/stamp.jsp?tp=&arnumber=9154512&isnumber=4358699
doi: 10.1109/TDSC.2020.3013817

Provided by University of Texas at Dallas

Cosmic Flashes Come In All Different Sizes (Planetary Science)

By studying the site of a spectacular stellar explosion seen in April 2020, a Chalmers-led team of scientists have used four European radio telescopes to confirm that astronomy’s most exciting puzzle is about to be solved. Fast radio bursts, unpredictable millisecond-long radio signals seen at huge distances across the universe, are generated by extreme stars called magnetars – and are astonishingly diverse in brightness.

On May 24, four European telescopes took part in the global effort to understand mysterious cosmic flashes. The telescopes captured flashes of radio waves from an extreme, magnetised star in our galaxy. All are shown in this illustration. ©Danielle Futselaar/artsource.nl

For over a decade, the phenomenon known as fast radio bursts has excited and mystified astronomers. These extraordinarily bright but extremely brief flashes of radio waves – lasting only milliseconds – reach Earth from galaxies billions of light years away.

In April 2020, one of the bursts was for the first time detected from within our galaxy, the Milky Way, by radio telescopes CHIME and STARE2. The unexpected flare was traced to a previously-known source only 25 000 light years from Earth in the constellation of Vulpecula, the Fox, and scientists all over the world coordinated their efforts to follow up the discovery.

In May, a team of scientists led by Franz Kirsten (Chalmers) pointed four of Europe’s best radio telescopes towards the source, known as SGR 1935+2154. Their results are published today in a paper in the journal Nature Astronomy. http://www.nature.com/articles/s41550-020-01246-3

“We didn’t know what to expect. Our radio telescopes had only rarely been able to see fast radio bursts, and this source seemed to be doing something completely new. We were hoping to be surprised!”, said Mark Snelders, team member from the Anton Pannekoek Institute for Astronomy, University of Amsterdam.

The radio telescopes, one dish each in the Netherlands and Poland and two at Onsala Space Observatory in Sweden, monitored the source every night for more than four weeks after the discovery of the first flash, a total of 522 hours of observation.

On the evening of May 24, the team got the surprise they were looking for. At 23:19 local time, the Westerbork telescope in the Netherlands, the only one of the group on duty, caught a dramatic and unexpected signal: two short bursts, each one millisecond long but 1.4 seconds apart.

Kenzie Nimmo, astronomer at Anton Pannekoek Institute for Astronomy and ASTRON, is a member of the team.

“We clearly saw two bursts, extremely close in time. Like the flash seen from the same source on April 28, this looked just like the fast radio bursts we’d been seeing from the distant universe, only dimmer. The two bursts we detected on May 24 were even fainter than that”, she said.

Onsala Space Observatory in western Sweden. ©Magnus Falck/Chalmers University of Technology

This was new, strong evidence connecting fast radio bursts with magnetars, the scientists thought. Like more distant sources of fast radio bursts, SGR 1935+2154 seemed to be producing bursts at random intervals, and over a huge brightness range.

“The brightest flashes from this magnetar are at least ten million times as bright as the faintest ones. We asked ourselves, could that also be true for fast radio burst sources outside our galaxy? If so, then the universe’s magnetars are creating beams of radio waves that could be criss-crossing the cosmos all the time – and many of these could be within the reach of modest-sized telescopes like ours”, said team member Jason Hessels (Anton Pannekoek Institute for Astronomy and ASTRON, Netherlands).

Neutron stars are the tiny, extremely dense remnants left behind when a short-lived star of more than eight times the mass of the Sun explodes as a supernova. For 50 years, astronomers have studied pulsars, neutron stars which with clock-like regularity send out pulses of radio waves and other radiation. All pulsars are believed to have strong magnetic fields, but the magnetars are the strongest known magnets in the universe, each with a magnetic field hundreds of trillions of times stronger than the Sun’s.

In the future, the team aims to keep the radio telescopes monitoring SGR 1935+2154 and other nearby magnetars, in the hope of pinning down how these extreme stars actually make their brief blasts of radiation.

Scientists have presented many ideas for how fast radio bursts are generated. Franz Kirsten, astronomer at Onsala Space Observatory, Chalmers, who led the project, expects the rapid pace in understanding the physics behind fast radio bursts to continue.

“The fireworks from this amazing, nearby magnetar have given us exciting clues about how fast radio bursts might be generated. The bursts we detected on May 24 could indicate a dramatic disturbance in the star’s magnetosphere, close to its surface. Other possible explanations, like shock waves further out from the magnetar, seem less likely, but I’d be delighted to be proved wrong. Whatever the answers, we can expect new measurements and new surprises in the months and years to come”, he said.

References: Kirsten, F., Snelders, M.P., Jenkins, M. et al. Detection of two bright radio bursts from magnetar SGR 1935 + 2154. Nat Astron (2020). https://www.nature.com/articles/s41550-020-01246-3 https://doi.org/10.1038/s41550-020-01246-3

Provided by Chalmers University Of Technology

New Technique Isolates Brain Cells Associated with Parkinson’s Disease (Neuroscience)

Analysis shows changes in how cells of symptomatic mice may sense oxygen.

Carnegie Mellon University researchers have developed a new technique for isolating a type of brain cell associated with Parkinson’s disease symptoms, enabling them to study that cell type in detail.

The technique, which works only in specially bred mice, costs less than previous methods for isolating these brain cells, said Alyssa Lawler, a Ph.D. student in biological sciences. By using it, she and her colleagues already have detected previously undiscovered changes to how the diseased neurons sense and use oxygen.

The researchers describe the technique and their findings in a research paper published online by the journal JNeurosci.

“Even a small chunk of brain tissue can have dozens of different cell types,” said Andreas Pfenning, an assistant professor in CMU’s Computational Biology Department. “Each of these cell types has different roles in the behavior of an animal and also in disease.” Separating cells of a certain type from their neighbors is thus a critical first step for researchers who want to study them.

In this case, the research team focused on parvalbumin-expressing (PV+) neurons, which have been implicated in Parkinson’s disease by the lab of Aryn Gittis, associate professor of biological sciences. Mice with Parkinson’s symptoms regain motor control and their ability to run around when these cells are stimulated.

Lab mice have been bred with PV+ cells that contain a protein called Cre that activates a fluorescent green protein. That fluorescence makes it possible for cell-sorting machines to isolate the cells from others in a mixture. But cell-sorting machines are extremely expensive, so Lawler developed a cheaper method, called Cre-Specific Nuclear Anchored Independent Labeling, or cSNAIL.

The new technique uses a virus commonly employed by researchers to deliver DNA to brain cells. When the virus enters PV+ cells, Cre causes the tag to fluoresce. The tag, anchored to the cell nucleus, can hold on even when the tissues are chopped up, Lawler said. Researchers then use antibodies to detect the tag and pull the PV+ nuclei away from the others.

“The technique turned out to be really specific, really efficient,” Lawler said, noting that it can be adapted to other mouse models that use the Cre protein.

In a subsequent analysis of the PV+ neurons, the researchers found that those from sick mice produced more RNA involved in the expression of genes that sense or use oxygen. Further study also showed that the DNA in the nucleus unwound in ways indicating that the oxygen-sensing genes were more active.

“Oxygen-sensing pathways have been implicated in other, earlier aspects of Parkinson’s disease, but not previously in PV+ cells,” Lawler said. These pathways are involved in both protecting and killing cells during neurodegeneration.

Pfenning noted that datasets from this study are part of a larger effort to build machine learning models that will help researchers interpret disease mechanisms by looking at how particular DNA sequences respond to different conditions across types of cells.

“We’re learning how to talk to cells, to speak their language,” Lawler said.

References: Alyssa J Lawler, Ashley R Brown, Rachel S Bouchard, Noelle Toong, Yeonju Kim, Nitinram Velraj, Grant Fox, Michael Kleyman, Byungsoo Kang, Aryn H Gittis and Andreas R Pfenning, “Cell type-specific oxidative stress genomic signatures in the globus pallidus of dopamine depleted mice”, Journal of Neuroscience 13 November 2020, https://www.jneurosci.org/content/early/2020/11/02/JNEUROSCI.1634-20.2020 JN-RM-1634-20; DOI: https://doi.org/10.1523/JNEUROSCI.1634-20.2020

Provided by Carnegie Mellon University

New Technology Allows More Precise View of the Smallest Nanoparticles (Engineering)

Current state-of-the-art techniques have clear limitations when it comes to imaging the smallest nanoparticles, making it difficult for researchers to study viruses and other structures at the molecular level.

Scientists have reported a new optical imaging technology, using a glass side covered with gold nanodiscs that allows them to monitor changes in the transmission of light and determine the characteristics of nanoparticles as small as 25 nanometers in diameter. ©Uni. Of Houston

Scientists from the University of Houston and the University of Texas M.D. Anderson Cancer Center have reported in Nature Communications a new optical imaging technology for nanoscale objects, relying upon unscattered light to detect nanoparticles as small as 25 nanometers in diameter. The technology, known as PANORAMA, uses a glass slide covered with gold nanodiscs, allowing scientists to monitor changes in the transmission of light and determine the target’s characteristics.

PANORAMA takes its name from Plasmonic Nano-aperture Label-free Imaging (PlAsmonic NanO-apeRture lAbel-free iMAging), signifying the key characteristics of the technology. PANORAMA can be used to detect, count and determine the size of individual dielectric nanoparticles.

Wei-Chuan Shih, professor of electrical and computer engineering at UH and corresponding author for the paper, said the smallest transparent object a standard microscope can image is between 100 nanometers and 200 nanometers. That’s mainly because – in addition to being so small – they don’t reflect, absorb or “scatter” enough light, which could allow imaging systems to detect their presence.

Labeling is another commonly used technique; it requires researchers to know something about the particle they are studying – that a virus has a spike protein, for example – and engineer a way to tag that feature with fluorescent dye or some other method in order to more easily detect the particle.

“Otherwise, it will appear as invisible as a tiny dust particle under the microscope, because it’s too small to detect,” Shih said.

Another drawback? Labeling is only useful if researchers already know at least something about the particle they want to study.

“With PANORAMA, you don’t have to do the labeling,” Shih said. “You can view it directly because PANORAMA does not rely on detecting the scattered light from the nanoparticle.”

Instead, the system allows observers to detect a transparent target as small as 25 nanometers by monitoring light transmission through the gold nanodisc-covered glass slide. By monitoring changes in the light, they are able to detect the nearby nanoparticles. The optical imaging system is a standard bright-field microscope commonly found in any lab. There is no need for lasers or interferometers which are required in many other label-free imaging technologies.

“The size limit has not been reached, according to the data. We stopped at 25 nm nanoparticles simply because that is the smallest polystyrene nanoparticle on the market,” Shih said.

References: Ohannesian, N., Misbah, I., Lin, S.H. et al. Plasmonic nano-aperture label-free imaging (PANORAMA). Nat Commun 11, 5805 (2020). https://doi.org/10.1038/s41467-020-19678-w

Provided by University of Houston

Paleontologists Uncover Three New species of extinct walruses in Orange County (Paleontology)

Millions of years ago, in the warm Pacific Ocean off the coast of Southern California, walrus species without tusks lived abundantly.

But in a new study, Cal State Fullerton paleontologists have identified three new walrus species discovered in Orange County and one of the new species has “semi-tusks” — or longer teeth.

Map & Skulls. ©Journal of Vertebrate Paleontology

The other two new species don’t have tusks and all predate the evolution of the long iconic ivory tusks of the modern-day walrus, which lives in the frigid Arctic.

The researchers describe a total of 12 specimens of fossil walruses from Orange, Los Angeles and Santa Cruz counties, all estimated to be 5 to 10 million years old. The fossils represent five species, with two of the three new species represented by specimens of males, females and juveniles.

Their research, which gives insights on the dental and tusk evolution of the marine mammal, was published today in the Journal of Vertebrate Paleontology.

Geology graduate Jacob Biewer, and his research adviser James F. Parham, associate professor of geological sciences, are authors of the study, based on fossil skull specimens.

Parham and Biewer worked with Jorge Velez-Juarbe, an expert in marine mammals at the Natural History Museum of Los Angeles County, who is a co-author of the paper. Velez-Juarbe is a former postdoctoral scholar in Parham’s lab and has collaborated on other CSUF fossil research projects. Parham is a research associate at the museum, which provides research opportunities for him and his students.

The researchers teamed to study and describe the anatomy of the specimens, most of which are part of the museum’s collection.

“Orange County is the most important area for fossil walruses in the world,” said Biewer, first author of the paper who conducted the research for his master’s thesis. “This research shows how the walruses evolved with tusks.”

Extinct Walrus Species Get Names

Today, there is only one walrus species and its scientific name is Odobenus.

For the new species found in Orange County, the researchers named the semi-tusked walrus, Osodobenus eodon, by combining the words Oso and Odobenus. Another is named Pontolis kohnoi in honor of Naoki Kohno, a fossil walrus researcher from Japan. Both of these fossils were discovered in the Irvine, Lake Forest and Mission Viejo areas.

Osodobenus eodon and Pontolis kohnoi are both from the same geological rock layer as the 2018 study by Parham and his students of another new genus and species of a tuskless walrus, Titanotaria orangensis, named after CSUF Titans. These fossils were found in the Oso Member of the Capistrano Formation, a geological formation near Lake Forest and Mission Viejo.

The third new walrus species, Pontolis barroni, was found in Aliso Viejo, near the 73 Toll Road. It is named after John Barron, a retired researcher from the U.S.Geological Survey and world expert on the rock layer where the specimens were found, Parham said.

Analysis of these specimens show that fossil walrus teeth are more variable and complex than previously considered. Most of the new specimens predate the evolution of tusks, Parham said.

“Osodobenus eodon is the most primitive walrus with tusk-like teeth,” Parham said. “This new species demonstrates the important role of feeding ecology on the origin and early evolution of tusks.”

Biewer explained that his work focused on getting a better understanding of the evolutionary history of the walrus in regards to its teeth.

“The importance of dental evolution is that it shows the variability within and across walrus species. Scientists assumed you could identify certain species just based on the teeth, but we show how even individuals of the same species could have variability in their dental setup,” said Biewer, who earned a master’s degree in geology in 2019.

“Additionally, everyone assumes that the tusks are the most important teeth in a walrus, but this research further emphasizes how tusks were a later addition to the history of walruses. The majority of walrus species were fish eaters and adapted to catching fish, rather than using suction feeding on mollusks like modern walruses.”

Biewer, now a paleontologist in the Modesto area, also examined whether climate changes in the Pacific Ocean had an impact on ancient walruses. His work suggests that a rise in water temperature helped to boost nutrients and planktonic life, and played a role in the proliferation of walruses about 10 million years ago, which may have contributed to their diversity.

Sidebar:

For the fossil walrus research project, geology graduate Jacob Biewer spent hours in the lab measuring and describing the walrus bones.

“I sat many hours with a handy caliper taking notes on the lengths of teeth and width of skulls, among many other measurements,” he said. “Describing bones is much more in depth and meticulous than it sounds. There are traits that the bones of each walrus species have — the size, shape and number of teeth. I recorded how the bones are different from, or similar to, other extinct walrus species.”

Biewer, a paleontologist who lives in Modesto, noted that despite the pandemic, he and Parham worked on the scientific paper with 300 miles of social distancing.

Completing his first journal publication, based on his master’s work, and conducting the research project helped him to understand scientific methods and techniques that he now uses in his career, where he monitors construction sites for paleontological resources. He also teaches undergraduate geology courses at Cal State Stanislaus, where he earned a bachelor’s degree in geology, and is considering pursuing a doctorate.

“The experiences I had in conducting this research, especially the presentations at national paleontological conferences, led to a big increase in my confidence in my scientific abilities,” Biewer said. “I credit my time working with Dr. Parham directly to the achievements in my current employment — from the skills he imparted to the doors he helped open.”

References: Jacob N. Biewer , Jorge Velez-Juarbe & James F. Parham, “Insights on the dental evolution of walruses based on new fossil specimens from California”, Journal Of Vertebrate Paleontology, 2020. Article: e1833896 | Received 06 Dec 2019, Accepted 01 Sep 2020, Published online: 16 Nov 2020. https://www.tandfonline.com/doi/full/10.1080/02724634.2020.1833896

Provided by Taylor and Francis Group

Peptide Is a Key Mediator in the Regulation of Compulsive Alcohol Drinking (Medicine)

Findings may open new avenues in the pharmacological treatment of alcohol use disorder which would target this system.

Researchers from Boston University School of Medicine (BUSM) have identified that a peptide, pituitary adenylate cyclase-activating mediator of compulsive consumption of alcohol. In addition, they have discovered that this protein acts in an area of the brain called the Bed Nucleus of the Stria Terminalis, or BNST, a region involved in fear, anxiety and stress responses, to exert these effects.

Alcohol use disorder or AUD is a chronic relapsing brain disorder characterized by an impaired ability to stop or control alcohol use despite adverse social, occupational or health consequences. An estimated 15 million people in the U.S. have AUD. Approximately 5.8 percent or 14.4 million adults in the U.S. ages 18 and older had AUD in 2018, including 9.2 million men and 5.3 million women.

Comparing two experimental models, the researchers observed anxiety-like behavior and spontaneous compulsive alcohol drinking among the alcohol dependent models when compared to control models that were not alcohol dependent. The researchers believe these observations suggest that during withdrawal the brain’s stress system gets recruited and is responsible for a negative emotional state that drives compulsive alcohol drinking through a negatively reinforced mechanism. “In other words, what we know from the literature and was confirmed by this study is that the negative reinforced mechanism consists of the insurgence of anxiety during withdrawal (which we call “dark side”) which in turn drives compulsive drinking as a form of paradoxical self-medication,” explained co-corresponding author Pietro Cottone, PhD, associate professors of pharmacology and psychiatry at BUSM.

During withdrawal the alcohol-dependent models show increased levels of the stress neuropeptide PACAP selectively in the BNST, compared to control models. This observation led the researchers to administer an experimental drug that blocks the effects of PACAP directly into the BNST of both the alcohol-dependent model and the controls. “We found that this treatment was able to completely block both the high anxiety-like behavior and the compulsive ethanol drinking of ethanol-dependent models without affecting behavior in the control models,” said co-corresponding author Valentina Sabino, PhD, associate professors of pharmacology and psychiatry at BUSM.

According to the researchers, these results provide further evidence that alcohol addiction, as many other forms of addictive disorders, is rooted in a negatively reinforced mechanism. “Compulsive alcohol drinking is mainly driven by a withdrawal-dependent negative emotional state. In this context, we found a new key player, PACAP, driving the negative reinforcing properties of alcohol and which can be targeted for the development of pharmacological therapies,” added Cottone.

References: http://dx.doi.org/10.1038/s41386-020-00904-4

Provided by Boston University School of Medicine

A New Diagnostic Method Predicts Which Cancer Patients Will Respond To Immunotherapy (Medicine)

Banafshe Larijani, the Ikerbasque professor at the Biofisika Institute, leads the international team that has developed the tool.

Immunotherapy is a type of cancer treatment that helps the patient’s immunological system to combat it and has a hugely positive impact in cancer treatments, even though it does not work in all cases: it is highly successful in some patients whereas in others it has little or no effect. Given the risks inherent in these procedures, a growing need has emerged to specify which patients are more likely to benefit from them, thus avoiding unnecessary exposure of those who will not benefit.

Dr Banafshe Larijani, an Ikerbasque researcher seconded to the Biofisika Institute (UPV/EHU-University of the Basque Country, CSIC), leads the international group that has developed the new diagnostic method. ©Ikerbasque – UPV/EHU

Fellow researchers from other centres in the Basque Country (Biocruces, PIE, BCAM), in Europe and the company FASTBASE Solutions Ltd have participated in the group led by Dr Larijani, who is also the director of the Centre for Therapeutic Innovation of the University of Bath (United Kingdom). The new predictive tool has been developed by using an advanced microscopy platform that identifies the interactions between the immune cells and the tumour cells and also informs about the activation state of the immune checkpoints that buffer the anti-tumour response.

The team has published its findings in the prestigious journal Cancer Research. Dr Larijani’s team has analysed one immune checkpoint. In a healthy individual these checkpoints closely regulate the body’s immune response, acting as a switch to prevent self-immune and inflammatory diseases.

Specifically, the immune checkpoint analysed comprises two proteins: PD-1 (present in immune cells known as T-lymphocytes) and PD-L1 (present in other types of immune cells and on the surface of many different types of tumours).

As a rule, when PD-1 on the surface of T-lymphocytes joins up with PD-L1 on the surface of other immune cells, it efficiently switches off the immune function of the T cell. And that is what tumour cells do: when PD-L1 is expressed on their surface, PD-1 is activated in the T-lymphocyte, so their anti-tumour function is deactivated and the tumour is allowed to survive and grow. The inhibitors used in immunotherapy function by interrupting the interaction between PD-L1 on the tumour and PD-1 in the T cell, thus restoring the patient’s anti-tumour activity. This new tool determines the scope of the PD-1 / PD-L1 interaction in a tumour biopsy by predicting whether therapy using checkpoint inhibitors is likely to bring significant clinical benefits.

“Right now, decisions about whether to proceed with checkpoint inhibitor treatment are simply based on whether PD-1 and PD-L1 are present in the biopsies rather than in their functional state. However, our work has shown that it is much more important to know that the two proteins actually interact and, therefore, that they are likely to have a functional impact on the survival of the tumour,” said Prof Larijani.

References: Lissete Sánchez-Magraner, James Miles, Claire L. Baker, Christopher J. Applebee, Dae-Jin Lee, Somaia Elsheikh, Shaimaa Lashin, Katriona Withers, Andrew G. Watts, Richard Parry, Christine Edmead, Jose Ignacio Lopez, Raj Mehta, Antoine Italiano, Stephen G. Ward, Peter J. Parker and Banafshé Larijani
High PD-1/PD-L1 checkpoint interaction infers tumour selection and therapeutic sensitivity to anti-PD-1/PD-L1 treatment
Cancer Research 80(19): 4244-4257. https://doi.org/10.1158/0008-5472.CAN-20-1117
DOI: 10.1158/0008-5472.CAN-20-1117

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