Current approaches to autism research involve observing and understanding the disorder through the study of its behavioral consequences, using techniques like functional magnetic resonance imaging that map the brain’s responses to input and activity, but little work has been done to understand what’s causing those responses.

However, researchers with UVA’s College and Graduate School of Arts & Sciences have been able to better understand the physiological differences between the brain structures of autistic and non-autistic individuals through the use of Diffusion MRI, a technique that measures molecular diffusion in biological tissue, to observe how water moves throughout the brain and interacts with cellular membranes. The approach has helped the UVA team develop mathematical models of brain microstructures that have helped identify structural differences in the brains of those with autism and those without.

“It hasn’t been well understood what those differences might be,” said Benjamin Newman, a postdoctoral researcher with UVA’s Department of Psychology, recent graduate of UVA School of Medicine’s neuroscience graduate program and lead author of a paper published this month in PLOS: One. “This new approach looks at the neuronal differences contributing to the etiology of autism spectrum disorder.”

Building on the work of Alan Hodgkin and Andrew Huxley, who won the 1963 Nobel Prize in Medicine for describing the electrochemical conductivity characteristics of neurons, Newman and his co-authors applied those concepts to understand how that conductivity differs in those with autism and those without, using the latest neuroimaging data and computational methodologies. The result is a first-of-its-kind approach to calculating the conductivity of neural axons and their capacity to carry information through the brain. The study also offers evidence that those microstructural differences are directly related to participants’ scores on the Social Communication Questionnaire, a common clinical tool for diagnosing autism.

“What we’re seeing is that there’s a difference in the diameter of the microstructural components in the brains of autistic people that can cause them to conduct electricity slower,” Newman said. “It’s the structure that constrains how the function of the brain works.”

One of Newman’s co-authors, John Darrell Van Horn, a professor of psychology and data science at UVA, said, that so often we try to understand autism through a collection of behavioral patterns which might be unusual or seem different.

“But understanding those behaviors can be a bit subjective, depending on who’s doing the observing,” Van Horn said. “We need greater fidelity in terms of the physiological metrics that we have so that we can better understand where those behaviors coming from. This is the first time this kind of metric has been applied in a clinical population, and it sheds some interesting light on the origins of ASD.”

Van Horn said there’s been a lot of work done with functional magnetic resonance imaging, looking at blood oxygen related signal changes in autistic individuals, but this research, he said “Goes a little bit deeper.”

“It’s asking not if there’s a particular cognitive functional activation difference; it’s asking how the brain actually conducts information around itself through these dynamic networks,” Van Horn said. “And I think that we’ve been successful showing that there’s something that’s uniquely different about autistic-spectrum-disorder-diagnosed individuals relative to otherwise typically developing control subjects.”

Newman and Van Horn, along with co-authors Jason Druzgal and Kevin Pelphrey from the UVA School of Medicine, are affiliated with the National Institute of Health’s Autism Center of Excellence (ACE), an initiative that supports large-scale multidisciplinary and multi-institutional studies on ASD with the aim of determining the disorder’s causes and potential treatments.

According to Pelphrey, a neuroscientist and expert on brain development and the study’s principal investigator, the overarching aim of the ACE project is to lead the way in developing a precision medicine approach to autism.

“This study provides the foundation for a biological target to measure treatment response and allows us to identify avenues for future treatments to be developed,” he said.

Van Horn added that study may also have implications for the examination, diagnosis, and treatment of other neurological disorders like Parkinson’s and Alzheimer’s.

“This is a new tool for measuring the properties of neurons which we are particularly excited about. We are still exploring what we might be able to detect with it,” Van Horn said.

Perez’s research team included two graduate students from UF, Arup Mondal and Bhumika Singh, and a handful of researchers from Rutgers University and Rensselaer Polytechnic Institute. The team published their findings in Angewandte Chemie, a leading chemistry journal based in Germany.

Named the AF-CBA Pipeline, this innovative tool offers unparalleled accuracy and speed in pinpointing the strongest peptide binders to a specific protein. It does this by using AI to simulate molecular interactions, sorting through thousands of candidate molecules to identify the molecule that interacts best with the protein of interest.

The AI-driven approach allows the pipeline to perform these actions in a fraction of the time it would take humans or traditional physics based-approaches to accomplish the same task.

“Think of it like a grocery store,” Perez explained. “When you want to buy the best possible fruit, you have to compare sizes and aspects. There are too many fruits to try them all of course, so you compare a few before making a selection. This AI method, however, can not only try them all, but can also reliably pick out the best one.”

Typically, the proteins of interest are the ones that cause the most damage to our bodies when they misbehave. By finding what molecules interact with these problematic proteins, the pipeline opens avenues for targeted therapies to combat ailments such as inflammation, immune dysregulation, and cancer.

“Knowing the structure of the strongest peptide binder in turn helps us in the rational designing of new drug therapeutics,” Perez said.

The groundbreaking nature of the pipeline is enhanced by its foundation on pre-existing technology: a program called AlphaFold. Developed by Google Deepmind, AlphaFold uses deep learning to predict protein structures. This reliance on familiar technology will be a boon for the pipeline’s accessibility to researchers and will help ensure its future adoption.

Moving forward, Perez and his team aim to expand their pipeline to gain further biological insights and inhibit disease agents. They have two viruses in their sights: murine leukemia virus and Kaposi’s sarcoma virus. Both viruses can cause serious health issues, especially tumors, and interact with as-of-now unknown proteins.

“We want to design novel libraries of peptides,” Perez said. “AF-CBA will allow us to identify those designed peptides that bind stronger than the viral peptides.”

In a new study, scientists at the Salk Institute help explain how CBN protects the brain against aging and neurodegeneration, then use their findings to develop potential therapeutics. The researchers created four CBN-inspired compounds that were more neuroprotective than the standard CBN molecule — one of which was highly effective in treating traumatic brain injury in a Drosophila fruit fly model.

The findings, published in Redox Biologyon March 29, 2024, suggest promise for CBN in treating neurological disorders like traumatic brain injury, Alzheimer’s disease, and Parkinson’s disease, and also highlight how further studies of CBN’s effects on the brain could inspire the development of new therapies for clinical use.

“Not only does CBN have neuroprotective properties, but its derivatives have the potential to become novel therapeutics for various neurological disorders,” says Research Professor Pamela Maher, senior author of the study. “We were able to pinpoint the active groups in CBN that are doing that neuroprotection, then improve them to create derivative compounds that have greater neuroprotective ability and drug-like efficacy.”

Many neurological disorders involve the death of brain cells called neurons, due to the dysfunction of their power-generating mitochondria. CBN achieves its neuroprotective effect by preventing this mitochondrial dysfunction — but how exactly CBN does this, and whether scientists can improve CBN’s neuroprotective abilities, has remained unclear.

The Salk team previously found that CBN was modulating multiple features of mitochondrial function to protect neurons against a form of cell death called oxytosis/ferroptosis. After uncovering this mechanism of CBN’s neuroprotective activity, they began applying both academic and industrial drug discovery methods to further characterize and attempt to improve that activity.

First, they broke CBN into small fragments and observed which of those fragments were the most effective neuroprotectors by chemically analyzing the fragment’s properties. Second, they designed and constructed four novel CBN analogs — chemical look-alikes — in which those fragments were amplified, then moved them on to drug screening.

“We were looking for CBN analogs that could get into the brain more efficiently, act more quickly, and produce a stronger neuroprotective effect than CBN itself,” says Zhibin Liang, first author and postdoctoral researcher in Maher’s lab. “The four CBN analogs we landed on had improved medicinal chemical properties, which was exciting and really important to our goal of using them as therapeutics.”

To test the chemical medicinal properties of the four CBN analogs, the team applied them to mouse and human nerve cell cultures. When they initiated oxytosis/ferroptosis in three different ways, they found that each of the four analogs 1) were able to protect the cells from dying, and 2) had similar neuroprotective abilities compared to regular CBN.

The successful analogs were then put to the test in a Drosophila fruit fly model of traumatic brain injury. One of the analogs, CP1, was especially effective in treating traumatic brain injury — producing the highest survival rate after condition onset.

“Our findings help demonstrate the therapeutic potential of CBN, as well as the scientific opportunity we have to replicate and refine its drug-like properties,” says Maher. “Could we one day give this CBN analog to football players the day before a big game, or to car accident survivors as they arrive in the hospital? We’re excited to see how effective these compounds might be in protecting the brain from further damage.”

In the future, the researchers will continue to screen and characterize these CBN analogs and refine their chemical designs. They will also begin looking more closely at age-related neurodegeneration and changes in brain cells, particularly in mitochondria, asking how we can better suit these drug-like compounds to promote cellular health and prevent neuronal dysfunction with age.

Other authors include David Soriano-Castell and Wolfgang Fischer of Salk; and Alec Candib and Kim Finley of the Shiley Bioscience Center at San Diego State University.

The work was supported by the Paul F. Glenn Center for Biology of Aging Research at the Salk Institute, the Bundy Foundation, the Shiley Foundation, the National Institutes of Health (R01AG067331, R21AG064287, R01AG069206, RF1AG061296, R21AG067334, NCI CCSG P30CA01495, NlA P30AG068635, S10OD021815), and the Helmsley Center for Genomic Medicine.

Despite the challenges posed by limited preservation of archaeological assemblages and organic remains in arid environments, these discoveries are reshaping our understanding of the region’s rich cultural heritage.

One such breakthrough led by Griffith University’s Australian Research Centre for Human Evolution (ARCHE), in collaboration with international partners, comes from the exploration of underground settings, including caves and lava tubes, which have remained largely untapped reservoirs of archaeological abundance in Arabia.

Through meticulous excavation and analysis, researchers have uncovered a wealth of evidence at Umm Jirsan, spanning from the Neolithic to the Chalcolithic/Bronze Age periods (~10,000-3,500 years ago).

“Our findings at Umm Jirsan provide a rare glimpse into the lives of ancient peoples in Arabia, revealing repeated phases of human occupation and shedding light on the pastoralist activities that once thrived in this landscape,” said Dr Mathew Stewart, the lead researcher and a Research Fellow at ARCHE.

“This site likely served as a crucial waypoint along pastoral routes, linking key oases and facilitating cultural exchange and trade.”

Rock art and faunal records attest to the pastoralist use of the lava tube and surrounding areas, painting a vivid picture of ancient lifeways.

Depictions of cattle, sheep, goat and dogs corroborate the prehistoric livestock practices and herd composition of the region.

Isotopic analysis of animal remains indicates that livestock primarily grazed on wild grasses and shrubs, while humans maintained a diet rich in protein, with a notable increase in the consumption of C3 plants over time, suggesting the emergence of oasis agriculture.

“While underground localities are globally significant in archaeology and Quaternary science, our research represents the first comprehensive study of its kind in Saudi Arabia,” added Professor Michael Petraglia, Director of ARCHE.

“These findings underscore the immense potential for interdisciplinary investigations in caves and lava tubes, offering a unique window into Arabia’s ancient past.”

The research at Umm Jirsan underscores the importance of collaborative, multidisciplinary approaches to archaeological inquiry and highlights the significance of Arabia’s archaeological heritage on the global stage.

Researchers involved in this study work in close partnership with the Heritage Commission, Saudi Ministry of Culture, and the Saudi Geological Survey. Additional partners include King Saud University and key institutions in the UK, the USA, and Germany.

The emergence of pandemic epidemics like COVID-19 has emphasized the necessity for rapid and precise analytical methods to prepare for potential future virus outbreaks. Raman spectroscopy, using gold nanostructures, offers information about the internal structure and chemical properties of materials by analyzing the distinct vibrations of molecules known as “molecular fingerprints,” using light with remarkable sensitivity. Therefore, it could play a crucial role in determining the positivity of a virus.

However, conventional high-sensitivity Raman spectroscopy sensors detect only one type of virus with a single device, thus posing limitations in terms of productivity, detection speed, and cost when considering clinical applications.

The research team successfully fabricated a one-dimensional structure at the millimeter scale, featuring gold nanogaps accommodating only a single molecule with a tight fit. This advancement enables large-area, high-sensitivity Raman spectroscopic sensing. Furthermore, they effectively integrated flexible materials onto the substrate of the gold nanogap spectroscopic sensor. Finally, the team developed a source technology for a broadband active nano-spectral sensor, allowing tailored detection of specific substances using a single device, by widening the nanogap to the size of a virus and freely adjusting its width to suit the size and type of materials, including viruses.

Furthermore, they improved the sensitivity and controllability of the sensor by combining adaptive optics technology used in fields such as space optics, such as the James Webb Telescope. Additionally, they established a conceptual model for extending the fabricated one-dimensional structure into a two-dimensional spectroscopic sensor, theoretically confirming the ability to amplify Raman spectroscopic signals by up to several billion times. In other words, it becomes possible to confirm the positivity of viruses in real-time within seconds, a process that previously took days for verification.

The achievements of the research team, currently pending patent approval, are expected to be utilized for the rapid response through high-sensitivity real-time testing in the event of unexpected infectious diseases such as COVID-19, to prevent indiscriminate spread. Taeyoung Moon, lead author of the paper, emphasized the significance of their achievement by stating, “This not only advances basic scientific research in identifying unique properties of materials from molecules to viruses but also facilitates practical applications, enabling rapid detection of a broad spectrum of emerging viruses using a single, tailored sensor.”

The collaborative research was jointly conducted with Professor Dai-Sik Kim’s team from UNIST’s Department of Physics and a team led by Professor Yung Doug Suh from UNIST’s Department of Chemistry who is Deputy Director of Center for Multidimensional Carbon Materials at the Institute for Basic Science (IBS). Additionally, Yeonjeong Koo, Mingu Kang, and Hyeongwoo Lee from POSTECH’s Department of Physics carried out measurements. The research findings have recently been published in the international journal Nano Letters.

Aiming to shorten recovery times, an Osaka Metropolitan University-led research group is focusing on plasma irradiation as a treatment method to speed up bone healing.

The Department of Orthopedic Surgery’s Kosuke Saito, a graduate student in the Graduate School of Medicine, Associate Professor Hiromitsu Toyoda, and Professor Hiroaki Nakamura, and Graduate School of Engineering Professor Jun-Seok Oh were among the researchers who used laboratory rats for their experiment.

The researchers broke the legs of the rats in two ways. One group of 24 rats had normal fractures that are generally easy to heal. The other group of 20 rats had fractures known as non-union ones where healing is usually prolonged or does not happen. Some were then irradiated with non-thermal atmospheric-pressure plasma, which didn’t offer the normal fracture group any significant advantages but boosted the healing and recovery time of the rats with non-union fractures. The strength of the healed areas of the irradiated non-union rats was also about 3.5 times stronger than that of the nonirradiated ones.

Furthermore, in vitro study of pre-osteoblastic cells irradiated with the plasma for 5 to 15 seconds showed that the activity of a protein that is an indicator of osteoblast differentiation increased, indicating that maturation of these bone-forming cells was progressing.

“Collaboration between the medical and engineering fields creates new medical technologies that have never before existed,” Professor Toyoda declared. “In the future, combining this treatment method with current fracture treatments is expected to contribute to more reliable bone fusion and shorter recovery times.”

Their findings are set for publication inPLOS ONEon April 16, 2024.

The research team, led by scientists at the U.S. National Science Foundation National Center for Atmospheric Research (NSF NCAR), used satellite observations and machine learning techniques to produce a unique database of WUI areas and fires worldwide, dating back about two decades.

The overall number of all fires worldwide has declined, as has the total area burned.

However, the scientists found that the fraction of global fires that occur in WUI areas increased by about 23% from 2005 to 2020. Even more significantly, the global area burned by WUI fires during the same time increased by about 35% as a fraction of all burned areas.

The research found that WUI areas are expanding worldwide, especially in rapidly urbanizing regions in Africa. As newly constructed developments move into areas of wild vegetation, the risk of fires increases. The paper did not focus on the role of climate change, although the authors said the database can help scientists better fingerprint the role of climate change in fires.

WUI areas are generally defined as the location where urban land use and wildland vegetation come into contact or intermingle. Fires in such areas are especially dangerous, both because they imperil large numbers of people and structures and because, by burning manufactured materials instead of vegetation, they emit far more toxins than forest and grassland fires.

“Wildland-urban interface fires are a major concern for many people in the United States and globally, and through this study we now know they have increased in recent years and will likely continue doing so in the future,” said NSF NCAR scientist Wenfu Tang, the lead author of the new paper. “This is important as a first step to looking at emissions from these fires and their impacts on human health.”

Funding for the research came from NOAA. The study was published in Environmental Research Letters.

Constructing a global database

WUI fires have caused catastrophic destruction in recent years, sometimes burning down thousands of buildings and killing 100 or more people. Especially destructive fires include the 2009 Black Saturday bushfires in Australia, which left 173 dead, and the 2017 Pedrosa Grande Fire in Portugal, which killed 66 people. Last year’s Lahaina Fire in Hawaii was the deadliest in the United States in more than a century, killing 100 people and destroying more than 2,200 structures.

To understand more about trends in WUI fires, Tang and her colleagues turned to a global high-resolution map of WUI fires in 2020, which had been created by Franz Schug of the University of Wisconsin-Madison. They also analyzed data about Earth’s surface from NASA’s Moderate Resolution Imaging Spectroradiometer (MODIS) satellite instrument.

By applying machine learning techniques to the map and satellite data, they quantified the relationship of fires with such variables as land cover and population density. They then used those quantitative relationships to generate a global database of WUI areas and WUI fires, going back 20 years at a resolution of 9 kilometers (5.6 miles).

The researchers successfully confirmed the accuracy of the database by comparing it with independent WUI datasets previously developed for a few years within the same time period, including for the continental United States and globally.

In analyzing the new database, the researchers found that WUI areas have grown in all populated continents by 24% from 2001 to 2020, with the largest increase occurring in Africa.

Largely as a result, fires in WUI areas have also become more common. Since 2005, they have increased from 3.5% to 4.3% of all fires. In North America, the WUI fraction of all fire counts is even higher (up to 9%), with WUI fires in 2015-2020 becoming particularly large and more destructive.

“This is the first map of its kind that enables us to look at how WUI fires have been evolving globally over the past two decades,” said NSF NCAR scientist Cenlin He, a co-author of the study. “It shows that WUI fires have increased on every populated continent.”

Even as WUI blazes loom as a greater threat, the scientists noted that fires overall have been on the decline. Since 2005, the total number of fires worldwide decreased by 10%, and the amount of burned areas decreased by 22%, according to satellite observations analyzed in their research.

Tang and her colleagues then turned to the future. They integrated the WUI database with the NSF NCAR-based Community Earth System Model, which simulates global climate and fires, to determine the likely trends in WUI fires through 2030 and 2040.

If WUI areas continue to expand and greenhouse gases continue to be emitted at a high rate, they found that the WUI fraction of burned areas worldwide will likely increase by about 2.6-3.2% by 2040. However, the picture can change somewhat depending on changes in WUI areas and greenhouse gas emissions under different future scenarios, according to their analysis.

“This study is an important step in quantifying WUI fires and how they are changing worldwide,” Tang said. “As WUI areas rapidly expand and WUI fires become more frequent, it is critical to understand the interactions between WUI fires and human activities as well as the impacts of the fires on air quality, human health, and the environment.”