“We have identified a new trigger of brain inflammation in these disorders,” said Elizabeth Ochoa, PhD, study author from UT Health San Antonio. The finding published in Science Advances is novel for this reason, she said.

Ochoa, a recent doctoral graduate, and her mentor, Bess Frost, PhD, study senior author, are investigators with the Sam and Ann Barshop Institute for Longevity and Aging Studies, the Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases, and the Department of Cell Systems and Anatomy at UT Health San Antonio. Frost is the Bartell Zachry Distinguished Professor for Research in Neurodegenerative Disorders.

Alzheimer’s disease and progressive supranuclear palsy are marked by toxic deposits of a protein called tau. Their research found that tau-induced “jumping genes” — which can relocate or copy themselves to other locations in the genome — form double-stranded RNA. This abnormal RNA mimics the inflammatory trigger that is also present in viral infections.

“Transposable elements — the so-called jumping genes — are a new area of interest in understanding Alzheimer’s disease. Our study provides new insights into how they can drive the disease process in addition to their ability to jump,” Ochoa said. “These double-stranded RNAs look like a virus to the immune system even though the jumping genes are a part of our normal genome.”

The researchers detected accumulation of double-stranded RNA in postmortem brain tissue from patients with Alzheimer’s disease and progressive supranuclear palsy and in brains of mouse and fruit fly models of tauopathy.

“We found substantial deposits of double-stranded RNA in astrocytes, which are cells that provide metabolic support for neurons, regulate neurotransmitters and maintain blood-brain barrier integrity,” Frost said. “In aging and disease, astrocytes respond to injury and disruption of the neuronal environment. Our findings open new doors for understanding astrocyte biology and their role in transposable element control.”

Loss of neurons, which are cells of the central nervous system, is progressive in Alzheimer’s and other neurodegenerative diseases.

The researchers conducted experiments in fruit flies to quickly test their questions about double-stranded RNA and inflammation in the brain. “To ensure that what we found in our fruit fly experiments is relevant to mammalian disease, we also studied brain tissue from mouse models and from postmortem human brains affected by tauopathy,” Ochoa said.

“As we are currently targeting jumping gene activation in a local Phase II clinical trial for patients with Alzheimer’s disease, it’s important to understand the full repertoire of toxic molecules, including double-stranded RNAs, that jumping genes produce,” Frost said.

Ochoa recently earned her PhD from the Cell Biology, Genetics and Molecular Medicine Discipline of the Integrated Biomedical Sciences program at UT Health San Antonio. She earned her undergraduate degree from Seattle University.

Frost, associate professor of cell systems and anatomy in the Barshop and Biggs institutes at UT Health San Antonio, received the highly competitive Edith and Peter O’Donnell Award in Medicine in 2020 from TAMEST, the Texas Academy of Medicine, Engineering, Science and Technology. She was also a Gold Medalist in 2022 for the Oskar Fischer Prize.

Acknowledgments

This study was supported by the National Institute of Neurological Diseases and Stroke, the Rainwater Foundation and the National Institute of General Medical Sciences. Coauthor Kevin Bieniek, PhD, is the director of the UT Health San Antonio Glenn Biggs Institute Brain Bank, which is supported by the National Institute on Aging, the Texas Alzheimer’s Research and Care Consortium, the Bill and Rebecca Reed Precision Medicine Center and the Bartell and Mollie Zachry Endowment for Alzheimer’s Research and Patient Care.

The Mayo Clinic Brain Bank provided human brain tissue. Coauthor William Ray, PhD, of the Neurodegeneration Consortium, Therapeutics Discovery Division at The University of Texas MD Anderson Cancer Center provided mouse brain tissue for analyses.

These cells assemble and maintain their own smaller, internal bits: the membrane-bound organelles like nuclei, which store genetic information, or mitochondria, which produce chemical energy. But much remains to be learned about how they organize themselves into these spatial compartments.

Physicists at Washington University in St. Louis conducted new experiments that show that eukaryotic cells can robustly control average fluctuations in organelle size. By demonstrating that organelle sizes obey a universal scaling relationship that the scientists predict theoretically, their new framework suggests that organelles grow in random bursts from a limiting pool of building blocks.

The study was published Jan. 6 in Physical Review Letters.

“In our work, we suggest that the steps by which organelles are grown — far from being an orderly ‘brick-by-brick’ assembly — occur in stochastic bursts,” said Shankar Mukherji, assistant professor of physics in Arts & Sciences.

“Such bursts fundamentally limit the precision with which organelle size is controlled but also maintain noise in organelle size within a narrow window,” Mukherji said. “Burstlike growth provides a general biophysical mechanism by which cells can maintain, on average, reliable yet plastic organelle sizes.”

Organelles must be flexible enough to allow cells to grow or shrink them as environments demand. Still, the size of organelles must be maintained within certain limits. Biologists have previously identified certain molecular factors that regulate organelle sizes, but this study provides new insights into the quantitative principles underlying organelle size control.

While this study used budding yeast as a model organism, the team is excited to explore how these assembly mechanisms are utilized across different species and cell types. Mukherji said that they plan to examine what these patterns of robustness can teach us about how to harness organelle assembly for bioengineering applications and how to spot defects in organelle biogenesis in the context of disease.

“The pattern of organelle size robustness is shared between budding yeast and human iPS cells,” Mukherji said. “The underlying molecular mechanisms producing these bursts are yet to be fully elucidated and are likely to be organelle-specific and potentially species-specific.”

Funding: This research was supported by the National Institutes of Health (NIH R35GM142704).

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Materials provided by Washington University in St. Louis. Original written by Talia Ogliore. Note: Content may be edited for style and length.

A team of researchers, led by Young-Shin Jun, professor of energy, environmental & chemical engineering in the McKelvey School of Engineering at Washington University in St. Louis, analyzed how light breaks down polystyrene, a nonbiodegradable plastic from which packing peanuts, DVD cases and disposable utensils are made. In addition, they found that nanoplastic particles can play active roles in environmental systems. In particular, when exposed to light, the nanoplastics derived from polystyrene unexpectedly facilitated the oxidation of aqueous manganese ions and formation of manganese oxide solids that can affect the fate and transport of organic contaminants in natural and engineering water systems.

The research, published in ACS Nano Dec. 27, 2022, showed how the photochemical reaction of nanoplastics through light absorption generates peroxyl and superoxide radicals on nanoplastic surfaces, and initiates oxidation of manganese into manganese oxide solids.

“As more plastic debris accumulates in the natural environment, there are increasing concerns about its adverse effects,” said Jun, who leads the Environmental Nanochemistry Laboratory. “However, in most cases, we have been concerned about the roles of the physical presence of nanoplastics rather than their active roles as reactants. We found that such small plastic particles that can more easily interact with neighboring substances, such as heavy metals and organic contaminants, and can be more reactive than we previously thought.”

Jun and her former student, Zhenwei Gao, who earned a doctorate in environmental engineering at WashU in 2022 and is now a postdoctoral scholar at the University of Chicago, experimentally demonstrated that the different surface functional groups on polystyrene nanoplastics affected manganese oxidation rates by influencing the generation of the highly reactive radicals, peroxyl and superoxide radicals. The production of these reactive oxygen species from nanoplastics can endanger marine life and human health and potentially affects the mobility of the nanoplastics in the environment via redox reactions, which in turn might negatively impact their environmental remediation.

The team also looked at the size effects of polystyrene nanoplastics on manganese oxidation, using 30 nanometer, 100 nanometer and 500 nanometer particles. The two larger-sized nanoparticles took longer to oxidize manganese than the smaller particles. Eventually, the nanoplastics will be surrounded by newly formed manganese oxide fibers, which can make them easily aggregated and can change their reactivities and transport.

“The smaller particle size of the polystyrene nanoplastics may more easily decompose and release organic matter because of their larger surface area,” Jun said. “This dissolved organic matter may quickly produce reactive oxygen species in light and facilitate manganese oxidation.”

“This experimental work also provides useful insights into the heterogeneous nucleation and growth of manganese oxide solids on such organic substrates, which benefits our understanding of manganese oxide occurrences in the environment and engineered materials syntheses,” Jun said. “These manganese solids are excellent scavengers of redox-active species and heavy metals, further affecting geochemical element redox cycling, carbon mineralization and biological metabolisms in nature.”

Jun’s team plans to study the breakdown of diverse common plastic sources that can release nanoplastics and reactive oxidizing species and to investigate their active roles in the oxidation of transition and heavy metal ions in the future.

Funding for this research was partially provided by the National Science Foundation (CHE-1905077) and the McDonnell International Scholars Academy at Washington University in St. Louis.

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Materials provided by Washington University in St. Louis. Original written by Beth Miller. Note: Content may be edited for style and length.

While buildup of amyloid protein has been associated with Alzheimer’s-related neurodegeneration, little is known about how the protein relates to normal brain aging, said University Professor Caleb Finch, the study’s senior author and holder of the ARCO/William F. Kieschnick Chair in the Neurobiology of Aging at the USC Leonard Davis School.

To explore the levels of Aβ in human brains, the researchers analyzed tissue samples from both healthy brains and brains of patients with dementia. More severe Alzheimer’s cases were indicated by higher Braak staging scores, a measurement of how widely signs of Alzheimer’s pathology are found within the brain.

The analysis revealed that older, cognitively healthy brains showed similar amounts of dissolvable, non-fibrillar amyloid protein as brains of Alzheimer’s patients. But, as the researchers expected, the brains of Alzheimer’s patients had higher amounts of insoluble Aβ fibrils, the form of amyloid protein that aggregates to form the telltale “plaques” seen in the disease, said Max Thorwald, the study’s first author and a postdoctoral researcher at the USC Leonard Davis School.

The findings challenge the idea that simply having higher amounts of amyloid protein in general is an underlying cause of Alzheimer’s, say Finch and Thorwald. Instead, the increase in soluble Aβ may be a general aging-related change in the brain not specific to Alzheimer’s, while higher levels of fibrillary amyloid appear to be a better indicator of poorer brain health.

Rather than Alzheimer’s simply involving increased production of Aβ protein, the more important issue may be a reduced ability to effectively clear the protein and stave off the creation of plaque-contributing fibrillary amyloid, Thorwald said.

“These findings further support the use of aggregated, or fibrillary, amyloid as a biomarker for Alzheimer’s treatments,” Thorwald said. “The site in which amyloid processing occurs has less precursor and enzyme available for processing, which may suggest the removal of amyloid as a key issue during Alzheimer’s.”

Increases in amyloid levels happen during early adulthood and differ by brain region. Further studies, including those investigating drugs to possibly break down amyloid, should incorporate positron emission tomography (PET) imaging in both healthy individuals and Alzheimer’s patients of a wide range of ages to determine how and where amyloid processing and removal changes in the brain over time, he added.

“The brain’s frontal cortex has more amyloid production compared to the cerebellum during the aging process in human brains, which coincides with their Alzheimer’s-correlated pathologies in late life,” Thorwald said. “Future projects should examine amyloid over the life course in both cognitively normal and Alzheimer’s patients with both modulation of amyloid processing or removal of amyloid through monoclonal antibodies currently used in clinical trials for Alzheimer’s treatment.”

Monoclonal antibody treatment lemanecab has been observed to reduce Aβ plaques in clinical trials and recently received FDA approval for its potential to slow cognitive decline in Alzheimer’s patients, but the results warrant further careful research regarding long-term impact, Finch said.

“Lecanemab clearly works to diminish fibrillar amyloid,” he said. “However, we are concerned with major side effects, including brain swelling and bleeding, that were 100% more than in controls, with unknown delayed or latent impact.”

Learning more about how the brain processes and removes proteins such as Aβ could provide important insights into Alzheimer’s disease and its causes. Finch noted that very few cases of dementia occur with amyloid plaques, or masses of aggregated Aβ protein, as the only pathology present in affected patients’ brains. Instead, most cases present with more complicated tissue abnormalities, from buildup of additional types of protein to small bleeds in the brain: “The aging brain is a jungle.”

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Materials provided by University of Southern California. Original written by Beth Newcomb. Note: Content may be edited for style and length.

The researchers said this work can help us understand the environmental challenges experienced by our ancestors and may also help us in predicting the effects of future environmental change on human societies.

“Through our research on modern humans, we noticed that we could predict the age at which people had children from the types of DNA mutations they left to their children,” said study co-author Matthew Hahn, Distinguished Professor of biology in the College of Arts and Sciences and of computer science in the Luddy School of Informatics, Computing and Engineering at IU Bloomington. “We then applied this model to our human ancestors to determine what age our ancestors procreated.”

According to the study, published today in Science Advances and co-authored by IU post-doctoral researcher Richard Wang, the average age that humans had children throughout the past 250,000 years is 26.9. Furthermore, fathers were consistently older, at 30.7 years on average, than mothers, at 23.2 years on average, but the age gap has shrunk in the past 5,000 years, with the study’s most recent estimates of maternal age averaging 26.4 years. The shrinking gap seems to largely be due to mothers having children at older ages.

Other than the recent uptick in maternal age at childbirth, the researchers found that parental age has not increased steadily from the past and may have dipped around 10,000 years ago because of population growth coinciding with the rise of civilization.

“These mutations from the past accumulate with every generation and exist in humans today,” Wang said. “We can now identify these mutations, see how they differ between male and female parents, and how they change as a function of parental age.”

Children’s DNA inherited from their parents contains roughly 25 to 75 new mutations, which allows scientists to compare the parents and offspring, and then to classify the kind of mutation that occurred. When looking at mutations in thousands of children, IU researchers noticed a pattern: The kinds of mutations that children get depend on the ages of the mother and the father.

Previous genetic approaches to determining historical generation times relied on the compounding effects of either recombination or mutation of modern human DNA sequence divergence from ancient samples. But the results were averaged across both males and females and across the past 40,000 to 45,000 years.

Hahn, Wang and their co-authors built a model that uses de novo mutations — a genetic alteration that is present for the first time in one family member as a result of a variant or mutation in a germ cell of one of the parents or that arises in the fertilized egg during early embryogenesis — to separately estimate the male and female generation times at many different points throughout the past 250,000 years.

The researchers were not originally seeking to understand the relationship of gender and age at conception over time; they were conducting a broader investigation about the number of mutations passed from parents to children. They only noticed the age-based mutation patterns while seeking to understand differences and similarities between these pattens in humans versus other mammals, such as cats, bears and macaques.

“The story of human history is pieced together from a diverse set of sources: written records, archaeological findings, fossils, etc.,” Wang said. “Our genomes, the DNA found in every one of our cells, offer a kind of manuscript of human evolutionary history. The findings from our genetic analysis confirm some things we knew from other sources (such as the recent rise in parental age), but also offer a richer understanding of the demography of ancient humans. These findings contribute to a better understanding of our shared history.”

Additional contributors to this research were Samer I. Al-Saffar, a graduate student at IU at the time of the study, and Jeffrey Rogers of the Baylor College of Medicine.

Scientists from the University of Nottingham, China, Germany and the UK led by Professor Liu Feng from Nanjing Institute of Geology and Palaeontology have developed a new method to detect plant’s sunscreen-like compounds in fossil pollen grains. The research has been published today in Science Advances.

The end-Permian mass extinction event (250 million years ago) is the most severe of the big five mass extinction events with the loss of ~80% of marine and terrestrial species. This catastrophic loss of biodiversity was a response to a palaeoclimate emergency triggered by the emplacement of a continental-scale volcanic eruption that covers much of modern-day Siberia. The volcanic activity drove the release of massive amounts of carbon that had been locked up in Earth’s interior into the atmosphere, generating large-scale greenhouse warming. Accompanying this global warming event was a collapse in the Earth’s ozone layer. Support for this theory comes from the abundant occurrence of malformed spores and pollen grains that testify to an influx of mutagenic UV irradiation.

Professor Barry Lomax from the University of Nottingham explains “Plants require sunlight for photosynthesis but need to protect themselves and particularly their pollen against the harmful effects of UV-B radiation. To do so, plants load the outer walls of pollen grains with compounds that function like sunscreen to protect the vulnerable cells to ensure successful reproduction.”

Professor Liu Feng adds: “We have developed a method to detect these phenolic compounds in fossil pollen grains recovered from Tibet, and detected much higher concentrations in those grains that were produced during the mass extinction and peak phase of volcanic activity.”

Elevated UV-B levels can have even further-reaching and longer-lasting impacts on the entire Earth System. Recent modelling studies have demonstrated that elevated UV-B stress reduces plant biomass and terrestrial carbon storage, which would exacerbate global warming. The increased concentration of phenolic compounds also makes plant tissue less easily digestible, making a hostile environment even more challenging for herbivores.

Summarising the groups findings Dr Wes Fraser based at Oxford Brookes University commented: “Volcanism on such a cataclysmic scale impacts on all aspects of the Earth system, from direct chemical changes in the atmosphere, through changes in carbon sequestration rates, to reducing volume of nutritious food sources available for animals.”

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The Brazilian Amazon encompasses the largest tropical forest area with the highest biodiversity in the world. Since 2000, Indigenous territories and protected areas have increased substantially in the region and by 2013, Indigenous territories and protected areas accounted for 43% of the total land area and covered approximately 50% of the total forest area.

However, tensions between forest conservation and socioeconomic development goals persist. In recent years, forest conservation has been threatened by large socio-ecological changes in Brazil. Weakened forest and environmental policies and enforcement as well as impacts from the COVID-19 pandemic had devastating impacts on Indigenous groups in the region.

In this U.S.-Brazil collaborative study, Yuanwei Qin, Ph.D., and Xiangming Xiao, Ph.D., of OU’s Center for Earth Observation and Modeling, with Fabio de Sa e Silva, Ph.D., assistant professor of international studies and Wick Cary Professor of Brazilian Studies in the OU College of International Studies, worked with collaborators from the Brazilian National Institute for Space Research and the National Institute for Research in Amazonia in Brazil. The research team combined multiple data sources to document and quantify the dynamics and impact of forest loss in the Brazilian Amazon over the past two decades.

Because of frequent cloud cover and fire-induced smoke in the Brazilian Amazon, annual forest maps from analyses of optical images have only moderate accuracy. In a 2019 paper published by the same journal, the research team combined image data from both optical and microwave sensors to generate annual Brazilian Amazon forest maps. Using these annual forest maps, they assessed the effects of Indigenous territories and protected areas on deforestation dynamics in the Brazilian Amazon through 2021.

“Between 2000 and 2021, the areas designated as Indigenous territories or protected areas increased to cover approximately 52% of forests in the Brazilian Amazon, accounting for only 5% of net forest loss and 12% of gross forest loss in the period,” said Qin. “This finding highlights the vital role of Indigenous territories and the protected areas for forest conservation in the region.”

The protected areas in the Brazilian Amazon are subject to different state and national governance arrangements and have different management objectives, including strict protection or sustainable use. They found that from 2003 through 2021, gross forest loss fell 48% in the protected areas subject to strict protection and 11% in the protected areas subject to sustainable use.

“These varying effects on forest conservation call for more in-depth causal analyses by researchers and invite stakeholders, decision-makers, and the public to reassess existing policies for these areas. Legal designations are important, but if the law is not enforced, the intended protection of forests and biodiversity will be illusional. This is an area in which Brazil is knowingly failing,” de Sa e Silva said.

The results from this study also show that annual forest area loss was affected by Brazilian forest policies, as evidenced by a large reduction of forest area loss in the early 2000s to mid-2010s, corresponding with Brazilian President Luiz Inácio Lula da Silva administration in 2003-2010, and renewed rise of forest area loss even among Indigenous territories and the protected areas in 2019-2021, corresponding with President Jair Bolsonaro’s administration in 2019-2022.

“How to rebuild effective policies and reduce forest area loss in the Brazilian Amazon in the coming years will be one of the grand challenges for Lula’s administration and international communities,” Xiao said.

This study adds to a portfolio of research efforts to document forest areas in the Brazilian Amazon by Qin and Xiao, including a 2019 paper, “Improved estimates of forest cover and loss in the Brazilian Amazon in 2000-2017,” published in Nature Sustainability; a 2021 paper, “Carbon loss from forest degradation exceeds that from deforestation in the Brazilian Amazon,” published in Nature Climate Change; as well as two others. 

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Materials provided by University of Oklahoma. Original written by Chelsea Julian. Note: Content may be edited for style and length.