Newswise A $53.6 million grant from the National Institutes of Health will aid brain scientists, including a researcher from The University of Texas Health Science Center at Houston (UTHealth), in studying the role of incidental white matter lesions, or WMLs, in dementia among diverse people with cognitive complaints.

The study is led by UC Davis School of Medicine in partnership with UTHealth. It is a new and critical part of the NIHsVascular Contributions to Cognitive Impairment and Dementia(VCID) research program.

Co-principal investigator isMyriam Fornage, PhD, professor of genetics at theBrown Foundation Institute of Molecular Medicine for the Prevention of Human Diseasesat McGovern Medical School at UTHealth. Fornage is a leading researcher on the molecular genetics of cerebrovascular disease.

Our team has been at the forefront of genetic studies of WMLs for two decades, Fornage said. Through the genetic risk profiles we will develop, we will have an opportunity to apply what we have discovered and improve the precision with which we identify patients with a higher prior probability of cognitive impairment and dementia. At the same time, we will be contributing new resources for dementia research everywhere.

The principal investigator isCharles DeCarli, MD, professor of neurology, director of theUC Davis Alzheimers Disease Centerand the nations foremost expert on the role of subcortical cerebrovascular disease in cognitive decline. In the last few years, DeCarli has been awarded national and state research grants exceeding $33 million.

The magnitude of this NIH grant underscores UC Davis Alzheimers Disease Centers national prominence and research leadership, said UC Davis School of Medicine Dean Allison Brashear,MD, a neurologist nationally known for her groundbreaking research in movement disorders. This multiyear research award will enable us to make game-changing advancements in our understanding and treatment of dementia.

WMLs occur when tissue deep in the brain becomes injured, often due to changes in small blood vessels. They are common and often found on brain MRIs of people who have concerns about their brain health.

Why or how WMLs are associated with cognitive decline is not known. Questions surround whether certain WML characteristics, such as size and location, make them greater risk factors for dementia. It also isnt clear how comorbidities additional health conditions such as heart disease or diabetes together with WMLs increase risk for cognitive decline. Defining these connections is essential to improving outcomes for the 5.7 million people in the U.S. affected by cognitive impairment and dementia.

DeCarli and Fornages landmark research is expected to answer these questions and lead to standards for assessing, diagnosing, and treating individuals with WML-related cognitive problems.

This grant gives us the chance to study WMLs from every angle and definitively understand their roles in age- and disease-related cognitive decline and risk for future dementia, DeCarli said. Its the culmination of our three decades of research that has given us great directions, but no final answers yet.

DeCarli and Fornage will conduct a study of patients with WMLs on their MRIs and concerns about cognitive symptoms, but no dementia diagnosis. It will be the first large study of a diverse population on the long-term effects of these lesions on thinking and dementia risk.

Beginning September 2021, study participants will be recruited at UC Davis Health and at least 10 other locations throughout the U.S. They will be from a variety of backgrounds, so the researchers can identify how WML outcomes differ by race, ethnicity, and sex, better representing those at risk for dementia.

Our ultimate goals are to develop a risk profile that identifies the likelihood of WML-related cognitive impairment and dementia over the course of five to 10 years and to identify clear targets for interventional trials, DeCarli said.

Resources to advance all dementia research

Another exciting part of the grant, according to the researchers, is the chance to fund additional studies aimed at refining diagnostic and predictive tools and methods for dementia. The outcomes will enhance dementia research and clinical care worldwide.

Data and samples from these studies will be shared with the wider research community via theNational Alzheimers Coordinating Center at the University of Washingtonand theNational Centralized Repository for Alzheimers Disease and Related Dementias at Indiana University. Images will be shared through theLaboratory of Neuro Imaging at the University of Southern California.

DeCarli and Fornage also participate in theMarkVCID Consortium, supported by the NIHsNational Institute of Neurological Disorders and Stroke. The consortium was established in 2016 to identify biological markers of vascular cognitive impairment and dementia.

This award is co-sponsored by the NIHs National Institute of Neurological Disorders and Stroke andNational Institute on Agingthrough grant 1U19NS120384.

The Brown Foundation Institute of Molecular Medicine (IMM) for the Prevention of Human Diseases is part of McGovern Medical School at The University of Texas Health Science Center at Houston (UTHealth). The IMM is focused on studying and preventing diseases at the genetic, cellular, and molecular levels using DNA and protein technologies and animal models. The IMM is part of the Texas Therapeutics Institute, a multi-institutional collaboration encouraging drug discovery. For more information, visitwww.uth.edu/imm/mission.htm.

The UC Davis Alzheimers Disease Research Center is one of only31 research centers designated and funded by the NIHs National Institute on Aging. The center's goal is to translate research advances into improved diagnosis and treatment for patients while focusing on the long-term goal of finding a way to prevent or cure Alzheimers disease and other dementias. The center also allows researchers to study the effects of the disease on a uniquely diverse population. For more information, visithealth.ucdavis.edu/alzheimers.

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Researchers receive more than $53 million to study role of white matter lesions in dementia - Newswise

Ohio State students with disabilities are adjusting to new accommodations for virtual learning. Credit: Mackenzie Shanklin | Assistant Photo Editor

Online classes are decreasing commute times, allowing students to rewatch live lectures and keeping the university community safe from COVID-19; however, for students with disabilities, the technological interface and isolation pose difficulties they dont face in a typical semester.

As a majority of Ohio State courses have moved to distance learning, Scott Lissner, the universitys Americans with Disabilities Act coordinator, said his office is working to provide students with disabilities a comprehensive education while also keeping them safe during the pandemic. For some of those accommodations, online learning is making the process easier.

If everybody is [taking classes] online, it removes a lot of challenges and simplifies things. We know how to integrate captioning in Zoom. We know how to integrate ASL interpreting into Zoom, Lissner said.

CarmenZoom offers captioning of class and lecture recordings, but did not offer live, automated captioning until recently.

Amy Shuman, a professor in the Department of English and former director of disability studies in the department, said although she records all her classes and uploads the videos with transcripts to make them more accessible, she hasnt seen a widespread shift toward the practice.

Ive talked to some of the older faculty who have hearing aids, and theyre frustrated by the lack of the closed captioning, Shuman said.

Lissner said in an email that Zoom tested live, automated captioning over the summer and Ohio State evaluated the system before releasing it Friday. A Friday press release from Ohio States IT department stated that live captioning is a setting Zoom meeting hosts must manually enable for their classes.

Lindsay Rogers, a first-year in molecular genetics who is hearing impaired, said online classes are easier for her than in-person classes because professors can talk directly into her hearing implants via Bluetooth, but shes had difficulty getting accommodations she typically gets each semester.

I requested [note taking assistance] for this semester, and no one contacted me about getting any sort of note taking assistance, Rogers said.

Lissner said students who do not have proper technology for their classes such as small monitors or devices that cannot connect to hearing aids via Bluetooth are sometimes able to borrow devices from the university. The university has screen-reader compatible monitors, for example, and high-quality speakers that can play sound at higher volumes.

Lissner said these loans are offered on a case-by-case basis depending on students specific disabilities. Students with disabilities are encouraged to participate in live class sessions and are provided with the materials necessary to successfully take part, he said.

We work with faculty and students to make sure accessible versions of whatever is being presented on the shared screen are distributed to students who need them prior to class. So they can either open it up in another window or have a dual monitor setup, Lissner said.

Hybrid courses and discussion-based courses can be difficult to replicate for students who require accommodations, but the ADA office tries to make students feel included while working virtually, Lissner said.

For example, if a student needs ADA accommodations in a hybrid class and is unable to attend in-person sessions, monitors can be set up in a circle around the student, with a wide angle camera used in the physical classroom. This creates an environment closer to that of an in-person class.

Isaac Meisner, a second-year in environmental policy and decision making, said having mostly online courses presents challenges with their mental illnesses.

When youre having classes that are completely online, it makes my mental disorders more difficult to handle just because I need that interaction with other people, and Im not really getting it outside of where I live, Meisner said.

Kayden Gill, a third-year in health sciences and co-president of Buckeyes for Accessibility, said as a wheelchair user and someone with a visual impairment, online courses present both positives and negatives. One of the main cons, Gill said, is it is harder to find ways to exercise without traveling across campus.

From a visual disability standpoint, its a lot easier not to have to worry about finding the place in the lecture hall that you can see, or just always having something as large as your screen can make it is nice, Gill said.

Students can register for accommodations on the Student Life Disability Services website.

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Students with disabilities, university accommodations adapt to virtual learning - OSU - The Lantern

It was Saturday, February 22, 1997, and Scottish researchers Ian Wilmut and Keith Campbell were expecting a final moment of calm before the results of their unprecedented scientific experiment were announced to the world.

The team had kept the breakthrough under wraps for seven months while they waited for their paper to be published in the prestigious journal Nature. Confidential press releases had gone out to journalists with the strict instruction not to leak the news before February 27.

But that night, the team was tipped off that journalist Robin McKie was going to break the story the very next day in the British newspaper The Observer.

Wilmut and Campbell raced to the lab at the Roslin Institute on Sunday morning as McKie's story hit the media like a thunderbolt. International news outlets had already started swarming at the institute for access to Wilmut and Campbell's creation: Dolly the sheep, the world's first mammal successfully cloned from a single adult cell. Shielded from the general public, she stuck her nose through the fence and munched calmly on the hay in her pen, unperturbed by the horde of news photographers. Dolly, a woolly, bleating scientific miracle, looked much like other sheep, but with a remarkable genetic difference.

By the end of that Sunday, February 23, nearly every major newspaper in the world carried headlines about Dolly the sheep.

Born on July 5, 1996, Dolly was cloned by Wilmut and Campbell's team at the Roslin Institute, a part of the University of Edinburgh, and Scottish biotechnology company PPL Therapeutics. The scientists cloned Dolly by inserting DNA from a single sheep mammary gland cell into an egg of another sheep, and then implanting it into a surrogate mother sheep. Dolly thus had three mothersone that provided the DNA from the cell, the second that provided the egg, and the third that carried the cloned embryo to term. Technically, though, Dolly was an exact genetic replica of only the sheep from which the cell was taken.

Following the announcement, the Roslin Institute received 3000 phone calls from around the world. Dolly's birth was heralded as one of the most important scientific advances of the decade.

But Dolly wasn't science's first attempt at cloning. Researchers had been exploring the intricacies of cloning for almost a century. In 1902, German embryologists Hans Spemann and Hilda Mangold, his student, successfully grew two salamanders from a single embryo split with a noose made up of a strand of hair. Since then, cloning experiments continued to become more sophisticated and nuanced. Several laboratory animal clones, including frogs and cows, were created before Dolly. But all of them had been cloned from embryos. Dolly was the first mammal to be cloned from a specialized adult cell.

Embryonic stem cells, which form right after fertilization, can turn into any kind of cell in the body. After they modify into specific types of cells, like neurons or blood cells, they're call specialized cells. Since the cell that gave rise to Dolly was already specialized for its role as a mammary gland cell, most scientists thought it would be impossible to clone anything from it but other mammary gland cells. Dolly proved them wrong.

Many scientists in the '90s were flabbergasted. Dollys advent showed that specialized cells could be used to create an exact replica of the animal they came from. It means all science fiction is true, biology professor Lee Silver of Princeton University told The New York Times in 1997.

The Washington Post reported that "Dolly, depending on which commentator you read, is the biggest story of the year, the decade, even the century. Wilmut has seen himself compared with Galileo, with Copernicus, with Einstein, and at least once with Dr. Frankenstein."

Scientists, lawmakers, and the public quickly imagined a future shaped by unethical human cloning. President Bill Clinton called for review of the bioethics of cloning and proposed legislation that would ban cloning meant ''for the purposes of creating a child (it didn't pass). The World Health Organization concluded that human cloning was "ethically unacceptable and contrary to human integrity and morality" [PDF]. A Vatican newspaper editorial urged governments to bar human cloning, saying every human has "the right to be born in a human way and not in a laboratory."

Meanwhile, some scientists remained unconvinced about the authenticity of Wilmut and Campbells experiment. Norton Zinder, a molecular genetics professor at Rockefeller University, called the study published in Nature "a bad paper" because Dolly's genetic ancestry was not conclusive without testing her mitochondriaDNA that is passed down through mothers. That would have confirmed whether Dolly was the daughter of the sheep that gave birth to her. In The New York Times, Zinder called the Scottish pair's work ''just lousy science, incomplete science." But NIH director Harold Varmus toldthe Times that he had no doubt that Dolly was a clone of an adult sheep.

Because she was cloned from a mammary gland cell, Dolly was nameddad joke alertafter buxom country music superstar Dolly Parton. (Parton didnt mind the attribution.) Like her namesake, Dolly the sheep was a bona fide celebrity: She posed for magazines, including People; became the subject of books, journal articles, and editorials; had an opera written about her; starred in commercials; and served as a metaphor in an electoral campaign.

And that wasn't all: New York Times reporter Gina Kolata, one of the first journalists to give readers an in-depth look at Dolly, wroteClone: The Road to Dolly, and the Path Ahead and contrasted the animal's creation with the archetypes in Frankenstein and The Island of Dr. Moreau. American composer Steve Reich was so affected by Dolly's story that he featured it in Three Tales, a video-opera exploring the dangers of technology.

The sheep also became an inadvertent political player when the Scottish National Party used her image on posters to suggest that candidates of other parties were all clones of one another. Appliance manufacturer Zanussi used her likeness for a poster with her name and the provocative caption "The Misappliance of Science" (the poster was later withdrawn after scientists complained). In fact, so widespread was the (mis)use of her name that her makers eventually trademarked it to stop the practice.

Following Dolly, many larger mammals were cloned, including horses and bulls. Roslin Biomed, set up by the Roslin Institute to focus on cloning technology, was later sold to the U.S.-based Geron Corporation, which combined cloning technology with stem cell research. But despite her popularityand widespread fearDolly's birth didn't lead to an explosion in cloning: Human cloning was deemed too dangerous and unethical, while animal cloning was only minimally useful for agricultural purposes. The sheep'sreal legacy is considered to be the advancement in stem cell research.

Dollys existence showed it was possible to change one cells gene expression by swapping its nucleus for another. Stem cell biologist Shinya Yamanaka told Scientific American that Dollys cloning motivated him to successfully develop stem cells from adult cells. He later won a Nobel Prize for his results, called induced pluripotent stem cells (iPS) because they're artificially created and can have a variety of uses. They reduced the need for embryonic stem cells in research, and today, iPS cells form the basis for most stem cell research and therapies, including regenerative medicine.

Dolly had sixoffspring, and led a productive, sociable life with many human fans coming to visit her. In 2003, a veterinary examination showed that Dolly had a progressive lung disease, and she was put down. But four clonescreated from the same cell line in 2007 faced no such health issues and aged normally.

Dolly is still a spectacle, though, nearly 25 years after her creation: Her body was taxidermied and puton display at the National Museum of Scotland in Edinburgh.

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Dolly the Sheep: '90s Media Sensation - Mental Floss

Fluorescent image shows chromosomes (green) segregating in two developing eggs. In each egg, one chromosome (the largest green one) has too many crossovers and is having problems segregating. The image was taken on a deconvolution fluorescent microscope. Credit: Image courtesy of Diana Libuda

University of Oregon and Northwestern University biologists show that too many crossover events can increase infertility.

The exchange of DNA between chromosomes during the early formation of sperm and egg cells normally is limited to assure fertility.

But when there are too many of these genetic exchanges, called crossover events, the segregation of chromosomes into eggs is flawed, biologists have learned in a project done across three labs at the University of Oregon and Northwestern University.

In a paper published online in September 2020 in the journal PLOS Genetics, researchers documented how the disruptions, as seen in basic research with microscopic roundworms (Caenorhabditis elegans), lead to a range of meiotic defects as the chromosomes are subjected to improper spindle forces.

Inaccurate chromosome segregation in humans is associated with Down syndrome and miscarriages. Such segregation defects as seen in the research can result in increased infertility, said UO biologist Diana E. Libuda, the studys principal investigator.

Over the past century, research has focused on making sure enough crossovers are made during sperm and egg development, said Libuda, a professor in the UOs Department of Biology and Institute of Molecular Biology. It was known that developing sperm and eggs had ways to make sure that not too many crossovers are made, but it was unclear why.

The research team identified two mechanisms that help counteract defects triggered by excess crossover activity in developing eggs and, thus, assist the coordination of the process that helps assure genomic integrity in new generations.

Libuda had reported in the October 9, 2013, issue of Nature the discovery of a mechanism that inhibits the overproduction of crossovers in roundworms. However, Libuda said, it was not possible at that time to study the downstream effects in cases where too many crossovers did occur. Since then, her lab developed a way to generate extra crossovers on a single chromosome.

That ability led to a National Institutes of Health-funded collaboration with Sadie Wignall of Northwestern University, an expert on high-resolution imaging of structures involved in segregation of chromosomes into developing eggs. What Wignall found led Libuda back to Bruce Bowermans UO lab to take a look at chromosome segregation in live developing eggs.

Overall, it was a great joining of scientific strengths to take a multipronged approach to answer this important question, Libuda said.

The research provides fundamental insights that can guide research in other organisms to better understand the mechanisms and, eventually, lead to potential clinical applications.

The same proteins that we are studying in C. elegans are also in humans, Libuda said. In fact, most proteins required for fertility are used across organisms that include yeast, fruit flies, nematodes, zebrafish, mice and humans. Research using these microscopic worms has been shown in numerous contexts to have relevance in human health.

Reference: Excess crossovers impede faithful meiotic chromosome segregation in C. elegans by Jeremy A. Hollis, Marissa L. Glover, Aleesa J. Schlientz, Cori K. Cahoon, Bruce Bowerman, Sarah M. Wignall and Diana E. Libuda, 4 September 2020, PLOS Genetics.DOI: 10.1371/journal.pgen.1009001

Co-authors with Libuda, Bowerman and Wignall on the paper were: Jeremy A. Hollis, a technician in Wignalls lab; former UO biology undergraduate student Marissa L. Glover, now a doctoral student at the University of California, Santa Cruz; Aleesa J. Schlientz, who earned a doctorate from the UO this year; and Cori K. Cahoon, a postdoctoral researcher working in Libudas lab under a fellowship from the Jane Coffin Childs Memorial Fund for Medical Research.

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Over-Exchange of DNA in Sperm and Eggs Results in Chromosome Defects That Can Increase Infertility - SciTechDaily