Curated science discoveries this week

• Key brain molecule may play role in many neuro disorders
• New multiple sclerosis subtypes identified using artificial intelligence
• Technique developed to produce transplantable livers in the laboratory
• Thirteen new Alzheimer’s disease genes identified in first-of-its-kind human genome study

Key brain molecule may play role in many neuro disorders

"We think abnormalities in microRNA-29 activity are likely to be a common theme in neurodevelopmental disorders and even in ordinary behavioral differences in individuals," said senior author Mohanish Deshmukh, PhD, professor in the UNC Department of Cell Biology & Physiology and member of the UNC Neuroscience Center. "Our work suggests that boosting levels of miR-29, perhaps even by delivering it directly, could lead to a therapeutic strategy for neurodevelopmental disorders such as autism."

A team led by scientists at the UNC School of Medicine identified a molecule called microRNA-29 as a powerful controller of brain maturation in mammals. Deleting microRNA-29 in mice caused problems very similar to those seen in autism, epilepsy, and other neurodevelopmental conditions. The results, published in Cell Reports, illuminate an important process in the normal maturation of the brain and point to the possibility that disrupting this process could contribute to multiple human brain diseases. MicroRNAs are short stretches of ribonucleic acid inside cells that regulate gene expression. Each microRNA, or miR, can bind directly to an RNA transcript from certain other genes, preventing it from being translated into a protein. MiRNAs thus effectively serve as inhibitors of gene activity, and the typical microRNA regulates multiple genes in this way so that genetic information is not overexpressed. These essential regulators have been intensively researched only in the past two decades. Therefore, much remains to be discovered about their roles in health and disease... LINK TO PRESS RELEASE / LINK TO STUDY

New multiple sclerosis subtypes identified using artificial intelligence

Explaining the research, lead author Dr Arman Eshaghi (UCL Queen Square Institute of Neurology) said: "Currently MS is classified broadly into progressive and relapsing groups, which are based on patient symptoms; it does not directly rely on the underlying biology of the disease, and therefore cannot assist doctors in choosing the right treatment for the right patients. "Here, we used artificial intelligence and asked the question: can AI find MS subtypes that follow a certain pattern on brain images? Our AI has uncovered three data-driven MS subtypes that are defined by pathological abnormalities seen on brain images."

Scientists at UCL have used artificial intelligence (AI) to identify three new multiple sclerosis (MS) subtypes. Researchers say the groundbreaking findings will help identify those people more likely to have disease progression and help target treatments more effectively. MS affects over 2.8 million people globally and 130,000 in the UK, and is classified into four* 'courses' (groups), which are defined as either relapsing or progressive. Patients are categorised by a mixture of clinical observations, assisted by MRI brain images, and patients' symptoms. These observations guide the timing and choice of treatment. For this study, published in Nature Communications, researchers wanted to find out if there were any - as yet unidentified - patterns in brain images, which would better guide treatment choice and identify patients who would best respond to a particular therapy... LINK TO PRESS RELEASE / LINK TO STUDY

Technique developed to produce transplantable livers in the laboratory

"The plan is to produce human livers in the laboratory to scale. This will avoid having to wait a long time for a compatible donor and reduce the risk of rejection of the transplanted organ," Luiz Carlos de Caires-Júnior, first author of the article, told Agência FAPESP. He is a postdoctoral fellow of HUG-CELL, one of the Research, Innovation and Dissemination Centers (RIDCs) funded by FAPESP.

Researchers at the Human Genome and Stem Cell Research Center (HUG-CELL), hosted by the University of São Paulo's Institute of Biosciences (IB-USP) in Brazil, have developed a technique to reconstruct and produce livers in the laboratory. The proof-of-concept study was conducted with rat livers. In the next stage of their research, the scientists will adapt the technique for the production of human livers in order in future to increase the supply of these organs for transplantation. The methodology is based on decellularization and recellularization, tissue bioengineering techniques developed in recent years to produce organs for transplantation. An organ from a deceased donor, in this case the liver, is treated with various solutions containing detergents or enzymes to remove all the cells from the tissue, leaving only the extracellular matrix with the organ's original structure and shape. The extracellular matrix is then seeded with cells taken from the patient. The technique avoids immune system reactions and the risk of rejection in the long term. "It's comparable to transplanting a 'reconditioned' liver. It won't be rejected because it uses the patient's own cells, and there's no need to administer immunosuppressants," said Mayana Zatz, HUG-CELL's principal investigator and last author of the article... LINK TO STUDY

Thirteen new Alzheimer’s disease genes identified in first-of-its-kind human genome study

"This paper brings us to the next stage of disease-gene discovery by allowing us to look at the entire sequence of the human genome and assess the rare genomic variants, which we couldn't do before," says Dmitry Prokopenko, PhD, of MGH's McCance Center for Brain Health, who is lead author of the study.

In the first study to use whole genome sequencing (WGS) to discover rare genomic variants associated with Alzheimer's disease (AD), researchers have identified 13 such variants (or mutations). In another novel finding, this study establishes new genetic links between AD and the function of synapses, which are the junctions that transmit information between neurons, and neuroplasticity, or the ability of neurons to reorganize the brain's neural network. These discoveries could help guide development of new therapies for this devastating neurological condition. Researchers at Massachusetts General Hospital (MGH), the Harvard T. H. Chan School of Public Health, and Beth Israel Deaconess Medical Center report these findings in Alzheimer's & Dementia: The Journal of the Alzheimer's Association. Over the last four decades, MGH has pioneered research on the genetic origins of AD, led by Rudolph Tanzi, PhD, vice chair of Neurology and director of the hospital's Genetics and Aging Research Unit. Notably, Tanzi and colleagues co-discovered genes that cause early onset (prior to age 60) familial AD (that is, a form that runs in families), including the amyloid protein (A4) precursor (APP), and the presenilin genes (PSEN1 and PSEN2). Mutations in these genes lead to accumulation of amyloid plaques in the brain, a hallmark of AD... LINK TO PRESS RELEASE

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