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Category: neuroscience – Page 734

Though many negative repercussions of human immunodeficiency virus infection can be mitigated with the use of antiretroviral therapy (ART), one area where medical advances haven’t made as much progress is in the reduction of cognitive impacts. Half of HIV patients have HIV-associated neurocognitive disorders (HAND), which can manifest in a variety of ways, from forgetfulness and confusion to behavior changes and motor deficiencies.

To better understand the mechanisms underlying HAND, researchers from Penn’s School of Dental Medicine and Perelman School of Medicine and from the Children’s Hospital of Philadelphia (CHOP) brought together their complementary expertise to create a laboratory model system using three of the types of brain cells thought to be involved. Led by doctoral student Sean Ryan, who was co-mentored by Kelly Jordan-Sciutto of Penn Dental Medicine and Stewart Anderson of CHOP and Penn Medicine, the model recapitulates important features of how HIV infection and ART affect the brain.

“Frankly the models we generally use in the HIV field have a lot of weaknesses,” says Jordan-Sciutto, co-corresponding author on the paper, which appears in the journal Stem Cell Reports. “The power of this system is it allows us to look at the interaction between different cell types of human origin in a way that is more relevant to patients than other models.”

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For the first time, scientists have reprogrammed cells from a 114-year-old woman into induced pluripotent stem cells (iPS cells), a move which they describe as a significant step toward understanding “the underlying mechanisms of extreme longevity and disease resistance.”

iPS cells are adult cells that have been genetically reprogrammed into an embryonic stem cell-like state and are able to give rise to any of the specialized cell types of the body, whether it’s neurons, blood cells, or heart cells.

Until this new project, researchers weren’t even certain whether they could create viable iPS cells from someone so elderly, let alone a supercentenarian. Now they have shown it’s possible to effectively make these aged cells resemble young pluripotent cells, the researchers believe they might have made a step towards the reversal of cellular aging.

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Our body’s ability to detect disease, foreign material, and the location of food sources and toxins is all determined by a cocktail of chemicals that surround our cells, as well as our cells’ ability to ‘read’ these chemicals. Cells are highly sensitive. In fact, our immune system can be triggered by the presence of just one foreign molecule or ion. Yet researchers don’t know how cells achieve this level of sensitivity.

Now, scientists at the Biological Physics Theory Unit at Okinawa Institute of Science and Technology Graduate University (OIST) and collaborators at City University of New York have created a simple model that is providing some answers. They have used this model to determine which techniques a cell might employ to increase its sensitivity in different circumstances, shedding light on how the biochemical networks in our bodies operate.

“This model takes a complex biological system and abstracts it into a simple, understandable mathematical framework,” said Dr. Vudtiwat Ngampruetikorn, former postdoctoral researcher at OIST and the first author of the research paper, which was published in Nature Communications. “We can use it to tease apart how cells might choose to spend their energy budget, depending on the world around them and other cells they might be talking to.”

By bringing a quantitative toolkit to this biological question, the scientists found that they had a different perspective to the biologists. “The two disciplines are complimentary to one another,” said Professor Greg Stephens, who runs the unit. “Biologists tend to focus on one area and delve deeply into the details, whereas physicists simplify and look for patterns across entire systems. It’s important that we work closely together to make sure that our quantitative models aren’t too abstract and include the important details.”

On their computers, the scientists created the model that represented a cell. The cell had two sensors (or information processing units), which responded to the environment outside the cell. The sensors could either be bound to a molecule or ion from the outside, or unbound. When the number of molecules or ions in chemical cocktail outside the cell changed, the sensors would respond and, depending on these changes, either bind to a new molecule or ion, or unbind. This allowed the cell to gain information about the outside world and thus allowed the scientists to measure what could impact its sensitivity.

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Revealing yet another super-power in the skillful squid, scientists have discovered that squid massively edit their own genetic instructions not only within the nucleus of their neurons, but also within the axon — the long, slender neural projections that transmit electrical impulses to other neurons. This is the first time that edits to genetic information have been observed outside of the nucleus of an animal cell.

The study, led by Isabel C. Vallecillo-Viejo and Joshua Rosenthal at the Marine Biological Laboratory (MBL), Woods Hole, is published this week in Nucleic Acids Research.

The discovery provides another jolt to the “central dogma” of molecular biology, which states that genetic information is passed faithfully from DNA to messenger RNA to the synthesis of proteins. In 2015, Rosenthal and colleagues discovered that squid “edit” their messenger RNA instructions to an extraordinary degree — orders of magnitude more than humans do — allowing them to fine-tune the type of proteins that will be produced in the nervous system.

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A new method to accurately record brain activity at scale has been developed by researchers at the Crick, Stanford University and UCL. The technique could lead to new medical devices to help amputees, people with paralysis or people with neurological conditions such as motor neurone disease.

The research in mice, published in Science Advances, developed an accurate and scalable method to record brain activity across large areas, including on the surface and in deeper regions simultaneously.

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