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Comment by Dr. Krishna Kumari Challa on August 17, 2023 at 1:08pm

Sugars affect brain 'plasticity,' helping with learning, memory, recovery

Can you recognize someone you haven't seen in years, but forget what you had for breakfast yesterday? Our brains constantly rearrange their circuitry to remember familiar faces or learn new skills, but the molecular basis of this process isn't well understood. Recently scientists reported that sulfate groups on complex sugar molecules called glycosaminoglycans (GAGs) affect "plasticity" in the brains of mice. Determining how GAGs function could help us understand how memory and learning work in humans, and provide ways to repair neural connectivity after injuries.

The researchers will present their results today at the fall meeting of the American Chemical Society (ACS).

The sugars that sweeten fruits, candies or cakes are actually just a few simple varieties of the many types of sugars that exist. When strung together, they can make a wide array of complex sugars. GAGs are formed by then attaching other chemical structures, including sulfate groups.

If we study the chemistry of GAGs in the brain, we can learn about brain plasticity and hopefully, in the future, use this information to restore or enhance neural connections involved in memory. These sugars regulate numerous proteins, and their structures change during development and with disease.

In the brain, the most common GAG form is chondroitin sulfate, which is found throughout the extra cellular matrix surrounding the brain's many cells. Chondroitin sulfate can also form structures known as "perineuronal nets," which wrap around individual neurons and stabilize the synaptic connections between them.

One way a GAG's function can be changed is through sulfation motifs, or patterns of sulfate groups tacked onto the sugar chains.

Source: Harnessing chemistry to understand the roles of glycans in neuroplasticity, ACS Fall 2023.

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Comment by Dr. Krishna Kumari Challa on August 17, 2023 at 12:57pm

Parabiosis: an experiment in which two animals are linked together by their blood circulation. When a young, sprightly animal is connected to an aging animal, the aging animal becomes more youthful–its muscles more resilient, its brain more capable of learning.

In 2014, researchers found that plasma, consisting of blood minus red blood cells, mimicked parabiosis: young blood plasma, injected into old animals, was restorative. When they compared young plasma to old plasma, they found it contained much more PF4. Just injecting PF4 into old animals was about as restorative as young plasma. It calmed down the aged immune system in the body and the brain. Old animals treated with PF4 performed better on a variety of memory and learning tasks.

PF4 actually causes the immune system to look younger, it's decreasing all of these active pro-aging immune factors, leading to a brain with less inflammation, more plasticity and eventually more cognition.

A decade ago, other researchers showed that klotho enhances cognition in young and old animals and also makes the brain more resistant to age-related degeneration. 

But the researchers knew its effects had to be indirect because klotho molecules, injected into the body, never reached the brain. They found that one connection was PF4, released by platelets after an injection of klotho. PF4 had a dramatic effect on the hippocampus, the brain region responsible for making memories, where it enhanced the formation of new neural connections at the molecular level.

Exercise can keep the mind sharp for decades. Researchers also found that platelets released PF4 into the bloodstream following exercise. So exercise  also improved cognition in old animals. 

But for a lot of people with health conditions, mobility issues or of advanced age, exercise isn't possible, so pharmacological intervention is an important area of research. We can now target platelets to promote neurogenesis, enhance cognition and counteract age-related cognitive decline.

Adam B. Schroer et al, Platelet factors attenuate inflammation and rescue cognition in ageing, Nature (2023). DOI: 10.1038/s41586-023-06436-3. www.nature.com/articles/s41586-023-06436-3

Park, C. et al. Platelet factors are induced by longevity factor klotho and enhance cognition in young and aging mice, Nature Aging (2023). DOI: 10.1038/s43587-023-00468-0. www.nature.com/articles/s43587-023-00468-0

Odette Leiter et al, Platelet-derived exerkine CXCL4/platelet factor 4 rejuvenates hippocampal neurogenesis and restores cognitive function in aged mice, Nature Communications (2023). DOI: 10.1038/s41467-023-39873-9

Part 2

Comment by Dr. Krishna Kumari Challa on August 17, 2023 at 12:50pm

Blood factor can turn back time in the aging brain

Platelets are behind the cognitive benefits of young blood, exercise and the longevity hormone klotho. In a remarkable convergence, scientists have discovered that the same blood factor is responsible for the cognitive enhancement that results from young blood transfusion, the longevity hormone klotho, and exercise.

In a trio of papers appearing in Nature, Nature Aging and Nature Communications, three research teams identify platelet factor 4 (PF4) as a common messenger of each of these interventions.

As its name suggests, PF4 is made by platelets, a type of blood cell that alerts the immune system when there is a wound and helps to form clots. It turns out that PF4 is also a cognitive enhancer. Under its influence, old mice recover the sharpness of middle age and young mice get smarter.

Young blood, klotho, and exercise can somehow tell your brain, 'Hey, improve your function'. With PF4, we're starting to understand the vocabulary behind this rejuvenation.

Part 1

Comment by Dr. Krishna Kumari Challa on August 16, 2023 at 1:26pm

The first step was to test blood samples from 519 glaucoma patients and 189 healthy controls. A significantly higher percentage of β7-expressing CD4+ T cells was found in glaucoma patients compared to healthy controls, and glaucoma patients with more of these cells in their blood had more severe eye damage.

Using an EIOP-induced mouse model of glaucoma, researchers next showed that to gain access to the retina, β7+ CD4+ T cells in these early stage glaucoma mice must make a detour through the gut.

The team found the β7+ CD4+ T cells of EIOP-induced mice were reprogrammed in the gut, so they could use integrin β7 as a kind of license, returning to the blood circulation functionally equipped to travel to the retina.

While normal T cells are unable to bind to MAdCAM-1 in the retina, the gut-licensed cells were able to do so, allowing them access to the eye tissue, which "eventually led to neuroinflammation".

The ability to induce MAdCAM-1 expression on retinal [vessels] might be one of the mechanisms whereby gut-licensed β7+ CD4+ T cells cross the blood-retina barrier and invade the retina, To investigate the link between these suspect cells and proteins and glaucoma damage, the team administered antibodies to mice that blocked the β7+ CD4+ T cells' interaction with MAdCAM-1. Inhibiting the communication with MAdCAM-1 significantly reduced the damage caused by glaucoma.

https://www.science.org/doi/10.1126/scitranslmed.adg1656

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Part 2

Comment by Dr. Krishna Kumari Challa on August 16, 2023 at 1:23pm

Mysterious Form of Vision Loss May Brew Inside The Gut!

In some glaucoma patients, vision loss mysteriously progresses despite treatment, and new research from China points to immune cells that migrate from the digestive tract to the eyes. These "gut-retina axis" cells bind a specific protein and gain access to the eye's light-sensitive tissue, where they damage retinal ganglion cells (RGCs). Glaucoma, classified as a group of neurodegenerative diseases, is an umbrella term for eye diseases caused by loss of RGCs, whose axons form the optic nerve which transmits visual information to the brain. Your optic nerve is sending this to your brain's visual cortex to process right now, if you're reading with your eyes. A leading cause of blindness, glaucoma is currently incurable; treatment aims to halt disease progression. These new findings emphasize the importance of the gut-retina axis in glaucoma pathogenesis and for the development of therapeutic strategies. Pressure inside the eyeball, called elevated intraocular pressure (EIOP), is the main risk factor for glaucoma. Lowering EIOP is a primary goal of treatment, but it isn't always successful in stopping progression of the disease.

Previous studies hinted that immune system T cells may play a role in glaucoma damage, but the underlying mechanism has been unclear. T cells and other circulating immune cells are normally denied permission to enter the retina.

These very scientists were part of a 2021 study that found a subset of CD4+ T cells express a gut-homing receptor, integrin β7, which somehow gained entry to the retina with a little help from a protein called mucosal addressin cell adhesion molecule 1 (MAdCAM-1). 

In their new study, tehy confirmed a link between CD4+ T cells that express integrin β7, MAdCAM-1, and glaucoma disease severity in patients.

Part 1

Comment by Dr. Krishna Kumari Challa on August 16, 2023 at 12:45pm

Annular Eclipse

Comment by Dr. Krishna Kumari Challa on August 16, 2023 at 12:42pm

In the new study, the researchers used EEG to examine 107 brain injury patients. The technique can determine when patients are trying, though unable, to respond to a command such as "keep opening and closing your right hand."

The analysis detected CMD in 21 of the patients. 
The researchers then analyzed structural MRI scans from all of the patients.

Using a technique they developed called bi-clustering analysis, they were able to identify patterns of brain injury that are shared among patients with CMD and contrast to those without CMD.

The researchers found that all of the CMD patients had intact brain structures related to arousal and command comprehension, supporting the notion that these patients were hearing and understanding the commands but were unable to carry them out.  They saw that all of the CMD patients had deficits in brain regions responsible for integrating comprehended motor commands with motor output, preventing CMD patients from acting on verbal commands.

The findings may allow researchers to better understand which brain injury patients have CMD, which will be useful for clinical trials that support recovery of consciousness.

Eva Franzova, Qi Shen, Kevin Doyle, Justine M Chen, Jennifer Egbebike, Athina Vrosgou, Jerina C Carmona, Lauren Grobois, Gregory A Heinonen, Angela Velazquez, Ian Jerome Gonzales, Satoshi Egawa, Sachin Agarwal, David Roh, Soojin Park, E Sander Connolly, Jan Claassen. Injury patterns associated with cognitive motor dissociation. Brain, 2023; DOI: 10.1093/brain/awad197

Part 2

Comment by Dr. Krishna Kumari Challa on August 16, 2023 at 12:39pm

Source of hidden consciousness in 'comatose' brain injury patients found

 Researchers have identified brain injuries that may underlie hidden consciousness, a puzzling phenomenon in which brain-injured patients are unable to respond to simple commands, making them appear unconscious despite having some level of awareness.

This study suggests that patients with hidden consciousness can hear and comprehend verbal commands, but they cannot carry out those commands because of injuries in brain circuits that relay instructions from the brain to the muscles.

The findings could help physicians more quickly identify brain-injured patients who might have hidden consciousness and better predict which patients are likely to recover with rehabilitation.

Hidden consciousness, also known as cognitive motor dissociation (CMD), occurs in about 15% to 25% of patients with brain injuries stemming from head trauma, brain hemorrhage, or cardiac arrest.

In previous research, researchers found that subtle brainwaves detectable with EEG are the strongest predictor of hidden consciousness and eventual recovery for unresponsive brain-injured patients. But the precise pathways in the brain that become disrupted in this condition were unknown.

Part 1

Comment by Dr. Krishna Kumari Challa on August 16, 2023 at 8:33am

Scientists theorize a hidden phase transition between liquid and a solid

Anything made out of plastic or glass is known as an amorphous material. Unlike many materials that freeze into crystalline solids, the atoms and molecules in amorphous materials never stack together to form crystals when cooled. In fact, although we commonly think of plastic and glass as "solids," they instead remain in a state that is more accurately described as a supercooled liquid that flows extremely slowly.

And although these "glassy dynamic" materials are ubiquitous in our daily lives, how they become rigid at the microscopic scale has long eluded scientists.

Now, researchers  have discovered molecular behavior in supercooled liquids that represents a hidden phase transition between a liquid and a solid.

Their improved understanding applies to ordinary materials like plastics and glass, and could help scientists develop new amorphous materials for use in medical devices, drug delivery, and additive manufacturing.

Specifically, using theory, computer simulations,  and previous experiments, the scientists explained why the molecules in these materials, when cooled, remain disordered like a liquid until taking a sharp turn toward a solid-like state at a certain temperature called the onset temperature—effectively becoming so viscous that they barely move. This onset of rigidity—a previously unknown phase transition—is what separates supercooled from normal liquids.

Any supercooled liquid continuously jumps between multiple configurations of molecules, resulting in localized particle movements known as excitations. In their proposed theory, the researchers treated the excitations in a 2D supercooled liquid as though they were defects in a crystalline solid.

As the supercooled liquid's temperature increased to the onset temperature, they propose that every instance of a bound pair of defects broke apart into an unbounded pair. At precisely this temperature, the unbinding of defects is what made the system lose its rigidity and begin to behave like a normal liquid. "The onset temperature for glassy dynamics is like a melting temperature that 'melts' a supercooled liquid into a liquid. This should be relevant for all supercooled liquids or glassy systems.

The theory and simulations captured other key properties of glassy dynamics, including the observation that, over short periods of time, a few particles moved while the rest of the liquid remained frozen.

Dimitrios Fraggedakis et al, Inherent-state melting and the onset of glassy dynamics in two-dimensional supercooled liquids, Proceedings of the National Academy of Sciences (2023). DOI: 10.1073/pnas.2209144120

Comment by Dr. Krishna Kumari Challa on August 15, 2023 at 9:59am

Changing flies into degradable plastics?

Imagine using insects as a source of chemicals to make plastics that can biodegrade later—with the help of that very same type of bug. That concept is closer to reality than you might expect. Researchers describe their progress to date, including isolation and purification of insect-derived chemicals and their conversion into functional bioplastics, at the fall meeting of the American Chemical Society (ACS).

Researchers have been developing methods for several years to transform natural products—such as glucose obtained from  sugar cane or trees—into degradable, digestible polymers that don't persist in the environment. But those natural products are harvested from resources that are also used for food, fuel, construction and transportation.

So some researchers began searching for alternative sources that wouldn't have these competing applications.

And they thought of using waste products left over from farming black soldier flies. The larvae of these flies contain many proteins and other nutritious compounds, so the immature insects are increasingly being raised for animal feed and to consume wastes. However, the adults have a short life span after their breeding days are over and are then discarded. How about using them instead of useless plastics?

When  researchers examined the dead flies, they determined that chitin is a major component. This nontoxic, biodegradable, sugar-based polymer strengthens the shell, or exoskeleton, of insects and crustaceans. Manufacturers already extract chitin from shrimp and crab shells for various applications, and researchers now  have been applying similar techniques using ethanol rinses, acidic demineralization, basic deproteinization and bleach decolorization to extract and purify it from the insect carcasses.

Fly-sourced chitin powder is probably purer, since it lacks the yellowish colour and clumpy texture of the traditional product. Researchers also note that obtaining chitin from flies could avoid possible concerns over some seafood allergies. Some other researchers isolate chitin or proteins from fly larvae, but this is the first time the use chitin from discarded adult flies, which—unlike the larvae—aren't used for feed.

Harvesting of building blocks from insect feedstocks for transformation into carbohydrate-derived superabsorbent hydrogels, ACS Fall 2023. www.acs.org/meetings/acs-meetings/fall-2023.html

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