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Comment by Dr. Krishna Kumari Challa on August 19, 2023 at 10:22am

Sniffing nanoparticles loaded with mRNA could lead to advanced lung therapeutics

Researchers  have optimized a polymer-based mRNA vehicle for targeted lung delivery and demonstrated the potential of the platform for mucosal vaccination against respiratory pathogens.

In a paper, "Polymer nanoparticles deliver mRNA to the lung for mucosal vaccination," published in Science Translational Medicine, the team introduces their creation of inhalable messenger RNA (mRNA) for therapeutic use.

Clinical research has been searching for an efficient and targeted way to deliver mRNA to the lungs for various therapeutic applications, including protein replacement therapies, gene editing and vaccination. The main challenges have been maintaining mRNA stability and avoiding immune interference.

Researchers now  created PACE (Polymerized Albumin Conjugates for mRNA Encapsulation) polymer formulations to deliver local mRNA to the lungs. The researchers optimized PACE polyplexes to enhance mRNA protection, transfection efficiency, and antigen presentation for effective lung-specific therapeutic and vaccination strategies.

To stabilize PACE, an optimized ratio of polyethylene glycol (PEG) molecules were integrated into the polymer structure during the enzymatic copolymerization process, which stabilized the polyplexes and modified key characteristics. PEG was able to affect the size, surface charge, and other properties of the polyplexes, making them more suitable for loading and effective at mRNA delivery to lung cells.

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The researchers encapsulated mRNA encoding the spike protein from SARS-CoV-2 into PACE and inoculated mice susceptible to SARS-CoV-2 infection. Mice received a 10-μg dose of PACE-mRNA delivered intranasally on days 0 and 28. The development of adaptive immunity in the mediastinal lymph nodes was tested and confirmed 14 days after the boost.

Part 1

Comment by Dr. Krishna Kumari Challa on August 18, 2023 at 8:31am

Climatic changes put the brakes on spider's 'gift-giving'

Being wary of gifts from males of the species takes on a new meaning among a South American spider species known to woo females with silk-wrapped food parcels.

Scientists in South America and Australia have discovered that environmental stresses, such as large variations in rainfall and floods in the rivers, tend to change the mating rituals of these semi-aquatic Neotropical spiders which live in riparian habitats in Uruguay and Brazil.

They found that during moderate to harsh lean times, gift-giving spider Paratrechalea ornata males often offer females a deceptive or worthless gift, rather than a food gift.

This study found this behavior probably corresponds with periods of time when food is more difficult to find so some males might 'cheat' by offering fake gifts.

While males of some spider populations offer prey to females as a way to convince them to mate, there might be less bountiful periods when males are more deceptive with their 'nuptial' gifts.

When local environmental conditions are harsh, these fake parcels become more common rather than the exception and both males and females become smaller and need less food, researchers say, warning of the long-term affects of climate change on spider, insect and other organisms' survival.

In times of plenty, females will usually reject males if they offer fake gifts but they may eventually have to accept the gifts with no food inside when most males are forced to cheat.

Maria J. Albo et al, Stressful environments favor deceptive alternative mating tactics to become dominant, BMC Biology (2023). DOI: 10.1186/s12915-023-01664-5

Comment by Dr. Krishna Kumari Challa on August 18, 2023 at 8:22am

Study discovers pairing of electrons in artificial atoms, a quantum state predicted more than 50 years ago

Researchers observed a quantum state that was theoretically predicted more than 50 years ago by Japanese theoreticians but so far eluded detection. By tailoring an artificial atom on the surface of a superconductor, the researchers succeeded in pairing the electrons of the so-called quantum dot, thereby inducing the smallest possible version of a superconductor. The work appears in the journal Nature.

Usually, electrons repel each other due to their negative charge. This phenomenon has a huge impact on many materials properties such as the electrical resistance. The situation changes drastically if the electrons are "glued" together to pairs thereby becoming bosons. Bosonic pairs do not avoid each other like single electrons, but many of them can reside at the very same location or do the very same motion.

One of the most intriguing properties of a material with such electron pairs is superconductivity, the possibility to let an electrical current flow through the material without any electrical resistance. For many years, superconductivity has found many important technological applications, including magnetic resonance imaging or highly sensitive detectors for magnetic fields.

Today, the continuous downscaling of electronic devices heavily guides investigations on how superconductivity can be induced into much smaller structures at the nanoscale.

Researchers have now realized the pairing of electrons in an artificial atom called quantum dot, which is the smallest building block for nanostructured electronic devices. They locked the electrons into tiny cages that they built from silver, atom-by-atom. By coupling the locked electrons to an elemental superconductor, the electrons inherited the tendency towards pairing from the superconductor.

the researchers related the experimental signature, a spectroscopic peak at very low energy, to the quantum state predicted in the early 1970s by Kazushige Machida and Fumiaki Shibata.

While the state has so far eluded  direct detection by experimental methods, recent work by researchers from the Netherlands and Denmark show it is beneficial for suppressing unwanted noise in transmon qubits, an essential building block of modern quantum computers.

 Lucas Schneider et al, Proximity superconductivity in atom-by-atom crafted quantum dots, Nature (2023). DOI: 10.1038/s41586-023-06312-0

Comment by Dr. Krishna Kumari Challa on August 17, 2023 at 1:55pm

Worms Frozen for 46,000 Years are the Oldest Known Living Animals

Nematodes buried in Siberian permafrost may be able to stay in a state of suspended animation indefinitely, according to recent findings.

Microscopic worms unearthed from Siberian permafrost might belong to a species that went extinct elsewhere on Earth long ago. Researchers said that the tiny, 46,000-year-old nematodes use genes similar to those of their modern-day relatives to enter a state of hibernation where the worms can live indefinitely across tens of thousands of years. The findings were recently published in PLOS Genetics

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Microplastics are adsorbing zinc oxide from sunscreens and microbea...

A new study by a research team from Diamond Light Source looks at how microplastics wastes may interact with zinc oxide (ZnO) nanomaterials in freshwater and seawater scenarios. It also evaluated, a ZnO-based sunscreen and an exfoliating cleanser with microbeads in its composition under the same conditions.

Comment by Dr. Krishna Kumari Challa on August 17, 2023 at 1:53pm

These ‘living’ rocks can give birth to baby stones

The staggering science behind trovants, the rocks that can grow, move – and reproduce.

Trovants are bulbous, otherworldly stones that grow over time, thus appearing to be alive. Parent rocks can even push out baby trovants, which then grow independently.

The sandstone structures are found mainly in Romania, with the most famous cluster in and around a village named Costeşti. There, a Trovants Museum Natural Reserve celebrates and protects them.

The stones’ smooth curves give the appearance of modern, man-made sculptures. They feature heavily in local folklore, with people at one time believing them to be giant dinosaur eggs, plant fossils or alien creations. The word trovant was coined by a naturalist and means cemented sand.

The stones are formed from sand grains or rocks bound together by a limestone – calcium carbonate – cement. Geologists think that the trovants were shaped by earthquakes in the Middle Miocene, over five million years ago.

The stones vary greatly in size and shape, from centimetres to metres in diameter. Whereas most rocks erode and reduce in size over years, trovants continue to expand. During heavy rain, the porous trovants absorb substances, including calcium carbonate from the water. Limestone cement then oozes from the stones to add to their circumference. When water only hits one side of a rock, a blob can emerge, finally breaking free to create a new trovant.

Trovant growth is too slow to be watched in real time. It is estimated that the rocks have only grown a handful of centimetres in over 1,000 years.

The sandstone beds that the stones reside in hint at ancient aquatic environments, with successive sedimentation of material transported by rivers. Indeed, bivalve, and gastropod fossils can sometimes be found hidden inside the trovants.

Source: SF

Comment by Dr. Krishna Kumari Challa on August 17, 2023 at 1:10pm

Cleaning water with 'smart rust' and magnets
Pouring flecks of rust into water usually makes it dirtier. But researchers have developed special iron oxide nanoparticles they call "smart rust" that actually makes it cleaner. Smart rust can attract many substances, including oil, nano- and microplastics, as well as the herbicide glyphosate, depending on the particles' coating. And because the nanoparticles are magnetic, they can easily be removed from water with a magnet along with the pollutants. Now, the team is reporting that they've tweaked the particles to trap estrogen hormones that are potentially harmful to aquatic life.
Using magnetic rust nanoparticles to clean water

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

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