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Comment by Dr. Krishna Kumari Challa on March 18, 2023 at 1:17pm

Sweetener reduces mouse immune response

In high doses, the calorie-free sugar substitute sucralose suppresses the immune system in mice. The sweetener impairs the rodents’ T cells, immune cells that fight.... Once the mice stopped being fed sucralose, their T-cell responses recovered. The researchers say that it is unlikely that eating sucralose in normal amounts is harmful to humans. There might even be a bright side for autoimmune conditions: mice predisposed to type 1 diabetes were less likely to develop the condition after consuming the sweetener.

https://www.nature.com/articles/s41586-023-05801-6.epdf?sharing_tok...

https://www.nature.com/articles/d41586-023-00784-w?utm_source=Natur...

Comment by Dr. Krishna Kumari Challa on March 18, 2023 at 12:45pm

How tumors transform blood vessels

Increasingly dense cell clusters in growing tumors convert blood vessels into fiber-filled channels. This makes immune cells less effective, as findings by researchers suggest.

It was almost ten years ago that researchers first observed that tumours occurring in different cancers—including colorectal cancer, breast cancer and melanoma—exhibit channels leading from the surface to the inside of the cell cluster. But how these channels form, and what functions they perform, long remained a mystery.

Through a series of elaborate and detailed experiments, scientists  have found possible answers to these questions. There is a great deal of evidence to suggest that these channels, which the researchers have dubbed tumour tracks, were once blood vessels.

These blood vessels start out by supplying the fast-growing cell clusters with glucose and oxygen. But then the vessels undergo a process that strips them of their original function of transporting blood: the vessel walls change and the vessel cavity gradually fills up.

This filler material consists mainly of cells and newly formed protein fibers, which make up what is known as the extracellular matrix. Collagen fibers are found here, as are fibronectin fibers. The latter play a role in growth processes that take place mainly during embryonic development or wound healing. In their article, the researchers show that the fibers within the tumor tracks are capable of trapping immune cells.

While this happens, the immune cells stretch out along the channels and stick to the loose fibronectin fibers. In this elongated form, the immune cells switch from fighting diseases to supporting healing processes. Instead of attacking the tumour cells, they excrete molecules that stimulate growth, thus helping the cancer cells to multiply.

It becomes clear that the tension of extracellular matrix fibers plays a key and previously unknown role in tumor development: in healthy tissue, the fibronectin fibers are stretched extremely taut; only in tumor tissue are they slack. In this looser, more relaxed form, surrounded by transformed blood vessel walls, the fibronectin fibers evidently create a recess in which cancer cells can grow undisturbed.

Charlotte M. Fonta et al, Infiltrating CD8+ T cells and M2 macrophages are retained in tumor matrix tracks enriched in low tension fibronectin fibers, Matrix Biology (2023). DOI: 10.1016/j.matbio.2023.01.002

Devadarssen Murdamoothoo et al, Tenascin‐C immobilizes infiltrating T lymphocytes through CXCL12 promoting breast cancer progression, EMBO Molecular Medicine (2021). DOI: 10.15252/emmm.202013270

Comment by Dr. Krishna Kumari Challa on March 18, 2023 at 12:34pm

An extra X chromosome-linked gene may explain decreased viral infection severity in females

It has long been known that viral infections can be more severe in males than females, but the question as to why has remained a mystery—until possibly now. The key may lie in an epigenetic regulator that boosts the activity of specialized anti-viral immune cells known as natural killer (NK) cells.

In a study published March 16 in the peer-reviewed journal Nature Immunology, a collaborative team of  researchers have found that female mouse and human NK cells have an extra copy of an X chromosome-linked gene called UTX. UTX acts as an epigenetic regulator to boost NK cell anti-viral function, while repressing NK cell numbers.

While it is well-known that males have more NK cells compared to females, researchers did not understand why the increased number of NK cells was not more protective during viral infections. It turns out that females have more UTX in their NK cells than do males, which allows them to fight viral infections more efficiently.

The researchers noted that this held true whether or not the mice had gonads (ovaries in females; testes in males), indicating that the observed trait was not linked to hormones. Furthermore, female mice with lower UTX expression had more NK cells which were not as capable of controlling viral infection.

This implicates UTX as a critical molecular determinant of sex differences in NK cells.

The findings suggest that therapies involving immune responses need to move beyond a "one-size-fits-all" approach and toward a precision medicine model, also known as personalized medicine, that tailors treatments that take into account people's individual differences, such as genetics, environment and other factors that influence health and disease risk, the researchers write.

Mandy I. Cheng et al, The X-linked epigenetic regulator UTX controls NK cell-intrinsic sex differences, Nature Immunology (2023). DOI: 10.1038/s41590-023-01463-8

Comment by Dr. Krishna Kumari Challa on March 18, 2023 at 12:23pm

The authors discuss some limitations of their study. The findings' generalizability to soccer players playing today is uncertain. As neurodegenerative disease usually occurs later in life, most players in the study who were old enough to have developed one of these conditions played elite soccer during the mid-20th century. Since then, soccer has changed in many ways that may impact the risk of neurodegenerative disease. It may be that switching from leather to synthetic balls (that do not soak up water and become heavier), having more rigorous training and better equipment, or switching towards a playstyle associated with less head trauma may have reduced the risk. On the other hand, the risk might be higher among soccer players who nowadays train and play more intensely from a young age. The study also looked at male elite soccer players only, so the study's generalizability to female elite players and to male and female amateur and youth players is uncertain.

Neurodegenerative disease among male elite football (soccer) players in Sweden: a cohort study, The Lancet Public Health (2023). DOI: 10.1016/S2468-2667(23)00027-0 , www.thelancet.com/journals/lan … (23)00027-0/fulltext

Part 2

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Comment by Dr. Krishna Kumari Challa on March 18, 2023 at 12:23pm

Elite soccer players are more likely to develop dementia, suggests new study

Elite male soccer players were 1.5 times more likely to develop neurodegenerative disease than population controls, according to an observational study published in The Lancet Public Health journal.

Among male soccer players playing in the Swedish top division, 9% (537 out of 6,007) were diagnosed with neurodegenerative disease, compared to 6% (3,485 out of 56,168) population controls.

The soccer players were both amateur and professional. Sweden was a prominent soccer nation during the 20th century and many of the players from the top division were competing at the highest international level. However, due to ideals of sportsmanship and amateurism, soccer clubs in Sweden were not allowed to pay salaries to their soccer players until the late 1960s.

In recent years, there have been growing concerns about exposure to head trauma in soccer (soccer) and whether it can lead to increased risk of neurodegenerative disease later in life. A previous study from Scotland suggested that soccer players were 3.5 times more likely to develop neurodegenerative disease. Following this evidence, certain footballing associations implemented measures to reduce heading in younger age groups and training settings.

While the risk increase in this study is slightly smaller than in the previous study from Scotland, it confirms that elite [soccer players] have a greater risk of neurogenerative disease later in life. As there are growing calls from within the sport for greater measures to protect brain health, this new study adds to the limited evidence base and can be used to guide decisions on how to manage these risks.

The authors caution that although 9% of soccer players and 6% of controls were diagnosed with neurodegenerative disease during their study, most participants were still alive at the end of data collection, so the lifetime risks of developing neurodegenerative disease for both groups are likely to be higher.

The risk of neurodegenerative disease was 1.5 times higher for outfield players than controls but was not significantly higher for goalkeepers compared to controls. Accordingly, in a direct comparison, outfield players had a risk of neurodegenerative disease 1.4 times higher than that of goalkeepers.

Soccer players had a risk of Alzheimer's disease and other dementias 1.6 times that of controls—with 8% (491 out of 6,007) of soccer players being diagnosed with the condition compared to 5% (2889 out of 56,168) of controls.

Part 1

Comment by Dr. Krishna Kumari Challa on March 18, 2023 at 12:17pm

New tool for organ repair: curvature of the environment

A ball, a saddle, or a flat plate. The curvature of biomaterials inhibits or stimulates bone cells to make new tissue. This is what TU Delft engineers show in research published in Nature Communications. This study of geometries could be an important step in research into repairing damaged tissues. In this video, Amir Zadspoor (professor of Biomaterials and Tissue Biomechanics) and Lidy Fratila-Apachitei (assistant professor of Biomaterials) explain exactly how this new tool for organ repair works.

Comment by Dr. Krishna Kumari Challa on March 18, 2023 at 11:46am

Casting light on counterfeit products through nano-optical technology

Each year, an estimated two trillion dollars is lost globally due to counterfeit products ranging from jewelry to medicine. As current security labels and product authentication methods are rapidly becoming obsolete or easy to hack, there is a rising urgency for more secure anti-counterfeiting labels.

A research team fabricated a 3D printed nano optical security label that provides 33100 possible combinations for heightened security in optical anti-counterfeiting. 

The research team achieved such a feat by exploiting higher dimensional structured light, i.e., colored Orbital Angular Momentum (OAM) beams, through the fabrication of 3D printed spiral phase plates. Importantly, these plates were miniaturized down to a diameter smaller than that of a strand of human hair and further integrated with structural color filters—spiky looking structures that allow specific colors of light through.

In their study, they included color, spatial position, and OAM of light (one degree of freedom of light) onto a small colored vortex beam (CVB) generator (25 μm). With only 10-by-10 CVB unit array to demonstrate, the optical security label they designed could open pathways for the next generation of optical anti-counterfeiting.
We see things clearly when we hold them up to the light. What this team has done is to learn how to use the natural light that surrounds us and extract tiny beams from it that carry information encoded in not just color, but also by how much we 'twist' its wavefront. This optical version of the combination lock that utilizes high-dimensional structured light provides us with a powerful platform for advanced anti-counterfeiting and information security.

Casting light on counterfeit products through nano-optical technology (2023, March 14)
retrieved 18 March 2023 from https://phys.org/news/2023-03-counterfeit-products-nano-opticaltech...

The video shows the optical security label or photonic tally, consisting of colored vortex beam array. The photonic tally turns into colorful dots when overlapped with each other. During this process, the color and OAM (orbital angular momentum) information is decoded. Credit: Singapore University of Technology and Design

Comment by Dr. Krishna Kumari Challa on March 17, 2023 at 7:26am

A new way to remove waste from the brain after hemorrhage

Intracerebral hemorrhage, and bleeding into the brain tissue, is a devastating neurological condition affecting millions of people annually. It has a high mortality rate, while survivors are affected by long-term neurological deficits. No medication has been found to support brain recovery following hemorrhage.

In an international collaboration, researchers investigated whether a protein called cerebral dopamine neurotrophic factor (CDNF) has potential as a treatment for brain hemorrhage.

Researchers suggest that cerebral dopamine neurotrophic factor, a protein being currently tested for Parkinson's disease treatment, also has therapeutic effects and enhances immune cell's response after brain hemorrhage.

The authors found that the administration of cerebral dopamine neurotrophic factor accelerates hemorrhagic lesion resolution, reduces brain swelling, and improves functional outcomes in an animal model of brain hemorrhage.

They found that found that cerebral dopamine neurotrophic factor acts on immune cells in the bleeding brain, by increasing anti-inflammatory mediators and suppressing the production of the pro-inflammatory cytokines that are responsible for cell signaling. This is a significant step towards the treatment of injuries caused by brain hemorrhage, for which we currently have no cure.

The administration of cerebral dopamine neurotrophic factor also resulted in the alleviation of cell stress in the area that surrounds the hematoma.

Finally, the researchers demonstrated that systemic administration of cerebral dopamine neurotrophic factor promotes scavenging by the brain's immune cells after brain hemorrhage and has beneficial effects in an animal model of brain hemorrhage. 

Kuan-Yin Tseng et al, Augmenting hematoma-scavenging capacity of innate immune cells by CDNF reduces brain injury and promotes functional recovery after intracerebral hemorrhage, Cell Death & Disease (2023). DOI: 10.1038/s41419-022-05520-2

Comment by Dr. Krishna Kumari Challa on March 17, 2023 at 7:20am

Deactivating mosquito sperm: A human bite back!

New  research makes it likely that proteins responsible for activating mosquito sperm can be shut down, preventing them from swimming to or fertilizing eggs.

The study could help control populations of Culex, the common house mosquito that transmits brain-swelling encephalitis and West Nile Virus.

During mating, mosquitoes couple tail to tail, and the males transfer sperm into the female reproductive tract. It can be stored there awhile, but it still has to get from point A to point B to complete fertilization. 

Key to completing that journey are the specialized proteins secreted during ejaculation that activate the sperm flagella, or 'tails,' that power their movement.

Without these proteins, the sperm cannot penetrate the eggs. They'll remain immotile, and will eventually just degrade.

The study, detailed in the journal PLOS ONE, details a full portrait of all the proteins in the insect's sperm, allowing researchers to find the specific ones that maintain the quality of the sperm while they're inactive, and that also activate them to swim.

To get this detailed information the researchers  worked with a team of graduate and undergraduate students who isolated as many as 200 male mosquitoes from a larger population. They then extracted enough sperm from the tiny reproductive tracts for mass spectrometry equipment to detect and identify the proteins.

Previously, the team determined that sperm need calcium upon entering a reproductive tract to power forward motion. They can now look in the completed protein profile they've created, find the calcium channel proteins, and design experiments to target these channels.

This kind of protein profiling offers a path toward controlling mosquitoes that is more environmentally friendly than other methods that can have unintended, toxic effects. 

This  work sets the foundation for a form of biological control, which most would agree is preferable.

The operative word is control, rather than eradicate. Even though immobilizing the sperm would be 100% effective for the treated mosquitoes, it is not possible or desirable to kill all mosquitoes. This technology would change the proportion of fertile to infertile males in a given mosquito population, rather than wiping them all out.

The team is hoping that information about sperm motility regulators in Culex will also apply to other species of mosquitoes. And other pests too! What we learn in one system, such as mosquitoes, can translate to others.

Catherine D. Thaler et al, Using the Culex pipiens sperm proteome to identify elements essential for mosquito reproduction, PLOS ONE (2023). DOI: 10.1371/journal.pone.0280013

Comment by Dr. Krishna Kumari Challa on March 17, 2023 at 7:10am

Although mRNA vaccines have dominated the U.S. response to the pandemic, the technology underlying those shots is expensive. The finicky, temperature-sensitive ingredients required for mRNA vaccines may be difficult to store in far-flung regions of the globe. To address the global need for a low-cost vaccine that can be produced locally, scientists have been developing alternatives, such as NDV-HXP-S.

The vaccine's initials, NDV-HXP-S, stand for Newcastle disease virus, HexaPro, and spike protein. Producing the vaccine involves a vector, which in this case is the Newcastle disease virus, an agent that infects birds. The vaccine is manufactured by way of egg-based technology, which has been used for decades to produce annual flu shots. The Newcastle viral vector is not used in the production of influenza vaccines.

The vector works exquisitely well in the NDV-HXP-S production process, ferrying vaccine components into embryonated chicken eggs. The result, in the case of the vaccine used in Thailand, is an inactivated vaccine, which is a viral particle displaying SARS-C0V-2's spike protein on its surface.

"NDV-HXP-S can be used as a live vaccine or as an inactivated vaccine

The team analyzed antibody responses after Thai volunteers were vaccinated in the phase 1 clinical study. Researchers studied serum samples from 210 Thai volunteers who received either a placebo or the inactivated NDV-HXP-S vaccine.

They compared antibodies from the Thai volunteers to those from 20 people who received the Pfizer mRNA vaccine in New York City. Antibodies elicited by NDV-HXP-S tended to target the receptor binding domain of the virus rather than the spike protein's S2 subunit, the researchers found.

"Neutralizing activity of sera from NDV-HXP-S vaccinees was comparable to that of [Pfizer] vaccinees, whereas spike protein binding activity of the NDV-HXP-S vaccinee samples was lower than that of sera obtained from mRNA vaccines," the researchers say. This led them to calculate ratios between binding and neutralizing antibody titers.

This work show that a vaccine candidate that can be produced locally in [low- and middle-income countries] at low-cost induces neutralizing antibody titers to SARS-CoV-2 comparable to those observed in cohorts having received mRNA-based COVID-19 vaccines.

Juan Manuel Carreño et al, An inactivated NDV-HXP-S COVID-19 vaccine elicits a higher proportion of neutralizing antibodies in humans than mRNA vaccination, Science Translational Medicine (2023). DOI: 10.1126/scitranslmed.abo2847

Part 2

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