Comment

Comment by Dr. Krishna Kumari Challa on April 8, 2023 at 11:18am

Study identifies two different regulatory T cell populations

A regulatory class of human T cells descends from two different origins, one that relates to autoimmunity and one that relates to protective immunity, according to a new study.

When it comes to autoimmunity, the present thinking has been that the only way to stop inflammation is to suppress the immune system broadly, making patients more susceptible to infection.

In teh present study, the researchers identified these two subpopulations of Tfr cells, they analyzed whether these two regulatory T cells express the surface protein CD38 differently. They found that iTfr cells express CD38, whereas nTfr cells do not. They were also able to catalog the precise location of these different subpopulations within the GCs, in addition to demonstrating their developmental path and ability so support B cell function.

"This study raises the question of whether we could selectively deplete iTfr cells through anti-CD38 treatments, while leaving nTfrs intact—using a silver bullet rather than a bomb to target specific T cells. A similar approach could also potentially be used in a therapeutic context to boost immunity in patients with weakened immune systems."

Carole Le Coz et al, Human T follicular helper clones seed the germinal center-resident regulatory pool, Science Immunology (2023). DOI: 10.1126/sciimmunol.ade8162. www.science.org/doi/10.1126/sciimmunol.ade8162

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Comment by Dr. Krishna Kumari Challa on April 8, 2023 at 9:36am

Yellow crazy ant males have two sets of DNA

A small international team of molecular and evolutionary scientists has discovered that male yellow crazy ants (also known as long-legged ants) have two sets of DNA throughout their bodies. In their paper published in the journal Science, the group describes the unique find and discusses possible reasons for it. 

Other scientists suggest in the same journal  that the unique genetic feature of the ants may explain why they are such a successful invasive species.

Prior research has shown that yellow crazy ants, which are native to Asia and West Africa, have the ability to adapt well to new environments, making them a successful invasive species.

Now it turns out that they may have an advantage that has not been seen before: Males have dual sets of DNA.

One of the most basic concepts of biological science is that multicellular organisms develop from a single-cell zygote into a creature with a unique genome. The only exceptions to this rule have been chimeras, which are generally considered accidents of nature. In this new effort, the research team found another exception—male yellow crazy ants with dual sets of DNA.

Prior research had shown anomalies in crazy yellow ant genetics, but until now, it was not clear what was behind apparent discrepancies between queens, males and worker ants. To clear up the mystery, the researchers conducted population genetic and phylogeographic studies of specimens collected from sites across Asia.

They discovered that male yellow crazy ants have two separate genetic lineages—no fusion between maternal and paternal nuclei occurs; thus, both remain active in all males of the species. The research team points out that their findings represent the first-ever discovery of obligate chimerism. They suggest that such chimerism may result from a conflict between competing genetic lineages. And Scientists  suggest that this unique genetic feature may help to prevent inbreeding, which could in turn help the ants survive in unfamiliar territory, explaining their success as an invasive species.

H. Darras et al, Obligate chimerism in male yellow crazy ants, Science (2023). DOI: 10.1126/science.adf0419

Daniel J. C. Kronauer, The unusual genetics of invasive ants, Science (2023). DOI: 10.1126/science.adh1664

Comment by Dr. Krishna Kumari Challa on April 7, 2023 at 12:43pm

Why chewing gum is harmful for the planet?

Globally, people chew roughly 100,000 tonnes of gum each year, but what happens once we’ve finished with it? Ancient civilisations chewed tree resins such as chicle, but by the 1950s this had been replaced by synthetic gums.

Alongside this gum base, modern chewing gum contains softeners such as vegetable oil, emulsifiers that reduce stickiness, fillers like talc to add bulk, plus flavourings, sweeteners, preservatives and colourings. Synthetic gums are generally not biodegradable, but in some cases, they can be recycled into new plastic products.

New, more sustainable chewing gum us alternative natural gums like tree sap or rubber.

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The future is bright for gold-based antibiotics

New research being presented at this year's European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) in Copenhagen, Denmark, (April 15-18) has identified several gold-based compounds with the potential to treat multidrug-resistant "superbugs."

Comment by Dr. Krishna Kumari Challa on April 7, 2023 at 9:58am

Not all itches are the same

Itch is a protective signal that animals use to prevent parasites from introducing potentially hazardous pathogens into the body. If a mosquito lands on a person's arm, they sense its presence on their skin and quickly scratch the spot to remove it. Itchiness due to something like a crawling insect is known as "mechanical" and is distinct from "chemical" itchiness generated by an irritant such as the mosquito's saliva if it were to bite the person's arm. While both scenarios cause the same response (scratching), recent research by  scientists has revealed that, in mice, a dedicated brain pathway drives the mechanical sensation and is distinct from the neural pathway that encodes the chemical sensation.

Their findings, published in Neuron on April 5, 2023, show that a small population of neurons relay mechanical itch information from the spinal cord to the brain and identify the neuropeptide signals that regulate both itch types.

"This study provides fundamental insights into how these two forms of itch are encoded by the brain and opens up new avenues for therapeutic interventions for patients that suffer from a range of chronic itch conditions, including ectopic dermatitis and psoriasis.

Researchers used genetic approaches combined with wearable miniaturized microscopes that allowed the researchers to see itch-induced activity in single neurons of mice. The scientists discovered that by removing an inhibitory pathway involved in itch, they could activate a mechanical itch. By observing subsequent activity and changes occurring in the brainstem, they saw that different cells were responding to either mechanical or chemical itch. This allowed them to classify distinctions between a chemical itch pathway and a mechanical itch pathway and clearly identify the molecules important for regulating them.

They found that if you sensitize one pathway, you can stimulate a pathological itch state, and vice versa. This indicates that these two pathways act together to drive chronic itch.

Next, the scientists plan to examine where in the brain these pathways converge, and then explore the parts of the brain that receive signals that determine the decision of whether to scratch an itch. They also want to better understand how the spinal cord and brainstem differentiate between pain and itch.

These findings should help leverage the development of new therapies for treating the itch.

 Xiangyu Ren et al, Identification of an essential spinoparabrachial pathway for mechanical itch, Neuron (2023). DOI: 10.1016/j.neuron.2023.03.013

Comment by Dr. Krishna Kumari Challa on April 7, 2023 at 9:35am

Light as a messenger offers a broad scope for future potential applications. As photons can be used in other types of cells and several animal species, it has wide-ranging implications for both basic research and clinical applications in neuroscience.

Using light to control and monitor neuronal activity can help researchers better understand the underlying mechanisms of brain function and complex behaviors, and how different brain regions communicate with each other, providing new ways of imaging and mapping brain activity with higher spatial and temporal resolution. It could also help researchers develop new treatments, and for example, be useful for repairing damaged brain connections without invasive surgeries.

However, there are still some limitations to the widespread use of the technology, and further improvements in the engineering of the bioluminescent enzymes and the ion channels or in the targeting of molecules would allow controlling optically the neuronal function, non-invasively and with higher specificity and precision.

Michael Krieg, Neural engineering with photons as synaptic transmitters, Nature Methods (2023). DOI: 10.1038/s41592-023-01836-9. www.nature.com/articles/s41592-023-01836-9

Part 2

Comment by Dr. Krishna Kumari Challa on April 7, 2023 at 9:35am

Using photons as neurotransmitters to control the activity of neurons

Our brains are made of billions of neurons, which are connected forming complex networks. They communicate between themselves by sending electrical signals, known as action potentials, and chemical signals, known as neurotransmitters, in a process called synaptic transmission.

Chemical neurotransmitters are released from one neuron, diffuse to the others and arrive at the targeted cells, generating a signal which excites, inhibits or modulates the cellular activity. The timing and strength of these signals are crucial for the brain to process and interpret sensory information, make decisions, and generate behaviour.

Controlling the connections between the neurons would allow us to understand and treat better neurological disorders, rewire or repair the malfunctions of the neural circuits after being damaged, improve our learning capabilities or expand our set of behaviours.

There are several approaches to controlling neuronal activity. One possible method is using drugs, that alter the levels of the chemical neurotransmitters in the brain and affect the activity of neurons. Another approach is to use electrical stimulation applied to specific brain regions to activate or inhibit the neurons. A third possibility is using light to control neural activity.

Using light to manipulate neuronal activity is a relatively new technique that has been explored in the past. It involves genetically modifying neurons to express light-sensitive proteins, ion channels, pumps or specific enzymes in the target cells. This technique allows researchers to precisely control the activity of concrete populations of neurons with higher precision.

However, light needs to be delivered very close to the neurons to achieve enough resolution at the level of the synapsis, as light scatters in the brain tissue. Thus, it is often invasive, requiring external interventions. 

To overcome these challenges, a team of ICFO researchers presents in Nature Methods a system that uses photons instead of chemical neurotransmitters as a strategy to control neuronal activity.

Part 1

Comment by Dr. Krishna Kumari Challa on April 6, 2023 at 1:36pm

Strains of S. aureus that are resistant to methicillin and other antibiotics are called MRSA, and while hospitals are making some ground in curbing MRSA infections, other drug-resistant superbugs are quick to take its place.

So, in this study, researchers experimented with the new class of antibacterial agent called endolysins.

Endolysins are enzymes that are naturally produced by bacteriophages, viruses that infect bacteria. After infection, they slice up molecules called peptidoglycans that form mesh-like scaffolds in the bacteria cell wall, destroying the bacteria from the inside.

Each bacterial species has unique peptidoglycans, which the right endolysin could selectively target. One endolysin, XZ.700, was tested in this study, on skin samples collected from people with healthy skin, and those with CTCL.

The great thing about this enzyme is that it has been designed to penetrate the wall of Staphylococcus aureus. This enables it to target and kill the harmful staphylococcus and leave harmless skin bacteria unharmed.

In lab experiments, endolysin XZ.700 killed off strains of S. aureus that had been isolated from CTCL patients, and blocked its tumor-promoting effects on lab-grown malignant T cells.

Endolysin treatment also "profoundly" stopped S. aureus from colonizing samples of healthy skin and biopsies of lesioned skin from people with CTCL. It also sloughed off S. aureus colonies that had already settled on biopsied skin.

 Lab tests have showed that endolysins do not just eradicate Staphylococcus aureus" from skin samples,  but that they "also inhibit their ability to promote cancer growth."

https://www.jidonline.org/article/S0022-202X(23)00175-6/fulltext

Comment by Dr. Krishna Kumari Challa on April 6, 2023 at 1:33pm

Scientists Find Antibiotic-Free Way to Treat Drug-Resistant Infections

Scientists have found an antibiotic-free way of treating 'golden staph' skin infections that are the scourge of some cancer patients, and a threat to hospital-goers everywhere.

The lab study from researchers  utilized an artificial version of an enzyme that's naturally produced by bacteriophages (viruses that infect bacteria), and used it to eradicate Staphylococcus aureus, or golden staph, in biopsy samples from people with skin lymphoma.

To people who are severely ill with skin lymphoma, staphylococci can be a huge, sometimes insoluble problem, as many are infected with a type of Staphylococcus aureus that is resistant to antibiotics. 

S. aureus is a common inhabitant of our skin and nasal tract, and generally harmless. But it is an opportunistic pathogen: When immunity is lowered, it can cause all manner of infections, from minor skin infections such as boils and abscesses, right through to life-threatening illnesses such as pneumonia and sepsis.

In a hospital setting, drug-resistant strains of the bacteria are a grave and growing problem. S. aureus can find its way into the bloodstream during surgery or via medical devices such as catheters, slipping past the body's first line of defense: the skin and mucosal barriers (snot).

People with weakened immune systems who visit hospitals for regular treatments such as chemotherapy are also at risk of picking up nasty 'superbugs' that have become resistant to mainstay antibiotics.

In particular, people with skin lymphoma are highly susceptible to bacterial infections. Called cutaneous T-cell lymphoma, CTCL is a rare form of non-Hodgkin lymphoma that starts with cancerous T cells migrating to the skin. There, these rogue immune cells cause rashes and lesions before spreading to other parts of the body.

S. aureus expels substances called enterotoxins which are thought to fuel the progression of CTCL, because when patients with CTCL finish a round of antibiotics, S. aureus can quickly appear in skin lesions and their cancer symptoms can worsen.

Part 1

Comment by Dr. Krishna Kumari Challa on April 6, 2023 at 12:42pm

Study finds evidence of no common blood microbes in healthy humans

There is no stable microbial community residing in the bloodstream of healthy humans, according to a new study.

The new Nature Microbiology paper makes an important confirmation as blood donations are a crucial part of medical practice. Understanding what types of microbes may be found in blood may allow the development of better microbial tests in blood donations, which would minimize the risk of transfusion-related infections.

Human blood is generally considered sterile. While sometimes microorganisms will enter the bloodstream such as via a wound or after tooth-brushing, mostly this is quickly resolved by the immune system.

But in recent decades this paradigm has been challenged by speculation that the blood could host a community of microbes. This new study has confirmed this is not the case, as most people's blood does not contain microbes, and the microbial species found in some people's blood varied substantially between individuals.

In these investigations, after accounting for contamination that is rife in microbiome investigations, the team found that microbes were only rarely and sporadically detected in blood, instead of existing as stable communities. Among their sample of 9,770 people, 84% of people did not have any microbes in their blood sample, and less than 5% of people shared the same species.

The scientists also found evidence that some bacteria in the blood of healthy individuals might be replicating and most of these bacteria are typically found in the human gut, oral, or skin microbiomes. Their findings suggest that microbes do occasionally enter the bloodstream from other body sites without causing disease, but there is no core set of species colonizing the blood of healthy individuals.

The findings also provide a useful resource for the types of microbes that one might expect to occasionally see in the blood of healthy humans. Characterizing the range of microbial species present in the blood of healthy individuals forms a crucial baseline for comparison with that of diseased individuals, shedding light on how blood microbial profiles may correlate with health status.

Cedric C. S. Tan et al, No evidence for a common blood microbiome based on a population study of 9,770 healthy humans, Nature Microbiology (2023). DOI: 10.1038/s41564-023-01350-w

No microbial community in the blood of healthy individuals, Nature Microbiology (2023). DOI: 10.1038/s41564-023-01364-4

Comment by Dr. Krishna Kumari Challa on April 6, 2023 at 12:31pm

Meanwhile, the abundance of the amino acid glycine was found to be lower in A0022 compared to C0008, while the abundance of β-Alanine showed the opposite trend. Accordingly, the ratio of β-Alanine to glycine was higher for A0022 than for C0008. This ratio was shown previously to be indicative of the extent of aqueous alteration operating on planetesimals. Accordingly, it was hypothesized that some reaction related to higher levels of aqueous alteration in A0022 may explain the high abundance of DMG in this particle, compared to C0008.

As such, the mineral phases were examined to see if any additional evidence for what reaction may be causing the different amino acids abundances between the Ryugu particles. It was found that the abundance of secondary minerals (formed after aqueous alteration), including carbonate, magnetite and Fe-sulfides, was higher in A0022 than in C0008.

In particular, the high abundance of carbonate pointed towards a larger quantity of CO or CO₂ within the region of the planetesimal where A0022 had been altered, compared to C0008. In conjunction with the evidence for more intense aqueous alteration from the β-Alanine to glycine ratio, this indicated that more ice in general may have been present in the precursor of A0022 than in C0008.

One way to commercially produce DMG, an important nutrient for humans, is the through the Eschweiler–Clarke reaction. This reaction requires the interaction of glycine with formic acid and formaldehyde in water and also produces CO₂. Glycine, formaldehyde and formic acid are all found in comets and so it is expected that they would be present in the planetesimal precursors of asteroids.

Therefore, if the Eschweiler–Clarke reaction occurred during aqueous alteration within the precursor of A0022, then it could explain the high level of DMG and lower abundance of glycine in this particle, compared to C0008. Additionally, the CO₂ produced could have further contributed to the formation of carbonates in A0022.

Overall, the findings of the study indicate that slight differences in the conditions present during aqueous alteration on planetesimals can have big effects on the end abundances of amino acids. Some amino acids can be destroyed and others created and this in turn will affect the availability of amino acids at the origin of life on Earth.

Christian Potiszil et al, Insights into the formation and evolution of extraterrestrial amino acids from the asteroid Ryugu, Nature Communications (2023). DOI: 10.1038/s41467-023-37107-6

Part 3

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