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Comment by Dr. Krishna Kumari Challa on October 30, 2024 at 12:17pm

Researchers identify key metabolites impacting lifespan in flies and humans

Discoveries that impact lifespan and healthspan in fruit flies are usually tested in mice before being considered potentially relevant in humans, a process that is expensive and time-intensive. A pioneering approach taken by researchers leapfrogs over that standard methodology.

Utilizing cutting-edge machine learning and systems biology, researchers have analyzed and correlated huge data sets from flies and humans to identify key metabolites that impact lifespan in both species. Results published in Nature Communications suggest that one of the metabolites, threonine, may hold promise as a potential therapeutic for aging interventions.

Threonine has been shown to protect against diabetes in mice. The essential amino acid plays an important role in collagen and elastin production and is also involved in blood clotting, fat metabolism and immune function.

In flies, threonine extended lifespan in a strain-and-sex-specific manner. Individuals with higher levels of threonine-related metabolites had longer, healthier lives.

Scientists are not saying that threonine is going to work in all conditions. This  research shows it works in subsets of both flies and people. However, this is not a magic bullet. 

The results also include findings that were not so positive for both species. Orotate, which is relatively understudied and has been linked with fat metabolism, was negatively associated with aging. In flies, orotate counteracted the positive impact of dietary restriction across every strain of the animals. In humans, orotate was linked to a shorter lifespan.

Tyler A. U. Hilsabeck et al, Systems biology approaches identify metabolic signatures of dietary lifespan and healthspan across species, Nature Communications (2024). DOI: 10.1038/s41467-024-52909-y

Comment by Dr. Krishna Kumari Challa on October 30, 2024 at 11:54am

The study delves into the methodical tracking of 139 medical conditions associated with both olfactory loss and heightened inflammation, uncovering insights into a shared pathway linking these factors. Olfactory loss, which often precedes conditions such as Alzheimer's and Parkinson's diseases, may serve as an early indicator of disease onset, allowing for more proactive therapeutic approaches.
It was difficult to track down the studies for so many medical conditions, say the scientists, reflecting on the complexity of linking olfactory loss to such a wide array of disorders. The challenge, they emphasize, underscores the importance of these findings in framing olfactory health as integral to overall well-being.
By showing how olfactory enrichment can mitigate inflammation, this research has laid a foundation for future studies aiming to explore the therapeutic use of scent to address a broader range of medical conditions.
The researchers are now working on a device to deliver olfactory therapy, which could hold promise as a novel, non-invasive way to improve health outcomes.

Michael Leon et al, Inflammation and olfactory loss are associated with at least 139 medical conditions, Frontiers in Molecular Neuroscience (2024). DOI: 10.3389/fnmol.2024.1455418

Part 2

Comment by Dr. Krishna Kumari Challa on October 30, 2024 at 11:51am

Smell loss is linked to more than 100 diseases in new study

Researchers reveal a powerful link between olfactory loss and inflammation in a staggering 139 medical conditions. 

This research  emphasizes a little-known but potentially life-altering connection: the role our sense of smell plays in maintaining our physical and mental health.

Olfactory dysfunction, often dismissed as a minor inconvenience, may actually be an early sign of various neurological and bodily diseases, as indicated by this research.

The data are particularly interesting because scientists had previously found that olfactory enrichment can improve the memory of older adults by 226%. Scientists  now know that pleasant scents can decrease inflammation, potentially pointing to the mechanism by which such scents can improve brain health.

This finding, they think, could hold key implications for mitigating symptoms and possibly even reducing the onset of certain diseases through therapeutic olfactory stimulation.

Part 1

Comment by Dr. Krishna Kumari Challa on October 30, 2024 at 11:40am

Less than 7 mm in length, this Atlantic Rainforest flea toad is the second-smallest vertebrate described in the world

Flea toads, as some species in the genus Brachycephalus are known, are less than 1 cm long in adulthood. Their size is far smaller than a fingernail.

The name of a new species, B. dacnis, pays tribute to Project Dacnis, a conservation, research and education NGO that maintains private areas of the Atlantic Rainforest, including the one where the animal was found, in Ubatuba, on the coast of Brazil's São Paulo state.

There are small toads with all the characteristics of large toads except for their size. This genus is different. During its evolution, it underwent what  biologists call miniaturization, which involves loss, reduction and/or fusion of bones, as well as fewer digits and absence of other parts of its anatomy.

The researchers' attention was drawn to the newly described species, B. dacnis, by its vocalizations. It has the same morphology as another species, B. hermogenesi. Both have yellowish-brown skin, live in leaf litter, do not have tadpoles but emerge from their eggs as fully formed miniatures of the adult morphology, and occur in the same region. Their calls are different, however.

DNA sequencing confirmed that B. dacnis was indeed a new species.

In their description of the new species, besides the requisite anatomical traits, the researchers included information about the skeleton and internal organs, as well as molecular data and details of its vocalizations. Descriptions of new species must include these details in order to distinguish them from others more precisely, given that many are cryptic and cannot be differentiated by external anatomy only.

 Luís Felipe Toledo et al, Among the world's smallest vertebrates: a new miniaturized flea-toad (Brachycephalidae) from the Atlantic rainforest, PeerJ (2024). DOI: 10.7717/peerj.18265

Comment by Dr. Krishna Kumari Challa on October 30, 2024 at 11:34am

But PRC1 doesn't act alone. Its activity is tightly controlled to ensure that microtubules assemble at the right time and place. The protein is controlled through a process called phosphorylation, where enzymes add small chemical tags to specific regions on its surface. These molecular tags can turn PRC1's activity up or down.
Scientists now discovered that manipulating the phosphorylation state of PRC1 can induce large-scale transitions between different states of cytoskeleton organization that are needed for cell division. The changes take only a few minutes to complete.
The researchers made this discovery by developing a new laboratory system where they can precisely control and even reverse the transitions of the cytoskeletal structures associated with different stages of cell division outside of a living system. The new technology can help researchers study the fundamental mechanisms governing cell division with greater control and detail than previously possible, and in real time.
The new system can eventually shed light on potential therapeutic strategies for conditions where cell division goes wrong, like cancer. However, for the scientists who discovered the process, the implications of the study are how it inspires a sense of wonder at the sophistication of the natural world.
Cells are incredibly small, yet within them exists a highly organized and very complex system that operates with great precision.

Nature Communications (2024). DOI: 10.1038/s41467-024-53500-1

Part 2

Comment by Dr. Krishna Kumari Challa on October 30, 2024 at 11:30am

Scientists create a molecular switch that can control cell division on demand outside of a living system

A living cell is a bustling metropolis, with countless molecules and proteins navigating crowded spaces in every direction. Cell division is a grand event which completely transforms the landscape. The cell starts behaving like the host of an international competition, reconfiguring entire streets, relocating buildings and rerouting its transportation systems.

For decades, researchers have been captivated by the cell's ability to organize such a dramatic transformation. Central to the process is the microtubule cytoskeleton, a network of fibers which provides structural support and facilitates movement within the cell, ensuring that chromosomes are correctly segregated. Errors in cell division can lead to a wide array of diseases and disorders, including cancer or genetic disorders.

Yet despite its critical importance, the exact mechanisms governing how cells reorganize their insides during cell division have not been studied well. How does a cell know when and how to rearrange its internal scaffolding? What are the molecular signals governing these changes? Who are the key players conducting it all? According to new research, some of the changes come down to a surprisingly simple and elegant system—the flip of a molecular switch. The findings are published in Nature Communications .
At the heart of the discovery is the protein PRC1. During cell division, PRC1 plays a key role in organizing cell division. It crosslinks microtubules, helping to form a structure in the crucial region where microtubules overlap and chromosomes are separated.

Part 1

Comment by Dr. Krishna Kumari Challa on October 30, 2024 at 11:22am

The findings have significant implications for the fight against bacterial and fungal infections that pose an increasing risk to human health, a problem that is exacerbated by the development of antimicrobial resistance and the emergence of multidrug-resistant strains. The World Health Organization has published lists of priority pathogens that pose the greatest risk, emphasizing the need for new antimicrobial strategies.

Addressing antimicrobial resistance will require a multifaceted strategy, including the discovery and characterization of new antimicrobial targets, along with assessing their potential for therapeutic use in innovative (co-)treatment approaches.

The authors of the study suggest that targeting the Zn-Macro pathway could reduce the virulence of major human pathogens, including Staphylococcus aureus and Streptococcus pyogenes. These pathogens rely on the crosstalk between lipoic acid metabolism and ADP-ribosylation signaling for their defense mechanisms. Disrupting this pathway could enhance the effectiveness of existing treatments and provide new therapeutic options.
The study's findings represent a significant step forward in the fight against antimicrobial resistance and highlight the potential of Zn-Macros as therapeutic targets.

Antonio Ariza et al, Evolutionary and molecular basis of ADP-ribosylation reversal by zinc-dependent macrodomains, Journal of Biological Chemistry (2024). DOI: 10.1016/j.jbc.2024.107770

Part 2

Comment by Dr. Krishna Kumari Challa on October 30, 2024 at 11:21am

Scientists uncover key mechanism in pathogen defense, paving way for new antimicrobial strategies

Researchers have made a significant breakthrough in understanding how certain pathogens defend themselves against the host's immune system.

This  new work focuses on the role of a group of enzymes known as zinc-dependent macrodomains (Zn-Macros) in reversing ADP-ribosylation, a vital cellular process.

This discovery could lead to innovative treatments to combat antimicrobial resistance, a growing global health threat. The work is published in the Journal of Biological Chemistry.

ADP-ribosylation is a reversible modification of proteins and DNA that regulates important cellular responses to stress. While this signaling mechanism is well-studied in higher eukaryotes, where it regulates responses to DNA damage, reactive oxygen species and infection, the importance of its role in microorganisms is also becoming increasingly evident, which includes the regulation of the host immune response, microbial immune evasion and adaptation to specific hosts.

The research team used a combination of phylogenetic, biochemical, and structural approaches to investigate the function of Zn-Macros. These enzymes are found in some pathogenic microbes and are essential for removing ADP-ribosyl modifications, thereby helping the pathogens survive oxidative stress.

The study revealed that the catalytic activity of Zn-Macros is strictly dependent on a zinc ion within the active site of these enzymes. The researchers also identified structural features that contribute to substrate selectivity within different types of Zn-Macro enzymes, which may be exploited for the development of future therapies.

Part 1

Comment by Dr. Krishna Kumari Challa on October 30, 2024 at 8:54am

In total, the researchers identified ninety (only 90? Come on, we ourselves 're involved in atleast 10, these researchers don't know about the incidents in India, then) incidents between 2010 and 2023. The team then conducted a systematic content analysis of the articles to categorize the problems mentioned: half of the traffic disruptions reported were traffic jams, while a third were caused by through traffic of heavy vehicles, especially on roads that were not designed for such volumes of traffic.

Reports of traffic rule violations and disturbances to residents were less common. The latter were caused, for example, by long lines of cars preventing drivers from being able to back out of their private parking spaces.

The safety hazards mentioned in the newspaper reports concerned accidents in a third of cases, but also damage to road surfaces and pollution.

Through studies such as this one, the team not only wants to categorize the problems perceived by society, but also develop solutions. The evaluation showed that in most cases, the aim is only to make adjustments at the local level.

The research team also has another suggestion that does not completely delegate responsibility to technology: the system could provide users with additional information about the suggested routes—and then let them choose for themselves.
It would be nice if people could voluntarily choose to be more considerate by providing the full information, they say.

Eve Schade et al, Traffic jam by GPS: A systematic analysis of the negative social externalities of large-scale navigation technologies, PLOS ONE (2024). DOI: 10.1371/journal.pone.0308260

Part 2

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Comment by Dr. Krishna Kumari Challa on October 30, 2024 at 8:48am

GPS systems often mislead drivers

We know this for sure!

Drivers blindly follow GPS instructions instead of paying attention to signs. Blindly following GPS navigation can lead to difficult situations on the road. A research team has analyzed such incidents and is in favour of delegating more personal responsibility to drivers.

As useful as GPS-controlled navigation systems are in everyday life, they often lead people astray and trigger outrage. Sometimes they even guide cars and lorries onto very challenging roads, unnecessarily endangering everyone involved.

(We know how the GPS took vehicles into water bodies, strange areas and put people into dangerous situations)

This is a technology that is used by more than a billion people worldwide. That's why it's important to understand the social implications.

Since there is no publicly available documentation, the researchers used a different method: they systematically combed the LexisNexis news database for newspaper articles and internet posts about incidents in which navigation systems caused chaos and problems. To avoid complications due to translations, they only looked at English texts, which unsurprisingly reported mostly on events in English-speaking countries. But as the examples above illustrate, such incidents also occur in other areas around the world. Yeah, in India for sure. 

In societies where navigation apps are increasingly used, we can expect to see more of these types of situations in the future.

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