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Comment by Dr. Krishna Kumari Challa on August 13, 2024 at 9:19am

Unknown mechanism essential for bacterial cell division

How does matter, lifeless by definition, self-organize and make us alive? One of the hallmarks of life, self-organization, is the spontaneous formation and breakdown of biological active matter. However, while molecules constantly fall in and out of life, one may ask how they "know" where, when, and how to assemble, and when to stop and fall apart.

Researchers tried to address  these questions in the context of bacterial cell division. They developed a computational model for the assembly of a protein called FtsZ, an example of active matter. 

A previously unknown mechanism of active matter self-organization essential for bacterial cell division follows the motto "dying to align": Misaligned filaments "die" spontaneously to form a ring structure at the center of the dividing cell. The study, led by the Šarić group at the Institute of Science and Technology Austria (ISTA), was published in Nature Physics. The work could find applications in developing synthetic self-healing materials.

During cell division, FtsZ self-assembles into a ring structure at the center of the dividing bacterial cell. This FtsZ ring–called the bacterial division ring–was shown to help form a new "wall" that separates the daughter cells.

 The researchers' computational work demonstrates how misaligned FtsZ filaments react when they hit an obstacle.

By "dying" and re-assembling, they favour the formation of the bacterial division ring, a well-aligned filamentous structure. These findings could have applications in the development of synthetic self-healing materials.

FtsZ forms protein filaments that self-assemble by growing and shrinking in a continuous turnover. This process, called "treadmilling," is the constant addition and removal of subunits at opposite filament ends. Several proteins have been shown to treadmill in multiple life forms—such as bacteria, animals, or plants.

Scientists have previously thought of treadmilling as a form of self-propulsion and modeled it as filaments that move forward. However, such models fail to capture the constant turnover of subunits and overestimate the forces generated by the filaments' assembly. 

Everything in our cells is in constant turnover. Thus, we need to start thinking of biological active matter from the prism of molecular turnover and in a way that adapts to the outside environment.

What they found was striking. In contrast to self-propelled assemblies that push the surrounding molecules and create a "bump" felt at long molecular distances, they saw that misaligned FtsZ filaments started "dying" when they hit an obstacle.

"Active matter made up of mortal filaments does not take misalignment lightly. When a filament grows and collides with obstacles, it dissolves and dies.  Treadmilling assemblies lead to local healing of the active material. When misaligned filaments die, they contribute to a better overall assembly.

By incorporating the cell geometry and filament curvature into their model, the researchers showed how the death of misaligned FtsZ filaments helped form the bacterial division ring.

Part 1

Comment by Dr. Krishna Kumari Challa on August 11, 2024 at 9:53am

Serotonin changes how people learn and respond to negative information

It is easy to advice, 'be positive, be happy, don’t respond to bad criticism, be in control of your emotions'. But can people really do this in real life situations without the help of their biochemistry?

And without a tough training to improve their behaviour?

NO!

Increasing serotonin can change how people react and learn from negative information, as well as improving how they respond to it, according to a new study published in the journal Nature Communications.

The study by scientists found people with increased serotonin levels had reduced sensitivity to punishing outcomes (for example, losing money in a game) without significantly affecting sensitivity to rewarding ones (winning money).

The researchers found that increasing serotonin made individuals better able to control their behaviour, particularly when exposed to negative information. The study also showed that elevated serotonin levels benefited different types of memory.

These findings shed new light on how serotonin shapes human behaviour, particularly in negative environments.

This provides us with some exciting new information about the role of serotonin in humans. It shows that serotonin, which has been implicated in depression and in the effects of antidepressants, has more of a role in processing negative things, rather than boosting  good responses.

These findings underscore the central role that serotonin plays in effortful cognitive processes, such as our ability to put the brakes on unwanted behaviors. This study helps to further understand why drugs that change serotonin levels are effective treatments for many mental illnesses, including depression, anxiety and obsessive-compulsive disorder. 

Michael J. Colwell et al, Direct serotonin release in humans shapes aversive learning and inhibition, Nature Communications (2024). DOI: 10.1038/s41467-024-50394-x

Comment by Dr. Krishna Kumari Challa on August 9, 2024 at 12:25pm

A crustacean positively too beautiful to eat

Rare "cotton candy" lobster found in New Hampshire

This lobster's shell was a swirling mass of blue, purple, and pink pigments, which looked like glazed, opalescent pottery when wet.

Comment by Dr. Krishna Kumari Challa on August 9, 2024 at 11:40am

The fat-gut-cancer link
A study in mice and people suggests why there is a link between obesity and some cancers: a high-fat diet increases the number of Desulfovibrio bacteria in the gut. These release leucine, an amino acid, which encourages the proliferation of a kind of cell that suppresses the immune system. With a suppressed immune system, breast cancer tumour growth increases. 

https://www.pnas.org/doi/10.1073/pnas.2306776121?utm_source=Live+Au...

Comment by Dr. Krishna Kumari Challa on August 9, 2024 at 10:23am

This research is the first empirical demonstration of the benefits of genetic diversity for collective judgments.
The findings suggest that genetic diversity enhances the collective cognitive abilities of groups, providing a deeper understanding of how diverse crowds can achieve wiser outcomes. By uniquely highlighting the genetic aspect, this research adds a new dimension to the 'wisdom of crowds' phenomenon.
These findings highlight the significant impact genetic diversity can have on collective decision-making, underscoring the importance of embracing diversity in all its forms to enhance our cognitive abilities and tackle complex challenges more effectively.

Meir Barneron et al, Genetically-diverse crowds are wiser, Personality and Individual Differences (2024). DOI: 10.1016/j.paid.2024.112823

Part 2

Comment by Dr. Krishna Kumari Challa on August 9, 2024 at 10:22am

Research demonstrates genetically diverse crowds are wiser

A new study by researchers reveals that genetically diverse groups make more accurate collective judgments compared to genetically homogeneous groups.

The research, published in Personality and Individual Differences, provides new insights into the origins of the 'wisdom of crowds' phenomenon, emphasizing the role of genetic diversity in enhancing collective intelligence.

Past studies have suggested that combining individual judgments can improve accuracy, especially when individuals differ in background, education, and demography.

The study involved 602 identical and fraternal twins, who participated by making numerical judgments in pairs. These pairs consisted either of co-twins (related pairs) or non-related individuals (unrelated pairs).

The results of this study revealed that judgments made by unrelated (i.e., heterogenous) pairs were more accurate than those made by related (i.e., homogeneous) pairs. Theoretically, however, this finding could emerge either from environmental or genetic factors.

In order to distinguish between environmental and genetic factors, the study compared the performance of related and unrelated pairs, separately among identical and fraternal twins.
This comparison is relevant as genetic influences make identical twins more similar to one another compared to fraternal twins, because the former share virtually 100% of their genetic variance, whereas fraternal twins share, on average, 50% of the genetic variance.


The findings revealed that the superior performance of unrelated versus related pairs was evident for the identical twins. This underscores the impact of genetic relatedness on collective judgment.

Comment by Dr. Krishna Kumari Challa on August 9, 2024 at 10:12am

Scientists unravel how the BCG vaccine leads to the destruction of bladder cancer cells

Using zebrafish "avatars," an animal model developed by the Cancer Development and Innate Immune Evasion lab, researchers studied the initial steps of the Bacillus Calmette-Guérin (BCG) vaccine's action on bladder cancer cells.

Their results, which are published in the journal Disease Models and Mechanisms, show that macrophages—the first line of immune cells activated after an infection—literally induce the cancer cells to commit suicide and then rapidly eat away the dead cancer cells.

The BCG vaccine was first used against TB in the 1920's and then started to be used as the first cancer immunotherapy around 1976. But decades before that, in the 1890's, William Coley, a surgeon working at the New York Hospital (now Weill Cornell Medical Center) had already tested a mix of different bacteria, coined "Coley's toxins," as a cancer immunotherapy.

Coley had noticed that several virtually hopeless cancer patients at the hospital went into seemingly "miraculous" remissions from their cancer when they caught a bacterial infection following the surgery performed to remove their tumors (sterile conditions for surgical procedures were then less than optimal). His idea was that such recoveries, far from being miraculous, were in fact caused by an immune response of the patients to the infection.

Coley started trying to induce bacterial infections in a number of sarcoma patients and was able to reproduce a few cancer remissions. At the time, though, his method was far from being proven and safe—and meanwhile, other treatment methods were developed, such as radiotherapy—so his research was not pursued. But in recent years, the field of immunotherapy has gained enormous momentum, bringing new and more scientifically robust ways of boosting the immune system to fight cancer. 

BCG immunotherapy is still rather empirically used. However, since it works for many people, it has become a gold standard treatment. Surprisingly, it is a very effective immunotherapy, even when compared to so many fancy immunotherapies that are being developed."

The treatment consists of instilling the BCG vaccine directly into the bladder. When the treatment works, the 15-year survival rate for patients with so-called "non-muscle-invasive" (early-stage) bladder cancer is 60% to 70%. However, in 30% to 50% of the cases, bladder tumors are unresponsive to BCG treatment. In these cases, the whole bladder has to be removed.

Macrophages directly kill bladder cancer cells through TNF signaling in an early response to BCG therapy, Disease Models & Mechanisms (2024). DOI: 10.1242/dmm.050693

Comment by Dr. Krishna Kumari Challa on August 9, 2024 at 9:25am

How intermittent fasting regulates aging through autophagy

Research published recently in Nature Cell Biology, sheds light on the mechanism through which spermidine regulates autophagy, a process that ensures the recycling of components within the cell, to promote the anti-aging effects of intermittent fasting.

The work demonstrated that intermittent fasting increases the levels of spermidine, a chemical compound (natural polyamine), that enhances the resilience and survival of cells and organisms, through the activation of autophagy.  

Autophagy is a process of cellular recycling, the destruction of non-functional/unnecessary components and organelles of the cell. Autophagy defects have been linked to aging, as well as, with the emergence of age-related disorders, such as diabetes, cardiovascular diseases, cancer and neurodegenerative diseases.

Dietary habits, such as low or high-fat diet, over-nutrition, or fasting can influence the development of these chronic diseases, the prevalence of which is expected to increase considerably in the coming years. Dietary interventions, such as caloric restriction and intermittent fasting, can slow down aging and promote longevity.

A key element of these interventions is the maintenance of cellular homeostasis through the induction of autophagy. Direct administration of spermidine is an alternative strategy for inducing autophagy and extending lifespan. However, the role of spermidine in the regulation of autophagy and aging upon intermittent fasting remains unclear.

Using a range of experimental models, ranging from the nematode (Caenorhabditis elegans), yeast (Saccharomyces cerevisiae), fruit fly (Drosophila melanogaster), mouse (Mus musculus), and human cell lines, the research teams of this study have shown that intermittent fasting increases the cellular levels of spermidine, which in turn induces autophagy, resulting in the prolongation of lifespan in these organisms.

Conversely, inhibition of spermidine synthesis, using appropriate inhibitors, counteracts the benefits of autophagy on lifespan through intermittent fasting.

The results of the research highlight the critical role of spermidine in regulating autophagy under intermittent fasting, thereby improving lifespan expectancy across all model organisms studied. The fact that the regulation of autophagy through spermidine and intermittent fasting is an evolutionarily conserved process, underscores its central role in monitoring and maintaining cellular homeostasis across different organisms.

Sebastian J. Hofer et al, Spermidine is essential for fasting-mediated autophagy and longevity, Nature Cell Biology (2024). DOI: 10.1038/s41556-024-01468-x

Comment by Dr. Krishna Kumari Challa on August 9, 2024 at 8:15am

Study observes that similarities between physical and biological systems might be greater than we think

A crowd or a flock of birds have different characteristics from those of atoms in a material, but when it comes to collective movement, the differences matter less than we might think. We can try to predict the behavior of humans, birds, or cells based on the same principles we use for particles.

This is the finding of a study published in the Journal of Statistical Mechanics: Theory and Experiment, JSTAT, conducted by an international team of researchers.  The study, based on the physics of materials, simulated the conditions that cause a sudden shift from a disordered state to a coordinated one in "self-propelled agents" (like biological ones).

"In a way, birds are flying atoms", say the researchers, " It may sound strange, but indeed, one of our main findings was that the way a walking crowd moves, or a flock of birds in flight, shares many similarities with the physical systems of particles". 

In the field of collective movement studies, it has been assumed that there is a qualitative difference between particles (atoms and molecules) and biological elements (cells, but also entire organisms in groups). It was especially believed that the transition from one type of movement to another (for example, from chaos to an orderly flow, known as a phase transition) was completely different.

The crucial difference for physicists in this case has to do with the concept of distance. Particles moving in a space with many other particles influence each other primarily based on their mutual distance. For biological elements, however, the absolute distance is less important.

Take a pigeon flying in a flock: what matters to it are not so much all the closest pigeons, but those it can see." In fact, according to the literature, among those it can see, it can only keep track of a finite number, due to its cognitive limits.

The pigeon, in the physicists' jargon, is in a "topological relationship" with other pigeons: two birds could be at quite a large physical distance, but if they are in the same visible space, they are in mutual contact and influence each other.

It was long thought that this type of difference led to a completely different scenario for the emergence of collective motion This new study, however, suggests that this is not a crucial difference.

These statistical models, based on the physics of particles, can  also help us understand biological collective movement.

Fluctuation-Induced First Order Transition to Collective Motion, Journal of Statistical Mechanics Theory and Experiment (2024). DOI: 10.1088/1742-5468/ad6428

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Comment by Dr. Krishna Kumari Challa on August 9, 2024 at 7:49am

Based on their findings, the researchers designed a lensless fluorescence system using large (1–2 mm2) LEDs and detectors, which have recently become available in UV wavelengths. It works by using UV light to excite proteins from harmful microbes and then detecting the resulting fluorescence.

In addition to demonstrating the lensless system's sensitivity, they also showed that it produced a fluorescence signal that is about double the strength of a lensed system. They found that the performance of the lensed system was limited by its numerical aperture, the use of larger sources and detectors and the finite imaging distance required between the components and the sample.

The researchers are now developing a pocket-sized version of the lensless fluorometers for field testing.

 Asim Maharjan et al, Lensless fluorometer outperforms lensed system, Optica (2024). DOI: 10.1364/OPTICA.527289

Part 2

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