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Comment by Dr. Krishna Kumari Challa on August 13, 2024 at 10:29am

How experience shapes neural connectivity in the brain

Our brain interprets visual information by combining what we see with what we already know. A study published in the journal Neuron, by researchers  reveals a mechanism for learning and storing this existing knowledge about the world.

They found that neurons are wired to connect seemingly unrelated concepts. This wiring may be crucial for enhancing the brain's ability to predict what we see based on past experiences, and brings us a step closer to understanding how this process goes awry in mental health disorders.

How do we learn to make sense of our environment? Over time, our brain builds a hierarchy of knowledge, with higher-order concepts linked to the lower-order features that comprise them.

This interconnected framework shapes our expectations and perception of the world, allowing us to identify what we see based on context and experience.

Part 1

Comment by Dr. Krishna Kumari Challa on August 13, 2024 at 10:25am

Rat poison is moving up through food chains, threatening carnivores around the world

Rats thrive around humans, for good reason: They feed off crops and garbage and readily adapt to many settings, from farms to the world's largest cities. To control them, people often resort to poisons. But chemicals that kill rats can also harm other animals.

The most commonly used poisons are called anticoagulant rodenticides. They work by interfering with blood clotting in animals that consume them. These enticingly flavored bait blocks are placed outside of buildings, in small black boxes that only rats and mice can enter. But the poison remains in the rodents' bodies, threatening larger animals that prey on them.

Researchers detected rodenticides in about one-third of the animals in these analyses, including bobcats, foxes and weasels. They directly linked the poisons to the deaths of one-third of the deceased animals—typically, by finding the chemicals in the animals' liver tissues.

When wild animals consume rat poison—typically, by eating a poisoned rat—the effects may include internal bleeding and lesions, lethargy and a reduced immune response, which can make them more susceptible to other diseases. In many cases the animal will die. Sometimes these deaths occur at scales large enough to reduce local predator populations.

 M. P. Keating et al, Global review of anticoagulant rodenticide exposure in wild mammalian carnivores, Animal Conservation (2024). DOI: 10.1111/acv.12947

Comment by Dr. Krishna Kumari Challa on August 13, 2024 at 10:10am

Toxoplasma parasites infect all animals, including humans. Infection can occur in multiple ways, including ingesting spores released in the stool of infected cats or consuming contaminated meat or water. Toxoplasmosis in otherwise healthy people produces only mild symptoms but can be serious in immunocompromised people and to gestating fetusus.

Unlike most pathogens, Toxoplasma can cross the blood-brain barrier and invade brain cells. Once inside neurons, the parasite releases a suite of proteins that alter gene expression in its host, which may be a factor in the behavioral changes it causes in infected animals and people.
In a new study, a global team of researchers hijacked the system Toxoplasma uses to secrete proteins into its host cell. The team genetically engineered Toxoplasma to make a hybrid protein, fusing one of its secreted proteins to a protein called MeCP2, which regulates gene activity in the brain—in effect, giving the MeCP2 a piggyback ride into neurons. Researchers found that the parasites secreted the MeCP2 protein hybrid into neurons grown in a petri dish as well as in the brains of infected mice.

A genetic deficiency in MECP2 causes a rare brain development disorder called Rett syndrome. Gene therapy trials using viruses to deliver the MeCP2 protein to treat Rett syndrome are underway. If Toxoplasma can deliver a form of MeCP2 protein into brain cells, it may provide another option to treat this currently incurable condition. It also may offer another treatment option for other neurological problems that arise from errant proteins, such as Alzheimer's and Parkinson's disease.
The road from laboratory bench to bedside is long and filled with obstacles, so don't expect to see engineered Toxoplasma in the clinic anytime soon.

The obvious complication in using Toxoplasma for medical purposes is that it can produce a serious, lifelong infection that is currently incurable. Infecting someone with Toxoplasma can damage critical organ systems, including the brain, eyes and heart.

However, up to one-third of people worldwide currently carry Toxoplasma in their brain, apparently without incident. Emerging studies have correlated infection with increased risk of schizophrenia, rage disorder and recklessness, hinting that this quiet infection may be predisposing some people to serious neurological problems.

The widespread prevalence of Toxoplasma infections may also be another complication, as it disqualifies many people from using it for treatment. Since the billions of people who already carry the parasite have developed immunity against future infection, therapeutic forms of Toxoplasma would be rapidly destroyed by their immune systems once injected.

In some cases, the benefits of using Toxoplasma as a drug delivery system may outweigh the risks. Engineering benign forms of this parasite could produce the proteins patients need without harming the organ—the brain—that defines who we are.

https://www.nature.com/articles/s41564-024-01750-6

Part 2

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Comment by Dr. Krishna Kumari Challa on August 13, 2024 at 10:08am

A common parasite could deliver drugs to the brain—how scientists are turning Toxoplasma gondii from foe into friend

Parasites take an enormous toll on human and veterinary health. But researchers may have found a way for patients with brain disorders and a common brain parasite to become frenemies.

A new study published in Nature Microbiology has pioneered the use of a single-celled parasite, Toxoplasma gondii, to inject therapeutic proteins into brain cells. The brain is very picky about what it lets in, including many drugs, which limits treatment options for neurological conditions.

Preventing and treating disease by co-opting the very microbes that threaten us has a history that long predates germ theory. Vaccines are a good example. 

The concept of inoculation has yielded a plethora of vaccines that have saved countless lives.

Viruses, bacteria and parasites have also evolved many tricks to penetrate organs such as the brain and could be retooled to deliver drugs into the body. Such uses could include viruses for gene therapy and intestinal bacteria to treat a gut infection known as C. diff.

Part 1

Comment by Dr. Krishna Kumari Challa on August 13, 2024 at 9:50am

It is not always so easy to spot the use of AI. But one clue is that ChatGPT tends to favor certain words.

At least 60,000 papers involved the use of AI in 2023—over one percent of the annual total. For 2024 we are going to see very significantly increased numbers.

Meanwhile, more than 13,000 papers were retracted last year, by far the most in history, according to the US-based group Retraction Watch.

AI has allowed the bad actors in scientific publishing and academia to "industrialize the overflow" of "junk" papers according to  Retraction Watch.

 Such bad actors include what are known as  paper mills.

These "scammers" sell authorship to researchers, pumping out vast amounts of very poor quality, plagiarized or fake papers. Two percent of all studies are thought to be published by paper mills, but the rate is "exploding" as AI opens the floodgates. 

The problem 's not just paper mills, but a broader academic culture which pushes researchers to "publish or perish". Publishers have created 30 to 40 percent profit margins and billions of dollars in profit by creating these systems that demand volume.

The insatiable demand for ever-more papers piles pressure on academics who are ranked by their output, creating a "vicious cycle". 

Many have turned to ChatGPT to save time—which is not necessarily a bad thing.

Because nearly all papers are published in English,  AI translation tools can be invaluable to researchers for whom English is not their first language.

But there are also fears that the errors, inventions and unwitting plagiarism by AI could increasingly erode society's trust in science.

Another example of AI misuse came last week, when a researcher discovered what appeared to be a ChatGPT re-written version of one his own studies had been published in an academic journal.

A good example: 

Samuel Payne, a bioinformatics professor at Brigham Young University in the United States,  revealed that he had been asked to peer review a study in March.

After realizing it was "100 percent plagiarism" of his own study—but with the text seemingly rephrased by an AI program—he rejected the paper.

Payne said he was "shocked" to find the plagiarized work had simply been published elsewhere, in a new Wiley journal called Proteomics.

It has not been retracted till now.

Source: AFP and other news agencies

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Part 2

Comment by Dr. Krishna Kumari Challa on August 13, 2024 at 9:42am

Flood of 'junk': How AI is changing scientific publishing

An infographic of a rat with a preposterously large penis. Another showing human legs with way too many bones. An introduction that starts: "Certainly, here is a possible introduction for your topic".

These are a few of the most egregious examples of artificial intelligence that have recently made their way into scientific journals, shining a light on the wave of AI-generated text and images washing over the academic publishing industry.

Several experts who track down problems in studies told AFP that the rise of AI has turbocharged the existing problems in the multi-billion-dollar sector.

All the experts emphasized that AI programs such as ChatGPT can be a helpful tool for writing or translating papers—if thoroughly checked and disclosed.

But that was not the case for several recent cases that somehow snuck past peer review.

Earlier this year, a clearly AI-generated graphic of a rat with impossibly huge genitals was shared widely on social media.

It was published in a journal of academic giant Frontiers, which later retracted the study.

Another study was retracted last month for an AI graphic showing legs with odd multi-jointed bones that resembled hands.

While these examples were images, it is thought to be ChatGPT, a chatbot launched in November 2022, that has most changed how the world's researchers present their findings.

A study published by Elsevier went viral in March for its introduction, which was clearly a ChatGPT prompt that read: "Certainly, here is a possible introduction for your topic".

Such embarrassing examples are rare and would be unlikely to make it through the peer review process at the most prestigious journals, several experts  say.

Part 1

Comment by Dr. Krishna Kumari Challa on August 13, 2024 at 9:29am

Scientists find oceans of water on Mars.  But it is too deep to tap!

Using seismic activity to probe the interior of Mars, geophysicists have found evidence for a large underground reservoir of liquid water—enough to fill oceans on the planet's surface.

The data from NASA's Insight lander allowed the scientists to estimate that the amount of groundwater could cover the entire planet to a depth of between 1 and 2 kilometers, or about a mile.

But this  reservoir won't be of much use to anyone trying to tap into it to supply a future Mars colony.

It's located in tiny cracks and pores in rock in the middle of the Martian crust, between 11.5 and 20 kilometers below the surface. Even on Earth, drilling a hole a kilometer deep is a challenge.

The finding does pinpoint another promising place to look for life on Mars, however, if the reservoir can be accessed. For the moment, it helps answer questions about the geological history of the planet.

Wright, Vashan, Liquid water in the Martian mid-crust, Proceedings of the National Academy of Sciences (2024). DOI: 10.1073/pnas.2409983121. doi.org/10.1073/pnas.2409983121

Comment by Dr. Krishna Kumari Challa on August 13, 2024 at 9:22am

Driven by the physical theories of molecular interactions, the researchers  soon made two independent encounters with experimental groups that helped confirm their results. 

At this meeting, they presented exciting experimental data showing that the death and birth of FtsZ filaments were essential for the formation of the division ring. This suggested that treadmilling had a crucial role in this process.

They also saw that the in vitro results closely matched the simulations and further confirmed the team's computational results.

Energy-driven self-organization of matter is a fundamental process in physics. Researchers are asking how to create living matter from non-living material that looks living. Thus, their present work could facilitate the creation of synthetic self-healing materials or synthetic cells.

Self-organisation of mortal filaments and its role in bacterial division ring formation, Nature Physics (2024). DOI: 10.1038/s41567-024-02597-8

Part 2

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

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