Complex, unfamiliar sentences make the brain's language network work harder, study reveals

With help from an artificial language network, MIT neuroscientists have discovered what kind of sentences are most likely to fire up the brain's key language processing centers.

The new study reveals that sentences that are more complex, either because of unusual grammar or unexpected meaning, generate stronger responses in these language processing centers. Sentences that are very straightforward barely engage these regions, and nonsensical sequences of words don't do much for them either.

The input has to be language-like enough to engage the system. And then within that space, if things are really easy to process, then you don't have much of a response. But if things get difficult, or surprising, if there's an unusual construction or an unusual set of words that you're maybe not very familiar with, then the network has to work harder.

In this study, the researchers focused on language-processing regions found in the left hemisphere of the brain, which includes Broca's area as well as other parts of the left frontal and temporal lobes of the brain.

To figure out what made certain sentences drive activity more than others, the researchers analyzed the sentences based on 11 different linguistic properties, including grammaticality, plausibility, emotional valence (positive or negative), and how easy it is to visualize the sentence content.

This analysis revealed that sentences with higher surprisal generate higher responses in the brain. This is consistent with previous studies showing people have more difficulty processing sentences with higher surprisal, the researchers say.

Another linguistic property that correlated with the language network's responses was linguistic complexity, which is measured by how much a sentence adheres to the rules of English grammar and how plausible it is, meaning how much sense the content makes, apart from the grammar.

Sentences at either end of the spectrum—either extremely simple, or so complex that they make no sense at all—evoked very little activation in the language network. The largest responses came from sentences that make some sense but require work to figure them out.

Researchers  found that the sentences that elicit the highest brain response have a weird grammatical thing and/or a weird meaning. There's something slightly unusual about these sentences.

Greta Tuckute et al, Driving and suppressing the human language network using large language models, Nature Human Behaviour (2024). DOI: 10.1038/s41562-023-01783-7

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Study demonstrates potency of synthetic antibiotic against serious chronic infections

A new synthetic antibiotic developed by  researchers is shown to be more effective than established drugs against "superbugs" such as MRSA, a new study shows.

The study, "Development of teixobactin  analogs containing hydrophobic, nonproteogenic amino acids that are highly potent against multidrug-resistant bacteria and biofilms," is published in the European Journal of Medicinal Chemistry.

The study demonstrates the potent activity of the antibiotic, teixobactin, against bacterial biofilms. Biofilms are clusters of bacteria that are attached to a surface and/or to each other—which are associated with serious chronic infections in humans.

Nearly 5 million people lose their lives due to antibiotic resistance-associated infections and millions more live with poor quality of life due to treatment failures. Antimicrobial resistance (AMR) is increasing and an AMR review commissioned by the UK Government has predicted that by 2050 an additional 10 million people will succumb to drug-resistant infections each year.

 A team of researchers  developed simplified synthetic versions of the natural molecule teixobactin, which is used by producer bacteria to kill other bacteria in soil.

They have tested a unique library of synthetic versions of the "game-changing" antibiotic, optimizing key features of the drug to enhance its efficacy and safety, plus enabling it to be inexpensively produced at scale. For this latest study, the researchers designed and synthesized highly potent teixobactin analogs but swapped out key bottleneck building block L-allo-enduracididine with the commercially available low-cost simplified building blocks such as non-proteogenic amino acids. As a result, the analogs are now effective against a broad range of resistant bacterial pathogens including bacterial isolates from patients and bacterial biofilms.

This is another important step in adapting the natural teixobactin molecule to make it suitable for human use.

Teixobactin molecules have the potential to provide new treatment options against multi-drug resistant bacterial and biofilm-related infections to improve and save lives globally. 

Anish Parmar et al, Development of teixobactin analogues containing hydrophobic, non-proteogenic amino acids that are highly potent against multidrug-resistant bacteria and biofilms, European Journal of Medicinal Chemistry (2023). DOI: 10.1016/j.ejmech.2023.115853

Surprising Study Links 'Good' Cholesterol With Up to 42% Higher Dementia Risk

When it comes to cholesterol, it's usually sorted into the 'good' kind and the 'bad' kind based on their effects on heart health – but now a new study has shown that the 'good' type of cholesterol could have other health risks attached.

This is High-Density lipoprotein cholesterol (HDL-C), and the latest research links an abundance of it with a higher risk of dementia in older adults. For those above 75 years of age, the risk increases by 42 percent, the analysis showed. The research, led by a team from Monash University, looked at data on 18,668 adults aged over 65 from Australia and the US. Overall, for those diagnosed as having high HDL-C levels the risk of dementia increased by 27 percent on average, with individuals followed for an average of 6.3 years. "This is the most comprehensive study to report high HDL-C and the risk of dementia in older people," write the researchers in their published paper. "Findings showed that high HDL-C was associated with dementia risk and the risk increased with age."

Most of the cholesterol in our bodies is the Low-Density lipoprotein (LDL) or 'bad' type, and if there's a lot of it in the blood, it can clog up arteries, increasing the risk of heart disease and strokes. The main benefit of HDL-C is keeping LDL-C levels in check. A normal level of HDL-C in the blood is considered to be 40–50 milligrams per deciliter (or mg/dL) for men, and 50–60 mg/dL for women – roughly 40–60 parts per thousand. Almost 15 percent of the participants (2,709 people) had what was regarded as high HDL-C levels as the study started, which is 80 mg/dL or above.

The increase in risk is quite a jump, and the association remained significant when adjusted for factors such as age, sex, education, alcohol consumption, and daily exercise. However, this doesn't prove the cholesterol is causing the increase in dementia – only that there's evidence of a link. "While we know HDL cholesterol is important for cardiovascular health, this study suggests that we need further research to understand the role of very high HDL cholesterol in the context of brain health.

https://www.thelancet.com/journals/lanwpc/article/PIIS2666-6065(23)00281-X/fulltext

Cognitive maps in some brain regions are compressed during goal-seeking decision-making

Human decision-making has been the focus of a wide range of research studies. Collectively, these research efforts could help to understand better how people make different types of everyday choices while also shedding light on the neural processes underpinning these choices.

Findings suggest that while making instantaneous decisions, or in other words, choices that need to be made quickly based on the information available at a given moment, humans greatly rely on contextual information. This contextual information can also guide so-called sequential decisions, which entails making a choice after observing the sequential unfolding of a process.

Researchers' findings, published in Neuron, suggest that goal-seeking 'compresses' spatial maps in the hippocampus and orbitofrontal cortices in the brain.

To explore what happens in the brain during goal-directed decision-making, the researchers carried out an experiment involving 27 human participants. The  results shed new light on the neural underpinnings of goal-directed decision-making, suggesting that the brain could utilize compression mechanisms to contextually modulate sensory information during decision-making to achieve a specific goal. In the future, new studies could further investigate these compression processes, which could lead to fascinating new discoveries.

Paul S. Muhle-Karbe et al, Goal-seeking compresses neural codes for space in the human hippocampus and orbitofrontal cortex, Neuron (2023). DOI: 10.1016/j.neuron.2023.08.021. www.sciencedirect.com/science/ … ii/S0896627323006323

The  resourceful ways bacteria thrive in the human gut

The gut microbiome is so useful to human digestion and health that it is often called an extra digestive organ. This vast collection of bacteria and other microorganisms in the intestine helps us break down foods and produce nutrients or other metabolites that impact human health in a myriad of ways.

New research  shows that some groups of these microbial helpers are amazingly resourceful too, with a large repertoire of genes that help them generate energy for themselves and potentially influence human health as well.

The paper, published January 4, 2024, in Nature Microbiology, identified 22 metabolites that three distantly related families of gut bacteria use as alternatives to oxygen for respiration in the anaerobic environment of the gut.

These bacteria also have up to hundreds of copies of genes for producing the enzymes that process these alternate metabolites—many more than have been measured in bacteria that live outside the gut. These results suggest that anaerobic gut bacteria may have the ability to produce energy from hundreds of other compounds as well. These are examples of some of the peculiar metabolisms that act on all these different metabolites produced by the gut microbiome.

This is interesting because one of the main ways the microbiome impacts our health is by making or modifying these small molecules that can then enter our bloodstream and act like drugs.

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At the organism level, we typically think of respiration as the process of breathing in oxygen. At the cellular level, respiration describes an energy-generating biochemical process. Most cells use oxygen for respiration, but in anaerobic environments like the inside of the intestine, cells have evolved to use other molecules.

Cells possess two main types of metabolism to produce energy: fermentation and respiration. In fermentation, the cell breaks down molecules to generate energy directly.

Respiration involves two molecules: an electron donor and an electron acceptor. A classic example of this process uses glucose as a donor and oxygen as the acceptor. The cells break down the glucose by shuttling extracted electrons through a series of steps before their final transfer to an oxygen molecule. This prompts the cell to generate ATP, or adenosine triphosphate : the basic source of energy for use and storage at the cellular level.

Most of the microbes living in the gut use fermentation, but there are also several known types of bacteria with respiratory metabolisms, including those that use carbon dioxide and sulfate electron acceptors.

For the new study, researchers analyzed a database of more than 1,500 genomes from a database of human gut bacteria. They saw a surprising distribution of genes that produce reductases, which are enzymes that use different respiratory electron acceptors. While most of the genomes encode just a few reductases, a small subset encodes more than 30 different ones.

These bacteria weren't closely related; they came from three distinct and distantly related families (Burkholderiaceae, Eggerthellaceae, and Erysipelotrichaceae) separated by hundreds of millions of years of evolutionary history.

These bacteria appear to be more resourceful than bacteria with respiratory metabolisms that live outside of a host organism, which mostly use inorganic compounds. The respiratory gut bacteria Light and team identified specialize in various organic metabolites, which makes sense given the constant food supply.

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There is so much organic matter in the gut that comes from the food we eat. It's chemically complex, and you need more enzymes to accommodate it in that environment. Scientists think this variety of genes enables gut bacteria to use a lot of different things that come their way.

Some of the metabolites they use also have interesting implications for human health in the gut. People with type 2 diabetes, for example, have higher levels of an amino acid byproduct called imidazole propionate in their blood. Another metabolite, resveratrol, impacts several metabolic and immune system processes, and itaconate is produced by macrophages in response to infections. Researchers hope that more research like this will help us understand the function of different microbes in the gut, which can in turn be leveraged to improve health.

Understanding of these different metabolisms and how they work will enable us to come up with strategies to intervene—either through the diet or pharmacologically—to modulate the flow of metabolites through these various pathways. So, in whatever context, like type 2 diabetes or following an infection, we could control which metabolites are being produced to have a therapeutic benefit.

Dietary- and host-derived metabolites are used by diverse gut bacteria for anaerobic respiration, Nature Microbiology (2024). DOI: 10.1038/s41564-023-01560-2 www.nature.com/articles/s41564-023-01560-2

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Researchers discover that tiredness experienced by long COVID patients has a physical cause

Researchers have discovered that the persistent fatigue in patients with long COVID has a biological cause, namely mitochondria in muscle cells that produce less energy than in healthy patients. The results of the study were published in Nature Communications.

Researchers seeing clear changes in the muscles in these patients. A total of 25 long COVID patients and 21 healthy control participants participated in the study. They were asked to cycle for 15 minutes. This cycling test caused a long-term worsening of symptoms in people with long COVID, called post-exertional malaise (PEM). Extreme fatigue occurs after physical, cognitive, or emotional exertion beyond an unknown, individual threshold. The researchers looked at the blood and muscle tissue one week before the cycling test and one day after the test.

Researchers saw various abnormalities in the muscle tissue of the patients. At the cellular level, they saw that the mitochondria of the muscle, also known as the energy factories of the cell, function less well and that they produce less energy.

So, the cause of the fatigue is really biological. The brain needs energy to think. Muscles need energy to move. This discovery means we can now start to research an appropriate treatment for those with long COVID.

The researchers also saw that the heart and lungs functioned well in the patients. This means that the long-lasting effect on patient's fitness is not caused by abnormalities in the heart or lungs.

Exercising is not always good for patients with long COVID. In concrete terms, scientists advise these patients to guard their physical limits and not to exceed them. They are asking the patients to think of light exertion that does not lead to worsening of the complaints. Walking is good, or riding an electric bike, to maintain some physical condition.  One has to keep in mind that every patient has a different limit.

Because symptoms can worsen after physical exertion, some classic forms of rehabilitation and physiotherapy are counterproductive for the recovery of these patients.

Long covid symptoms: Although the majority of people infected with the SARS-CoV-2 virus recover within weeks, a subgroup, estimated to be around one in eight, will get long COVID. Symptoms in patients with long COVID, post-acute sequelae or COVID or post-COVID syndrome (PCS) include severe cognitive problems (brain fog), fatigue, exercise intolerance, autonomic dysregulation, postural orthostatic tachycardia syndrome (POTS), orthostatic intolerance, and worsening of symptoms after PEM.

Muscle Abnormalities Worsen After Post-Exertional Malaise in Long COVID, Nature Communications (2024). DOI: 10.1038/s41467-023-44432-3 www.nature.com/articles/s41467-023-44432-3

Scientists use high-tech brain stimulation to make people more hypnotizable

How deeply someone can be hypnotized—known as hypnotizability—appears to be a stable trait that changes little throughout adulthood, much like personality and IQ. But now, for the first time,  researchers have demonstrated a way to temporarily heighten hypnotizablity—potentially allowing more people to access the benefits of hypnosis-based therapy.

In the new study, published Jan. 4 in Nature Mental Health, the researchers found that less than two minutes of electrical stimulation targeting a precise area of the brain could boost participants' hypnotizability for about one hour.

Approximately two-thirds of adults are at least somewhat hypnotizable, and 15% are considered highly hypnotizable, meaning they score 9 or 10 on a standard 10-point measure of hypnotizability.

Hypnosis is a state of highly focused attention, and higher hypnotizability improves the odds of your doing better with techniques using hypnosis.

Earlir researchers found that highly hypnotizable people had stronger functional connectivity between the left dorsolateral prefrontal cortex, which is involved in information processing and decision making; and the dorsal anterior cingulate cortex, involved in detecting stimuli.

It made sense that people who naturally coordinate activity between these two regions would be able to concentrate more intently. It's because you're coordinating what you are focusing on with the system that distracts you.

Clinically, a transient bump in hypnotizability may be enough to allow more people living with chronic pain to choose hypnosis as an alternative to long-term opioid use.

The new results could have implications beyond hypnosis. Neurostimulation may be able to temporarily shift other stable traits or enhance people's response to other forms of psychotherapy.

Stanford Hypnosis Integrated with Functional Connectivity-targeted Transcranial Stimulation (SHIFT): a preregistered randomized controlled trial, Nature Mental Health DOI: 10.1038/s44220-023-00184-z www.nature.com/articles/s44220-023-00184-z

Why are bees making less honey?

Honey yields  have been declining since the 1990s, with honey producers and scientists unsure why, but a new study by  researchers has uncovered clues in the mystery of the missing honey.

Using five decades of data from across the U.S., the researchers analyzed the potential factors and mechanisms that might be affecting the number of flowers growing in different regions—and, by extension, the amount of honey produced by honey bees.

The study, recently published in the journal Environmental Research Letters, found that changes in honey yields over time were connected to herbicide application and land use, such as fewer land conservation programs that support pollinators. Annual weather anomalies also contributed to changes in yields.

Overall, researchers found that climate conditions and soil productivity—the ability of soil to support crops based on its physical, chemical and biological properties—were some of the most important factors in estimating honey yields. States in both warm and cool regions produced higher honey yields when they had productive soils.

The eco-regional soil and climate conditions set the baseline levels of honey production, while changes in land use, herbicide use and weather influenced how much is produced in a given year, the researchers summarized.

Gabriela M Quinlan et al, Examining spatial and temporal drivers of pollinator nutritional resources: evidence from five decades of honey bee colony productivity data, Environmental Research Letters (2023). DOI: 10.1088/1748-9326/acff0c

Scientists discover why chicken farms are a breeding ground for antibiotic resistant bacteria

Scientists  are one step closer to understanding how bacteria, such as E. coli and Salmonella enterica, share genetic material which makes them resistant to antibiotics.

Antimicrobial resistance (AMR), the capability of organisms to be resistant to treatment with antibiotics and other antimicrobials, is now one of the most threatening issues worldwide. Livestock farms, their surrounding environments and food products generated from husbandry, have been highlighted as potential sources of resistant infections for animals and humans.

In livestock farming, the misuse and overuse of broad-spectrum antimicrobials administered to reduce production losses is a major known contribution to the large increase and spread of AMR.

In this latest study, scientists provide a significant contribution to demonstrating that different bacteria species, co-existing within the same microbial community (for example, within the chicken gut), are able to share AMR-associated genetic material and end-up implementing similar resistance mechanisms. The discovery has important implications as it affects our understanding of AMR and poses further challenges to the implementation of solutions for surveillance and treatment/control.

This study, published in Nature Communications, looks at two important bacteria found in food animals—Escherichia coli and Salmonella enterica, which both show high levels of drug resistance, are common in farming settings, have high levels of transmissibility to humans and cause food poisoning.

These species of bacteria can share genetic material both within, and potentially between species, a way in which AMR is spread. That is why understanding the extent to which these bacteria within the same environment, and importantly, the same host, can co-evolve and share their genome could help the development and more efficient treatments to fight AMR.

The insurgence and spread of AMR in livestock farming is a complex phenomenon arising from an entangled network of interactions happening at multiple spatial and temporal scales and involving interchanges between bacteria, animals and humans over a multitude of connected microbial environments.

Michelle Baker et al, Convergence of resistance and evolutionary responses in Escherichia coli and Salmonella enterica co-inhabiting chicken farms in China, Nature Communications (2024). DOI: 10.1038/s41467-023-44272-1

HIV vaccine takes step forward with confirmation of neutralizing antibodies

The path to a successful HIV vaccine depends on a critical first step—activating specific immune cells that induce broadly neutralizing antibodies.

Reporting Jan. 4 in the journal Cell, a research team has achieved that requisite initial step in a study using monkeys. The next phase of the work will now move to testing in humans. This study confirms that the antibodies are, at the structural and genetic levels, similar to the human antibody that we need as the foundation for a protective HIV vaccine.

 In earlier work, the research team had isolated naturally occurring broadly neutralizing antibodies from an individual, and then back-tracked through all the changes the antibody and the virus underwent to reach a point of origin for the native antibody and its binding site on the HIV envelope.
With that knowledge, they engineered a molecule that elicits antibodies that mimic the native antibody and its binding site on the HIV envelope.

Four years ago, they published a  study in Science in which they established that monkeys made neutralizing antibodies when vaccinated with the engineered immunogen, but it was uncertain if those antibodies were like the broadly neutralizing antibody that is needed for a human vaccine.

In the current study, the researchers made a new, more potent formulation of the vaccine and delivered it to monkeys. This time, their goal was to determine whether the neutralizing antibodies generated in the animals were structurally and genetically similar to the antibodies needed in humans. They were.

Kevin O. Saunders et al, Vaccine induction of CD4-mimicking HIV-1 broadly neutralizing antibody precursors in macaques, Cell (2024). DOI: 10.1016/j.cell.2023.12.002

Evolution is not as random as previously thought, finds new study

A new study has found that evolution is not as unpredictable as previously thought, which could allow scientists to explore which genes could be useful to tackle real-world issues such as antibiotic resistance, disease, and climate change.

The study, which is published in the Proceedings of the National Academy of Sciences (PNAS), challenges the long-standing belief about the unpredictability of evolution and has found that the evolutionary trajectory of a genome may be influenced by its evolutionary history, rather than determined by numerous factors and historical accidents.

By demonstrating that evolution is not as random as scientists once thought, they've opened the door to an array of possibilities in synthetic biology, medicine, and environmental science.

The team carried out an analysis of the pangenome—the complete set of genes within a given species, to answer a critical question of whether evolution is predictable or whether the evolutionary paths of genomes are dependent on their history and so not predictable today.

Using a machine learning approach known as Random Forest, along with a dataset of 2,500 complete genomes from a single bacterial species, the team carried out several hundred thousand hours of computer processing to address the question.

After feeding the data into their high-performance computer, the team first made "gene families" from each of the gene of each genome.

In this way, they could compare like-with-like across the genomes.

Once the families had been identified, the team analyzed the pattern of how these families were present in some genomes and absent in others.

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They found that some gene families never turned up in a genome when a particular other gene family was already there, and on other occasions, some genes were very much dependent on a different gene family being present.
In effect, the researchers discovered an invisible ecosystem where genes can cooperate or can be in conflict with one another.

"These interactions between genes make aspects of evolution somewhat predictable and furthermore, we now have a tool that allows us to make those predictions
The implications of the research are far-reaching and could lead to:

Novel Genome Design—allowing scientists to design synthetic genomes and providing a roadmap for the predictable manipulation of genetic material.
Combating Antibiotic Resistance—Understanding the dependencies between genes can help identify the 'supporting cast' of genes that make antibiotic resistance possible, paving the way for targeted treatments.
Climate Change Mitigation—Insights from the study could inform the design of microorganisms engineered to capture carbon or degrade pollutants, thereby contributing to efforts to combat climate change.
Medical Applications—The predictability of gene interactions could revolutionize personalized medicine by providing new metrics for disease risk and treatment efficacy.

Alan Beavan et al, Contingency, repeatability, and predictability in the evolution of a prokaryotic pangenome, Proceedings of the National Academy of Sciences (2023). DOI: 10.1073/pnas.2304934120

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Study Discovers Novel Biomarker for Vascular Aging and Neurodegeneration

Renal macrophages observed playing crucial role in preventing kidney stones

Researchers have investigated how the body's innate immune system of renal macrophages works to prevent kidney stones. In a paper, "Renal macrophages monitor and remove particles from urine to prevent tubule obstruction," published in Immunity, the authors detail their findings of mechanistic actions and strategic positioning of macrophages to surveil epithelial cells and intratubular environments.

When urine passes through the tubular system of the kidneys, it generates various microscopic sediment particles, including mineral crystals, from the concentrated urine. Pathological conditions can lead to the presence of proteins and inflammatory cells. These particles can become lodged in the tubules, blocking urine flow and causing renal dysfunction.

The researchers observed renal macrophages adjacent to the tubules in real-time, using high-resolution microscopy, live recordings and two-photon microscopy techniques. They were able to record macrophages extending transepithelial protrusions and interacting with intratubular particles, as well as their migration to assist in the excretion of urine particles.

These techniques captured the association of macrophages with particles in urine and demonstrated the role of macrophages in particle removal. Renal macrophages located near medullary tubules display specific behaviors, extending transepithelial protrusions and constantly sampling urine contents. The macrophages were then seen to migrate and surround intratubular particles, aiding in their removal from the tubular system.

To confirm the role of the macrophages, the latex bead experiment was repeated with mice lacking renal macrophages. Macrophage-depleted mice showed increased retention of the fluorescent beads even after 36 hours despite the more prolonged exposure to natural urine flushing.

This result suggests that normal urine flushing alone could not efficiently remove big particles in the renal tubule system without the macrophage pre-disposal assistance.

 Jian He et al, Renal macrophages monitor and remove particles from urine to prevent tubule obstruction, Immunity (2023). DOI: 10.1016/j.immuni.2023.12.003

When bad cells go good: Harnessing cellular cannibalism for cancer treatment

Scientists have solved a cellular murder mystery nearly 25 years after the case went cold. Following a trail of evidence from fruit flies to mice to humans revealed that cannibalistic cells likely cause a rare human immunodeficiency. Now the discovery shows promise for enhancing an up-and-coming cancer treatment.

This paper takes us from very fundamental cell biology in a fly, to explaining a human disease and harnessing that knowledge for a cancer therapy.

The primary character in this story is a gene, Rac2, and the protein it encodes. Rac2 is one of three Rac genes in humans. Rac is very ancient in evolution, so it must serve a fundamental function.

Rac proteins help build a cell's scaffolding, called the cytoskeleton. The cytoskeleton is made of dynamic filaments that allow cells to maintain their shape or deform, as needed. In 1996, while studying a small group of cells in the fruit fly ovary, scientists determined that Rac proteins are instrumental in cell movement. Since then, it has become clear that Rac is a nearly universal regulator of cell motility in animal.

In nineties, they also noticed that a hyperactive form of the Rac1 protein, expressed in only a few cells in a fly's egg chamber, destroyed the whole tissue. Just expressing this active Rac in six to eight cells kills the entire tissue, which is composed of about 900 cells.

A few years ago, evidence began to mount implicating cell eating, also known as cannibalism, in tissue destruction. There's a step in normal fly egg development where certain cells similar to the border cells consume their neighbors because they are no longer needed. Indeed, cellular cannibalism is not as rare as you might expect: Millions of old red blood cells are eliminated from the human body this way every second.

Rac2 is one component of the complex eating process. Rac helps the eating cell to envelop its target. The researchers were curious if a hyperactive form of the protein was causing border cells to prematurely consume their neighbours.

For this to occur, the border cells need to recognize their targets, which requires a particular receptor. Indeed, when  this receptor was blocked by scientists, the border cells expressing activated Rac didn't consume their neighbors, and the egg chamber remained alive and healthy.

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Around the time that they made their breakthrough, these researchers caught wind of an intriguing study in the journal Blood. This paper found that three unrelated people suffering from recurrent infections had the exact same mutation, which hyperactivates Rac2, a Rac protein produced in blood cells. They suspected their lab's recent revelation in fruit flies might shed light on this enigma.

The patients' mutation was just mildly activating, and yet it was enough that they all suffered from multiple infections and ultimately needed bone marrow transplants. Blood tests revealed that these patients had nearly no T cells, a specialized kind of white blood cells crucial to the immune system. The team at the National Institutes of Health inserted the Rac2 mutation into mice and found the same mysterious loss of T cells. They also found that the T cells with hyperactive Rac developed normally in the animals' bone marrow, and migrated to the thymus, where they continued to mature without incident. But then they just seemed to disappear. So, the paper ended with a mystery: what was causing the T cells to disappear?

The authors of that journal study had noticed that many of the patients' neutrophils—another type of white blood cell—were enlarged. They seemed to be consuming quite a lot of material, unusual behavior in an otherwise healthy person.
The researchers wondered if the patients' T cells were disappearing because their innate immune cells like neutrophils with active Rac2 were eating them, much like the fruit fly border cells with active Rac were eating the egg chamber. So they turned their attention to macrophages—the neutrophil's more voracious counterpart—to investigate. They cultured human macrophages with and without hyperactive Rac2 together with T cells. They observed that macrophages with hyperactive Rac consumed more cells, confirming the group's hypothesis from their work with fruit flies.

To test whether this might cause the observed immunodeficiency, co-author Melanie Rodriguez (a graduate student in Montell's lab) took bone marrow samples from mice with the same hyperactive Rac2 mutation found in the patients. She then grew the marrow stem cells into macrophages, and performed a similar experiment to earlier researchers' work , but this time mixing both macrophages and T cells with and without the Rac2 mutation.

She found that macrophages with active Rac2 consumed significantly more T-cells than their normal counterparts. However, T-cells with active Rac2 were also more vulnerable to consumption from either kind of macrophage. So the most likely explanation for the patients' missing T cells was a combination of increased consumption by macrophages as well as increased vulnerability of the T cells themselves. A human medical mystery was solved based on fundamental observations in fruit flies.
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Harnessing haywire cells: The implications of these insights expanded in January 2020. They thought of programming macrophages to eat cancer cells as a novel treatment for the disease, an approach called CAR-M.
They found that adding a CAR receptor to macrophages promoted this behavior. But it was also clear that inducing the macrophages to eat more would make the approach more effective—especially if they would specifically consume, and kill, entire cancer cells.
There is a current cancer treatment called CAR-T, which uses the CAR receptor and a patient's own T-cells to attack and destroy cancers. It is highly effective against some cancers, but there are many that do not respond. CAR-M, a newer cousin to CAR-T, has recently entered into clinical trials in humans and so far seems safe.
Researchers now are interested in harnessing Rac-enhanced CAR macrophages to increase the efficacy of CAR-M treatments. They've filed a provisional patent for the technique—which they call Race CAR-M—and are inviting biotech companies to partner in further developing the approach.
This new multifaceted paper raises both basic science and practical questions, which the lab has begun to tackle. They're investigating whether the technique, which is so effective in the lab, will also work in freshly collected human immune cells and in animal cancer models, in mice and zebrafish. The team is also exploring how Rac2 is making this all happen at the molecular level, deep inside the cells.

 Abhinava K. Mishra et al, Hyperactive Rac stimulates cannibalism of living target cells and enhances CAR-M-mediated cancer cell killing, Proceedings of the National Academy of Sciences (2023). DOI: 10.1073/pnas.2310221120

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Bottled water can contain hundreds of thousands of previously uncounted tiny plastic bits, study finds

In recent years, there has been rising concern that tiny particles known as microplastics are showing up basically everywhere on Earth, from polar ice to soil, drinking water and food. Formed when plastics break down into progressively smaller bits, these particles are being consumed by humans and other creatures, with unknown potential health and ecosystem effects.

One big focus of research: bottled water, which has been shown to contain tens of thousands of identifiable fragments in each container.

Now, using newly-refined technology, researchers have entered a whole new plastic world: the poorly known realm of nanoplastics, the spawn of microplastics that have broken down even further.

For the first time, they counted and identified these minute particles in bottled water. They found that on average, a liter contained some 240,000 detectable plastic fragments—10 to 100 times greater than previous estimates, which were based mainly on larger sizes.

The study was published in the journal Proceedings of the National Academy of Sciences.

Nanoplastics are so tiny that, unlike microplastics, they can pass through intestines and lungs directly into the bloodstream and travel from there to organs including the heart and brain. They can invade individual cells, and cross through the placenta to the bodies of unborn babies. Medical scientists are racing to study the possible effects on a wide variety of biological systems.

Unlike natural organic matter, most plastics do not break down into relatively benign substances; they simply divide and redivide into smaller and smaller particles of the same chemical composition. Beyond single molecules, there is no theoretical limit to how small they can get.

Microplastics are defined as fragments ranging from 5 millimeters (less than a quarter inch) down to 1 micrometer, which is 1 millionth of a meter, or 1/25,000th of an inch. (A human hair is about 70 micrometers across.) Nanoplastics, which are particles below 1 micrometer, are measured in billionths of a meter.

Plastics in bottled water became a public issue largely after a 2018 study detected an average of 325 particles per liter; later studies multiplied that number many times over. Scientists suspected there were even more than they had yet counted, but good estimates stopped at sizes below 1 micrometer—the boundary of the nano world.

The new study uses a technique called stimulated Raman scattering microscopy .This involves probing samples with two simultaneous lasers that are tuned to make specific molecules resonate. Targeting seven common plastics, the researchers created a data-driven algorithm to interpret the results. It is one thing to detect, but another to know what you are detecting .

The researchers tested three popular brands of bottled water sold in the United States (they declined to name which ones), analyzing plastic particles down to just 100 nanometers in size.
They spotted 110,000 to 370,000 particles in each liter, 90% of which were nanoplastics; the rest were microplastics. They also determined which of the seven specific plastics they were, and charted their shapes—qualities that could be valuable in biomedical research.

Part 1

One common one was polyethylene terephthalate or PET. This was not surprising, since that is what many water bottles are made of. (It is also used for bottled sodas, sports drinks and products such as ketchup and mayonnaise.) It probably gets into the water as bits slough off when the bottle is squeezed or gets exposed to heat. One recent study suggests that many particles enter the water when you repeatedly open or close the cap, and tiny bits abrade.
However, PET was outnumbered by polyamide, a type of nylon that probably comes from plastic filters used to supposedly purify the water before it is bottled. Other common plastics the researchers found: polystyrene, polyvinyl chloride and polymethyl methacrylate, all used in various industrial processes.
A somewhat disturbing thought: the seven plastic types the researchers searched for accounted for only about 10% of all the nanoparticles they found in samples; they have no idea what the rest are. If they are all nanoplastics, that means they could number in the tens of millions per liter.

But they could be almost anything, "indicating the complicated particle composition inside the seemingly simple water sample," the authors write. "The common existence of natural organic matter certainly requires prudent distinguishment."

Rapid single-particle chemical imaging of nanoplastics by SRS microscopy, Proceedings of the National Academy of Sciences (2024). DOI: 10.1073/pnas.2300582121. doi.org/10.1073/pnas.2300582121

Part 2

Different biological variants discovered in Alzheimer's disease

Scientists recently have discovered five biological variants of Alzheimer's disease, which may require different treatments. As a result, previously tested drugs may incorrectly appear to be ineffective or only minimally effective.

In those with Alzheimer's disease, the amyloid and tau proteins clump in the brain. In addition to these clumps, other biological processes such as inflammation and nerve cell growth are also involved. Using new techniques, the researchers have been able to measure these other processes in the cerebrospinal fluid of patients with amyloid and tau clumps.

Researchers examined 1,058 proteins in the cerebrospinal fluid of 419 people with Alzheimer's disease. They found that there are five biological variants within this group. The first variant is characterized by increased amyloid production. In a second type, the blood-brain barrier is disrupted, and there is reduced amyloid production and less nerve cell growth.
Furthermore, the variants differ in the degree of protein synthesis, the functioning of the immune system, and the functioning of the organ that produces cerebrospinal fluid. Patients with different Alzheimer's variants also showed differences in other aspects of the disease. For example, the researchers found a faster course of the disease in certain subgroups.

The findings are of great importance for drug research. They could mean that a certain drug might only work in one variant of Alzheimer's disease. For example, medication that inhibits amyloid production may work in the variant with increased amyloid production, but may be harmful in the variant with decreased amyloid production. It is also possible that patients with one variant would have a higher risk of side effects, while that risk would be much lower with other variants.

The next step for the research team is to show that the Alzheimer's variants do indeed react differently to medicines, in order to treat all patients with appropriate medicines in the future.

Cerebrospinal fluid proteomics in Alzheimer's disease patients reveals five molecular subtypes with distinct genetic risk profiles, Nature Aging (2024).

Researchers engineer skin bacteria that are able to secrete and produce molecules that treat acne

International research has succeeded in efficiently engineering Cutibacterium acnes, a type of skin bacterium, to produce and secrete a therapeutic molecule suitable for treating acne symptoms.

The engineered bacterium has been validated in skin cell lines and its delivery has been validated in mice. This finding opens the door to broadening the way for engineering non-tractable bacteria to address skin alterations and other diseases using living therapeutics.

The results of the study, published in Nature Biotechnology, show that researchers have successfully edited the genome of Cutibacterium acnes to secrete and produce NGAL protein known to be a mediator of the acne drug isotretinoin, which has been shown to reduce sebum by inducing the death of sebocytes.

Delivery of a sebum modulator by an engineered skin microbe in mice, Nature Biotechnology (2024). DOI: 10.1038/s41587-023-02072-4

How fruit bats evolved to consume so much sugar may have implications for diabetes research

A high-sugar diet is bad news for humans, leading to diabetes, obesity and even cancer. Yet fruit bats survive and even thrive by eating up to twice their body weight in sugary fruit every day.

Now scientists have discovered how fruit bats may have evolved to consume so much sugar, with potential implications for the millions of people with diabetes. The findings, published in Nature Communications, point to adaptations in the fruit bat body that prevent their sugar-rich diet from becoming harmful.

 Fruit bats have a genetic system that controls blood sugar without fail. Scientists are learning from that system to make better insulin- or sugar-sensing therapies for people.

They found that the fruit bat pancreas, compared to the pancreas of an insect-eating bat, had extra insulin-producing cells as well as genetic changes to help it process an immense amount of sugar. Additionally, fruit bat kidneys had adapted to ensure that vital electrolytes would be retained from their watery meals.

Even small changes, to single letters of DNA, make this diet viable for fruit bats. We need to understand high-sugar metabolism like this to make progress helping the people who are prediabetic.

Part 1

In fruit bats, the compositions of the pancreas and kidneys evolved to accommodate their diet. The pancreas had more cells to produce insulin, which tells the body to lower blood sugar, as well as more cells to produce glucagon, the other major sugar-regulating hormone. The fruit bat kidneys, meanwhile, had more cells to trap scarce salts as they filtered blood.

Zooming in, the regulatory DNA in those cells had evolved to turn the appropriate genes for fruit metabolism on or off. The big brown bat, on the other hand, had more cells for breaking down protein and conserving water. The gene expression in those cells was tuned to handle a diet of bugs.

The organization of the DNA around the insulin and glucagon genes was very clearly different between the two bat species. The DNA around genes used to be considered 'junk,' but new data shows that this regulatory DNA likely helps fruit bats react to sudden increases or decreases in blood sugar.

While some of the biology of the fruit bat resembled what's found in humans with diabetes, the fruit bat appeared to evolve something that humans with a sweet tooth could only dream of: a sweet tooth without consequences. Bats biology has figured it out, and it's all in their DNA, the result of natural selection!

The study benefited from a recent ground swell of interest in studying bats to better human health.  One of the Jamaican fruit bats was used in the sugar metabolism study.

As one of the most diverse families of mammals, bats include many examples of evolutionary triumph, from their immune systems to their peculiar diets and beyond.

Bats are like superheroes, each one with an amazing super power, whether it is echolocation, flying, blood sucking without coagulation, or eating fruit and not getting diabetes.

Scientists are trying to learn all these tricks from bats.

Wei Gordon et al, Nature Communications (2024). www.nature.com/articles/s41467-023-44186-y

Part 2

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Fighting superbugs with medical nanomachines

Instruments smaller than a human hair are being designed to eradicate antibiotic-resistant bacteria and fight cancer.

Because even in an age of antibiotics, people are dying of infections. 'Are we going back in time?' is the question experts are posing as our antibiotics are no longer effective. This is a global challenge. Almost 5 million deaths worldwide were linked to antibiotic-resistant bugs in 2019, according to The Lancet medical journal.

Six types of resistant bacteria inflict the most harm. The World Health Organization has warned that drug-resistant diseases could directly cause 10 million deaths by 2050.

In an arms race, microorganisms evolved various defenses to survive antibiotics.

Antibiotics often latch onto a specific bacterial protein, much like a key fits into a lock. The trouble is that bacteria can undergo a physical change so that the key no longer fits the lock. The antibiotics are left outside.

So the idea behind the nanomachines is that they would be tougher for bacteria to evade as these are bug-killing machines.

Part 1

Their two parts are smaller than 100 nanometers, so 1,000th the width of a human hair—effectively making them minnows alongside larger bacteria.

Researchers released many millions of nanomachines in clumps of bacteria in the laboratory. The machines bound to the bacteria and, once exposed to light, began spinning and drilling into them.

The scene under the microscope: bacteria cells riddled with tiny holes. Further experiments showed that the tiny drills can kill an array of strains that commonly infect people.Having a lower concentration of machines would lessen the risk of damage to human cells.

The instruments punctured the MRSA with enough holes so that it was once again vulnerable to antibiotics.

It is very hard for bacteria to develop resistance against this action.

To deploy this new weapon against resistant bacteria, the researchers will need to ensure that the nanomachines are safe to use on patients. That means being sure that bacteria rather than human cells get targeted.

One early reason for optimism is that the nanomachines are positively charged. As a result, they prefer to attach themselves to negatively charged bacteria rather than to human cells, which are more neutral.
In the experiments by researchers, the nanomachines caused no harm to worms when injected into them.
next step: safety tests in mice.

If successful, the first patients treated might be ones with wound infections—especially people with severe burns, which are prone to infection.

The nanomachines could be placed on their skin and switched on by light to drill into bacteria that are infecting the wound.
Part 2

Nanomachines: what are they?
Professor Ben Feringa at the University of Groningen in the Netherlands won the Nobel Prize in Chemistry in 2016 for nanomachines with molecular motors that could be turned on by ultraviolet light.

The molecules change shape when struck by light and, as a result, can be used as switches or triggers.
Some of these nanomachines have the potential to treat cancer patients in ways that excite scientists and doctors. Today's cancer drugs often inflict side effects such as loss of hair, nausea, fatigue or immune-system weakness. This is because the drugs can maim healthy bystander cells.
A future scenario could involve nanomachines delivering cell-killing drugs precisely to a patient's cancer, perhaps burrowing inside any tumor. So some researchers are constructing materials that can be used to ferry vaccines or nanomedicines inside cells, including cancers.
Some are creating polymer nanoparticles to deliver future gene therapies to precise locations inside patients. The particles are often coated sugars because they are able to act as a key to open cells in the body. These synthetic sugars can interact with cell membranes and can give the particle a key to open the door and get a gene inside the cell.
Others are working on lipid nanoparticles, which are tiny spheres made of fats that can safely get inside cells. Lipid nanoparticles were the real breakthrough needed for COVID-19 vaccines.
The next big change for the pharma industry will be to train our genes to prevent cancer or to fight against cancer.

Source: 

• REBELLION
• BIOMOLMACS

Part 3

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Deforestation in the Amazon may be decreasing the frequency of thun...

For the first time, researchers from Tel Aviv University have determined that due to the ongoing deforestation in the Amazon basin in recent decades, the number of thunderstorms in the region has decreased significantly, and the area over which they occur has shrunk.

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Shape matters: Study finds microplastic fibers may travel as far as...

How far microplastics travel in the atmosphere depends crucially on particle shape, according to a recent study by scientists at the University of Vienna and the Max Planck Institute for Dynamics and Self-Organization in Göttingen. Although spherical particles settle quickly, microplastic fibers might travel as far as the stratosphere.

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The first breath of green

The oldest fossil evidence of photosynthesis has been found inside tiny cyanobacteria that lived around 1.75 billion years ago, 1.2 billion years earlier than the previous record-holder. The photosynthetic structures, known as thylakoids, were found inside fossilized Navifusa majensis. Cyanobacteria are thought to have triggered the Great Oxidation Event more than 2 billion years ago, which transformed Earth’s atmosphere. “One idea is that, perhaps, they invented thylakoids at this time and this increased the quantity of oxygen on Earth,” says paleobiologist Emmanuelle Javaux, who contributed to the discovery. “Now that we’ve found very old thylakoids and that they can be preserved in very old rocks, we think that we could go further back in time and try to test this hypothesis.”

https://www.nature.com/articles/s41586-023-06896-7.epdf?sharing_tok...

New Scientist

AI discovers that not every fingerprint is unique

From "Law and Order" to "CSI," not to mention real life, investigators have used fingerprints as the gold standard for linking criminals to a crime. But if a perpetrator leaves prints from different fingers in two different crime scenes, these scenes are very difficult to link, and the trace can go cold.

It's a well-accepted fact in the forensics community that fingerprints of different fingers of the same person—"intra-person fingerprints"—are unique and, therefore, unmatchable.

A team of under graduates who had no prior knowledge of forensics, found a public U.S. government database of some 60,000 fingerprints and fed them in pairs into an artificial intelligence-based system known as a deep contrastive network. Sometimes the pairs belonged to the same person (but different fingers), and sometimes they belonged to different people.

Over time, the AI system, which the team designed by modifying a state-of-the-art framework, got better at telling when seemingly unique fingerprints belonged to the same person and when they didn't. The accuracy for a single pair reached 77%. When multiple pairs were presented, the accuracy shot significantly higher, potentially increasing current forensic efficiency by more than tenfold.

Study findings challenge–and surprise–forensics community

Once the team verified their results, they quickly sent the findings to a well-established forensics journal, only to receive a rejection a few months later. The anonymous expert reviewer and editor concluded that "It is well known that every fingerprint is unique," and therefore, it would not be possible to detect similarities even if the fingerprints came from the same person.

The team did not give up. They doubled down on the lead, fed their AI system even more data, and the system kept improving. Aware of the forensics community's skepticism, the team opted to submit their manuscript to a more general audience. The paper was rejected again, but Lipson, who is the James and Sally Scapa Professor of Innovation in the Department of Mechanical Engineering and co-director of the Makerspace Facility, appealed.

The undergraduates said: We don't normally argue editorial decisions, but this finding was too important to ignore. If this information tips the balance, then we imagine that cold cases could be revived and even that innocent people could be acquitted.

While the system's accuracy is insufficient to decide a case officially, it can help prioritize leads in ambiguous situations. After more back and forth, the paper was finally accepted for publication by Science Advances.

A new kind of forensic marker to precisely capture fingerprints

One of the sticking points was the following question: What alternative information was the AI actually using that has evaded decades of forensic analysis? After carefully visualizing the AI system's decision process, the team concluded that the AI was using a new forensic marker.

The AI was not using 'minutiae,' which are the branchings and endpoints in fingerprint ridges—the patterns used in traditional fingerprint comparison. Instead, it was using something else, related to the angles and curvatures of the swirls and loops in the center of the fingerprint. Just imagine how well this will perform once it's trained on millions instead of thousands of fingerprints!

However, the team is aware of potential biases in the data. The authors present evidence that indicates that the AI performs similarly across genders and races where samples were available. However, they note that more careful validation needs to be done using datasets with broader coverage if this technique is to be used in practice.

This discovery is an example of more surprising things to come from AI, note  the under graduates. Many people think that AI cannot really make new discoveries–that it just regurgitates knowledge. But this research is an example of how even a fairly simple AI, given a fairly plain dataset that the research community has had lying around for years, can provide insights that have eluded experts for decades.

Even more exciting is the fact that an undergraduate student, with no background in forensics whatsoever, can use AI to challenge a widely held belief of an entire field successfully. We are about to experience an explosion of AI-led  scientific discovery by non-experts, and the expert community, including academia, needs to get ready.

Agreed!

Gabriel Guo et al, Unveiling Intra-Person Fingerprint Similarity via Deep Contrastive Learning, Science Advances (2024). DOI: 10.1126/sciadv.adi0329. www.science.org/doi/10.1126/sciadv.adi0329

Volume of gray brain matter significantly lower in people with early onset psychosis, finds study

New research from the Institute of Psychiatry, Psychology & Neuroscience has found an association between a reduction in gray matter in the brain and early onset psychosis (EOP).

EOP occurs before the age of 18 during a critical period of development in the brain. Individuals diagnosed with the illness are likely to experience severe and long-lasting symptoms that respond less well to treatment. Early onset psychosis can have a devastating impact on a person's life.

The new study, published in Molecular Psychiatry, is the largest ever brain imaging study in EOP and has provided unprecedented levels of detail about the illness. It shows that in contrast to other mental health disorders, people with EOP have a reduced volume of gray matter across nearly all regions of their brain. Researchers hope that this detailed mapping could be used to assist in future diagnosis, as well as to track the effects of treatment in patients with EOP.

The study represents an international effort, combining brain scans from Norway, Spain, Canada, Italy, Australia and the UK, 482 individuals with EOP being compared to 469 healthy controls. An analysis of the data revealed that individuals with EOP had lower volumes of gray matter in almost all regions of the brain compared to the healthy controls, with a marked effect in the left median cingulate—an area of the brain associated with the formation and processing of emotions, learning and memory.

Further analysis of the data revealed that those individuals who developed EOP at a later age had lower volumes of gray matter in a number of small brain regions compared to those with an earlier age of onset.

Gray matter's primary purpose is to process information in the brain and plays a significant role in day-to-day functions like memory, emotions and movement. 

Mapping gray and white matter volume abnormalities in early-onset psychosis—an ENIGMA multicenter voxel-based morphometry study, Molecular Psychiatry (2024). DOI: 10.1038/s41380-023-02343-1

New study finds that traumatic stress is associated with a smaller cerebellum

Adults with posttraumatic stress disorder (PTSD) have smaller cerebellums, according to new research from a brain imaging study.

The cerebellum, a part of the brain well-known for helping to coordinate movement and balance, can influence emotion and memory, which are impacted by PTSD. What isn't known yet is whether a smaller cerebellum predisposes a person to PTSD or PTSD shrinks the brain region.

The differences were largely within the posterior lobe, where a lot of the more cognitive functions attributed to the cerebellum seem to localize, as well as the vermis, which is linked to a lot of emotional processing functions.

PTSD is a mental health disorder brought about by experiencing or witnessing a traumatic event, such as a car accident, sexual abuse, or military combat.

Though most people who endure a traumatic experience are spared from the disorder, about 6% of adults develop PTSD, which is often marked by increased fear and reliving the traumatizing event.

Researchers have found several brain regions involved in PTSD, including the almond-shaped amygdala that regulates fear, and the hippocampus, a critical hub for processing memories and routing them throughout the brain.

The cerebellum (Latin for "little brain"), by contrast, has received less attention for its role in PTSD.

A grapefruit-sized lump of cells that looks like it was clumsily tacked underneath the back of the brain as an afterthought, the cerebellum is best known for its role in coordinating balance and choreographing complex movements, like walking or dancing. But there is much more to it than that.

It's a really complex area. If you look at how densely populated with neurons it is relative to the rest of the brain, it's not that surprising that it does a lot more than balance and movement.

Dense may be an understatement. The cerebellum makes up just 10% of the brain's total volume, but packs in more than half of the brain's 86 billion nerve cells.

Researchers have recently observed changes to the size of the tightly-packed cerebellum in PTSD. Most of that research, however, is limited by either a small dataset (fewer than 100 participants), broad anatomical boundaries, or a sole focus on certain patient populations, such as veterans or sexual assault victims with PTSD.

Part 1

To overcome those limitations, Researchers containing over 40  research groups that are part of a larger data-sharing initiative, pooled together their brain imaging scans to study PTSD as broadly and universally as possible. The group ended up with images from 4,215 adult MRI scans, about a third of whom had been diagnosed with PTSD.

The result of this thorough methodology was a fairly simple and consistent finding: PTSD patients had cerebellums about 2% smaller.

The results are an important first step at looking at how and where PTSD affects the brain.

Smaller Total And Subregional Cerebellar Volumes In Posttraumatic Stress Disorder: A Mega-Analysis By The ENIGMA-PGC PTSD Workgroup, Molecular Psychiatry (2024). DOI: 10.1038/s41380-023-02352-0. www.nature.com/articles/s41380-023-02352-0

Part 2

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More than 900 chemicals, many found in consumer products and the environment, display breast-cancer causing traits

With tens of thousands of synthetic chemicals on the market, and new ones in development all the time, knowing which ones might be harmful is a challenge both for the federal agencies that regulate them and the companies that use them in products. Now scientists have found a quick way to predict whether a chemical is likely to cause breast cancer based on whether the chemical harbors specific traits.

This new study provides a roadmap for regulators and manufacturers to quickly flag chemicals that could contribute to breast cancer in order to prevent their use in consumer products and find safer alternatives.

The study titled "Application of the Key Characteristics framework to identify potential breast carcinogens using publicly available in vivo, in vitro, and in silico data," published in Environmental Health Perspectives.

The researchers identified a total of 921 chemicals that could promote the development of breast cancer. Ninety percent of the chemicals are ones to which people are commonly exposed in consumer products, food and drink, pesticides, medications, and workplaces.

A breakdown of the list revealed 278 chemicals that cause mammary tumors in animals. More than half of the chemicals cause cells to make more estrogen or progesterone, and about a third activate the estrogen receptor.

Breast cancer is a hormonal disease, so the fact that so many chemicals can alter estrogen and progesterone is concerning.

Since damage to DNA can also trigger cancer, the researchers searched additional databases and found that 420 of the chemicals on their list both damage DNA and alter hormones, which could make them riskier. What's more, the team's analysis found that chemicals that cause mammary tumors in animals are more likely to have these DNA-damaging and hormone-disrupting characteristics than ones that don't.

These findings show that screening chemicals for these hormonal traits could be an effective strategy for flagging potential breast carcinogens.

Application of the Key Characteristics framework to identify potential breast carcinogens using publicly available in vivo, in vitro, and in silico data, Environmental Health Perspectives (2024). DOI: 10.1289/EHP13233. ehp.niehs.nih.gov/ehp13233

Higher viral load during HIV infection can shape viral evolution

A new paper in Molecular Biology and Evolution finds that HIV populations in people with higher viral loads also have higher rates of viral recombination. In effect, the more HIV in the blood, the easier it is for the virus to diversify.

One of the reasons HIV has historically been so difficult to combat is the virus's exceptionally high rate of recombination. Recombination enables the exchange of genetic information across strains of the virus and drives HIV's evolution within people. This genetic exchange helps the virus evade the immune system and become resistant to many drugs designed to treat HIV.

More generally, recombination is an important evolutionary driver, permitting organisms to purge destructive mutations and combine beneficial ones.

Understanding the factors that impact recombination rate in a well-studied system such as HIV can help uncover some of the effects that recombination has on evolution more broadly.

One important yet understudied step in HIV recombination is coinfection, in which two different virus particles infect the same cell.

The researchers involved with the new study hypothesized that people with higher viral loads (more HIV in the blood) would have more cells that were coinfected, which would lead to higher rates of recombination for the virus. To investigate this hypothesis, they developed a new approach called Recombination Analysis via Time Series Linkage Decay (RATS-LD) to quantify recombination using genetic associations between mutations over time.

This investigation found that while HIV populations with viral loads in the lowest third of the data set have recombination rates in line with previous estimates, while populations with viral loads in the upper third have a median recombination rate that is nearly six-fold higher. Furthermore, the researchers observe patterns of viral load and effective recombination rate increasing simultaneously within single individuals.

 Elena Romero et al, Elevated HIV viral load is associated with higher recombination rate in vivo, Molecular Biology and Evolution (2023). DOI: 10.1093/molbev/msad260. academic.oup.com/mbe/article-l … .1093/molbev/msad260

Is Vitamin D that importnat?
For a time, vitamin D was touted as a potential miracle vitamin, thought to prevent everything from heart disease to cancer to diabetes. But several recent randomized controlled trials showed no significant benefit of vitamin D for any major condition. To be sure, vitamin D plays a vital role in health, but most people get all they need in several minutes of daily sunlight.

Why this matters: Overtesting by doctors of vitamin D serum levels remains widespread. Experts disagree about how to interpret the test and many doctors still unnecessarily recommend vitamin D supplements. The supplements represent more than a $1 billion market, despite the lack of evidence that they are necessary for the majority of people (not to mention the fact that vitamins are not independently tested for purity or dosing).

What the experts say: “There’s a religiosity around vitamin D,” says Clifford Rosen, an endocrinologist at the Maine Medicine Center's Research Institute. “The evidence is out there. People don’t want to pay attention to it.”

 no significant benefit of vitamin D

Scientists tame chaotic protein fueling 75% of cancers

MYC is the shapeless protein responsible for making the majority of human cancer cases worse. Researchers have now found a way to rein it in, offering hope for a new era of treatments.

In healthy cells, MYC helps guide the process of transcription, in which genetic information is converted from DNA into RNA and, eventually, into proteins. Normally, MYC's activity is strictly controlled. In cancer cells, it becomes hyper active, and is not regulated properly.

MYC is less like food for cancer cells and more like a steroid that promotes cancer's rapid growth. That is why MYC is a culprit in 75% of all human cancer cases.

In 2018, the researchers noticed that changing the rigidity and shape of a peptide improves its ability to interact with structureless protein targets such as MYC.

Peptides can assume a variety of forms, shapes, and positions. Once you bend and connect them to form rings, they cannot adopt other possible forms, so they then have a low level of randomness. This helps with the binding.

Part 1

In a new paper, scientists describe a new peptide that binds directly to MYC with what is called sub-micro-molar affinity, which is getting closer to the strength of an antibody. In other words, it is a very strong and specific interaction.

Researchers now improved the binding performance of this peptide over previous versions by two orders of magnitude. This makes it closer to their drug development goals.

Currently, the researchers are using lipid nanoparticles to deliver the peptide into cells. These are small spheres made of fatty molecules, and they are not ideal for use as a drug. Going forward, the researchers are developing chemistry that improves the lead peptide's ability to get inside cells.

Once the peptide is in the cell, it will bind to MYC, changing MYC's physical properties and preventing it from performing transcription activities.

MYC represents chaos, basically, because it lacks structure. That, and its direct impact on so many types of cancer make it one of the holy grails of cancer drug development.

Zhonghan Li et al, MYC-Targeting Inhibitors Generated from a Stereodiversified Bicyclic Peptide Library, Journal of the American Chemical Society (2024). DOI: 10.1021/jacs.3c09615

Part 2

Watching others visibly dislike vegetables might make onlookers dislike them, too

Humans learn which behaviours pay off and which don't from watching others. Based on this, we may draw conclusions about how to act—or eat. In the latter's case, people may use each other as guides to determine what and how much to eat. This is called social modeling and is one of the most powerful social influences on eating behaviour.

In a new study, researchers  investigated whether observing others' facial expressions while eating raw broccoli influenced young women's liking and desire to eat raw broccoli.

They show that watching others eating a raw vegetable with a negative facial expression reduces adult women's liking of that vegetable, but not their desire to eat it. This highlights the power of observing food dislike on adults' eating behaviour. 

Previous research shows that behaviors are more likely to be imitated if positive consequences are observed, while the reverse is true if negative outcomes are witnessed. In the present study, however, this correlation was observed only partially: Exposure to models eating broccoli while conveying negative facial expressions resulted in a greater reduction in liking ratings, whereas the reverse did not hold. Watching others eating a raw vegetable with a positive facial expression did not increase adults' vegetable liking or eating desire.

One possible explanation may be that avoiding any food—irrespective of whether it is commonly liked or disliked—that appears disgusting can protect us from eating something that tastes bad or is harmful. Another reason may be that smiling while eating is perceived as an untypical display of liking a certain food.

"This might imply that watching someone eating a raw vegetable with positive facial expressions does not seem an effective strategy for increasing adults' vegetable consumption.

Part 1

Copy and taste

There is still much that needs to be understood about the interplay of obvious enjoyment and the liking of food. For example, the researchers have focused on adults, and while this has not been tested for on this occasion, they said that given the power of negative facial expressions and because children tend to be less willing to try vegetables by default, these findings could generalize to kids.

"For example, if a child sees their parent showing disgust while eating vegetables, this could have negative consequences on children's vegetable acceptance.

In the present study, participants also watched short video clips rather than watching people eat in front of them. This allowed them to observe the dynamic nature of reactive facial expressions, which is more realistic than looking at static pictures; however, in the future, an important focus will be to examine the effect of watching live food enjoyment on eating behavior, the researchers said.

"We also need more research to see whether the findings from this study translate to adults' actual intake of vegetables.

Katie L. Edwards et al, Facial expressions and vegetable liking, Frontiers in Psychology (2024). DOI: 10.3389/fpsyg.2023.1252369

Part 2

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Lab-grown retinas explain why people see colours some animals can't

With human retinas grown in a petri dish, researchers discovered how an offshoot of vitamin A generates the specialized cells that enable people to see millions of colors, an ability that dogs, cats, and other mammals do not possess.

These retinal organoids allowed scientists for the first time to study this very human-specific trait. It's a huge question about what makes us human, what makes us different.

The findings, published in PLOS Biology, increase understanding of color blindness, age-related vision loss, and other diseases linked to photoreceptor cells. They also demonstrate how genes instruct the human retina to make specific color-sensing cells, a process scientists thought was controlled by thyroid hormones. By tweaking the cellular properties of the organoids, the research team found that a molecule called retinoic acid determines whether a cone will specialize in sensing red or green light. Only humans with normal vision and closely related primates develop the red sensor.

Scientists for decades thought red cones formed through a coin toss mechanism where the cells haphazardly commit to sensing green or red wavelengths—and research from researchers recently hinted that the process could be controlled by thyroid hormone levels. Instead, the new research suggests red cones materialize through a specific sequence of events orchestrated by retinoic acid within the eye.

The team found that high levels of retinoic acid in early development of the organoids correlated with higher ratios of green cones. Similarly, low levels of the acid changed the retina's genetic instructions and generated red cones later in development.

There still might be some randomness to it, but the big finding is that you make retinoic acid early in development.This timing really matters for learning and understanding how these cone cells are made.

Part1

Green and red cone cells are remarkably similar except for a protein called opsin, which detects light and tells the brain what colours people see. Different opsins determine whether a cone will become a green or a red sensor, though the genes of each sensor remain 96% identical. With a breakthrough technique that spotted those subtle genetic differences in the organoids, the researchers tracked cone ratio changes over 200 days.

The researchers also mapped the widely varying ratios of these cells in the retinas of 700 adults. Seeing how the green and red cone proportions changed in humans was one of the most surprising findings of the new research.

Retinoic acid signaling regulates spatiotemporal specification of human green and red cones, PLoS Biology (2024). DOI: 10.1371/journal.pbio.3002464. journals.plos.org/plosbiology/ … journal.pbio.3002464

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Scientists still don't fully understand how the ratio of green and red cones can vary so greatly without affecting someone's vision.

To build understanding of diseases like macular degeneration, which causes loss of light-sensing cells near the center of the retina, the researchers are working with other Johns Hopkins labs. The goal is to deepen their understanding of how cones and other cells link to the nervous system.

Part 2

Biomaterials contribute greatly to reduction of greenhouse gas emis...

On average, bio-based products emit 45% less greenhouse gas emissions than the fossil materials they replace, according to research conducted by Radboud University, published in Nature Communications. At the same time, there is a large variation between individual bio-based products and more efforts are required to achieve climate neutrality. Additionally, biomaterials may have less favorable environmental impacts in other areas.

On average, bio-based products emit 45% less greenhouse gas emissions than the fossil materials they replace, according to research conducted by  scientists, published in Nature Communications. At the same time, there is a large variation between individual bio-based products and more efforts are required to achieve climate neutrality. Additionally, biomaterials may have less favourable environmental impacts in other areas.

Globally, there is a lot of investment in developing new materials from biomass, commonly known as biomaterials, to mitigate CO₂ emissions from fossil materials. Biomaterials are derived from plants and are intended to replace materials made from fossil fuels, such as bio-plastics or bio-fibers (for clothing). It is assumed that biomaterials are better in terms of environmental impact.

Research shows that, on average, new biomaterials emit 45% less CO2 than their counterparts made from fossil fuels. The researchers analyzed data from 98 new biomaterials reported in 130 international studies. "These studies considered the entire chain: from raw material extraction, production itself, to the final waste processing.

Part 1

Even though CO₂ emissions on the whole decrease, significant differences exist between and among biomaterials, necessitating more action to achieve complete climate neutrality across the entire production chain. No material is 100% climate-neutral. Some are close, but others even emit more CO₂ than the fossil materials they replace.

Another consideration is that, despite reducing CO₂ emissions, the production of biomaterials may still cause other environmental impacts. For instance, through the use of fertilizers in the production of biomass used for biomaterials. This can lead to eutrophication: an excess of nutrients resulting in oxygen depletion in surface waters.

The researchers calculated that, on average, the production of biomaterials contributed to an increase in eutrophication impact. Reducing CO2 emissions is very important in mitigating climate change, however, we should avoid shifting the impact to other areas. Extra attention is therefore needed if we decide to transition to biomaterials on a large scale.

Emma A. R. Zuiderveen et al, The potential of emerging bio-based products to reduce environmental impacts, Nature Communications (2023). DOI: 10.1038/s41467-023-43797-9

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Mouse study finds aging sperm affects microRNA, increasing the risk of neurodevelopmental disorders

A recent study has reported that changes in mice sperm microRNAs brought about by aging may affect the growth and development of offspring. The finding adds to the growing literature on the effects of paternal aging on offspring.

Marriages and childbearing later in life are increasingly becoming the norm. While the impacts of maternal age on offspring, such as a higher risk of miscarriage and Down syndrome, are widely understood, the impacts from the paternal side are less so. Yet this is changing.

Recent epidemiological studies have demonstrated that paternal aging exerts a more substantial influence on the heightened risk of neurodevelopmental disorders such as autism spectrum disorder.

A research team has Previously revealed* that epigenetic factors, including histone modifications in spermatogenesis and DNA methylation in mice sperm, undergo changes with age. These alterations might lead to transgenerational effects.

However, the impact of paternal aging on microRNAs (miRNAs), small, non-coding RNA molecules that play a crucial role in regulating gene expression, remains under-explored.

* Misako Tatehana et al. Comprehensive histochemical profiles of histone modification in male germline cells during meiosis and spermiogenesis: Comparison of young and aged testes in mice, PLOS ONE (2020). DOI: 10.1371/journal.pone.0230930

Part 1

To rectify this, the same research team has conducted a comprehensive analysis of age-related variations in microRNAs in mice sperm. They compared microRNAs in sperm from mice aged 3, 12, and 20 months and identified the microRNAs that had changed in quantity.

The researchers discovered significant age-associated differences in the microRNAs. Some changes were in microRNAs responsible for regulating the nervous system and genes related to autism spectrum disorder, and these altered microRNAs included those transferred to fertilized eggs.

The present study reveals the potential association between alteration in sperm microRNAs caused by paternal aging, underscoring the significance of investigating the impact of sperm microRNAs on offspring, an aspect that has been relatively overlooked in previous research.

The anticipation is that further exploration of epigenetic factors, specifically microRNAs, will not only contribute to unraveling the pathogenic mechanisms underlying neurodevelopmental disorders but will also offer insights into promoting the health and disease prevention of successive generations.

Kazusa Miyahara et al, Investigating the impact of paternal aging on murine sperm miRNA profiles and their potential link to autism spectrum disorder, Scientific Reports (2023). DOI: 10.1038/s41598-023-47878-z

Part 2

Bizarre Galaxy Discovered With Seemingly No Stars Whatsoever

A newly discovered object is stretching our understanding of what constitutes a galaxy.

Called J0613+52, this massive blob of something some 270 million light-years away appears to have no stars whatsoever. At least, none that can be seen. It's just a haze made of the kind of gas that's found between stars in normal galaxies, drifting around by its lone self .

Its mass and motion appear to be normal for what we'd expect of a spiral galaxy… in fact, if you extracted the stars from a spiral galaxy like the Milky Way or Andromeda, J0613+52 is pretty much what you'd end up with.

According to a team of astronomers  it could be the first discovery of a primordial galaxy in the nearby Universe – a galaxy made up mostly of the gas that formed at the beginning of time.

The object appears to be isolated and undisturbed, having experienced no gravitational interactions over the 13.8 billion-year course that would have disrupted the gas, either tearing it apart, or pushing it into the clumps needed to trigger significant star formation. This makes J0613+52 an object unlike any other we've ever seen before.

It's a galaxy made only out of gas – it has no visible stars. Stars could be there, we just can't see them.

The discovery – one made purely by chance – has been presented at the 243rd meeting of the American Astronomical Society.

Startling Signs of Gravity's Laws Breaking Down Detected in Twin Stars

In 1859, French astronomer and mathematician Urbain Le Verrier detected something strange: Mercury deviated in its dance around the Sun, defying the orderly precession predicted by Newtonian physics.

This odd anomaly couldn't be explained by unknown planets tugging at Mercury's orbit; only by physicist Albert Einstein's 1915 general theory of relativity, which describes how gravity creates curves in the fabric of space-time.

Einstein's general theory has held strong in the century since, but there are a few things about the Universe his mind-bending model can't explain. It breaks down in the centers of black holes and at the dawn of the Universe, for example, and doesn't fit very easily with quantum mechanics, leading some physicists to ponder alternative takes on how gravity works.

While those ideas remain fringe theories, the discovery of gravitational anomalies in widely separated twin stars at infinitesimally low acceleration is once again challenging Einstein's general theory.