Surprising New Role for Lungs: Making Blood

Cells in Mouse Lungs Produce Most Blood Platelets and Can Replenish Blood-Making Cells in Bone Marrow, Study Shows

Using video microscopy in the living mouse lung, UC San Francisco scientists have revealed that the lungs play a previously unrecognized role in blood production. As reported online March 22, 2017, in Nature, the researchers found that the lungs produced more than half of the platelets – blood components required for the clotting that stanches bleeding – in the mouse circulation.

In another surprise finding, the scientists also identified a previously unknown pool of blood stem cells capable of restoring blood production when the stem cells of the bone marrow, previously thought to be the principal site of blood production, are depleted.

This finding definitely suggests a more sophisticated view of the lungs – that they’re not just for respiration but also a key partner in formation of crucial aspects of the blood. What scientists  observed  in mice strongly suggests the lung may play a key role in blood formation in humans as well.

The findings could have major implications for understanding human diseases in which patients suffer from low platelet counts, or thrombocytopenia, which afflicts millions of people and increases the risk of dangerous uncontrolled bleeding. The findings also raise questions about how blood stem cells residing in the lungs may affect the recipients of lung transplants.

Lungs Produce More Than 10 Million Platelets Per Hour

The new study was made possible by a refinement of a technique known as two-photon intravital imaging recently . This imaging approach allowed the researchers to perform the extremely delicate task of visualizing the behavior of individual cells within the tiny blood vessels of a living mouse lung.

Researchers were using this technique to examine interactions between the immune system and circulating platelets in the lungs. Using a mouse strain engineered so that platelets emit bright green fluorescence,  they noticed a surprisingly large population of platelet-producing cells called megakaryocytes in the lung vasculature. Though megakaryocytes had been observed in the lung before, they were generally thought to live and produce platelets primarily in the bone marrow.

More detailed imaging sessions soon revealed megakaryocytes in the act of producing more than 10 million platelets per hour within the lung vasculature, suggesting that more than half of a mouse’s total platelet production occurs in the lung, not the bone marrow, as researchers had long presumed. Video microscopy experiments also revealed a wide variety of previously overlooked megakaryocyte progenitor cells and blood stem cells sitting quietly outside the lung vasculature – estimated at 1 million per mouse lung.

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The discovery of megakaryocytes and blood stem cells in the lung raised questions about how these cells move back and forth between the lung and bone marrow. To address these questions, the researchers conducted a clever set of lung transplant studies:

First, the team transplanted lungs from normal donor mice into recipient mice with fluorescent megakaryocytes, and found that fluorescent megakaryocytes from the recipient mice soon began turning up in the lung vasculature. This suggested that the platelet-producing megakaryocytes in the lung originate in the bone marrow.

It’s fascinating that megakaryocytes travel all the way from the bone marrow to the lungs to produce platelets. It’s possible that the lung is an ideal bioreactor for platelet production because of the mechanical force of the blood, or perhaps because of some molecular signaling we don’t yet know about.

In another experiment, the researchers transplanted lungs with fluorescent megakaryocyte progenitor cells into mutant mice with low platelet counts. The transplants produced a large burst of fluorescent platelets that quickly restored normal levels, an effect that persisted over several months of observation — much longer than the lifespan of individual megakaryocytes or platelets. To the researchers, this indicated that resident megakaryocyte progenitor cells in the transplanted lungs had become activated by the recipient mouse’s low platelet counts and had produced healthy new megakaryocyte cells to restore proper platelet production.

Finally, the researchers transplanted healthy lungs in which all cells were fluorescently tagged into mutant mice whose bone marrow lacked normal blood stem cells. Analysis of the bone marrow of recipient mice showed that fluorescent cells originating from the transplanted lungs soon traveled to the damaged bone marrow and contributed to the production not just of platelets, but of a wide variety of blood cells, including immune cells such as neutrophils, B cells and T cells. These experiments suggest that the lungs play host to a wide variety of blood progenitor cells and stem cells capable of restocking damaged bone marrow and restoring production of many components of the blood.

To our knowledge this is the first description of blood progenitors resident in the lung, and it raises a lot of questions with clinical relevance for the millions of people who suffer from thrombocytopenia.

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Lungs as Resource for Platelet Production

In particular, the study suggests that researchers who have proposed treating platelet diseases with platelets produced from engineered megakaryocytes should look to the lungs as a resource for platelet production. The study also presents new avenues of research for stem cell biologists to explore how the bone marrow and lung collaborate to produce a healthy blood system through the mutual exchange of stem cells.

These observations alter existing paradigms regarding blood cell formation, lung biology and disease, and transplantation.

The observation that blood stem cells and progenitors seem to travel back and forth freely between the lung and bone marrow lends support to a growing sense among researchers that stem cells may be much more active than previously appreciated

https://www.nature.com/articles/nature21706

https://www.ucsf.edu/news/2017/03/406111/surprising-new-role-lungs-....

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A sweater made from new aerogel fiber tests warmer than one made from down

A team of chemical engineers and materials scientists has developed a new type of aerogel fiber that has proven to be warmer than down when woven into a sweater. In their paper published in the journal Science, the group describes the inspiration for their fibers, how they were made and how well they worked when tested in a cold environment.

Aerogels are types of gels where the liquid is replaced by air. They were invented in the 1930s and have been used for a variety of applications, including NASA space vehicles. Because of their positive thermal properties, material scientists have been trying to make fibers using them that could be used to create warm textiles. Thus far, such attempts have mostly failed, however, due to a lack of moisture permeability and strength. In this new study, a research team in a has found a way to overcome both problems.

The work by the researchers began as an effort to mimic the thermal properties of polar bear fur. They note that the reason the bears can keep warm in such cold temperatures is that the hairs that make up their fur coat have both a porous core and a dense shell. To recreate such attributes, the group created what they describe as an encapsulated aerogel fiber by starting with a precursor, which they spun as it was frozen. This process led to a sol-gel transition. The material was then freeze-dried and coated with a semi-hard shell.

The result was a thin round fiber that could be produced in desired lengths. The researchers note that no post-processing was needed to produce textiles, suggesting their fibers could be produced more cheaply than those currently in use.

The research team next produced batches of their fibers in long strands that they used to weave a sweater. They then tested the warmth of the sweater by exposing it to temperatures as low as −20°C. They claim the sweater demonstrated thermal protection that was better than similar sweaters made of down, wool, or cotton. They also stretched the sweater 10,000 times and found it suffered little damage. They also note that the fiber can be stretched, dyed, and flexed.

Mingrui Wu et al, Biomimetic, knittable aerogel fiber for thermal insulation textile, Science (2023). DOI: 10.1126/science.adj8013

Zhizhi Sheng et al, Mimicking polar bear hairs in aerogel fibers, Science (2023). DOI: 10.1126/science.adm8388

Scientists develop 'flying dragon' robot to fight fires from a distance

Imagine a flying dragon that doesn't spout fire, but instead extinguishes it with blasts of water. Thanks to a team of  researchers, this new kind of beast may soon be recruited to firefighter teams around the world, to help put out fires that are too dangerous for their human teammates to approach.

The blueprint of this novel firefighter robot, called the Dragon Firefighter, has been published in Frontiers in Robotics and AI. And as it has been published as Open Science, roboticists around the world may freely use the plans to build their own Dragon Firefighters, for the benefit of all.

Development of a remotely controllable 4 m long aerial-hose-type firefighting robot, Frontiers in Robotics and AI (2023). DOI: 10.3389/frobt.2023.1273676

Light color is less important for the internal clock than originally thought, new study finds

Vision is a complex process. The visual perception of the environment is created by a combination of different wavelengths of light, which are decoded as colors and brightness in the brain. Photoreceptors in the retina first convert the light into electrical impulses: with sufficient light, the cones enable sharp, detailed, and colored vision. Rods only contribute to vision in low light conditions, allowing for different shades of gray to be distinguished, but leaving vision much less precise.

The electrical nerve impulses are finally transmitted to ganglion cells in the retina and then via the optic nerve to the visual cortex in the brain. This region of the brain processes the neural activity into a coloured image.

Ambient light, however, does not only allow us to see; it also influences our sleep-wake rhythm. Specialized ganglion cells are significantly involved in this process, which—like the cones and rods—are sensitive to light and react particularly strongly to short-wavelength light at a wavelength of around 490 nanometers. If light consists solely of short wavelengths of 440 to 490 nanometers, we perceive it as blue. If short-wavelength light activates the ganglion cells, they signal to the internal clock that it is daytime. The decisive factor here is how intense the light is per wavelength; the perceived color is not relevant. However, the light-sensitive ganglion cells also receive information from the cones. This raises the question of whether the cones, and thereby the light color, also influence the internal clock. After all, the most striking changes in brightness and light color occur at sunrise and sunset, marking the beginning and end of a day.

A study in mice in 2019 suggested that yellowish light has a stronger influence on the internal clock than bluish light. However, there is reason to think that the color of light, which is encoded by the cones, could also be relevant for the internal clock.

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To get to the bottom of this, the researchers exposed 16 healthy volunteers to a bluish or yellowish light stimulus for one hour in the late evening, as well as a white light stimulus as a control condition. The light stimuli were designed in such a way that they differentially activated the color-sensitive cones in the retina in a very controlled manner.

However, the stimulation of the light-sensitive ganglion cells was the same in all three conditions. Differences in the effect of the light were therefore directly attributable to the respective stimulation of the cones and ultimately the color of the light.

This method of light stimulation allows us to separate the light properties that may play a role in how light effects humans in a clean experimental way.

In order to understand the effects of the different light stimuli on the body, in the sleep laboratory the researchers determined whether the internal clock of the participants had changed depending on the color of the light. Additionally, they assessed how long it took the volunteers to fall asleep and how deep their sleep was at the beginning of the night. The researchers also enquired about their tiredness and tested their ability to react, which decreases with increasing sleepiness.

The conclusion: The researchers  found no evidence that the variation of light color along a blue-yellow dimension plays a relevant role for the human internal clock or sleep. This contradicts the results of the mouse study mentioned above. Rather, these new results support the findings of many other studies that the light-sensitive ganglion cells are most important for the human internal clock.

These findings show that it is probably most important to take into account the effect of light on the light-sensitive ganglion cells when planning and designing lighting. The cones, and therefore the color, play a very subordinate role.

It remains to be seen whether the color of the light also has no effect on sleep if the parameters change, and—for example—the duration of the light exposure is extended or takes place at a different time. Follow-up studies should answer questions like these.

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Night mode on screens—useful or not?

We often hear that the short-wavelength component of light from smartphone and tablet screens affects biological rhythms and sleep. The recommendation is therefore to put your mobile phone away early in the evening or at least use the night shift mode, which reduces the short-wavelength light proportions and looks slightly yellowish.  However, the yellowish color adjustment is a by-product that could be avoided.

Technologically, it is possible to reduce the short-wavelength proportions even without color adjustment of the display; however, this has not yet been implemented in commercial mobile phone displays.

 Effects of calibrated blue–yellow changes in light on the human circadian clock, Nature Human Behaviour (2023). DOI: 10.1038/s41562-023-01791-7

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Cancer-fighting cells made inside body

Viruses that infect immune cells could turn them into cancer-targeting agents — without having to remove the cells from the person receiving treatment, genetically edit them and then reintroduce them to their body. Genetically engineered chimeric antigen receptor (CAR) T cells have yielded dramatic recoveries from some blood cancers — but are notoriously expensive and technically difficult, placing them out of reach for many people. In tests with monkeys, an injection of a virus that inserts genes into the animal’s immune cells mimicked the action of approved CAR-T therapies.

https://www.nature.com/articles/d41586-023-03969-5?utm_source=Live+...

It's a classic tale of apocalyptic fiction. The sun, our precious source of heat and light, collapses into a black hole. Or perhaps a stray black hole comes along and swallows it up. The End is Nigh! If a stellar-mass black hole swallowed our sun, then we'd only have about eight minutes before, as the kids say, it gets real. But suppose the sun swallowed a small primordial black hole? Then things get interesting, and that's definitely worth a paper on the arXiv preprint server.

Primordial black holes are hypothetical black holes that formed during the earliest moments of the universe. Unlike stellar-mass black holes or supermassive black holes, primordial black holes would typically be tiny, with a mass roughly that of an asteroid and a size smaller than a baseball. They show up in certain theoretical models and have been used to try to explain everything from dark matter to a distant Planet X. Many of these models argue that primordial black holes are common, so it's inevitable that a star would eventually capture one. Such stars with a black hole center are known as Hawking stars.
As this new work points out, a captured primordial black hole would initially have almost no effect on a sun-like star. Compared to the mass of the sun, an asteroid's worth of mass might as well be a speck of dust. Even if it were a black hole it couldn't consume much of the sun quickly. But it would affect things over time. A black hole in a star would consume matter in the stellar core and grow over time. If it could grow quickly on a cosmological scale, then it could consume a star completely. If not, it could still affect the evolution and end life of the star.
The study shows that it largely comes down to the initial size of the primordial black hole. For ones at the largest mass range not excluded by observations, around a billionth of a solar mass, it could essentially consume a star in less than half a billion years. If this has happened, then there should be solar mass black holes out there, which are too small to have formed from supernovae like traditional stellar-mass black holes.
If the primordial black hole is much smaller, say less than a trillionth of a solar mass, then things get more complicated. The tiny black hole would consume some matter within the star, but not at a fast pace. It would, however, stir things up in the core, heating it up more than fusion alone. As a result, a star could swell into a "red straggler" which would be cooler and redder than usual red giant stars. All that turbulence in the core could also affect the surface activity of the star. The effects would be subtle, but the authors suggest that the presence of a primordial black hole could be seen through stellar seismology.
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Based on the helioseismology studies we've done, there is almost certainly NOT a black hole in our sun. Or if there is, it would need to be exceedingly tiny. So there's no need to pack your bug-out bag for a solar doomsday. But perhaps there are some Hawking stars out there if we only care to look.

Researchers develop 'electronic soil' that enhances crop growth

Barley seedlings grow on average 50% more when their root system is stimulated electrically through a new cultivation substrate. In a study published in the journal PNAS, researchers  have developed an electrically conductive "soil" for soilless cultivation, known as hydroponics.

The world population is increasing, and we also have climate change. So it's clear that we won't be able to cover the food demands of the planet with only the already existing agricultural methods. But with hydroponics we can grow food also in urban environments in very controlled settings.

Researchers  now developed an electrically conductive cultivation substrate, tailored to hydroponic cultivation, that they call eSoil. The researchers have shown that barley seedlings grown in the conductive "soil" grew up to 50% more in 15 days when their roots were stimulated electrically.

Hydroponic cultivation means that plants grow without soil, needing only water, nutrients and something their roots can attach to—a substrate. It is a closed system that enables water recirculation so that each seedling gets exactly the nutrients it needs. Therefore, very little water is required and all nutrients remain in the system, which is not possible in traditional cultivation.

Hydroponics also enables vertical cultivation in large towers to maximize space efficiency. Crops already being cultivated in this manner include lettuce, herbs and some vegetables. Grains are not typically grown in hydroponics apart for their use as fodder. In this study the researchers show that barley seedlings can be cultivated using hydroponics and that they have a better growth rate thanks to electrical stimulation. They have have found  that seedlings process nitrogen more effectively, but it's not clear yet how the electrical simulation impacts this process.

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Mineral wool is often used as cultivation substrate in hydroponics. Not only is this non-biodegradable, it is also produced with a very energy-intensive process. The electronic cultivation substrate eSoil is made of cellulose, the most abundant biopolymer, mixed with a conductive polymer called PEDOT. This combination as such is not new, but this is the first time it has been used for plant cultivation and for creating an interface for plants in this manner.

Previous research has used high voltage to stimulate the roots. The advantage of the new work is that it has very low energy consumption and no high voltage danger. The new study will open the pathway for new research areas to develop further hydroponic cultivation, the researchers say.

They also say, "We can't say that hydroponics will solve the problem of food security. But it can definitely help particularly in areas with little arable land and with harsh environmental conditions".

 A low-power bioelectronic growth scaffold that enhances crop seedling growth, Proceedings of the National Academy of Sciences (2023). DOI: 10.1073/pnas.2304135120. doi.org/10.1073/pnas.2304135120

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Hormone secreted by fetus causes morning sickness: study

A hormone produced by the human fetus is to blame for morning sickness in pregnant women, a study has found, paving the way to possible prevention and treatment.

Nausea and vomiting affect approximately 70 percent of pregnant women, according to the study published in Nature recently  by researchers.

 In its worst form, hyperemesis gravidarum, the nausea and vomiting is so severe that women are unable to eat or drink normally. The culprit is a hormone produced by the fetus—a protein known as GDF15. But how sick the mother feels depends on a combination of how much of the hormone is produced by the fetus and how much exposure the mother had to this hormone before becoming pregnant.

The discovery points to a potential way to prevent pregnancy sickness by exposing mothers to GDF15 ahead of pregnancy to build up their resilience. It makes us more confident that preventing GDF15 from accessing its highly specific receptor in the mother's brain will ultimately form the basis for an effective and safe way of treating this disorder.

Stephen O'Rahilly, Gdf15 linked to maternal risk of nausea and vomiting during pregnancy, Nature (2023). DOI: 10.1038/s41586-023-06921-9. www.nature.com/articles/s41586-023-06921-9

Could One Physics Theory Unlock the Mysteries of the Brain?

The ability of the phenomenon of criticality to explain the sudden emergence of new properties in complex systems has fascinated scientists in recent decades. When systems are balanced at their “critical point,” small changes in individual units can trigger outsized events, just as falling pebbles can start an avalanche. That abrupt shift in behavior describes the phase changes of water from ice to liquid to gas, but it’s also relevant to many other situations, from flocks of starlings on the wing to stock market crashes. In the 1990s, the physicist Per Bak and other scientists suggested that the brain might be operating near its own critical point. Ever since then, neuroscientists have been searching for evidence of fractal patterns and power laws at work in the brain’s networks of neurons. What was once a fringe theory has begun to attract more mainstream attention, with researchers now hunting for mechanisms capable of tuning brains toward criticality.

Gut microbes may determine patients' response to a drug that delays onset of type 1 diabetes

The microbiome offers a motherlode of data about health and disease, and new findings suggest that antibodies to gut microbes can determine how well patients respond to a new monoclonal antibody drug that delays the onset of type 1 diabetes.

Increasingly, scientists are finding that the gut microbiome has unexpected relationships with health and disease. Research into the gut-brain axis, for example, has unveiled a surprising relationship between gut microbes and mental health. But medical investigators say the list is longer and the link to gut microbes equally complex.

Now, clinical trial data have allowed researchers to track how the gut microbiome can influence patients' response to tepluzimab, a medication that delays type 1 diabetes. The monoclonal antibody therapy targets T cells and prevents them from destroying insulin-producing beta cells. The antibody is the first treatment approved by the Food and Drug Administration to postpone the metabolic disorder in high-risk individuals.

The FDA approved the drug based on results from a randomized clinical trial known as TrialNet-10 study, or the TN-10 study for short. Medical investigators from the University of Toronto revisited the TN-10 trial, studying more than 200 blood samples from 63 participants before and after teplizumab treatment. Findings from the Toronto analysis, reported in the journal Science Translational Medicine, casts a new spotlight on the immune system's relationship with the microbiome, revealing how gut microbes can shape the progression of type 1 diabetes. With this new knowledge in hand, clinicians may better pinpoint patients who are most likely to respond to teplizumab.

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Once known as juvenile diabetes because the disorder most frequently begins in childhood, the condition is linked to a constellation of potential causes. The disorder is tied to a turncoat immune system, which destroys insulin-producing beta cells in the pancreatic islets of Langerhans. Destruction of beta cells leads to lifelong insulin dependence.

Doctors say there are two other possible causes of type 1 diabetes: a genetic predisposition to the disease, and exposure to certain viruses. Either way—faulty DNA or viral exposure—the end result is a T cell attack on beta cells in the pancreas. Type 1 diabetes is categorized as an autoimmune disease, but is more precisely defined as an autoinflammatory condition.

"Immune-targeted therapies have efficacy for treatment of autoinflammatory diseases. 

For example, treatment with the T cell–specific anti-CD3 antibody teplizumab delayed disease onset in participants at high risk for type 1 diabetes in the TrialNet 10 trial.

"However, heterogeneity in therapeutic responses in TrialNet-10 and other immunotherapy trials identifies gaps in understanding disease progression and treatment responses.

The FDA approved tepluzimab in November of 2022 amid findings that revealed not all patients in the TN-10 study experienced the same benefits. The reason for that discrepancy.

may be explained by specific commensal bacteria. Commensal bacteria are so-called "friendly bacteria." They make up the microbiota, a diverse community numbering in the trillions inhabiting mucosal and epidermal surfaces in humans. These bacteria play critical roles in defense against pathogens and apparently in response to the drug teplizumab.

Researchers  investigated anti-commensal antibody responses against a panel of taxonomically diverse intestinal bacteria species in sera from TN-10 participants before and after teplizumab or placebo treatment. They theorized that differences in patients' responses might be explained by anti-commensal antibodies directed against commensal microbes in the gut microbiome. The team then analyzed antibody profiles in 228 serum samples from 63 participants in the TN-10 trial before and after teplizumab treatment.

Patients who had longer-lived antibody responses to three species of gut bacteria—Bifidobacterium longum, Enterococcus faecalis, and Dialister invisus—had more time on teplizumab treatment before being diagnosed as having type 1 diabetes. Clinical trial data revealed that patients with stronger immune responses against the three gut microbes tended to gain the most benefit from the drug's disease-delaying effects.

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The intestinal microbiome is a potential source of biomarkers. The researchers "previously reported that antibody responses to gut commensal bacteria were associated with type 1 diabetes diagnosis, suggesting that certain antimicrobial immune responses may help predict disease onset."

Quin Yuhui Xie et al, Immune responses to gut bacteria associated with time to diagnosis and clinical response to T cell–directed therapy for type 1 diabetes prevention, Science Translational Medicine (2023). DOI: 10.1126/scitranslmed.adh0353

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AI predicts the influence of microplastics on soil properties

Plastic waste and its buildup in nature has become a major environmental concern in recent times. While plastic pollution in the oceans is undoubtedly a problem, the presence of plastics in soils around the world is also known to cause severe environmental and health issues.

As plastics fragment into smaller pieces known as microplastics (MPs) in the soil through natural and anthropogenic processes, they drastically alter soil properties. Moreover, they are also absorbed by plants, potentially entering human food chain and causing health complications.

Grasping the impact of MPs on soil properties bears significant relevance for corporate sustainability, notably within the "Environmental" aspect of Environmental, Social, and Governance (ESG) goals. Global corporations are often confronted with mounting expectations to embrace eco-friendly strategies, with a particular emphasis on handling plastic-related concerns being the core of these initiatives.

However, the underlying mechanisms governing the environmental impact of soil MPs still remain unknown. Soil-MP interactions are complex due to soil heterogeneity and MP diversity, challenging prediction and mitigation of their effects on soil properties.

To address this paucity in research on soil MPs, a team of scientists 

used machine learning (ML) algorithms to assess and predict the influence of MPs on soil properties.

ML is a dynamic and transformative field of artificial intelligence (AI) that uses algorithms and models to learn and make predictions from vast datasets with great accuracy. Using ML to comprehensively understand the role of MPs in soil systems is time- and resource-efficient and provides a foundation for future research on this subject.

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The results of their study were made available online on 5 November 2023 in Environmental Pollution, following Prof. Ok's two critical reviews published under the collection "Plastics in the Environment" in Nature Reviews Earth and Environment.

The ML algorithms were programmed to predict the influence of MPs on soil properties and found that different MP factors, such as type, size, shape, and dosage, significantly altered soil properties. Specifically, MP size was identified as a major factor that affects soil properties. Besides this, the shape, type, and dosage of MP was also found to distinctly influence the soils' chemical properties.

This pioneering study contributes essential data to support informed decision-making on plastic waste management, aligning with the global focus on sustainability and ESG principles. It underscores the importance of innovative research in guiding corporate sustainability efforts, where plastic-related issues are a growing concern. The application of ML techniques to this problem demonstrates the potential for advanced technology to drive sustainable practices and create a greener, more eco-conscious future.

These quantitative insights into the influence of MPs on soil characteristics represents a breakthrough in comprehending and mitigating the plastic waste dilemma. The study's utilization of ML algorithms marks a groundbreaking shift from traditionally complex and resource-intensive methods for predicting and interpreting the impact of MPs on soil properties.

 Piumi Amasha Withana et al, Machine learning prediction and interpretation of the impact of microplastics on soil properties, Environmental Pollution (2023). DOI: 10.1016/j.envpol.2023.122833

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Scientists Destroy 99% of Cancer Cells in The Lab Using Vibrating Molecules

Scientists have discovered a new way to destroy cancer cells. Stimulating aminocyanine molecules with near-infrared light caused them to vibrate in sync, enough to break apart the membranes of cancer cells. Aminocyanine molecules are already used in bioimaging as synthetic dyes. Commonly used in low doses to detect cancer, they stay stable in water and are very good at attaching themselves to the outside of cells. The new approach is a marked improvement over another kind of cancer-killing molecular machine previously developed, called Feringa-type motors, which could also break the structures of problematic cells. It is a whole new generation of molecular machines that scientists call molecular jackhammers. They are more than one million times faster in their mechanical motion than the former Feringa-type motors, and they can be activated with near-infrared light rather than visible light. The use of near-infrared light is important because it enables scientists to get deeper into the body. Cancer in bones and organs could potentially be treated without needing surgery to get to the cancer growth. In tests on cultured, lab-grown cancer cells, the molecular jackhammer method scored a 99 percent hit rate at destroying the cells. The approach was also tested on mice with melanoma tumors, and half the animals became cancer-free. The structure and chemical properties of aminocyanine molecules mean they stay in sync with the right stimulus – such as near-infrared light. When in motion, the electrons inside the molecules form what's known as plasmons, collectively vibrating entities that drive movement across the whole of the molecule.

https://www.nature.com/articles/s41557-023-01383-y

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A Surprising Link Between Oral Health And Your Brain

A new study  has once again raised questions about the relationship between oral health and brain health; which most experts agree are surprisingly interconnected.

It investigated whether problems in the mouth like periodontitis (gum disease) and tooth loss can increase the risk of neurodegenerative disorders like stroke,

 Alzheimer's, and other forms of dementia.

The results were clear: both issues are associated with a faster rate of atrophy in the hippocampus – the part of the brain that governs memory, learning, and emotion. This is a significant result, however it is not the first time such a link has been made.

a US study of more than 40,000 adults enrolled in the UK Biobank research project found that poor oral health appears to be a key risk factor for stroke and dementia.

Researchers find risk of miscarriage increases with benzodiazepine use in pregnancy

After accounting for measurable confounders, the risk for miscarriage is increased in association with benzodiazepine use during pregnancy, according to a study published online Dec. 27 in JAMA Psychiatry.

Benzodiazepines (Benzos) Benzodiazepines are a class of medications that slow down activity in your brain and nervous system. They're most often used for treating anxiety and related mental health conditions, as well as brain-related conditions like seizures.

Researchers quantified the risk for miscarriage associated with benzodiazepine use during pregnancy in a nationwide, population-based case-time-control study.

The researchers found that the risk for miscarriage was increased in association with use of benzodiazepines during pregnancy (odds ratio, 1.69); across multiple sensitivity analyses considering different time windows and accounting for misclassification, the results were consistent. An increased risk for miscarriage was seen in association with commonly used benzodiazepines, ranging from case-time-control odds ratios of 1.39 to 2.52 for alprazolam and fludiazepam, respectively. "These findings suggest that caution is warranted when using benzodiazepines during early pregnancy," the researchers  say. "The findings of this study also provide evidence to guide clinicians in making informed decisions regarding the treatment of psychiatric and sleep disorders in pregnant women."

Lin-Chieh Meng et al, Benzodiazepine Use During Pregnancy and Risk of Miscarriage, JAMA Psychiatry (2023). DOI: 10.1001/jamapsychiatry.2023.4912

Gut Bacteria Contribute to Anorexia

Microbiomes transplanted from women with anorexia nervosa into mice enhanced symptoms of the eating disorder, such as rapid weight loss and reduced appetite.

Trillions of bacteria living in the human gut regulate the health of the body, but a disrupted microbiome can lead to a slew of diseases, including inflammatory bowel disease, multiple sclerosis, and type 2 diabetes. Now, metagenomics researchers  have found that the gut microbiome could also contribute to the eating disorder anorexia nervosa, potentially by altering gene expression in the brain.

The researchers began by comparing stool samples from 70 healthy women and 77 women with anorexia. There were massive changes in the abundance of bacteria, including 27 bacteria that were elevated in anorexic participants and 43 that were depleted. They also found differences in the expression of bacterial genes and in the blood levels of bacterial metabolites, which can affect human physiology. For example, the anorexic group showed an increase in indole-3-propionic acid, which slows down the passage of food and reduces feelings of hunger.

Comparing bacteria, however, is not enough to pin down their effects. To test whether the microbiome directly affected symptoms, the team transplanted fecal samples from three anorexic and three healthy participants into mice lacking gut microbiomes. The mice were then put on restrictive diets to mimic anorexic eating patterns. Those with anorexic microbiomes experienced a quicker drop in weight and put weight back on more slowly, indicating that the anorexic microbiome was conducive to weight loss. 

This proves that there is a causal aspect to it. The team then analyzed gene expression in the mice. In mice with anorexic microbiomes, they found increased expression of the appetite suppressor genes Bdnf and Cartpt in the hypothalamus, the brain’s appetite control center. “Browning” genes that convert white fat that stores energy into brown fat that burns energy to heat the body were also upregulated in fat tissue. 

These changes may explain why the mice lost weight and struggled to regain it, providing a possible mechanism for how the microbiome seemingly intensifies anorexia symptoms. 

Y. Fan et al., “The gut microbiota contributes to the pathogenesis of anorexia nerv...,” Nat Microbiol, ISSN 2058-5276, 2023. 

Space Anemia: A Rocket Launch Might Cause Your Blood Cells to Burst
In the roughly eight minutes it takes to shoot a human being off the face of our planet and into orbit, their body encounters a crushing force of gravity like nothing felt on Earth.
Scientists working with the European Space Observatory's Large Diameter Centrifuge are now testing whether that massive launch can weaken the membranes of an astronaut's blood cells, putting them at risk of bursting.

If that turns out to be true, it could help explain why astronauts tend to suffer from 'space anemia'.

Studies show human bodies destroy about 54 percent more red blood cells traveling into space than they would normally on Earth, lowering the availability of iron transporters in the bloodstream.

Researchers think that is why astronauts often experience fatigue, weakness, or dizziness when they return back to normal gravity. Their blood cells are still readjusting from a life in microgravity.
Historically, space flight has exerted forces of gravity three to six times that of Earth's gravity.
Previous studies on mice have found that white blood cells may be destroyed under conditions of hypergravity, and hypergravity also shows signs of weakening the cells that form a barrier between the blood stream and the brain in mice.

The very inner surface of blood vessels, which help control cell survival, proliferation, death, and migration, show signs of stress from hypergravity.

Scientists still know surprisingly little about how changing gravity impacts the human body.

https://www.sciencealert.com/space-anemia-a-rocket-launch-might-cau...

AI Translates Thoughts Directly From Brainwaves – Without Implants

A world-first, non-invasive AI system can turn silent thoughts into text while only requiring users to wear a snug-fitting cap.

Researchers who developed the technology, called DeWave, tested the process using data from more than two dozen subjects.

Participants read silently while wearing a cap that recorded their brain waves via electroencephalogram (EEG) and decoded them into text.

With further refinement, DeWave could help stroke and paralysis patients communicate and make it easier for people to direct machines like bionic arms or robots.

Other methods of translating brain signals into language require invasive surgeries to implant electrodes or bulky, expensive MRI machines, making them impractical for daily use – and they often need to use eye-tracking to convert brain signals into word-level chunks.

When a person's eyes dart from one word to another, it's reasonable to assume that their brain takes a short break between processing each word. Raw EEG wave translation into words – without eye tracking to indicate the corresponding word target – is harder.

Brain waves from different people don't all represent breaks between words quite the same way, making it a challenge to teach AI how to interpret individual thoughts.

After extensive training, DeWave's encoder turns EEG waves into a code that can then be matched to specific words based on how close they are to entries in DeWave's 'codebook'.

"It is the first to incorporate discrete encoding techniques in the brain-to-text translation process, introducing an innovative approach to neural decoding," explain the researchers.

The integration with large language models is also opening new frontiers in neuroscience and AI.

https://arxiv.org/abs/2309.14030

Part 2

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Food-as-Medicine study finds no improvements in type 2 diabetes patients

Recent research has found that an intensive food-as-medicine program showed no improvement in glycemic control in patients with type 2 diabetes and food insecurity.

In their paper, "Effect of an Intensive Food-as-Medicine Program on Health and Health Care Use—A Randomized Clinical Trial," published in JAMA Internal Medicine, a research team details a randomized clinical trial  of 349 type 2 diabetes patients with previous food insecurity to assess if short-term access to healthy food options could improve glycemic control and influence health care usage.

The study targeted patients with type 2 diabetes and elevated HbA1c levels, providing intensive support and food supplies. Subjects in the treatment group (n=170) were given groceries for 10 healthy meals per week for the household, dietitian consultations, nurse evaluations, health coaching, and diabetes education for one year with a one-year follow-up. A control group (n=179) did not receive any of the benefits of the treatment program for the first six months. Hemoglobin A1C (HbA1c) tests six months into the program showed substantial declines in both the treatment (1.5%) and control (1.3%) groups, resulting in no significant difference between groups. This might indicate that factors beyond the program contributed to the lower blood sugar levels, though what these factors might be is unclear.

Part 1

Access to the program did increase engagement with preventive health care. More dietitian visits, active prescription drug orders, and self-reported improved diets were noted in the treatment group. These increases did not result in improved glycemic control compared to usual care with food insecurity.

No significant differences between treatment and control were observed in cholesterol, triglycerides, fasting glucose, or blood pressure at six or 12 months. It is unclear why a healthy and secure diet and increased access to medical professionals had no effect on any of these measures in the study.

The study seems to show that the damage caused by prolonged food insecurity is not easily reversible. It also suggests that any effort to assist people struggling with food insecurity and diabetes cannot be helped by diet alone.

According to the Centers for Disease Control, people who experience food and nutrition insecurity are two to three times more likely to have diabetes than people who do not. Healthy eating is essential for managing blood sugar levels and can help prevent type 2 diabetes.

Nutritious foods can be expensive or difficult to find for individuals living below the poverty level, often leaving them dependent on calories from highly processed food sources. For people who already have diabetes, buying healthy foods can compete with health care expenses for medicines, devices, and supplies, creating a dire "treat" or "eat" scenario.

While the study found no significant short-term improvements in the subjects recruited for the study, the problem of food and nutrition insecurity is rising along with a rise in diet-related chronic diseases.
Part 2

Food-as-medicine programs are gaining popularity, with variations like produce prescription programs and medically tailored meals. The current study may hint that a short-term intervention diet is insufficient in creating clinically measurable change and that longer-term food and nutrition security is required.

Disorders, diseases associated with childlessness identified

Mental-behavioral disorders, congenital anomalies, and endocrine-nutritional-metabolic disorders are most strongly associated with childlessness, according to a study published online Dec. 18 in Nature Human Behaviour.

Researchers examined 1,035,928 men born in 1956 to 1968 and women born in 1956 to 1973 in Finland and 1,509,092 born in Sweden to the completion of their reproductive lifespan in 2018. Using a population and matched-pair case-control design of siblings discordant for childlessness (71,524 full sisters and 77,622 full brothers), sociodemographic and reproductive information was associated with 414 diseases across 16 categories.

The researchers found the associations were strongest for mental-behavioral disorders (especially among men), congenital anomalies, and endocrine-nutritional-metabolic disorders (strongest among women). New associations were identified for inflammatory and autoimmune diseases. The associations were dependent on age at onset; singlehood and education were mediators of the associations.

Researchers have comprehensively described the associations between different diseases, particularly those with onset prior to the peak reproductive age, and the chance of being childless over a lifetime. 

 Aoxing Liu et al, Evidence from Finland and Sweden on the relationship between early-life diseases and lifetime childlessness in men and women, Nature Human Behaviour (2023). DOI: 10.1038/s41562-023-01763-x

Closing in on the ultimate quest to regenerate insulin in pancreatic stem cells

Researchers are zeroing in on the ultimate quest to regenerate insulin in pancreatic stem cells and replace the need for regular insulin injections.

researchers have demonstrated in an article published in Signal Transduction and Targeted Therapy that newly made insulin cells can respond to glucose and produce insulin following stimulation with two approved drugs in as little as 48 hours.

Further, they confirmed this pathway of awakening the insulin-producing cells is viable in age groups from 7 to 61, providing much-needed insights into the mechanisms underlying the regeneration of beta cells.

Using pancreatic cells derived from a child and adult type 1 diabetic donors, and from a non-diabetic person, a research  team demonstrated how insulin-producing cells that are destroyed in people with type 1 diabetes can be regenerated into glucose sensing and functionally secreting insulin cells. In this latest study by the Human Epigenetics team, they show small molecule inhibitors that are currently used for rare cancers and approved  can rapidly return insulin production in pancreatic cells destroyed by diabetes. While current pharmaceutical options for diabetes treatment help control blood glucose levels they do not prevent, stop or reverse the destruction of insulin-secreting cells.

The novel therapeutic approach holds the potential to become the first disease modifying treatment for type 1 diabetes by facilitating glucose responsive insulin production by harnessing the patient's remaining pancreatic cells, thereby enabling people living with diabetes to potentially achieve independence from round-the-clock insulin injections.

This disease-modifying treatment also represents a promising solution for the significant number of people living with insulin dependent diabetes, who account for 30% of those with type 2 diabetes.

 Keith Al-Hasani et al, EZH2 inhibitors promote β-like cell regeneration in young and adult type 1 diabetes donors, Signal Transduction and Targeted Therapy (2024). DOI: 10.1038/s41392-023-01707-x

Researchers identify new coding mechanism that transfers information from perception to memory

Our memories are rich in detail: we can vividly recall the color of our home, the layout of our kitchen, or the front of our favorite café. How the brain encodes this information has long puzzled neuroscientists.

In a new study, researchers identified a neural coding mechanism that allows the transfer of information back and forth between perceptual regions to memory areas of the brain. The results are published in Nature Neuroscience.

The researchers found that memory-related brain areas encode the world like a 'photographic negative' in space. And that 'negative' is part of the mechanics that move information in and out of memory, and between perceptual and memory systems.

In a series of experiments, participants were tested on perception and memory while their brain activity was recorded using a functional magnetic resonance imaging (fMRI) scanner. The team identified an opposing push-pull like coding mechanism, which governs the interaction between perceptual and memory areas in the brain.

Part 1

The results showed that when light hits the retina, visual areas of the brain respond by increasing their activity to represent the pattern of light. Memory areas of the brain also respond to visual stimulation, but, unlike visual areas, their neural activity decreases when processing the same visual pattern.

The researchers report that the study has three unusual findings. The first is their discovery that a visual coding principle is preserved in memory systems.

The second is that this visual code is upside-down in memory systems. When you see something in your visual field, neurons in the visual cortex are driving while those in the memory system are quieted.

Third, this relationship flips during memory recall. If you close your eyes and remember that visual stimuli in the same space, you'll flip the relationship: your memory system will be driving, suppressing the neurons in perceptual regions.

These results provide a clear example of how shared visual information is used by memory systems to bring recalled memories in and out of focus.

Adam Steel et al, A retinotopic code structures the interaction between perception and memory systems, Nature Neuroscience (2024). DOI: 10.1038/s41593-023-01512-3

Part 2

 Synthetic carbon dioxide fixation in living cells

Synthetic biology offers the opportunity to build biochemical pathways for the capture and conversion of carbon dioxide (CO₂). Researchers have developed a synthetic biochemical cycle that directly converts CO₂ into the central building block Acetyl-CoA.

The researchers were able to implement each of the three cycle modules in the bacterium E.coli, which represents a major step towards realizing synthetic CO2 fixing pathways within the context of living cells.
Developing new ways to capture and convert CO2 is key to tackling the climate emergency. Synthetic biology opens avenues for designing new-to-nature CO2-fixation pathways that capture CO2 more efficiently than those developed by nature.

However, realizing those new-to-nature pathways in different in vitro and in vivo systems is still a fundamental challenge. Researchers have now designed and constructed a new synthetic CO2-fixation pathway, the so-called THETA cycle.

It contains several central metabolites as intermediates and has the central building block, acetyl-CoA, as its output. This characteristic makes it possible to be divided into modules and integrated into the central metabolism of E. coli.

The entire THETA cycle involved 17 biocatalysts and was designed around the two fastest CO2-fixing enzymes known to date: crotonyl-CoA carboxylase/reductase and phosphoenolpyruvate carboxylase.

The researchers found these powerful biocatalysts in bacteria. Although each of the carboxylases can capture CO2 more than ten times faster than RubisCO, the CO2-fixing enzyme in chloroplasts, evolution itself has not brought these capable enzymes together in natural photosynthesis.

The THETA cycle converts two CO2 molecules into one acetyl-CoA in one cycle. Acetyl-CoA is a central metabolite in almost all cellular metabolism and serves as the building block for a wide array of vital biomolecules, including biofuels, biomaterials, and pharmaceuticals, making it a compound of great interest in biotechnological applications. Upon constructing the cycle in test tubes, the researchers could confirm its functionality.
Part 1

Through rational and machine learning-guided optimization over several rounds of experiments, the team was able to improve the acetyl-CoA yield by a factor of 100. In order to test its in vivo feasibility, incorporation into the living cell should be carried out step by step.

To this end, the researchers divided the THETA cycle into three modules, each of which was successfully implemented into the bacterium E. coli. The functionality of these modules was verified through growth-coupled selection and/or isotopic labeling.

What is special about this cycle is that it contains several intermediates that serve as central metabolites in the bacterium's metabolism. This overlap offers the opportunity to develop a modular approach for its implementation.
Bringing parts of the THETA cycle into living cells is an important proof-of-principle for synthetic biology.

Shanshan Luo et al, Construction and modular implementation of the THETA cycle for synthetic CO₂ fixation, Nature Catalysis (2023). DOI: 10.1038/s41929-023-01079-z

Part 2

Matabele ants recognize infected wounds and treat them with antibiotics

The African Matabele ants are often injured in fights with termites. Their conspecifics recognize when the wounds become infected and initiate antibiotic treatment.

The Matabele ants (Megaponera analis), which are widespread south of the Sahara, have a narrow diet: They only eat termites. Their hunting expeditions are dangerous because termite soldiers defend their conspecifics—and use their powerful mandibles to do so. It is therefore common for the ants to be injured while hunting.

If the wounds become infected, there is a significant survival risk. However, Matabele ants have developed a sophisticated health care system: They can distinguish between non-infected and infected wounds and treat the latter efficiently with antibiotics they produce themselves. This is reported by a research team  in the journal Nature Communications.

Researchers have shown that the hydrocarbon profile of the ant cuticle changes as a result of a wound infection.

 It is precisely this change that the ants are able to recognize and thus diagnose the infection status of injured nestmates.

For treatment, they then apply antimicrobial compounds and proteins to the infected wounds. They take these antibiotics from the metapleural gland, which is located on the side of their thorax. Its secretion contains 112 components, half of which have an antimicrobial or wound-healing effect. And the therapy is highly effective: The mortality rate of infected individuals is reduced by 90%, as the research group discovered.

Erik. T. Frank et al, Targeted treatment of injured nestmates with antimicrobial compounds in an ant society, Nature Communications (2023). DOI: 10.1038/s41467-023-43885-w

Going dry could reduce risk of some types of cancers

A large international team of doctors and medical researchers has found evidence that suggests people who stop consuming alcoholic beverages can reduce their risk of developing some types of cancers. In their study, reported in the New England Journal of Medicine, the group analyzed the results of multiple prior research efforts to learn more about the impact of alcohol cessation.

Prior research has suggested that regularly consuming alcoholic beverages can raise the risk of developing some types of cancer, such as oral, esophageal and laryngeal cancer and also, in some cases, colon and breast cancer. And last year, the WHO went so far as to claim that no level of alcohol consumption is safe.

The research team wondered if cancer risks associated with regularly drinking alcohol would be reduced if a person stopped. To find out, they analyzed data from more than 90 studies involving alcohol-related cancers, including cessation. They found sufficient evidence that cutting back or ceasing alcohol consumption does reduce the risk of some types of cancers, most particularly those involving the mouth and esophagus. There was less evidence of reduction in the risk of breast, laryngeal or colorectal cancers.

The researchers note that it is not the alcohol in the drinks that causes cancer, but acetaldehyde, which is considered to be a toxin. It is generated by enzymes in the liver during the metabolism of alcohol. Notably, it is the same substance that can give a person a hangover. Reducing alcohol consumption, they noted, reduces the amount of acetaldehyde produced by the body, which in turn reduces the likelihood of developing some types of cancer.

The research team was not able to determine the degree of reduced risk associated with cessation of alcohol, or how long after cessation a person experiences such benefits. They do note, however, that stopping drinking for just one month, only to resume again the next, is not likely to have much effect on cancer risk. Thus, drinkers choosing to go dry in January must maintain their new habit going forward if they wish to reap such rewards.

Mouse study shows gut biome plays a role in social anxiety disorder

A large team of medical, psychological and social researchers has found that certain microbes in the gut biome may play a role in social anxiety disorder. In their study reported in the Proceedings of the National Academy of Sciences the group conducted experiments with fecal transplants in mice and tested them for anxiety.

Social anxiety disorder (SAD) is a condition in which a person experiences higher than normal levels of anxiety when exposed to people in a social setting, particularly people they don't know. Such settings can include parties, participating in classroom discussions or even standing in line at the grocery store.

Prior research has suggested that conditions in the gut microbiome can have an impact on emotions, which led the team on this new effort to wonder if certain microbes in the gut microbiome might play a role in SAD. To find out, they designed and carried out an experiment with lab mice.

The researchers gave the mice drugs to kill their gut microbiomes and then gave some of them fecal transplants from people with SAD. Others were given fecal transplants from people who did not have the disorder to serve as a control. After administering the transplants, the researchers exposed the test mice to a variety of social environments, which included interacting with groups of mice they knew and groups that they did not know. They found that the test mice given the SAD fecal transplants displayed symptoms of SAD, while those given the control did not. They also noted that they saw no differences in anxiety between the groups when the mice were interacting with mice they already knew.

The research team also found what they describe as substantial differences in the mix of microbes in the microbiomes of the two groups—most specifically, they found lower numbers of three types of bacteria in the mice who had been given SAD fecal transplants. They also found different levels of brain chemicals (such as oxytocin) in the two groups, and differences that appeared to promote inflammation in the SAD group.

Nathaniel L. Ritz et al, Social anxiety disorder-associated gut microbiota increases social fear, Proceedings of the National Academy of Sciences (2023). DOI: 10.1073/pnas.2308706120

What makes urine yellow? Scientists discover the enzyme responsible

Researchers at the University of Maryland and National Institutes of Health have identified the microbial enzyme responsible for giving urine its yellow hue, according to a new study published in the journal Nature Microbiology.

The discovery of this enzyme, called bilirubin reductase, paves the way for further research into the gut microbiome's role in ailments like jaundice and inflammatory bowel disease.

This enzyme discovery finally unravels the mystery behind urine's yellow colour. It's remarkable that an everyday biological phenomenon went unexplained for so long.

When red blood cells degrade after their six-month lifespan, a bright orange pigment called bilirubin is produced as a byproduct. Bilirubin is typically secreted into the gut, where it is destined for excretion but can also be partially reabsorbed. Excess reabsorption can lead to a buildup of bilirubin in the blood and can cause jaundice—a condition that leads to the yellowing of the skin and eyes. Once in the gut, the resident flora can convert bilirubin into other molecules.

Gut microbes encode the enzyme bilirubin reductase that converts bilirubin into a colourless byproduct called urobilinogen. Urobilinogen then spontaneously degrades into a molecule called urobilin, which is responsible for the yellow color we are all familiar with.

Urobilin has long been linked to urine's yellow hue, but the research team's discovery of the enzyme responsible answers a question that has eluded scientists for over a century.

Aside from solving a scientific mystery, these findings could have important health implications. The research team found that bilirubin reductase is present in almost all healthy adults but is often missing from newborns and individuals with inflammatory bowel disease. They hypothesize that the absence of bilirubin reductase may contribute to infant jaundice and the formation of pigmented gallstones.

Now that we've identified this enzyme, we can start investigating how the bacteria in our gut impact circulating bilirubin levels and related health conditions like jaundice. This discovery lays the foundation for understanding the gut-liver axis.

In addition to jaundice and inflammatory bowel disease, the gut microbiome has been linked to various diseases and conditions, from allergies to arthritis to psoriasis. This latest discovery brings researchers closer to achieving a holistic understanding of the gut microbiome's role in human health.

BilR is a gut microbial enzyme that reduces bilirubin to urobilinogen, Nature Microbiology (2024). DOI: 10.1038/s41564-023-01549-x

Pathogenic bacteria use molecular 'shuttle services' to fill their injection apparatus with the right product

Disease-causing bacteria of the genus Salmonella or Yersinia can use tiny injection apparatuses to inject harmful proteins into host cells, much to the discomfort of the infected person. However, it is not only with a view to controlling disease that researchers are investigating the injection mechanism of these so-called type III secretion systems also known as "injectisomes."

If the structure and function of the injectisome were fully understood, researchers could hijack it to deliver specific drugs into cells, such as cancer cells. In fact, the structure of the injectisome has already been elucidated. However, it remained unclear how the bacteria load their syringes so that the right proteins are injected at the right time.

In a study published in Nature Microbiology, a team of scientists  has now been able to answer this question: mobile components of the injectisome comb through the bacterial cell in search of the proteins to be injected, so-called effectors. When they encounter an effector, they transport it like a shuttle bus to the gate of the injection needle.

How proteins of the sorting platform in the cytosol bind to effectors and deliver the cargo to the export gate of the membrane-bound injectisome is comparable to the processes at a freight terminal.

Scientists think that this shuttle mechanism helps to make the injection efficient and specific at the same time—after all, the bacteria have to inject the right proteins quickly to avoid being recognized and eliminated by the immune system. 

 Cytosolic sorting platform complexes shuttle type III secretion system effectors to the injectisome in Yersinia enterocolitica., Nature Microbiology (2024). DOI: 10.1038/s41564-023-01545-1

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.

Part 1

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.

Par t2

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

Part 3

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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