Protected droplets a new transport route for medicines

Microgels form a thin protective shell around a droplet until the temperature rises above 32 degrees. Then the microgels shrink and the droplet dissolves in the surrounding liquid. A study by researchers from the University of Gothenburg now reveals the underlying mechanism behind this process. The discovery could revolutionise methods of targeting medicines to specific locations within the body.
Emulsions consist of numerous droplets that are present in a liquid without dissolving and mixing with the liquid. For example, milk consists of fat droplets stabilised by milk proteins that are dispersed in water. In many applications such as medicine delivery, it is important to not only maintain the droplet structure but also to be able to control when the droplets dissolve. This is because the encapsulated active ingredients in the droplet should only be released once the medicine has entered the body.
Temperature-sensitive emulsions
Researchers from several universities, including the University of Gothenburg, have introduced a concept of responsive emulsions to control when the droplets dissolve.
“The idea is to stabilise emulsions using temperature-sensitive microgel particles that adapt their shape to the ambient temperature. At room temperature, they swell in water, but above 32°C, they shrink and contract,” explains Marcel Rey, a researcher in Physics at the University of Gothenburg and lead author of the study published in Nature Communications.
Understanding the mechanism
What happens when the temperature rises above 32°C is that the droplets dissolve in the surrounding liquid as they are no longer sufficiently stabilized by the protective microgel shell. While this phenomenon has been known in science for an extended period, the researchers have now uncovered that the fundamental mechanism driving stimuli-responsive emulsions involves morphological changes in the stabilizing microgels.

“The morphological changes in the stabilizing microgels, triggered by external stimuli, play a crucial role in influencing the stability of the associated emulsions. This understanding is fundamental to the design of microgels capable of stabilizing emulsions at room temperature while facilitating dissolution at body temperature,” explains Marcel Rey.
The stabilising microgels can be regarded as both particles and polymers. The particle character leads to a high stability of the emulsion, while the polymer character makes the microgels responsive to external influences leading to dissolution of the droplets. Achieving temperature-sensitive emulsions necessitates a delicate balance, requiring a minimal particle character for stability and a substantial polymer character for rapid and reliable dissolution of the droplets.
Emulsions can be tailored
“Now that we understand how responsive emulsions function, we can customize them to specific requirements. While our current efforts have been confined to laboratory experiments with temperature dependence, we are actively exploring the development of microgel-stabilized emulsions that respond to the pH of the surrounding fluid,” explains Marcel Rey.
Pharmaceutical research focussing on targeted medicines is crucial. The goal is to deliver medication in a higher concentration to specific diseased areas of the body rather than affecting the entire body.
“Responsive emulsions hold great potential as a precise tool for delivering medicine to specific areas in the body. Although additional research is needed, the future looks promising, and advancements can be expected over the next 10 years,” expresses Marcel Rey.

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Brain waves usually found in sleep can protect against epileptic activity

Slow waves that usually only occur in the brain during sleep are also present during wakefulness in people with epilepsy and may protect against increased brain excitability associated with the condition, finds a new study led by researchers at UCL.
The research, published in Nature Communications and involving the National Institute for Health and Care Research (NIHR) UCLH Biomedical Research Centre, examined electroencephalogram (EEG) scans from electrodes in the brains of 25 patients with focal epilepsy (a type of epilepsy characterised by seizures arising from a specific part of the brain), while they carried out an associative memory task.
The electrodes had been placed in the patients’ brains to localise abnormal activity and inform surgical treatment.
During the task, participants were presented with 27 pairs of images that remained on a screen for six seconds. The images were in nine groups of three — each group featuring a picture of a person, a place and an object. In each case, participants had to remember which images had been grouped together. EEG data were recorded continuously throughout the task.
After reviewing the EEG data, the team found that the brains of people with epilepsy were producing slow waves — lasting less than one second — while they were awake and taking part in the task.
The occurrence of these “wake” slow waves increased in line with increases in brain excitability and decreased the impact of epileptic spikes on brain activity.
In particular, there was a decrease in the “firing” of nerve cells, which the researchers say could protect against epileptic activity.

Senior author, Professor Matthew Walker (UCL Queen Square Institute of Neurology), said: “Sleep is crucial for repair, maintenance and resetting brain activity. When we are awake we experience a progressive increase in brain excitability, which is redressed during sleep.
“Recent studies have indicated that a specific form of brain activity, slow waves during sleep, play a crucial role in these restorative functions. We wanted to address whether these ‘sleep’ slow waves could occur during wakefulness in response to abnormal increases in brain activity associated with epilepsy.
“This study unveils, for the first time, a potential protective mechanism, ‘wake’ slow waves, employed by the brain to counteract epileptic activity. This mechanism takes advantage of protective brain activity that normally occurs during sleep, but, in people with epilepsy, can occur during wakefulness.”
As part of the research, the team also wanted to test if the occurrence of “wake” slow waves had any negative effects on cognitive function.
During the memory task, researchers found that the “wake” slow waves reduced nerve cell activity and so affected cognitive performance — increasing the length of time required by patients to complete the task.
The team reported that for each increase of one slow wave per second, the reaction time increased by 0.56 seconds.

Professor Walker said: “This observation suggests that the cognitive difficulties — in particularly, memory deficits — experienced by individuals with epilepsy may be attributed, in part, to the brief impairments induced by these slow waves.”
The team hope that future studies will be able to increase such activity as a potential novel treatment for people with epilepsy.
Lead author, Dr Laurent Sheybani (UCL Queen Square Institute of Neurology), said: “The parallel between the function of slow waves during sleep and, here, their beneficial impact in a pathological condition, is particularly interesting.
“Our study suggests that a naturally occurring activity is employed by the brain to offset pathological activities; however, this comes with a price, since ‘wake’ slow waves are shown to impact on memory performance.
“From a purely neurobiological perspective, the research also reinforces the idea that sleep activity can happen in specific areas of the brain, rather than occurring evenly throughout the brain.”
The research was funded by the Medical Research Council, Wellcome, UCLH Biomedical Research Centre and The Swiss National Science Foundation.

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Loss of auditory nerve fibers uncovered in individuals with tinnitus

A new study from Mass Eye and Ear investigators shows that individuals who report tinnitus, which present as a ringing in the ears in more than one out of ten adults worldwide, are experiencing auditory nerve loss that is not picked up by conventional hearing tests. This work is part of a P50 grant awarded by the National Institutes of Health (NIH) to Mass Eye and Ear researchers within the Eaton-Peabody Laboratories (EPL) for their work on cochlear synaptopathy, which is commonly referred to as “hidden hearing loss.” The results from this study provide a better understanding on the origins of tinnitus and are published November 30th in Scientific Reports.
“Beyond the nuisance of having persistent ringing or other sounds in the ears, tinnitus symptoms are debilitating in many patients, causing sleep deprivation, social isolation, anxiety and depression, adversely affecting work performance, and reducing significantly their quality of life,” said senior author Stéphane F. Maison, PhD, CCC-A, a principal investigator at Mass Eye and Ear, a member of Mass General Brigham, and clinical director of the Mass Eye and Ear Tinnitus Clinic. “We won’t be able to cure tinnitus until we fully understand the mechanisms underlying its genesis. This work is a first step toward our ultimate goal of silencing tinnitus.”
Many individuals with hearing loss report a buzzing, humming, ringing or even roaring sound in their ears. It’s been a longstanding idea that these symptoms, known as tinnitus, arise as a result of a maladaptive plasticity of the brain. In other words, the brain tries to compensate for the loss of hearing by increasing its activity, resulting in the perception of a phantom sound, tinnitus. Until recently though, this idea was disputed as some tinnitus sufferers have normal hearing tests.
However, the discovery of cochlear synaptopathy back in 2009 by Mass Eye and Ear investigators brought back to life this hypothesis as it was evidenced that patients with a normal hearing test can have a significant loss to the auditory nerve. In view of this paradigm shift in the way researchers and clinicians think about hearing loss, Maison and his team sought to determine if such hidden damage could be associated with the tinnitus symptoms experienced by a cohort of normal hearing participants. By measuring the response of their auditory nerve and brainstem, the researchers found that chronic tinnitus was not only associated with a loss of auditory nerve but that participants showed hyperactivity in the brainstem.
“Our work reconciles the idea that tinnitus may be triggered by a loss of auditory nerve, including in people with normal hearing,” said Maison.
In terms of future directions, the investigators aim to capitalize on recent work geared toward the regeneration of auditory nerve via the use of drugs called neurotrophins.
“The idea that, one day, researchers might be able to bring back the missing sound to the brain and, perhaps, reduce its hyperactivity in conjunction with retraining, definitely brings the hope of a cure closer to reality,” Maison added.
Disclosures: The authors declare no competing interests.
Funding: This work was supported by a grant from the NIDCD (P50 DC015857) and the Lauer Tinnitus Research Center at the Mass Eye and Ear.

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Lost brain function restored in mice after stroke

Researchers have succeeded in restoring lost brain function in mouse models of stroke using small molecules that in the future could potentially be developed into a stroke recovery therapy. “Communication between nerve cells in large parts of the brain changes after a stroke and we show that it can be partially restored with the treatment,” says Tadeusz Wieloch, senior professor of neurobiology at Lund University in Sweden.
“Concomitantly, the rodents regain lost somatosensory functions, something that around 60 per cent of all stroke patients experience today. The most remarkable result is that the treatment began several days after a stroke,” Wieloch continues.
In an ischemic stroke, lack of blood flow to the brain causes damage, which rapidly leads to nerve cell loss that affects large parts of the the vast network of nerve cells in the brain. This may lead to loss of function such as paralysis, sensorimotor impairment and vision and speech difficulties, but also to pain and depression. There are currently no approved drugs that improve or restore the functions after a stroke, apart from clot-dissolving treatment in the acute phase (within 4.5 hours of the stroke). Some spontaneous improvements occur, but many stroke patients suffer chronic loss of function. For example, about 60 per cent of stroke sufferers, experience lost somatosensori functions such as touch and position sense.
An international study published recently in the journal Brain and led by a research team from Lund University in collaboration with University of Rome La Sapeinza and Washington University at St. Louis, shows promising results in mice and rats that were treated with a class of substances that inhibit the metabotropic glutamate receptor (mGluR5), a receptor that regulates communication in the brain’s nerve cell network.
“Rodents treated with the GluR5 inhibitor regained their somatosensori functions,” says Tadeusz Wieloch, who led the study published in BRAIN.
Two days after the stroke, i.e. when the damage had developed and function impairment was most prominent, the researchers started treating the rodents that exhibited the greatest impaired function.
“A temporary treatment effect was seen after just 30 minutes, but treatment for several weeks is needed to achieve a permanent recovery effect. Some function improvement was observed even when the treatment started 10 days after a stroke,” says Tadeusz Wieloch.

Importantly, sensorimotor functions improved, even though the extent of the brain damage was not diminished. This, explains Tadeusz Wieloch, is due to the intricate network of nerve cells in the brain, known as the connectome, i.e. how various areas of the brain are connected and communicate with each to form the basis for various brain functions.
“Impaired function after a stroke is due to cell loss, but also because of reduced activity in large parts of the connectome in the undamaged brain. The receptor mGluR5 is apparently an important factor in the reduced activity in the connectome, which is prevented by the inhibitor which therefore restores the lost brain function,” says Tadeusz Wieloch.
The results also showed that sensorimotor function was further improved if treatment with the mGluR5 inhibitor is combined with somatosensory training by housing several rodents in cages enriched with toys, chains, grids, and plastic tubes.
The researchers hope that in the future their results could lead to a clinical treatment that could be initiated a few days after an ischemic stroke.
“Combined with rehabilitation training, it could eventually be a new promising treatment. However, more studies are needed. The study was conducted on mice and rats, and of course needs to be repeated in humans. This should be possible since several mGluR5 inhibitors have been studied in humans for the treatment of neurological diseases other than stroke, and shown to be tolerated by humans,” says Tadeusz Wieloch.
The research is conducted with support from the Swedish Research Council, Alborada Trust, Hans-Gabriel and Alice Wachtmeister Foundation, and Multipark Strategic Research Area.

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Progress toward improved vaccines

To ensure that vaccines provide strong and lasting immunization, it is often necessary to supplement the actual vaccine (antigen) with additives that stimulate the immune system: adjuvants. Today, only a few substances have been approved for use as adjuvants. In the journal Angewandte Chemie, a research team has now introduced a spectrum of potential adjuvants. They started with the immune stimulant α-glactosyl ceramide (α-GalCer) and synthesized many different variants from a set of four building blocks.
α-GalCer is a synthetic glycolipid (a compound made from fat and sugar building blocks) based on similar compounds found in sea sponges. It binds to CD1-d, a special receptor on antigen-presenting cells. This activates certain immune cells and induces secretion of cytokines that stimulate the immune system. In this way, this substance boosts the immune response, assists in the battle against pathogens and tumor cells, and reduces autoimmune reactions. Among the newly synthesized α-GalCer analogs, the team led by Berhnard Westermann, Daniel G. Rivera, and Carlos A. Guzmán from the Leibniz Institute of Plant Biochemistry (Halle/Saale) and the Helmholtz Center for Infection Research (Braunschweig) identified a number of compounds that have significantly better and/or somewhat different activity.
The key to their success was the use of a special reaction for the synthesis of the α-GalCer analogs: in a reaction known as the Ugi four-component reaction, the target molecules are assembled in one step from four individual building blocks. The team varied these four components broadly in a combinatorial method and synthesized a collection of different α-GalCer derivatives. In particular, they used a functional group (N-substituent of the amide bond) that had not been employed in the derivatization of α-GalCer before. This allowed the team to introduce many different additional functionalities into their α-GalCer analogs.
This strategy led to the discovery of compounds that trigger stronger antigen-specific T-cell stimulation and higher antibody reaction when they are administered to mice together with a model antigen, either by injection or through the nasal mucosa. In addition, various functionalized α-GalCer analogs demonstrated stronger adjuvant activity in vitro and in animal studies that an α-GalCer previously optimized (conjugated with polyethylene glycol) for this purpose.
Interestingly, some of the new analogs showed somewhat different effects on the immune system, making it possible to elicit differently balanced immune responses through controlled variation of the derivatization. This could make it possible to develop adjuvants that can be tailored precisely to the requirements of the pathogens in question. In addition, it may be possible to introduce an additional binding site through which the antigen could be bound directly to the adjuvant without compromising its effect — a requirement for the development of self-adjuvating vaccines.

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Early body contact develops premature babies' social skills

Skin-to-skin contact between parent and infant during the first hours after a very premature birth helps develop the child’s social skills. This is according to a new study published in JAMA Network Open by researchers from Karolinska Institutet and others. The study also shows that fathers may play a more important role than previous research has shown.
In current practice, very premature babies are usually placed in an incubator to keep them warm and to stabilize them during the first hours after birth. In the “Immediate parent-infant skin-to-skin study” (IPISTOSS), 91 premature babies born at 28 to 33 weeks were randomized to either traditional care in an incubator or immediate skin-to-skin contact with one of the parents. The study has generated several results that show, among other things, that immediate skin-to-skin contact is safe for babies and beneficial for their cardiorespiratory stabilization and temperature maintenance, and that it is perceived as valuable by the parents.
Now, as part of this study, the researchers have also studied the social development at four months of age of 71 of these premature babies. The children were randomly assigned to receive either standard care in an incubator or to receive care resting on one of their parents’ breasts, either the mother’s or the father’s, for the first six hours after birth.
“What is new about our study is that we also allowed the fathers to have skin-to-skin contact immediately after the birth. In most previous studies, it is the mother who is the primary caregiver, but in our study it was the fathers who had the most skin-to-skin contact,” says Wibke Jonas, midwife, senior lecturer and associate professor at Karolinska Institutet’s Department of Women’s and Children’s Health, as well as research leader and last author of the study.
“The study has identified fathers as a previously untapped resource that really has an important function in having immediate skin-to-skin contact with their infant if the mother is not available,” says Siri Lilliesköld, PhD student at the same department and specialist nurse in neonatal care, and first author of the study.
After four months, the social interaction between mother and infant was filmed and assessed by two psychologists who did not know which infant had received early skin-to-skin contact and which had not.
The quality of the interaction was measured according to the Parent-Child Early Relational Assessment (PCERA) scale, where different elements are graded between one and five, with one being cause for concern and five being very good quality.

The infants who received immediate skin-to-skin contact had significantly better results in a subscale measuring the infant’s communicative and social skills. On the five-point scale, their average score was closer to four, while the infants cared for according to current practice were just above three.
“What you could see was that the infants in the skin-to-skin group had slightly better communication skills, they were a bit more social and happier,” says Wibke Jonas.
Premature babies have developmental challenges as they grow up and need a lot of support. Even though medical developments have come a long way, the care of these babies still needs to be developed, the researchers say.
“If we combine the immediate medical care of the very premature babies with a relatively simple intervention such as skin-to-skin contact, it has effects on the infants social skills,” says Jonas Wibke and continues.
“Previous studies have shown that premature babies perform slightly poorer when socially interacting, for example, they do not give as clear signals in the interaction with their mothers. The closeness between babies and their parents at birth may therefore stimulate later interaction and thus the development of the infant.”
The benefits of immediate skin-to-skin contact are so clear that both Wibke Jonas and Siri Lilliesköld believe it should be introduced now in Swedish neonatal care. And this work is already underway, they say.
‘We have worked very actively to minimize separation between infants and parents in general, and now we have the evidence to do the same with these very premature babies,” says Siri Lilliesköld.
The research team will continue to report on the development of the infants at 12 and 24 months.
The study is a collaboration between researchers from Karolinska Institutet and the University Hospital of Stavanger, Norway, and the University of Turku, Finland. The research was funded by, among others, the Swedish Research Council, Region Stockholm and Stiftelsen Barnavård. The researchers declare that there are no conflicts of interest.

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Twin research indicates that that a vegan diet improves cardiovascular health

In a study with 22 pairs of identical twins, Stanford Medicine researchers and their colleagues have found that a vegan diet improves cardiovascular health in as little as eight weeks.
Although it’s well-known that eating less meat improves cardiovascular health, diet studies are often hampered by factors such as genetic differences, upbringing and lifestyle choices. By studying identical twins, however, the researchers were able to control for genetics and limit the other factors, as the twins grew up in the same households and reported similar lifestyles.
“Not only did this study provide a groundbreaking way to assert that a vegan diet is healthier than the conventional omnivore diet, but the twins were also a riot to work with,” said Christopher Gardner, PhD, the Rehnborg Farquhar Professor and a professor of medicine. “They dressed the same, they talked the same and they had a banter between them that you could have only if you spent an inordinate amount of time together.”
The study will publish Nov. 30 in JAMA Network Open. Gardner is the senior author. The study was co-first authored by Matthew Landry, PhD, a former Stanford Prevention Research Center postdoctoral scholar, now at the University of California, Irvine, and Catherine Ward, PhD, a post-doctoral scholar at the center.
Twin participants
The trial, conducted from May to July 2022, consisted of 22 pairs of identical twins for a total of 44 participants. The study authors selected healthy participants without cardiovascular disease from the Stanford Twin Registry — a database of fraternal and identical twins who have agreed to participate in research studies — and matched one twin from each pair with either a vegan or omnivore diet.
Both diets were healthy, replete with vegetables, legumes, fruits and whole grains and void of sugars and refined starches. The vegan diet was entirely plant-based, included no meat or animal products such as eggs or milk. The omnivore diet included chicken, fish, eggs, cheese, dairy and other animal-sourced foods.

During the first four weeks, a meal service delivered 21 meals per week — seven breakfasts, lunches and dinners. For the remaining four weeks, the participants prepared their own meals.
A registered dietitian, or “diet whisperer,” according to Gardner, was on call to offer suggestions and answer questions regarding the diets during the duration of the study. The participants were interviewed about their dietary intake and kept a log of the food they ate.
Forty-three participants completed the study which, Gardner said, demonstrates how feasible it is to learn how to a prepare a healthy diet in four weeks.
“Our study used a generalizable diet that is accessible to anyone, because 21 out of the 22 vegans followed through with the diet,” said Gardner, who is a professor in the Stanford Prevention Research Center. “This suggests that anyone who chooses a vegan diet can improve their long-term health in two months, with the most change seen in the first month.”
Improving health
The authors found the most improvement over the first four weeks of the diet change. The participants with a vegan diet had significantly lower low-density lipoprotein cholesterol (LDL-C) levels, insulin and body weight — all of which are associated with improved cardiovascular health — than the omnivore participants.

At three time points — at the beginning of the trial, at four weeks and at eight weeks — researchers weighed the participants and drew their blood. The average baseline LDL-C level for the vegans was 110.7 mg/dL and 118.5 mg/dL for the omnivore participants; it dropped to 95.5 for vegans and 116.1 for omnivores at the end of the study. The optimal healthy LDL-C level is less than 100.
Because the participants already had healthy LDL-C levels, there was less room for improvement, Gardner said, speculating that participants who had higher baseline levels would show greater change.
The vegan participants also showed about a 20% drop in fasting insulin — higher insulin level is a risk factor for developing diabetes. The vegans also lost an average of 4.2 more pounds than the omnivores.
“Based on these results and thinking about longevity, most of us would benefit from going to a more plant-based diet,” Gardner said.
The vegan participants (and the omnivores to some extent) did the three most important things to improve cardiovascular health, according to Gardner: They cut back on saturated fats, increased dietary fiber and lost weight.
A global flair
Gardner emphasizes that although most people will probably not go vegan, a nudge in the plant-based direction could improve health. “A vegan diet can confer additional benefits such as increased gut bacteria and the reduction of telomere loss, which slows aging in the body,” Gardner said.
“What’s more important than going strictly vegan is including more plant-based foods into your diet,” said Gardner, who has been “mostly vegan” for the last 40 years. “Luckily, having fun with vegan multicultural foods like Indian masala, Asian stir-fry and African lentil-based dishes can be a great first step.”
Gardner is a member of the Stanford Cardiovascular Institute, the Wu Tsai Human Performance Alliance, the Maternal and Child Health Research Institute, and the Stanford Cancer Institute.
The study was funded by the Vogt Foundation; the Stanford Clinical and Translational Science Award; and the National Heart, Lung and Blood Institute.

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A mineral produced by plate tectonics has a global cooling effect

MIT geologists have found that a clay mineral on the seafloor, called smectite, has a surprisingly powerful ability to sequester carbon over millions of years.
Under a microscope, a single grain of the clay resembles the folds of an accordion. These folds are known to be effective traps for organic carbon.
Now, the MIT team has shown that the carbon-trapping clays are a product of plate tectonics: When oceanic crust crushes against a continental plate, it can bring rocks to the surface that, over time, can weather into minerals including smectite. Eventually, the clay sediment settles back in the ocean, where the minerals trap bits of dead organisms in their microscopic folds. This keeps the organic carbon from being consumed by microbes and expelled back into the atmosphere as carbon dioxide.
Over millions of years, smectite can have a global effect, helping to cool the entire planet. Through a series of analyses, the researchers showed that smectite was likely produced after several major tectonic events over the last 500 million years. During each tectonic event, the clays trapped enough carbon to cool the Earth and induce the subsequent ice age.
The findings are the first to show that plate tectonics can trigger ice ages through the production of carbon-trapping smectite.
These clays can be found in certain tectonically active regions today, and the scientists believe that smectite continues to sequester carbon, providing a natural, albeit slow-acting, buffer against humans’ climate-warming activities.
“The influence of these unassuming clay minerals has wide-ranging implications for the habitability of planets,” says Joshua Murray, a graduate student in MIT’s Department of Earth, Atmospheric, and Planetary Sciences. “There may even be a modern application for these clays in offsetting some of the carbon that humanity has placed into the atmosphere.”
Murray and Oliver Jagoutz, professor of geology at MIT, have published their findings today in Nature Geoscience.

A clear and present clay
The new study follows up on the team’s previous work, which showed that each of the Earth’s major ice ages was likely triggered by a tectonic event in the tropics. The researchers found that each of these tectonic events exposed ocean rocks called ophiolites to the atmosphere. They put forth the idea that, when a tectonic collision occurs in a tropical region, ophiolites can undergo certain weathering effects, such as exposure to wind, rain, and chemical interactions, that transform the rocks into various minerals, including clays.
“Those clay minerals, depending on the kinds you create, influence the climate in different ways,” Murray explains.
At the time, it was unclear which minerals could come out of this weathering effect, and whether and how these minerals could directly contribute to cooling the planet. So, while it appeared there was a link between plate tectonics and ice ages, the exact mechanism by which one could trigger the other was still in question.
With the new study, the team looked to see whether their proposed tectonic tropical weathering process would produce carbon-trapping minerals, and in quantities that would be sufficient to trigger a global ice age.
The team first looked through the geologic literature and compiled data on the ways in which major magmatic minerals weather over time, and on the types of clay minerals this weathering can produce. They then worked these measurements into a weathering simulation of different rock typesthat are known to be exposed in tectonic collisions.

“Then we look at what happens to these rock types when they break down due to weathering and the influence of a tropical environment, and what minerals form as a result,” Jagoutz says.
Next, they plugged each weathered, “end-product” mineral into a simulation of the Earth’s carbon cycle to see what effect a given mineral might have, either in interacting with organic carbon, such as bits of dead organisms, or with inorganic , in the form of carbon dioxide in the atmosphere.
From these analyses, one mineral had a clear presence and effect: smectite. Not only was the clay a naturally weathered product of tropical tectonics, it was also highly effective at trapping organic carbon. In theory, smectite seemed like a solid connection between tectonics and ice ages.
But were enough of the clays actually present to trigger the previous four ice ages? Ideally, researchers should confirm this by finding smectite in ancient rock layers dating back to each global cooling period.
“Unfortunately, as clays are buried by other sediments, they get cooked a bit, so we can’t measure them directly,” Murray says. “But we can look for their fingerprints.”
A slow build
The team reasoned that, as smectites are a product of ophiolites, these ocean rocks also bear characteristic elements such as nickel and chromium, which would be preserved in ancient sediments. If smectites were present in the past, nickel and chromium should be as well.
To test this idea, the team looked through a database containing thousands of oceanic sedimentary rocks that were deposited over the last 500 million years. Over this time period, the Earth experienced four separate ice ages. Looking at rocks around each of these periods, the researchers observed large spikes of nickel and chromium, and inferred from this that smectite must also have been present.
By their estimates, the clay mineral could have increased the preservation of organic carbon by less than one-tenth of a percent. In absolute terms, this is a miniscule amount. But over millions of years, they calculated that the clay’s accumulated, sequestered carbon was enough to trigger each of the four major ice ages.
“We found that you really don’t need much of this material to have a huge effect on the climate,” Jagoutz says.
“These clays also have probably contributed some of the Earth’s cooling in the last 3 to 5 million years, before humans got involved,” Murray adds. “In the absence of humans, these clays are probably making a difference to the climate. It’s just such a slow process.”
“Jagoutz and Murray’s work is a nice demonstration of how important it is to consider all biotic and physical components of the global carbon cycle,” says Lee Kump, a professor of geosciences at Penn State University, who was not involved with the study. “Feedbacks among all these components control atmospheric greenhouse gas concentrations on all time scales, from the annual rise and fall of atmospheric carbon dioxide levels to the swings from icehouse to greenhouse over millions of years.”
Could smectites be harnessed intentionally to further bring down the world’s carbon emissions? Murray sees some potential, for instance to shore up carbon reservoirs such as regions of permafrost. Warming temperatures are predicted to melt permafrost and expose long-buried organic carbon. If smectites could be applied to these regions, the clays could prevent this exposed carbon from escaping into and further warming the atmosphere.
“If you want to understand how nature works, you have to understand it on the mineral and grain scale,” Jagoutz says. “And this is also the way forward for us to find solutions for this climatic catastrophe. If you study these natural processes, there’s a good chance you will stumble on something that will be actually useful.”
This research was funded, in part, by the National Science Foundation.

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Distinct brain activity triggered by memories of trauma

It is well known that people who have lived through traumatic events like sexual assault, domestic abuse, or violent combat can experience symptoms of post-traumatic stress disorder (PTSD), including terrifying flashbacks, severe anxiety, and uncontrollable thoughts about the incident. But what exactly happens in the brains of PTSD patients as they recall these traumatic events? Are they remembered the same way as, say, the loss of a beloved pet — or, for that matter, a relaxing walk on the beach?
A new study co-led by Yale researchers finds that the brain activity triggered by recollections of traumatic experiences among people with PTSD is in fact markedly different from that which occurs when remembering sad or “neutral” life experiences.
In the study, which involved 28 different patients diagnosed with PTSD, researchers found that brain patterns were consistent across all individuals when they recalled their more typical life experiences. But when reminded of traumatic events from their past, neural responses differed significantly among the individuals.
“When people recall sad or neutral events from their past experience, the brain exhibits highly synchronous activity among all PTSD patients,” said Yale’s Ilan Harpaz-Rotem, professor of psychiatry and psychology at Yale and co-senior author of the paper. “However, when presented with stories of their own traumatic experiences, brain activity was highly individualized, fragmented, and disorganized.
“They are not like memories at all.”
The study, conducted with researchers at Icahn School of Medicine at Mount Sinai in New York, is published Nov. 30 in the journal Nature Neuroscience.
For the study, the researchers asked each of the 28 participants a range of questions, which pertained to their traumatic experiences, events in their lives that caused sadness (such as the death of a family member), and moments when they felt relaxed. Each person’s story was written down and then read back to them while they underwent fMRI (functional magnetic resonance imaging) scans, which are used to map brain activity based on blood flow.

The researchers found that activity in the hippocampus — the area of the brain that forms memories of our experiences — followed similar patterns of activity among all subjects when they were reminded of sad or relaxing experiences from their lives, suggesting typical normal memory formation.
But when stories about their traumatic experiences were read back to them, the similarities in hippocampal activity among the group members disappeared. Instead, the hippocampus of each subject exhibited highly individualized and fragmented activity, unlike the more synchronous patterns of brain activity during normal memory formation.
The results could explain why PTSD patients have difficulty recalling traumatic experiences in a coherent way and hints at why these past experiences can trigger disabling symptoms, the researchers say.
These insights may help psychotherapists guide PTSD patients to develop narratives about their experiences which may help them eliminate the sense of immediate threat caused by their trauma, Harpaz-Rotem said.

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This 'gross' mixture has big benefits for the study of bacteria

Animal models are a necessary research tool for understanding how diseases develop and how therapies work in biological systems and can be credited for breakthroughs ranging from effective antibiotics to the COVID vaccines.
The responsible and judicious use of animal models is prioritized by research institutions around the world and a unique research protocol developed by Melanie Pearson, Ph.D., of the Department of Microbiology & Immunology, and her team at University of Michigan Medical School is garnering widespread interest among microbiologists.
In a recent paper in the journal Infection and Immunity, her group describes a product called organ agar that could be deployed to more efficiently screen bacteria that cause urinary tract infections.
Agar is a gelatinous product made of seaweed routinely used in laboratories to grow colonies of bacteria in petri dishes.
Pearson discovered that creating a mixture composed of the agar plus human urine and the organ her team wanted to study, specifically the bladder and kidneys, enabled their team to screen more than 1,700 mutants of the UTI-causing bacteria Proteus mirabilisusing a quarter of the mice typically required.
Pearson explains that in a classic mouse study of a urinary tract infection, mutated bacteria — bacteria that are missing individual genes — are introduced into an animal’s bladder and then the dominant strains assessed to determine what bacterial genes are important for infection. Knowing this could enable researchers to target specific variants for drug development, for example.
The use of organ agar has multiple potential benefits, explains Pearson.

For one, it can help microbiologists get around what is known as the bottleneck problem.
In a living system, only a certain number of mutants are able to gain a foothold, with the rest lost at random.
When Pearson tried the screening method using organ agar, her team found that the dominant bacteria reproduced those that were dominant in a live animal.
What’s more, bacteria that did not do well on organ agar also did not do well in a live animal.
Furthermore, organ agar could enable researchers without access to animal models to create physiologically relevant models of infection or colonization and allow for more efficient screening of bacterial and other microorganism candidates for further study.

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