Tech

New research shows that crustaceans such as shrimps, lobsters and crabs have more in common with their insect relatives than previously thought - when it comes to the structure of their brains.

Both insects and crustaceans possess mushroom-shaped brain structures known in insects to be required for learning, memory and possibly negotiating complex, three-dimensional environments, according to the study, led by University of Arizona neuroscientist Nicholas Strausfeld.

The research, published in the open-access journal eLife, challenges a widely held belief in the scientific community that these brain structures - called "mushroom bodies" - are conspicuously absent from crustacean brains.

In 2017, Strausfeld's team reported a detailed analysis of mushroom bodies discovered in the brain of the mantis shrimp, Squilla mantis. In the current paper, the group provides evidence that neuro-anatomical features that define mushroom bodies - at one time thought to be an evolutionary feature proprietary to insects - are present across crustaceans, a group that includes more than 50,000 species.

Crustaceans and insects are known to descend from a common ancestor that lived about a half billion years ago and has long been extinct.

"The mushroom body is an incredibly ancient, fundamental brain structure," said Strausfeld, Regents Professor of neuroscience and director of the University of Arizona's Center for Insect Science. "When you look across the arthropods as a group, it's everywhere."

In addition to insects and crustaceans, other arthropods include arachnids, such as scorpions and spiders, and myriapods, such as millipedes and centipedes.

Characterized by their external skeletons and jointed appendages, arthropods make up the most species-rich group of animals known, populating almost every conceivable habitat. About 480 million years ago, the arthropod family tree split, with one lineage producing the arachnids and another the mandibulates. The second group split again to provide the lineage leading to modern crustaceans, including shrimps and lobsters, and six-legged creatures, including insects - the most diverse group of arthropods living today.

Decades of research has untangled arthropods' evolutionary relationships using morphological, molecular and genetic data, as well as evidence from the structure of their brains.

Mushroom bodies in the brain have been shown to be the central processing units where sensory input converges. Vision, smell, taste and touch all are integrated here, as studies on honeybees have shown. Arranged in pairs, each mushroom body consists of a column-like portion, called the lobe, capped by a dome-like structure, called the calyx, where neurons that relay information sent from the animal's sensory organs converge. This information is passed to neurons that supply thousands of intersecting nerve fibers in the lobes that are essential for computing and storing memories.

Recent research by other scientists has also shown that those circuits interact with other brain centers in strengthening or reducing the importance of a recollection as the animal gathers experiences from its environment.

"The mushroom bodies contain networks where interesting associations are being made that give rise to memory," Strausfeld said. "It's how the animal makes sense of its environment."

A more evolutionarily "modern" group of crustaceans called Reptantia, which includes many lobsters and crabs, do indeed appear to have brain centers that don't look at all like the insect mushroom body. This, the authors suggest, helped create the misconception crustaceans lack the structures altogether.

Brain analysis of crustaceans has revealed that while the mushroom bodies found in crustaceans appear more diverse than those of insects, their defining neuroanatomical and molecular elements are all there.

Using crustacean brain samples, the researchers applied tagged antibodies that act like probes, homing in on and highlighting proteins that have been shown to be essential for learning and memory in fruit flies. Sensitive tissue-staining techniques further enabled visualization of mushroom bodies' intricate architecture.

"We know of several proteins that are necessary for the establishment of learning and memory in fruit flies," Strausfeld said, "and if you use antibodies that detect those proteins across insect species, the mushroom bodies light up every time."

Using this method revealed that the same proteins are not unique to insects; they show up in the brains of other arthropods, including centipedes, millipedes and some arachnids. Even vertebrates, including humans, have them in a brain structure called the hippocampus, a known center for memory and learning.

"Corresponding brain centers - the mushroom body in arthropods, marine worms, flatworms and, possibly, the hippocampus of vertebrates - appear to have a very ancient origin in the evolution of animal life," Strausfeld said.

So why do the most commonly studied crustaceans have mushroom bodies that can appear so drastically different from their insect counterparts? Strausfeld and his co-authors have a theory: Crustacean species that inhabit environments that demand knowledge about elaborate, three-dimensional areas are precisely the ones whose mushroom bodies most closely resemble those in insects, a group that has also mastered the three-dimensional world by evolving to fly.

"We don't think that's a coincidence," Strausfeld says. "We propose that that the complexity of inhabiting a three-dimensional world may demand special neural networks that allow a sophisticated level of cognition for negotiating that space in three dimensions."

Lobsters and crabs, on the other hand, spend their lives confined mostly to the seafloor, which may explain why they've historically been said to lack mushroom bodies.

"At the risk of offending colleagues who are partial to crabs and lobsters: I view many of these as flat-world inhabitants," Strausfeld says. "Future studies will be able to tell us which are smarter: the reef dwelling mantis shrimp, a top predator, or the reclusive lobster."

Strausfeld co-authored the paper with two of his former students - Gabriella Wolff, now a post-doctoral fellow at the University of Washington, and Marcel Sayre, now a doctoral student at Lund University in Sweden. They hope that the study of mushroom bodies will further help in resolving how brains may have evolved and what environmental conditions shaped that process.

"This research moves us closer to answering the ultimate question," Strausfeld says. "We want to know: What was the earliest brain like?"

Eating too much salt can have significant negative health implications, and modern processed food typically contains high levels of salt to improve taste and preservation.

But new processing technology out of Washington State University called microwave assisted thermal sterilization (MATS) could make it possible to reduce sodium while maintaining safety and tastiness.

In a new study published in the Journal of Food Science, WSU researchers found that the MATS processing, which uses microwave technology to kill any pathogens in food, doesn't reduce the flavor intensity of other ingredients. The current method of food processing preservation, called retort, does reduce flavor intensity.

The study looked at mashed potatoes cooked fresh, using retort, and using MATS. They had tasting panels and used WSU's e-tongue to measure the impact of reducing salt and the intensity of other ingredients, like pepper and garlic.

"The intensity of pepper is the same in MATS and in fresh potatoes, but is reduced in retort processing," said Carolyn Ross, the lead author of this paper. "The heating process of retort, which takes longer to get up to temperature and longer to cool off, changes the texture and flavor of food. MATS is much faster, so it doesn't have nearly as big an impact on those areas."

If flavor intensity of pepper remains high, then not as much salt is required to make the food palatable, or tasty, Ross said.

The researchers, including WSU's Sasha Barnett, Shyam Sablani, and Juming Tang, found that MATS-prepared mashed potatoes could have up to a 50 percent reduction in salt and it was still enjoyed by the tasting panel.

"They could tell it wasn't as salty, but they still liked it because the flavor intensity of other ingredients was higher," said Ross, a professor in WSU's School of Food Science. "Basically, if you can enhance the flavors of herbs, the food still seems salty enough to be enjoyed."

The MATS technology is still relatively new, but Ross thinks it could go a long way to helping reduce the salt used in processed foods.

"We have to make a product that people want to eat," she said. "And there are a lot of older adults that eat prepared meals because of convenience and safety. So if we can reduce salt intake from those foods, and still have pleasant flavors, it could be hugely beneficial."

Nonalcoholic fatty liver disease (NAFLD) is mostly diagnosed in overweight and obese people. However, severe forms of NAFLD can also be detected in rare genetic diseases such as lipodystrophy or in patients with HIV, putting them at a high risk for developing liver failure, diabetes and cardiovascular diseases. Norbert Stefan and colleagues have now detected a yet unknown cause of NAFLD in lean people. They report a case of a woman who received immune checkpoint blockade therapy for skin cancer, which may have triggered inflammation of her subcutaneous fat, resulting in a dramatic loss of fat mass and severe NAFLD.

The world-wide epidemic of NAFLD is thought to mainly be driven by an unhealthy lifestyle with little physical activity and a diet high in saturated fats, sugar and fructose. In these overweight and obese patients, weight-loss brought about by lifestyle modification is considered most effective and safe to treat NAFLD and reduce the risk of advanced forms of liver diseases, such as cirrhosis or liver cancer, type 2 diabetes and cardiovascular diseases (CVD). However, NAFLD can also be found in lean people. These patients either have genetically-determined lipodystrophy, acquired lipodystrophy syndromes or HIV-lipodystrophy, which are all characterized by a dramatic reduction in fat mass under the skin and an increase of fat inside the abdomen and in the liver.

Thomas Eigentler and Diana Lomberg from the Department of Dermatology of the University Hospital of Tübingen, Germany, and Jürgen Machann and Norbert Stefan, from the Department of Internal Medicine IV of the University Hospital of Tübingen, the Helmholtz Zentrum München and the German Center for Diabetes Research (DZD), have now detected a novel cause of acquired lipodystrophy. They report the case of a 45-year-old woman having malignant melanoma, a skin cancer, which was effectively treated with the programmed cell death protein 1 (PD-1) inhibitor Nivolumab. This and other so-called "checkpoint inhibitors" have revolutionized the treatment of cancer, especially malignant melanoma.

However, therapy with these checkpoint inhibitors is also associated with adverse events that commonly affect the skin, gastrointestinal tract, lungs and endocrine system. Towards the end of treatment with Nivolumab, Stefan and colleagues found in their patient very high levels of lipids, a newly developed diabetes and a severe form of NAFLD. This was completely unexpected, particularly because their patient lost 31 kg of body weight. Tissue biopsy of her subcutaneous fat and magnetic resonance imaging resulted in the diagnosis of acquired lipodystrophy with a severe form of inflammation of her fat. This may have been triggered by the immonomodulatory function of checkpoint inhibitors in the patient, who was previously diagnosed with asymptomatic mastocytosis, an immune-cell related disorder. Intensive pharmacological treatment, particularly with pioglitazone, which induces an increase in fat mass under the skin, resulted in that her liver fat, liver enzymes and lipid levels returned to almost normal values.

Stefan, who is a Professor of Diabetology at the University of Tübingen, and a Visiting Professor at the Harvard Medical School, Boston, concludes that "it is important that clinicians treating patients with checkpoint inhibitors should be aware of a newly-identified adverse event associated with such therapy. Inflammation of adipose tissue, resulting in severe fatty liver may occur. In such conditions specific pharmacotherapy, possibly involving mechanisms to increase the amount of subcutaneous fat mass, and, thereby, keeping the lipids in a safe storage space, may be very helpful in these patients."

PROVIDENCE, R.I. [Brown University] -- A team of researchers has developed a new technique to map the three-dimensional forces that clusters of human cells exert on their surrounding environment. The method could potentially help scientists better understand how tissue forms, how wounds heal or how tumors spread.

"We know that the way groups of cells interact with their extracellular matrix is important, and we want to understand the instructions that tell these clusters to become organized into tissue-like architecture, or alternatively to become disorganized like an invasive tumor," said Ian Y. Wong, an assistant professor in Brown University's School of Engineering and corresponding author of a paper describing the work in the Proceedings of the National Academy of Sciences. "This technique gives us a way to profile these mechanical interactions between cells and matrix in a way that we couldn't before."

The new technique makes use of traction force microscopy (TFM), an imaging method that has been widely used to study the forces exerted by single cells. To make TFM measurements, researchers place cells within biomaterials that mimic an extracellular matrix and contain thousands of tiny fluorescent beads. By tracking the motion of the beads as the cell moves inside the gel, researchers can record the ways in which the cell is pushing, pulling and twisting the biomaterial in three dimensions.

The goal of this new technique is to bring TFM to bear on multicellular clusters.

"We know that tumors, for example, tend to be spatially heterogeneous, with cells behaving differently throughout a tumor," said co-first author Susan Leggett, who led this research while a Ph.D. student at Brown and is currently a postdoctoral researcher at Princeton University. "So elucidating heterogenous behaviors across a multicellular cluster is something that's important in a clinical context."

Doing so wasn't easy, however. Groups of cells each behaving differently can quickly make an analysis messy and imprecise. One of the challenges when dealing with large three-dimensional data sets is how to depict them in a convenient, quick and reader-friendly format. So Leggett and her colleagues came up with what they call DART (Displacement Arrays of Rendered Tractions), which virtually divides the volume around each cluster into 16 distinct regions. By mapping the forces that dominate each of the regions into a "DART-board" display, the technique can capture the differing forces in play within a cluster in an easy-to-interpret format. The approach is similar to the way three-dimensional terrain features are depicted in common landscape or hiking maps, the researchers say.

Co-first author Mohak Patel, who was also a Ph.D. student at Brown in solid mechanics and computer science, helped the team to streamline the image processing required to track the fluorescent beads embedded in the biomaterial. That streamlining enables the technique to image many clusters at a time, arrayed on 96-well cell culture plates. That high throughput, which hadn't been feasible previously, makes the technique even more powerful, the researchers say.

To validate their method, the researchers cultured clusters of mammary cells. On some of the clusters, the researchers used a drug to stimulate what's known as the epithelial to mesenchymal transition (EMT). It's a process by which compact and fairly docile epithelial cells transform into elongated and highly mobile mesenchymal cells. In the study, the researchers were able to establish distinct force signatures for the epithelial clusters, the mesenchymal clusters, and clusters that were in a transitory state in between the two. From there, the team was able to train a machine learning algorithm that could accurately identify clusters from each group.

The team says the technique could have a variety of applications, from basic biology research to clinical cancer research or precision medicine. "Basically in any setting where cells need to move in an extracellular matrix, we can use this technique to look for patterns," said co-author Christian Franck, an associate professor of mechanical engineering at the University of Wisconsin, Madison.

This technique could be used to study organoids, small clusters of cells whose architecture and function mimic tissues and organs in the body. This approach is based on culturing primary human cells on a dish in order to screen personalized drug treatment. "You could imagine isolating patient cells from a tumor biopsy, culturing them on a 96-well plate, then treating with different drugs to see whether they affect how these cells migrate and divide," Wong said.

Scientists at St. Jude Children's Research Hospital and Princess Margaret Cancer Centre in Toronto, Canada, have reported that subpopulations of leukemic cells present at diagnosis can cause relapse in children with acute lymphoblastic leukemia. The findings have implications for current and future therapy. The work recently appeared as an advance online publication in Cancer Discovery.

While there have been significant advances in the treatment of ALL, the disease recurs in 15-20% of pediatric and 40-75% of adult patients. Prognosis for patients who relapse is poor. Treatment for ALL eliminates some leukemia cells, while others survive and progress to relapse; but why this happens has remained a key question in cancer research.

Read the full text of the article:
"Relapse fated latent diagnosis subclones in acute B lineage leukaemia are drug tolerant and possess distinct metabolic programs."
Cancer Discovery, Published Feb. 21, 2020

There are distinct populations of ALL cells called subclones, whose behavior and properties differ from their fellow leukemia cells in part based on their underlying genetics. Researchers identified and isolated subclones, present at diagnosis, that somehow survive therapy and eventually initiate relapse. The scientists called these cells diagnosis relapse initiating clones, or dRI.

"We didn't just want to do a genetic analysis; we wanted to understand what the precise clonal hierarchy looks like to get a better understanding of when relapse arises and how it can be affected by treatment," said co-senior author Charles Mullighan, M.D., MBBS, of the St. Jude Department of Pathology. "This work helped us show that treatment-resistant clones may be present at diagnosis, before treatment commences, and to determine how these subclones at diagnosis behave during therapy."

The researchers conducted advanced genomic and transcriptomic analysis on the cells. Results showed that dRI clones have increased tolerance to standard chemotherapy. Findings also show that dRI clones have alterations in epigenetic, metabolic and pro-survival pathways that provide new avenues for overcoming resistance.

Advanced genomics coupled with sophisticated modeling

In addition to advanced genomic and transcriptomic analysis, the researchers relied on sophisticated modeling with patient-derived xenografts to conduct this study. The scientists created the models using differing doses of leukemia cells in mice. This increased their ability to capture rare subclones in the models. This step was instrumental in showing the existence of subclones at diagnosis that harbor latent or relapse-specific genetic variants.

"Xenografting added considerable new insight into the evolutionary fates and patterns of subclones obtained from diagnosis samples," said co-senior author John Dick, Ph.D., senior scientist at Princess Margaret Cancer Centre, professor of molecular genetics at the University of Toronto, and scientific co-leader of the Acute Leukemia Translational Research Initiative at the Ontario Institute for Cancer Research. "We were able to gather extensive information about the genetics of the subclones from our models, which helped us describe the trajectories of each subclone and the order in which they acquired mutations. With such subclones isolated by xenografting, we could go on to examine the reasons why these subclones uniquely could both survive therapy and regenerate relapse disease."

The research described in the Cancer Discovery paper is a companion study to work published in Blood Cancer Discovery in January 2020. The Blood Cancer Discovery paper described the genomic landscape, patterns and mechanisms of clonal evolution from diagnosis to relapse in 92 patients on the Total Therapy protocols for ALL treatment at St. Jude. Together, these papers provide an integrated genomic and functional approach to describing the underlying genetics and mechanisms of relapse for ALL.

Improving the care and treatment of ALL

These findings have important implications for the clinical care of patients with ALL. When clinicians know that a patient is at risk of relapse, they can increase treatment up-front to try to prevent relapse. Additionally, knowing which subpopulation of cells is going to drive the relapse provides a clue for developing new treatment approaches.

Magnetic (anti)skyrmions are microscopically small whirls that are found in special classes of magnetic materials. These nano-objects could be used to host digital data by their presence or absence in a sequence along a magnetic stripe. A team of scientists from the Max Planck institutes (MPI) of Microstructure Physics in Halle and for Chemical Physics of Solids in Dresden and the Martin Luther University Halle-Wittenberg (MLU) has now made the observation that skyrmions and antiskyrmions can coexist bringing about the possibility to expand their capabilities in storage devices. The results were published in the scientific journal "Nature Communications".

With the ever-increasing volumes of digital data from the growing numbers of devices, the demand for data storage capacity has been enhanced dramatically over the past few years. Conventional storage technologies are struggling to keep up. At the same time, the ever-increasing energy consumption of these devices - hard disk drives (HDD) and random-access memories (RAM) - is at odds with a "green" energy landscape. Required are entirely new devices that have greater performance at a drastically reduced energy consumption.

A promising proposal is the magnetic racetrack memory-storage device. It consists of nanoscopic magnetic stripes (the racetracks) in which data is encoded in magnetic nano-objects, typically by their presence or absence at specified positions. One possible nano-object is a magnetic (anti)skyrmion: this is an extremely stable whirl of magnetization with a size that can be varied from micrometers to nanometers. These objects can be written and deleted, read and, most importantly, moved by currents, therefore allowing the racetrack to be operated without any moving parts. "By stacking several racetracks, one on top of each other, to create an innately three-dimensional memory-storage device, the storage capacity can be drastically increased compared to solid state drives and even hard disk drives. Moreover, such a racetrack memory device would operate at a fraction of the energy consumption of conventional storage devices. It would be much faster, and would be much more compact and reliable", explains Prof Stuart Parkin, director of the MPI of Microstructure Physics in Halle and Alexander von Humboldt Professor at the MLU.

"Skyrmions and antiskyrmions are 'opposite' magnetic whirls. However, until recently, it was believed that these two distinct objects can only exist in different classes of materials." explains Prof Ingrid Mertig from the institute of physics at MLU. The research team from Max Planck institutes in Halle and Dresden and the MLU has now discovered that antiskyrmions and skyrmions can coexist under certain conditions in the same material. Dr Börge Göbel, a member of Mertig's research group, provided the theoretical explanation for the unexpected experimental observations that were carried out by Jagannath Jena in Parkin's group. The measured single crystal materials, Heusler compounds, were prepared by Dr Vivek Kumar in the group of Prof Claudia Felser at the MPI in Dresden.

Skyrmions and antiskyrmions are stabilized in different materials by a magnetic interaction that is directly tied to the structure of the host material. In some materials only skyrmions can form, while in other materials, antiskyrmions are energetically preferred by this interaction. However, what was previously overlooked is that the individual magnets in each material (the "magnetic dipoles") also significantly interact with each other via their dipole-dipole interaction. This interaction always prefers skyrmions. For this reason, even "antiskyrmion materials" can exhibit skyrmions (but not vice versa). This happens preferably as the temperature is lowered. At a critical transition temperature, the two distinct objects coexist.

Besides its fundamental relevance, this finding allows for an advanced version of the racetrack memory data storage, where a bit sequence could, for example, be encoded by a sequence of skyrmions ('1' bit) and antiskyrmions ('0' bit). This concept would be more reliable than conventional racetracks.

By incorporating the architecture of city drainage systems and readings from flood gauges into a comprehensive statistical framework, researchers at Texas A&M University can now accurately predict the evolution of floods in extreme situations like hurricanes. With their new approach, the researchers said their algorithm could forecast the flow of flood water in almost real-time, which can then lead to timelier emergency response and planning.

"Not knowing where flood water will flow next is particularly detrimental for first responders who need to gauge the level of flooding for their rescue operations," said Dr. Ali Mostafavi, assistant professor in the Zachry Department of Civil and Environmental Engineering. "Our new algorithm considers the underground drainage channels to provide an accurate representation of how floods propagate. This tool, we think, can vastly help disaster management because first responders will be able to see which way flood water will flow in real time."

A description of the researchers' algorithm can be found in the December issue of the journal Computer-Aided Civil and Infrastructure Engineering.

Hurricanes are notorious for wreaking havoc on shorelines, toppling trees, tearing down power lines and above all, causing severe floods. Conventionally, scientists have used physics-based models to predict where water might collect, overflow and cause flooding. In essence, these models capture how physical features of the earth's surface and urban landscapes affect the flow of water over the ground.

While robust at predicting when and where floods will happen under most rainfall conditions, Mostafavi said these traditional models do not perform as well at predicting floods during incidents of torrential rainfall, like Hurricane Harvey.

"Physics-based models offer one perspective on how floods can spread, which is extremely useful, but the picture they provide is somewhat incomplete," he said. "We wanted to use existing data on how past floods have spread through the drainage channels to develop a model that would be able to predict, within a certain level of preciseness, how future floods will spread."

Drainage channels are an elaborate network of intertwined channels that meet together at junctions called nodes. Thus, flooding in one channel can directly or indirectly affect other channels and cause floods to spread, much like a domino effect.

To predict which way flood water will flow along drainage channels and cause an inundation, Mostafavi and his team developed a probability-based model that was fed, as one of its inputs, the water-level readings on flood gauges. These readings were for different time points during two major flooding events in Texas -- Hurricane Harvey in 2017 and Houston's Memorial Day flood in 2015.

Once their algorithm was trained on water flow patterns through the drainage network for these heavy rainfall events, the researchers tested if their model worked by checking if it could predict the flood patterns that had been observed during Houston's Tax Day flood in 2016.

They found that their model achieved an accuracy of 85% in predicting how the flood propagated through the city's drainage system during the Tax Day flood. Although the model was validated using a past flood event, Mostafavi said that the model's success suggests that it will also be able to predict how new floods will propagate through the city's drainage networks. This insight could help emergency responders take preemptive steps towards evacuations, he said.

Noting the caveats of their model, Mostafavi said that the performance of their algorithm could be compromised if the sensors on flood gauges fail. However, complementing the predictions coming from physics-based models with those from their team's new algorithm can once again restore the accuracy of flood prediction.

"Traditional models and our data-driven models can be used to complement each other to give a more precise picture of where flood water will go next," said Mostafavi. "Hurricanes of the magnitude of Harvey or Katrina are generally considered a one-in-a-thousand-year event, but they may not be as rare if we consider the changes in global weather patterns because of climate change. But we now have more robust tools to weather the storm."

Scientists have identified a sub-atomic particle that could have formed the "dark matter" in the Universe during the Big Bang.

Up to 80% of the Universe could be dark matter, but despite many decades of study, its physical origin has remained an enigma. While it cannot be seen directly, scientists know it exists because of its interaction via gravity with visible matter like stars and planets. Dark matter is composed of particles that do not absorb, reflect or emit light.

Now, nuclear physicists at the University of York are putting forward a new candidate for the mysterious matter - a particle they recently discovered called the d-star hexaquark.

The particle is composed of six quarks - the fundamental particles that usually combine in trios to make up protons and neutrons. Importantly, the six quarks in a d-star result in a boson particle, which means that when many d-stars are present they can combine together in very different ways to the protons and neutrons.

The research group at York suggest that in the conditions shortly after the Big Bang, many d-star hexaquarks could have grouped together as the universe cooled and expanded to form the fifth state of matter - Bose-Einstein condensate.

Dr MIkhail Bashkanov and Professor Daniel Watts from the the department of physics at the University of York recently published the first assessment of the viability of this new dark matter candididate.

Professor Daniel Watts from the department of physics at the University of York said: "The origin of dark matter in the universe is one of the biggest questions in science and one that, until now, has drawn a blank. Our first calculations indicate that condensates of d-stars are a feasible new candidate for dark matter. This new result is particularly exciting since it doesn't require any concepts that are new to physics."

Co-author of the paper, Dr Mikhail Bashkanov from the Department of Physics at the University of York said: "The next step to establish this new dark matter candidate will be to obtain a better understanding of how the d-stars interact - when do they attract and when do they repel each other.

"We are leading new measurements to create d-stars inside an atomic nucleus and see if their properties are different to when they are in free space. "

The influence of artificial sweeteners on the brain and ultimately metabolism has been hotly debated in recent years. Some studies have found adverse effects on blood sugar and insulin levels, while others have not. In a study publishing March 3 in the journal Cell Metabolism, researchers say the discrepancies in these studies may be due to how the sweeteners are consumed--or, more specifically, what they are consumed with.

Investigators report that the artificial sweetener sucralose seems to have no negative impact on its own, but when it is consumed with a carbohydrate, it induces deleterious changes in insulin sensitivity and decreases the brain's response to sweet taste as measured by fMRI.

"When we set out to do this study, the question that was driving us was whether or not repeated consumption of an artificial sweetener would lead to a degrading of the predictive ability of sweet taste," says senior author Dana Small, a neuroscientist who is a professor of psychiatry and the director of the Modern Diet and Physiology Research Center at Yale University. "This would be important because sweet-taste perception might lose the ability to regulate metabolic responses that prepare the body for metabolizing glucose or carbohydrates in general."

The trial enrolled 45 volunteers between the ages of 20 and 45 who didn't normally consume low-calorie sweeteners. All of them were of healthy weight and had no metabolic dysfunction. Other than consuming seven beverages in the lab over a two-week period, they didn't make any changes to their diet or other habits. The investigators conducted studies on the volunteers before, during, and after the testing period, including performing fMRI scans to look at changes in the brain in response to sweet tastes, as well as other tastes like salty and sour. They also measured taste perception and did an oral glucose tolerance test to look at insulin sensitivity.

The sweeteners were consumed as fruit-flavored beverages with added sucralose, or with table sugar for comparison. In what was intended to be a control group: some of the volunteers had the carbohydrate maltodextrin added to their sucralose drinks. The researchers chose maltodextrin, a non-sweet carbohydrate, to control for the calories of sugar without adding more sweet taste to the beverage. Surprisingly, it was this control group that showed changes in the brain's response to sweet taste and the body's insulin sensitivity and glucose metabolism. Given the surprising result, the researchers added a second control group, in which the participants drank beverages with maltodextrin alone. They found no evidence that consuming maltodextrin-containing beverages over the seven-day period alters insulin sensitivity and glucose metabolism.

"Perhaps the effect resulted from the gut generating inaccurate messages to send to the brain about the number of calories present," Small says. "The gut would be sensitive to the sucralose and the maltodextrin and signal that twice as many calories are available than are actually present. Over time, these incorrect messages could produce negative effects by altering the way the brain and body respond to sweet taste."

She notes that a subset of the previous studies of artificial sweeteners have involved mixing the sweeteners with plain yogurt, adding carbohydrates from the yogurt and leading to the same effects seen here as with the maltodextrin. This could explain why previous findings about artificial sweeteners have been in conflict with each other.

Small says that her team began doing similar studies in adolescents, but they ended the trial early when they saw that two of the kids who were getting the sucralose-carbohydrate combination had their fasting insulin skyrocket.

"Previous studies in rats have shown that changes in the ability to use sweet taste to guide behavior can lead to metabolic dysfunction and weight gain over time. We think this is due to the consumption of artificial sweeteners with energy," she notes.

Future studies will look at whether other artificial sweeteners, as well as more natural sweeteners like stevia, have the same effects as sucralose. Small expects that many of them will. "It's hard to say, because we still don't fully understand the mechanism," she concludes. "That's also something we hope to study further, especially in mice."

A vapour product that contains new-to-world technology has significantly fewer and lower levels of certain toxicants compared to cigarette smoke*, a study has shown.

Scientists at British American Tobacco (BAT) performed a series of chemistry tests designed to look for specific compounds in the vapour from iSwitch, BAT's new vapour product which uses a stainless-steel blade to heat e-liquid. The emissions from iSwitch were compared to those from a reference cigarette (1R6F).

The results -- published today in Chemical Research in Toxicology -- show the iSwitch vapour to have fewer and lower levels of certain toxicants than cigarette smoke. Some toxicants found in smoke are not in iSwitch vapour at all and others are much reduced by around 99%.*

"We are constantly innovating to seek to expand our potentially reduced-risk product portfolio," says Dr Chris Proctor, Group Head of Potentially Reduced-Risk Product Science at BAT.

Most conventional vaping devices are based on a coil-and-wick system whereby e-liquid is drawn up from a reservoir by a cotton wick. A metal coil is wrapped around the wick and, when heated, turns the liquid into vapour. The resulting vapour contains substantially fewer and lower levels of certain toxic substances than cigarette smoke.

However, some low-quality coil-and-wick systems, or those not used in accordance with the manufacturer's instructions, can dry out or overheat, known as dry-wicking. This can cause the thermal breakdown of humectants in the e-liquid, leading to the formation of toxic compounds, such as carbonyls.

iSwitch's puretech stainless-steel blade replaces the coil-and-wick, and it is constantly fed e-liquid by a capillary system. This means it does not overheat or dry out, overcoming the issue of dry-wicking.

"As well as improving the performance of vaping devices, puretech lessens the risk of humectant thermal breakdown, further reducing emissions of potentially harmful substances," says Chuan Liu, Senior Principal Scientist at BAT.

"This was reflected in our study, which showed that, even when used at high power settings, iSwitch emissions contain no or extremely low levels of analytes."

Human studies are needed to further substantiate the results of these tests.

Several studies in recent years have reported that low-calorie sweeteners in foods and beverages disrupt the human metabolism, promoting the development of diabetes and obesity. But other studies have found that consuming low-calorie drinks and food has little impact on metabolism and might actually aid in weight loss.

A new study by Yale researchers published March 3 in the journal Cell Metabolism may help reconcile these conflicting findings.

The study showed that people who periodically drank beverages with the low-calorie sweetener sucralose, which is found in low-cal soft drinks, candy, breakfast bars, and other products, did experience problematic metabolic and neural responses -- but only when a carbohydrate in the form of a tasteless sugar was added to the drink. In contrast, people drinking beverages with low-calorie sweeteners alone, or beverages with real sugar, showed no changes in brain or metabolic response to sugars.

"The subjects had seven low-calorie drinks, each containing the equivalent of two packages of Splenda, over two weeks," said senior author Dana Small, professor of psychiatry and psychology and director of the Modern Diet and Physiology Research Center. "When the drink was consumed with just the low-calorie sweetener, no changes were observed; however, when this same amount of low-calorie sweetener was consumed with a carbohydrate added to the drink, sugar metabolism and brain response to sugar became impaired."

The study was designed to test the theory that consuming sweet foods and beverages without calories "uncouples" sweet taste perception from energy intake, resulting in a diminished physiological response to sugar that could ultimately lead to weight gain, glucose intolerance and diabetes.

The new study of 45 individuals demonstrates that the uncoupling hypothesis is wrong, the researchers reported: Rather, the findings suggest, consuming low-calorie sweeteners with a carbohydrate impairs metabolism.

"The bottom line," said Small, who also directs Yale's newly formed division of nutritional psychiatry, "is that, at least in small quantities, individuals can safely drink a diet soda, but they shouldn't add French fries."

"This is an important information, particularly for people with diabetes who shouldn't consume sugars," Small said.

Excessive weight around our middle gives our brain's resident immune cells heavy exposure to a signal that turns them against us, setting in motion a crescendo of inflammation that damages cognition, scientists say.

It's known this visceral adiposity, characterized by an apple-shaped physique, is considered particularly bad for our bodies and brains.

But Medical College of Georgia scientists have shown for the first time one way visceral fat is bad for brains is by enabling easy, excessive access for the proinflammatory protein signal interleukin-1 beta, they report in The Journal of Clinical Investigation.

"We have moved beyond correlations saying there is a lot of visceral fat here, and there is cognitive decline here so they may be interacting with each other," says Dr. Alexis M. Stranahan, neuroscientist in the MCG Department of Neuroscience and Regenerative Medicine at Augusta University.

"We have identified a specific signal that is generated in visceral fat, released into the blood that gets through the blood brain barrier and into the brain where it activates microglia and impairs cognition."

The brain typically does not see much of this interleukin-1 beta, but Stranahan and her colleagues have found that visceral adiposity generates high, chronic levels of the signal that in turn over-activate the usually protective microglia, the resident immune cells in our brain.

A bit like a smoldering pot, this chronic inflammation from visceral fat prompts formation of inflammasome complexes that further amplify the immune response and inflammation. The protein NLRP3 is a core component of the inflammasome complex in the fat, and it's what promotes the production and release of interleukin-1 beta by fat cells, and stokes the inflammation fire.

It was known these reactions were causing problems in the body, and now the MCG scientists have evidence they are causing problems in the brain.

To explore brain effects, the scientists knocked NLRP3 out of mice and found the mice were protected against obesity-induced inflammation of the brain and the cognitive problems that can result. They also transplanted visceral adipose tissue from obese mice and obese mice missing NLRP3 into lean mice recipients and found the transplant from the NLRP3 knockout mouse had essentially no effect.

But the transplant from the obese but genetically intact mice increased levels of interleukin-1 beta in the hippocampus, a center of learning and memory in the brain, and impaired cognition.

They looked further and found that just transplanting the visceral fat caused essentially the same impact as obesity resulting from a high-fat diet, including significantly increasing brain levels of interleukin-1 beta and activating microglia. Mice missing interleukin-1 beta's receptor on the microglia also were protected from these brain ravages.

Their findings enabled the scientists to start putting together the pieces that NLRP3 was working through interleukin-1 beta, which led them to also knock out the receptor for interleukin-1 beta on microglia and confirm that action in the brain.

Microglia typically function as watchdogs, constantly surveilling and roaming the brain, eliminating dead cells and other debris as well as a myriad of other tasks like forming and pruning connections between neurons. Microglia also have receptors for interleukin-1 beta, and the protein, whose many actions include promoting inflammation, easily passes through the protective blood brain barrier.

Microglia's helpful -- or harmful -- actions likely result from signals they are exposed to, and another thing interleukin-1 beta appears to do is prompt microglia to wrap around synapses, possibly exerting damaging pressure and/or releasing substances that actually interfere with conversations between neurons, Stranahan says. In the absence of disease, microglia also are known to embrace synapses but to release good things like brain-derived neurotrophic factor, which is like fertilizer for these invaluable connections.

Happy microglia also have long processes that enable them to reach out and do their many tasks; and inflammation retracts those processes. The scientists found much shorter processes and less complex microglia in mice on a high-fat diet, more changes that didn't happen when NLRP3 was knocked out.

To measure cognitive ability, the scientists looked at mice's ability to navigate a water maze after 12 weeks on a high- or low-fat diet. They found it took the normal, or wild type, mice consuming the higher fat diet as well as the visceral transplant recipients with NLRP3 intact longer to negotiate the water maze. In fact, while they could reach a platform they could see, they had trouble finding one beneath the water's surface that they had been taught to find. Mice with the interleukin-1 receptor knocked out, could find it just fine, Stranahan says.

The high-fat diet, transplant mice also had weaker connections, or synapses, between neurons involved in learning and memory. Mice on a high-fat diet but missing NLRP3 were spared these changes, like mice on a low-fat diet.

Also, like many of us, mice tend to prefer new toys and those on a low-fat diet or with NLRP3 removed were better at recognizing novel objects to play with and their synapses were stronger. The high-fat diet transplant mice seemed not to remember so well which toy they'd already played with.

There is already potential protection out there from brain effects, Stranahan says, noting biologics in use in humans for problems like rheumatoid arthritis and Crohn's disease, that target interleukin-1 beta. "Obesity-induced inflammation occurs over years and so does inflammation in some of these chronic inflammatory diseases," Stranahan says.

There is also emerging evidence that bariatric surgery, which sometimes includes removing visceral fat, can improve attention, mood and executive function.

There are many hypotheses about why visceral fat is so inflamed, including its proximity to the gut microbiota, a centerpiece of our immune response, which is programmed to attack invaders.

Increased rates of cognitive decline have been linked to obesity in humans, including shrinkage of key brain areas like the hippocampus, although there also have been contradicting reports about the overall health impact of obesity, the scientists report.

The contradiction in impact may relate to where the fat is found, says Stranahan, whose next goals include studying the apparent protective effects of fat deposited under the skin, called subcutaneous fat, whose benefits may include allowing you to store energy away from the highly inflammatory abdominal area.

Waist to hip ratio is a better indicator of visceral adiposity than the standard body mass index, or BMI, that divides weight by height.

Researchers at the University of California San Diego developed a wearable technology that can hide its wearer from heat-detecting sensors such as night vision goggles, even when the ambient temperature changes--a feat that current state of the art technology cannot match. The technology can adapt to temperature changes in just a few minutes, while keeping the wearer comfortable.

The device, which is at the proof-of-concept stage, has a surface that quickly cools down or heats up to match ambient temperatures, camouflaging the wearer's body heat. The surface can go from 10 to 38 degrees Celsius (50 to 100.5 degrees Fahrenheit) in less than a minute. Meanwhile, the inside remains at the same temperature as human skin, making it comfortable for the wearer. The wireless device can be embedded into fabric, such as an armband. A more advanced version could be worn as a jacket.

To build the device, the team turned to a phase-changing material that's similar to wax but with more complex properties. The melting point of the material is 30 degrees Celsius (roughly 86 degrees F), the same temperature as the surface temperature of human skin. If the temperature on the outside of the device is higher than that, the material will melt and stabilize, insulating the wearer; if colder, it will slowly solidify, still acting as an insulating layer.

The team, led by UC San Diego mechanical and aerospace engineering professor Renkun Chen, detailed their work in a recent issue of the journal Advanced Functional Materials.

At the technology's core are materials that can create heating or cooling effects when the ambient temperature changes, and flexible electronics that can be embedded into clothing. The outside layer of the device is driven by a technology that Chen and colleagues detailed in a paper in Science Advances in May 2019. It is made of thermoelectric alloys--materials that use electricity to create a temperature difference--sandwiched between stretchy elastomer sheets. It is powered by a battery and controlled by a wireless circuit board. The device physically cools or heats to a temperature that the wearer chooses.

Current state of the art heat camouflage technology consists of a surface coating that changes how much heat clothing emits at the surface. The coating absorbs the heat from the wearer's body and reflects only enough energy to match the ambient temperature. However, the coating only works at a predetermined temperature. If the ambient temperature rises or falls, it no longer works.

The researchers' biggest challenge now is to scale up the technology. Their goal is to create a jacket with the technology built-in, but under current conditions, the garment would weigh 2 kilograms (about 4.5 lbs.), be about 5 millimeters thick and only function for one hour. The team will be looking to find lighter, thinner materials so the garment could weigh two or three times less.

SAN ANTONIO -- March 3, 2020 -- Southwest Research Institute (SwRI) conducted room burn comparisons to better understand how country-specific fire codes in the U.S., France and the United Kingdom affect the fire safety of home furnishings and their contributions to flashover. Reducing the rate for flashover in a room burn can significantly save lives translating to more time for people to escape a fire. Flashover occurs when temperatures at the ceiling reach 1,000 degrees C and all the combustibles in the room ignite.

The study found the American and French-furnished rooms reached flashover in just five to six minutes whereas the United Kingdom room took 22 minutes to reach flashover.

The upholstered furniture from the U.K. contained the most fire-retardant protection. The smoke toxicity measured was also recorded as less acutely toxic than the U.S. and French furnished rooms.

"Most countries test upholstered furniture for fire performance, however, fire preventative measures and testing standards applied to consumer products vary greatly by country," said Dr. Matthew Blais, SwRI director of Fire Technology and principal investigator.

SwRI fire engineers conducted nine room burns to better understand the variances in fire standards from different countries and to study how quickly flashover occurs in a replicated realistic environment. Each of the three identically furnished sets of rooms contained a three-cushion couch, a chair and a flat panel television. However, for testing purposes, SwRI purchased these specific items from each respective country given that the materials and retardants vary. Each room set up also included an identical coffee table, end table, curtain, bookcase and books, which were all purchased in the U.S. Because these items are typically not treated with a fire retardant, the fire performance should not vary from country to country. The Institute conducted the room burn tests using the international standard for full-scale room test specifications, standard ISO 9705. The U.S. and France use a smolder only flammability standard while the U.K. combines a smolder and open flame ignition test to evaluate the flammability.

When the living room furnishings are the first item ignited in a fire, there tends to be a higher incident of death. SwRI selected three ignition sources that represent a passing standard used in the UK during a room burn with an open flame ignition. For each room configuration, ignition started in the center couch cushion.

"In the U.S. and other countries, there is a push to eliminate chemical flame retardants due to an anti-chemical movement," Blais said. "When testing consumer products, one of the methods employed is to reduce the requirement to test consumer products, especially furniture, against open flame ignition sources. This study shows the impact of country fire codes only requiring smoldering ignition compared to a country testing with open flame ignition. When an open flame standard is applied to consumer products that have been treated with fire preventative material, the results show the room would reach flashover at a much slower rate allowing people five to six times the number of minutes to escape from a house fire when the first item ignited is a couch."

Researchers from Tokyo Medical and Dental University (TMDU) discover a novel mechanism by which claudin-1 contributes to the progression of tongue squamous cell carcinoma

Tokyo, Japan - While it is known that most cancers try to grow and spread to the rest of the body, for many cancers it is unclear how they actually achieve taking over the host's body. In a new study published in Cancer Science, researchers from Tokyo Medical and Dental University (TMDU) revealed a novel mechanism by which tongue squamous cell carcinoma (TSCC) exploits a protein whose task actually is to keep the tissue together.

A group of cells, also called tissue, is held together by a number of proteins that form a complex called tight junctions on the cell surface. Their function is to provide stability to the tissue as well as to prevent leakage of transported solutes and water by ensuring that molecules only pass through, and not between, the cells. One of the proteins that is part of tight junctions is claudin-1. Several studies have shown that claudin-1 plays an important role in several cancers, such as oral, gastric, liver and colon cancer.

"The amount of claudin-1 that a cancer makes has not been shown to correlate with how malignant that cancer is," says corresponding author of the study Miki Hara-Yokoyama. "The goal of our study was to understand at the molecular level how claudin-1 is involved in cancer progression."

To achieve their goal, the researchers investigated specimens from patients with TSCC for the amount of claudin-1 produced by the cancer, as well as where in the cancer cell the protein is located. Given that claudin-1 is part of tight junctions, one might expect that they are naturally localized to the cell surface. It turns out it is not that simple.

"We know that localization is a key determinant of protein function. So we wanted to know if the localization of claudin-1 was connected to the progression of TSCC," says lead author of the study Daisuke Yamamoto.

The researchers found that although the total amount of claudin-1 in TSCC cells and the invasiveness of the cancer were not associated, the amount of claudin-1 localized to the interior of the cell increased with the degree of cervical lymph node metastasis. They then isolated cells from TSCC and showed that when claudin-1 is locked within the cells or when the cells are entirely depleted of claudin-1, the cancer cells become more migratory.

"These are striking results that show how cancer cells break free from a tissue and increase their motility to invade lymph nodes and other organs of the body," says Hara-Yokoyama. "Invasive cancers that are capable of spreading and disabling vital organ functions are often very difficult to contain. Our findings could offer a novel therapy to prevent cancers from progressing and metastasizing."