Tech

America's most widely consumed oil causes genetic changes in the brain

image: Edible fats and oils consumed in the U.S., 2017/18.

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USDA

New UC Riverside research shows soybean oil not only leads to obesity and diabetes, but could also affect neurological conditions like autism, Alzheimer's disease, anxiety, and depression.

Used for fast food frying, added to packaged foods, and fed to livestock, soybean oil is by far the most widely produced and consumed edible oil in the U.S., according to the U.S. Department of Agriculture. In all likelihood, it is not healthy for humans.

It certainly is not good for mice. The new study, published this month in the journal Endocrinology, compared mice fed three different diets high in fat: soybean oil, soybean oil modified to be low in linoleic acid, and coconut oil.

The same UCR research team found in 2015 that soybean oil induces obesity, diabetes, insulin resistance, and fatty liver in mice. Then in a 2017 study, the same group learned that if soybean oil is engineered to be low in linoleic acid, it induces less obesity and insulin resistance.

However, in the study released this month, researchers did not find any difference between the modified and unmodified soybean oil's effects on the brain. Specifically, the scientists found pronounced effects of the oil on the hypothalamus, where a number of critical processes take place.

"The hypothalamus regulates body weight via your metabolism, maintains body temperature, is critical for reproduction and physical growth as well as your response to stress," said Margarita Curras-Collazo, a UCR associate professor of neuroscience and lead author on the study.

The team determined a number of genes in mice fed soybean oil were not functioning correctly. One such gene produces the "love" hormone, oxytocin. In soybean oil-fed mice, levels of oxytocin in the hypothalamus went down.

The research team discovered roughly 100 other genes also affected by the soybean oil diet. They believe this discovery could have ramifications not just for energy metabolism, but also for proper brain function and diseases such as autism or Parkinson's disease. However, it is important to note there is no proof the oil causes these diseases.

Additionally, the team notes the findings only apply to soybean oil -- not to other soy products or to other vegetable oils.

"Do not throw out your tofu, soymilk, edamame, or soy sauce," said Frances Sladek, a UCR toxicologist and professor of cell biology. "Many soy products only contain small amounts of the oil, and large amounts of healthful compounds such as essential fatty acids and proteins."

A caveat for readers concerned about their most recent meal is that this study was conducted on mice, and mouse studies do not always translate to the same results in humans.

Also, this study utilized male mice. Because oxytocin is so important for maternal health and promotes mother-child bonding, similar studies need to be performed using female mice.

One additional note on this study -- the research team has not yet isolated which chemicals in the oil are responsible for the changes they found in the hypothalamus. But they have ruled out two candidates. It is not linoleic acid, since the modified oil also produced genetic disruptions; nor is it stigmasterol, a cholesterol-like chemical found naturally in soybean oil.

Identifying the compounds responsible for the negative effects is an important area for the team's future research.

"This could help design healthier dietary oils in the future," said Poonamjot Deol, an assistant project scientist in Sladek's laboratory and first author on the study.

"The dogma is that saturated fat is bad and unsaturated fat is good. Soybean oil is a polyunsaturated fat, but the idea that it's good for you is just not proven," Sladek said.

Indeed, coconut oil, which contains saturated fats, produced very few changes in the hypothalamic genes.

"If there's one message I want people to take away, it's this: reduce consumption of soybean oil," Deol said about the most recent study.

Credit: 
University of California - Riverside

Charge model for calculating the photoexcited states of one-dimensional Mott insulators

image: Schematic diagram of the charge model.
The effect of electron-electron interactions is integrated by adding multiple-holon-doublon-pair basis states (right) to one-holon-doublon basis states (left). Here, black dots represent singly occupied sites.

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Nagoya Institute of Technology

Assistant Professor Ohmura Shu and Professor Takahashi Akira of the Nagoya Institute of Technology and others have developed a charge model to describe photoexcited states of one-dimensional Mott insulators*1) under the JST Strategic Basic Research Programs. They have also succeeded in constructing a many-body Wannier function*2) as the localized basis state of the photoexcited states and calculating large-system, optical conductivity spectra that can be compared with experimental results.

There has been growing interest in recent years in how the electronic state of a strongly correlated electron system*3) changes on ultrafast time-scales through electric field application or photoirradiation. For example, experiments demonstrate that when a Mott insulator is excited with a strong light, holon and doublon*4) are created and metallize swiftly. To understand this physical mechanism, it is necessary to conduct a theoretical calculation of the wave function of the system. The electronic state of a strongly correlated electron system can be described with an extended Hubbard model*5). However, given the capacity of existing computers, it was not possible to calculate the wave function for a large system that can be compared with experimental results or to use it to obtain the light spectrum even for one-dimensional systems with the simplest of electronic states.

Therefore, a charge model has been developed under the one-dimensional extended Hubbard model that can be used to accurately handle charge fluctuation*6) in addition to the spin-charge separation*7) characteristics of one-dimensional Mott insulators. By comparing the precisely calculated optical conductivity spectra of the extended Hubbard model and the charge model, it was demonstrated that charge fluctuation is essential to the description of the photoexcited states and that the charge model is effective. Moreover, a many-body Wannier function that integrated the effects of electron-electron interactions by applying information science methods to the charge model was constructed, resulting in the successful acquisition of optical conductivity spectra for systems consisting of more than 100 atoms or molecules that could be directly compared with experimental results.

The information-science technology used in this research should be applicable to the theoretical analysis of photoinduced phenomena of a wide variety of strongly correlated electron systems. This discovery of the mechanism of the photoinduced electron dynamics is expected to lead to the development of ultrahigh-speed optical devices using strongly correlated electron systems.

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Japan Science and Technology Agency

Digital athletics in analogue stadiums

Globally, arenas and stadiums that seat tens of thousands of people are filling up for whole weekends with crowds excited to their favourite sports stars sit on chairs and stare at screens. These fans are here to watch men and women play computer games, and researchers from Aalto and Tampere University are studying why.

Competitive professional video gaming, or esports, is a rapidly growing part of the entertainment industry, with an estimated global audience of 335 million people in 2017, with 143 million being active spectators. Esports events have become increasingly popular, attracting tens of thousands of attendees in real life, and hundreds of thousands online. But very little research has been done into what motivates these audiences.

"Esports has emerged as a new form of culture and entertainment, that is unique in comparison to other forms of entertainment, as it is almost fully reliant on computer-human interaction and the internet," says Dr Max Sjöblom, a former PhD student at Aalto University and project researcher at Gamification Group of Tampere University, now at tech startup Kast. He was one of the pioneers of investigating the behaviour of these new audiences.

Person-v-person computer gaming as a competitive sport grew out of LAN-parties, where gamers would gather and connect their computers together by a network.

But the move to large audiences in big arenas means that events are now taking on more of the characteristics of traditional sporting events. To fully understand the appeal of live events for esports spectators, and how this appeal related to how fans watch esports online at home, researchers set out to question attendees of live esports events and online-only fans. This study combined quantitative data from both an online sample (N = 888) and a sample obtained at the Assembly 2016 live event (N = 221).

Social Interaction key

The results show that fans around the world are travelling to areas drawn primarily by social interaction and the excitement of being near the sports stars they're fans of. Fans watching at home online rated: 'drama', 'acquisition of knowledge', 'appreciation of skill', 'novelty', 'aesthetics' and 'enjoyment of aggression' higher than live attendees. Meanwhile the fans in the stadium rate social interaction and physical attractiveness higher than those at home

"To us, it seems logical that fans of live esports events are fans of the social interaction element. Esports are predominantly consumed via online broadcasts, where social interaction is facilitated only through instant messaging chat windows. The typical mode of consumption offers less direct human interaction between spectators than in live events. So it seems natural that those who seek gratification through social aspects of the games are more drawn to attend live events." explained Dr Sjöblom

Enjoying 'Vicarious achievement' and 'novelty' was positively associated with whether or not a fan would recommend esports to others. As esports continues to rapidly grow into a big business, the researchers predict more work into its audiences "a final concluding quote, maybe from a coauthor, about future work"

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Aalto University

Chemists have managed to stabilize the 'capricious' phosphorus

An international team of Russian, Swedish and Ukrainian scientists has identified an effective strategy to improve the stability of two-dimensional black phosphorus, which is a promising material for use in optoelectronics.

The most effective mechanism of fluorination has been revealed. In addition to increased stability compared to previously proposed structures, the materials predicted by the researchers showed high antioxidative stability. The main results of the work have been presented in The Journal of Physical Chemistry Letters.

Black phosphorus is obtained from white phosphorus under conditions of high pressure and elevated temperature. The material has a layered structure and resembles graphite in appearance and properties. However, unlike graphite, it is a good semiconductor.

"Phosphorene is a monolayer of black phosphorus with interesting physical properties (high anisotropic electrical and thermal conductivity, flexible band gap variability depending on the number of layers), which makes it a promising material for use in various fields of optoelectronics (transistors, inverters, flexible electronics, solar panels). Unfortunately, one of its main problems is instability in the environment. Unlike its volumetric analogue, which is almost immune to external conditions, phosphorene quickly begins to attach oxygen from the air and degrades within a few hours. As one of the strategies for improving the stability of phosphorene, mechanism of fluorination was proposed. Over the past five years, scientists have proposed several theoretically possible options for such a "coupling". An experiment was conducted that showed a significant increase in the stability of phosphorus in ambient conditions after fluorination. However, the features of the obtained material structure remained unexplained.

Using various theoretical approaches, my colleagues and I showed that the previously proposed structures of "stabilized" phosphorus were actually unstable. It is known that phosphorus is able to form compounds with 3 or 5 fluorine atoms. Our calculations also confirmed that the characteristic coordination of the phosphorus atom in the PF system is 3 or 5. By sequential addition of atoms, it was possible to identify the most effective and really working mechanism by which fluorine atoms should attach to the surface of phosphorene. Thus, we have determined the type of structures that are likely to have been obtained by our predecessors in the above-mentioned experiment," -- said Artem Kuklin, a research fellow of SibFU.

Scientists note that the materials formed by the predicted mechanism are really stable and have increased antioxidant ability (that is, they are not quickly degradable) and their electronic properties, which do not differ much from the properties of pure phosphorus, provide the possibility of their practical application in optoelectronic devices, i.e. transistors, solar panels, flexible electronics, LEDs, photosensors, biomedical devices, optical devices for storing and transmitting information, etc.

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Siberian Federal University

Miniature double glazing

image: The newly developed material conducts heat well along the layers, while at the same time providing thermal insulation vertically.

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Copyright: MPI-P, Licence CC-BY-SA.

Styrofoam or copper - both materials have very different properties with regard to their ability to conduct heat. Scientists at the Max Planck Institute for Polymer Research (MPI-P) in Mainz and the University of Bayreuth have now jointly developed and characterized a novel, extremely thin and transparent material that has different thermal conduction properties depending on the direction. While it can conduct heat extremely well in one direction, it shows good thermal insulation in the other direction.

Thermal insulation and thermal conduction play a crucial role in our everyday lives - from computer processors, where it is important to dissipate heat as quickly as possible, to houses, where good insulation is essential for energy costs. Often extremely light, porous materials such as polystyrene are used for insulation, while heavy materials such as metals are used for heat dissipation. A newly developed material, which scientists at the MPI-P have jointly developed and characterized with the University of Bayreuth, can now combine both properties.

The material consists of alternating layers of wafer-thin glass plates between which individual polymer chains are inserted. "In principle, our material produced in this way corresponds to the principle of double glazing," says Markus Retsch, Professor at the University of Bayreuth. "It only shows the difference that we not only have two layers, but hundreds".

Good thermal insulation is observed perpendicular to the layers. In microscopic terms, heat is a movement or oscillation of individual molecules in the material that is transferred to neighbouring molecules. By building up many layers on top of each other, this transfer is reduced: Each new boundary layer blocks part of the heat transfer. In contrast, the heat within a layer can be conducted well - there are no interfaces that would block the heat flow. Overall, the heat transfer within a layer is 40 times higher than perpendicular to it.

The thermal conductivity along the layers is comparable to the thermal conductivity of thermal paste, which is used, among other things, to apply heat sinks to computer processors. For electrically insulating materials based on polymer/glass, this value is exceptionally high - it exceeds that of commercially available plastics by a factor of six.

For the material to function efficiently and also be transparent, the layers had to be produced with very high precision - any inhomogeneity would disturb the transparency similar to a scratch in a piece of Plexiglas. Each layer is only one millionth of a millimeter high - i.e. one nanometer. In order to investigate the homogeneity of the layer sequence, the material was characterized in the group of Josef Breu, Professor of Inorganic Chemistry at the University of Bayreuth.

"We use X-rays to illuminate the material," says Breu. "By superimposing these rays, which are reflected by the individual layers, we were able to show that the layers could be produced very precisely."

Prof. Fytas, member of Prof. Hans-Jürgen Butt's department, was able to give an answer to the question why this layer-like structure has such extraordinarily different properties along or perpendicular to the individual glass plates. Using a special laser-based measurement, his group was able to characterize the propagation of sound waves, which is like heat also related to the movement of the material's molecules. "This structured yet transparent material is excellent for understanding how sound propagates in different directions," says Fytas. The different sound velocities allow direct conclusions to be drawn about the direction-dependent mechanical properties, which are not accessible with any other method.

In their further work, the researchers hope to gain a better understanding of how sound and heat propagation can be influenced by the structure of the glass plate and the polymer composition. The researchers see a possible application in the field of high-performance light-emitting diodes, in which the glass-polymer layer serves on the one hand as a transparent encapsulation and on the other hand can dissipate the released heat laterally.

The scientists have now published their results in the renowned journal Angewandte Chemie - International Edition.

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Universität Bayreuth

Study: Neuron found in mice could have implications for effective diet drugs

Ever eaten something, gotten sick and then didn't want to eat that food again because of how it made you feel? That's because a signal from the gut to the brain produced that sickness, creating a taste aversion.

Conventional wisdom renders there's one circuit in the brain that suppresses eating -- it comes from the stomach and makes you feel sick if you activate it too hard. Eating a portioned meal makes your body happy, though, even while stimulating a signal to the brain to stop eating, according to Michigan Diabetes Research Center's director, Martin Myers Jr., M.D. Ph.D.

"Therefore, there must be a circuit that stops normal feeding without the adverse effects, right?" says Myers.

Now, a Cell Metabolism study may have discovered this second circuit in mice. Myers, Randy Seeley, Ph.D, the director of the Michigan Nutrition Obesity Research Center, and a team of researchers sought to better understand which part of the brain curbs appetite and which neurons play a role in making mice want to eat or not eat.

The gut-brain signal that suppresses appetite is triggered by a type of neuron, containing calcitonin receptor (CALCR), which lives in a structure of the hindbrain called the medulla. Interestingly enough, these neurons didn't need to be active in the brain for gut sickness to cause an aversive response.

"This suggested we might be able to dissociate the brainstem systems that stop feeding from those that cause nausea," says Myers, whose group found they could genetically activate those CALCR neurons to do just that.

Singling out the responsible neuron

Since there are neurons that can suppress eating but also cause aversive effects, that must mean there are different types of neurons, or circuits, in the brain that can terminate feeding with differing emotional responses.

When the researchers inactivated the CALCR neurons, they were surprised to make another discovery, which contradicted the idea that the brain only controls short term meal sizes and consumption.

Turning these neurons "off" didn't only interfere with the suppression of feeding by gut signals, but it also caused an ongoing increase in food intake. The mice became obese, suggesting that the brainstem systems don't only control meal size, but the amount of food consumed long term. This created a predisposition to obesity because of the energy imbalance in the mice (more input than output).

Similarly, activating CALCR neurons decreased the mice's food intake and body weight without any aversive gut effects. In the study, Myers and his team found another neuron, CCK, also decreased food intake and body weight but created an aversive internal response, unlike the CALCR neurons. The difference between the two neurons were found in their circuits.

"CCK activates what we would call a 'yucky circuit'," says Myers. "The neurons activate a certain cell, CGRP cells, which create that sick feeling." Unlike CCK, activated CALCR neurons follow a "yummy circuit", activating non-CGRP cells.

Potential implications in humans

Obesity affects more than one-third of the adult population in developed countries, which can lead to diabetes or other serious, long-term health conditions like heart disease, explains Myers, who is also the director of MDiabetes.

Unfortunately, many diet drugs work, but they make people feel nauseous after they take them. Obesity remains a condition difficult to pharmaceutically manage, since the treatment options have limited therapeutic utility. A drug that turns "on" CALCR and turns off "CGRP" could greatly benefit patients with obesity by suppressing feeding and creating a long term control of food intake and body weight.

"If we could figure out a drug for individuals with obesity that suppresses food intake to produce long term weight loss without the negative side effects, it could absolutely change someone's life," says Myers.

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Michigan Medicine - University of Michigan

Hookah smoke may be associated with increased risk of blood clots

DALLAS, Jan. 16, 2019 - For the first time, in a study conducted in mice, researchers found that tobacco smoke from a hookah caused blood to function abnormally and be more likely to clot and quickly form blood clots, which can increase the risk of heart attack or stroke, according to new research published today in the American Heart Association's journal Arteriosclerosis, Thrombosis and Vascular Biology (ATVB).

Researchers found that tobacco smoke from a hookah caused blood clots to form within an average of about 11 seconds, compared to an average of 5 minutes for clotting without exposure to hookah smoke. Exposure to the hookah smoke also caused other abnormalities related to the way the blood flows.

"Hookah smoking, which is becoming more popular in Western countries, is perceived as less harmful than cigarettes, yet hookahs carry a toxic profile that is thought to be comparable or to even exceed that of traditional cigarettes. Some studies have found that the smoke emitted from one hookah tobacco smoking episode contains significantly more harmful chemicals compared to a single cigarette," said Fadi Khasawneh, Ph.D., associate professor and chair of pharmaceutical sciences at The University of Texas at El Paso.

Hookah, also known as waterpipe smoking, is a unique method of smoking tobacco. It consists of a head (which holds the tobacco), a body, a chamber filled with water, a hose and a mouthpiece. Charcoal briquettes are used to "burn" the tobacco.

In this study, researchers exposed mice to hookah smoke from a smoking machine that mimicked real-life smoking habits. The smoking machine used 12 grams of commercially available, flavored tobacco that included tobacco, glycerin, molasses and natural flavor with nicotine and tar. Researchers then compared platelet activity among the exposed vs. the unexposed mice.

The study simulated the type of nicotine exposure that occurs with smoking a hookah, which the researchers verified by measuring the levels of cotinine, the nicotine metabolite.

"Our findings provide new evidence that hookah smoking is as unhealthy - if not more so - than traditional cigarettes," Khasawneh said. "Smoking a hookah, cigarettes, e-cigarettes or other forms of tobacco all increase your risk for heart disease and stroke."

In May 2019, the American Heart Association published a Scientific Statement, "Water Pipe (Hookah) Smoking and Cardiovascular Disease Risk," to analyze available research on the health effects of hookah smoking. The Statement notes that hookah smoking results in inhaling significant levels of toxic chemicals such as carbon monoxide and particulates from tobacco that can harm blood vessels, the heart and lungs, as well as creating a dependence on nicotine.

"This study provides additional evidence that, contrary to popular belief, hookah smoking adversely affects cardiovascular health. From 2011 to 2015, the number of United States-based waterpipe establishments is estimated to have more than doubled, and interest has grown among both teens and adults," said Aruni Bhatnagar, Ph.D., chair of the Scientific Statement writing group. "Although the tobacco industry has found novel ways to popularize and increase the use of new products, studies like this highlight the high risk of hookah smoking."

Credit: 
American Heart Association

Police platform patrols create 'phantom effect' that cuts crime in London Underground

A massive experiment that deployed regular police patrols on platforms in the London Underground has shown that four 15-minute patrols a day in some of the capital's most crime-ridden stations reduced reported crime and disorder by 21%.

Researchers from Cambridge University's Institute of Criminology worked with the British Transport Police (BTP) to conduct the experiment across six months in 2011-2012. The findings have been published in the journal Criminology.

The team identified the 115 London stations where reported crime was highest. They randomly allocated 57 of these stations with four daily "doses" of platform patrols - two officers on foot for quarter of an hour - four days a week, and compared the effects to the remaining "untreated" stations.

The researchers found that, while the experiment was running, a total of 3,549 calls to police from the platform came from stations without patrols, compared to 2,817 in the stations receiving a policing "dosage" - a relative difference of 21%.

The team also looked at crime data from the six months prior to the experiment, and found that recorded crime fell 14% overall during the experimental period in those stations treated with the new patrols.

Strikingly, they discovered that the vast majority of reduction in both crime and calls for assistance occurred when these police patrols were absent - some 97% of the measured effect. The criminologists have dubbed this the "London Underground paradox".

"The total crime prevention benefit of police patrols may be greater when they are absent than when they are present," said study co-author Prof Lawrence Sherman. "In the London Underground experiment we see a huge residual effect of brief appearances by patrolling officers after they leave"

"This phantom effect suggests that crime declines when potential offenders are apprehensive about a possible police presence based on recent patrolling patterns - even when there are no police in the vicinity," he said.

"In London stations, it may be that more professional kinds of offenders are particularly sensitive to changes in police presence, such as pickpockets and distraction thieves."

"The London Underground paradox could have implications for debates on police priorities in an age of austerity, such as the benefits of investigating past crimes compared with the benefits of preventing future crimes," Sherman said.

London's Underground opened in 1863, the first underground railway in the world, and provides more than 1.3 billion passenger rides per year.

The majority of crime in the transport network occurs on the trains and in concourse areas. Crime on platforms constitute 11% of the total, and historically platforms have had no regular police patrols.

As such, platforms offered an opportunity to conduct an experiment on spaces within a major metropolis that had never seen proactive police presence - ideal for gauging patrol effectiveness without previous "contamination", say researchers.

"Platforms are small, stable and confined places with finite entry and exit points. These characteristics make them optimal for measuring the localised deterrence effects of police patrols," said first author Dr Barak Ariel.

"We wanted to measure what happens when police patrols are introduced into an urban environment for the first time in over 150 years."

The team targeted "hot spots" - areas where crime is more concentrated, and preventative patrols can have greatest effect - by ranking stations based on the previous year's crime rates, and including the top 115 of Greater London's 270 stations in the experiment.

Researchers also narrowed the experiment's focus based on "hot hours" and "hot days". Previous data showed the sample platforms experienced more crime and calls to police from Wednesday to Saturday between 3pm and 10pm.

Twenty uniformed BTP officers were selected and trained to work exclusively on patrolling the platforms of the "treatment" stations during "hot" days and hours. Each two-person unit was allocated between three and five stations, with platforms patrolled for fifteen minutes four times a day.

Officers were asked to conduct these patrols in a random or unpredictable order within the "hot hours", and encouraged to engage with the public while patrolling.

Police were most effective at preventing platform crime during periods and days when patrols were scheduled - but just 3% of that reduction came when officers were actually scheduled to patrol.

The researchers also found "regional" effects: crime in the rest of the station fell almost as much as crime on platforms during the four days when regular patrols were deployed.

"Our findings indicate that consistent patrols can cause large reductions in both crime and emergency calls in areas that have never before been proactively patrolled by police in this way," added Sherman.

"The more that uniformed police have been there, and the more recently, the less likely future crimes may be to occur."

Credit: 
University of Cambridge

Why can't Bertrand Might cry? Scientists offer an answer: missing water channels

image: 11-year-old Bertrand Might (center) surrounded by his family, including his father, Matt Might (second from right), and his mother, Cristina Might (second from left).

Image: 
The Might family

LA JOLLA, CALIF. - January 16, 2020 - Scientists at Sanford Burnham Prebys Medical Discovery Institute have shown that cells from children with NGLY1 deficiency--a rare disorder first described in 2012--lack sufficient water channel proteins called aquaporins. The discovery was published in Cell Reports and may help explain the disorder's wide-ranging symptoms--including the inability to produce tears, seizures and developmental delays--and opens new avenues to find therapies to treat the disorder.

"Our findings uncover a new and completely unexpected 'job' for NGLY1, which was originally thought to only cleave sugars from proteins," says Hudson Freeze, Ph.D., director and professor of the Human Genetics Program at Sanford Burnham Prebys and senior author of the study. "This new information, which includes the molecular signals NGLY1 uses to drive aquaporin production, fundamentally shifts how we approach drug development. Most immediately, we can begin to screen for existing FDA-approved drugs that may increase aquaporin levels."

The first patient with NGLY1 deficiency, then-four-year-old Bertrand Might, was diagnosed in 2012. The condition occurs when both copies of the NGLY1 gene contain mutations. As a result, children with NGLY1 deficiency produce little or no N-glycanase1--a protein that removes sugars from proteins during the cell's regular recycling process. Today, approximately 60 people in the world have been identified with NGLY1 deficiency. There is no cure, and existing treatments only address a few of the disorder's symptoms.

"This discovery is a giant leap forward in our understanding of NGLY1 deficiency and our ability to find a drug for the condition," says Matt Might, Ph.D., Bertrand Might's father and chief scientific officer of NGLY1.org, which funded the research. "In addition to exploring new treatment avenues, we can immediately start to test currently available drugs to see if they may help Bertrand and other children living with NGLY1 deficiency."

A surprise discovery unlocks new insights into NGLY1

Because of NGLY1's established role in helping recycle proteins, scientists predicted that cells that lack NGLY1 would fill with unrecycled proteins. However, despite numerous experiments by Freeze and others, this has not been observed.

Mitali Tambe, Ph.D., a postdoctoral associate in the Freeze lab and the first author of the study, set out to shed light on this mystery when she made an unexpected discovery. While normal cells burst open when placed in distilled water, cells from children with an NGLY1 mutation refused to pop open.

"At first I thought what every scientist initially thinks: I made a mistake," says Tambe. "But this observation actually revealed a previously unknown role for NGLY1 protein."

The unexpected finding prompted the scientists to dig in deeper. In addition to studying skin cells from three children with NGLY1 deficiency, the researchers created human and obtained mouse cells that either lacked NGLY1 or produced excess amounts of the protein. In these studies, they found that cells that lacked the NGLY1 protein had fewer aquaporins--proteins that connect the inside and outside of a cell and control water movement--and were resistant to bursting open when placed in water. These results were reversed in cells that were given excess levels of NGLY1. The researchers also identified the molecular signals NGLY1 uses to instruct cells to produce aquaporins, proteins called Atf1 and Creb1, which may lead to useful drug targets.

"In addition to regulating tear and saliva production, aquaporins are involved in many brain functions, such as cerebrospinal fluid production," explains Tambe. "Lack of aquaporins may explain many of the symptoms seen in children who are NGLY1-deficient."

The scientists devised a clever experiment to determine if NGLY1 is regulating aquaporin levels through its expected sugar-removal function or in another manner. They created two cell types that either produced a normal NGLY1 protein or NGLY1 with the sugar-cleaving area disabled. The altered protein successfully altered aquaporin levels--indicating that NGLY1 has a second function in addition to its sugar-removing (enzymatic) activities.

"Our study shows there is more to NGLY1 than its well-known function of removing sugars from proteins," says Freeze. "Together, our findings open important new paths to understanding the pathogenesis of NGLY1 deficiency and ultimately finding treatments."

Credit: 
Sanford Burnham Prebys

Compact broadband acoustic absorber with coherently coupled weak resonances

image: Schematic (left) and absorption comparison (right) of hybrid metasurfaces consisting of perfect and imperfect components;

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©Science China Press

Deep-subwavelength acoustic absorbers have received great attention due to their scientific and application values. Porous materials and micro-perforated absorbers, as the most conventional solutions, generally possess a structural thickness comparable to working wavelength, which hinders their potentials in the low frequency region. The recent advance in acoustic metamaterial/metasurface brings forward perfect absorbers (resonators) that possess ultra-thin thickness but relatively narrow working frequency bandwidth. Then these perfect resonators with quasi-perfect absorption are combined to piece together a broad absorbing band. However, the requirement of quasi-perfect absorption substantially places a very strict restriction on the impedance and thickness of the resonators.

Recently, the research teams from Tongji University and The Hong Kong Polytechnic University go a counter-intuitive way -- coupling imperfect components that possess low absorption peaks to achieve a compact broadband acoustic absorber. Their work opens a new pathway for this challenging goal by exerting the coherent coupling effect among the imperfect components to an unprecedentedly dominant role. This lifts the major restrictions on each component and frees the manipulation of coherent coupling effect. Results show that although each of the components exhibits rather low absorption peak individually, by suitably modulating the coherent coupling effect among the imperfect components, they work collectively to provide a broadband (870 - 3224 Hz) quasi-perfect absorption (average coefficient reaches 0.957). This work explores compact broadband acoustic absorbers with coherently coupled weak resonances and provides deep insight into the fundamental characteristics of these coupling systems, which may pave the way for developing novel acoustic devices against low frequency noise, and pave a way to modulate the surface acoustic impedance arbitrarily in broadband.

Credit: 
Science China Press

Body's natural signal carriers can help melanoma spread

image: The image shows a dividing melanoma cell with its hedgehog-like spikes. The cell is also secreting vesicles.

Image: 
Kirsi Rilla

A new study from Finland sheds fresh light on how melanoma cells interact with other cells via extracellular vesicles they secrete. The researchers found that extracellular vesicles secreted by melanoma cells use the so-called hedgehog signalling pathway to intensify the malignant properties of the cells they are targeting. The discovery can help in the development of better treatment and diagnostics for melanoma. Published in Cellular and Molecular Life Sciences, the study was carried out in collaboration between researchers from the University of Eastern Finland and the University of Helsinki.

Many of the mechanisms regulating the function of our body have remained unchanged throughout evolution. This means that the same genes regulate the development and function of all multicellular animals. One example of such gene survival is the so-called hedgehog signalling pathway. The gene family associated with this signalling pathway gets its unique name from a mutation it caused in fruit fly larvae, making them look spiky, just like a hedgehog. The most common of the three hedgehog genes found in mammals, the Sonic hedgehog gene, was aptly named after the famous video game character. In mammals, members of the hedgehog gene family are essential regulators of foetal development, but they are also associated with stem cell division in later stages of development and even in adults. Recent studies suggest that their expression is also associated with many different types of cancer, including skin cancers. Melanoma is the most severe form of skin cancer, and it is becoming more and more common.

Extracellular vesicles carry signals between cells - and they can also carry packaged drugs

Traditionally, signalling in the body is thought to take place via freely circulating signals, such growth factors and hormones. According to a more recent view, however, it is believed that some signals are packaged for transportation to protect them against breakage and to ensure their delivery to the correct address. Extracellular vesicles are small, bubble-like packages made of cell membrane, serving as natural carriers of signals in the body. They regulate the function of the body already during the foetal stage, via breast milk and also later in life as our tissue regenerates. Cancer cells, too, use extracellular vesicles to deliver signals and to modify their environment, making it favourable to growth. Extracellular vesicles can also be used as diverse carriers of drugs to combat diseases and to repair tissue damage - and this is why they are being studied so actively at the moment.

In the newly published study, the researchers discovered a new link between extracellular vesicles and hedgehog molecules. They found that vesicles secreted by melanoma cells intensify the malignant properties of the cells they are targeting, such as division and spreading, via the hedgehog signalling pathway. The researchers used cultured human melanoma cells and normal skin cells, confirming their findings from the cell culture by analysing tissue samples from patients with melanoma.

"It is quite a coincidence that these signal-carrying vesicles originate from cells that are also known as hedgehog cells due to their microscopically small, spike-like protrusions. These protrusions, however, don't have anything to do with fruit fly larvae; instead, they are typically found in cells that are active in producing hyaluronan, the most common sugar molecule in the extracellular matrix," Docent Kirsi Rilla from the University of Eastern Finland says.

"Hyaluronan also plays a key role in vesicle mediated signalling, as hyaluronan found on the surface of vesicles protruding from the cell surface facilitates their binding to the target cell."

The hedgehog signalling pathway holds great promise as a target for drug therapy in melanoma and other cancers. The regulation mechanism now discovered by the researchers can be made use of in the development of better diagnostics and drug therapy for patients with melanoma.

Docent Rilla's research group has been studying the biology of extracellular vesicles since 2013.

Credit: 
University of Eastern Finland

Brain imaging may improve diagnosis and treatment of mental health disorders

Brain imaging may one day be used to help diagnose mental health disorders--including depression and anxiety--with greater accuracy, according to a new study conducted in a large sample of youth at the University of Pennsylvania and led by Antonia Kaczkurkin, PhD and Theodore Satterthwaite, MD.

And knowing more about the neurobiology behind psychiatric disorders could inform decisions about who might benefit from different therapies.

When diagnosing psychiatric disorders, clinicians currently rely heavily on the symptoms a person experiences, which can be subjective. In addition, the symptoms that clinicians see don't always align with what researchers have observed about brain structure and function in people with psychiatric disorders. And if neurobiology and psychological symptoms are at odds, that calls into question whether the psychological symptoms should drive treatment.

"Researchers are becoming more aware that our traditional symptom-based diagnostic categories do not align with underlying neurobiology," says Dr. Kaczkurkin.

Part of the difficulty in treating depression and anxiety is that not all people respond to a given treatment. Identifying subtypes based on neurobiology rather than symptoms alone might lead to more targeted early intervention or more personalized treatment.

Studying the brains of children and adolescents, the researchers observed that youth can have similar symptoms but different neurobiological patterns. Drs. Kaczkurkin and Satterthwaite and their team used a type of machine learning called HYDRA to interpret information from the brain scans of over 1,100 children and adolescents who had symptoms of depression and anxiety. They focused on several variables: brain volume, thickness of the cortex (the outer layers of the brain), a particular type of brain connectivity (the magnitude of slow fluctuations in brain activity), white matter integrity (the organization of brain white matter tracts), participants' performance on cognitive tests, and patterns of psychiatric symptoms.

Two main clinical subtypes of disorders emerged. The youth in the first subgroup had deficits in brain structure, brain function, and cognition, as well as more marked psychological symptoms than other participants in the study. Those in the second subtype still showed high levels of clinical symptoms of depression and anxiety but didn't have the same deficits in brain structure, brain function, and cognition.

"These results suggest that there may be distinct underlying neurobiological signatures of these common symptoms despite similar clinical presentations," says Dr. Kaczkurkin.

Credit: 
American College of Neuropsychopharmacology

Self-assembled artificial microtubule like LEGO building blocks developed

image: Hierarchical self-assembly of polypseudorotaxanes into artificial microtubules.

Image: 
Kimoon Kim (POSTECH)

Simple LEGO bricks can be assembled to more complicated structures, which can be further associated into a wide variety of complex architectures, from automobiles, rockets, and ships to gigantic castles and amusement parks. Such an event of multi-step assembly, so-called 'hierarchical self-assembly', also happens in living organisms.

Professor Kimoon Kim (Department of Chemistry, POSTECH) and his research team (Center for Self-assembly and Complexity, Institute for Basic Science) discovered that a cucurbituril1)-based host-guest complex polymerized into a linear polymer chain, which was further associated with each other into a hollow microtubule via van der Waals interactions arising from their shape self-complementarity.2) Their novel findings are introduced as a breaking news in Angewandte Chemie International Edition, which is one of the world's renowned journals in Chemistry.

Microtubules exist in living cells of plants and animals and they are essential in maintaining cellular structures, migration of cells, intracellular transport and more. In other words, essential cellular functions such as cellular divisions and intracellular transport cannot be performed when problems occur in formation or dissociation of microtubules.

These microtubules are formed via hierarchical self-assembly of globular proteins in nanometer size, tubulins3), which grow into linear protofilaments.4) Subsequently, these protofilaments are assembled together to build a multi-stranded tubular structure with a length over tens of micrometers.

Before their findings, many attempts have been made to mimic the self-assembly of microtubules in depth for years. However, the formation mechanism of natural microtubules at the molecular level is still ambiguous.

To make artificial microtubules, the research group utilized the cucurbituril-based host-guest complex with two thiol groups attached at the both ends as a building block. This building block assembled into one-dimensional linear polymers by disulfide bond formation. Then, these polymers were laterally associated into a hollow cylindrical architecture similar to natural microtubules through van der Waals interactions. The formation of artificial microtubules was characterized by various spectroscopic and microscopic studies including X-ray diffraction at Pohang Light Source.

Especially, the research team found that the polymer chain became straight and stiff by itself, and eventually LEGO brick-like shape self-complementarity was emerged during the growth of polymer. Strikingly, the convex structures of one chain matched well with the concave parts of the neighboring chains, which allowed lateral association of polymer chains.

The first author of the paper, Wooseup Hwang explained, "Studies before our discovery were focused on mimicking architecture of microtubules. What differentiates our research from the conventional ones is that we attempt to mimic the formation mechanism of microtubules as well as architecture."

Dr. Kangkyun Baek, the other co-corresponding author commented, "We are planning to extend our study to mimic dynamic behaviors and various biological functions of natural microtubules." and "This novel approach based on the shape self-complementarity will make a step forward to understand the formation mechanism of natural microtubules, and offer new opportunities to explore unconventional hierarchical self-assemblies and novel functional materials."

Credit: 
Pohang University of Science & Technology (POSTECH)

Terrain may help identify habitats that are resilient to the effects of climate change

A new paper in The Condor: Ornithological Applications, published by Oxford University Press, finds that models which use terrain features offer both practical and theoretical advantages in identifying climate resilient habitats for migratory birds whose populations are impacted by climate change.

Biodiversity is currently dropping at unprecedented rates, in large part to the fragmentation, alteration, and destruction of natural spaces. Habitat conservation efforts for migratory birds are particularly difficult as they depend on multiple environments spanning the bounds of state parks, national borders, and even continents. This is compounded by the ever-increasing growth of human developments and the competing interests of various stakeholders. These assorted and complex challenges limit the number of territories that can be restored or preserved. It is vital then to identify, and subsequently protect, climate-resilient habitats that have a stronger likelihood of remaining suitable over a longer period of time.

This study focused on three forest birds that have received considerable conservation attention in the Canadian Maritimes due to steep drops in population: the Rusty Blackbird (85% decline), Olive-sided Flycatcher (79% decline), and the Canada Warbler (71% decline). Over the past few decades, species distribution models (SDMs) have emerged as useful tools for understanding a habitat's value for a species. Previous SDMs were created for the three birds in this study, but these models did not consider the implications of climate change. Moreover, prior studies discouraged the inclusion of topographical features.

This study finds that certain terrain features can assist in predicting suitable habitat areas. For instance, an increased depth from the water table in a given terrain decreased the sustainability for both the Rusty Blackbird and the Canada Warbler. As for the Olive-sided Flycatcher, the study indicates that their population was more abundant in valleys and low-slope areas. The study further puts forward the idea that, as these terrain features are generally less affected by climate change than are variables such as temperature and precipitation, they should assist in identifying habitat areas which are more likely to remain suitable for target species over the long-term.

Though differences in forest features may have a more direct impact on a species distribution, these models demonstrate that terrain features do have predictive value, and can sometimes provide a stronger explanation for certain species. The stability of these features, and their ability to predict climate resilient habitats, is especially important in an era of climate change, as shifts in other environmental factors are expected to significantly alter forest ecosystems.

"In this brave new world of climate change, habitat loss, and increasing demands on the environment, a great many bird species, including the Rusty Blackbird, Olive-sided Flycatcher, and Canada Warbler are at serious risk of being lost forever. Nonetheless, using terrain features to help plan habitat protection and recovery efforts may improve the likelihood these beautiful species continue to persist into an uncertain future."

Credit: 
Oxford University Press USA

New point-of-care diagnostic test may revolutionize early diagnosis of Mediterranean rickettsiosis spotted fever

Philadelphia, January 16, 2020 - Rickettsiae are bacteria that cause severe, potentially lethal human infections, including Mediterranean spotted fever (MSF) and Rocky Mountain spotted fever. Delays in diagnosing and treating MSF can cause significant morbidity and mortality, due in part to the lack of a test for early detection. A new study in the American Journal of Pathology, published by Elsevier, reports the discovery of a sensitive and specific marker that may enable early diagnosis, treatment, and accurate public health notification of spotted fever rickettsial infections including MSF.

The assay currently used to diagnose rickettsial diseases lacks sensitivity, especially during the first week of infection, which can lead to mis- and under-diagnosis.

Researchers used a quantitative proteomics pipeline to identify a biomarker for rickettsial infection, rickettsial putative N-acetylmuramoyl-L-alanine amidase (RC0497), for the diagnosis of MSF. After identifying rickettsial RC0497 protein from the culture medium of primary human umbilical vein endothelial cells infected with the MSF-causing pathogen Rickettsia conorii, assays were developed for the detection of RC0497 in blood. The presence of RC0497 was confirmed in the blood of a mouse model of R. conorii and the serum samples from a cohort of humans presenting with acute rickettsioses.

This study shows that RC0497 can significantly differentiate infected individuals from healthy controls, and that the circulating levels of RC0497 are proportional to the severity of infection. Many species of the spotted fever group rickettsiae were also found to express proteins with sequence highly homologous to RC0497.

"The detection of RC0497 has the potential to diagnosis a wide variety of rickettsial spotted fever infections, including Rocky Mountain spotted fever," stated co-lead investigator Yingxin Zhao, PhD, the Department of Internal Medicine and Sealy Center for Molecular Medicine, University of Texas Medical Branch (UTMB), Galveston, TX, USA. Differences in RC0497 levels between infected patients and healthy controls were most striking during the acute phase of infection, although levels of RC0497 were still elevated during convalescence.

"It is our long-term goal to convert this into a point-of-care diagnostic test that will revolutionize the diagnosis of spotted fever rickettsioses, making it available as therapeutic decisions are being made," commented co-author David H. Walker, MD, Director, UTMB Center for Biodefense and Emerging Infectious Disease, Department of Pathology, UTMB, Galveston, TX, USA.

If validated with a larger cohort, this biomarker will enable early detection and timely treatment for rickettsia patients and advance the epidemiological study of spotted fever rickettsial infections.

"This discovery opens the door for a deeper understanding of the spectrum and epidemiology of this re-emerging tick-borne disease. Importantly, the work is the product of an interdisciplinary team of infectious disease specialists, experts in tick-borne diseases, advanced proteomics/analytical chemists, and informaticists who collectively combined their skills to advance this field," noted co-lead investigator Allan R. Brasier, MD, who participated in the study while affiliated with the Department of Internal Medicine and Sealy Center for Molecular Medicine, University of Texas Medical Branch (UTMB), Galveston, TX, USA .

"The rickettsioses represent an important unmet need in human and veterinary medicine. Rickettsioses are a spectrum of potentially lethal diseases whose diagnosis and definitive treatment require a high index of suspicion," explained Drs. Zhao and Brasier.

MSF, one of the most severe diseases caused by rickettsiae, is prevalent throughout the Mediterranean basin, Africa, the Middle East, and India. It presents as an eschar (dry, dark scab), acute fever, headache, and maculopapular rash. After entering the body, rickettsiae can cause vascular leakage, such as pulmonary or cerebral edema.

Credit: 
Elsevier