The scientists believe their research could aid efforts to develop treatments for a serious eating disorder called anorexia nervosa, which has the highest mortality rate of any mental disorder, according to the National Institute of Mental Health. People with anorexia nervosa avoid food, severely restrict food, or eat very small quantities of only certain foods. Even when they are dangerously underweight, they may see themselves as overweight.

“We have identified a part of the brain in a mouse model that controls the impact of emotions on eating,” said Qingchun Tong, PhD, the study’s senior author and an associate professor in the Center for Metabolic and Degenerative Disease at McGovern Medical School at UTHealth.

Because mice and humans have similar nervous systems, Tong, the Cullen Chair in Molecular Medicine at UTHealth, believes their findings could shed light on the part of the human brain that regulates hunger.

The investigators believe they are among the first to demonstrate the role of this neurocircuit in the regulation of both stress and hunger.

While previous research has established that stress can both reduce and increase a person’s desire to eat, the neural mechanisms that act on the regulation of eating by stress-related responses largely remain a mystery.

Tong’s team focused on a neurocircuit connecting two parts of the mouse brain: the paraventricular hypothalamus, an eating-related zone in the brain, and the ventral lateral septum, an emotional zone in the brain. The neurocircuit acts as an on/off switch.

When researchers activated the neurocircuit, there was an increase in anxiety levels and a decrease in appetite. Conversely, when the investigators inhibited the neurocircuit, anxiety levels dropped and hunger increased.

The scientists used a research technique called optogenetics to turn the neurons in question on and off.

Yuanzhong Xu, PhD, the study’s lead author and an instructor at McGovern Medical School, said additional preclinical tests are needed to confirm their findings.

Coauthors from UTHealth include Yungang Lu, PhD; Ryan Cassidy; Leandra Mangieri, PhD; Canjun Zhu, PhD; Zhiying Jiang, PhD; Xugen Huang, PhD; and Nicholas Justice, PhD. Also contributing to the paper were Yong Xu, MD, PhD, and Benjamin Arenkiel, PhD, of Baylor College of Medicine.

Tong and Justice are on the faculty of The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences.

The site also points to a new location for where modern humans may have first encountered their mysterious cousins, the now extinct Denisovans, said Nicolas Zwyns, an associate professor of anthropology and lead author of the study.

Zwyns led excavations from 2011 to 2016 at the Tolbor-16 site along the Tolbor River in the Northern Hangai Mountains between Siberia and northern Mongolia.

The excavations yielded thousands of stone artifacts, with 826 stone artifacts associated with the oldest human occupation at the site. With long and regular blades, the tools resemble those found at other sites in Siberia and Northwest China — indicating a large-scale dispersal of humans across the region, Zwyns said.

“These objects existed before, in Siberia, but not to such a degree of standardization,” Zwyns said. “The most intriguing (aspect) is that they are produced in a complicated yet systematic way — and that seems to be the signature of a human group that shares a common technical and cultural background.”

That technology, known in the region as the Initial Upper Palaeolithic, led the researchers to rule out Neanderthals or Denisovans as the site’s occupants. “Although we found no human remains at the site, the dates we obtained match the age of the earliest Homo sapiens found in Siberia,” Zwyns said. “After carefully considering other options, we suggest that this change in technology illustrates movements of Homo sapiens in the region.”

Their findings were published online in an article in Scientific Reports.

The age of the site — determined by luminescence dating on the sediment and radiocarbon dating of animal bones found near the tools — is about 10,000 years earlier than the fossil of a human skullcap from Mongolia, and roughly 15,000 years after modern humans left Africa.

Evidence of soil development (grass and other organic matter) associated with the stone tools suggests that the climate for a period became warmer and wetter, making the normally cold and dry region more hospitable to grazing animals and humans.

Preliminary analysis identifies bone fragments at the site as large (wild cattle or bison) and medium size bovids (wild sheep, goat) and horses, which frequented the open steppe, forests and tundra during the Pleistocene — another sign of human occupation at the site.

The dates for the stone tools also match the age estimates obtained from genetic data for the earliest encounter between Homo sapiens and the Denisovans.

“Although we don’t know yet where the meeting happened, it seems that the Denisovans passed along genes that will later help Homo sapiens settling down in high altitude and to survive hypoxia on the Tibetan Plateau,” Zwyns said. “From this point of view, the site of Tolbor-16 is an important archaeological link connecting Siberia with Northwest China on a route where Homo sapiens had multiple possibilities to meet local populations such as the Denisovans.”

Co-authors of the paper include UC Davis anthropology graduate students Roshanne Bakhtiary and Kevin Smith, former graduate student Joshua Noyer, and undergraduate alumna Aurora Allshouse, now a graduate student at Harvard University.

Other members of the team included colleagues from universities and institutes in South Carolina, the United Kingdom, Mongolia, Germany, Belgium and Russia.

Besides the use in textiles, it was discovered that some nylons also exhibit so called “ferroelectric properties.” This means that positive and negative electric charges can be separated and this state can be maintained. The ferroelectric materials are used in sensors, actuators, memories and energy harvesting devices. The advantage in using polymers is that they can be liquified using adequate solvents and therefore processed from solution at low cost to form flexible thin-films which are suitable for electronic devices such as capacitors, transistors and diodes. This makes ferroelectric polymers a viable choice for integration with e-textiles. Although nylon polymers have found over the years significant commercial applications in fabrics and fibers, their application in electronic devices was hindered because it was impossible to create high quality thin films of ferroelectric nylons by solution processing.

Scientists at the MPI-P, in collaboration with researchers from the Johannes Gutenberg University of Mainz and Lodz University of Technology, have now solved this forty year old problem, and developed a method to fabricate ferroelectric nylon thin-film capacitors by dissolving nylon in a mixture of trifluoroacetic acid and acetone and solidifying it again in vacuum. They were able to realize thin nylon films that are typically only a few 100 nanometers thick, several 100 times thinner than human hair. “Using this method, we have produced extremely smooth thin-films. This is very important because it prevents electrical break down of for example capacitors and destroying the electronic circuits. At the same time, the smoothness allows for having transparent thin-films and eventually transparent electronic devices,” says Dr. Kamal Asadi, group leader at the MPI-P.

By using their newly developed method, the group around Kamal Asadi was able to produce high performance nylon capacitors. The scientists subjected the prototypes of the capacitors to extended stress cycles and demonstrated robustness of ferroelectric nylons under millions of operation cycles. The thin nylon films could become an important component for use in flexible electronics in the future and find applications in bendable electronic devices or for electronics in clothing. These new findings pave the way towards multi-functional fabrics that serve as cloth for covering our body and at the same time can generate electricity from our body movement.

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Especially the molecular factors that help enteroviruses to open up and release its genome in human cells are not well understood.

Using real-time uncoating measurements and high-resolution structures, a research team comprised of docent Varpu Marjomäki´s group (Nanoscience Center at the University of Jyväskylä) and professor Sarah Butcher´s group (University of Helsinki) found that the common molecule in serum and interstitial fluids, albumin, and an ion composition that is typically developed in cellular vesicles, trigger expansion of the virion.

This expanded and fenestrated virus then allows more small molecules such as ions to enter the virus. The results of this study suggest that before entering cells, albumin primes the virus to form a metastable yet infectious intermediate particle. Then, ionic changes that are likely to occur in cellular vesicles further contribute to opening and promote release of the genome.

“The successful release of the genome is one of the rate-limiting steps in virus infection. It needs to occur in the right place in the right time to ensure efficient infection. This work provides new insight into understanding this fundamental aspect of enterovirus life cycle and may yield targets for therapeutic development,” says docent Varpu Marjomäki from the Nanoscience Center at the University of jyväskylä.

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In a paper published as a “First Release,” in the journal Science, lead authors Kirill Martemyanov, PhD, and Brock Grill, PhD, describe how they designed and implemented a new, unbiased approach for decoding the genetic network that controls actions of opioids in a nervous system.

They used a small soil dwelling animal, the nematode worm, to discover something surprising about one of the most-studied drug receptors.

“A study like this makes it clear that even though we may think we know everything there is to know about the opioid response, we’re actually just scratching the surface,” Martemyanov says.

Their system relies upon the nematode c. elegans, engineered to express the mammalian surface receptor for painkilling drugs, the μ (mu) opioid receptor (MOR). The receptor is not normally found in the worms’ DNA, and adding it made the transgenic animals respond to opioids like morphine and fentanyl. The researchers then exposed the worms to mutagens and selected the ones with abnormal responses to opioids. Whole-genome sequencing and CRISPR engineering was then used to pinpoint the genes responsible for those aberrant responses.

“Forward genetics — unbiased genetic discovery — has never been applied to probing an opioid receptor like this,” Grill says. “The opioid epidemic is a huge problem and we don’t have good solutions. This type of approach can bring a whole new array of targets and a new way of thinking about and going after an old problem.”

The work ultimately led the researchers to the worms’ FRPR-13 receptor, conserved in all animals, and known as GPR139 in mammals. It is considered an “orphan” G-protein coupled receptor (GPCR) with poorly understood biology and unknown role in physiology. Further studies in mice showed that GPR139 was expressed on the same neurons as MOR and counteracted the effects of opioids on neuronal firing.

When researchers administered drugs that activate GPR139, mice dependent on opioid intake stopped taking the drug. Conversely, genetic elimination of GPR139 augmented the pain-killing effects of opioids. The genetically modified mice lacking GPR139 also showed something remarkable — they showed very minimal withdrawal symptoms following chronic exposure to opioids. Withdrawal syndrome, a set of extremely unpleasant symptoms, usually sets in upon the discontinuation of opioids following their prolonged use. This compels people to resume drug-taking, fueling the dependence, Martemyanov says. The discovery could point a way toward lessening the suffering associated with opioid withdrawal, Grill says.

“A lot of addicts know that if they stop using, they are going to deal with anxiety, nausea, tremor and they are going to be in a lot of pain. That probably has a very negative impact on people wanting to go into rehab,” Grill says.

Opioids, a group of drugs that include fentanyl, Vicodin, OxyContin and morphine, are highly effective at blunting severe pain, however prolonged use can create tolerance and dependence. Excessive use can cause overdose.

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They hope that one day, monitoring perspiration could bypass the need for more invasive procedures like blood draws, and provide real-time updates on health problems such as dehydration or fatigue.

In a paper appearing today (Friday, August 16) in Science Advances, the team describes a new sensor design that can be rapidly manufactured using a “roll-to-roll” processing technique that essentially prints the sensors onto a sheet of plastic like words on a newspaper.

They used the sensors to monitor the sweat rate, and the electrolytes and metabolites in sweat, from volunteers who were exercising, and others who were experiencing chemically induced perspiration.

“The goal of the project is not just to make the sensors but start to do many subject studies and see what sweat tells us — I always say ‘decoding’ sweat composition,” said Ali Javey, a professor of electrical engineering and computer science at UC Berkeley and senior author on the paper.

“For that we need sensors that are reliable, reproducible, and that we can fabricate to scale so that we can put multiple sensors in different spots of the body and put them on many subjects,” said Javey, who also serves as a faculty scientist at Lawrence Berkeley National Laboratory.

The new sensors contain a spiraling microscopic tube, or microfluidic, that wicks sweat from the skin. By tracking how fast the sweat moves through the microfluidic, the sensors can report how much a person is sweating, or their sweat rate.

The microfluidics are also outfitted with chemical sensors that can detect concentrations of electrolytes like potassium and sodium, and metabolites like glucose.

Javey and his team worked with researchers at the VTT Technical Research Center of Finland to develop a way to quickly manufacture the sensor patches in a roll-to-roll processing technique similar to screen printing.

“Roll-to-roll processing enables high-volume production of disposable patches at low cost,” Jussi Hiltunen of VTT said. “Academic groups gain significant benefit from roll-to-roll technology when the number of test devices is not limiting the research. Additionally, up-scaled fabrication demonstrates the potential to apply the sweat-sensing concept in practical applications.”

To better understand what sweat can say about the real-time health of the human body, the researchers first placed the sweat sensors on different spots on volunteers’ bodies — including the forehead, forearm, underarm and upper back — and measured their sweat rates and the sodium and potassium levels in their sweat while they rode on an exercise bike.

They found that local sweat rate could indicate the body’s overall liquid loss during exercise, meaning that tracking sweat rate might be a way to give athletes a heads up when they may be pushing themselves too hard.

“Traditionally what people have done is they would collect sweat from the body for a certain amount of time and then analyze it,” said Hnin Yin Yin Nyein, a graduate student in materials science and engineering at UC Berkeley and one of the lead authors on the paper. “So you couldn’t really see the dynamic changes very well with good resolution. Using these wearable devices we can now continuously collect data from different parts of the body, for example to understand how the local sweat loss can estimate whole-body fluid loss.”

They also used the sensors to compare sweat glucose levels and blood glucose levels in healthy and diabetic patients, finding that a single sweat glucose measurement cannot necessarily indicate a person’s blood glucose level.

“There’s been a lot of hope that non-invasive sweat tests could replace blood-based measurements for diagnosing and monitoring diabetes, but we’ve shown that there isn’t a simple, universal correlation between sweat and blood glucose levels,” said Mallika Bariya, a graduate student in materials science and engineering at UC Berkeley and the other lead author on the paper. “This is important for the community to know, so that going forward we focus on investigating individualized or multi-parameter correlations.”

This work was supported by the NSF Nanomanufacturing Systems for Mobile Computing and Mobile Energy Technologies (NASCENT), the Berkeley Sensor and Actuator Center (BSAC), and the Bakar fellowship.