Culture

Scientists from Dalian Institute of Chemical Physics (DICP) and Shanghai Institute of Biochemistry and Cell Biology (SIBCB) of the Chinese Academy of Sciences revealed that UDP-glucose accelerates SNAI1 mRNA decay and impairs lung cancer metastasis. Their findings were published in Nature.

Metastasis is the primary cause of cancer morbidity and mortality, and accounts for up to 95% of cancer-related deaths. UDP-glucose 6-dehydrogenase (UGDH) is a key enzyme in the uronic acid pathway that converts UDP-glucose to UDP-glucuronic acid; Hu antigen R (HuR) is a ubiquitously expressed RNA-binding protein that binds to the 3'-untranslated region (UTR) region of many short-lived mRNAs and increases their stability.

Dr. YANG Weiwei's group from SIBCB has performed the experimental research. The results show that, upon EGFR activation, phosphorylated UGDH interacts with HuR and converts UDP-glucose to UDP-glucuronic acid. The resulting UDP-glucoronic acid attenuated the UDP-glucose-mediated inhibition of the association of HuR with SNAI1 mRNA, thus enhancing SNAI1 mRNA stability.

Increased SNAIL expression initiates the epithelial-mesenchymal transition, thereby promoting tumor cell migration and lung cancer metastasis. These findings reveal a tumor-suppressive role for UDP-glucose in lung cancer metastasis and uncover the mechanism by which UGDH promotes tumor metastasis by increasing SNAI1 mRNA stability.

Dr. Li Guohui's group from DICP has performed molecular dynamics (MD) simulations to elucidate the structural basis underlying the UDP-Glc- or UDP-GlcUA-regulated binding of HuR to mRNA. The MD results showed that both UDP-Glc and UDP-GlcUA bound to the same RNA-binding domain of HuR.

The binding affinity of UDP-Glc with HuR is stronger than UDP-GlcUA with HuR, which is consistent with experimental results. Essentially, two mutants of HuR(Y63F) and HuR(N134A) were generated and studied. It was found that HuR(N134A) had a much lower affinity for both metabolites than HuR(WT) and HuR(Y63F), but still bound to SNAI1 mRNA, and tumor cells rescued with rHuR(N134A) showed more migration.

In the early 20th century, researchers in Massachusetts studied the first community-based health intervention in the world, the Framingham Health and Tuberculosis Demonstration, deeming it highly successful in controlling tuberculosis (TB) and reducing mortality. Now a new study, which used recently digitized data on causes of death during that period, has concluded that the effort was not as successful as initially thought, and suggests that the intervention cannot be cited as evidence for the success of health policies in the era before antibiotics became available. Because the intervention inspired a number of contemporary health demonstrations and projects used in developing countries today, the new study raises serious questions.

The new study, by researchers at Carnegie Mellon University, the University of Southern Denmark, the University of Copenhagen, and the University of Michigan, appears in a working paper of the National Bureau of Economic Research.

"Our findings imply that the original intervention was unsuccessful," says Karen Clay, professor of economics and public policy at Carnegie Mellon University's Heinz College, who led the study. "Our results also contribute to the ongoing debate over whether public-health interventions mattered for the decline in mortality from TB prior to modern medicine. And they raise questions about this particular type of intervention--a community-based program that didn't assign people randomly to treatment options--as a method for evaluating policy interventions."

In the new study, researchers rigorously analyzed the effects of the first public health demonstration on mortality from TB, total mortality, and infant mortality. In that demonstration, begun in 1917, the National Association for the Study and Prevention of Tuberculosis, funded by Metropolitan Life Insurance Company, chose Framingham, Massachusetts, as a typical American community. Located 32 miles west of Boston, Framingham had an immigrant population of 27% that mirrored the immigrant population of the United States as a whole.

The six-year intervention featured a number of efforts to control TB in the town. A survey of sickness was done, as were studies of sanitary conditions in schools and factories; there was also a tuberculin survey of area cattle. The demonstration also initiated a consultation service; led by a doctor, it helped local physicians diagnose TB and connected patients with doctors and treatment options. In addition, infant welfare clinics helped mothers and babies receive adequate care, informational campaigns provided tips on how to prevent TB, and increased funding boosted health efforts in schools.

In 1923, at the end of the intervention, the association announced that TB and infant mortality had decreased 69% in Framingham; in seven similar communities that did not receive the intervention, TB and infant mortality decreased just 32%, the association said.

In the current study, researchers used newly digitized vital statistics for towns and cities in Massachusetts from 1901 to 1934 to gauge mortality associated with TB and in infants. To evaluate the effect of the original intervention, the researchers constructed a counterfactual city using data from other cities and different statistical methods to determine what would have happened in a city like Framingham if the demonstration had not been carried out there.

In contrast to the positive conclusions of the original study and the subsequent historical narrative, the current study found that the Framingham intervention did not reduce mortality from TB, total mortality, or infant mortality. The intervention did increase the number of TB cases that were discovered.

"The implication of our findings is that the Framingham Demonstration was not as successful as believed and that public health policy was not a decisive factor in the reduction of TB mortality," Clay says.

Archaeologists working in two Italian caves have discovered some of the earliest known examples of ancient humans using an adhesive on their stone tools--an important technological advance called "hafting."

The new study, which included CU Boulder's Paola Villa, shows that Neanderthals living in Europe from about 55 to 40 thousand years ago traveled away from their caves to collect resin from pine trees. They then used that sticky substance to glue stone tools to handles made out of wood or bone.

The findings add to a growing body of evidence that suggests that these cousins of Homo sapiens were more clever than some have made them out to be.

"We continue to find evidence that the Neanderthals were not inferior primitives but were quite capable of doing things that have traditionally only been attributed to modern humans," said Villa, corresponding author of the new study and an adjoint curator at the CU Museum of Natural History.

That insight, she added, came from a chance discovery from Grotta del Fossellone and Grotta di Sant'Agostino, a pair of caves near the beaches of what is now Italy's west coast.

Those caves were home to Neanderthals who lived in Europe during the Middle Paleolithic period, thousands of years before Homo sapiens set foot on the continent. Archaeologists have uncovered more than 1,000 stone tools from the two sites, including pieces of flint that measured not much more than an inch or two from end to end.

In a recent study of the tools, Villa and her colleagues noticed a strange residue on just a handful of the flints--bits of what appeared to be organic material.

"Sometimes that material is just inorganic sediment, and sometimes it's the traces of the adhesive used to keep the tool in its socket" Villa said.

To find out, study lead author Ilaria Degano at the University of Pisa conducted a chemical analysis of 10 flints using a technique called gas chromatography/mass spectrometry. The tests showed that the stone tools had been coated with resin from local pine trees. In one case, that resin had also been mixed with beeswax.

Villa explained that the Italian Neanderthals didn't just resort to their bare hands to use stone tools. In at least some cases, they also attached those tools to handles to give them better purchase as they sharpened wooden spears or performed other tasks like butchering or scraping leather.

"You need stone tools to cut branches off of trees and make them into a point," Villa said.

The find isn't the oldest known example of hafting by Neanderthals in Europe--two flakes discovered in the Campitello Quarry in central Italy predate it. But it does suggest that this technique was more common than previously believed.

The existence of hafting also provides more evidence that Neanderthals, like their smaller human relatives, were able to build a fire whenever they wanted one, Villa said--something that scientists have long debated. She said that pine resin dries when exposed to air. As a result, Neanderthals needed to warm it over a small fired to make an effective glue.

"This is one of several proofs that strongly indicate that Neanderthals were capable of making fire whenever they needed it," Villa said.

The existing approach to brain stimulation for rehabilitation after a stroke does not take into account the diversity of lesions and the individual characteristics of patients' brains. This was the conclusion made by researchers of the Higher School of Economics (HSE University) and the Max Planck Institute of Cognitive Sciences in their article, 'Predicting the Response to Non-Invasive Brain Stimulation in Stroke'.

Among the most common causes of death worldwide, stroke ranks second only to myocardial infarction (heart attack). In addition, a stroke is also a chronic disease that leaves patients disabled for many years.

In recent decades, non-invasive neuromodulation methods such as electric and magnetic stimulation of various parts of the nervous system have been increasingly used to rehabilitate patients after a stroke. Stimulation selectively affects different parts of the brain, which allows you to functionally enhance activity in some areas while suppressing unwanted processes in others that impede the restoration of brain functions. This is a promising mean of rehabilitation after a stroke. However, its results in patients remain highly variable.

The study authors argue that the main reason for the lack of effectiveness in neuromodulation approaches after a stroke is an inadequate selection of patients for the application of a particular brain stimulation technique.

According to the authors, the existing approach does not take into account the diversity of lesions after a stroke and the variability of individual responses to brain stimulation as a whole. Researchers propose two criteria for selecting the optimal brain stimulation strategy. The first is an analysis of the interactions between the hemispheres. Now, all patients, regardless of the severity of injury after a stroke, are offered a relatively standard treatment regimen. This approach relies on the idea of interhemispheric competition.

'For a long time, it was believed that when one hemisphere is bad, the second, instead of helping it, suppresses it even more,' explains Maria Nazarova, one of the authors of the article and a researcher at the HSE Institute of Cognitive Neurosciences. 'In this regard, the suppression of the activity of the "unaffected" hemisphere should help restore the affected side of the brain. However, the fact is that this particular scheme does not work in many patients after a stroke. Each time it is necessary to check what the impact of the unaffected hemisphere is -- whether it is suppressive or activating.'

The second criterion, scientists call the neuronal phenotype. This is an individual characteristic of the activity of the brain, which is 'unique to each person like their fingerprints'. Such a phenotype is determined, firstly, by the ability of the brain to build effective structural and functional connections between different areas (connectivity). And, secondly, the individual characteristics of neuronal dynamics, including its ability to reach a critical state. This is the state of the neuronal system in which it is the most plastic and capable of change.

Only by taking these criteria into account, the authors posit, can neuromodulation methods be brought to a new level and be effectively used in clinical practice. To do this, it is necessary to change the paradigm of the universal approach and select methods based on the individual characteristics of the brain of a particular person and the course of his or her disease.

For the first time, researchers have decoded the genetic programmes that control the development of major organs in humans and other selected mammals - rhesus monkeys, mice, rats, rabbits, and opossums - before and after birth. Using next-generation sequencing technologies, the molecular biologists at Heidelberg University analysed the brain, heart, liver, kidney, testicles, and ovaries. Their large-scale study demonstrated, among other things, that all the organs studied exhibit fundamental and original gene activity networks that must have originated early on in mammalian evolution more than 200 million years ago. In a second large study, the scientists explored for the first time the developmental roles of a hitherto poorly understood but large category of genes, so-called RNA genes, which produce ribonucleic acids and not proteins, like "normal" genes.

A finely tuned and complex interaction of the activity of a large number of genes - also known as gene expression - controls development from a fertilised egg cell to an adult organism. Previously, the understanding of these essential genetic programmes in mammals was restricted to individual protein genes and specific organs or development phases. Furthermore, most previous work focused on the mouse. "The genetic foundations that account for the differences in size, structure, and function of organs in different mammals were largely unknown," says Prof. Dr Henrik Kaessmann, group leader of the "Functional evolution of mammalian genomes" research team at the Center for Molecular Biology of Heidelberg University (ZMBH).

To fully investigate the developmental programmes, the Kaessmann team turned to innovative high-throughput approaches. These next-generation sequencing technologies (NGS) enable analysing the expression of all genes in the respective genome at the same time. Using NGS, more than 100 billion expression fragments for both protein and RNA genes from various organs and mammals were read. "This allowed us to quantify and compare the shifting gene activities over the course of development," explain Dr Margarida Cardoso-Moreira and Ioannis Sarropoulos, the first authors of the two publications that describe the studies.

The bioinformatic analyses of the data were performed using high-powered computers at the Heidelberg University Computing Centre. They provided new insights into the genetic control of organ development in mammals. The fundamental and original gene activity networks that the researchers discovered function similarly and determine key developmental processes in all the mammals studied, including humans. That means that these molecular networks already controlled organ development of early mammals 200 million years ago.

The researchers also found a surprisingly large number of genes whose activity patterns deviated significantly from one another in the various species of mammals. These differences, which arose during the course of evolution, explain the specific organ traits of the respective species. For the genes that control brain development, for example, the Heidelberg researchers were able to identify distinct expression patterns in humans. The scientists also discovered that a surprisingly large number of RNA genes are involved in the control of organ development. Thus, this type of gene, which was previously difficult to characterise, plays an important role in mammalian development, emphasises Prof. Kaessmann.

In their large-scale studies, the ZMBH researchers identified a higher-level pattern in the sequence of the genetic programmes. Whereas they were still very similar in the early, i.e. prenatal, phase of organ development between all the mammals studied, they deviated more and more as time progressed. "The traits of the organs that characterise a species do not originate until later during development", explains Prof. Kaessmann. "Using modern molecular methods, we were able for the first time to confirm a groundbreaking hypothesis in biology from the 19th century." The Baltic German naturalist Karl Ernst von Baer (1792 to 1876) discovered that the embryos of various species of mammal were increasingly difficult to differentiate the younger they were.

Bats are creatures of the night and are accustomed to complete darkness. They harness their hypersensitive hearing to feed, to fend off prey and to mate.

But that's not the entire story. A new Tel Aviv University study finds that fruit bats actually integrate vision and echolocation to flourish in the dead of night. The new research was led by Prof. Yossi Yovel and conducted by Dr. Sasha Danilovich, both of TAU's George S. Wise Faculty of Life Sciences, and was published on June 26 in Science Advances.

The study focuses on several aspects of fruit bats' integrated vision-echolocation abilities. Bats translate an echo into a visual image and then use their vision to find their way out of a maze and determine the shapes of objects.

"Contrary to popular belief, bats do indeed see, and many of them do use their eyes as much as they use echolocation," Dr. Danilovich says. "But how they integrate vision and echolocation is poorly understood. Our new findings shed light on how fruit bats really operate in darkness."

"How animals -- including humans -- integrate information from different sensory modalities is a major question that still puzzles scientists," Prof. Yovel explains. "Imagine, for example, that you see a car coming from the right, but you hear another one coming from the left. How will your brain process and integrate this information?

"Bats are useful models for studying this and other related phenomena because of their dual reliance on two remote sensory systems: vision and echolocation."

Over several months, the scientists trained the bats hoping to test the extent of their echolocation and vision skills. "These experiments take months, because the bats have to first understand what it is we want of them," says Dr. Danilovich.

In one experiment, the researchers trained the model bats to land on one of two objects in complete darkness for a reward. They also trained them to distinguish between a smooth object and an object perforated with holes.

The team first conducted the experiments under the cloak of darkness and then turned on the lights, eliminating echolocation.

"We found that their brains actually transformed echoes into visual images," Dr. Danilovich says. "It was amazing to see them harness their aural experience and translate it into useful visual data."

The researchers also demonstrated that fruit bats predominantly use vision to find their way out of a maze and to learn the shape of an object.

"When we afforded them the opportunity to attempt to distinguish between a triangle and a cylinder, they only used their vision," Prof. Yovel notes. "When they were tested in total darkness, they were unable to perform the task.

"We have shown that bats are able to translate the acoustic echoes of some objects into visual representations," Prof. Yovel concludes. "We next hope to harness this new echo-to-image paradigm to examine whether bats can build a 3D representation of the world based on echoes alone."

Hospital-wide introduction of new female external catheter technology halved the number of catheter-associated urinary tract infections (CAUTIs) according to new research presented last week in Philadelphia at the 46th Annual Conference of the Association for Professionals in Infection Control and Epidemiology (APIC).

After identifying a slow climb in the number of CAUTIs from 2016 to the first quarter of 2018, infection preventionists (IPs) at NYC Health + Hospitals/Coney Island introduced the hospital's healthcare provers to new female external catheter technology - an alternative and non-invasive method of managing incontinent patients.

"The leading risk factor for CAUTI development is prolonged use of indwelling Foley catheters," said study author Briana Episcopia, BS, RN, CIC. "The female external catheter gave doctors and nurses an alternative that eliminated the need for an indwelling catheter, ultimately eliminating some patients' risk of developing this type of infection."

Utilizing data from the Center for Disease Control and Prevention's National Healthcare Safety Network (NHSN), researchers compared inpatient infections, Foley utilization, and the standardized infection ratio (SIR) pre- and post-implementation (October 2017 to September 2018). Highlights included:

A hospital-wide reduction of inpatient CAUTIs by 51.7 percent.

Reduction of the Foley utilization rate from 15.7 to 10.7, which resulted in a decline in the number of Foley days for the hospital.

"CAUTI reduction is a top priority for the overall reduction of healthcare-associated infections," said 2019 APIC President Karen Hoffmann, RN, MS, CIC, FSHEA, FAPIC. "The female external catheter may provide an important advancement as we strive to reduce the risk of infection."

An interdisciplinary approach to antimicrobial stewardship involving comprehensive blood culture identification (BCID) testing decreased broad spectrum antibiotic use, according to new research presented last week in Philadelphia at the 46th Annual Conference of the Association for Professionals in Infection Control and Epidemiology (APIC).

The microbiology lab at Einstein Medical Center Montgomery in Pennsylvania, in collaboration with the antimicrobial stewardship team, implemented a new protocol to treat sepsis patients. Rapid BCID polymerase chain reaction (PCR) tests were administered to identify the bacteria making the patient sick, and pharmacists made recommendations on how to manage or readjust the previously prescribed antibiotic regimen.

Data collected for four months before and after implementation showed that the new BCID PCR test protocol resulted in providers adjusting patients' antibiotic treatment a full 25 hours sooner on average, decreasing patients' time on broad spectrum antibiotics.

"Reducing the use of broad spectrum antibiotics is essential in slowing the growth of resistant bacteria," said lead study author David Ezdon, PharmD. "Through rapid blood culture identification tests, we are able to tailor patients' antibiotic regimen and ultimately improve their care."

Pharmacists' recommendations were developed using an algorithm that determines the best course of treatment for the type of bacteria indicated by the BCID PCR test results.

By optimizing antibiotic use, Montgomery Hospital observed a length of stay reduction of 1.45 days per patient, which resulted in a cost avoidance of $322,508 over four months.

"This scenario illustrates the success that antimicrobial stewardship programs can achieve when healthcare providers, pharmacists, and infection preventionists work together," said 2019 APIC President Karen Hoffmann, RN, MS, CIC, FSHEA, FAPIC. "Antimicrobial stewardship programs require coordination across multiple disciplines to achieve the larger goal of preserving antibiotic therapy for future generations."

Antimicrobial stewardship programs encourage the appropriate use of antimicrobials (including antibiotics) to minimize overuse, improve patient outcomes, reduce microbial resistance, decrease the spread of infections, and preserve the efficacy of antibiotics. Multidrug-resistant organisms cause a significant proportion of serious healthcare-associated infections (HAIs) and are more difficult to treat because there are fewer and, in some cases, no antibiotics that will cure the infection. The Centers for Disease Control and Prevention (CDC) states that each year in the United States at least 2 million people become infected with bacteria that are resistant to antibiotics and at least 23,000 people die as a result.

Researchers at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, have retrieved nuclear genome sequences from the femur of a male Neandertal discovered in 1937 in Hohlenstein-Stadel Cave, Germany, and from the maxillary bone of a Neandertal girl found in 1993 in Scladina Cave, Belgium. Both Neandertals lived around 120,000 years ago, and therefore predate most of the Neandertals whose genomes have been sequenced to date.

By examining the nuclear genomes of these two individuals, the researchers could show that these early Neandertals in Western Europe were more closely related to the last Neandertals who lived in the same region as much as 80,000 years later, than they were to contemporaneous Neandertals living in Siberia. "The result is truly extraordinary and a stark contrast to the turbulent history of replacements, large-scale admixtures and extinctions that is seen in modern human history", says Kay Prüfer who supervised the study.

Intriguingly, unlike the nuclear genome, the mitochondrial genome of the Neandertal from Hohlenstein-Stadel Cave in Germany is quite different from that of later Neandertals - a previous report showed that more than 70 mutations distinguish it from the mitochondrial genomes of other Neandertals. The researchers suggest that early European Neandertals may have inherited DNA from a yet undescribed population. "This unknown population could represent an isolated Neandertal population yet to be discovered, or may be from a potentially larger population in Africa related to modern humans", explains Stéphane Peyrégne who led the analysis.

A Frog Worth Kissing: Natural Defense Against Red Tide Toxin Found in Bullfrogs

By ALIYAH KOVNER

A team led by Berkeley Lab faculty biochemist Daniel Minor has discovered how a protein produced by bullfrogs binds to and inhibits the action of saxitoxin, the deadly neurotoxin made by cyanobacteria and dinoflagellates that causes paralytic shellfish poisoning.

The findings, published this week in Science Advances, could lead to the first-ever antidote for the compound, which blocks nerve signaling in animal muscles, causing death by asphyxiation when consumed in sufficient quantities.

"Saxitoxin is among the most lethal natural poisons and is the only marine toxin that has been declared a chemical weapon," said Minor, who is also a professor at the UCSF Cardiovascular Research Institute. About one thousand times more potent than cyanide, saxitoxin accumulates in tissues and can therefore work its way up the food chain - from the shellfish that eat the microbes to fish, turtles, marine mammals, and us.

Minor and his colleagues elucidated the mechanism of the protective protein, called saxiphilin, by mapping the atomic structure of free saxiphilin and saxitoxin-bound saxiphilin using high-resolution X-ray crystallography performed at Berkeley Lab's Advanced Light Source.

"Climate change is making blooms of toxic algae more common," said Minor. "Understanding how frogs have developed molecules that help them to resist toxic environments holds important lessons that could help us have a defense at the ready. "

To learn more about this research, read the full UCSF News Article

Scientists Capture Atomic Motion in 4D for the First Time

Adapted from a story by WAYNE LEWIS

Everyday transitions from one state of matter to another - such as freezing, melting, or evaporation - start with a process called "nucleation," in which tiny clusters of atoms or molecules (called "nuclei") begin to coalesce. Nucleation plays a critical role in circumstances as diverse as the formation of clouds and the onset of neurodegenerative disease.

Scientists have gained a never-before-seen view of nucleation - capturing how the atoms rearrange at 4D atomic resolution (that is, in three dimensions of space and across time). The findings, published in the journal Nature, differ from predictions based on the classical theory of nucleation that has long appeared in textbooks.

The UCLA-led team, which includes collaborators from Berkeley Lab, used a state-of-the-art electron microscope located at the Molecular Foundry. In much the same way a CAT scan generates a 3D X-ray of the human body, atomic electron tomography uses electrons to create stunning 3D images of atoms within a material as the sample is rotated under the microscope.

"Nucleation is basically an unsolved problem in many fields," said co-author Peter Ercius, a staff scientist at Berkeley Lab's Molecular Foundry. "Once you can image something, you can start to think about how to control it."

Scientists Find a Molecular Switch for Better Biofuels

Adapted from a story by ANNE STARK

Plant cell walls contain a renewable, nearly-limitless supply of sugar that can be used as a carbon source for microbe-based chemical and biofuel production. However, retrieving these sugars isn't all that easy.

Imidazolium ionic liquid (IIL) solvents are some of the best agents for extracting sugars from plants. But the sugars from IIL-treated biomass are inevitably contaminated with residual IILs that inhibit growth in bacteria and yeast, blocking biochemical production by these organisms.

Lawrence Livermore National Laboratory (LLNL) scientists and collaborators at the Joint BioEnergy Institute have identified a molecular mechanism in bacteria that can be manipulated to promote IIL tolerance, and therefore overcome a key roadblock in biofuel and biochemical production processes. The research appears in the Journal of Bacteriology.

According to lead author and LLNL biologist Michael Thelen, the team discovered that two bacillus strains and one mutant E. coli strain can withstand high levels of two widely used IILs thanks to special membrane pumps that transport the toxic solvents out of cells.

"Our results demonstrate the critical roles that transporter genes and their genetic controls play in IIL tolerance in their native bacterial hosts," Thelen said. "This is another step toward engineering IIL tolerance into industrial strains."

Read the full release from LLNL

A robotic gripping arm that uses engineered bacteria to "taste" for a specific chemical has been developed by engineers at the University of California, Davis, and Carnegie Mellon University. The gripper is a proof-of-concept for biologically-based soft robotics.

"Our long-term vision is about building a synthetic microbiota for soft robots that can help with repair, energy generation or biosensing of the environment," said Cheemeng Tan, assistant professor of biomedical engineering at UC Davis. The work was published June 26 in the journal Science Robotics.

Soft robotics uses lightweight, flexible and soft materials to create machines that match the versatility of living things, and soft robot designs often draw inspiration form nature. Adding actual living cells to soft robots brings scientists another step closer to creating biological-mechanical hybrid machines.

"By combining our work in flexible electronics and robotic skin with synthetic biology, we are closer to future breakthroughs like soft biohybrid robots that can adapt their abilities to sense, feel and move in response to changes in their environmental conditions," said Carmel Majidi, a co-author and associate professor of mechanical engineering at CMU.

Biosensing with engineered bacteria

The new device uses a biosensing module based on E. coli bacteria engineered to respond to the chemical IPTG by producing a fluorescent protein. The bacterial cells reside in wells with a flexible, porous membrane that allows chemicals to enter but keeps the cells inside. This biosensing module is built into the surface of a flexible gripper on a robotic arm, so the gripper can "taste" the environment through its fingers.

When IPTG crosses the membrane into the chamber, the cells fluoresce and electronic circuits inside the module detect the light. The electrical signal travels to the gripper's control unit, which can decide whether to pick something up or release it.

As a test, the gripper was able to check a laboratory water bath for IPTG then decide whether or not to place an object in the bath.

So far, this biohybrid bot can only taste one thing and it's difficult to design systems that can detect changing concentrations, Tan said. Another challenge is to maintain a stable population of microbes in, or on, a robot -- comparable to the microbiome or ecosystem of bacteria and fungi that live in or on our own bodies and carry out many useful functions for us.

Biohybrid systems potentially offer more flexibility than conventional robotics, he said. Bacteria could be engineered for different functions on the robot: detecting chemicals, making polymers for repairs or generating energy, for example.

CORVALLIS, Ore. - Consumers are more willing to pay for wine that comes with an organic or organic grape label but providing information about certification standards and organic production practices reduces consumer willingness to pay for all wines, according to an Oregon State University-led study.

Further, the study found that additional information about conventional wine making practices restores consumer willingness to pay for wine labeled organic, but not for wines made with organic grapes, or conventional wines.

The study published today in the journal PLOS ONE.

The study provides insight on consumer perception of organic and organic grape labeling, and how labels that highlight the absence of ingredients are perceived by consumers who aren't familiar with standard production practices, said study lead author Nadia Streletskaya, an economist at Oregon State University who collaborated on the research with colleagues at Cornell University.

The difference between organic wine and wine made from organic grapes is the amount of sulfites added for preservation, and whether other ingredients used in production, such as egg whites or yeasts, are certified organic.

The results have implications for winemakers who are increasingly providing information to consumers about how wine is made, either on their websites or in their tasting rooms, said Streletskaya, an assistant professor in OSU's College of Agricultural Sciences.

"Not many wineries will take people through all of the steps of production, but there is a growing tendency to share more details on production, and that might be counterproductive," she said.

The researchers found that given no information about how wine is made, consumers would be willing to pay more for wine labeled as either organic or made with organic grapes compared to conventional wine. When consumers were given information about certification standards for labeling wine as organic or made with organic grapes, willingness to pay for all wines declined, but willingness to pay for organic wine, wine made with organic grapes, and conventional wine remained the same.

Consumers were less willing to pay for two out of three types of wine - conventional or made with organic grapes - when they were given additional information about conventional wine production practices that consumers might be less familiar with, such as the use of yeasts, the protein casein or egg whites, among others, in wine production, or genetically modified wine yeast.

Willingness to pay for organic wine, however, rebounded to original levels when information about conventional wine making practices was provided.

Information about wine production practices might "remove the cultural and mythical appeal of wine," Streletskaya said.

"Wine is a very peculiar product," she said. "A lot of people who consume wine don't really know much about wine. They think it grows in a bottle in a wine cellar. For example, once people find out something is added that doesn't make it spoil they aren't as excited. Another strong possibility for their less willingness to pay is that adding information might make it harder for people to choose a product because they have more information to work through."

In their study, the researchers conducted a series of auctions with three different groups of people, in which each person was given $35 to bid on a bottle of wine. In one case they weren't given any information about production practices. In the second, they were provided information about organic and organic grape labels.

In the third, they were given information about conventional winemaking practices in addition to the information about organic and organic grape certification standards provided in the second treatment.

"This is where we found a very strong impact," Streletskaya said. "Suddenly their willingness to pay for pure organic wine shoots up, compared to organic grape wine and conventional wine. But their absolute level of willingness to pay for organic wine is the same as when no production information is given."

Parkinson's disease can begin in the gut and spread to the brain via the vagus nerve, researchers report June 26th in the journal Neuron. This pathway was observed in a new mouse model, which recapitulates both motor and non-motor deficits as well as early-stage and late-stage features associated with Parkinson's disease.

"Since this model starts in the gut, one can use it [to] study the full spectrum and time course of the pathogenesis of Parkinson's disease," says co-senior study author Ted Dawson, professor of neurology at the Johns Hopkins University School of Medicine. "For instance, one could test preventive therapies at early pre-symptomatic stages of Parkinson's disease all the way to full-blown Parkinson's disease in one animal model."

Hallmarks of Parkinson's disease include the aggregation of misfolded forms of a neuronal protein called α-synuclein and the selective death of neurons that produce dopamine in a brain region called the substantia nigra pars compacta (SNc). The disorder causes motor symptoms such as tremors, rigidity, slowness of movement, and difficulties with balance, speech, and coordination. There is no cure, and currently available treatments do not slow or stop disease progression or adequately relieve the wide range of symptoms at more advanced stages.

Based on evidence in the post-mortem human brain, German neuroanatomist Heiko Braak and colleagues proposed in 2003 that α-synuclein pathology can spread from the gastrointestinal tract via the vagus nerve to the SNc, where it selectively kills dopamine-producing neurons. Accumulating evidence supports this gut-brain connection, but until now, animal models have not demonstrated the spread of pathologic α-synuclein from the gut via the vagus nerve to the SNc, as proposed by Braak.

In the new study, Dawson and co-senior study author Han Seok Ko of the Johns Hopkins University School of Medicine developed a mouse model that supports Braak's hypothesis. The authors injected mouse α-synuclein preformed fibrils into gastrointestinal muscles densely innervated by the vagus nerve. The key to success was optimizing the injection site as well as the amount and size of α-synuclein preformed fibrils injected. "When the initial experiments started to work, we were utterly amazed," Dawson says. "Now it is fairly routine for our research team."

One month after injection, the researchers observed that pathologic α-synuclein had spread to the dorsal motor nucleus of the vagus, located in the lowest part of the brainstem; this corresponds to Braak's stage 1. Within three months, pathologic α-synuclein had spread up the brainstem to the locus coeruleus and higher to the SNc, and even reached beyond the brainstem to the amygdala, hypothalamus, and prefrontal cortex, corresponding to later Braak stages. By seven months, pathologic α-synuclein had spread to additional brain regions, including the hippocampus, striatum, and olfactory bulb.

By this time, there was also significant loss of dopamine-producing neurons in the SNc and striatum. In addition to motor deficits, mice that received gastrointestinal injections of α-synuclein preformed fibrils developed signs of depression and anxiety, olfactory dysfunction, and cognitive deficits affecting spatial learning and memory, novel object recognition, fear memory, and working memory. The transmission of pathologic α-synuclein from the gut to the brain and the resulting neuronal death and symptoms did not occur in mice whose vagal nerve fibers were cut.

"There are at least three major implications of the study," Dawson explains. "One: it is likely to galvanize future studies exploring the gut-brain connection. Two: it will spur investigations focused on the factors, molecules, or infections that might start the misfolding and propagation of α-synuclein. And three: it suggests that treatments could be aimed at preventing the spread of pathologic α-synuclein from the gut to brain."

According to Dawson and Ko, the findings strongly support Braak's hypothesis, but it may be difficult to provide the same kind of evidence for the gut-brain connection in humans. However, studies in humans have shown that truncal vagotomy--a specific surgical procedure on the vagus nerve, typically used to treat ulcers--may reduce the risk of Parkinson's disease.

"Patients should not pursue vagotomies as a preventive therapy for Parkinson's disease," Dawson cautions. "But if one could find the major initiating factor in the gut, then one could target this in a future study and show that it prevents Parkinson's disease. Patients with pathologic α-synuclein in the gastrointestinal tract would be ideal candidates for future neuroprotective studies."

Moving forward, the researchers plan to assess whether the findings extend to non-human primates and to further investigate the mechanisms underlying the spread of pathologic α-synuclein from the gut to the brain and the resulting motor and non-motor symptoms. They will also look for potential gastrointestinal biomarkers associated with early pre-symptomatic stages of the disease and test potential therapeutic interventions that interfere with the spread of pathologic α-synuclein and mitigate the risk of developing Parkinson's disease.

Many psychiatric drugs act on the receptors or transporters of certain neurotransmitters in the brain. However, there is a great need for alternatives, and research is looking at other targets along the brain's metabolic pathways. Lack of glycine betaine contributes to brain pathology in schizophrenia, and new research from the RIKEN Center for Brain Science (CBS) shows that betaine supplementation can counteract psychiatric symptoms in mice.

Betaine comes from a normal diet but is also synthesized in the body where it contributes to metabolism in various ways, including as an anti-inflammatory agent. Levels of betaine (glycine betaine or trimethylglycine) in the blood plasma of patients with schizophrenia has previously been found to be low, which suggested it is a possible therapeutic target.

In the new study, mice missing the Chdh gene, which is involved in making betaine, showed depressive behaviors and greatly reduced betaine levels in both the brain and blood. Betaine levels in the brain recovered when the it was given to the mice as a supplement in drinking water, demonstrating that betaine can pass through the blood-brain barrier.

Psychedelic drugs like PCP and methamphetamine can also produce schizophrenia-like behaviors in both humans and mice. The researchers tested whether betaine supplementation could help alleviate symptoms induced by PCP and methamphetamine in mice. They found that betaine not only improved cognitive deficits and behavioral abnormalities, it also reversed oxidative stress at the molecular level. Oxidative stress is thought to be one mechanism through which these drugs cause psychiatric symptoms in humans.

Finally, investigation of postmortem human brain samples did indeed show reduced betaine levels in patients with schizophrenia, which was unrelated to the amount of antipsychotic drugs taken before death. They also found a subset of brains with "betaine-deficit oxidative stress", a pathology that occurred in cases with severe psychotic symptoms. The researchers were able to replicate this pathology in induced pluripotent stem cells that simulate the oxidative stress condition, and counteract it with the betaine treatment.

"We suggest that one of betaine's functions is to promote antioxidant activity in the metabolic cycles in which it participates," says senior author Takeo Yoshikawa of RIKEN CBS. "However, supplementation of betaine is not a silver bullet for schizophrenia or other psychiatric conditions." The researchers also identified a genetic variant that could predict betaine's treatment efficacy, a potential example of precision medicine in psychiatry. Betaine is already used as a drug for the autosomal recessive metabolic disorder homocystinuria, so it could be considered as therapy for psychiatric conditions with minimal concern for adverse effects.

Men who want to improve their libido or build body mass may want to think twice before using testosterone-boosting supplements - also known as "T boosters" - as research shows these alternatives to traditional testosterone replacement therapy may not have ingredients to support their claims, according to Mary K. Samplaski, MD, assistant professor of clinical urology at the Keck School of Medicine of USC.

"Many supplements on the market merely contain vitamins and minerals, but don't do anything to improve testosterone," says Samplaski. "Often, people can be vulnerable to the marketing component of these products, making it difficult to tease out what is myth and what is reality."

Testosterone is the primary male sex hormone and the reason why men produce sperm and have Adam's apples. It's also why men develop more "masculine" features like bulging muscles, a deep voice, broad shoulders and a hairy chest. After age 30, most men experience a gradual decline in testosterone, sometimes causing these features to diminish or new symptoms to occur, like erectile dysfunction. In an attempt to turn back the hands of time, some men will turn to T boosters.

Using a structured review approach, Samplaski and a team of researchers explored the active ingredients and advertised claims of 50 T boosting supplements. Their findings were published as an original article in The World Journal of Men's Health.

Researchers performed a Google search with the search term "Testosterone Booster," thus mimicking a typical internet research for someone looking to increase testosterone levels, and then selected the first 50 products that came up in their search. Then, the team reviewed published scientific literature on testosterone and the 109 components found in the supplements. Zinc, fenugreek extract and vitamin B6 were three of the most common components in the supplements.

The team also compared the content for each supplement with the Food and Drug Administration's (FDA) Recommended Daily Allowance (RDA) and the upper tolerable intake level (UL) as set by the Institute of Medicine of the National Academy of Science.

Of the 150 supplements, researchers came across 16 general claims to benefit patients, including claims to "boost T or free T", "build body lean mass or muscle mass", or "increase sex drive or libido."

While 90% of the T booster supplements claimed to boost testosterone, researchers found that less than 25% of the supplements had data to support their claims. Many also contained high doses of vitamins and minerals, occasionally more than the tolerable limit.

Unlike drugs, supplements are not intended to treat, diagnose, prevent, or cure diseases, according to the FDA. As such, Samplaski would like to see more regulation around testosterone-boosting supplements to protect consumers. She also would like to explore disseminating handouts to her patients with more accurate information in the hopes that it encourages patients to seek a medical professional for low testosterone issues.

While no one can escape the effects of aging, Samplaski says there is something men can do to address their concerns. "The safest and most effective way for men to boost low testosterone levels is to talk with a medical professional or a nutritionist."