Culture

Long ago, during the European Renaissance, Leonardo da Vinci wrote that we humans "know more about the movement of celestial bodies than about the soil underfoot." Five hundred years and innumerable technological and scientific advances later, his sentiment still holds true.

But that could soon change.

In a report published in Nature Communications a team of scientists from the Department of Energy's Lawrence Berkeley National Laboratory (Berkeley Lab) detailed the first-ever successful use of a technique called BONCAT to isolate active microbes present in a sample of soil - an achievement could enable a tidal wave of new research.

"Soils are probably the most diverse microbial communities on the planet," said Estelle Couradeau, first author of the study. "In every gram of soil, there are billions of cells from tens of thousands of species that, all together, perform important Earth nutrient cycles. They are the backbone of terrestrial ecosystems, and healthy soil microbiomes are key to sustainable agriculture. We now have the tools to see who these species are, but we don't yet know how they do what they do. This proof-of-concept study shows that BONCAT is an effective tool that we could use to link active microbes to environmental processes."

For the past two years, Couradeau, her co-authors, and many other researchers from around the U.S. have been collaborating in a Berkeley Lab-led scientific focus area called ENIGMA (for Ecosystems and Networks Integrated with Genes and Molecular Assemblies) in order to dig deeper into the inner-workings of soil microbiomes. ENIGMA's projects are a high priority for biologists and energy and Earth scientists not only because they help fill gaps in our knowledge of how the environment functions, but also because these fundamental insights could help applied scientists more effectively harness microbiomes to improve drought-resistance in crops, remove contaminants from the environment, and sustainably produce fuels and other bioproducts.

However, because most soil microbes won't grow in cultures in a laboratory, and because of their truly mind-boggling abundance in their natural habitats, investigating which microbial species do what is incredibly difficult. "There are many barriers to measuring microbial activities and interactions," said Trent Northen, lead author and director of biotechnology for ENIGMA. "For example, soil microbiomes that remove waste from underground water reservoirs are found hundreds of feet below the surface. And in some ecosystems, up to 95% of the microbes are inactive at any given time."

Because direct observation is off the table, microbiologists typically collect environmental samples and rely on indirect approaches such as DNA sequencing to characterize the communities. However, most of the commonly used techniques fail to differentiate active microbes from those that are dormant or from the plethora of free-floating bits of DNA found in soil and sediment.

BONCAT, short for Bioorthogonal Non-Canonical Amino Acid Tagging, was invented by Caltech geneticists in 2006 as a way to isolate newly made proteins in cells. In 2014, Rex Malmstrom, Danielle Goudeau, and others at the U.S. Department of Energy (DOE) Joint Genome Institute (JGI), an Office of Science user facility managed by Berkeley Lab, collaborated with Victoria Orphan's lab at Caltech to adapt BONCAT into a tool that could identify active, symbiotic clusters of dozens to hundreds of marine microbes within ocean sediment. After further refining their approach, called BONCAT Fluorescent Activated Cell Sorting (BONCAT+FACS), they were able to detect individual active microbes.

As the name suggests, BONCAT+FACS allows scientists to sort single-cell organisms based on the presence or absence of fluorescent tagging molecules, which bind to a modified version of the amino acid methionine. When fluid containing the modified methionine is introduced to a sample of microbes, only those that are creating new proteins - the hallmark of activity - will incorporate the modified methionine into cells.

In addition to being far more streamlined and reliable than previous methods of microbial identification, the entire process takes just a few hours - meaning it can tag active cells even if they are not replicating.

Given that some soil microbes are notoriously slow-growing, many scientists were immediately interested in applying BONCAT+FACS to terrestrial soils. After three months of experimentation and optimization, the team of ENIGMA and JGI researchers devised a protocol that works smoothly and, most importantly, gives very reproducible results.

"BONCAT+FACS is a powerful tool that provides a more refined method to determine which microbes are active in a community at any particular time," said Malmstrom, who is also an author of the current study. "It also opens the door for us to experiment, to assess which cells are active under condition A and which cells become active or inactive when switched to condition B."

Moving forward, BONCAT+FACS will be a capability available to researchers who wish to collaborate through the JGI's user programs. Northen and Malmstrom have already received several proposals from research groups eager to start working with the tool, including groups from Berkeley Lab who hope to use BONCAT to assess how environmental changes stimulate groups of microbes. "With BONCAT, we will be able to get immediate snapshots of how microbiomes react to both normal habitat fluctuations and extreme climate events - such as drought and flood - that are becoming more and more frequent," said Northen.

According to Couradeau, the team expects the approach will catalyze a variety of other important and intriguing lines of study, such as improving agricultural land practices, assessing antibiotic susceptibility in unculturable microbes, and investigating the completely unknown roles of Candidatus Dormibacteraeota - a phylum of soil bacteria, found across the world, that appear to remain dormant most of the time.

Reflecting on how he and his colleagues achieved a goal that many have been pursuing, Malmstrom cited the diversity of scientists within ENIGMA and JGI. "This a true example of team science, because no single person had or will ever have the expertise to do it all."

Vienna, 24 June 2019: Zillionaires like Amazon founder Jeff Bezos who see the 'colonisation' of space as an answer to the Earth's ever threatened resources will be reassured to learn that human sperm retains its complete viability within the different gravitational conditions found in outer space.

In a study reported today at the 35th Annual Meeting of ESHRE investigators said that the lack of difference in a range of sperm characteristics observed in frozen sperm samples exposed to microgravity and those maintained in ground conditions 'open the possibility of safely transporting male gametes to space and considering the possibility of creating a human sperm bank outside Earth'.

The results are presented here in Vienna by Dr Montserrat Boada from Dexeus Women's Health in Barcelona, whose group worked with microgravity engineers from the Polytechnic University of Barcelona. The Aeroclub Barcelona-Sabadell of Spain was responsible for the parabolic flights to create microgravity conditions.

As background to the study, Dr Boada explained that, while the effects of microgravity on the cardiovascular, musculo-skeletal and central nervous systems are well known and tested in space flight, relatively little is known about the effects of different gravitational environments on human sperm and eggs. 'Some studies suggest a significant decrease in the motility of human fresh sperm samples,' said Dr Boada, 'but nothing has been reported on the possible effects of gravitational differences on frozen human gametes, in which state they would be transported from Earth to space.'

The study was performed using a small aerobatic training aircraft (CAP10), which can provide short-duration hypogravity exposure. The plane executed a series of 20 parabolic manoeuvres, providing 8 seconds of microgravity for each parabola. Overall, ten sperm samples obtained from ten healthy donors were analysed after exposure to the different microgravities found in space and ground gravity.

The sperm analysis comprised a full range of measurements currently performed for fertility testing - concentration, motility, vitality, morphology and DNA fragmentation - and results found no difference whatsoever in any of the parameters between the microgravity space samples and the control group samples from Earth. Indeed, said Dr Boada, there was 100% concordance in DNA fragmentation rate and vitality, and 90% concordance in sperm concentration and motility. These minor differences, she added, 'were more probably related to heterogeneity of the sperm sample than to the effect of exposure to different gravity conditions'.

Dr Boada described this as a preliminary study and her group will now move on to validate the results and then to larger sperm samples, longer periods of microgravity and even fresh sperm. 'But we do need to know,' she added. 'If the number of space missions increases in the coming years, and are of longer duration, it is important to study the effects of long-term human exposure to space in order to face them. It's not unreasonable to start thinking about the possibility of reproduction beyond the Earth.'

Dr Boada noted that one reason for using frozen sperm in this study was the known effect of radiation on fresh sperm. 'Radiation impairs the quality and viability of human sperm,' she explained, 'and these effects are expected to be greater on fresh sperm than on frozen samples, which are cryopreserved in special cryostraws and transported in cryotanks. So our first step was to investigate gravity conditions and frozen sperm samples. Our best option will be to perform the experiment using real spaceflight, but access is very limited.'

San Francisco, CA - June 23, 2019 - New research has found that Cannnabidiol is active against Gram-positive bacteria, including those responsible for many serious infections (such as Staphyloccocus aureus and Streptococcus pneumoniae), with potency similar to that of established antibiotics such as vancomycin or daptomycin. The research is presented at ASM Microbe, the annual meeting of the American Society for Microbiology.

Cannabidiol, the main non-psychoactive chemical compound extracted from cannabis and hemp plants, has been approved by FDA for the treatment of a form of epilepsy, and is being investigated for a number of other medical conditions, including, anxiety, pain and inflammation. While there is limited data to suggest Cannabidiol can kill bacteria, the drug has not been thoroughly investigated for its potential as an antibiotic.

Work led by Dr Mark Blaskovich at The University of Queensland's Institute for Molecular Bioscience's Centre for Superbug Solutions, in collaboration with Botanix Pharmaceuticals Ltd, an early stage drug discovery company investigating topical uses of synthetic cannabidiol for a range of skin conditions, found that Cannabidiol was remarkably effective at killing a wide range of Gram-positive bacteria, including bacteria that have become resistant to other antibiotics, and did not lose effectiveness after extended treatment.

"Given cannabidiol's documented anti-inflammatory effects, existing safety data in humans, and potential for varied delivery routes, it is a promising new antibiotic worth further investigation," said Dr. Blaskovich. "The combination of inherent antimicrobial activity and potential to reduce damage caused by the inflammatory response to infections is particularly attractive."

Importantly, the drug retained its activity against bacteria that have become highly resistant to other common antibiotics. Under extended exposure conditions that lead to resistance against vancomycin or daptomycin, Cannabidiol did not lose effectiveness. Cannabidiol was also effective at disrupting biofilms, a physical form of bacteria growth that leads to difficult-to-treat infections.

The project was co-funded by Botanix and Innovation Connections, an Australian government grant scheme to commercialize new products, processes and services. The paper will be presented on Sunday June 23rd from 11am-1 pm at the annual conference of the American Society for Microbiology, ASM Microbe 2019, at the Moscone Convention Center in San Francisco.

San Francisco, CA - June 23, 2019 - Researchers have now shown that patients who are heavily colonized with Candida auris on their skin can shed the fungus and contaminate their surroundings. This finding provides an explanation for the extensive contamination that often occurs in healthcare facilities with C. auris outbreaks. These results can help inform infection control efforts. The research is presented at ASM Microbe, the annual meeting of the American Society for Microbiology.

C. auris is an emerging fungal pathogen that can cause large outbreaks in healthcare facilities. Understanding how C. auris spreads in healthcare facilities is essential for infection control. Because C. auris can be present on the skin without causing symptoms, it has been hypothesized that the spread of C. auris occurs as patients naturally shed their skin cells. This process could lead to substantial contamination of the surrounding environment and therefore increase chances of transmitting C. auris.

To test this hypothesis, the researchers developed methods to count C. auris in samples collected from patients' skin and their rooms. We found that patients can have very high concentrations of C. auris on their skin, and higher levels of C. auris on their skin were correlated with higher levels of C. auris on the patient's bed.

"This finding supported our hypothesis that patients are actively shedding C. auris cells into their environment," said Joe Sexton, ORISE post-doctoral fellow in the Mycotic Diseases Branch at the Centers for Disease Control and Prevention, who designed and led the study. The researchers were able to culture live C. auris from the beds of all patients who tested positive, and even beds that were previously, but no longer, occupied by patients with C. auris.

"These results should be considered in developing more effective strategies for infection control efforts during a C. auris outbreak," said Dr. Sexton.

Patient and environmental samples were processed in the Mycotic Diseases Branch laboratory in Atlanta by Joe Sexton, Meghan Bentz, and Rory Welsh and Anastasia Litvintseva, who served as a principal investigator (PI). These samples were collected by the City of Chicago's Public Health Department led by Massimo Pacilli.

Additional groups within CDC also supported this work including the Department of Scientific Resources and the Division of Healthcare Quality and Promotion, and the Oak Ridge Institute for Science and Education. This work will be presented at American Society of Microbiology (ASM) Microbe 2019 conference in San Francisco, California (June 20-24, 2019).

San Francisco, CA - June 23, 2019 - Researchers from the New York Institute of Technology (NYIT) have discovered bacteriophages, viruses that infect bacteria, living in their kitchen sponges. As the threat of antibiotic resistance increases, bacteriophages, or phages for short, may prove useful in fighting bacteria that cannot be killed by antibiotics alone. The research is presented at ASM Microbe, the annual meeting of the American Society for Microbiology.

A kitchen sponge is exposed to all kinds of different microbes, which form a vast microbiome of bacteria. Phages are the most abundant biological particles on the planet and are typically found wherever bacteria reside. With this understanding, kitchen sponges seemed a likely place to find them.

Students in a research class isolated bacteria from their own used kitchen sponges and then used the bacteria as bait to find phages that could attack it. Two students successfully discovered phages that infect bacteria living in their kitchen sponges. "Our study illustrates the value in searching any microbial environment that could harbor potentially useful phages," said Brianna Weiss, a Life Sciences student at New York Institute of Technology.

The researchers decided to "swap" these two phages and see if they could cross-infect the other person's isolated bacteria. Consequently, the phages did kill the other's bacteria. "This led us to wonder if the bacteria strains were coincidentally the same, even though they came from two different sponges," said Weiss.

The researchers compared the DNA of both isolated strains of bacteria and discovered that they were both members of the Enterobacteriaceae family. These bacteria belong to a rod-shaped group of microbes commonly found in feces, where some cause infections in hospital settings. Although the strains are closely related, when performing biochemical testing they found chemical variations between them.

"These differences are important in understanding the range of bacteria that a phage can infect, which is also key to determining its ability to treat specific antibiotic-resistant infections," said Weiss. "Continuing our work, we hope to isolate and characterize more phages that can infect bacteria from a variety of microbial ecosystems, where some of these phages might be used to treat antibiotic-resistant bacterial infections."

This project began as part of an undergraduate research class with seven students at the New York Institute of Technology (NYIT) in Old Westbury, New York. The course was funded through internal grants provided by (NYIT), which also supported our later work to further characterize the isolated bacteria and bacteriophages. This second phase of our work will be presented on a poster at ASM Microbe on Sunday, June 23rd.

San Francisco, CA - June 22, 2019 - Antibiotic-resistant infections are a threat to global public health, food safety and an economic burden. To prevent these infections, it is critical to understand how antibiotic-resistant bacteria and their genes are transmitted from both meat and plant-foods. Researchers have now shown how plant-foods serve as vehicles for transmitting antibiotic resistance to the gut microbiome. The research is presented at ASM Microbe, the annual meeting of the American Society for Microbiology.

The U.S. Centers for Disease Control and Prevention estimated that of the 2 million antibiotic-resistant infections per year in the U.S., 20 percent are linked to agriculture. This estimate is based on patients who directly acquire antibiotic-resistant superbugs from eating meat. Little has been done to determine how eating plants contributes to the spread of antibiotic-resistant "superbugs."

"Our findings highlight the importance of tackling foodborne antibiotic-resistance from a complete food chain perspective that includes plant-foods in addition to meat," said Marlène Maeusli, PhD candidate at Keck School of Medicine at the University of Southern California, who is the lead author on the study.

Spread of antibiotic-resistant superbugs from plants to humans is different from outbreaks of diarrheal illnesses caused immediately after eating contaminated vegetables. Superbugs can asymptomatically hide in (or "colonize") the intestines for months or even years, when they then escape the intestine and cause an infection, such as a urinary infection.

The researchers developed a novel, lettuce-mouse model system that does not cause immediate illness to mimic consumption of superbugs with plant-foods. They grew lettuce, exposed the lettuce to antibiotic-resistant E. coli, fed it to the mice and analyzed their fecal samples over time.

"We found differences in the ability of bacteria to silently colonize the gut after ingestion, depending on a variety of host and bacterial factors," said Maeusli. "We mimicked antibiotic and antacid treatments, as both could affect the ability of superbugs to survive passage from the stomach to the intestines."

Exposure to one type of antibiotic did not increase the ability of superbugs to hide in the mouse intestines, whereas a second antibiotic resulted in stable gut colonization after ingestion. Ingestion of bacteria with food also changed colonization, as did administering an antacid before ingesting the bacteria.

"We continue to seek the plant characteristics and host factors that result in key microbial community shifts in the gut that put us at risk for colonization and those that prevent it," said Maeusli. "The environment and human health - in this context via agriculture and microbiomes - are inextricably linked."

San Francisco, CA - June 22, 2019 - Swimming in the ocean alters the skin microbiome and may increase the likelihood of infection, according to research presented at ASM Microbe 2019, the annual meeting of the American Society for Microbiology.

"Our data demonstrate for the first time that ocean water exposure can alter the diversity and composition of the human skin microbiome," said Marisa Chattman Nielsen, MS, a PhD student at the University of California, Irvine, the lead author on the study. While swimming normal resident bacteria were washed off while ocean bacteria were deposited onto the skin."

The researchers detected ocean bacteria on all participants after air drying and at six and 24 hours post-swim, but some participants had acquired more ocean bacteria and/or had them persist for longer.

The research was motivated by previous studies which have shown associations between ocean swimming and infections, and by the high prevalence of poor water quality at many beaches, due to wastewater and storm water runoff. Recent research has demonstrated that changes in the microbiome can leave the host susceptible to infection, and influence disease states. Exposure to these waters can cause gastrointestinal and respiratory illness, ear infections, and skin infections.

The investigators sought 9 volunteers at a beach who met criteria of no sunscreen use, infrequent exposure to the ocean, no bathing within the last 12 hours, and no antibiotics during the previous six months. The researchers swabbed the participants on the back of the calf before they entered the water, and again after subjects had air dried completely following a ten-minute swim and at six and 24 hours post swim.

Before swimming, all individuals had different communities from one-another, but after swimming, they all had similar communities on their skin, which were completely different from the "before swim" communities. At six hours post swim, the microbiomes had begun to revert to their pre-swim composition, and at 24 hours, they were far along in that process.

"One very interesting finding was that Vibrio species--only identified to the genus level--were detected on every participant after swimming in the ocean, and air drying," said. Nielsen. (The Vibrio genus includes the bacterium that causes cholera.) At six hours post swim, they were still present on most of the volunteers, but by 24 hours, they were present only on one individual.

"While many Vibrio are not pathogenic, the fact that we recovered them on the skin after swimming demonstrates that pathogenic Vibrio species could potentially persist on the skin after swimming," said Nielsen. The fraction of Vibrio species detected on human skin was more than 10 times greater than the fraction in the ocean water sample, suggesting a specific affinity for attachment to human skin.

Skin is the body's first line of defense, both physically and immunologically, during exposure to contaminated water. "Recent studies have shown that human skin microbiome plays an important role in immune system function, localized and systemic diseases, and infection," said Nielsen. "A healthy microbiome protects the host from colonization and infection by opportunistic and pathogenic microbes."

Alexandria, Va., USA - At the 97th General Session & Exhibition of the International Association for Dental Research (IADR), held in conjunction with the 48th Annual Meeting of the American Association for Dental Research (AADR) and the 43rd Annual Meeting of the Canadian Association for Dental Research (CADR), Dandara Haag, University of Adelaide, Australia, gave an oral presentation on "Indigenous Oral Health Inequalities Begin in Childhood: A Multi-country Study." The IADR/AADR/CADR General Session & Exhibition is held at the Vancouver Convention Centre West Building in Vancouver, BC, Canada from June 19-22, 2019.

There is limited documentation on the magnitude of oral health inequalities between Indigenous and non-Indigenous people across a range of countries and comparable oral health indicators that focus specifically on children. This study compared relative oral health inequalities between Indigenous and non-Indigenous children and adolescents ages five to 15 years-old from Brazil, New Zealand and Australia.

Data were collected from the most recent nationally representative oral health surveys in each country and gingival inflammation, dental caries experience, untreated decayed teeth and missing and filled teeth were assessed in the primary and permanent dentitions. Parent-reported child oral health was also evaluated.

The authors found that irrespective of country, Indigenous children had worse oral health than their non-Indigenous counterparts in all indicators. The magnitude of these differences was greatest in Australia for the proportion with dental caries experience, untreated decay or gingival inflammation. For missing teeth, filled teeth and poor parent-reported child oral health, the magnitude of inequality was greatest among Brazilian children. These findings suggest that Indigenous and non-Indigenous oral health inequalities begin in childhood. This reinforces the need for equity in social and economic policies, along with culturally appropriate and early oral health interventions.

This oral presentation, #3470, was held on Saturday, June 22, 2019 at 2:45 p.m. in Room 303 of the Vancouver Convention Centre West Building, Vancouver, BC, Canada.

CHAPEL HILL, North Carolina -- Efforts to control health care costs in the United States often focus on the listed prescription drug prices, but a perspective published by the Journal of the American Medical Association suggests that unregulated pharmacy benefit manager practices also may contribute to escalating expenses.

Researchers from the University of North Carolina Lineberger Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine and Boston University Questrom School of Business examined the impact of Ohio Medicaid's switch in 2011 from a fee-for-service model to a managed care model to administer its outpatient prescription drug benefits.

They report that an independent audit in 2018 found the change to a managed care program, which uses pharmacy benefit managers, saved the Ohio Medicaid $145 million annually. Pharmacy benefit managers are intermediaries in the drug supply chain that function as third-party administrators of pharmacy benefits. The savings were largely derived by the lower prescription claims prices the pharmacy benefit managers billed.

These savings, however, came at a cost, said Trevor Royce, MD, MS, MPH, the paper's corresponding author and an assistant professor of Radiation Oncology at UNC School of Medicine and UNC Lineberger. His coauthors were Sheetal Kircher, MD, MS, of Northwestern and Rena M. Conti, PhD, of Boston University.

"Ohio policymakers should be applauded for their empirical approach in tackling the cost of prescription drugs," said Royce. "The Ohio audit found pharmacy benefit managers engage in opaque pricing practices that likely contribute to the rising costs of care and prescription drugs."

The authors identified several issues of concern. Ohio pharmacists believed pharmacy benefit managers used anti-competitive practices and manipulated drug pricing. This included offering different drug pricing to affiliated pharmacies than independent pharmacies. Some pharmacy benefit managers implemented "gag clauses" that prevented pharmacies from counseling patients on the most cost-effective medication options. A more controversial practice, said Royce, was the use of "spread pricing," in which pharmacy benefit managers charged Ohio Medicaid a high price for a drug but paid pharmacies a lower price.

The pricing difference could produce significant revenue for the pharmacy benefit managers. An analysis in 2017 found that a 30-day supply of the generic form of imatinib mesylate, a drug to treat leukemia, cost $3,859, but Ohio Medicaid was charged $7,201.

The independent review of pharmacy benefit manager practices commissioned by Ohio found an 8.8 percent difference between what the pharmacy benefit managers billed to Ohio Medicaid managed care plans and what it paid to the pharmacies between March 2017-2018. The more than 39 million prescription transactions produced a spread pricing difference of $223.7 million.

Ohio officials have implemented several policy changes following the audit. The state's managed care plans ended its contracts with pharmacy benefit managers. They also implemented a "pass through" pricing model in which the managed care plan pays the pharmacy benefit managers the exact amount paid to the pharmacy for a prescription drug plus a dispensing fee and an administrative fee.

They also tried to ban the gag clauses used by pharmacy benefit managers, but the Ohio Senate didn't vote on the bill before the legislative session ended in 2018. This was remedied on the federal level in October 2018, when the Patient Right to Know Drug Prices Act and Know the Lowest Prices Act, which banned gag clauses, were signed into law.

Royce said other states wanting to reduce health care costs can learn from what took place in Ohio.

"The Ohio Medicaid experience provides an important window into pharmacy benefit manager practices," said Royce. "Efforts to address drug pricing tend to focus on the pharmaceutical company or the drug manufacturer, while traditionally the pharmacy benefit managers may be overlooked. This is likely changing as a growing number of states have introduce bills pertaining to pharmacy benefit manager practices, and more are surely to come."

More than three decades ago, scientists discovered that a chemical found in a synthetic opioid, MPTP, induced the onset of a form of Parkinson's disease. In a new study led by scientists from the School of Veterinary Medicine, researchers found that an enzyme in the body can metabolize compounds formed in the brain from alkaloids present in certain foods and tobacco into MPTP-like chemicals, triggering a neurodegenerative condition in mice.

The researchers, led by Narayan Avadhani and Mrittika Chattopadhyay, suggest that the enzyme, mitochondrial CYP2D6, presents a potentially powerful new target for Parkinson's treatment.

"Over the past two or three decades, researchers have tried inhibiting the process by which they believed MPTP was metabolized, with mixed success," says Avadhani. "We believe that mitochondrial CYP2D6 is the more direct drug target, which might prove better in treating idiopathic Parkinson's disease."

The study, which appears in the Journal of Biological Chemistry, investigates the mechanism of Parkinson's disease when a specific cause cannot be pinpointed, which is a majority of examples of the chemically induced disease.

Previous studies have shown that MPTP and similar toxic compounds induce Parkinson's disease in rodents and primates. The mechanism of action, as scientists understood it, involved the compounds being oxidized to form MPP+, a toxic metabolite. The enzyme that was believed to be responsible is called monoamine oxidase B (MAO-B), present in the nervous system's glial cells. In that conception of the mechanism, MPP+ was thought to then be transferred to dopamine neurons by dopamine transporter proteins, and, indeed, Parkinson's is characterized by unusually low dopamine levels in the brain.

Researchers have tried to stem the effects of Parkinson's by targeting two players in this presumed pathway, both MAO-B and the dopamine transporter protein, with only mixed success.

Yet the Penn-led study implicates an entirely separate mechanism. In earlier work, Avadhani and colleagues had shown that the enzyme CYP2D6, localized to the body's energy factories, the mitochondria, could play a role in metabolizing MPTP to MPP+. In the new investigation, they took a closer look at beta-carbolines and isoquinolines, toxins that resemble MPTP which the body produces from substances found in tobacco smoke, alcohol, and some foods.

They found that, instead of MAO-B, it was mitochondrial CYP2D6 that activate the beta-carbolines and isoquinolines inside the dopamine-producing neurons, rather than the glial cells. This route of activation, in a mouse model, results in neuronal damage and oxidative stress, symptoms akin to Parkinson's.

"CYP2D6 is known to play a role in influencing the activity of a number of drugs," says Avadhani.

In an attempt to target this pathway, the researchers showed that mice lacking CYP2D6 did not exhibit the severe symptoms that mice with the protein did. In addition, an inhibitor of CYP2D6 prevented neuronal damage in the nice.

"The CYP2D6 inhibitor ajmalicine is a member of the reserpine family of alkaloids, found in the plant Rauwolfia serpentine and was long used in India for treating mental illness, such as paranoia and schizophrenia," Avadhani says. "Mitochondrial targeting of such compounds is likely to be effective in treating Parkinson's patients, and pursuing that is our future strategy."

As students learn a new concept, measuring how well they grasp it has often depended on traditional paper and pencil tests. Dartmouth researchers have developed a machine learning algorithm, which can be used to measure how well a student understands a concept based the student’s brain activity patterns. The findings are published in Nature Communications.

The study is one of the first to look at how knowledge learned in school is represented in the brain. To test knowledge of concepts in STEM, Dartmouth researchers examined how novices and intermediate learners' knowledge and brain activity compared when testing mechanical engineering and physics concepts, and then developed a new method to assess their conceptual understanding.

"Learning about STEM topics is exciting but it can also be quite challenging. Yet, through the course of learning, students develop a rich understanding of many complex concepts. Presumably, this acquired knowledge must be reflected in new patterns of brain activity. However, we currently don't have a detailed understanding of how the brain supports this kind of complex and abstract knowledge, so that's what we set out to study," said senior author David Kraemer, an assistant professor of education at Dartmouth College.

Twenty-eight Dartmouth students participated in the study, broken into two equal groups: engineering students and novices. Engineering students had taken at least one mechanical engineering course and an advanced physics course, whereas novices had not taken any college-level engineering or physics classes. The study was comprised of three tests, which focused on how structures are built and assessed participants' understanding of Newton's third law--for every action there is an equal and opposite reaction. Newton's third law is often used to describe the interactions of objects in motion, but it also applies to objects that are static, or nonmoving: all of the forces in a static structure need to be in equilibrium, a principle fundamental to understanding whether a structure will collapse under its own weight or whether it can support more weight.

At the start of the study, participants were provided with a brief overview of the different types of forces in mechanical engineering. In an fMRI scanner, they were presented with images of real-world structures (bridges, lampposts, buildings, and more) and were asked to think about how the forces in a given structure balanced out to keep the structure in equilibrium. Then, participants were prompted with a subsequent image of the same structure, where arrows representing forces were overlaid onto the structure. Participants were asked to identify if the Newtonian forces had been labeled correctly in this diagram. Engineering students (intermediate learners) answered 75 percent of the diagrams correctly and outperformed the novices, who answered 53.6 percent correctly.

Before the fMRI session, participants were also asked to complete two standardized, multiple-choice tests that measured other mechanical engineering and physics knowledge. For both tests, the engineering students had significantly higher scores than the novices with 50.2 percent versus 16.9 percent, and 79.3 percent versus 35.9 percent.

In cognitive neuroscience, studies on how information is stored in the brain often rely on averaging data across participants within a group, and then comparing their results to those from another group (such as experts versus novices). For this study, the Dartmouth researchers wanted to devise a data-driven method, which could generate an individual "neural score" based on the brain activity alone, without having to specify which group the participant was a part of. The team created a new method called an informational network analysis, a machine learning algorithm which "produced neural scores that significantly predicted individual differences in performance" testing knowledge of specific STEM concepts. To validate the neural score method, the researchers compared each student's neural score with his/her performance on the three tests. The results demonstrated that the higher the neural score, the higher the student scored on the concept knowledge tests.

"In the study, we found that when engineering students looked at images of real-world structures, the students would automatically apply their engineering knowledge, and would see the differences between structures such as whether it was a cantilever, truss or vertical load," explained Kraemer. "Based on the similarities in brain activity patterns, our machine learning algorithm method was able to distinguish the differences between these mechanical categories and generate a neural score that reflected this underlying knowledge. The idea here is that an engineer and novice will see something different when they look at a photograph of a structure, and we're picking up on that difference," he added.

The study found that while both engineering students and novices use the visual cortex similarly when applying concept knowledge about engineering, they use the rest of the brain very differently to process the same visual image. Consistent with prior research, the results demonstrated that the engineering students' conceptual knowledge was associated with patterns of activity in several brain regions, including the dorsal frontoparietal network that helps enable spatial cognition, and regions of ventral occipitotemporal cortex that are implicated in visual object recognition and category identification.

The informational network analysis could also have broader applications, as it could be used to evaluate the effectiveness of different teaching approaches. The research team is currently testing the comparison between hands-on labs versus virtual labs to determine if either approach leads to better learning and retention of knowledge over time.

San Antonio, Texas (June 19, 2019) - The global obesity epidemic is so far-reaching it now has an overarching name: globesity. Texas Biomed Staff Scientist Raul Bastarrachea, M.D., is part of a team that discovered a new mutation in the gene that regulates the key hormone suppressing hunger called leptin. This new mutation could help researchers understand why people develop excess of body fat. Dr. Bastarrachea's research is aimed at helping tackle metabolic disorders like cardiovascular disease and diabetes which are fueled by obesity and impact millions of people around the world.

"We keep learning more and more about the role of fat in normal-weight people," Bastarrachea said. "By researching what goes wrong when genes don't code correctly for the production of leptin, we are coming closer to answers that could help millions of people with metabolic disorders."

In the field of metabolic diseases, the pinpointing of the protein Leptin in the year 2000 was a huge breakthrough. Researchers at Rockefeller University found this hormone was missing in rats that randomly became extremely fat in a laboratory setting. Humans also need adequate leptin circulating levels to inform the brain that their body fat content is enough and they do not need to keep eating more food. In other words, leptin signals mammals to stop eating.

Leptin is a protein produced by fat cells (also known as adipose tissue). It travels through the circulation to the brain where the hormone hooks up to a leptin receptor in the hypothalamus to signal to the body that there is enough fat and no more food is needed. In other words, it is a hunger-suppressing hormone. The name leptin is derived from the Greek work "leptos" meaning thin. It is sometimes referred to as the "Fat Controller."

A congenital leptin deficiency is a recessive genetic disorder associated with severe early-onset obesity. In an article in the journal Genes, Dr. Bastarrachea and his co-investigators examined the case of two sisters in Colombia who started off their lives as normal weight babies but who quickly suffered from childhood-onset severe obesity. Prior cases have studied people whose genetics can be traced to Pakistan, Turkey, Egypt, India and China. This is the first case studied in the Americas.

What scientists found is that these two women - now in their 20s - have a mutation in the leptin gene on chromosome 7. The sisters' leptin levels were so low they were below the detection limit of the manufactured test kit.

The gene mutation caused the Leptin proteins to be "misfolded," rendering them ineffective and destroying their function.

When researching the genetics of the family, scientist noted these women were children of lineal consanguinity which means several generations before them married blood relatives. This is a common practice in about a fifth of the world population, mostly in the Middle East, West Asia and North Africa. However, health risks for children of these unions include rare diseases caused by recessive genes.

While more work is needed to figure out how to combat leptin deficiencies on a large scale, the two Colombian women are in the queue to take Metreleptin - a synthetic analog of leptin - a very expensive injected drug. Its effects, however, can be quite dramatic and life changing.

With obesity now a global problem, scientists around the world are searching for ways to keep the issue from becoming a healthcare burden for years to come. Texas Biomed is playing an important role.

Harmful algal blooms can cause big problems in coastal areas and lakes across the United States. When toxin-containing aquatic organisms multiply and form a bloom, it can sicken people and pets, contaminate drinking water, and force closures at boating and swimming sites.

With limited resources to monitor these often-unpredictable blooms, water managers are turning to new technologies from NASA and its partners to detect and keep track of potential hazards. This is particularly critical in lakes and reservoirs that people use for both recreation and water supply.

A new app for Android mobile devices, from the U.S. Environmental Protection Agency (EPA) and now available on Google play, will alert officials and members of the public when a harmful algal bloom could be forming, depending on specific changes in the color of the water observed by satellites. The app is a product of the multi-agency Cyanobacteria Assessment Network, or CyAN.

"The interest is to use remote sensing as an eye-in-the-sky, early warning system to get a picture of harmful cyanobacteria in U.S. inland lakes," said Jeremy Werdell, the NASA Goddard Space Flight Center lead for CyAN, which also includes the EPA, the U.S. Geological Survey (USGS) and the National Oceanic and Atmospheric Administration (NOAA).

"Resources are limited, and it's not possible for everyone on the ground to be monitoring all inland water bodies all of the time," he said. "Satellites are providing a tool to help inform how and when to expend resources to go and collect water samples."

NASA has been studying water quality from space for decades, beginning in 1978 with the Coastal Zone Color Scanner instrument that used the color of the ocean to study phytoplankton populations. With later instruments, like the Moderate Resolution Imaging Spectroradiometer on NASA's Terra and Aqua satellites, the resolution was fine enough to distinguish larger inland lakes and reservoirs, and scientists began to use the data to detect the signatures of cyanobacteria in fresh water.

Cyanobacteria occur naturally in many bodies of water, from the Great Lakes to small neighborhood ponds. In small numbers, these algae are not a problem. But under the right conditions - warm water, sunlight, plus nutrients that often wash off agricultural fields - cyanobacteria can multiply and form potentially toxic blooms.

Even though the individual algae are microscopic, blooms can be seen from space. In massive numbers, cyanobacteria blooms can appear as large green swaths and patches due to their main photosynthetic pigment. Their presence can also be detected using fluorescence, which algal blooms emit in response to exposure to sunlight. Using the bloom's unique characteristics, instruments on the NASA/USGS Landsat satellites, the European Space Agency's Copernicus Senteinel-2 and Copernicus Sentinel-3 satellites, as well as several others, are able to pinpoint the presence of algae.

With computer programs developed to crunch those satellite observations from Sentinel-3, NASA supercomputers produce weekly reports on the color - and other water quality information -- of more than 2,000 lakes across the United States as part of the CyAN project, said Bridget Seegers, a research scientist at Goddard in Greenbelt, Maryland.

Users of the new CyAN app will be able to mark a particular lake with a pin - which will appear as green if the lake appears bloom free, yellow if algae are present but below a certain threshold of concern, or red, indicating that a bloom is likely present. It's designed not only for water quality managers, Seegers said, but for people putting a canoe on their car and debating where to go, or an outfitter directing people to the best lake for kayaking.

CyAN started in 2015, and has worked with state and local agencies to identify potentially harmful blooms, said Blake Schaeffer, a research ecologist with the EPA and that agency's lead for the program.

Water quality managers with EPA Regions and Office of Water teamed up with CyAN to test and evaluate the app and satellite data, he said, furthermore, citizen scientist groups, tribal groups and the public have shown interest in the data as well.

"We're putting the power of the satellite information directly into the hands of the people," Schaeffer said. "They don't have to mine for data; they can opt to have the data pushed to them."

The program does have limitations, however. The satellites can't see through clouds, and because of the resolution of Sentinel-3A, lakes would need to be a bit more than half a mile (900 meters) wide to track with the highest-quality data.

To peer at even smaller lakes and reservoirs, Schaeffer and others are turning to Landsat. Because of issues with clouds (and a less frequent revisit), Landsat satellites, scientists get about one clear measurement of a given site every month. But with Landsat's higher spatial resolution, they can track water quality information from more than 60% of the U.S. lakes and reservoirs, or more than 170,000 waterbodies.

Landsat and Sentinel-3 are complementary; Landsat has greater spatial resolution whereas Sentinel-3 gathers data over individual sites more frequently and detects wavelengths more appropriate for cyanobacteria. In addition, Landsat satellites have thermal sensors that can be used to monitor surface temperature of lakes, which is useful, since warmer temperatures promote bloom growth. Schaeffer is investigating how to add that additional factor into the monitoring program.

Ultimately, the goal is to create a water quality monitoring system that leverages data from many sources - Sentinel-2, Landsat, and other satellites, as well as information gathered on the water, said Nima Pahlevan, a researcher at Goddard and member of the Landsat science team.

He and his team are working on how to best use Landsat and Sentinel data to identify lakes, rivers, reservoirs and other water bodies with excessive algae present. The Landsat mission has been operating since the late 1970s, so researchers and water managers can track the history of a given lake to determine if each lake - or potentially even an individual pixel within an image of a lake - has changed, and if it indicates a bloom.

"We're hoping that with these images, produced in near-real time - within as little as 3 to 4 hours - we can build a system to issue warnings that are specific to each lake or reservoir," Pahlevan said.

One challenge the group is facing is that there aren't many water measurements being taken across the different lakes to compare with, and verify, what the satellite is reporting. With support from the Landsat Project Science Office, Pahlevan and collaborators have placed three instruments in Green Bay, Wisconsin, Lake Okeechobee, Florida, and Grizzly Bay, California, to take measurements of the water for comparison with Landsat and other satellite measurements.

With those data from the field, and work this summer which includes tracking a handful of lakes using Landsat and Sentinel-2, Pahlevan hopes to build up the program and expand it to an operational system with more locations by summer 2020.

For people like Donalea Dinsmore, who works for the Wisconsin Department of Natural Resources (DNR), more satellite monitoring tools would be a welcome addition to the suite of methods the state uses to keep a handle on where harmful algal blooms occur. Each summer, the department receives questions about whether the green muck floating on lakes is harmful, or reports of dogs sickened after swimming in or drinking from a lake, she said. Wisconsin's DNR has staff who monitor many of the thousands of lakes in the state, but they can't reach everywhere.

"With 15,000 lakes, can you visit them all? And depending on when you visit, you might just miss a bloom," Dinsmore said. "It can be a really complicated and expensive monitoring program if you go in blind."

This image shows an irregular galaxy named IC 10, a member of the Local Group -- a collection of over 50 galaxies in our cosmic neighborhood that includes the Milky Way.

IC 10 is a remarkable object. It is the closest-known starburst galaxy, meaning that it is undergoing a furious bout of star formation fueled by ample supplies of cool hydrogen gas. This gas condenses into vast molecular clouds, which then form into dense knots where pressures and temperatures reach a point sufficient to ignite nuclear fusion, thus giving rise to new generations of stars.

As an irregular galaxy, IC 10 lacks the majestic shape of spiral galaxies such as the Milky Way, or the rounded, ethereal appearance of elliptical galaxies. It is a faint object, despite its relative proximity to us of 2.2 million light-years. In fact, IC 10 only became known to humankind in 1887, when American astronomer Lewis Swift spotted it during an observing campaign. The small galaxy remains difficult to study even today, because it is located along a line-of-sight which is chock-full of cosmic dust and stars.

A version of this image was entered into the Hubble's Hidden Treasures image processing competition by contestant Nikolaus Sulzenauer, and went on to win 10th prize.

Non-classical monocytes were long thought to play a purely surveillance role in the immune system. With the aid of a novel marker (PD-L1), Ludwig-Maximilians-Universitaet (LMU) in Munich researchers have now shown that they are directly involved in the regulation of immune response.

Monocytes comprise a functionally specific group of white blood cells and are known to play a role in the immune system. Based on the sets of proteins found on their surfaces, they can be divided into two major subtypes, known respectively as classical and non-classical monocytes, which serve different functions in the immune system. Up to now, non-classical monocytes have been viewed solely as surveillance cells that circulate in the bloodstream and serve to recruit other immune cells to sites of damage in the walls of blood vessels. However, an international team led by Dr. Johan Duchêne, Mariaelvy Bianchini, Dr. Remco Megens and Professor Christian Weber of the Institute for Cardiovascular Prevention (IPEK) at the LMU Medical Center has now identified a specific marker for these cells. Using this tool, they then went on to show, in a mouse experimental model, that non-classical monocytes also play a direct regulatory role in the adaptive immune response in certain tissues. The new study appears in the journal Science Immunology.

Classical monocytes migrate to sites of inflammation in the body, where they differentiate further to produce a range of specialized immune cells that activate other components of the immune response. "We were interested in whether or not non-classical monocytes might also be able to regulate other types of immune cells in addition to acting as lookouts," says Duchêne. The problem was that no specific marker, with which they could be reliably identified, had been found for them. But this obstacle has now been overcome. In the course of their studies on mice, Duchêne and his colleagues characterized a specific surface protein as a suitable marker with which to track non-classical monocytes. "The protein concerned (PD-L1) is a known and well-studied molecule that is found on the surface of cancer cells and serves to inactivate the immune response to malignant tumor cells. "It was a great surprise for us to discover that this protein is also strongly expressed on the surface of non-classical monocytes," says Bianchini, who is first joint author on the study.

The new marker made it possible for the authors of the new study to show that classical monocytes, which develop in the bone marrow, are converted into non-classical monocytes when they first come into contact with specialized blood vessels in the vicinity of the cortical bone. "This is the first experimental proof that both types of monocytes originate in the bone marrow. Altered conditions in this microenvironment, caused by inflammation reactions, for instance can have a negative effect on the conversion process," explains Megens. "We have shown that this is in fact the case in the bone marrow of aging mice."

In addition, the team demonstrated that non-classical monocytes are not bit players in the adaptive immune system. They can do more than acting as sentinels that raise the alarm. They are able to infiltrate a specific type of inflamed tissue - known as tertiary lymphatic organs - for instance in the context of myocardial infarction, where they function as direct regulators of the adaptive immune response by modulating the activities of specific subsets of other immune cells. "Our new marker has shown itself to be a very valuable tool, and it will help to further elucidate the biological roles of non-classical monocytes," says Weber. "It might even allow us to discover new molecular mechanisms that contribute to the development of inflammatory disorders such as cardiovascular disease and cancer."