Culture

A new protein involved in Alzheimer's disease (AD) has been identified by researchers at the RIKEN Center for Brain Science (CBS). CAPON may facilitate the connection between the two most well-known AD culprits, amyloid plaques and tau pathology, whose interactions cause brain cell death and symptoms of dementia. This latest finding from the Takaomi Saido group at RIKEN CBS uses a novel mouse model of AD. The study was published in Nature Communications on June 3.

Alzheimer's disease is a complex and devastating condition characterized by plaques of amyloid-β and neurofibrillary tangles, also known as tau pathology, in the brain. Investigating the connection between these features, the research team identified CAPON, a protein that binds to tau. The CAPON gene is a known risk for other psychiatric disorders, and because AD can be accompanied by psychiatric symptoms, the team guessed that CAPON could form a link between these conditions. Indeed, when they examined one type of AD mouse, they found accumulation of CAPON in the hippocampus, an important memory center in the brain. Furthermore, CAPON accumulation was even greater in the presence of amyloid-β pathology.

After creating another type of AD mouse model using a novel App/MAPT double knock-in process, the team inserted CAPON DNA into the brain, which resulted in CAPON overexpression. These mice exhibited significant neurodegeneration, elevated tau, and hippocampal shrinkage. "The implication is that accumulating CAPON increases AD-related pathology," says lead author Shoko Hashimoto of RIKEN CBS. "Although cell death resulting from CAPON can occur through many different pathways, we definitely think this protein is a facilitator between neuroinflammation and tau pathology." This is the first study to use App/MAPT double knock-in mice, which are engineered to have human-like MAPT and App genes containing pathogenic mutations.

If CAPON accumulation exacerbates AD pathology, the team reasoned that CAPON deficiency could have the opposite effect. For this test, the team knocked out CAPON in another type of AD model mouse that typically has increased tau pathology. They found that CAPON deficiency led to less tau, less amyloid-β, less neurodegeneration, and less brain atrophy. Thus, reducing CAPON levels in AD mice effectively reduced many of the physiological AD symptoms.

"Neurodegeneration is complex but we think CAPON is an important mediator between amyloid-β, tau, and cell death. Breaking this link with drugs is a promising avenue for treating AD," says Saido. "The App/MAPT double knock-in mice developed by our lab are an improved tool for the entire Alzheimer's research field."

Halide perovskite solar cells hold promise as the next generation of solar cell technologies, but while researchers have developed techniques for improving their material characteristics, nobody understood why these techniques worked. New research sheds light on the science behind these engineering solutions and paves the way for developing more efficient halide perovskite solar cells.

"This is about material design," says Aram Amassian, co-corresponding author of a paper on the work and an associate professor of materials science and engineering at North Carolina State University.

"If you want to intentionally engineer halide perovskite solar cells that have the desirable characteristics you're looking for, you have to understand not only how the material behaves under different conditions, but why," Amassian says. "This work gives us a fuller understanding of this class of materials, and that understanding will illuminate our work moving forward."

Halide perovskites are basically salts, with positively and negatively charged components that come together to form a neutral compound. And they have several characteristics that make them desirable for manufacturing high-efficiency solar cells. They can be dissolved into a liquid and then form high-quality crystals at low temperatures, which is attractive from a manufacturing standpoint. In addition, they are easy to repair and can tolerate defects in the material without seeing a big drop-off in their semiconductor properties.

An international team of researchers delved into a key phenomenon related to halide perovskite solar cell synthesis and processing. It involves the fact that adding cesium and rubidium into the synthesis process of mixed halide perovskite compounds makes the resulting solar cell more chemically homogeneous - which is desirable, since this makes the material's characteristics more uniform throughout the cell. But until now, no one knew why.

To investigate the issue, the researchers used time-resolved, X-ray diagnostics to capture and track changes in the crystalline compounds formed throughout the synthesis process. The measurements were performed at the Cornell High Energy Synchrotron Source.

"These studies are critical in defining the next steps toward the market readiness of perovskite-based solar cells," says Stefaan De Wolf, co-corresponding author of the paper and an associate professor of materials science and engineering at the King Abdullah University of Science and Technology (KAUST).

"What we found is that some of the precursors, or ingredients, want to form several compounds other than the one we want, which can cluster key elements irregularly throughout the material," Amassian says. "That was something we didn't know before.

"We also found that introducing cesium and rubidium into the process at the same time effectively suppresses the formation of those other compounds, facilitating the formation of the desired, homogeneous halide perovskite compound that is used to make high performance solar cells."

Next steps for the work include translating these lessons from laboratory-based spin-coating to large area manufacturing platforms which will enable the high throughput fabrication of perovskite solar cells.

The paper, "Multi-Cation Synergy Suppresses Phase Segregation in Mixed-Halide Perovskites," is published in the journal Joule. First author of the paper is Hoang Dang, a research scientist at NC State. The paper was co-authored by Masoud Ghasemi, a postdoctoral researcher at NC State; Kai Wang, Ming-Chung Tang, Michele De Bastiani, Emilie Dauzon and Dounya Barritt of KAUST; Jun Peng of Australian National University; and Detlef-M. Smilgies of Cornell University. The work was done with support from KAUST and the National Science Foundation, under grants 1332208 and 1542015.

Nematodes, worms found in virtually all environmental habitats, are among the most studied model organisms. They reproduce quickly and their genome contains nearly the same number of genes as the human genome.

A new Tel Aviv University study finds a mechanism exhibited in nematodes allows the nervous system cells -- neurons -- to communicate with germ cells, the cells that contain the information (genetic and epigenetic) that is transmitted to future generations. The research identifies the mode by which neurons transmit messages to these future generations.

The study was led by Prof. Oded Rechavi of TAU's George S. Wise Faculty of Life Sciences and Sagol School of Neuroscience and was published in Cell on June 6.

"The mechanism is controlled by small RNA molecules, which regulate gene expression," says Prof. Rechavi. "We found that small RNAs convey information derived from neurons to the progeny and influence a variety of physiological processes, including the food-seeking behavior of the progeny.

"These findings go against one of the most basic dogmas in modern biology. It was long thought that brain activity could have absolutely no impact on the fate of the progeny. The Weismann Barrier, also known as the Second Law of Biology, states that inherited information in the germline is supposed to be isolated from environmental influences."

According to the study, co-authored by Prof. Rechavi's students Rachel Posner and Itai A. Toker, this is the first time a mechanism has been identified that can transmit neuronal responses across generations. The discovery may have major implications for our understanding of heredity and of evolution.

"In the past, we've found that small RNAs in worms can produce transgenerational changes, but the discovery of a transgenerational transfer of information from the nervous system is a Holy Grail," explains Toker. "The nervous system is unique in its ability to integrate responses about the environment as well as bodily responses. The idea that it could also control the fate of an organism's progeny is stunning."

"We discovered that synthesis of small RNAs in neurons is needed for the worm to efficiently be attracted to odors associated with essential nutrients -- to look for food. The small RNAs produced in the parents' nervous system influenced this behavior, as well as the expression of many germline genes that persisted through at least three generations," explains Prof. Rechavi.

In other words, nematodes that did not create the small RNAs exhibited defective food identification skills. When the researchers restored the ability to produce small RNAs in neurons, the nematodes moved toward food efficiently once again. This effect was maintained for multiple generations even though the progeny did not have the ability to produce small RNAs themselves.

"It's important to stress that we don't know yet whether any of this translates to humans," Prof. Rechavi concludes. "If it does, then studying the mechanism could have a practical use in medicine. Many diseases might have some epigenetically inherited component. Deeper understanding of nonconventional forms of inheritance would be crucial to better understand these conditions and to design better diagnostics and therapies."

"It would be fascinating to see if specific neuronal activities can impact the inherited information in a way that would give specific advantages to the progeny," Toker adds. "Through this route, parents could potentially transmit information that would be beneficial to the progeny in the context of natural selection. It could therefore potentially influence an organism's evolutionary course."

CLEMSON, South Carolina - A faculty-led team of graduate and undergraduate researchers from Clemson University's Eukaryotic Pathogens Innovation Center (EPIC) has unveiled new findings that may help pave the way to an eventual cure for a parasitic infection that affects millions around the nation and world.

Research led by Zhicheng Dou, an assistant professor in the College of Science's department of biological sciences, has been published in PLOS Pathogens, a high-profile microbiology journal. The study titled "An ortholog of P. falciparum chloroquine resistance transporter (PfCRT) plays a key role in maintaining the integrity of the endolysosomal system in Toxoplasma gondii to facilitate host invasion" focuses on the usefulness of Toxoplasma - a human pathogen with a high infection rate - in examining ways to combat other pathogens, including malaria.

Brock Thornton, a Ph.D. student in Dou's lab, said the goal of the research is to derive a better understanding of what is vital for the parasite to remain infective and, ultimately, to find targets for treatment.

"We discovered that by altering one of the parasite's organelle, specifically by disrupting a certain transporter, we were able to remove the function of the parasites being able to process their invasion proteins so that they weren't as infective as before," Thornton said.

Dou said about 40 million Americans have toxoplasmosis, but few are aware of it because it does not typically cause strong symptoms.

"Most people have immunity strong enough so that they can quickly eliminate the initial acute infections, but Toxoplasma parasites can hibernate inside the central nervous system of their hosts to sustain their chronic infections," Dou said. "Certain groups, such as cancer patients, HIV carriers and organ-transplant patients, exhibit significant and even lethal symptoms because their immunity is dramatically suppressed to control the infections."

Currently available treatment for toxoplasmosis can cure it during the acute infection stage, but Dou said strong side effects from the drug mean many patients are unable to complete the month-long treatment.

"This is important," he said. "We have to identify new compounds and new chemicals to cure the toxoplasmosis."

But before this can happen, more information is needed about the basic biology of Toxoplasma parasites. That's where the team's research comes in. It might also have an important impact on the treatment of malaria, a related pathogen that has become resistant to traditional chloroquine treatment.

"Malaria parasites contain a similar organelle called the food vacuole, which displays similar functions as the organelle investigated in our research article," Dou said. "It has a very acidic environment for food digestion and nutrient utilization, like the human stomach. If we can find a way of neutralizing it, this organelle cannot digest food efficiently, which will cause the death of parasites."

Dou said that many years ago, people applied chloroquine to treat malaria infections because this basic compound can enter the food vacuole to neutralize its acidity, further compromising its digestive function. However, after years and years, this strategy did not work anymore because malaria parasites mutated one protein called the chloroquine resistant transporter, which can pump out the chloroquine from the food vacuole.

"We identified this protein in the Toxoplasma parasites," Dou said. "Since Toxoplasma and malaria parasites are from the same phylum - like siblings - the Toxoplasma research provides hints for malaria studies. Plus, Toxoplasma is easier to culture than malaria parasites and carries a better genetic system for gene modification. In our research article, we studied the native roles of this protein."

Dou said Thornton and the paper's other authors played important roles in the research.

"Brock joined the lab as a master's student," Dou said. "She tried to finish this study during the last almost two years. She did very compelling work, which I think triggered her interest in pursuing a Ph.D. Generally, such high-level research is driven by post-docs - not by junior graduate students and undergrad students. This is a very good opportunity for them to experience real biomedical research, especially at the molecular level. I want to provide this environment for graduate and undergrad students who plan to pursue research as career goals. These next-generation M.D./Ph.D. students are the hope of our future biomedical research."

Thornton has an undergraduate degree from Mississippi State University and spent two years in a fellowship with the National Institutes of Health at the Rocky Mountain Laboratories in Montana. She came to Clemson for a master's degree in microbiology, but Dou's mentorship made a profound impact on her career path.

"Dr. Dou was really supportive the whole time and was encouraging me to keep my options open," Thornton said. "My first plan was to get my master's degree and go work in a lab and be done with school. Ultimately, I realized that getting my Ph.D. will allow me to go further and really accomplish what I think will make me satisfied in the long run in my career."

Amy Bergmann is the lab manager and also conducts her own research.

"The main goal in all of our research is for potential treatments to help save lives in the future," Bergmann said. "That's what we all want to happen."

Katherine Floyd, a junior majoring in biochemistry and microbiology, said that participating in published research is not something she expected to do at the undergraduate level.

"Working in the lab has made me definitely want to do a Ph.D.," Floyd said. "Before, I knew I was going to do something after undergrad, but I wasn't sure how far I wanted to go. I definitely want to continue doing research as a career. I feel a lot more prepared for graduate school, and I know I will like it once I'm there because I'm simulating as much as I can as an undergrad."

Thornton echoed that enthusiasm.

"Definitely not all grad school experiences are this way," she said. "I feel super lucky to have gotten to work in Dr. Dou's lab and have him be so supportive, forward-moving and forward-thinking with things like this. Getting a paper published within my first couple of years being here has been incredibly exciting."

Bergmann said Dou sets the tone of the lab through his hands-on research and concern about those who work there.

"Working in this lab, we are a family," she said. "You don't see that in a lot of labs, but we basically are a family. I joke and say I'm the lab mom and I take care of everybody, but we take care of each other. That's why we're all on this paper, because we work so well together. It's not cutthroat. It's 'Let me help you' and 'I've got your back,' which is very beneficial when you're doing work like this."

For undergraduate students like Floyd, the work means gaining even more than what can be found in a classroom.

"They are the most important part of my college experience," she said. "They really are a family."

Researchers from EPIC are making important discoveries toward future treatments of parasitic infections while cultivating an atmosphere that challenges students and affords them opportunities to excel beyond their years. Dou said the research is important, but only part of the equation.

"Yes, it's a good paper, but if I can change people and change their confidence, this is something I want to do," he said. "I was changed by my post-doc adviser, Dr. Vern Carruthers at the University of Michigan. I wanted to go into industry, get a job. But Vern changed me and made me feel confident that I can do independent research and lead my own research team. This is the reason I applied as an assistant professor at Clemson. This is what I want to do. If I can change someone's confidence, it has more meaning."

London, June 6, 2019 - Packaging is the first impression consumers have of food products that influences the likelihood of purchasing. A new study in the journal Heliyon, published by Elsevier, evaluates the effect of chocolate packaging design on sensory liking and willingness to purchase. Researchers found that participants expressed stronger emotional associations with the packaging than they did from tasting the chocolate. The study concluded that while taste is the predominant factor in determining subsequent purchases, perception of taste is influenced by emotions evoked by packaging.

"There's a difference in how consumers perceive intrinsic product cues - like flavor, aroma, and texture - which are associated with sensory and perceptual systems, and how they perceive external cues - like packaging materials, information, brand name, and price - which are associated with cognitive and psychological mechanisms," explained co-lead investigator Frank R. Dunshea, PhD, School of Agriculture and Food, Faculty of Veterinary and Agricultural Sciences, The University of Melbourne, VIC, Australia. "The information provided via packaging can influence customers' expectations and affect their emotional response when their sensory experience confirms or doesn't confirm their initial impression."

The researchers set out to identify how packaging affects the liking of a taste; explore the emotions evoked by the packaging and the chocolate; and determine whether these factors affected subsequent willingness to purchase. Seventy-five participants (aged 25-55 years old, 59 percent female) were asked to evaluate chocolates under three conditions: a blind taste test of chocolate; packaging concepts only; and chocolate plus packaging. The same chocolate was wrapped in six different packaging designs representing bold, fun, every day, special, healthy, and premium concepts. At each step, participants were asked to associate the samples with a lexicon of emotion-based terms.

How much participants liked the taste of the chocolates was affected by their expectations based on the different wrapper designs, especially when expectations created by packaging were not met. Participants selected stronger emotional words to describe the packaging than they did when describing what they blindly tasted the chocolate. The investigators found that there was moderate positive correlation between liking the packaging and the taste of the chocolate when it was wrapped in packaging described with positive terms such as happy, healthy, fun, bright, relaxing, peace, achievement, togetherness, balance, excitement and friendship. Participants' association of positive emotions with the packaging therefore had a direct influence on the acceptability of the chocolate.

"An estimated 60 percent of consumers' initial decisions about products are made in stores solely by judging the packaging. As a result, our findings offer important insights that can be used in product design and development to control product intrinsic and extrinsic attributes by enhancing the emotional attachment towards the food products," explained co-lead investigator Sigfredo Fuentes, PhD, also of the School of Agriculture and Food, Faculty of Veterinary and Agricultural Sciences, The University of Melbourne, VIC, Australia.

The investigators note that participants preferred the taste of the samples more when they were eaten in blind conditions, as opposed to evaluating them after assessing the packaging, and that taste guides subsequent purchases. "This research proposed a cross-disciplinary approach with a combination of sensory and consumer science as well as psychology- and physiology-based assessments, which are important to understand the implicit response of consumers to meet the expectations of products in the market," explained first author Nadeesha Gunaratne, PhD, Scholar, School of Agriculture and Food, Faculty of Veterinary and Agricultural Sciences, The University of Melbourne, VIC, Australia.

Defining mental disorders and illnesses is not straightforward. Notions of whether a certain phenomenon should be classified as an illness or disorder, or something falling within the category of normal emotional fluctuations or personality traits, have changed significantly over the years, and continue to do so.

"It's difficult to draw a definite line between normal and abnormal behaviour, or to know when mental symptoms should be called a disease. For instance, grief and anxiety can be normal reactions to a difficult stage in life, but they may also underlie severe depression or an anxiety disorder," says Kari Tikkinen, the principal author of a research article on this topic who is an Academy of Finland clinical researcher and adjunct professor at the University of Helsinki.

In a study carried out with a Finnish dataset, an international group of researchers looked into which mental conditions from a group of 20 were considered illnesses and which were not by five different groups of people. The questionnaire was distributed to 6,200 individuals, of whom 3,000 were Finns chosen randomly from the Population Register. The rest included 1,500 physicians - a number of psychiatrists and other specialists - 1,500 nurses and, in addition, all of the 200 members of the Finnish Parliament. The researchers received 3,259 responses (53%).

The respondents were asked whether they would define the following conditions as diseases: ADHD, alcoholism, anorexia, autism, bulimia, premature ejaculation, homosexuality, drug addiction, depression, panic disorder, gambling addiction, personality disorder, absence of sexual desire, schizophrenia, social anxiety disorder, grief, transsexualism, work exhaustion, insomnia and generalised anxiety disorder.

At least 75% of respondents in all groups considered schizophrenia and autism illnesses, while a corresponding share did not consider homosexuality and grief illnesses.

In all groups, ADHD, anorexia, bulimia, depression, panic disorder, personality disorder and generalised anxiety disorder were classified as diseases by 50-75% of respondents. The same number of respondents did not classify premature ejaculation, absence of sexual desire and transsexualism as diseases.

The widest range of views concerned alcoholism, drug and gambling addiction, social anxiety disorder, insomnia and work exhaustion.

Psychiatrists were most inclined to classify the conditions included in the questionnaire as diseases, followed by other physicians, nurses, members of parliament and laypeople.

"In other words, the more psychiatric training you had, the more likely you were to consider the conditions diseases. The difference between psychiatrists and laypeople was substantial," Tikkinen says.

People's notions of what is and is not a disease is very important in the discourse on mental health and human behaviour. These notions also influence the allocation of society's resources and the stigmatisation of various groups of people.

"Society's attitude towards alcoholics and drug addicts largely depends on whether substance abuse is considered an illness or a life choice," Tikkinen points out.

"The medicalisation of various problems is not a positive trend either; it may result in non-medical causes being overlooked, solving problems with an approach that is too reliant on pharmaceuticals."

Japanese scientists have - for the first time - developed an efficient way to make organic molecules that have so far been difficult to synthesize because of their overall bulky structure and general instability.

By designing a carefully planned sequence of synthesis steps, the researchers were able to efficiently create intricate molecules that have several practical properties. Potential applications include tool compounds for biomedical study and to serve as scaffolds for the design of therapeutic agents with new shapes to materials designs, specifically in the creation of dyes and electronically active materials

The research findings were published in Organic Letters in March 2019.

Designing complex organic molecules that can be of use in a wide range of applications is not always straightforward. Often, these molecules are complex, meaning that they are a combination of several cyclical structures that are all attached to one atom. While beautiful, their synthesis is difficult for several reasons. Their bulkiness makes them energetically unfavorable - or unstable - which means they are difficult to synthesize.

On the other hand, if they are eventually synthesized, there is not enough compound to be of use for any subsequent application. An example of such complex molecules are those that involve several cyclic structures that are attached to carbon-hydrogen atoms within it. Previous methods have relied not only on several reaction steps but have resulted in very little compound yield.

Now, Keiji Mori, PhD, Associate Professor at the Department of Applied Chemistry, Graduate School of Engineering, Tokyo University of Agriculture and Technology, Japan and his team have come up with a straightforward method that overcomes the shortcomings of pervious synthesis sequences.

The researchers focused on the carbon-hydrogen bond within their starting step and proceeded with a series of bond editions that involved sequential transformations of the molecule. After achieving the desired cyclic conformations, the scientists introduced a few more carbon-hydrogen groups to obtain an ultimate molecule with the energetically preferred conformation. "It is important to note that even the simplest idea can lead to an important synthetic method. Along those lines, subtle differences in the substrate can dramatically alter the reaction mechanism," adds Mori.

The researchers hope that this new synthesis will provide access to a host of useful molecules in future. "The synthesis of compounds whose molecular structure is composed of several kinds of circular structures has been difficult to achieve via conventional methods. As such, the final goal of the project is the synthesis of various spiro (or twisted-shaped) compounds that have a variety of different atoms," Mori adds. These new molecules could greatly enhance both medical as well as materials sciences.

This work was partially supported by a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science, and by grants from The Uehara Memorial Foundation and The Naito Foundation.

LOS ANGELES (June 6, 2019) -- Scientists can't make a living copy of your brain outside your body. That's the stuff of science fiction. But in a new study, they recreated a critical brain component, the blood-brain barrier, that functioned as it would in the individual who provided the cells to make it. Their achievement - detailed in a study published today in the peer-reviewed journal Cell Stem Cell - provides a new way to make discoveries about brain disorders and, potentially, predict which drugs will work best for an individual patient.

The blood-brain barrier acts as a gatekeeper by blocking toxins and other foreign substances in the bloodstream from entering brain tissue and damaging it. It also can prevent potential therapeutic drugs from reaching the brain. Neurological disorders such as amyotrophic lateral sclerosis (Lou Gehrig's disease), Parkinson's disease and Huntington's disease, which collectively affect millions of people, have been linked to defective blood-brain barriers that keep out biomolecules needed for healthy brain activity.

For their study, a team led by Cedars-Sinai investigators generated stem cells known as induced pluripotent stem cells, which can produce any type of cell, using an individual adult's blood samples. They used these special cells to make neurons, blood-vessel linings and support cells that together make up the blood-brain barrier. The team then placed the various types of cells inside Organ-Chips, which recreated the body's microenvironment with the natural physiology and mechanical forces that cells experience within the human body.

The living cells soon formed a functioning unit of a blood-brain barrier that functions as it does in the body, including blocking entry of certain drugs. Significantly, when this blood-brain barrier was derived from cells of patients with Huntington's disease or Allan-Herndon-Dudley syndrome, a rare congenital neurological disorder, the barrier malfunctioned in the same way that it does in patients with these diseases.

While scientists have created blood-brain barriers outside the body before, this study further advanced the science by using induced pluripotent stem cells to generate a functioning blood-brain barrier, inside an Organ-Chip, that displayed a characteristic defect of the individual patient's disease.

The study's findings open a promising pathway for precision medicine, said Clive Svendsen, PhD, director of the Cedars-Sinai Board of Governors Regenerative Medicine Institute. "The possibility of using a patient-specific, multicellular model of a blood-brain barrier on a chip represents a new standard for developing predictive, personalized medicine," he said. Svendsen, professor of Medicine and Biomedical Sciences, was the senior author of the study.

The research combined the innovative stem cell science from investigators at Cedars-Sinai in Los Angeles with the advanced Organs-on-Chips technology of Emulate, Inc. in Boston. Emulate's Human Emulation System recreates the microenvironment that cells require to exhibit an unprecedented level of biological function and to behave like they do in the human body. The system consists of instrumentation, software apps, and Organ-Chips, about the size of AA batteries, with tiny fluidic channels lined with tens of thousands of living human cells.

The co-first authors of the study are Gad Vatine, PhD, from Ben-Gurion University of the Negev in Beer Sheva, Israel, a former postdoctoral scientist at Cedars-Sinai; Riccardo Barrile, PhD, of Emulate, a former postdoctoral fellow at Cedars-Sinai; and Michael Workman, a PhD student in the Cedars-Sinai Graduate School of Biomedical Sciences.

The research is one of several collaborative projects involving Cedars-Sinai and Emulate, Inc., which In February 2018 announced a joint Patient-on-a-Chip program to help predict which disease treatments would be most effective based on a patient's genetic makeup and disease variant. The program is an initiative of Cedars-Sinai Precision Health, whose goal is to drive the development of the newest technology and best research, coupled with the finest clinical practice, to rapidly enable a new era of personalized health.

Just as a computer requires code to work, our bodies are regulated by molecular "programs" that are written early in life and then have to do their job properly for a lifetime. But do they? It's a question that has intrigued researchers for years.

Claes Wahlestedt, M.D., Ph.D., professor of psychiatry and behavioral sciences and associate dean for therapeutic innovation at the University of Miami Miller School of Medicine, is senior author of a new study - Longevity Related Molecular Pathways Are Subject to Midlife 'Switch' in Humans - published today in Aging Cell [DOI: 10.1111/acel.12970].

Working with first author Jamie Timmons, Ph.D., of King's College London and Stirling University Science Park, United Kingdom, and an international group of researchers on human aging, Dr. Wahlestedt made a striking observation: Key molecular programs known to promote longevity do not last beyond midlife.

The study provides a possible new reason why human disease burden increases so sharply from the sixth decade of life onward as health-protective mechanisms disappear. Which raises the question: If one wishes to boost these established "anti-aging" programs with drugs, nutrients, or lifestyle choices, is it too late to start by the time you reach your 60s? Possibly, said Dr. Wahlestedt - at least if you hope to benefit fully from such interventions.

"For over a decade, it has been clear that key biochemical events regulate the longevity of small short-lived animals such as worms, flies, and mice, but these mechanisms had not been observed to be active in humans," Dr. Wahlestedt said. "In this international clinical and genomic study, we report for the first time that humans use these same biochemical pathways during aging. Surprisingly, however, humans appear to stop using these pathways from about 50 years of age onward. Therefore, how long and how 'hard' each person regulates these pathways may influence human lifespan."

Dr. Wahlestedt said the new study was the result of two decades of persistent efforts initiated while he and Dr. Timmons worked at the Karolinska Institutet in Stockholm, Sweden. They made their discovery when using a new method for quantifying comprehensive gene expression patterns, applied to carefully curated sets of tissue samples from humans at various ages.

With a primary focus on muscle and brain, these novel observations in humans align well with previous work in short-lived species. This included a dominant role for the so-called mTOR protein complex - a mechanism that regulates numerous protective cell programs - as well as mitochondrial reactive oxygen species production. These two cellular mechanisms combined to explain about two-thirds of the molecular aging profile in humans.

"Our study revealed that the complexity of regulation of aging programs may be much greater in humans as compared to other species," Dr. Wahlestedt said. "This is related to our more complex genome, which may have evolved to allow for longer and healthier lifespan. But perhaps humans were not really meant to last beyond their 50s."

From a molecular aging research perspective, humans are unique among species. Yet, like our shorter-lived distant relatives, the researchers also noted that, in humans, the molecular responses during aging don't follow a linear pattern. This counters an idea deeply entrenched in human epidemiology studies.

"Beyond the need to consider different 'phases' of molecular aging, clinical variables such as aerobic capacity and insulin resistance are also important to quantify," Dr. Timmons said. "They interact with some of the same genes as aging, are partly inherited, and are important predictors of health. We were able to look at these for the first time when modeling human aging."

While the key protein regulators of longevity and health-span in short-lived animals have been found for the first time to be central to human molecular aging, this new study also determined that many little-studied so-called non-protein-coding genes are involved in human aging. Considered the "dark matter" of the human genome, these non-protein-coding genes are widely present in human cells, but often not found in lower organisms. It now appears they could play an important role in fine-tuning the molecular features of aging.

"We've demonstrated that the most valid of 'anti-aging' programs are naturally active in humans and for some reason stop when we reach our 50s," Dr. Wahlestedt said. "This not only provides a specific time window to now study human aging, it also indicates that these established anti-aging strategies may no longer be effective (if too active there can be side effects) and so new approaches will be needed in long-lived humans."

Spatial resolution of optical microscopy and spectroscopy is determined by how much one can confine light in space, which is usually restricted to about half-micrometer at the best due to the diffraction limit. However, light can be confined into nanometer scale by using metallic nanostructures through excitation of localized surface plasmon resonance (LSPR). Having such "nanolight" at a sharp metallic tip is particularly useful because it can be used in scanning tunneling luminescence (STL) and scattering-type scanning near-field optical microscopy (s-SNOM) performing nanoscale imaging and spectroscopy to look at nanomaterials and even single molecules. However, precise manipulation of nanolight in nanoscale junction has remained an outstanding problem. Because the nature of nanolight (LSPR) is determined by the nanoscopic structure of the tip, its manipulation requires a fine processing technique at the nanoscale. In addition, nanolight confined into nanocavities is of key importance due to the strong enhancement effect of an electromagnetic field, which enables ultrasensitive nanoscale imaging and spectroscopy.

A research team at the Fritz-Haber Institute in Berlin, headed by Dr. Takashi Kumagai, now demonstrated that manipulation of nanolight spectrum can be attained by shaping accurately plasmonic gold tips with a focused ion beam (FIB) milling technique. As an exemplary demonstration, they produced a very sharp tip with a single groove on its shaft as shown in the scanning electron microscope picture. The spectral response of nanolight confined in the nanocavity formed by the grooved tip and an atomically flat silver surface was investigated by using STL that is the combination of electronic and optical spectroscopies using scanning tunneling microscopy. The STML spectra with the grooved tips exhibit a characteristic modulation resulting from Fabry-Pérot type interference of surface plasmon polaritons (SPPs) on the tip shaft as the standing wave formation is visualized in the electrodynamic simulation. The spectral modulation can be precisely controlled by the groove position on the shaft. They also demonstrated that the SPP Fabry-Pérot interference can be improved by optimizing the overall tip shape.

This work shows a great potential of the combination of scanning probe techniques and nano-fabrication of plasmonic tips using FIB in order to study the nature of nanolight and light-matter interactions in nanocavities, which are an important frontier of plasmonics and nanooptics. In addition, the FIB-fabricated plasmonic tips are generally applicable to s-SNOM techniques, thus paving the way for nanoscale imaging and spectroscopy with a high degree of accuracy. Moreover, spectral control of the intense near-field at the apex of plasmonic tips may open up new opportunities for the realization of coherent laser-triggered electron point sources for low-energy electron microscopy and holography techniques.

Our brains are notoriously bad at regenerating cells that have been lost through injury or disease. While therapies using neural stem cells (NSCs) hold the promise of replacing lost cells, scientists need to better understand how NSCs behave in the brain in order to develop effective treatments.

Now research led by the University of Plymouth helps to shed new light on the mechanisms used by NSCs to 'wake up' - going from their usual dormant state to one of action.

NSCs produce neurons (nerve cells) and surrounding glial cells in the brain. By understanding how NSCs work, it could pave the way for therapies to speed up the neurons' and glial cells' regeneration.

The new study, conducted using Drosophila fruit flies, shows that molecules that form a complex called STRIPAK are essential to promote reactivation in NSCs. STRIPAK (Striatin-interacting phosphatase and kinase) is found in organisms from fungi to humans, and the team uncovered it when comparing the genetic messages of dormant and reactivated NSCs in live fly brains.

The researchers then discovered that STRIPAK components act as a switch to turn off dormancy (or quiescence) and turn on reactivation.

Lead author Dr Claudia Barros, from the Institute of Translational and Stratified Medicine at the University of Plymouth, acknowledges there is still a long way to go until such findings can be translated into human treatments. But she explains the significance of the new work:

"So little is currently known about how neural stem cells coordinate cues to become active and direct the production of more brain cells," she said. "These stem cells last throughout life mainly in a dormant state, so learning how they work is critical to our understanding of cell regeneration.

"This study reveals that STRIPAK molecules are essential to enable reactivation in NSCs, and we are very pleased with the outcomes. But we are only at the beginning. We are working to expand our findings and bring us closer to the day when human neural stem cells can be controlled and efficiently used to facilitate brain damage repair, or even prevent brain cancer growth that is fuelled by stem-like cells."

The full study, entitled STRIPAK Members Orchestrate Hippo and Insulin Receptor Signaling to Promote Neural Stem Cell Reactivation, is available to view now in the journal Cell Reports (doi: 10.1016/j.celrep.2019.05.023).

Sloths once roamed the Americas, ranging from tiny, cat-sized animals that lived in trees all the way up to massive ground sloths that may have weighed up to six tons. The only species we know and love today, however, are the two-toed and three-toed sloths--but paleontologists have been arguing how to classify them, and their ancestors, for decades.

A pair of studies published June 6 have shaken up the sloth family tree, overturning a longstanding consensus on how the major groups of sloths are related. According to the results, the three-toed sloth is more closely related to a large family that included ancient elephant-sized ground sloths; meanwhile, the two-toed sloth appears to be the last survivor of an ancient lineage previously thought extinct.

"The results are surprising on many levels," said Graham Slater, an assistant professor of geophysical sciences at the University of Chicago who co-authored one of the papers. "Not only do they rewrite sloth classification, they suggest much of what we thought we knew about how sloths evolved may be wrong."

Slater's study, published in Nature Ecology & Evolution, uses a pioneering approach that uses proteins in fossils to discover evolutionary relationships--marking the first time an entire lineage has been mapped with the method.

"All of these ancient sloths must have occupied really important roles in grazing and browsing the landscape, and so they're important to understanding how these ecosystems worked, but getting a handle on their evolution has been difficult," said Slater, who specializes in analyzing the patterns of evolution in mammals.

The existing hierarchy is built on how physically similar the fossils look to one another. But Slater, working with Ross MacPhee with the American Museum of Natural History and Samantha Presslee at the University of York, wanted to explore the possibilities of an emerging field called paleoproteomics--extracting information from proteins inside fossilized bone.

Instead of DNA, which is a fragile molecule that needs specific conditions to survive inside fossils--"getting ancient DNA is a bit of a lottery," Slater said--scientists have been looking at proteins instead. Protein molecules are sturdier, and since DNA is translated directly into proteins, they hold much of the same information. So the scientists extracted collagen from multiple fossils, analyzed it to reconstruct the sequences of amino acids, and then compared these to one another to piece together relationships between the species.

"What came out was just remarkable. It blew our minds--it's so different from anything that's ever been suggested," Slater said.

Previously, scientists thought that the unau--the three-toed sloth with cute black lines around its eyes--was an outlier species that diverged early in the group's evolution. But based on the new evidence, it actually appears to be nested within a large group of different ground sloths that includes those gigantic, elephant-sized sloths.

Meanwhile, the ai (or two-toed sloth) had been classified in with a family called Megalonychidae, which includes everything from Central American and Caribbean sloths to an Ice Age-era American ground sloth that was first described by Thomas Jefferson (due to the fossil's large claws, he thought it was a lion). But according to the findings, two-toed sloths are actually the last survivors of a branch previously thought to be extinct, which likely split off about 20 million years ago.

The protein evidence also revealed that those extinct Caribbean sloths were the descendants of an early branch that split from other sloths around 30 million years ago. This is interesting evidence for another longstanding question: whether there was a short-lived land bridge connecting South America and what would become the West Indies, many millions of years ago. If wanderlust drove ancient sloths across the bridge, their presence in the islands would support that idea. Thus far no conclusive fossil evidence has turned up, but the genetic split 30 million years ago makes sense if those sloths were then geographically isolated after the land bridge disappeared.

The new conclusions also cast doubt on our picture of how sloths evolved, because the West Indian sloths look as though they lived in trees. "We've been used to thinking that today's sloths each evolved independently for life in the trees from a ground-dwelling ancestor, but our results suggest that the ancestral sloth may have been at home in both," Slater said.

Though revolutionary, the results square with a DNA analysis released the same day by a group with the French National Centre for Scientific Research and other institutions. That group was able to pull mitochondrial DNA from several critical fossils, and the two independent analyses align very closely. "Exceptional results demand exceptional verification," said MacPhee, so the two groups agreed to publish simultaneously.

The team is excited about pushing the boundaries of the field of paleoproteomics. Evolutionary paleobiology is greedy for more and older data, and proteins could provide it.

"The very oldest DNA you can get is 800,000 years old, but in theory we should be able to get protein data from specimens that are millions of years old," Slater said. "A whole bunch of questions suddenly come into reach. It opens doors that we were only dreaming of."

A new model is providing insight into the impact of invasive lionfish on coral reefs in the Atlantic Ocean and Caribbean Sea. The venomous predatory fish has invaded more than 7.3 million square kilometres in the Atlantic and Caribbean, wreaking havoc among native fish populations.

The method, developed and tested with coral reef fish in the Bahamas through an international collaboration of scientists in Canada, the United States, and United Kingdom, is based on the behaviours used by prey to avoid being eaten by predators that use different hunting tactics.

"Many scientists have speculated that invasive lionfish are so successful in the Atlantic because prey don't recognize them as a predator," explained Stephanie Green, assistant professor in the University of Alberta's Department of Biological Sciences and lead author.

Stephanie Green, assistant professor in the Department of Biological Sciences, swims alongside a lionfish.

"However, we found that reef fish enter the 'danger zone'--close enough to be eaten--around invasive lionfish at similar rates to native predators. But for those prey that stray too close to lionfish, they are up to twice as likely to be captured than by predators that are naturally found on Caribbean reefs."

The ranges of many predators are expected to grow, due to climate change and future invasions. The new method is designed to help both scientists and conservationists better understand how predators select their prey. In the case of lionfish, the scientists' hope the model can help them identify areas where native species are most vulnerable to the novel stalking hunting strategy of lionfish as the invasion spreads.

"As invasions take hold, scientists have few tools to help them predict what the effects will be,and as a result, we often don't understand how invasive predators have changed environments until it is too late," added Mark Hixon, professor at the University of Hawai'i and co-author of the study.

The authors hope their approach can be used by researchers in the Mediterranean who are keen to understand which kinds of fishes and fisheries there will be most affected by the recent invasion of lionfish in this region. Green is also adapting the model to examine predator-prey interactions for albacore tuna with respect to climate change. "We hope that using knowledge of species behaviours can help scientists and managers predict who will eat whom when predators and prey encounter one another in new settings," added Green, who is also a Sloan Research Fellow.

CORVALLIS, Ore. - Females who identify as sexual minorities face an increased risk of substance use that shows up as early as age 13, suggesting early adolescence is a critical period for prevention and intervention efforts, a new study from Oregon State University has found.

The odds of substance use among females who identify as sexual minorities - an umbrella term for those who identify with any sexual identity other than heterosexual or who report same-sex attraction or behavior - is 400% higher than their heterosexual female peers.

"We saw this striking difference in substance use at age 13 and there was rapid increase in the rate of cigarette and alcohol use from there," said Sarah Dermody, an assistant professor in the School of Psychological Science in OSU's College of Liberal Arts and the study's lead author. "That tells us we need to find ways to intervene as early as possible to help prevent substance use in this population."

The findings were published recently in the Journal of LGBT Youth. Co-authors are James McGinley of McGinley Statistical Consulting and director of behavioral analytics at the Vector Psychometric Group; Kristen Eckstrand, a physician at the University of Pittsburgh Medical Center; and Michael P. Marshal of the University of Pittsburgh.

Among youth, alcohol, marijuana and nicotine are the three most commonly used drugs. That is a concern because youth who use those substances are at risk of negative health and social outcomes, including addiction and poor cognitive, social and academic function.

Past research has shown that sexual minority youth reported nearly three times more substance use than heterosexual youth. The disparity may be due in part to stress from discrimination, violence and victimization rooted in their sexual minority status, Dermody said.

The pattern of increased substance use for youth who identify as sexual minorities is magnified significantly for females. In the new study, researchers hoped to gain better understanding of how substance use rates develop over time for this group in particular, Dermody said.

Using data from about 2,200 participants in the Pittsburgh Girls Study, a large, longitudinal study of the lives of urban girls, researchers examined substance use among females over time from age 13 to 20, comparing those who identified as heterosexual to those identifying as lesbian/gay or bisexual.

They looked at when disparities in use between heterosexual and sexual minority identifying females began to emerge; rates of change over time for both groups; and how rates change as the girls approach young adulthood.

The researchers found that disparities in substance use between heterosexual and sexual minority girls were already present at age 13. The difference in use between heterosexual and sexual minority girls persisted and increased as they entered their 20s.

The findings suggest that early prevention and intervention efforts may be needed to reduce initial use and slow the escalation of substance use among the population. Such efforts could also help decrease substance use disparities over time, Dermody said.

"It's already a risky and vulnerable period for youths' social development, and it's also a vulnerable time for brain development," Dermody said.

It's also important to remember that within the population of youths who identify as sexual minorities, there are many youths who are not using any substances at all, or who are not using them as heavily, Dermody said.

"This is a subgroup that we are concerned about," she said. "In future research, it would useful to explore how individual youths' experiences influence where they fall on the spectrum of substance use."

Galaxies with no dark matter are impossible to understand in the framework of the current theory of galaxy formation, because the role of dark matter is fundamental in causing the collapse of the gas to form stars. In 2018, a study published inNature magazine announced the discovery of a galaxy that lacked dark matter, which made a strong impact, and occupied the covers of popular scientific magazines.

Now, according to an article published in the Monthly Notices of the Royal Astronomical Society (MNRAS) a group of researchers at the Instituto de Astrofísica de Canarias (IAC) has solved this mystery via a very complete set of observations of KKS2000]04 (NGC1052-DF2), previously nicknamed "the galaxy without dark matter".

In this study the researchers, perplexed because all the parameters that depended on the distance of the galaxy were anomalous; have revised the available distance indicators. Using five independent methods to estimate the distance of the object they found that all of them coincided in one conclusion: the galaxy is much nearer than the value presented in the previous research.

The original article published in Nature stated that the galaxy is at a distance of some 64 million light years from the Earth. However, this new research has revealed that the real distance is much less, around 42 million light years.

Thanks to these new results, the parameters of the galaxy inferred from its distance have become "normal" and fit the observed trends traced by galaxies with similar characteristics.

The most relevant datum that has been found via the new distance analysis is that the total mass of this galaxy is around a half of the mass estimated previously, but the mass of its stars is only about quarter of the previously estimated mass. This implies that a significant part of the total mass must be made up of dark matter. The results of this work show the fundamental importance of the correct measurement of extragalactic distances. It has always been one of the most challenging tasks in astrophysics: how to measure the distances to objects which are very far away and which we cannot touch.