Culture

New research led by the Johns Hopkins Center for Communication Programs, Ifakara Health Institute and the Zanzibar Malaria Elimination Program suggests that a better understanding of human behavior at night - when malaria mosquitoes are biting - could be key to preventing lingering cases. The Center for Communication Programs (CCP) is based at the Johns Hopkins Bloomberg School of Public Health.

The new study, published July 1 in Malaria Journal, found that targeting men who work and socialize outside the home in the evenings and travelers and seasonal workers who may bring malaria to the islands from mainland Tanzania could accelerate elimination of the disease.

Zanzibar has maintained malaria prevalence below one percent for the past decade, but elimination of the deadly mosquito-borne disease remains elusive, despite the widespread use of insecticide-treated bed nets and indoor spraying.

"We've seen such great progress, but it's hard to eliminate the remaining cases," says CCP's April Monroe, PhD, who led the research. "It's the typical last mile problem: Sometimes the hardest part of the journey comes at the end. To get there, we need to focus our attention now on human behavior, instead of solely on mosquito behavior as we did in the past."

The World Health Organization estimates that between 2000 and 2015, the rate of new malaria cases declined by 37 percent globally and malaria deaths fell by 60 percent, with 6.2 million lives saved. Three quarters of those gains can be attributed to interventions such as insecticide-treated bed nets and indoor spraying for mosquitoes.

But those interventions are only designed to work indoors.

For the study, Monroe and her colleagues analyzed data from 62 in-depth interviews with community members and leaders conducted in December 2016 and April/May 2017. The researchers also looked at data from night time observation of routine community activities, such as buying and selling at local shops, watching television in public spaces and socializing in small groups, as well as large-scale community events such as weddings and religious ceremonies.

The researchers found little evidence of people using protection against mosquitoes outdoors. "Participants reported that topical repellants were not widely available in the community and were only sold at shops in town," the authors noted.

As one woman who was interviewed remarked, "When you are outside, you really can't wear the bed nets, can you?"

In low-transmission settings like Zanzibar, children under five are no longer considered the population most at risk for malaria infection. They are sleeping under their nets and are typically at home or near home after dark. It is men who are often outside at night, whether working or socializing, which could put them at higher risk.

Zanzibar is made up of a series of islands in the Indian Ocean off the coast of Tanzania, where transmission of malaria is more common. Travelers from the mainland are understood to bring many of the malaria cases found in Zanzibar with them. When a mosquito bites a person infected with the parasite, it infects the mosquito which can then transmit the disease to someone else.

Seasonal workers from mainland Tanzania come to Zanzibar for a variety of reasons, including to work in the fields from planting to harvest time and they often do not have mosquito nets. Some communities in Zanzibar have instituted a process by which newcomers register with community leaders who can connect them with testing for malaria (and treatment, if need be) as well as to offer malaria prevention information. Monroe says these community-designed systems could be scaled up in other areas of Zanzibar.

There is a great opportunity to explore the use of mosquito control tools beyond nets and spraying alongside social and behavior change interventions to help address these identified gaps in malaria prevention that occur after dark, she says.

"Building on these existing systems to target interventions should be explored so as to limit both local and imported malaria cases," the authors note.

"Human behaviour and residual malaria transmission in Zanzibar: findings from in-depth interviews and direct observation of community events" was written by April Monroe, Kimberly Mihayo, Fredros Okumu, Marceline Finda, Sarah Moore, Hannah Koenker, Matthew Lynch, Faiza Abbas, Abdullah Ali, George Greer and Steven Harvey.

ITHACA, N.Y. - Using nature's color palette from early Earth, Cornell University astronomers have created a cosmic "cheat sheet" in order to understand where discovered exoplanets may fall along their own evolutionary spectrum.

Jack O'Malley-James, a research associate at the Carl Sagan Institute, and Lisa Kaltenegger, professor of astronomy and director of the Carl Sagan Institute, co-authored "Expanding the Timeline for Earth's Photosynthetic Red Edge Biosignature" published in The Astrophysical Journal Letters.

"In our search to understand exoplanets, we're using the early Earth and its biological milestones in history as a Rosetta stone," O'Malley-James said. "Scientists can observe surface biosignatures beyond vegetation on Earth-like exoplanets by using our own planet as the key for what to look for."

For the last half-billion years - roughly 10 percent of our planet's lifetime - chlorophyll, present in many familiar forms of plant life such as leaves and lichen, has been the key component in Earth's biosignature. But other flora, such as cyanobacteria and algae, are much older than land-based vegetation, but their chlorophyll-containing structures leave their own telltale signs on a planet's surface.

"Astronomers had concentrated only on vegetation before, but with a better color palette, researchers can now look beyond a half-billion years and up to 2.5 billion years back on Earth's history to match like periods on exoplanets," Kaltenegger said. "If an alien had used color to observe if our Earth had life, that alien would see very different colors throughout our planet's history - going back billions of years - when different life forms dominated Earth's surface."

O'Malley-James and Kaltenegger modeled spectra of Earth-like exoplanets with different surface organisms that use chlorophyll.

Lichens (a symbiotic fungal and photosynthetic partnership) may have colonized Earth's land masses some 1.2 billion years ago and would have painted Earth in sage to mint green colors. This coverage would have generated a "nonvegetative" photosynthetic red-edge signature. A red-edge signature is the part of the spectrum that helps keep plants from getting burned by the sun.

"When we discover an exoplanet, this research gives us a much wider range to look back in time," Kaltenegger said. "We extend the time that we can find surface biota from 500 million years (widespread land vegetation) to about 1 billion years ago with lichen and up to 2 or 3 billion years ago with cyanobacteria."

A large observational cohort study examining male veterans aged over 50 years with type 2 diabetes found that metformin use was associated with a significantly lower risk of dementia in African American patients. The study included data from 73,500 patients who received care through the Veteran's Health Administration from 2000-2015 and were diabetes- and dementia-free at baseline and who subsequently developed type 2 diabetes and began treatment with either metformin or sulfonylurea. Cox proportional hazards models, using propensity scores and inverse probability treatment to balance confounding factors, were computed to measure the association of both drugs and incident dementia across race and age groups. For African American patients aged 50-64 years, the hazard ratio for developing dementia was 0.60 (CI, 0.45-0.81), and for African American patients aged 65-74 years, the hazard ratio was 0.71 (CI, 0.53-0.94). The study showed modest to no association between metformin and lower risk for dementia in white patients 65-74 and no association in other age groups. The present results may point to a novel approach for reducing dementia risk in African Americans with type 2 diabetes mellitus.

Crouching in the boot-sucking mud of the Baylands Nature Preserve in Palo Alto, Manu Prakash, associate professor of bioengineering at Stanford University, peered through his Foldscope - a $1.75 origami microscope of his own invention - scrutinizing the inhabitants of the marsh's brackish waters. With his eye trained on a large single-cell organism, called Spirostomum, he watched it do something that immediately made it his next research subject.

"I still remember for the very first time, seeing this organism swim by under the Foldscope," said Prakash. "This is a massive cell but it contracts in less than a blink of an eye, accelerating faster than almost any other single cell. When you aren't expecting it, it's like it disappears. I remember being so excited, I had to bring the cells back to the lab and take a careful look."

This observation, made through a simple tool only five miles from Prakash's lab, has now led him and colleagues to the discovery of a new form of communication between cells, which they detail in a paper published July 10 in Nature. Without touching and without electrical or chemical signals, individual Spirostomum can coordinate their ultrafast contractions so closely that groups of them appear to shrink simultaneously - a reaction to predators that makes them release paralyzing toxins in sync.

"There are many different ways of communication in biology but this is really a new kind of signaling between cells that we're trying to understand," said Arnold Mathijssen, a postdoctoral scholar in the Prakash lab and lead author of the paper. "It's possible this is more universal than we've described so far and is a way many different kinds of organisms communicate."

From benches to black holes

The Prakash lab gathers wild samples of various tiny organisms from an area they call Peggy's Bench - so named for a nearby memorial bench - and they've been coming here for years, often a couple times a week. Mixed salt and fresh waters, changing tides and bird migrations make the marsh a potential biodiversity hot spot. Although, Prakash knew none of that when he first visited.

"Lake Lagunita had dried out and I was looking for a new place to sample," recalled Prakash, referring to a small seasonal lake on Stanford campus. "I looked in the GPS map on my phone and I saw this blue spot. I didn't know anything about it in the beginning, but it was worth a try."

Back in the lab, the group studied wild samples of Spirostomum while also growing their own cultures of Spirostomum ambiguum, and began a deep dive into details of this ultra-fast contraction. Using high-speed imaging, they found it happens in 5 milliseconds - the human eye takes 100-400 milliseconds to blink - and that the cell endures about 14 times the force of gravity in the process. As it shrinks, pouches of toxin break off from the cell's edges and release their contents into the surrounding fluid.

During one late night in the lab, the researchers also noticed that, when in clumps, the cells seemed to all contract at the same time.

"We wondered, 'How can cells that are almost centimeters away from each other synchronize to do something almost simultaneously?'" said Saad Bhamla, a former postdoctoral fellow in the Prakash lab who is now an assistant professor at Georgia Tech.

The researchers solved this mystery by applying insights from separate research being conducted by Deepak Krishnamurthy, another graduate student in the Prakash lab, on how an individual cell can sense the movement of water around it. Once they observed the flow fields around Spirostomum, it became clear that they were communicating via hydrodynamic flows.

"The first cell contracts and generates a flow, which triggers the second and that one triggers the third. So, you get this propagating trigger wave that passes through the whole colony," described Mathijssen. "These are big, long-range vortex flows and the velocities of the communication rise up to meters per second - even though each cell is only 1 to 4 millimeters long."

Mathijssen figured out what triggers the first cell to contract through an experiment that Prakash and Krishnamurthy had already built for Krishnamurthy's research. By sucking liquid ever so carefully out of a small hole in a pair of slides containing S. ambiguum, Mathijssen mimicked the eating action of its predators. The closer to the hole the cell moved, the more one end of its body was stretched relative to the other - as happens when an object approaches a black hole. With this simple and relatively large-scale experiment, researchers determined that a specific amount of bodily tension likely causes the opening or closing of tension gated ion channels within S. ambiguum, making it contract.

Where the wild things are

The Prakash lab and Bhamla lab continue to work on S. ambiguum to learn more about how, when and why these cells contract. They also want to know whether the hydrodynamic communication they've discovered is used by other organisms, because in nature both generating and sensing flows is essential for survival. As part of this research and other work, the Prakash lab has been regularly returning to Peggy's Bench.

"Even though this spot was an accidental discovery for me, we're working on several projects in the lab that have been inspired by what we've collected right here," said Prakash, while standing at the edge of the marsh. "This work is just one example of many hidden gems we can find when we step outside the lab - and literally anyone with simple frugal tools, like Foldscope, can uncover and start exploring."

In the near future, Prakash is planning an extensive biodiversity survey in the marsh where they collect Spirostomum, which would include setting up a microscope-based live feed video of their subjects' watery world and bringing undergraduate students to explore this swampy field.

NUST MISIS scientists together with the colleagues from P.N. Lebedev Physical Institute of the Russian Academy of Sciences of the Russian Academy of Sciences, Skobeltsyn Institute of Nuclear Physics Lomonosov Moscow State University and Dagestan State University have published the first results of a "scan" obtained by the method of muon radiography of the underground space in the Derbent fortress of Naryn-Kala. The preliminary conclusion of the scientists -- the hypothesis of archaeologists about the use of the building as a Christian temple is most likely to be true. If this theory is confirmed, this building is one of the oldest churches in the world.

The 12-meter building is almost completely hidden under the ground, only a fragment of a half-destroyed dome is visible above the surface. This building in the northwestern part of the Naryn-Kala fortress in Derbent dates back to about 300 A.D. To date, the issue of the function of the building has not been resolved: a reservoir, a Christian temple, or a Zoroastrian fire temple. If this is really a Christian temple, then we can talk about the oldest in the country and one of the oldest in the world Christian churches, which was covered with soil by Arabs after the capture of Derbent in about 700 A.D.

It is not possible for archaeologists to come to a consensus because the excavations of the temple, used for two centuries as a reservoir, can destroy a UNESCO cultural heritage site. Therefore, to study the premises, scientists used the method of muon radiography, placing several innovative detectors with a nuclear emulsion inside a buried building at a depth of 10 meters from the surface of the earth. The research lasted from May to September 2018, the first data obtained confirmed the effectiveness of the method for the study of this specific object.

The purpose of the experiment was to find out the possibility of studying the selected archaeological object using muon radiography, determine the optimal exposure, the number, size, and location of the detectors, get the first images of the object using nuclear emulsions. The results obtained from the muon detector made it possible to confirm the reliability of the study of the building using muon radiography (which was not obvious given the similar density of soil around the building and the shell-limestone walls) and suggest a plan for a full-scale experiment to identify the contours of the building as a whole.

In addition, already in the first test experiment, physicists "saw" an unusual distribution of muon fluxes in the western wing of the building, which may be related to the architectural features, indistinguishable by fragments of walls located above ground. The construction, built of local shell-limestone, is about 11 meters high and extends 15 meters from south to north and 13.4 meters from west to east. Segments (arm) of a cruciform design have a width of about 5 meters, three arms of a length of about 4.2 m, and the fourth (northern) -- more than 6 meters. The brackets are covered with vaults, and a dome wire frame with a diameter of 5 meters is located above the central part.

In a number of historical and reference sources, this construction is referred to as an underground water tank, as it was in the XVII -- XVIII centuries. However, the first experiment gave reason to doubt this hypothesis. The main reasons for the interpretation of this building as the original religious building were the unusual for reservoirs, but common for early churches and fire temples cross shape of the building and its orientation to the sides of the world.

"It seems very strange to me to interpret this building as a water tank. In the same fortress of Naryn-Kala, there is an equal underground structure of 10 meters depth, and it really is a tank. This is just a rectangular building. The unusual building, in which we have put our detectors, has the shape of a cross, oriented strictly to the sides of the world, one side is 2 meters longer than the others. As the archaeologists who began excavations say, during construction, the building was entirely on the surface and it stands on the highest point of the Naryn-Kala. What is the sense to put the tank on the surface, and even on the highest mountain? It is strange. Currently, there are more questions than answers," says the head of the scientific group, Ph.D. in Physics and Mathematics, NUST MISIS leading expert Natalia Polukhina.

As the authors of the study emphasize, the characteristics of the probing radiation at this object require the subsequent irradiation of muon detectors in the area under study, and therefore, the continuation of the experiments. The installation of detectors on the western slope of the fortress outside the walls of the building will be especially effective in order to obtain its full-size underground image. The main result of the next stage of the experiments will be the final three-dimensional tomogram of the underground building, which will help to define the purpose of this unusual facility.

Bottom Line: The 1978 novel "The House of God" is a fictional account of the internship experience of Samuel Shem, the pen name of Stephen Bergman, at Beth Israel Hospital in 1973-1974. Funny, angry, honest, and absurd, the book spotlighted the injustices of medical training and the patient care of that era and was pilloried by establishment medicine for years after publication for its razor-sharp version of the truth. This short documentary, produced on the 40th anniversary of the novel's debut, details the book's origins and the people and events that inspired its stories.

What The Study Did: This randomized clinical trial of 143 men tested a short-term treatment for internet and computer game addiction.

Authors: Klaus Wölfling, Ph.D., of the University Medical Center of the Johannes Gutenberg-University Mainz in Germany, is the corresponding author

(doi:10.1001/jamapsychiatry.2019.1676)

Editor's Note: The article contains funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

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Media advisory: The full study and podcast are linked to this news release.

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What The Study Did: This observational study of nearly 5,700 hospital employees who used the workplace cafeteria reports on whether food placement and traffic light labeling (green for healthy, yellow for less healthy and red for least healthy) was associated with a reduction in calories in the food purchased by employees.

Authors: Anne N. Thorndike, M.D., M.P.H., of the Massachusetts General Hospital in Boston, is the corresponding author.

(doi:10.1001/jamanetworkopen.2019.6789)

Editor's Note: The article includes conflict of interest and funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

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About JAMA Network Open: JAMA Network Open is the new online-only open access general medical journal from the JAMA Network. Every Wednesday and Friday, the journal publishes peer-reviewed clinical research and commentary in more than 40 medical and health subject areas. Every article is free online from the day of publication.

A newly described form of stress called chromatin architectural defect, or chromatin stress, triggers in cells a response that leads to a longer life. Researchers at Baylor College of Medicine and the Houston Methodist Research Institute report in the journal Science Advances that moderate chromatin stress levels set off a stress response in yeast, the tiny laboratory worm C. elegans, the fruit fly and mouse embryonic stem cells, and in yeast and C. elegans the response promotes longevity. The findings suggest that chromatin stress response and the longevity it mediates may be conserved in other organisms, opening the possibility of new ways to intervene in human aging and promote longevity.

"Chromatin stress refers to disruptions in the way DNA is packed within the nucleus of the cell," said corresponding author Dr. Weiwei Dang, assistant professor of molecular and human genetics and the Huffington Center on Aging and member of the Dan L Duncan Comprehensive Cancer Center at Baylor. "One of the factors that influences chromatin structure is proteins called histones."

In the nucleus of cells, DNA wraps itself around histone proteins forming a 'beads-on-a-string' structure called chromatin. Other proteins bind along chromatin and the structure folds further into more complicated configurations. Everything involving DNA would have to deal with this chromatin structure, Dang explained. For example, when a particular gene is expressed, certain enzymes interact with the chromatin structure to negotiate access to the gene and translate it into proteins. When chromatin stress happens, disruption of the chromatin structure can lead to unwanted changes in gene expression, such as expression of genes when they are not supposed to or lack of gene expression when it should occur.

In this study, Dang and his colleagues worked in the lab with the yeast Saccharomyces cerevisiae to investigate how the dosage of histone genes would affect longevity.

They expected that yeast genetically engineered to carry fewer copies of certain histone genes than normal or control yeast would have chromatin changes that would result in the yeast living less than controls.

"Unexpectedly, we found that yeast with fewer copies of histone genes lived longer than the controls," said first author Ruofan Yu, research assistant in molecular and human genetics in the Dang lab.

Yeast with a moderately low dose of histone genes showed a moderate reduction of histone gene expression and significant chromatin stress. Their response to chromatin disruption was changes in the activation of a number of genes that eventually promoted longevity.

In previous work Dang and colleagues had shown that in aging cells chromatin structure progressively falls apart. Histone alterations, such as a decrease in their protein levels, are a characteristic of the aging process, but the researchers showed that if they compensated for this age-related decrease in histone levels by overexpressing certain histone genes they extended the lifespan of aging yeast cells. In this study they discovered that moderately reducing the number of copies of histone genes in young yeast also promoted longevity.

"We have identified a previously unrecognized and unexpected form of stress that triggers a response that benefits the organism," Yu said. "The mechanism underlying the chromatin stress response generated by moderate reduction of histone dosage is different from the one triggered by histone overexpression we had previously described, as shown by their different profiles of protein expression responses."

Dang, Yu and their colleagues found that chromatin stress also occurs in other organisms such as the laboratory worm C. elegans, the fruit fly and mouse embryonic stem cells, and in yeast and C. elegans the chromatin stress response promotes longevity.

"Our findings suggest that the chromatin stress response may also be present in other organisms. If present in humans, it would offer new possibilities to intervene in the aging process," Dang said.

Childhood obesity has reached epidemic proportions, affecting children's health and wellbeing and leading to obesity, heart disease, diabetes and cancer later in life. The number of children with obesity continues to rise globally, particularly for children living in poverty.

Leeds, England's third largest city, has bucked the global trend and seen a significant fall in obesity, according to a recent study published in the journal Pediatric Obesity by Prof. Mary Rudolf, Head of the Department of Population Health at the Azrieli Faculty of Medicine of Bar-Ilan University. Furthermore, the largest decrease in obesity occurred among the city's poorest and most disadvantaged children.

Prof. Rudolf conducted her research on the growth measurements of children in England from 2009 to 2017. She found that, unlike England as a whole and comparable cities, the numbers of obese children in Leeds fell by 6.4%. "We used nationally collected data in our study, so it was very obvious that something different was happening in Leeds," she says.

Next week Prof. Rudolf will present the findings of her study to the Food and Health Forum at the British Parliament. This cross-party forum meets regularly and advises Parliament on how the health of the nation can be improved.

The decline in obesity coincided with a strategy introduced by the city in 2009 which aimed to tackle the obesity epidemic through focusing on families with preschool children in the poorest areas of Leeds. At its heart was HENRY - Health Exercise Nutrition for the Really Young -- an intervention developed by Prof. Rudolf and colleagues for children under the age of five. HENRY, which has been widely adopted in the UK over the past ten years, offers a range of programs and trains health and community practitioners to work in innovative ways to help parents provide their families with a healthier start in life.

In Israel, where Prof. Rudolf is now based, one in five children are obese or overweight by the time they start first grade, rising to one in three by seventh grade. In an effort to address the problem, the Israel Ministry of Health brought HENRY to Israel in 2014. A team of four professionals was sent to Oxford to learn the approach, and subsequently trained nurses, dieticians and social workers who worked directly with families that participated in the program, and in particular specialists in early childhood. Training was also provided to parents participating in the program. HENRY has been translated into Hebrew and Arabic and has been piloted in a variety of disadvantaged towns, such as Safed, Kiryat Yam, Daliyat al-Karmel, Ussefiya, Baqa al-Gharbiyye, Ramle, Jerusalem, Yeruham, and Dimona.

Known in Israel as Efshari bari mishpachti ("A Healthy Family is Possible") the program has been tailored to families with children under the age of three, and is under evaluation by Prof. Orna Baron-Epel, of the University of Haifa. Results show that group work with parents was particularly successful in changing family lifestyle. Plans are now being considered to extend the program to the nation's kupot holim (healthcare service providers).

Prof. Rudolf says it remains to be seen whether Israeli cities can be as successful as Leeds in tackling the problem of child obesity, but when society invests in early childhood, it gets the best returns for doing so. "If we are going to make a difference we must start at a young age, before the onset of obesity. This can reduce the impact of poor lifestyle later on," concludes Rudolf, who was born in London and worked in Leeds before moving to Israel in 2012.

Antibodies are the biomolecules our immune systems deploy to find, tag, and destroy invading pathogens. They work by binding to specific targets, called epitopes, on the surfaces of antigens - like locks to keys.

For many decades, scientists have cleverly exploited this selective tagging mechanism in natural antibodies to engineer antibody-based probes that let them purify and study different types of proteins within cells. One tried and true technique, epitope tagging, involves fusing an epitope to a protein of interest and using fluorescently labeled antibodies to make those proteins visible - but only in fixed, dead cells.

A useful complement to the green fluorescent protein

Now, a cross-disciplinary team of researchers from Tokyo Tech and CSU have added a new tool to the arsenal of antibody-based probes, but with a powerful distinction: their genetically encoded probe works in living cells. The work, led by CSU Monfort Professor Tim Stasevich and Tokyo Tech Professor Hiroshi Kimura, was published on July 3rd, 2019 in the journal Nature Communications.

They engineered the frankenbody as a hybrid of single-chain variable fragments that retains the stability of the scaffold and the specificity of the grafted complementarity determining regions (Fig.1). "We're interested in intracellular antibodies because you can use them as imaging reagents in a live cell," said Stasevich, an assistant professor in the Department of Biochemistry and Molecular Biology at CSU. "You don't need a tag, like a green fluorescent protein (GFP), because instead you have this fluorescent antibody that will bind to your protein that you want to visualize."

The new probe would be a useful complement to the GFP, a widespread biochemistry tool and Nobel prize winner that involves genetically fusing a light-up green tag to a protein of interest. However, the GFP is limited by its relatively large size and the time it takes to fluoresce; with the new probe, the tag is smaller and becomes fluorescent faster, so the "birth" of a protein of interest can be captured in real time.

With the goal of making their tool immediately useful, the scientists designed their probe to work with the classic HA tag. HA is a widely used small linear epitope tag that's derived from a portion of the human influenza virus protein hemagglutinin (Fig.2).

"For the longest time, people have been looking at HA-tagged proteins in fixed, dead cells," Stasevich explained. "Now we can image the dynamics of those proteins in live cells."

A limitless probe

The possibilities of how scientists may use the new probe are limitless. Stasevich's lab is particularly interested in studying RNA translation, and they plan to use their new system to more easily design new RNA imaging experiments.

The frankenbody is genetically encoded on a plasmid that can be easily distributed to other labs. This is in contrast to traditional antibodies, which can cost a lab several hundreds of dollars per order and suffer from lot-to-lot variability. The new probe from Stasevich's team therefore provides a lost-cost solution for protein and RNA translation imaging.

In the paper, the scientists demonstrated applications, including single-protein tracking, single-RNA translation imaging, and amplified fluorescence imaging in zebrafish embryos, all of which pose challenges for more traditional fluorescent protein tags.

The work strengthens ties between CSU and the Tokyo Tech. "We have several new imaging reagents in the works that build off of this success, so I see great things ahead," said Stasevich.

Scientists have developed an animal model that may provide a path toward improving the diagnosis and treatment of the devastating brain disease chronicled in the bestselling autobiography "Brain on Fire." The book, along with a 2017 movie by the same name, traces newspaper reporter Susannah Cahalan's harrowing descent into the throes of the disease.

The autoimmune disease is triggered by an attack on one of the key neurotransmitter receptors in the brain, the NMDA receptor. The disease is characterized by intellectual changes, severe memory loss, seizures, and even death. The study, published today in the journal Science Translational Medicine, reports an original animal model for this puzzling disease.

Scientists with the Vollum Institute at OHSU in Portland, Oregon, say the discovery clears the way for developing a near-atomic image of how the immune system attacks the NMDA receptor. With that information, researchers could specifically block the damaging autoimmune reaction and test new therapeutic strategies using their newly developed model for the disease in mice.

"The goal is a cure that is specific to this disease," said senior author Gary Westbrook, M.D., senior scientist in the Vollum Institute.

Brian Jones, a doctoral student in OHSU's neuroscience graduate program, and Westbrook collaborated with scientists in the lab of co-author Eric Gouaux, Ph.D. In 2014, Gouaux, also a senior scientist in the Vollum and investigator with the Howard Hughes Medical Institute, published an unprecedented three-dimensional view of the NMDA receptor in the journal Nature.

NMDA receptors are present in almost every neuron in the brain. Crucial for learning and memory, these receptors are required for the formation of new memories in the hippocampus of humans and animals, and have been implicated in several neurological and psychiatric conditions including Alzheimer's disease, schizophrenia and depression.

The disease in people occurs unexpectedly when antibodies produced by the body's own immune system attack NMDA receptors in the brain.

"It's a human disease that we don't know enough about," Westbrook said.

Westbrook, also the Dixon professor of neurology in the OHSU School of Medicine, said the animal model will be especially useful in determining the distinct site or sites on the NMDA receptor that trigger disease.

"If we know the exact site, one could potentially intervene early to abort the progression of the disease," Westbrook said.

Westbrook's collaboration with Gouaux's team started three years ago when they developed a strategy to model the disease by active immunization of mice with the fully formed NMDA receptor. Almost 90% of mice developed signs that mimicked the human disease.

According to the research team, the development of an animal model is important because there are few samples of brain tissue from people who have developed the disease. The animal model provides a unique opportunity to recognize early signs of the disease, and to develop therapeutic approaches that could precisely target the site on the receptor, known as an epitope, that is attacked by the immune system.

Sea urchins have gotten a bad rap on the Pacific coast. The spiky sea creatures can mow down entire swaths of kelp forest, leaving behind rocky urchin barrens. An article in the New York Times went so far as to call them "cockroaches of the ocean." But new research suggests that urchins play a more complex role in their ecosystems than previously believed.

A team led by Christie Yorke, a postdoctoral scholar at UC Santa Barbara's Marine Science Institute, studied how urchins might function to break up tough kelp into more manageable pieces that can feed other scavengers, also known as detritivores, living on the kelp forest floor. The paper, published in the Proceedings of the Royal Society B, is the first to look at sea urchins' role as shredders in the kelp forest ecosystem.

Urchins can have an outsized effect on kelp forests, especially when their predators aren't around to keep their population in check, Yorke explained. Overhunting of the sea otter, one of urchins' most significant predators, has allowed some urchin populations to clear cut vast tracts of kelp forest, drastically reducing the productivity and biodiversity of sites they've munched through. Some groups have even taken to indiscriminately smashing urchins to stem this scourge.

Nevertheless, urchins may be crucial to the health of the kelp forest ecosystem. Giant kelp is highly productive, growing up to 18 inches per day under ideal conditions. But a significant amount of this material gets transported away from the ecosystem, washing up on beaches, getting swept out to the open ocean or drifting into the deep sea. Kelp is also rather unpalatable compared to single-celled phytoplankton.

Despite its incredible growth rate and availability, giant kelp is not the first choice for many animals, as it is tough to digest.

Yorke and her colleagues were curious whether anything might be able to retain this food source within the kelp forest. "We know that kelp affects animals by providing habitat for fish and other species, but does it actually feed any of these animals?" said Bob Miller, a research biologist at the Marine Science Institute and one of the paper's coauthors.

Scientists have hypothesized that kelp sheds small particles that could be a food source. But the team's previous work found that kelp didn't appear to be nourishing the filter feeders in this way. The activity of sloppy sea urchins offered a promising alternative pathway for funneling nutrients from kelp to the ecosystem's detritivore.

Urchins as Marine Shredders

To test their hypothesis, Yorke set up several tanks with a number of detritivore from several species, along with some labeled kelp. Half of the tanks also got sea urchins.

To label the kelp, the team spiked it with rare forms of carbon and nitrogen by letting the algae photosynthesize in seawater enriched with these isotopes for three days, allowing them to trace the extent to which the tank residents ate the kelp. After 28 days, the researchers compared the isotope measurements for the specimens after the experiment to baselines they had established beforehand.

"We found that a whole host of detritivores can take advantage of kelp as long as urchins are there to process it for them, whereas otherwise they can't," said Miller. Indeed, only one species, a type of brittle star, ate a significant amount of kelp in the absence of sea urchins.

"Even then, the brittle stars used much more kelp when the urchins were present," added Yorke.

Urchins excel in their role of processing kelp for other detritivores. They are remarkably messy eaters, scattering all sorts of bits and pieces as they chow down on giant kelp. What's more, sea urchins digest remarkably little of what they actually eat. Meanwhile, their guts contain a rich assortment of microbes, some of which can pull nitrogen from the seawater itself, enriching the urchin's waste. Some studies have shown that urchin feces can be more nutritious than fresh algae, said Yorke.

"Essentially, they create a kelp smoothie for the reef," Miller said.

Yorke agreed and stated that "without the urchins there, it's possible that this kelp would just get washed out of the kelp forest by the current and be unavailable altogether."

A Broader Perspective

Extrapolating from small experiments in the lab to the processes out in the environment can be difficult, so the team used historical data collected by the Santa Barbara Coastal Long Term Ecological Research project (SBC LTER) to place their results in context. SBC is one of several long-term research sites throughout the country funded by the National Science foundation. It is one of two overseen by UC Santa Barbara.

The scientists looked at 11 years of relevant data, including the amount of kelp litter over time, as well as sea urchin abundance and biomass. Their analysis suggested that the amount of kelp that urchins shred and process could be a significant portion of the resources available to the creatures that live on the seafloor.

"A lot of times urchins are portrayed as grazers," said Yorke, "but that's actually an uncommon condition. Most of the time the urchins are just sedentary detritivores that wait for leaf litter from the kelp to fall and drift past them. They capture this detritus and consume it.

"Urchins switch from this sedentary behavior to active grazing if drift kelp becomes limited," she explained. This can happen for a number of reasons. If urchins become super-abundant there may not be enough drift kelp to sustain them. Alternatively, oceanographic conditions like El Niño can impact kelp productivity.

In this way, urchins are more like grasshoppers. Under normal conditions, grasshoppers are a healthy part of their ecosystem. But in certain circumstances, some species will swarm, becoming a plague of locusts.

"Urchins are generally cast as the villain in the kelp forest," said Miller, "but this study shows that they can play an important role as an intermediary in the food web."

"We should not go around and vilify or smash sea urchins before we understand their role in the ecosystem better," he added. "They're not necessarily always the bad guy they're made out to be."

Researchers at the University of Helsinki have discovered how regenerative capacity of intestinal epithelium declines when we age. Targeting of an enzyme that inhibits stem cell maintaining signaling rejuvenates the regenerative potential of an aged intestine. This finding may open ways to alleviate age-related gastrointestinal problems, reduce side-effects of cancer treatments, and reduce healthcare costs in the ageing society by promoting recovery.

"This study highlights the importance of cellular interactions. Alterations inside one cell resulted in secretion of an aging factor that can be targeted with drugs, providing multiple attractive points for interventions", says the principal investigator Pekka Katajisto, Associate Professor at the University of Helsinki and Karolinska Institutet.

The age-induced reduction in tissue renewal makes dosing of many common drugs challenging. Targeting of inhibitor called Notum may provide a new way to increase the therapeutic window and to promote recovery in societies with the aging population. Researchers believe that in addition to direct targeting of Notum, lifestyle factors such as diet may also provide means to reduce Notum, and thus improve tissue renewal and repair.

Using organoid culture methods, researchers understood that poor function of tissue repairing stem cells in old intestine was due to aberrant signals from the neighboring cells, known as Paneth cells.

"Modern techniques allowed us to examine tissue maintenance at a single cell level, and revealed which cell types contribute to the decline in tissue function. We were surprised to find that even young stem cells lost their capacity to renew tissue when placed next to old neighbors", says the lead author, PhD candidate Nalle Pentinmikko from the University of Helsinki.

Normally intestinal epithelium is renewed by stem cells that rely on activity of Wnt-signaling pathway. Surrounding cells produce molecules that activate this pathway. The study shows that during ageing, Paneth cells begin to express a secreted Wnt-inhibitor called Notum. Notum enzymatically inactivates Wnt-ligands in the stem cell niche, decreasing regenerative potential of intestinal stem cells. However, pharmacologic inhibition of Notum rejuvenated stem cell activity and promoted the recovery of old animals after treatment with a commonly used chemotherapeutic drug with severe side-effects in the gut.

A study led by scientists of the Universitat Autònoma de Barcelona (UAB) and the National Centre for Genomic Analysis (CNAG-CRG) from the Centre for Genomic Regulation (CRG) reveals the three-dimensional genomic structure of male germ cells and how this structure determines their function.

The study, published in the journal Cell Reports, represents a significant advance in our understanding of how the dynamics of insulator proteins and transcriptional activity are coupled during the 3D genome re-organisation that takes place during the formation of male germ cells.

The code of life (genome) is not just a linear sequence of letters, but is also folded (compartmentalised) into a specifically tailored chromatin structure within the cell nuclei. This three-dimensional genomic structure is fundamental, given that it determines which genes "turn on" and which are "turned off" in each cell types.

A new study led by scientists from the UAB and the CNAG-CRG and published in Cell Reports reveals the three-dimensional genomic structure of male germ cells. The study, carried out on mice, shows that this structure is extremely dynamic during the formation of germ cells (gamete precursor cells). Moreover, the study revealed a fine-tuned balance between chromatin remodelling, architectural proteins such as cohesins and gene expression during this process.

All sexually reproducing organisms form haploid gametes (oocytes and sperm) - each cell type carrying only one copy of each chromosome - through two consecutive cell divisions preceded by one round of genome replication. This process is known as meiosis and implies that the genome must be packaged and unpackaged in a precise and highly regulated manner.

"Our work shows the dynamics of chromatin remodelling during the formation of male gametes, by comparing changes in chromatin folding and gene transcription at different moments throughout male meiosis", says coordinator of the study Aurora Ruiz-Herrera, researcher at the Department of Cell Biology, Physiology and Immunology of the Institute of Biotechnology and Biomedicine (IBB) at the UAB, where she leads the research group in Animal Genomics. "We have thus demonstrated the existence of different degrees of genome folding and how these different levels of genome organization are related to structural proteins such as cohesins and gene expression. The results will pave the way for new investigations into the molecular mechanisms regulating these changes."

"This study has been possible only thanks to the combination of complementary techniques in biology such as molecular genetics, microscope imaging and computer simulations. It truly is a multidisciplinary project", explains Marc A. Marti-Renom, ICREA researcher and head of the Structural Genomics Group at the CNAG-CRG and co-leader of the study.

The project represents a significant advance in the study of the mechanisms generating and regulating the 3D structure and function of the genome during the formation of gametes. Determining these mechanisms is fundamental, given that the deregulation of this process can lead to diseases such as infertility and chromosome alterations like trisomy 21.

According to scientists, the research also represents an example of the importance of synergy among specialists from different fields such as molecular and cell biology, genomics and bioinformatics in advancing in our knowledge of the regulation and structure of the genome. Participating in the study were seven research teams, including the UAB, the CNAG-CRG, the CSIC-University of Salamanca, the Sequentia Biotech and the University of New South Wales in Sydney.