Monkey caloric restriction study shows big benefit; contradicts earlier study

The latest results from a 25-year study of diet and aging in monkeys shows a significant reduction in mortality and in age-associated diseases among those with calorie-restricted diets. The study, begun at the University of Wisconsin-Madison in 1989, is one of two ongoing, long-term U.S. efforts to examine the effects of a reduced-calorie diet on nonhuman primates.The study of 76 rhesus monkeys, reported Monday in Nature Communications, was performed at the Wisconsin National Primate Research Center in Madison. When they were 7 to 14 years of age, the monkeys began eating a diet reduced in calories by 30 percent. The comparison monkeys, which ate as much as they wanted, had an increased risk of disease 2.9 times that of the calorie-restricted group, and a threefold increased risk of death.”We think our study is important because it means the biology we have seen in lower organisms is germane to primates,” says Richard Weindruch, a professor of medicine at the School of Medicine and Public Health, and one of the founders of the UW study. “We continue to believe that mechanisms that combat aging in caloric restriction will offer a lead into drugs or other treatments to slow the onset of disease and death.”Restricting the intake of calories while continuing to supply essential nutrients extends the lifespan of flies, yeast and rodents by as much as 40 percent. Scientists have long wanted to understand the mechanisms for caloric restriction. “We study caloric restriction because it has such a robust effect on aging and the incidence and timing of age related disease,” says corresponding author Rozalyn Anderson, an assistant professor of geriatrics. “Already, people are studying drugs that affect the mechanisms that are active in caloric restriction. There is enormous private-sector interest in some of these drugs.”Still, the effects of caloric restriction on primates have been debated. …

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Sleep boosts production of brain support cells

Sep. 3, 2013 — Sleep increases the reproduction of the cells that go on to form the insulating material on nerve cell projections in the brain and spinal cord known as myelin, according to an animal study published in the September 4 issue of The Journal of Neuroscience. The findings could one day lead scientists to new insights about sleep’s role in brain repair and growth.Scientists have known for years that many genes are turned on during sleep and off during periods of wakefulness. However, it was unclear how sleep affects specific cells types, such as oligodendrocytes, which make myelin in the healthy brain and in response to injury. Much like the insulation around an electrical wire, myelin allows electrical impulses to move rapidly from one cell to the next.In the current study, Chiara Cirelli, MD, PhD, and colleagues at the University of Wisconsin, Madison, measured gene activity in oligodendrocytes from mice that slept or were forced to stay awake. The group found that genes promoting myelin formation were turned on during sleep. In contrast, the genes implicated in cell death and the cellular stress response were turned on when the animals stayed awake.”These findings hint at how sleep or lack of sleep might repair or damage the brain,” said Mehdi Tafti, PhD, who studies sleep at the University of Lausanne in Switzerland and was not involved with this study.Additional analysis revealed that the reproduction of oligodendrocyte precursor cells (OPCs) — cells that become oligodendrocytes — doubles during sleep, particularly during rapid eye movement (REM), which is associated with dreaming.”For a long time, sleep researchers focused on how the activity of nerve cells differs when animals are awake versus when they are asleep,” Cirelli said. “Now it is clear that the way other supporting cells in the nervous system operate also changes significantly depending on whether the animal is asleep or awake.”Additionally, Cirelli speculated the findings suggest that extreme and/or chronic sleep loss could possibly aggravate some symptoms of multiple sclerosis (MS), a disease that damages myelin. Cirelli noted that future experiments may examine whether or not an association between sleep patterns and severity of MS symptoms exists.This research was funded by the University of Wisconsin-Madison Department of Psychiatry.

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Unprecedented control of genome editing in flies promises insight into human development, disease

Aug. 23, 2013 — In an era of widespread genetic sequencing, the ability to edit and alter an organism’s DNA is a powerful way to explore the information within and how it guides biological function.A paper from the University of Wisconsin-Madison in the August issue of the journal Genetics takes genome editing to a new level in fruit flies, demonstrating a remarkable level of fine control and, importantly, the transmission of those engineered genetic changes across generations.Both features are key for driving the utility and spread of an approach that promises to give researchers new insights into the basic workings of biological systems, including embryonic development, nervous system function, and the understanding of human disease.”Genome engineering allows you to change gene function in a very targeted way, so you can probe function at a level of detail” that wasn’t previously possible, says Melissa Harrison, an assistant professor of biomolecular chemistry in the UW-Madison School of Medicine and Public Health and one of the three senior authors of the new study.Disrupting individual genes has long been used as a way to study their roles in biological function and disease. The new approach, based on molecules that drive a type of bacterial immune response, provides a technical advance that allows scientists to readily engineer genetic sequences in very detailed ways, including adding or removing short bits of DNA in chosen locations, introducing specific mutations, adding trackable tags, or changing the sequences that regulate when or where a gene is active.The approach used in the new study, called the CRISPR RNA/Cas9 system, has developed unusually fast. First reported just one year ago by scientists at the Howard Hughes Medical Institute and University of California, Berkeley, it has already been applied to most traditional biological model systems, including yeast, zebrafish, mice, the nematode C. elegans, and human cells. The Wisconsin paper was the first to describe it in fruit flies and to show that the resulting genetic changes could be passed from one generation to the next.”There was a need in the community to have a technique that you could use to generate targeted mutations,” says Jill Wildonger, a UW-Madison assistant professor of biochemistry and another senior author of the paper. “The need was there and this was the technical advance that everyone had been waiting for.””The reason this has progressed so quickly is that many researchers — us included — were working on other, more complicated, approaches to do exactly the same thing when this came out,” adds genetics assistant professor Kate O’Connor-Giles, the third senior author. “This is invaluable for anyone wanting to study gene function in any organism and it is also likely to be transferable to the clinical realm and gene therapy.”The CRISPR RNA/Cas9 system directs a DNA-clipping enzyme called Cas9 to snip the DNA at a targeted sequence. This cut then stimulates the cell’s existing DNA repair machinery to fill in the break while integrating the desired genetic tweaks. The process can be tailored to edit down to the level of a single base pair — the rough equivalent of changing a single letter in a document with a word processor.The broad applicability of the system is aided by a relatively simple design that can be customized through creation of a short RNA sequence to target a specific sequence in the genome to generate the desired changes. …

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Eavesdropping plants prepare to be attacked

Aug. 7, 2013 — In a world full of hungry predators, prey animals must be constantly vigilant to avoid getting eaten. But plants face a particular challenge when it comes to defending themselves.”One of the things that makes plants so ecologically interesting is that they can’t run away,” says John Orrock, a zoology professor at the University of Wisconsin-Madison. “You can’t run, you can’t necessarily hide, so what can you do? Some plants make themselves less tasty.”Some do this either by boosting their production of toxic or unpleasant-tasting chemicals (think cyanide, sulfurous compounds, or acids) or through building physical defenses such as thorns or tougher leaves.But, he adds, “Defense is thought to come at a cost. If you’re investing in chemical defenses, that’s energy that you could be putting into growth or reproduction instead.”To balance those costs with survival, it may behoove a plant to be able to assess when danger is nigh and defenses are truly necessary. Previous research has shown that plants can induce defenses against herbivores in response to airborne signals from wounded neighbors.But cues from damaged neighbors may not always be useful, especially for the first plant to be attacked, Orrock says. Instead he asked whether plants — here, black mustard, a common roadside weed — can use other types of cues to anticipate a threat.In a presentation Aug. 6 at the 2013 Ecological Society of America Annual Meeting in Minneapolis, he and co-author Simon Gilroy, a UW-Madison botany professor, reported that the plants can eavesdrop on herbivore cues to mount a defensive response even before any plant is attacked.Slugs and snails are generalist herbivores that love to munch on mustard plants and can’t help but leave evidence of their presence — a trail of slime, or mucus. Where there’s slime, there’s a snail. …

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New catalyst could cut cost of making hydrogen fuel

July 2, 2013 — A discovery at the University of Wisconsin-Madison may represent a significant advance in the quest to create a “hydrogen economy” that would use this abundant element to store and transfer energy.Theoretically, hydrogen is the ultimate non-carbon, non-polluting fuel for storing intermittent energy from the wind or sun. When burned for energy, hydrogen produces water but no carbon dioxide. Practically speaking, producing hydrogen from water, and then storing and using the gas, have proven difficult.The new study, now published online at the Journal of the American Chemical Society, introduces a new catalyst structure that can facilitate the use of electricity to produce hydrogen gas from water.Significantly, the catalyst avoids the rare, expensive metal platinum that is normally required for this reaction. (Catalysts speed up chemical reactions without themselves being consumed.)The material under study, molybdenum disulfide, contains two common elements, notes Mark Lukowski, a Ph.D. student working with associate professor Song Jin in the UW-Madison chemistry department. “Most people have tried to reduce the cost of the catalyst by making small particles that use less platinum, but here we got rid of the platinum altogether and still got reasonably high performance.”The research group has produced milligram quantities of the catalyst, “but in principle you could scale this up,” says Lukowski. “Molybdenum disulfide is a commercially available product. To control purity and structure, we go through the trouble of synthesizing it from the bottom up, but you could buy it today.”To make the new material, Lukowski and Jin deposit nanostructures of molybdenum disulfide on a disk of graphite and then apply a lithium treatment to create a different structure with different properties.Just as carbon can form diamond for jewelry and graphite for writing, molybdenum disulfide can be a semiconductor or a metallic phase, depending on structure. When the compound is grown on the graphite, it is a semiconductor, but it becomes metallic after the lithium treatment. Lukowski and Jin discovered that the metallic phase has far greater catalytic properties.”Like graphite, which is made up of a stack of sheets that easily separate, molybdenum disulfide is made up of individual sheets that can come apart, and previous studies have shown that the catalytically active sites are located along the edges of the sheets,” says Lukowski.”The lithium treatment both causes the semiconducting-to-metallic phase change and separates the sheets, creating more edges. …

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Mapping the benefits of our ecosystems

July 1, 2013 — We rely on our physical environment for many things — clean water, land for crops or pastures, storm water absorption, and recreation, among others. Yet it has been challenging to figure out how to sustain the many benefits people obtain from nature — so-called “ecosystem services” — in any given landscape because an improvement in one may come at the cost of another.Two ecologists at the University of Wisconsin-Madison report this week (July 1) in the Proceedings of the National Academy of Sciences a novel approach to analyzing the production and location of 10 different ecosystem services across a landscape, opening the door to being able to identify factors governing their synergies and tradeoffs.Monica Turner, the Eugene P. Odum Professor of Zoology, and graduate student Jiangxiao Qiu mapped the production, distribution, and interactions of the services in three main categories: provisioning (providing resources like food, fiber, or fresh water), cultural (such as aesthetics and hunting), and regulating (including improving ground and surface water quality, handling floodwater, preventing erosion, and storing carbon). They focused on the Yahara River watershed, which covers much of central portion of Dane County and parts of Columbia and Rock Counties in southern Wisconsin and includes the chain of Madison lakes.”We found that the main ecosystem services are not independent of each other. They interact spatially in very complex ways,” says Qiu, lead author of the new study.Some of those interactions were not surprising — for example, higher levels of crop production were generally associated with poorer surface and ground water quality. However, two other sets of services showed positive associations: flood regulation, pasture and freshwater supply all went together, as did forest recreation, soil retention, carbon storage and surface water quality.”If you manage for one of these services, you can probably enhance others, as well,” says Turner. “It also means that you can’t take a narrow view of the landscape. You have to consider all of the things that it produces for us and recognize that we have to manage it very holistically.”Even in the expected tradeoff between crop production and water quality, the researchers found something unexpected.”There is a strong tradeoff between crop production and surface and groundwater quality,” Qiu says. “But despite this, there are still some locations that can be high for all three services — exceptions that can produce high crop yield and good water quality in general.”Preliminary analysis of these “win-win” areas suggests that factors like flat topography, a deep water table, less field runoff, soil with high water-holding capacity, more adjoining wetlands and proximity to streams with riparian vegetation may contribute to maintaining both crop production and good water quality.The results also show that nearly all of the land in the watershed provides a high level of at least one of the measured services but that they are not uniformly distributed. Most areas offer a high level of just one or two services. …

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Decline in snow cover spells trouble for many plants, animals

May 7, 2013 — For plants and animals forced to tough out harsh winter weather, the coverlet of snow that blankets the north country is a refuge, a stable beneath-the-snow habitat that gives essential respite from biting winds and subzero temperatures.

But in a warming world, winter and spring snow cover in the Northern Hemisphere is in decline, putting at risk many plants and animals that depend on the space beneath the snow to survive the blustery chill of winter.

In a report published May 2 in the journal Frontiers in Ecology and the Environment, a team of scientists from the University of Wisconsin-Madison describes the gradual decay of the Northern Hemisphere’s “subnivium,” the term scientists use to describe the seasonal microenvironment beneath the snow, a habitat where life from microbes to bears take full advantage of warmer temperatures, near constant humidity and the absence of wind.

“Underneath that homogenous blanket of snow is an incredibly stable refuge where the vast majority of organisms persist through the winter,” explains Jonathan Pauli, a UW-Madison professor of forest and wildlife ecology and a co-author of the new report. “The snow holds in heat radiating from the ground, plants photosynthesize, and it’s a haven for insects, reptiles, amphibians and many other organisms.”

Since 1970, snow cover in the Northern Hemisphere — the part of the world that contains the largest land masses affected by snow — has diminished by as much as 3.2 million square kilometers during the critical spring months of March and April. Maximum snow cover has shifted from February to January and spring melt has accelerated by almost two weeks, according to Pauli and his colleagues, Benjamin Zuckerberg and Warren Porter, also of UW-Madison, and John P. Whiteman of the University of Wyoming in Laramie.

“The winter ecology of Wisconsin and the Upper Midwest is changing,” says Zuckerberg, a UW-Madison professor of forest and wildlife ecology. “There is concern these winter ecosystems could change dramatically over the next several years.”

As is true for ecosystem changes anywhere, a decaying subnivium would have far-reaching consequences. Reptiles and amphibians, which can survive being frozen solid, are put at risk when temperatures fluctuate, bringing them prematurely out of their winter torpor only to be lashed by late spring storms or big drops in temperature. Insects also undergo phases of freeze tolerance and the migrating birds that depend on invertebrates as a food staple may find the cupboard bare when the protective snow cover goes missing.

“There are thresholds beyond which some organisms just won’t be able to make a living,” says Pauli. “The subnivium provides a stable environment, but it is also extremely delicate. Once that snow melts, things can change radically.”

For example, plants exposed directly to cold temperatures and more frequent freeze-thaw cycles can suffer tissue damage both below and above ground, resulting in higher plant mortality, delayed flowering and reduced biomass. Voles and shrews, two animals that thrive in networks of tunnels in the subnivium, would experience not only a loss of their snowy refuge, but also greater metabolic demands to cope with more frequent and severe exposure to the elements.

The greatest effects on the subnivium, according to Zuckerberg, will occur on the margins of the Earth’s terrestrial cryosphere, the parts of the world that get cold enough to support snow and ice, whether seasonally or year-round. “The effects will be especially profound along the trailing edge of the cryosphere in regions that experience significant, but seasonal snow cover,” the Wisconsin scientists assert in their report. “Decay of the subnivium will affect species differently, but be especially consequential for those that lack the plasticity to cope with the loss of the subnivium or that possess insufficient dispersal power to track the retreating range boundary of the subnivium.”

As an ecological niche, the subnivium has been little studied. However, as snow cover retreats in a warming world, land managers, the Wisconsin researchers argue, need to begin to pay attention to the changes and the resulting loss of habitat for a big range of plants and animals.

“Snow cover is becoming shorter, thinner and less predictable,” says Pauli. “We’re seeing a trend. The subnivium is in retreat.”

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Brain can be trained in compassion, study shows

May 22, 2013 — Until now, little was scientifically known about the human potential to cultivate compassion — the emotional state of caring for people who are suffering in a way that motivates altruistic behavior.

A new study by researchers at the Center for Investigating Healthy Minds at the Waisman Center of the University of Wisconsin-Madison shows that adults can be trained to be more compassionate. The report, published Psychological Science, a journal of the Association for Psychological Science, investigates whether training adults in compassion can result in greater altruistic behavior and related changes in neural systems underlying compassion.

“Our fundamental question was, ‘Can compassion be trained and learned in adults? Can we become more caring if we practice that mindset?'” says Helen Weng, lead author of the study and a graduate student in clinical psychology. “Our evidence points to yes.”

In the study, the investigators trained young adults to engage in compassion meditation, an ancient Buddhist technique to increase caring feelings for people who are suffering. In the meditation, participants envisioned a time when someone has suffered and then practiced wishing that his or her suffering was relieved. They repeated phrases to help them focus on compassion such as, “May you be free from suffering. May you have joy and ease.”

Participants practiced with different categories of people, first starting with a loved one, someone whom they easily felt compassion for, like a friend or family member. Then, they practiced compassion for themselves and, then, a stranger. Finally, they practiced compassion for someone they actively had conflict with called the “difficult person,” such as a troublesome coworker or roommate.

“It’s kind of like weight training,” Weng says. “Using this systematic approach, we found that people can actually build up their compassion ‘muscle’ and respond to others’ suffering with care and a desire to help.”

Compassion training was compared to a control group that learned cognitive reappraisal, a technique where people learn to reframe their thoughts to feel less negative. Both groups listened to guided audio instructions over the Internet for 30 minutes per day for two weeks. “We wanted to investigate whether people could begin to change their emotional habits in a relatively short period of time,” says Weng.

The real test of whether compassion could be trained was to see if people would be willing to be more altruistic — even helping people they had never met. The research tested this by asking the participants to play a game in which they were given the opportunity to spend their own money to respond to someone in need (called the “Redistribution Game”). They played the game over the Internet with two anonymous players, the “Dictator” and the “Victim.” They watched as the Dictator shared an unfair amount of money (only $1 out of $10) with the Victim. They then decided how much of their own money to spend (out of $5) in order to equalize the unfair split and redistribute funds from the Dictator to the Victim.

“We found that people trained in compassion were more likely to spend their own money altruistically to help someone who was treated unfairly than those who were trained in cognitive reappraisal,” Weng says.

“We wanted to see what changed inside the brains of people who gave more to someone in need. How are they responding to suffering differently now?” asks Weng. The study measured changes in brain responses using functional magnetic resonance imaging (fMRI) before and after training. In the MRI scanner, participants viewed images depicting human suffering, such as a crying child or a burn victim, and generated feelings of compassion towards the people using their practiced skills. The control group was exposed to the same images, and asked to recast them in a more positive light as in reappraisal.

The researchers measured how much brain activity had changed from the beginning to the end of the training, and found that the people who were the most altruistic after compassion training were the ones who showed the most brain changes when viewing human suffering. They found that activity was increased in the inferior parietal cortex, a region involved in empathy and understanding others. Compassion training also increased activity in the dorsolateral prefrontal cortex and the extent to which it communicated with the nucleus accumbens, brain regions involved in emotion regulation and positive emotions.

“People seem to become more sensitive to other people’s suffering, but this is challenging emotionally. They learn to regulate their emotions so that they approach people’s suffering with caring and wanting to help rather than turning away,” explains Weng.

Compassion, like physical and academic skills, appears to be something that is not fixed, but rather can be enhanced with training and practice. “The fact that alterations in brain function were observed after just a total of seven hours of training is remarkable,” explains UW-Madison psychology and psychiatry professor Richard J. Davidson, founder and chair of the Center for Investigating Healthy Minds and senior author of the article.

“There are many possible applications of this type of training,” Davidson says. “Compassion and kindness training in schools can help children learn to be attuned to their own emotions as well as those of others, which may decrease bullying. Compassion training also may benefit people who have social challenges such as social anxiety or antisocial behavior.”

Weng is also excited about how compassion training can help the general population. “We studied the effects of this training with healthy participants, which demonstrated that this can help the average person. I would love for more people to access the training and try it for a week or two — what changes do they see in their own lives?”

Both compassion and reappraisal trainings are available on the Center for Investigating Healthy Minds’ website. “I think we are only scratching the surface of how compassion can transform people’s lives,” says Weng.

Other authors on the paper were Andrew S. Fox, Alexander J. Shackman, Diane E. Stodola, Jessica Z. K. Caldwell, Matthew C. Olson, and Gregory M. Rogers.

The work was supported by funds from the National Institutes of Health; a Hertz Award to the UW-Madison Department of Psychology; the Fetzer Institute; The John Templeton Foundation; the Impact Foundation; the J. W. Kluge Foundation; the Mental Insight Foundation; the Mind and Life Institute; and gifts from Bryant Wanguard, Ralph Robinson, and Keith and Arlene Bronstein.

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Understanding the past and predicting the future by looking across space and time

May 25, 2013 — Studying complex systems like ecosystems can get messy, especially when trying to predict how they interact with other big unknowns like climate change.

In a new paper published this week (May 20) in the Proceedings of the National Academy of Sciences, researchers from the University of Wisconsin-Madison and elsewhere validate a fundamental assumption at the very heart of a popular way to predict relationships between complex variables.

To model how climate changes may impact biodiversity, researchers like Jessica Blois and John W. (Jack) Williams routinely use an approach called “space-for-time substitution.” The idea behind this method is to use the information in current geographic distributions of species to build a model that can predict climate-driven ecological changes in the past or future. But does it really work?

“It’s a necessary assumption, but it’s generally untested,” says lead study author Blois, a former postdoctoral fellow with Williams at UW-Madison. She is now an assistant professor at the University of California, Merced. “Yet we’re using this every day when we make predictions about biodiversity going into the future with climate change.”

Their results should give other ecologists — and potentially others such as economists who use similar models — more confidence in their methods.

“At these spatial and temporal scales, the space-for-time assumption does work well,” says Williams, professor of geography and director of the Center for Climatic Research at the UW-Madison Nelson Institute for Environmental Studies. “Our fossil data did support the idea that you can use spatial relationships as a source of information for making these predictions for the future.”

Their research focus is paleoecology, the study of ancient ecosystems. By looking at fossilized pollen trapped in cores of sediment from the bottoms of lakes, the scientists reconstructed information about the plant communities present at locations across eastern North America during the past 21,000 years.

If climate has influenced communities the same way across space and through time, Blois explains, then a model based on the spatial data should make the same predictions as a model based on their temporal data. And in fact, they did.

The space-for-time model explained about 72 percent of the variation seen in their time data, and the remainder is likely due to other biological and environmental factors that the simplified model does not include, Blois says.

Though the testing does not capture all the ways space-for-time substitutions are used in other predictive fields, she says that the results are very encouraging for questions spanning large geographic and time scales — scales at which collecting good temporal data can be very challenging.

“We found that at these broad time scales we’re looking at, that space does substitute for time relatively well,” Blois says. “It makes me more confident in my analyses going forward.”

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