Culture

Researchers: A power failure in your fat cells could short-circuit your health

A specialized fat molecule, called cardiolipin, that is made within the body's own fat cells, is far more significant to the body's overall state of health than previously realized.

Large amounts of cardiolipin produced in the fat cells' mitochondria - or so-called powerhouses - result in stronger calorie-burning while low amounts of the molecule are related to obesity and type 2 diabetes, a new study conducted at the University of Copenhagen shows.

- Brown fat is a fascinating and unique type of fat tissue that actually burns calories rather than stores them. Now we have learned that the fat molecule, cardiolipin, functions almost like an "on-off switch" for the activity of our brown fat. Switching off production of cardiolipin in mice leads to insulin resistance, which is the cornerstone of diabetes, says Associate Professor Zach Gerhart-Hines from the Novo Nordisk Foundation Center for Basic Metabolic Research and senior author of the study.

Burn More Calories

A brown fat cell functions as a microscopic biological furnace that warms the body. The study, which has just been published in the scientific journal, Cell Metabolism, started out by examining what happens in the fat cells of mice that are exposed to cold temperature, where brown fat is pushed to burn energy at full throttle. The researchers found that the mitochondria produced a lot of the molecule, cardiolipin. However, in order to understand how this could affect energy balance and health, they had to develop new tools.

- We generated mouse models in which we could switch off cardiolipin production in brown fat. After decreasing cardiolipin levels, the mice became insulin resistant and thus provided a clear link to diabetes. What really surprised us was that when we turned up the production of cardiolipin in both mouse and human fat cells, we increased the amount of calories the fat cells were able to burn, Zach Gerhart-Hines explains.

Conclusions Supported by Human Genetics and Diabetic Patients

The researchers further uncovered promising evidence that strongly suggests the scientific findings are relevant to humans.

When the researchers investigated the genetics of metabolic disease, they found that people with a gene mutation linked to low cardiolipin production have a higher risk of being overweight and developing type 2 diabetes than others.

The researchers also examined the levels of the enzyme that makes cardiolipin in fat cells from healthy and diabetic patients. They found that fat cells from healthy, insulin-sensitive people had significantly more cardiolipin-producing enzyme.

"We're excited that what we find in the petri dish and animal models seems to also be true in humans. This could open up new approaches to improve metabolic health by finding ways to boost the amount of cardiolipin in the body's fat cells, says Elahu Sustarsic, the postdoctoral researcher at the University of Copenhagen who led the studies.

Boosting Brown Fat Power in the Future

This work has revealed for the first time that a single fat molecule in the powerhouse of fat cells can have a profound influence on the health of the whole body. The researchers now hope to uncover ways to boost cardiolipin in fat cells to increase insulin sensitivity and combat metabolic disease.

The highly collaborative effort is the result of several research groups' cross-disciplinary exploration of the brown fat cells' production of cardiolipin. Researchers from Harvard Medical School in the US, the Helmholtz Diabetes Center in Germany, and several Danish institutions including the University of Southern Denmark and University of Copenhagen have contributed to the project.

Credit: 
University of Copenhagen - The Faculty of Health and Medical Sciences

How just drops of viper venom pack a deadly punch

image: Researchers studying venom from Bothrops jararaca (shown) and related South American vipers report a structural analysis of glycoproteins in the venom that may give insight into toxic proteins' solubility and stability.

Image: 
Leandro Avelar

A bite from a lancehead snake can be fatal. Species in the family, found throughout Central and South America, have venom that can disrupt blood clotting and cause hemorrhage, strokes and kidney failure.

Solange Serrano, a researcher at the Laboratory of Applied Toxicology at the Instituto Butantan in Sao Paulo, Brazil, studies the protein toxins in venom from these snakes. In a recent article in the journal Molecular & Cellular Proteomics, scientists from Serrano's laboratory, in collaboration with researchers at the University of New Hampshire, report on the sweet side of snake venom toxins.

The researchers looked at glycans, a group of sugar molecules attached in a complex chain, often with many branches, that can be attached to proteins. According to Serrano, most proteins in lancehead venom are modified with glycans, which can affect the proteins' folding, stability and binding. But very little is known about glycan structure in the snakes' venom.

Serrano's graduate student Debora Andrade-Silva visited the laboratory of glycomics expert Vernon Reinhold in New Hampshire to learn techniques for structural characterization of glycans. While there, Andrade-Silva and colleagues characterized the structure of 60 glycan chains in eight lancehead, or Bothrops, species' venoms. The researchers isolated the glycans and analyzed them by mass spectrometry, breaking down each complex molecule into smaller, simpler ions. By piecing together the spectra of many such ions, it was possible to tell which sugars were present and how they were linked into tree-like glycan structures.

Lancehead venom contains nearly 100 milligrams of protein per milliliter of liquid. At this concentration, protein solutions tend to become very viscous or form gels. Analyzing the structures of glycans attached to the proteins, the researchers found that a disproportionate number were tipped with sialic acid, a sugar with a negative charge. "Glycans containing sialic acid may help in venom solubility and increase toxin half-life," said Serrano. Sialic acid on a toxic enzyme may also bind to host proteins called siglecs, pulling the enzyme closer to target cells for greater effect; this has been observed in other types of venom.

While Serrano's group conducts basic research on venom composition, the applications are very close to home. Another department of the Instituto Butantan produces most of the antivenom available in Brazil. Serrano said she hopes that basic research into venom toxins will help researchers develop improved treatments for envenomation.

"The antivenoms do a reasonable job, but they are not so good at neutralizing the local effects of snakebite," including swelling, hemorrhage and necrosis, Serrano said. These effects can be severe enough that doctors must sometimes amputate bitten limbs. Better understanding how venom differs between snake species could improve the efficacy of antivenom treatment. Andrade-Silva and Serrano are now working to map the structures from the glycan inventory back onto the proteins they modify. Because some venom proteins have been repurposed as medicines, knowing more about how glycosylation helps each protein fold, hold its shape, and attach to binding partners may further have applications in biotechnology.

Credit: 
American Society for Biochemistry and Molecular Biology

Weight changes associated with reduced bone strength

BOSTON -- Researchers from Hebrew SeniorLife's Institute for Aging Research, Boston University, Beth Israel Deaconess Medical Center, and University of Calgary have found evidence that weight loss can result in worsening bone density, bone architecture and bone strength. The results were published in the Journal of Bone and Mineral Research.

Douglas P. Kiel, MD, MPH, principal investigator for the study said, "The study is significant because it used data on weight changes over 40 years in participants in the Framingham Study. We showed that men and women with both shorter term weight loss over 4-6 years and longer term weight loss over 40 years had more micro-architectural deterioration of their bones than persons who did not lose weight."

The magnitude of changes to the skeleton were clinically significant and translated into an almost three-fold increase in the risk of fracture for those who lost 5% or more weight over 40 years.

Elizabeth (Lisa) Samelson, PhD, senior author of the paper cautioned that "Older adults who are losing weight should be aware of the potential negative effects on the skeleton and may want to consider counteracting these effects through interventions such as weight-bearing exercise and eating a balanced diet. Given that weight loss is highly common in older adults, further work is needed to evaluate if these bone deficits can be prevented through interventions or therapy."

Credit: 
Hebrew SeniorLife Hinda and Arthur Marcus Institute for Aging Research

Study shows nail treatments do not affect readings of patients' oxygen levels, despite widespread concern

New research at this year's Euroanaesthesia congress in Copenhagen, Denmark, suggests that nail treatments such as acrylic nails or nail polishes do not, as previously thought, affect readings from digital pulse oximetry (DPO) devices used to monitor patients' blood oxygen saturation (SpO2) levels in hospital.

DPO is universally used to measure blood oxygen levels in patients, however there are concerns that the readings they produce can be affected by treatments such as nail polish or acrylic nails. The DPO device fits around the fingertip including the nail, and the side facing the nail is emitting light which is detected by a sensor on the far side of the fingertip. Since changes in SpO2 levels affect the levels and types of medical intervention, as well as impacting patient monitoring in critical care and anaesthesia, determining whether nail treatments affect DPO readings is crucial.

This study by Dr James Purcell and colleagues at University College Cork, and South Infirmary Victoria University Hospital, Cork, Ireland. aimed to survey attitudes and approaches to the issue among healthcare professionals, and experimentally assess the effect of nail treatments on SpO2 measurements under different physiological conditions. The nail treatments the team studied were acrylic nails and differing colours of nail polish/varnish.

The team issued a questionnaire-based survey to clinical staff at four university hospitals to assess their knowledge and opinions on how nail treatments impact clinical decisions pertaining to DPO. They also conducted an experiment on 12 volunteers to analyse the effects of nail polish of different colours and acrylic nails from popular brands on SpO2 under varying physiological conditions (healthy, venous congestion, and venous constriction). Congestion was modelled by applying a blood pressure cuff to restrict blood flow, while constriction was modelled by immersing the subject's hand in cold water at 10? for 10 minutes.

There were 86 responses to the survey questionnaire (55 doctors, 21 nurses) with 45% of respondents saying that nail treatments affected the way they conducted their clinical practice. More than 30% of those surveyed had intervened to remove nail treatments to prevent them affecting DPO readings.

The experimental part of the study found that none of the nail treatments examined caused more than a 1% variation in SpO2 readings under any of the physiological conditions tested compared to untreated nails. Furthermore, none of the treatments resulted in an SpO2 of

The authors found that: "Knowledge of, and approach to potential complications of nail treatments on DPO varies amongst healthcare staff, with poor knowledge or understanding of effects". They suggest that hospitals should establish policies that do not require the removal of any of the nail treatments examined in this study prior to the use of DPO equipment.

They conclude that: "Experimental data indicate the nail treatments specified do not contribute significantly to a difference in blood oxygen readings, therefore have no clinical impact on patient care".

Credit: 
The European Society of Anaesthesiology and Intensive Care (ESAIC)

UA study links sleep loss with nighttime snacking, junk food cravings, obesity, diabetes

TUCSON, Ariz. - Nighttime snacking and junk food cravings may contribute to unhealthy eating behaviors and represent a potential link between poor sleep and obesity, according to a study by University of Arizona Health Sciences sleep researchers.

The study was conducted via a nationwide, phone-based survey of 3,105 adults from 23 U.S. metropolitan areas. Participants were asked if they regularly consumed a nighttime snack and whether lack of sleep led them to crave junk food. They also were asked about their sleep quality and existing health problems.

About 60 percent of participants reported regular nighttime snacking and two-thirds reported that lack of sleep led them to crave more junk food.

The researchers found that junk food cravings were associated with double the increase in the likelihood of nighttime snacking, which was associated with an increased risk for diabetes. They also found that poor sleep quality seemed to be a major predictor of junk food cravings, and that junk food cravings were associated with a greater likelihood of participants reporting obesity, diabetes and other health problems.

"Laboratory studies suggest that sleep deprivation can lead to junk food cravings at night, which leads to increased unhealthy snacking at night, which then leads to weight gain. This study provides important information about the process, that these laboratory findings may actually translate to the real world," noted Michael A. Grandner, PhD, MTR, UA assistant professor of psychiatry and director of the UA Sleep and Health Research Program and the UA Behavioral Sleep Medicine Clinic. "This connection between poor sleep, junk food cravings and unhealthy nighttime snacking may represent an important way that sleep helps regulate metabolism."

"Sleep is increasingly recognized as an important factor in health, alongside nutrition," said Christopher Sanchez, UA undergraduate nutrition and dietetics major, who is the lead author of the study and a student research assistant in the Sleep and Health Research Program directed by Dr. Grandner. "This study shows how sleep and eating patterns are linked and work together to promote health."

William D. "Scott" Killgore, PhD, UA professor of psychiatry, medical imaging and psychology, and director of the UA Social, Cognitive and Affective Neuroscience (SCAN) Lab, also contributed to the study.

UA Health Sciences sleep researchers work as interdisciplinary teams, conducting research and leading clinical trials to assess how sleep affects memory, mental health, stress, alertness and decision-making, and how environmental factors affect sleep. Sleep and wakefulness disorders affect an estimated 15 to 20 percent of U.S. adults, according to the U.S. Department of Health and Human Services.

The research abstract, "Nighttime Snacking: Prevalence and Associations With Poor Sleep, Health, Obesity, and Diabetes," will be presented at SLEEP 2018, the 32nd annual meeting of the Associated Professional Sleep Societies LLC (APSS), which is a joint venture of the American Academy of Sleep Medicine and the Sleep Research Society, June 2-6 in Baltimore. The meeting is the world's premier forum to present and discuss the latest developments in clinical sleep medicine and sleep and the roughly 24-hour cycle that influences physiology and behavior, known as circadian science.

Credit: 
University of Arizona Health Sciences

How to achieve a peaceful coexistence between wolves and humans

The persecution of wolves in order to remove them from human settlements has culminated in their near-disappearance in numerous European countries, like Spain and Sweden. Following a recovery of the species, a team of scientists has determined what geographic areas in the Scandinavian country would be most suitable for a redistribution of the specie's range, in the interests of increasing the social acceptance of wolves.

The conflict between wolves and humans is a fight over territory and livestock. This centuries-long struggle has led to the near extinction of this great carnivore in 1970s Spain, as well as in other countries such as Sweden in the middle of the last century. In the 60s, there were no breeding populations in Sweden and only 10 specimens extant in Scandinavia.

It is for this reason that, in 1966, the Swedish government formally protected the species in a country where 70% of its surface is characterized by large forests, most of them intended for trade.

Of the 438,600 km2 of the country, only 3% has buildings and 8% corresponds to agriculture. Under government protection, the first reproduction of wolves took place in 1978 and the population began to grow about fifteen years later. At present, the population of Swedish wolves exceeds 400 individuals.

These animals are concentrated "in the central parts of southern Sweden, with high regional densities that cause conflicts in local communities," Fredrik Dalerum, a researcher at the University of Oviedo and the University of Stockholm (Sweden), has told Sinc.

These conflicts have resulted in illegal wolf hunting. According to experts, the problem will continue as long as the authorities fail to simultaneously manage the interests of the towns closest to wildlife habitats and those of the wolves themselves.

In this regard, Sweden's national management plan for wolves aims to "redirect the geographical distribution of the wolf population to other parts of the country, including the previously unoccupied reindeer husbandry area, in order to decrease densities in areas where they are currently high," Dalerum points out.

In a study, recently published in Biological Conservation, this researcher, together with the scientist Therese Eriksson from the University of Stockholm, has analyzed the spatial and demographic progression of the population of Swedish wolves from 2000 to 2015 with modern spatial modelling techniques. These scientists were able to identify the appropriate areas for expanding the spatial distribution of these carnivores.

The best areas for wolves

During the fifteen year record, the population of Swedish wolves increased from 10 to 60 breeding pairs of stable territories, occupying a maximum annual range of 34,800 km2, corresponding to 8% of Sweden's land area.

Most of the animals stayed within the central parts of the country´s south. This concentration was mainly due to "a successful management strategy to keep the wolves out of the reindeer breeding area, which takes up almost half of the surface," says the researcher.

Although only one tenth of the Scandinavian country was inhabited in 2015, close to 50% is regarded as an adequate range for wolves. Much of northern Sweden, for example, comprises boreal forests that could make a suitable habitat for this canid.

"We identified possible areas of expansion in south western Sweden and within the reindeer husbandry area, mainly in its southern and central parts and along the Baltic coast," adds Dalerum.

The future success of Swedish wolf management requires an approach that promotes local acceptance by people who coexist with wolves. "Our results can be used to identify those areas where it may be more important to work on achieving this social acceptance," concludes the researcher.

Credit: 
Spanish Foundation for Science and Technology

Pilot study examines the effects of virtual reality on reducing anxiety and improving pregnancy rate of women having fertility treatment

New research presented at this year's Euroanaesthesia congress in Copenhagen, Denmark, shows that giving women different types of virtual reality (VR) sessions prior to sedation for IVF treatment (to become pregnant) reduces their anxiety and could improve successful pregnancy rate. The study is by Professor Fabienne Roelants, Saint-Luc Hospital, Catholic University of Louvain, Brussels, Belgium, and colleagues.

Along with many other hospital procedures, undergoing fertility treatment can cause stress and anxiety for women. In this study, the authors assessed the effects of two different VR sessions on the level of women's anxiety during their hospital visit.

After written informed consent, 100 women between 18 and 42 years old scheduled for oocyte retrieval (OR: for in-vitro fertilisation) under sedation were included in a prospective randomised double-blinded study. A visual anxiety scale (VAS) as well as a Spielberger's Scale Trait Anxiety Inventory (STAI) were performed before (t1) and after VR (t2) session and before leaving the hospital (t3).

For OR, remifentanil (0.1μg/kg/min) and ketamine (0.15mg/kg) were used and propofol added as needed. The women were randomly assigned one of two types of VR session. In the distraction group (n=56), women received a VR session (an underwater walk cut off from all ambient noise) and the hypnosis group (n=44) received a VR session with hypnosis focused on breathing, slowing respiratory rhythm, along with suggestions to repeat the technique later to find well-being and calm as needed (AQUA Oncomfort ®).

There was no statistically significant difference regarding anxiety scores between groups, but in each group anxiety scores decreased (both statistically significant): on the VAS of 100 points, the distraction group women's average anxiety score fell from 34 before the VR session to 23 after. In the hypnosis group, the score fell from 40 to 26 points. In both groups, anxiety scores fell further just before leaving hospital, to 12 points in the distraction group and 14 in the hypnosis group.

In the distraction group, 48 of 55 women had embryos successfully transferred, but only 10 of these women (22%) were biologically confirmed as pregnant, and only seven of these women (15%) had an ultrasound confirmed successful pregnancy at 12 weeks gestation (termed clinical pregnancy). In the hypnosis group, 35 women had embryos successfully transferred, with 16 of these (46%) biologically confirmed as pregnant, and eight of these (23%) went on the have an ultrasound confirmed clinical pregnancy at 12 weeks. However, the difference between the hypnosis group and the distraction group for clinical pregnancy was not statistically significant.

The 23% successful clinical pregnancy rate in the hypnosis group is similar to the rate seen in women with no VR session in the authors' clinic: in 2016, their most year with complete data, around 1 in 4 (25%) of 1000 treatments given resulted in a successful pregnancy, although they emphasise that the successful pregnancy rate can vary from year to year.

Professor Roelants says: "The preliminary results of this study show that VR sessions before sedation for fertility treatment significantly reduce women's anxiety. The type of suggestions used during hypnosis RV session might show a significant positive impact on the biological pregnancy rate, but not on clinical pregnancy rate at 12 weeks. The small number of patients included at this time precludes any definitive conclusion. We need to repeat the study with around 300 patients in each group to come to definitive conclusions."

He adds: "The effectiveness of virtual reality distraction has been the subject of a systematic review*. Virtual reality distraction was shown to be effective to reduce experimental pain as well as the discomfort associated with burn injury care. The technology is being used more and more in medicine, notably in psychiatry to treat phobias."

Credit: 
The European Society of Anaesthesiology and Intensive Care (ESAIC)

New machine learning approach could accelerate bioengineering

image: A new approach developed by Zak Costello (left) and Hector Garcia Martin brings the the speed and analytic power of machine learning to bioengineering.

Image: 
Marilyn Chung a Berkeley Lab

Scientists from the Department of Energy's Lawrence Berkeley National Laboratory (Berkeley Lab) have developed a way to use machine learning to dramatically accelerate the design of microbes that produce biofuel.

Their computer algorithm starts with abundant data about the proteins and metabolites in a biofuel-producing microbial pathway, but no information about how the pathway actually works. It then uses data from previous experiments to learn how the pathway will behave. The scientists used the technique to automatically predict the amount of biofuel produced by pathways that have been added to E. coli bacterial cells.

The new approach is much faster than the current way to predict the behavior of pathways, and promises to speed up the development of biomolecules for many applications in addition to commercially viable biofuels, such as drugs that fight antibiotic-resistant infections and crops that withstand drought.

The research is published May 29 in the journal npj Systems Biology and Applications.

In biology, a pathway is a series of chemical reactions in a cell that produce a specific compound. Researchers are exploring ways to re-engineer pathways, and import them from one microbe to another, to harness nature's toolkit to improve medicine, energy, manufacturing, and agriculture. And thanks to new synthetic biology capabilities, such as the gene-editing tool CRISPR-Cas9, scientists can conduct this research at a precision like never before.

"But there's a significant bottleneck in the development process," said Hector Garcia Martin, group lead at the DOE Agile BioFoundry and director of Quantitative Metabolic Modeling at the Joint BioEnergy Institute (JBEI), a DOE Bioenergy Research Center funded by DOE's Office of Science and led by Berkeley Lab. The research was performed by Zak Costello (also with the Agile BioFoundry and JBEI) under the direction of Garcia Martin. Both researchers are also in Berkeley Lab's Biological Systems and Engineering Division.

"It's very difficult to predict how a pathway will behave when it's re-engineered. Trouble-shooting takes up 99% of our time. Our approach could significantly shorten this step and become a new way to guide bioengineering efforts," Garcia Martin added.

The current way to predict a pathway's dynamics requires a maze of differential equations that describe how the components in the system change over time. Subject-area experts develop these "kinetic models" over several months, and the resulting predictions don't always match experimental results.

Machine learning, however, uses data to train a computer algorithm to make predictions. The algorithm learns a system's behavior by analyzing data from related systems. This allows scientists to quickly predict the function of a pathway even if its mechanisms are poorly understood -- as long as there are enough data to work with.

The scientists tested their technique on pathways added to E. coli cells. One pathway is designed to produce a bio-based jet fuel called limonene; the other produces a gasoline replacement called isopentenol. Previous experiments at JBEI yielded a trove of data related to how different versions of the pathways function in various E. coli strains. Some of the strains have a pathway that produces small amounts of either limonene or isopentenol, while other strains have a version that produces large amounts of the biofuels.

The researchers fed this data into their algorithm. Then machine learning took over: The algorithm taught itself how the concentrations of metabolites in these pathways change over time, and how much biofuel the pathways produce. It learned these dynamics by analyzing data from the two experimentally known pathways that produce small and large amounts of biofuels.

The algorithm used this knowledge to predict the behavior of a third set of "mystery" pathways the algorithm had never seen before. It accurately predicted the biofuel-production profiles for the mystery pathways, including that the pathways produce a medium amount of fuel. In addition, the machine learning-derived prediction outperformed kinetic models.

"And the more data we added, the more accurate the predictions became," said Garcia Martin. "This approach could expedite the time it takes to design new biomolecules. A project that today takes ten years and a team of experts could someday be handled by a summer student."

Credit: 
DOE/Lawrence Berkeley National Laboratory

Cautious prawns win battle for food

video: These are rockpool prawns foraging, eating and fighting. Two prawns fight at the end of this video, and one then retreats.

Image: 
Callum Duffield / Daniel Maskrey

Prawns have personalities - and cautious crustaceans do better in the battle for food, new research shows.

Scientists from the University of Exeter studied rockpool prawns (Palaemon elegans) and found some were consistently shy, while others were bolder.

But this bravery may come at a cost - as the risk takers tended to do worse than other prawns when competing for food.

"We found that the shyer prawns were better at controlling a food source," said first author Daniel Maskrey, formerly of the University of Exeter but now at the University of Liverpool.

"This means that when they found food and possible rivals were nearby, they stayed and fed for longer than bolder prawns.

"The reasons for this aren't clear, but it's possible that bolder prawns have a higher urge to go on and continue exploring.

"We witnessed prawns fighting over food, and it could be that some use a bold exploration strategy because they favour searching for new food over competing with stronger rivals."

Boldness was tested by repeatedly putting prawns into an unfamiliar tank and seeing how much they explored and ventured into the middle.

Dr Tom Houslay, of the Centre for Ecology and Conservation on the University of Exeter's Penryn Campus in Cornwall, said the study could help scientists understand why members of one species - and even the prawns in a single rockpool - have different personalities.

"Some individuals are more successful at monopolising food, while others are more willing to engage in potentially risky exploration," he said.

"In different conditions and situations, either of these strategies might pay off - which might explain why evolution has not led to a single personality type.

"The rockpools where these prawns live change with each high tide, and having such variation among prawns could be crucial when it comes to adapting to these and other changes."

The prawns in the study were all from Gyllyngvase beach in Falmouth, and their feeding behaviour was tested using parcels of brine shrimp. Prawns were split into groups of similarly sized individuals to compete for access to food.

Credit: 
University of Exeter

A new understanding of how glucose makes you fat

image: Drs. Keun Ryu (left) and W. Lee Kraus examined individual compartments inside cells that house NAD+ molecules to determine how they activate genes that make fat cells.

Image: 
UT Southwestern

DALLAS - May 31, 2018 - Glucose is the energy that fuels cells, and the body likes to store glucose for later use. But too much glucose can contribute to obesity, and scientists have long wanted to understand what happens within a cell to tip the balance.

To solve this riddle, researchers at UT Southwestern's Cecil H. and Ida Green Center for Reproductive Biology Sciences examined specialized compartments inside the cell to reveal the role of a molecule termed NAD+ in turning on genes that make fat cells.

A Google search for NAD+ reveals that the molecule is found in every cell of the body and that some scientists believe that boosting its production may be tied to better health and to the slowing down of the aging process.

What is NAD+?

NAD+ stands for nicotinamide adenine dinucleotide. It's a molecule found inside cells in the body that helps transfer energy between molecules.

Why is it important?

NAD+ is believed to play important roles in longevity, aging, and diseases ranging from neurodegenerative disorders to cancer.

Where can I find out more?

Scientific American primer on NAD
Green Center's Science paper
Kraus Lab

UT Southwestern biologists examined individual compartments inside cells that house NAD+ molecules to determine how they control genes that are essential to the fat-storing process - knowledge that could help in a wide range of ailments, including metabolic disorders, neurodegenerative diseases, inflammation and aging, and cancer.

"This compartmentalization ends up having profound effects on gene expression in the nucleus, as well as metabolism in the cytoplasm," (the jellylike substance outside the cell's nucleus), said Dr. W. Lee Kraus, Director of the Green Center and senior author on the research. "We found that these processes play key roles in fat cell differentiation and in cancer cells."

"The previous thinking in the field was that NAD+ was evenly distributed throughout cells and moved freely between different subcellular compartments," said Dr. Kraus, Professor of Obstetrics and Gynecology and Pharmacology. "We showed that NAD+ is actually compartmentalized - there are separate nuclear and cytoplasmic pools of NAD+ whose levels change under certain cellular conditions."

The research team's breakthrough is reported in the journal Science.

Accounting for the levels of NAD+ biosynthesis separately rather than in their totality helped increase the understanding of the biology involved, said first author Dr. Keun Ryu, a postdoctoral researcher in Obstetrics and Gynecology.

"Our study provides a new understanding of NAD+ biology," he said.

Credit: 
UT Southwestern Medical Center

Green tea molecule could prevent heart attacks

Green tea could hold the key to preventing deaths from heart attacks and strokes caused by atherosclerosis, according to research funded by the British Heart Foundation and published in the Journal of Biological Chemistry.

Scientists from Lancaster University and the University of Leeds have discovered that a compound found in green tea, currently being studied for its ability to reduce amyloid plaques in the brain in Alzheimer's disease, also breaks up and dissolves potentially dangerous protein plaques found in the blood vessels.

Atherosclerosis is the build-up of fatty material inside our arteries that can reduce the flow of blood to the heart and brain. In advanced stages of the condition, a protein called apolipoprotein A-1 (apoA-1) can form amyloid deposits, which are similar in structure to those associated with Alzheimer's disease. These deposits build up within atherosclerotic plaques. Here, they increase the size of the plaques, further restricting blood flow, and may also make the plaques less stable, increasing the risk of a heart attack or stroke.

Researchers found that epigallocatechin-3-gallate (EGCG), most commonly associated with green tea, binds to the amyloid fibres of apoA-1. This converts the fibres to smaller soluble molecules that are less likely to be damaging to blood vessels.

Now, the team are working on finding ways of introducing effective amounts of EGCG into the bloodstream without it being necessary to drink large and potentially harmful quantities of green tea. This could involve modifying the chemical structure of EGCG, making it easier to be absorbed from the stomach and more resistant to metabolism, or developing new methods to deliver the molecule to the plaques - such as via an injection.

David Middleton, Professor in Chemistry at Lancaster University, said:

"The health benefits of green tea have been widely promoted and it has been known for some time that EGCG can alter the structures of amyloid plaques associated with Alzheimer's disease.

"Our results show that this intriguing compound might also be effective against the types of plaques which can cause heart attacks and strokes."

Professor Jeremy Pearson, Associate Medical Director at the British Heart Foundation, said:
"Our bodies are very good at breaking down EGCG so swapping your cuppa for green tea is unlikely to make a big difference with respect to your heart health.
"But by engineering the molecule slightly, we might be able to make new medicines to treat heart attack and stroke."

Professor Sheena Radford, Director of the Astbury Centre for Structural Molecular Biology at the University of Leeds and co-author of the research, said:
"The findings of this round of studies are very encouraging. We now need to apply the best scientific techniques to find how we can take the molecular EGCG element from green tea, and turn it into a functioning tool to combat life-limiting health issues."

Credit: 
British Heart Foundation

The brain is able to anticipate painful movements following injury

image: The experimental set-up used in the study combined the use of transcranial magnetic stimulation with a robotized exoskeleton interfaced with a 2D virtual reality environment and with a laser delivering painful stimulation to the participant's right elbow.

Image: 
Michaël Bertrand-Charette

When people are injured, how does the brain adapt the body's movements to help avoid pain? New research published in The Journal of Physiology investigates this question.

After an injury, our body will rapidly associate pain to a particular movement and modify which muscles we use accordingly. This new research shows that the message from motor brain areas toward a muscle is reduced if this muscle is responsible for producing a painful movement and increased if it the muscle counteracts that movement.

They also observed that if the brain knows the movement will cause pain then the reaction time to perform the movement is longer, but the movements are performed quicker, suggesting a strategy of 'getting it over and done with'.

This shows that the brain is able to anticipate that particular movements will cause pain, allowing us to adapt and move differently. This research is focused on how the body responds to the anticipation of an experimental acute pain (i.e. a transient pain lasting a fraction of a second during the execution of a movement) but it may be possible to use these findings to help preventing musculoskeletal pain disorders.

When people are injured they can quickly learn to associate pain to a given movement and change the way the body moves to avoid or minimize pain. Understanding how this occurs in the brain is crucial for identifying the mechanisms that lead to the long-term maintenance of pain.

The research conducted by Laval University, Quebec, in conjunction with the Center for Interdisciplinary Research in Rehabilitation and Social Integration, Quebec, involved measuring the link between motor brain areas and the biceps as they prepared to move. The investigation was carried out on thirty healthy participants, in which half received painful stimulations during flexion movements and the other half during extension movements.

Importantly, as the experimental pain was induced with laser simulations, the results cannot be directly transferred to a population of patients suffering from clinical pain.

Catherine Mercier, corresponding author of the study, said:

'This discovery is important because it confirms the establishment of protective strategies during the anticipation of acute pain. It marks an important advance to further our understanding of the mechanisms involved in the transition from acute to chronic pain. Indeed, a recent theory on the effect of pain on motor control states that while protective strategies may be initially relevant and lead to short-term pain alleviation, they may potentially have detrimental long-term consequences and lead to chronic pain.'

Credit: 
The Physiological Society

SF State study finds US Forest Service lands underused by minorities

image: San Francisco State University's Rec, Parks & Tourism department engages diverse students in internship programs with public lands agencies.

Image: 
Nina Roberts

Our national forests and grasslands -- 193 million acres throughout the United States -- are a national treasure intended for use by everyone. But a new study by San Francisco State University Professor of Recreation, Parks & Tourism Nina Roberts and the U.S. Forest Service finds that many ethnic minorities are not using or enjoying these places.

The researchers compared U.S. Census data on minorities living within 50 miles of a national forest boundary within the contiguous United States with the percentage of visitors to those national forests who are people of color. They found that although 35.5 percent of the people living within 50 miles of a national forest are racial and ethnic minorities, those minorities represent only 11.7 percent of national forest visitors each year, on average. Even in Forest Service regions surrounded by highly diverse populations, the results were the same.

"We have these amazing spaces in this country that many people of color are not using or enjoying," said Roberts. She says this is because there is a fundamental lack of understanding on the part of public land agencies about how and why minorities use national forests and parks. "The Forest Service public lands are open to everyone, but institutional barriers and fears persist," she said.

She noted that the Forest Service and other agencies have been striving to engage communities in some ways for decades. But according to Roberts, they need to increase their efforts to understand how diverse people use national forests and other public lands to better serve the communities they're trying to reach.

"The Forest Service needs to put more effort into developing relationships with surrounding communities. One example might be to create special programs for them," Roberts said. "It's not about working harder, but about working smarter to create sustainable programs and more ongoing efforts -- to not just check a box." And she thinks agencies need to try harder to hire people of color, as that disparity has persisted for years.

With the white population predicted to be the minority in the U.S. by 2042, Roberts says, the study also highlights the need to build a multicultural constituency that will value and vote to preserve our public lands. "There's a misperception that if legislation has protected these lands in perpetuity, then we're all set, and we don't need to vote or worry about preservation or protection," she said. "Yet that is not true as laws and policies can change and be reversed as quickly as they are enacted."

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San Francisco State University

One in four intensive care patients return to hospital, study shows

A quarter of intensive care patients are readmitted to hospital shortly after returning home and some of these readmissions are avoidable, research suggests.

High levels of carer stress, difficulty understanding health and social care packages and psychological trauma all contribute to high rates of return, the findings show.

Pinpointing the reasons for unplanned readmissions is key to developing care packages that support patients at home and could save vital funds, researchers say.

After-hospital care packages vary between hospitals but unplanned hospital readmissions are thought to cost the NHS in England £2 billion per year.

The study refers to patients who have had stays in intensive care units (ICU) - specialised wards that look after people who are extremely ill and need close monitoring, including patients with sepsis, car crash victims and those recovering from heart attack.

Findings from more than 55,000 anonymised records from ICU patients in Scotland showed that one in four patients experienced unplanned readmissions within three months of leaving hospital.

Researchers led by the University of Edinburgh interviewed 58 ICU patient volunteers and unpaid carers about their wellbeing, care services and other issues that they felt contributed to their return to hospital.

Findings showed that in some cases, readmission was medically unavoidable and linked to acute illness. However, around half of the patients felt that their readmission was linked to a 'perfect storm' of factors, including carers stress, psychological trauma after facing near-death and poor understanding of health and social care systems.

Contributing factors that were commonly mentioned by patients and carers were grouped into ten categories including poor communications between acute and community based care and inadequate psychological care.

One patient who took part in the study, said: "I've suffered with depression for 20 years on and off. It's reactive depression and this whole thing has been so traumatic. When I got out of hospital it was a downward spiral..."

Another patient who was interviewed, said: "I have good support from my husband but totally rely on him. Then he wasn't here. He had two weeks work... I was on my own. Not eating properly. I think that's how I ended up in hospital."

Researchers say the findings highlight the need for services to take into account complex psychological and social needs and for patients to be better supported in the months leaving ICU.

The study, published in the journals Thorax and BMJ Quality and Safety, was funded by the Chief Scientist Office, part of the Scottish Government Health Directorates.

Lead researcher, Professor Tim Walsh, Director of the Edinburgh Critical Care Research Group at the University of Edinburgh, said: "This is a fascinating chance to learn from patients and understand avoidable reasons why they might be readmitted to hospital, so that we might spot those most at risk. Our findings show that we have some way to go to improve quality of life for intensive care survivors.

"We have launched a further project to improve the care of the most vulnerable patients by bringing together staff and charities working in hospitals, community health and social care."

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University of Edinburgh

Symptoms worsen around menses for people with borderline personality disorder

Symptoms associated with borderline personality disorder -- a severe and chronic mood disorder characterized by an inability to manage strong emotions -- tend to worsen just before and during menses, according to a study in Psychological Medicine.

Borderline personality disorder is a mental illness marked by an ongoing pattern of varying moods, self-image and behavior, according to the National Institute of Mental Health. These symptoms often result in impulsive actions and problems in relationships. People with borderline personality disorder often experience intense episodes of anger, depression, and anxiety that can last from a few hours to days. Recurrent thoughts and behaviors related to self-injury or suicide are also common, and approximately 10 percent of people with borderline personality disorder die from suicide.

"Our study provides the first evidence that females with borderline personality disorder are at risk for worsened symptoms during the perimenstrual window of their menstrual cycle -- the week before and during menses," said Tory Eisenlohr-Moul, assistant professor of psychiatry at the University of Illinois at Chicago and lead author on the paper. "This is particularly important since people with borderline personality disorder are at a high risk of suicide, so anything that can help patients and clinicians reliably predict changes in their symptoms is very useful."

Eisenlohr-Moul and her colleagues wanted to investigate whether the menstrual cycle might be a contributing factor to the instability of symptoms associated with borderline personality disorder in females.

"While we didn't expect females with borderline personality disorder to have higher or different hormone levels over the course of the menstrual cycle compared to those without the disorder, we suspect that, similar to females who suffer from severe premenstrual syndrome, women with BPD may simply be more sensitive to normal hormone changes, which we do know have an effect on mood," Eisenlohr-Moul said.

The researchers recruited healthy women with normal menstrual cycles between the ages of 18 and 45 who were not taking any psychiatric medications or birth control. Of the 310 females who met the original screening criteria, 17 met the criteria for borderline personality disorder, and 15 women ultimately completed the study. This is the largest prospective study examining cyclical mood changes in patients with BPD to date.

Participants completed several questionnaires at the beginning of the study related to borderline personality symptoms, past traumas, demographics, anxiety and depression and menstrual cycle symptoms. Participants kept a record of daily symptoms related to borderline personality disorder and menstruation for 35 consecutive days. Urine tests for luteinizing hormone and saliva tests for progesterone were used to confirm ovulation and track the phases of the menstrual cycle.

The researchers used the Carolina Premenstrual Assessment Scoring System, a questionnaire for evaluating clinically significant menstrual cycle effects on emotional symptoms, to evaluate whether the patients showed cyclical mood changes large enough to impact their day-to-day functioning.

The researchers found that most symptoms attributable to borderline personality disorder were significantly exacerbated in the week before and during menstruation. "Symptoms, on average for the females in our study, worsened by at least 30 percent during the perimenstrual phase," said Eisenlohr-Moul. "This is equivalent to going from moderate depression to extreme depression on the rating scale."

For a patient population where almost every day is a difficult day in terms of coping with mood and stress, a 30 percent worsening of symptoms is a very significant uptick, explained Eisenlohr-Moul. "Because this group is at such a high risk for suicide, knowing that things get even worse for them during this time of the month around onset of their period, is a piece of information that we can work with to help prepare patients for a time when we know, based on solid research, that things could get worse."

The perimenstrual phase of the cycle may be risky for people with borderline personality disorder because levels of estrogen and progesterone fall off rapidly, according to Eisenlohr-Moul.

"For some women, or individuals who are freely cycling independent of their gender identity, it may be as though the plug is being pulled on these hormones that we know can help regulate mood," she said. "Stable levels of estrogen and progesterone can improve mood and have an anti-anxiety effect. When these drop so precipitously around menses, it's not surprising that some women with trouble regulating mood and emotions have an even harder time."

Eisenlohr-Moul hopes to investigate the impact of hormone-stabilizing treatment on borderline personality disorder symptoms in women in the future. "If we can smooth out the hormonal peaks and valleys over the course of the month, it would be interesting to see if we can reduce emotional symptoms by eliminating those hormonal triggers," she said.

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University of Illinois Chicago