Culture

Bottom Line: Population aging and growth largely fueled an increase in cancer cases between 2006 and 2016, and large disparities continue to exist between countries in cancer incidence, deaths and the disease's associated disability.

Why The Research Is Interesting: An assessment of the impact of cancer over time can help to frame policy discussions, resource allocation and research focus.

What and When: Cancer incidence, mortality and related disability evaluated for 195 countries and territories with a focus on changes in the last decade (2006-2016).

Study Design: This was a systematic analysis.

Authors: Christina Fitzmaurice, M.D., M.P.H., at the Institute for Health Metrics and Evaluation at the University of Washington, Seattle, and coauthors in the Global Burden of Disease Cancer Collaboration

Results:

17.2 million cancer cases worldwide and 8.9 million deaths in 2016

Cancer cases up 28% in 2006-2016; population aging, growth were drivers

Prostate cancer most common cancer for men

Breast cancer most common cancer for women

Limitations: Estimations can vary widely; data collection would be improved through the expansion and creation of vital registration systems, cancer registries, health surveys and other data systems

Study Conclusions: Cancer control planning and implementation, along with strategic investments, are needed to fulfill global commitments for the control of cancer and noncommunicable diseases.

During the first days of life, the heart of a newborn mouse adapts to entirely new physiological conditions, larger volume loads and an increased energy demand. As a result, fundamental changes occur in the heart. Studies have shown that the heart of neonate mouse retains its ability to effectively repair tissue damage. This ability of the cardiac muscle to regenerate, however, gradually disappears during the first week of life.

One major problem in the treatment of heart disease is the inability of adult myocardial cells to regenerate. Thus, tissue damaged by, for example, myocardial infarction is not revived. New approaches for developing novel treatments are being sought to help patients regain heart function after myocardial infarction.

A research collaboration at Meilahti campus investigates the molecular mechanisms underlying myocardial regenerative ability. Research groups from the Medical Faculty at the University of Helsinki, the Institute of Molecular Medicine Finland (FIMM) and the Minerva Foundation Institute for Medical Research have recently published an analysis that combined three different systems-level methods on mechanisms associated with the loss of regenerative ability of the heart soon after birth.

The researchers used a large scale analytical platforms approach combining RNA sequencing, quantitative proteomics and metabolomics as well as bioinformatics to characterize the events initiated in the hearts of newborn mice during the first week after birth.

"We used a combination of different systems-level techniques and utilized the tools of transcriptomics, proteomics, metabolomics and bioinformatics. Co-operating with the top experts from different groups at the Meilahti campus, we were able to get a very comprehensive view of how the heart's metabolism is re-programmed within the first postnatal week", says Docent Esko Kankuri.

"Utilizing a 'multiomics' approach, we identified several cellular message pathways and processes that affect the re-programming of heart metabolism after birth. We discovered core molecular level events behind the regenerative capacity of the heart. Through our research, 1 937 proteins, 612 metabolites and 2 586 gene loci were associated with these processes", Kankuri adds.

Fructose-induced glycolysis was a key factor for myocardial regenerative ability, an activity associated with an increased proliferation of cardiac muscle cells during the first days after birth.

-These results also help us to understand the mechanisms of the human heart disease and what molecular factors affect myocardial regeneration. Understanding these mechanisms can open up possibilities for developing new types of treatments, says Docent Maciej Lalowski.

Around two to six per cent of all people with obesity develop obesity already in early childhood; it's in their genetic cards. Obesity-causal mutations in one of their 'appetite genes' gives them a strong genetic predisposition for developing obesity, also called monogenic obesity. Their experience of hunger is overruling and their feeling of satiety limited.

In addition, this group of people with obesity respond less well to existing treatments than others. Diets and surgery can help them lose weight, but the long-term effect is poor, as they are unable to maintain the weight loss.

Now there is hope for this group of people. In a new study published in the scientific journal Cell Metabolism researchers at the University of Copenhagen have discovered that this group of people with obesity can lose weight with the help of the medicine liraglutide, which is a modified form of the appetite-inhibiting hormone GLP-1 naturally secreted from the intestine when we eat.

'These people develop obesity because they are genetically programmed to do so. That is, they are struggling with what is probably the strongest human drive: the desire to eat and thus to survive. However, the appetite-inhibiting drug liraglutide has a positive effect on them. They feel less hungry and lose six per cent of their body weight within four months', says the the lead of the study, Associate Professor Signe Sørensen Torekov from the Department of Biomedical Sciences and the Novo Nordisk Foundation Center for Basic Metabolic Research.

Receptor Confusion

In this study the researchers have examined 14 persons with obesity caused by pathogenic mutations in the so-called MC4R gene and 28 persons with obesity without the mutations. Both groups were treated with the medicine for four months; no changes were made to their diet and level of exercise in this period.

The individuals with this most common form of monogenic obesity lost 7 kg of their body weight compared to 6 kg for the people with common obesity.

'We are positively surprised to see that the treatment has a good effect on this group of people. Many researchers have believed that the function of the medicine was mainly to inhibit the appetite by stimulating this specific appetite receptor in the brain which does not work in this particular group of people with obesity. However, our study shows that the medicine still has an appetite-inhibiting effect and thus must affect the appetite in a different way', says Signe Sørensen Torekov.

Already Available

Medicine acting as an analogue to our natural GLP-1 hormone is already available, as it has been FDA and EMA licensed for the treatment of obesity and type 2 diabetes. The new study thus makes it possible to treat the most common form of genetically caused obesity, where patients respond poorly to existing treatments.

'People who have suffered from obesity all their lives probably are not aware that it is caused by this mutation. It can therefore be a huge relief for many to learn why they have developed obesity and that there is actually a treatment that works', says first-author of the study, PhD Student Eva Winning Iepsen at the Department of Biomedical Sciences and the Novo Nordisk Foundation Center for Basic Metabolic Research.

She also points out that the medicine makes it easier for people with this monogenic form of obesity to control their blood sugar. The medicine can thus also have an effect on diabetes and pre-diabetes often seen in this particular group of individuals with genetically determined obesity.

As MC4R mutations cause obesity already in early childhood, the researchers hope the results can pave the way for new studies on young people in the future. If they are able to prevent this condition before the young people reach adulthood, it will have a great positive effect on their health and perhaps also social stigmatization, the researchers believe.

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.

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.

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."

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".

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.

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.

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."

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."

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.

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.

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."

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.'