Brain

Army ant (Eciton) soldiers are bigger but do not have larger brains than other workers within the same colony that fulfill more complex tasks, according to a study published in the open access journal BMC Zoology. A collaborative team of researchers led by Drexel University in Philadelphia, US and German colleagues suggests that because the very specific and limited tasks soldiers fulfill place limited cognitive demands on them, investment in the development of brain tissue is also limited.

Prof. Sean O'Donnell, lead author of the study said: "To compare different types of ant castes - soldiers and other workers - we took advantage of the dramatically distinct soldier class of workers in Eciton army ant colonies. Soldiers are morphologically distinct - they are bigger than their nest mates - but also behaviorally distinct: they have a simpler behavioral repertoire. Our findings support the idea that the simple behaviors of soldiers allow for reduced investment in brain development."

Ants are eusocial insects and as such variations in individual abilities are organized based on what benefits the colony as a whole rather than the individual. The authors hypothesized that this colony-level selection may lead to different brain sizes in different castes of ant workers, depending on the cognitive demands placed on them by the function they perform within the colony.

The authors compared total brain size against body size for 109 army ant workers and 39 soldiers across eight species and subspecies of Eciton. Examining the ants' antennal lobes, which receive olfactory information, and their mushroom bodies, higher brain centers involved in learning and memory, the authors also investigated if brain architecture differed between workers and soldiers. They found that although soldiers were larger than workers, their total brain size was not significantly different. They also had relatively smaller antennal lobes and smaller mushroom bodies.

The findings suggest that as brain tissue development and maintenance is costly to a single organism as well as to the ants' colonies as a whole, natural selection at the colony level favors reduced investment in brain tissue in soldiers which deal with fewer cognitive demands than other workers. The authors also found that soldiers have relatively large muscles attached to their mandibles - which are used in fighting off attackers - which suggests that brain investment may trade off against muscle development in different kinds of ant workers.

Prof. O'Donnell said: "We believe this is the first study to explore the possibility of reduced brain investment in social group members, with the evolutionary advantages accruing at the colony level, despite potential cognitive costs to the individuals. Most previous studies of this kind compared different species, or explored which factors could favor increased brain investment at the individual level. Our study explores how a reduction in behavioral capacity, and an associated reduction in brain investment in individuals, could benefit social groups as a whole."

All liars have classic tells: the lack of eye contact, the fidgeting, the overly elaborate stories. Except when they don't.

In fact, researchers say, the most adept deceivers often don't present any of those signs and, further, the average observer's tendency to rely on such visual cues impedes their ability to tell when someone is lying. But those detection skills can be improved markedly with as little as one hour of training.

That is among the primary findings of new research from Norah Dunbar, a UC Santa Barbara professor of communication who has been studying deception and credibility for 20 years, now online in the journal Computers in Human Behavior. The publication culminates a National Science Foundation-funded project to develop a video game that trains participants in deception detection.

That game, VERITAS (Veracity Education and Reactance Instruction through Technology and Applied Skills), has now been built and tested repeatedly with college students and with law enforcement officers.

And it works.

"This was a proof of concept prototype to see if we can move the needle, and it seems that we can," said Dunbar, chair of UCSB's communication department and faculty research affiliate with the Center for Information Technology and Society, who recently presented her research to members of Congress at special event put on by NSF. "Even a single session can improve the ability to accurately detect truth and lies."

Looking at whether or not participants could tell the difference between truth and lies, on average, players at the start of the game scored "not much better than chance -- about 56 percent accurate. By the end of the game they're 68 percent accurate, and that's just playing for about an hour. Law enforcement participants started the game with higher accuracy, 62 percent, and improved to 78 percent. That's a big jump."

The game presents players with two different scenarios -- one revolves around a job interview, the other a workplace theft -- and challenges them to discern whether the actors in those scenarios are lying or telling the truth. They're also asked to identify the basis of their conclusion.

"Sometimes they guess right but are using incorrect cues, so we give feedback about what cues they should use instead," Dunbar explained. "There are some reliable cues for deception but the average person doesn't know about them. The average person thinks a lot of myths and stereotypes and they use their biases and make judgments based on things that aren't very accurate or scientific.

"If a person said, 'I think she wasn't truthful because wasn't looking at me,' the game would tell them, 'Eye contact not a reliable cue, instead you should rely on these real cues,'" she continued. "We try to teach people not to look for individual cues, like tapping a foot or looking up. There is no Pinocchio's nose, no one thing that will tell you definitively if someone is lying. People will be different, and do different things."

Here's where the training comes in. VERITAS improves knowledge of deceptive behavior, Dunbar said, by coaching participants to watch for clusters of cues, or patterns. One such cluster (and potential red flag): uncertainty, tension and cognitive load. Call it a liar's trifecta.

"Lying is cognitively difficult -- you have to think about what you know, what you already said, what the other person said, if you're consistent -- so liars will often indicate that they are thinking harder," Dunbar explained. "They might repeat themselves a lot, or repeat your questions before answering, or wait longer to answer. Those are all cognitive load cues. A liar may show signs of uncertainty or what we call a 'lack of embracement' of their story. They might seem tense -- stiff, rigid, not gesturing much -- like they're trying not to show anything. We call it 'freeze mode' and it's very unnatural.

"There is no one cue that's our magic bean to tell us when someone is lying," Dunbar added, "but all these cues added up together - that says something."

Intriguingly, when asked to assess statements made by actors in the game, most VERITAS players defaulted to the same determination: truth. That commonality reflects what is known as truth bias, "which is that we guess truth when we feel there is no good reason to suspect lying."

"One interesting finding is that people tend to be better at detecting truthful statements, because of that truth default," said Dunbar. (She also is studying how people develop trust when they are lying as part of a Multidisciplinary University Research Initiative grant funded by the Department of Defense.) "Their accuracy in assessing lies is often below 50 percent because they don't guess 'lie' often enough. And the game doesn't make them more accurate in guessing lies, but it does improve accuracy in guessing truth and overall knowledge about deception."

"We compared results from the game to those from a Powerpoint lecture and found that with the game, people were more engaged, they were more motivated, they got better at detecting truth and they improved their knowledge about deception detection," Dunbar added. "So it holds a lot of promise in how to train people how to detect lies."

Which is why she hopes to expand it.

With broad potential for application in a range of fields, VERITAS in its current iteration already has great success rates. And those numbers would surely grow, Dunbar said, with an extended version.

"If we get more funding we would like to make more scenarios for the game," she said. "Lie detection is an important skill in the medical community. Doctors sometimes have trouble telling if patients are being truthful -- opioid seekers, for instance. I had someone contact me to say he wanted to use it for insurance fraud investigators. There are a lot of situations where it could be useful."

BIDMC Research Briefs showcase groundbreaking scientific advances that are transforming medical care.

Special cells called podocytes aid the kidneys as they clean the blood and balance the body's fluid levels. Podocytes filter blood as it passes through the cells' foot-like projections they are named for, interwoven like the fingers of clasped hands. Podocyte damage - indicated by proteinuria or abnormal proteins in the urine - is a common symptom of diseases including the autoimmune disorder lupus and non-immune diseases and can result in kidney failure requiring dialysis or organ transplant.

In a research article published in the Journal of Clinical Investigation on July 9, a team of scientists led by George C. Tsokos, MD, Chief of the Division of Rheumatology at Beth Israel Deaconess Medical Center (BIDMC), describes how overexpression of an immune regulating molecule called CaMK4 can destroy podocytes' structure and function. What's more, the researchers demonstrated that inhibiting CaMK4 can prevent and even reverse podocyte damage in lupus-prone mice.

"When we looked at human tissue samples from kidney biopsies, we observed that people with lupus and non-autoimmune kidney disease showed increased levels of CaMK4," said Tsokos, who is also a Professor of Medicine at Harvard Medical School. "We wondered what would happen if we inhibited CaMK4 specifically?"

Working in mice which develop lupus spontaneously, Tsokos and colleagues - including bioengineers at Yale University and Yale Medical School - blocked CaMK4's deleterious effects on podocytes by delivering an inhibitor directly to the special cells. The podocytes maintained their structure and function in the lupus-prone mice. In fact, the inhibitor prevented podocyte damage in mice with autoimmune disease and reversed podocyte damage in mice injected with Adriamycin, a drug known to cause kidney damage - a finding Tsokos says opens the door to potential new therapies not just for people with lupus, but also other autoimmune and non-autoimmune diseases that impact the kidney.

"The finding that preserving the structure and function of podocytes through inhibition of CaMK4 inhibits inflammatory immune complexes and thus prevents damage reverses the classical dogma - widely accepted for the last 60 years - that inflammation instigates damage to the kidney," said Tsokos. "Only if podocytes are damaged can the immune complexes be deposited."

Next, Tsokos and colleagues would like to learn more about how podocyte damage occurs, how late in the process inhibiting CaMK4 can reverse podocyte damage and how these findings apply to other renal diseases, including diabetes. They also hope to initiate a clinical trial.

Study underlines importance of physical activity within learning

Awareness of how objects move over time underpins mathematical thinking

School is already acting on the findings of the research

Young children with better eye-to-hand co-ordination were more likely to achieve higher scores for reading, writing and maths according to new research - raising the possibility schools could provide extra support to children who are clumsy.

Just over 300 children aged four to 11 took part in computer tasks to measure their co-ordination and interceptive timing - their ability to interact with a moving object.

The study, led by researchers at the University of Leeds, is published in the peer-review journal Psychological Science.

The tasks designed to measure eye-to-hand coordination involved steering, taking aim and tracking objects on a computer screen.

In the 'interceptive timing' task, the children had to hit a moving object with an on-screen bat.

This task taps into a fundamental cognitive ability - how the brain predicts the movement of objects through time and space. The researchers suggest that this skill may have provided the evolutionary foundations for the emergence of cognitive abilities related to mathematics, a theory first proposed by the famous Swiss psychologist Jean Piaget in the 1950s.

After controlling for age, the results revealed that the children who did better at the eye-to-hand coordination tasks tended to have higher academic attainment in reading, writing and maths.

Those with the best performance at the 'steering task' in particular were on average nine months ahead of classmates who struggled.

However, the researchers found that while the children's interceptive timing skills tended to predict their attainment in mathematics, it did not influence reading and writing development.

This was an observational study, identifying statistically significant associations between the ability to process what is happening in the physical world and educational attainment. It does not demonstrate direct cause and effect.

Mark Mon-Williams, Professor of Cognitive Psychology at the University of Leeds who supervised the research, said: "The results show that eye-to-hand co-ordination and interceptive timing are robust predictors of how well young children will perform at school."

This research builds on recent findings from other studies which suggested that the ability of babies aged between six and 13 months to understand the world around them had an impact on their ability to manipulate numbers when they reached the age of four.

Professor Mon-Williams said: "The current thinking among psychologists is that the neural circuitry used to build up a child's understanding of their external environment, the way they orientate themselves spatially and understand their world is also used to process numbers and more abstract thinking. It also raises the question: should schools be identifying those children who are seen as clumsy or not so well coordinated and giving them extra support?

"The study identifies the important relationship between a child's ability to physically interact with their environment and their cognitive development, those skills needed by the child to think about and understand the world around them."

The University of Leeds' study was conducted at Lilycroft Primary School in Bradford, West Yorkshire, where Headteacher Nicola Roth is applying the findings of the research.

The school has remodelled its reception, indoor and outdoor areas to include a space where children can develop their motor skills and the ability to call on large muscle groups to co-ordinate movement.

She said: "As a school we decided to harness the research findings. We have decided that our pupils should be encouraged to develop motor skill and eye to hand co-ordination throughout their time at the school.

"Playing with construction equipment toys used to stop when children reached the ages of five or six but we have decided to continue with that until they are nine years old. This is one of the ways we have implemented the findings, it is a simple step that can have significant benefits for the children's wider education."

Cellular functions rely on several communications networks that allow cells to rapidly respond to signals affecting the organism. A new study published in the prestigious journal Molecular Cell has revealed a mechanism that shuts down a major cell-to-cell communications pathway implicated in a number of diseases. INRS professor Nicolas Doucet and his research team contributed to the discovery of this new molecular switch, shedding new light on the role of receptor tyrosine kinases, a well-known protein family whose function is still being explored.

In a complex organism, cells have to coordinate and control widely separated actions to allow the organism to develop normally and carry out its vital functions. For example, a hormone secreted by one organ might act on the cells of another. A host of messages are constantly travelling throughout the body to keep biological processes running smoothly.

Why you cannot live without cell receptors

If we could observe a human cell in enough detail, it would appear to be bristling with all kinds of molecular sensors and receivers, like a forest of antennas on a roof performing a bewildering variety of different tasks. Most are specialized proteins--known as receptor proteins.

Receptor tyrosine kinases (RTKs) are a family of proteins that carry out many tasks required for organism growth and maintenance. They are found in every cell of the human body and broadly act on processes ranging from cell organization to nutrient management. Despite their distinct roles, they conserve a high degree of structural similarity at the molecular level, suggesting that each component of their three-dimensional structure plays an important role in their biological function. However, only recently has technology become sufficiently precise to peer into key molecular interactions of RTKs at the atomic level.

A design honed through evolution

RTK receptors embedded in the cell membrane stick their 'sensory receivers' outside the cell and extend their enzymatic machinery inside the cell. Part of their equipment is a kinase, an enzyme that activates other proteins by adding a phosphate group to specific amino acids on their surface. This process is known as phosphorylation.

To activate a cellular signaling pathway, RTKs pair up as soon as a receiver picks up a signal. Linking together involves reciprocal action, with each partner accepting a phosphate group from the other. All partners then line up in such a way that they can interact with a new molecule, thus initiating the required cellular function.

The riddle of the shutdown switch

Université Laval and INRS researchers were trying to figure out how signal pathways were shut down. Some of the mechanisms that inactivate and recycle RTKs are known, but they are too slow to account for what has been observed inside cells. These observations suggest that there is a faster way to shut down these cellular processes.

To better understand what happens at the molecular level between RTK complexes, a family of signaling pathways was analyzed--the one involving the RTK EPHA4 and the adaptor protein NCK, which regulates fundamental processes such as cytoskeletal reorganization, cell migration, and the establishment of neuronal circuitry.

At INRS, Prof. Doucet's team analyzed the 3D structure of the protein partners at the atomic level. Using nuclear magnetic resonance (NMR) and computer-assisted molecular modelling, they showed that NCK contains a tyrosine amino acid that is extremely important in cellular signalling. This tyrosine is also conserved in these proteins throughout evolution. When NCK binds to EPHA4, the protein partners are perfectly aligned to allow the tyrosine to receive a phosphate group.

Proteins: giants among molecules

One of the main difficulties Prof. Doucet's research team had to face was the need to clearly demonstrate that NCK and EPHA4 could recognize each other at the molecular level. If not, phosphorylation would be off the table.

"The thing is," said Prof. Doucet, a molecular engineering specialist, "you cannot assume two proteins will simply recognize each other out of the blue just because you want them to based on your hypothesis. Since what they do is invisible to the naked eye, it takes some pretty advanced molecular technology to convincingly illustrate that this actually happens."

"This requires credible computer models grounded both in known experimental data and calculation algorithms that analyze the probability of forming these protein complexes," he continues. "What complicates matters is the fact that proteins are enormous molecules on the atomic scale. There are thousands of atoms to account for in our calculations, each of them simultaneously repelling or attracting the others. All those interactions are governed by physical and mathematical forces that are well known but extremely complex, and it takes a lot of computing power to analyze them all at once."

But the team delivered the goods, refining the algorithms and measurements. In collaboration with researchers at Université Laval, they successfully observed the cellular mechanism both in vitro and in vivo.

A new key for cell-to-cell communications

The key discovery of this study is the following--as soon as NCK is phosphorylated on this particular tyrosine, it drops whatever its doing and shuts down the cell-to-cell communication circuit. The researchers, many of whom are members of PROTEO, the Québec Network for Research on Protein Function, Engineering, and Applications, characterized this shutdown effect both in vitro and in vivo.

The newfound switch adds to our understanding of cell-to-cell signalling because it partially accounts for the speed at which the message is controlled from outside the cell. NCK turns signals off without the need to dismantle the RTK complex, which remains active on the cell surface and continues to pick up new signals. Other uncharacterized events control when the complex and NCK resume activity.

The team has uncovered a big piece of the cell signalling puzzle, opening up new possibilities for research on diseases such as cancer and diabetes, where RTK receptors are known to play important roles. The new key for controlling RTKs is certainly exciting, but plenty of research lies ahead before anyone gets to flip the switch.

A new study finds that severe childhood trauma and stresses early in parents' lives are linked to higher rates of behavioral health problems in their own children.

The types of childhood hardships included divorce or separation of parents, death of or estrangement from a parent, emotional, physical or sexual abuse, witnessing violence in the home, exposure to substance abuse in the household or parental mental illness.

"Previous research has looked at childhood trauma as a risk factor for later physical and mental health problems in adulthood, but this is the first research to show that the long-term behavioral health harms of childhood adversity extend across generations from parent to child," said the study's lead author, Dr. Adam Schickedanz. He is a pediatrician and health services researcher and assistant professor in the department of pediatrics at the David Geffen School of Medicine at UCLA.

The study showed that the children of parents who themselves had four or more adverse childhood experiences were at double the risk of having attention deficit hyperactivity disorder and were four time more likely to have mental health problems.

A mother's childhood experiences had a stronger adverse effect on a child's behavioral health than the father's experiences, the study found.

Parents who lived through adverse childhood experiences were more likely to report higher levels of aggravation as parents and to experience mental health problems, the researchers found. However, these mental health and attitude factors only explained about a quarter of the association to their child's elevated behavioral health risks. The remainder of how the parent's adverse childhood experiences are transmitted to their child's behavior deserves further study.

The findings add to the evidence supporting standardized assessment of parents for adverse childhood experiences during their child's pediatric health visits.

"If we can identify these children who are at a higher risk, we can connect them to services that might reduce their risk or prevent behavioral health problems," Schickedanz said.

The researchers used information from a national survey containing information from four generations of American families, including information from parents about whether they were abused, neglected or exposed to other family stressors or maltreatment while growing up, and information on their children's behavior problems and medical diagnoses of attention deficit disorder.

With this data, they were able to find strong associations between the parents' adversity histories and their children's behavioral health problems, while controlling for factors such as family poverty and education level.

The next step for researchers is to look at how resilience factors, such as the support of mentors or teachers, could offset the harms of childhood traumas, Schickedanz said.

The study was published in the journal Pediatrics.

People from smaller cities are more likely to migrate than people from larger cities, according to a new study by UCL academics.

The study, published today in the open access journal PLOS ONE, looked at internal migration patterns across the USA, finding that the size of origin and destination cities play a crucial role in the behaviour of people who move from one place to another.

Inhabitants of smaller cities - of fewer than 100,000 inhabitants - are twice as likely to migrate than those of cities with a population greater than ten million. Those who do migrate are more likely to move to a city of a similar size.

People already living in larger cities are less likely to migrate, but when they do, they are more likely to move to similarly sized large cities.

Lead researcher, UCL PhD student Rafael Prieto Curiel (UCL Mathematics), said: "The results could have an impact on future integration policies as governments can more accurately predict where citizens are likely to move from and to within their country.

"Migrants contribute to the prosperity of their destination with skills and activities, but migration requires integration policies and social support systems to allow newcomers to settle into a new environment and therefore fully contribute locally."

Ensuring newcomers are able to settle into a new area and contribute their skills and expertise can be important in combatting issues such as segregation, inequality and loneliness.

Professor Steven Bishop (UCL Mathematics) said: "The new scaling model has not previously been used to identify migration patterns. It applies a mathematical formula to migratory patterns relative to city size. When taken into account along with other existing models that focus on the distance between origin and destination cities, we have found that the laws of scaling are a significant feature of human migration patterns.

"The model can be used to more accurately predict population movement as it corrects biases which occur in other methods. This is an important, data-led development in revealing how communities and regions will grow and develop in the future."

The study considered a city as having more than 50,000 inhabitants, with anywhere less than this considered to be a rural area. The cities considered varied from populations of just over 50,000 to nearly 20 million in the New York metropolitan area.

The researchers found that international migration follows a different pattern, with individuals more likely to head to a large city where they are perhaps more likely to find jobs, housing and other people of a similar culture. More data on the origins of international migrants is needed to extend this work.

Researchers have recently begun to realize that biological sex plays a key role in disease risk. Sex plays a role in hypertension, diabetes, arthritis - and in many neurological and psychiatric disorders. Depression and anxiety affect females more, while neurodevelopmental disorders, including autism spectrum disorders, early onset schizophrenia, and attention deficit hyperactivity, affect more males. Males are also more sensitive to prenatal insults, such as gestational stress, maternal infection and drug exposure.

To better understand the molecular underpinnings of this disparity, Tracy Bale of the University of Maryland School of Medicine, along with several colleagues, focused on a molecule that plays a key role in placental health. In a study of mice, they found that the molecule, O-linked N-acetylglucosamine transferase (OGT) works by establishing sex-specific patterns of gene expression.

The study was published this week in the journal Nature Communications.

OGT seems to work via an epigenetic modification that broadly controls transcription, H3K27me3. Epigenetics is the study of changes in how genes are expressed. Dr. Bale showed that high levels of H3K27me3 in the female placenta produce resilience to stress experienced by the mother. This indicates at least one molecular pathway that allows females to be more resilient to maternal stress than males.

"This pathway could help explain why we see this profound neurodevelopmental difference in humans," said Dr. Bale. "OGT and H3K27me3 in the placenta are crucial to a lot of protein encoding that occurs during pregnancy, and so this process has a lot of downstream effects. The OGT gene is on the X chromosome, and seems to provide a level of protection for the female fetus to perturbations in the maternal environment."

Dr. Bale has focused much of her research on the links between stress and subsequent risk for neurodevelopmental disorders, including autism and schizophrenia in offspring. Her previous work on the placenta has found novel sex differences that may predict increased prenatal risk for disease in males.

She has previously found that, in mice, a father's stress can affect the brain development of offspring. This stress can alter the father's sperm, which can alter the brain development of the child. Dr. Bale has also found that male mice experiencing chronic mild stress have offspring with a reduced hormonal response to stress; this response has been linked to some neuropsychiatric disorders, including PTSD. This suggests that even mild environmental challenges can have a significant effect on the health of offspring.

Barcelona, 3 July 2018: Forty years after the birth of Louise Brown, the world's first test-tube baby, an international committee monitoring progress in assisted reproduction reports today that the global total of babies born as a result of IVF and other advanced fertility treatments is "more than 8 million".(1) Dr David Adamson speaking at this congress on behalf of the International Committee for Monitoring ART (ICMART) said: "Based on ICMART's annual collection of global IVF data, it is estimated that since Louise Brown's birth in 1978 over 8 Million babies have been born from IVF around the world."

The figure, calculated from data collected from regional registries from 1991 to 2014, represent another steep rise in the cumulative use of IVF in the treatment of infertility. Estimates are that more than a half million babies are now born each year from IVF and ICSI from more than 2 million treatment cycles performed.

In Europe, Spain remains the most active country in assisted reproduction. ESHRE has collected the national registry data of ART cycles performed in Europe since 1997 and for its latest report (for 2015) found that a record 119,875 treatment cycles were performed in Spain, which now sets the pace of European treatment ahead of Russia (110,723 cycles), Germany (96,512) and former front runner France (93.918). The cycles monitored by ESHRE include treatments with IVF, ICSI, and egg donation.(2)

The report covers a total of almost 800,000 treatment cycles performed in 2015 and 157,449 babies born - and represents the largest and most accurate snapshot of ART in Europe.(3) Dr Christian de Geyter, chairman of ESHRE's European IVF Monitoring Consortium, will present the results today in Barcelona at the 34th Annual Meeting of ESHRE.

Dr de Geyter estimates that around 80% of all European assisted reproduction fertility treatments are included in the monitoring programme - but this year (ie, for 2015) without the data so far from the UK. The UK usually performs around 60,000 treatments a year.

Among other findings:

Clinics in Europe continue to favour ICSI over IVF by around two-to-one (356,351 ICSI, 131,221 IVF), a pattern now evident throughout the world. ICSI was developed in the early 1990s as a specific treatment for male infertility (low sperm counts, poor sperm quality) but is now clearly used for fertilisation in non-male cases.

Pregnancy rates (as measured per embryo transfer) seem to have stabilised in Europe at about 36% for both IVF and ICSI. Pregnancy rates are higher with five-day old embryos (blastocysts) than with three-day.

Pregnancy rates from egg donation continue to rise (now at about 50%).

The rate of twin pregnancy continues to decline in Europe, in 2015 to around 14%. Similarly, the rate of single embryo transfers continues to rise - from 11% in 1997 to 38% in 2015.

"Success rates have stabilised," said ESHRE's EIM committee chairman Christian De Geyter, "although outcome in egg donation and with use of frozen embryos is still moving upwards. The biggest upwards movement, however, is from treatments with frozen eggs, which have been revolutionised by the widespread introduction of vitrification."

Also gaining ground is embryo freezing. All embryos in 15% of all treatment cycles monitored in 2015 were frozen before thawing and transfer in a subsequent cycle. Uptake of this "freeze-all" approach increased by 7% on the previous year. Freezing by vitrification would also explain the increase in egg donation treatments, no doubt made possible by egg banking and the greater availability of donor eggs.

De Geyter also noted that the availability of assisted reproduction treatment remains very patchy in Europe, with Denmark and Belgium each offering more than 2500 treatment cycles per million population, while others (such as Austria and Italy) offer considerably fewer. A study calculated that the global need for advanced fertility treatments was around 1500 cycles per million population per year. "Only a minority of European countries meet this need," said De Geyter.

Researchers from Japan's Tohoku University and colleagues have found that a simple DNA test can predict if East Asian patients are likely to have bad reactions to thiopurine medications.

Thiopurine drugs are prescribed to patients with inflammatory bowel disease, leukaemia and rheumatic disease to suppress abnormal activities of the immune system. However, some patients develop severe side effects to the drugs, including drops in white blood cell counts (called leukopenia) and hair loss (called alopecia). There is a higher rate of severe side effects among East Asians taking thiopurines than in Caucasians, even when taking much smaller doses.

Tohoku researchers and collaborators from more than 30 medical centres all over Japan screened the DNA of more than 2,600 patients with inflammatory bowel disease and compared the results with their reactions to thiopurines. They found it was only necessary to screen a tiny section of DNA to predict which patients had severe reactions.

Previous research had linked severe thiopurine side effects with different expressions of the gene that codes for the enzyme NUDT15. Specifically to blame were variations in codon 139, which consists of three nucleotides. Of the four possible basic genetic building blocks -- adenine, cytosine, guanine, and thymine -- patients with a cytosine at the first nucleotide of codon 139 were at greater risk for side effects.

For the current study, published in the Journal of Gastroenterology, the researchers screened patients' DNA to determine which versions of NUDT15 codon 139 they had and compared that against the patients' reactions to thiopurines. They also conducted several other genome-wide association studies to determine if any other genes should be tested to predict adverse reactions. They confirmed that it was only necessary to screen codon 139.

Based on these findings, the scientists worked with Medical and Biological Laboratories Co., Ltd. to develop a DNA sequencing kit for codon 139 that produces accurate results within two hours. The test kit has been approved for clinical use in Japan, and the developers hope the kit will soon be available for clinical application in other East Asia countries, such as Korea and China.

The researchers anticipate that this research and kit can help patients avoid severe side effects, and help advise doctors on appropriate medication levels for patients with different expressions of the NUDT15 gene. However, they note that further study is required to evaluate dosage recommendations.

The public debate on endocrine disrupting chemicals (EDCs) - exogenous substances that have the same or similar effects as endogenous hormones - has been going on for some time. Chemicals such as bisphenol A or phthalates, the latter of which are used to soften plastics, may be connected to rising infertility rates among men and women.

In an experiment with pigs, researchers from ETH Zurich and the Technical University of Munich have demonstrated for the first time that the administration of even extremely low doses of an endocrine disruptor - in this case, an endogenous oestrogen - leads to epigenetic changes in a pregnant sow's DNA. Moreover, these changes were also observed in the sows' embryos, and similar changes were even evident after the offspring had reached adulthood. The study was recently published in the journal Scientific Reports.

A time window of increased sensitivity

"EDCs, especially oestrogens, are highly effective even at very low doses," says Susanne Ulbrich, Full Professor of Animal Physiology at ETH Zurich. Whether endo- or exogenous chemicals have an effect, and how strong that effect is, also depends on the point in time during which the exposure occurs. "For example," Ulbrich explains, "the body is particularly susceptible to external disruptive hormonal influences during the embryonic phase of early pregnancy."

Ulbrich and her colleagues examined exactly such a time window in their study with pigs: to simulate the intake of EDCs via drinking water or food, they exposed pregnant sows to varying doses of oestradiol-17β, a natural oestrogen, via their daily feed either over the course of the whole gestation period or only during the first ten days after fertilisation.

The lowest dose corresponded to the acceptable daily intake for humans (0.05 micrograms per kilogram body weight). In the same experiment, the scientists administered two other dosages: one close to the "no observed effect" level (10 micrograms per kilogram body weight daily) as well as a higher dosage (1,000 micrograms per kilogram daily) - the latter to simulate the accidental taking of the contraceptive pill in early pregnancy. The experiment included a control group of pigs that received no oestradiol.

The scientists tested the gene expression and the epigenetic changes in various tissues of the pregnant sows as well as in their offspring, both in the ten-day-old embryos (blastocysts) and in one-year-old mature females.

Changes in gene expression

Their efforts bore fruit: of the 57 oestrogen-related genes, oestradiol affected the tissue-specific expression of about two dozen of the genes tested, according to dosage. Most of these genes regulate the cell cycle or suppress the growth of tumours. The changes were most pronounced in the pregnant sows' corpora lutea, endometria, hearts and skeletal muscle.

In addition, the researchers observed epigenetic changes in a few selected genes in the sows' liver. Similar changes to these genes also appeared in the embryos and in the adult offspring: even in the one-year-old female offspring, the researchers were able to determine that the epigenetic pattern of these genes had been altered.

Epigenetic changes occur for example through the addition or removal of small chemical groups, such as methyl groups, at certain points in the DNA. This can alter the expression of the affected gene, and in turn change the cell's function.

Lasting changes

"We didn't find any serious impact on the health of the adult offspring; we saw only slight changes, such as in bone density and the ratio of fat to muscle mass," Ulbrich explains. However, it remains unclear what long-term effects the epigenetic changes might have, and whether the interaction of the many EDCs humans are exposed to on a daily basis render the situation more acute.

"There is an urgent need to observe this phenomenon over several generations in a long-term study," says the ETH professor. "Epigenetic changes can emerge within just one generation, but in certain circumstances they will continue to be transmitted to succeeding generations. We can already clearly demonstrate that hormones, even after a brief exposure period and in very small amounts, can have a measurable effect," she concludes.

Based on these results, Ulbrich, an expert in reproductive physiology, is calling for a re-assessment of the acceptable daily intake value and the "no observed effect level" dosage. She notes that pigs' hormonal changes during pregnancy closely resemble those in humans, so the results of the study are highly applicable to humans; they may even be more appropriate than findings from a study of, say, mice.

"At the moment, recommended threshold levels are probably too high," Ulbrich says. No matter how tiny the oestrogen dosage, the epigenetic changes she and her team observed clearly evidenced that the test subjects had been exposed to an EDC. She continues: "How exactly that resulted in the changes and what impact these changes will have in the long run requires closer study. The sensitivity of embryos in the early days of pregnancy should under no circumstances be underestimated."

Researchers from the University of North Carolina at Chapel Hill and Texas A&M University used satellite images, on-the-ground measurements and a statistical model to determine how much of the earth is covered by rivers and streams. They found that global river and stream surface area is about 45 percent greater than what was indicated by previous studies.

Rivers and streams are a major source of greenhouse gas emissions, so the significantly higher river and stream surface area calculation has important implications for understanding carbon emissions.

The research paper, authored by hydrologists Tamlin Pavelsky of UNC-Chapel Hill and George Allen of Texas A&M University, will be published in the journal Science on June 28.

"As we try to mitigate the effects of climate change, it's really important that we clearly understand where the carbon that we are emitting goes, and that requires us to accurately quantify the global carbon cycle," said Tamlin Pavelsky, senior author and associate professor of global hydrology in the College of Arts and Sciences at UNC-Chapel Hill. "Our new calculation helps scientists better assess how much carbon dioxide is moving from rivers and streams into the atmosphere each year."

This research differed from past studies of global river and stream surface areas that were based on theoretical extrapolations of small amounts of actual data. In this study, the research team was able to directly measure both the smallest streams and world's largest rivers through on-the-ground measurements and satellite images, and then use a statistical model to estimate river and stream coverage across the globe. As part of the study, the researchers built the Global River Widths from Landsat database, which contains almost 60 million measurements of river width worldwide.

NASA will use data from this research to identify river segments during its NASA Surface Water and Ocean Topography (SWOT) satellite mission, which will launch in 2021. The mission will be NASA's first satellite mission specifically focused on measuring rivers and lakes.

ARLINGTON, Va. - Advances in rapid molecular testing mean infectious diseases can be accurately diagnosed in minutes or hours rather than days or weeks and patients can receive appropriate treatment sooner. A guide released by the Infectious Diseases Society of America (IDSA) and American Society for Microbiology (ASM) helps health care providers keep up with the latest technology and know what tests to order and when. The new utilization of microbiology laboratory diagnosis for infectious diseases guide is published in the journal Clinical Infectious Diseases.

The guide updates recommendations published in 2013. "As fast as technology is moving, especially with the genetic and molecular tests, this update was necessary," said J. Michael Miller, PhD, lead author of the guide and director of Microbiology Technical Services, Dunwoody, Ga. "It also provides guidance in the careful and precise collection and management of blood, urine, skin or other tissue specimens, which is the cornerstone of accurate diagnosis and treatment of an infectious disease and the key to good patient care."

For example, tissue or fluid is the specimen of choice, but many health care providers send only a swab, which may not even contain the microbe that's causing the infection. Or the area wasn't adequately cleaned before blood was drawn or the wound scraped, resulting in a contaminated specimen. The guide also notes the importance of specifically labeling where the specimen came from (such as a cut at "top of right ear" vs. "skin") helping microbiologists rule out microbes in the culture that aren't problematic because they normally reside in certain areas of a healthy body. Sometimes a test isn't necessary at all, the guide notes. For example, there is one standard treatment for ear infections in children and the microbe causing the infection can only be accurately collected by inserting a needle behind the eardrum, which is very painful.

Guidance in lab diagnostics is vital because choosing the incorrect test or providing a contaminated or inadequate tissue specimen can lead to a wrong diagnosis and treatment that's not only harmful for the patient, but costly, such as leading to an extra day in the hospital.

Extensive tables provide detailed guidance in the use and limitations of the tests, organized by type of infection (such as urinary tract or upper respiratory) to help health care providers determine not only which test might be best, but which type of specimen is most appropriate. The guide also includes expanded information on pediatric needs and testing for tick-borne diseases such as Lyme disease as well as information on the advancements in diagnostics, including nucleic acid amplification tests that can identify organisms faster and far less expensively than in the past.

"Instead of using a shotgun approach and prescribing broad spectrum antibiotics, these new rapid diagnostic tests can help health care providers target the specific organism causing the infection much sooner than traditional microbiologic tests," said Melvin P. Weinstein, MD, FIDSA a co-author of the guide and chief of Infectious Diseases, Allergy and Immunology at Rutgers Robert Wood Johnson Medical School, New Brunswick, N.J.

The guide underscores the need for microbiologists to receive special training and for the laboratory to be led by a board-certified microbiology director or have access to board certification through a consultant in order to ensure high quality care. The guide also notes that excellent patient care is only possible through a collaborative, multidisciplinary approach.

"ID physicians are microbiologists' closest colleagues in supporting the need for a high-quality diagnostic process, start to finish," said Dr. Miller. "They understand the microbiology component and can serve as liaisons between the lab and other health care providers as can board certified microbiologists."

The IDSA/ASM guide panel includes experts in the fields of infectious diseases, microbiology, pathology and pediatrics. In addition to Drs. Miller and Weinstein, the panel includes: Mathew J. Binnicker, PhD; Sheldon Campbell, MD, PhD; Karen C. Carroll, MD, FIDSA; Kimberle C. Chapin, MD; Peter H. Gilligan, PhD; Mark D. Gonzalez, PhD; Robert C. Jerris, PhD; Sue C. Kehl, PhD; Robin Patel, MD, FIDSA; Bobbi S. Pritt, MD; Sandra S. Richter, MD, FIDSA; Barbara Robinson-Dunn, PhD, FIDSA; Joseph D. Schwartzman, MD, FIDSA; James W. Snyder, PhD; Sam Telford, III, SD; Elitza S. Theel, PhD; Richard B. Thomson Jr. PhD; and Joseph D. Yao, MD, FIDSA.

IDSA has published more than 50 treatment guidelines on various conditions and infections, ranging from HIV/AIDS to skin and soft tissue infections.. The full guide is available free on the Clinical Infectious Diseases website at https://academic.oup.com/cid/article-lookup/doi/10.1093/cid/ciy381.

Note: For an advance copy of the lab diagnosis guide, to be published online June 28, 2018, please contact Sam Guckenberger at (312) 558-1770 or sguckenberger@pcipr.com. The guide is embargoed until 1:05 a.m. ET on June 28.

A new family of enzymes has been discovered which paves the way to convert plant waste into sustainable and high-value products such as nylon, plastics, chemicals, and fuels.

The discovery was led by members of the same UK-US enzyme engineering team which, in April, improved a plastic-digesting enzyme, a potential breakthrough for the recycling of plastic waste.(Kate to add LINK)

The study published in Nature Communications was led by Professor John McGeehan at the University of Portsmouth, Dr Gregg Beckham at the US Department of Energy's National Renewable Energy Laboratory (NREL), Professor Jen Dubois at Montana State University, and Professor Ken Houk at the University of California, Los Angeles.

The new family of enzymes are active on the building blocks of lignin - one of the main components of plants, which scientists have been trying for decades to find a way of breaking down efficiently.

Professor McGeehan, Director of the Institute of Biological and Biomedical Sciences in the School of Biological Sciences at Portsmouth, said: "We have assembled an international team for the discovery and engineering of naturally occurring enzymes. Enzymes are biological catalysts that can perform incredible reactions, breaking down some of our toughest natural and man-made polymers.

"To protect their sugar-containing cellulose, plants have evolved a fascinatingly complicated material called lignin that only a small selection of fungi and bacteria can tackle. However, lignin represents a vast potential source of sustainable chemicals, so if we can find a way to extract and use those building blocks, we can create great things."

Lignin acts as scaffolding in plants and is central to water-delivery. It provides strength and also defence against pathogens.

"It's an amazing material," Professor McGeehan said, "cellulose and lignin are among the most abundant biopolymers on earth. The success of plants is largely due to the clever mixture of these polymers to create lignocellulose, a material that is challenging to digest."

The research team found a way of releasing a key bottleneck in the process of breaking down lignin to its basic chemicals. The results provide a route to making new materials and chemicals such as nylon, bioplastics, and even carbon fibre, from what has previously been a waste product.

The discovery also offers additional environmental benefits - creating products from lignin reduces our reliance on oil to make everyday products and offers an attractive alternative to burning it, helping to reduce CO2 emissions.

The research team was made up of experts in biophysics, structural biology, synthetic biology quantum chemistry, biochemistry, and molecular dynamics at the University of Portsmouth and NREL, and at the US universities of Montana State, Georgia, and California and Brazil's University of Campinas.

Sam Mallinson, a PhD student in structural biology at the University of Portsmouth and first author on the paper said: "There is a long-standing phrase - you can make anything out of lignin except money - but by harnessing the power of enzymes, this is set to change. Using advanced techniques, from X-ray crystallography at the Diamond Light Source synchrotron, to advanced computer modelling, we have been able to understand the detailed workings of a brand new enzyme system."

The enzyme is a new class of cytochrome P450, and it is promiscuous, meaning it's able to work on a wide range of molecules.

Dr Beckham said: "This new cytochrome P450 enzyme can degrade a lot of different lignin-based substrates. That's good because it means it can then be engineered to be a specialist for a specific molecule and we can evolve it further to push it in a certain direction.

"We now have one of the most well-known, versatile, engineerable and evolvable classes of enzymes ready to go as a foothold for biotechnology to move forward and make the enzyme better."

The research comes on the heels of another study just published in the journal PNAS, led by Professor Ellen Neidle at the University of Georgia together with members of this team, which found a way of speeding up the evolution of this enzyme. The group are now working together to discover and evolve even faster enzymes for turning lignin into high-value sustainable products.

Evidence from rocks in Yosemite National Park suggests that granite stored in the Earth's crust is partially molten at 500 degrees Celsius, nearly 200 degrees lower than had previously been believed. The finding, published online today in Nature, challenges long-held assumptions that underlie our views about the state of magma in volcanically active regions, the location of economically important ore deposits, and Earth's geothermal gradient.

"In making predictions, geologists have relied on a crystallization temperature for granite that was established more than half a century ago, using the best tools available at the time," said Michael Ackerson, lead author of the paper. Ackerson's adviser and corresponding author E. Bruce Watson, Institute Professor at Rensselaer Polytechnic Institute, added, "with advances in science and technology, our tools have improved. This finding will affect our understanding of where we find molten rock at depth in the Earth - knowledge that impacts several sub-fields of geology."

The finding draws on research establishing the effects of temperature and pressure on the titanium content of quartz, and builds on previous work which, in 2005, used the relationship between the titanium content of zircon and the temperature at which the zircon crystallized to reveal that early Earth contained liquid water near its surface only 200 million years after the solar system formed.

Beneath the surface of the Earth, temperature and pressure increase with depth. Changes in temperature and pressure with depth in the Earth impart unique chemical signatures in minerals that can subsequently be used to unravel the conditions in which the minerals formed. Quartz is primarily four atoms of oxygen arranged around one atom of silicon, but under certain temperatures and pressures, titanium atoms can replace silicon atoms in the quartz structure.

Through extensive experimentation and analysis, the Watson lab calibrated a "thermobarometer" that relates the concentration of titanium in a quartz crystal to the temperature and pressure under which it formed. In general, higher temperature and lower pressure allow more titanium to infiltrate the crystal, whereas lower temperature and higher pressure impede the incorporation of titanium into the crystal.

When applied to the titanium content of quartz crystals from the Tuolumne Intrusive Suite - a series of granites in Yosemite National Park that constitute a portion of the Sierra Nevada Mountains - the thermobarometer indicates a crystallization temperature of 474 to 561 degrees Celsius, well below the prevailing accepted crystallization temperature of 650-700 degrees Celsius.

These findings are supported by a comparison between quartz crystals from the Tuolumne Intrusive Suite and computer models predicting how titanium concentrations in a growing crystal will change as a function of initial crystallization temperature and cooling rate. Ackerson mapped titanium concentrations in cross-sections of quartz crystals using an electron microprobe. The maps show variations in titanium concentrations as the crystal grew from a central nucleation point, much as tree rings in the cross section of a tree trunk show the growth of a tree across time. Steep gradients in the cross-sections mark areas where titanium concentrations change rapidly. Ackerson extracted titanium concentration profiles from those gradients and compared them to computer diffusion models of titanium in quartz under varying initial crystallization temperatures and cooling rates. Diffusion models with an initial crystallization temperature of 500 degrees matched the gradients in Tuolumne suite quartz, thereby confirming the cool crystallization temperatures of quartz.

"Both tests, the 'thermometer' and the diffusion model, use titanium and quartz, but with two completely independent mechanisms to produce observations that show you these quartz crystals are crystallizing from melt at 500 degrees," said Ackerson. "Once you eliminate all the other possibilities, you're left with cold crystallization. And that is surprising."

The result is sufficiently unexpected that Ackerson and Watson said they are just beginning to consider applications. One will certainly be a new perspective on the geothermal gradient, which describes how temperature changes with depth, and therefore where molten materials will be found in the Earth's crust. Because many economically important ores, like porphyry copper and gold, are underlain by granites, the finding will likely impact the temperature regime under which they are predicted to form. And it may influence how geophysicists interpret data at active magmatic centers like Yellowstone, proving that current interpretations are recording temperatures lower than had been thought possible.

"Low-temperature crystallization of granites and the implications for crustal magmatism" appears in Nature. Watson and Ackerson were joined by co-authors B.O. Mysen of the Carnegie Institution of Washington, and N.D. Tailby of the American Museum of Natural History. Their research was partially funded by the Carnegie Institution of Washington's Postdoctoral Fellowship Program.

Geochemical research fulfills The New Polytechnic, an emerging paradigm for higher education which recognizes that global challenges and opportunities are so great they cannot be adequately addressed by even the most talented person working alone. Rensselaer serves as a crossroads for collaboration -- working with partners across disciplines, sectors, and geographic regions -- to address complex global challenges, using the most advanced tools and technologies, many of which are developed at Rensselaer. Research at Rensselaer addresses some of the world's most pressing technological challenges -- from energy security and sustainable development to biotechnology and human health. The New Polytechnic is transformative in the global impact of research, in its innovative pedagogy, and in the lives of students at Rensselaer.