May 31, 2016

Scientists find brain area responsible for learning from immediate experience

Scientists have confirmed one of the brain areas responsible for rapid updating of information during learning -- the sort of information we use to negotiate many changing situations in everyday life.
Scientists have confirmed one of the brain areas responsible for rapid updating of information during learning -- the sort of information we use to negotiate many changing situations in everyday life.

In a study funded by the Medical Research Council and published in journal eLife, a team from Oxford University and Imperial College looked at an area called the mediodorsal thalamus (MD), known to be involved in decision making and learning.

Senior author and Oxford researcher Dr Anna Mitchell explained: 'We already knew that the mediodorsal thalamus is involved in learning and decision making but did not fully understand the role it played. A key question in neurosciences is how the brain computes functions like planning a day's activities or making a decision to do one thing rather than another. We process information using widespread networks across the brain, so it is useful to focus on the contribution of particular areas to the overall task. In this case, we chose to look at how the mediodorsal thalamus supports optimal processing of new learning and decision making.'

The study used Rhesus macaque monkeys, who were taught cognitive tasks on touchscreen computers that released food rewards for learning new information and making good choices. These tests were then repeated after surgery that induced selective lesions to the MD.

Monkeys who could not use their MD were less able to respond to changes that required them to adapt their behaviour to continue making the right choices to maximise rewards. They also struggled with their decisions when they were presented with a choice of several differently rewarded options.

Dr Mitchell said: 'Previously, some had thought that in these cases the monkeys would just keep repeating the same choice as before. We found that they could make different choices but they had a reduced ability to integrate information from recent choices that they had made combined with the result of their most recent choice to optimally guide their decisions.

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Tobacco smoke makes germs more resilient

The mouth is one of the dirtiest parts of the body, home to millions of germs, and smoking makes it worse, say researchers.
The mouth is one of the dirtiest parts of the body, home to millions of germs. But puffing cigarettes can increase the likelihood that certain bacteria like Porphyromonas gingivalis will not only set up camp but will build a fortified city in the mouth and fight against the immune system.

University of Louisville School of Dentistry researcher David A. Scott, Ph.D., explores how cigarettes lead to colonization of bacteria in the body. Scott and his research team have identified how tobacco smoke, composed of thousands of chemical components, is an environmental stressor and promotes bacteria colonization and immune invasion.

Scott says since this initial finding several years ago, a recent literature review published in Tobacco Induced Diseases revealed that cigarette smoke and its components also promote biofilm formation by several other pathogens including Staphylococcus aureus, Streptococcus mutans, Klebsiella pneumonia and Pseudomonas aeruginosa.

Biofilms are composed of numerous microbial communities often made up of complex, interacting and co-existing multispecies structures. Bacteria can form biofilms on most surfaces including teeth, heart valves and the respiratory tract.

"Once a pathogen establishes itself within a biofilm, it can be difficult to eradicate as biofilms provide a physical barrier against the host immune response, can be impermeable to antibiotics and act as a reservoir for persistent infection," Scott said. "Furthermore, biofilms allow for the transfer of genetic material among the bacterial community and this can lead to antibiotic resistance and the propagation of other virulence factors that promote infection."

One of the most prevalent biofilms is dental plaque, which can lead to gingivitis -- a gum disease found in almost half the world's population -- and to more severe oral diseases, such as chronic periodontitis. Bacterial biofilms also can form on heart valves resulting in heart-related infections, and they also can cause a host of other problems.

"We are continuing research to understand the interactions of the elaborate communities within biofilms and how they relate to disease. Many studies have investigated biofilms using single species, but more relevant multispecies models are emerging. Novel treatments for biofilm-induced diseases also are being investigated, but we have a long way to go," Scott said.

Scott elaborates on this research in a short question and answer style blog to be published May 31 on the BioMedCentral website: http://blogs.biomedcentral.com/on-health/2016/05/31/wntd-author-qa/

Attention to Scott's work comes as the World Health Organization observes World No Tobacco Day on May 31 to encourage a global 24-hour abstinence from all forms of tobacco consumption. The effort points to the annual 6 million worldwide deaths linked to the negative health effects of tobacco use.

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3-D model reveals how invisible waves move materials within aquatic ecosystems

Garbage, nutrients and tiny animals are pushed around, suspended in the world's oceans by waves invisible to the naked eye according to a new 3-D model developed by mathematicians at the University of Waterloo. The image shows the 3-D model of mode 2 internal waves.
Garbage, nutrients and tiny animals are pushed around, suspended in the world's oceans by waves invisible to the naked eye according to a new 3-D model developed by mathematicians at the University of Waterloo.

David Deepwell, a graduate student, and Professor Marek Stastna in Waterloo's Faculty of Mathematics have created a 3-D simulation that showcases how materials such phytoplankton, contaminants, and nutrients move within aquatic ecosystems via underwater bulges called mode-2 internal waves.

The simulation can help researchers understand how internal waves can carry materials over long distances. Their model was presented in the American Institute of Physics' journal Physics of Fluids earlier this week.

In the simulation, fluids of different densities are layered like the layers of a cake, creating an environment similar to that found in large aquatic bodies such as oceans and lakes. A middle layer of fluid, known as a pycnocline, over which the layers are closely packed together is created, and it is in this layer that materials tend to be caught.

"When the fluid behind the gate is mixed and then the gate is removed, the mixed fluid collapses into the stratification because it is both heavier than the top layer and lighter than the bottom one," explained Deepwell, "Adding dye to the mixed fluid while the gate is in place simulates the material we want the mode-2 waves -- the bulges in the pycnocline formed once the gate is taken away -- to transport. We can then measure the size of the wave, how much dye remains trapped within it, and how well the wave carries its captured material."

Deepwell and Statsna found that the larger the bulge within the pycnocline, the larger the amount of material carried by the mode-2 wave.

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Remains of rice and mung beans help solve a Madagascan mystery

Residues of plant remains were obtained from sediments in the archaeological layers.
Researchers have helped solve one of the enduring mysteries of the ancient world: why the inhabitants of Madagascar speak Malagasy, a language otherwise unique to Southeast Asia and the Pacific -- a region located at least 6,000 km away. An international research team has identified that ancient crop remains excavated from sites in Madagascar consist of Asian species like rice and mung beans. This is thought to be the first archaeological evidence that settlers from South Asia are likely to have colonised the island over a thousand years ago. The findings are published in the journal, Proceedings of the National Academy of Sciences.

Genetic research has confirmed that the inhabitants of Madagascar do indeed share close ancestry with Malaysians, Polynesians, and other speakers of what is classed the Austronesian language family. To date, archaeological research has identified human settlements in Madagascar that belong to the first millennium. There are also findings suggesting that Madagascar may have been occupied by hunter-gatherers who probably arrived from Africa by the first or second millennium. Until now, however, archaeological evidence of the Austronesian colonisation has been missing.

The team were able to identify the species of nearly 2,500 ancient plant remains obtained from their excavations at 18 ancient settlement sites in Madagascar, on neighbouring islands and on the eastern African coast. They examined residues obtained from sediments in the archaeological layers, using a system of sieves and water. They looked at whether the earliest crops grown on the sites were African crops or were crops introduced to Africa from elsewhere. They found both types, but noted a distinct pattern, with African crops primarily concentrated on the mainland and the islands closest to the mainland. In Madagascar, in contrast, early subsistence focused on Asian crops. The data suggested an introduction of these crops, both to Madagascar and the neighbouring Comoros Islands, by the 8th and 10th century.

Senior author Dr Nicole Boivin, from the School of Archaeology at the University of Oxford and Director of the Department of Archaeology at the Max Planck Institute for the Science of Human History, said: 'Southeast Asians clearly brought crops from their homeland and grew and subsisted on them when they reached Africa. This means that archaeologists can use crop remains as evidence to provide real material insights into the history of the island. There are a lot of things we still don't understand about Madagascar's past; it remains one of our big enigmas. But what is exciting is that we finally have a way of providing a window into the island's highly mysterious Southeast Asian settlement and distinguishing it from settlements by mainland Africans that we know also happened.'

The analyses also suggest that Southeast Asians colonised not only Madagascar but also the nearby islands of the Comoros, because again the crops that grew there were dominated by the same Asian species. By contrast, crops identified on the eastern African coast and near coastal islands like Mafia and Zanzibar were mainly African species like sorghum, pearl millet and baobab.

Commenting on the Southeast Asian influence in the Comoros, study lead author Dr Alison Crowther, from the University of Queensland, Australia, said: 'This took us by surprise. After all, people in the Comoros speak African languages and they don't look like they have Southeast Asian ancestry in the way that populations on Madagascar do. What was amazing to us was the stark contrast that emerged between the crops on the Eastern African coast and the offshore islands versus those on Madagascar, but also the Comoros.'

Read more at Science Daily

May 30, 2016

Arctic Ocean methane does not reach the atmosphere

Ocean floor observatories, research ship and airplane were deployed to a area of 250 active methane gas flares in the Arctic Ocean.
250 methane flares release the climate gas methane from the seabed and into the Arctic Ocean. During the summer months this leads to an increased methane concentration in the ocean. But surprisingly, very little of the climate gas rising up through the sea reaches the atmosphere.

"Our results are exciting and controversial," says senior scientist Cathrine Lund Myhre from NILU -- Norwegian Institute for Air Research, who is cooperating with CAGE through MOCA project.

The results were published in Geophysical Research Letters.

The scientist performed simultaneous measurements close to seabed, in the ocean and in the atmosphere during an extensive ship and air campaign offshore Svalbard Archipelago in summer 2014. As of today, three independent models employing the marine and atmospheric measurements show that the methane emissions from the sea bed in the area did not significantly affect the atmosphere.

"This is an important message to bring to the debate on the state of the ocean and atmospheric system in the Arctic. It is also important to emphasize that the Arctic has in recent years experienced major changes and average temperatures well above normal values. A thorough description of the present state of the Arctic environment, possible only with adequate measurements, is essential to the detection of future changes of potentially global significance." says Lund Myhre.

Methane increase since 2006

Levels of methane in the atmosphere have risen by an average of 6 parts per billion (ppb) globally per year since 2006, and slightly more over the Arctic and Norway. Since methane is the most important greenhouse gas after CO2, it is very important to explore why.

Vast quantities of methane gas are stored under the seabed in ice-like substances called methane hydrates. One possible explanation for the increased methane concentration in the atmosphere is that these hydrates dissolve as the oceans become warmer. Methane gas leaks from the methane hydrates under the seabed, and rises through the water. The scientists want to find out if these emissions are increasing, and just how much methane is reaching the atmosphere.

"Estimates on how much methane gas is stored beneath the seabed as hydrates vary enormously. A recent calculation suggests that we are talking about 74,000 gigatonnes, and one gigatonne is a billion tonnes," says professor Jürgen Mienert, director at CAGE.

If any of the methane stored in the Arctic hydrate reservoirs is released into the atmosphere as a result of climate change, this could have a global impact in terms of further climate warming, in addition to what human activities are already contributing.

Why is methane not released to the atmosphere?


Sea ice, the obvious obstacle to such emissions, is not found here in the summer. So what is stopping the methane? Emissions from the sea bed are after all clearly visible both on the seabed and in the water column.

"We are talking about 250 active methane seeps found at relatively shallow depths: 90 to 150 meters" says oceanographer Benedicte Ferré from CAGE.

According to her, it is the sea itself that adds obstacles to methane emissions to the atmosphere in the summer. The weather is generally calm during summer, with little wind. This leads to stratification of the water column whereby layers of different density form, much like oil over water.

This means there is no or low exchange of water masses between the surface layer and the layers below. A natural barrier occurs, acting as a ceiling, preventing the methane from reaching the surface.But this condition does not last forever: wind blowing over the ocean can mix these layers, causing this natural barrier to disappear. Thus the methane may break the surface and enter the atmosphere.

"There is still a lot we do not know about seasonal variations. The methane can also be transported by water masses, or dissolve and be eaten by bacteria in the ocean. Thus long term observations are necessary to understand the emissions throughout the year. The only way to obtain these measurements are to use observatories that remain on the seabed for a long time," says Benedicte Ferré.

CAGE set out two such observatories last year, which have been retrieved in May with data waiting to be analysed.

Read more at Science Daily

Deep, old water explains why Antarctic Ocean hasn't warmed

Observed warming over the past 50 years (in degrees Celsius per decade) shows rapid warming in the Arctic, while the Southern Ocean around Antarctica has warmed little, if at all.
The waters surrounding Antarctica may be one of the last places to experience human-driven climate change. New research from the University of Washington and the Massachusetts Institute of Technology finds that ocean currents explain why the seawater has stayed at roughly the same temperature while most of the rest of the planet has warmed.

The study resolves a scientific conundrum, and an inconsistent pattern of warming often seized on by climate deniers. Observations and climate models show that the unique currents around Antarctica continually pull deep, centuries-old water up to the surface -- seawater that last touched Earth's atmosphere before the machine age, and has never experienced fossil fuel-related climate change. The paper is published May 30 in Nature Geoscience.

"With rising carbon dioxide you would expect more warming at both poles, but we only see it at one of the poles, so something else must be going on," said lead author Kyle Armour, a UW assistant professor of oceanography and of atmospheric sciences. "We show that it's for really simple reasons, and ocean currents are the hero here."

Gale-force westerly winds that constantly whip around Antarctica act to push surface water north, continually drawing up water from below. The Southern Ocean's water comes from such great depths, and from sources that are so distant, that it will take centuries before the water reaching the surface has experienced modern global warming.

Other places in the oceans, like the west coast of the Americas and the equator, draw seawater up from a few hundred meters depth, but that doesn't have the same effect.

"The Southern Ocean is unique because it's bringing water up from several thousand meters [as much as 2 miles]," Armour said. "It's really deep, old water that's coming up to the surface, all around the continent. You have a lot of water coming to the surface, and that water hasn't seen the atmosphere for hundreds of years."

The water surfacing off Antarctica last saw Earth's atmosphere centuries ago in the North Atlantic, then sank and followed circuitous paths through the world's oceans before resurfacing off Antarctica, hundreds or even a thousand years later.

Delayed warming of the Antarctic Ocean is commonly seen in global climate models. But the culprit had been wrongly identified as churning, frigid seas mixing extra heat downward. The study used data from Argo observational floats and other instruments to trace the path of the missing heat.

"The old idea was that heat taken up at the surface would just mix downward, and that's the reason for the slow warming," Armour said. "But the observations show that heat is actually being carried away from Antarctica, northward along the surface."

In the Atlantic, the northward flow of the ocean's surface continues all the way to the Arctic. The study used dyes in model simulations to show that seawater that has experienced the most climate change tends to clump up around the North Pole. This is another reason why the Arctic's ocean and sea ice are bearing the brunt of global warming, while Antarctica is largely oblivious.

"The oceans are acting to enhance warming in the Arctic while damping warming around Antarctica," Armour said. "You can't directly compare warming at the poles, because it's occurring on top of very different ocean circulations."

Read more at Science Daily

The brain clock that keeps memories ticking

Just as members of an orchestra need a conductor to stay on tempo, neurons in the brain need well-timed waves of activity to organize memories across time. In the hippocampus -- the brain's memory center -- temporal ordering of the neural code is important for building a mental map of where you've been, where you are, and where you are going. Published on May 30 in Nature Neuroscience, research from the RIKEN Brain Science Institute in Japan has pinpointed how the neurons that represent space in mice stay in time.

As a mouse navigates its environment, the central hippocampal area called CA1 relies on rhythmic waves of neural input from nearby brain regions to produce an updated map of space. When researchers turned off the input from nearby hippocampal area CA3, the refreshed maps became jumbled. While mice could still do a simple navigation task, and signals from single neurons appeared to represent space accurately, the population level code, or 'orchestra' was out of time and contained errors. "The neural music didn't change," said senior author Thomas McHugh, "but by silencing CA3 input to CA1 in the hippocampus we got rid of the conductor."

McHugh and co-author Steven Middleton accomplished this by genetically engineering mice to express a nerve toxin in CA3 that shut down the synaptic junctions between CA3 and other brain areas. The overall neuronal activity was preserved, but with synaptic communication effectively muted, they could measure the impact of removing CA3 input on the space map in area CA1.

While mice ran up and down a track, the authors recorded multiple individual neurons as well as the summed electric current from a larger group of neurons, called local field potentials. This allowed them to monitor each theta cycle, the time period over which the hippocampus updates its neural map of space as the mouse moves.

Comparing the individual and population activity in normal and transgenic mice, they made an apparently paradoxical observation. As the transgenic mice moved in the enclosure, individual neurons continued to update their activity at a regular interval of 8 Hz, known as theta-cycle phase precession. This cyclic organization of information, however, was absent across the population of neurons. "Without input from CA3, there was no global organization of the neural signals across the theta cycle to define where the mouse came from or where it was going," said McHugh.

The discovery of the mental map of space in the hippocampus was awarded the 2014 Nobel Prize in Physiology or Medicine, but the circuitry connecting ensembles of place cells, which are also used for memory processing, and how they update in realtime was not known. Without CA3 input, accurate prediction of the spatial location from the ensemble neural code is impaired. The mouse still knows where it is, but small errors in representing space from individual neurons become compounded without CA3 directing the CA1 ensemble. "If neurons don't activate in sequence, you can't organize memories across time," says McHugh. "Whether in mice or humans, you need temporal organization to get from here to there, to make decisions and reach goals." If shutdown of CA3 was possible in humans, McHugh suggests, memories would likely become useless and jumbled. Earlier work with these same mice pointed to a similar role for the CA3 neurons in organizing information during sleep, a process required for long-term memory storage.

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Remains of bizarre group of extinct snail-eating Australian marsupials discovered

These are maxilla of the young malleodectid -- a snail-eating marsupial -- found in the fossil cave deposit at Riversleigh. Because this is a juvenile, the massive premolar is still unerupted below the tooth row.
Fossil remains of a previously unknown family of carnivorous Australian marsupials that lived 15 million years ago have been discovered at the Riversleigh World Heritage Fossil Site in north-western Queensland by a UNSW Australia-led team of researchers.

"Malleodectes mirabilis was a bizarre mammal, as strange in its own way as a koala or kangaroo," says study lead author UNSW Professor Mike Archer.

"Uniquely among mammals, it appears to have had an insatiable appetite for escargot--snails in the whole shell. Its most striking feature was a huge, extremely powerful, hammer-like premolar that would have been able to crack and then crush the strongest snail shells in the forest."

Research describing the new marsupials is published in the journal Scientific Reports.

Isolated teeth and partial dentitions of this unusual group, known as malleodectids, had been unearthed over the years at Riversleigh, where Professor Archer and his colleagues have excavated for almost four decades. But the profoundly different nature of the marsupials was not realised until a well-preserved portion of the skull of a juvenile was found in a 15 million year old Middle Miocene cave deposit at Riversleigh.

This juvenile specimen was only recently extracted from its limestone casing, using an acid bath at UNSW, which made it available for study with modern techniques including micro-computed tomography. The young animal still had its baby teeth, and was teething, with adult teeth that had been about to erupt when it was alive still embedded in its jaw.

"Details of the canine, premolar and molar teeth of this specimen have enabled its relationships to other Australian marsupials to be determined with reasonable confidence," says Professor Archer, of the PANGEA Research Centre in the UNSW School of Biological, Earth and Environmental Sciences.

"Although it is very different from the others, it appears to have been related to the dasyures -- marsupial carnivores such as Tasmanian Devils and the extinct Tasmanian Tigers that are unique to Australia and New Guinea."

Nothing remains of the cave at Riversleigh, known as AL90 site, except its limestone floor, which contains the bones of thousands of animals that fell into, or lived in, the ancient cave.

"The juvenile malleodectid could have been clinging to the back of its mother while she was hunting for snails in the rocks around the cave's entrance, and may have fallen in and then been unable to climb back out," says team member UNSW Professor Suzanne Hand.

"Many other animals that lived in this lush forest met a similar fate with their skeletons accumulating one on top of another for perhaps thousands of years, until the cave became filled with palaeontological treasures.

"Over millions of years the walls and ceiling of the cave were eroded away, leaving only the fossil-rich floor, which was discovered by our Riversleigh Project team members in 1990."

Subsequent quarrying of the cave floor has produced thousands of exquisite fossils including the articulated skeletons of the ram-sized, sloth-like Nimbadon -- an extinct marsupial that fell in while moving overhead in the tree tops.

The Riversleigh World Heritage fossil deposits, which span the last 24 million years of Australian history, have produced many previously unknown kinds of animals such as Thingodonta, which may have been a woodpecker-like marsupial; Fangaroo, a tusked kangaroo; Drop crocs, which are strange leopard-like crocodiles that may have been arboreal; and Dromornis -- the Demon Duck of Doom, which was one of the largest birds in the world.

The Riversleigh Project, which has been a major focus of the palaeontological team at UNSW, is about to carry out its 40th annual expedition to Riversleigh.

Once again, the team expects to discover yet more strange creatures that once populated Australia's ancient rainforests at a time when the northern regions of the continent looked more like Amazonian rainforests than the arid zone the area has become today.

Of particular interest for this year's expedition will be younger apparently Late Miocene rocks discovered by the team, assisted by funding from the Australian Research Council and the National Geographic Society, in a remote area now called "New Riversleigh." These will fill a key time period for the rich, long record of environmental change at Riversleigh.

Among the first tantalising discoveries from "New Riversleigh" has been yet another bizarre, hyper-carnivorous marsupial that looks like it might be a younger, far more powerful cousin of the earlier snail-eating malleodectids.

Like so many of the strange creatures continuously being discovered in Riversleigh's rocks, malleodectids went extinct long before humans arrived.

Read more at Science Daily

May 29, 2016

How the brain makes, and breaks, a habit

Working with a mouse model, an international team of researchers demonstrates what happens in the brain for habits to control behavior.
Not all habits are bad. Some are even necessary. It's a good thing, for example, that we can find our way home on "autopilot" or wash our hands without having to ponder every step. But inability to switch from acting habitually to acting in a deliberate way can underlie addiction and obsessive compulsive disorders.

Working with a mouse model, an international team of researchers demonstrates what happens in the brain for habits to control behavior.

The study is published in Neuron and was led by Christina Gremel, assistant professor of psychology at the University of California San Diego, who began the work as a postdoctoral researcher at the National Institute on Alcohol Abuse and Alcoholism of the National Institutes of Health. Senior authors on the study are Rui Costa, of the Champalimaud Centre for the Unknown in Lisbon, and David Lovinger of the NIAAA/NIH.

The study provides the strongest evidence to date, Gremel said, that the brain's circuits for habitual and goal-directed action compete for control -- in the orbitofrontal cortex, a decision-making area of the brain -- and that neurochemicals called endocannabinoids allow for habit to take over, by acting as a sort of brake on the goal-directed circuit.

Endocannabinoids are a class of chemicals produced naturally by humans and other animals. Receptors for endocannabinoids are found throughout the body and brain, and the endocannabinoid system is implicated in a variety of physiological processes -- including appetite, pain sensation, mood and memory. It is also the system that mediates the psychoactive effects of cannabis.

Earlier work by Gremel and Costa had shown that the orbitofrontal cortex, or OFC, is an important brain area for relaying information on goal-directed action. They found that by increasing the output of neurons in the OFC with a technique called optogenetics -- precisely turning neurons on and off with flashes of light -- they increased goal-directed actions. In contrast, when they decreased activity in the same area with a chemical approach, they disrupted goal-directed actions and the mice relied on habit instead.

"Habit takes over when the OFC is quieted," Gremel said.

In the current study, since endocannabinoids are known to reduce the activity of neurons in general, the researchers hypothesized that endocannabinoids may be quieting or reducing activity in the OFC and, with it, the ability to shift to goal-directed action. They focused particularly on neurons projecting from the OFC into the dorsomedial striatum.

They trained mice to perform the same lever-pressing action for the same food reward but in two different environments that differentially bias the development of goal-directed versus habitual actions. Like humans who don't suffer from neuropsychiatric disorders, healthy mice will readily shift between performing the same action using a goal-directed versus habitual action strategy. To stick with the earlier example of getting home, we can switch the homing autopilot off and shift to goal-directed behavior when we need to get to a new or different location.

To test their hypothesis on the role played by endocannabinoids, the researchers then deleted a particular endocannabinoid receptor, called cannabinoid type 1, or CB1, in the OFC-to-striatum pathway. Mice missing these receptors did not form habits -- showing the critical role played by the neurochemicals as well as that particular pathway.

"We need a balance between habitual and goal-directed actions. For everyday function, we need to be able to make routine actions quickly and efficiently, and habits serve this purpose," Gremel said. "However, we also encounter changing circumstances, and need the capacity to 'break habits' and perform a goal-directed action based on updated information. When we can't, there can be devastating consequences."

Read more at Science Daily

Why malnutrition is an immune disorder

Malnourished children are most likely to die from common infections, not starvation. New experimental evidence, reviewed May 26 in Trends in Immunology, indicates that even with a healthy diet, defects in immune system function from birth could contribute to a malnourished state throughout life. Researchers speculate that targeting immune pathways could be a new approach to reduce the poor health and mortality caused by under- and overnutrition.

"That traditional image of malnutrition that we're unfortunately so familiar with--of someone wasting away--that's just the external picture," says Review first author Claire Bourke, a postdoctoral research assistant in the Centre for Genomics and Child Health at Queen Mary University of London. "Those height and weight defects that we see are the tip of the iceberg--there are a whole range of pro-inflammatory conditions, impaired gut function, weakened responses to new infections, and a resulting high metabolic burden underlying them."

The most common form of undernutrition globally is stunting -- where children fail to achieve their full height potential. Despite looking healthy, children in developing countries who are stunted in height may also have stunted immune development, making them more vulnerable to death by common infections.

Only recently have researchers had access to technology that can accurately study immunodeficiency. Even though immune parameters in undernourished children have been looked at for decades, much of that data is outdated. How malnutrition and immune function are related is actually still poorly understood; however, there is wide acceptance that malnutrition comes with a range of immune problems. These include reduced numbers of white blood cells, skin and gut membranes that are easier for pathogens to break through, and malfunctioning lymph nodes.

What's also emerging is that the relationship between malnutrition and immune dysfunction may be a bit "chicken and egg," with both causing and being the consequence of the other. Immune dysfunction results when people consume too few calories because of lack of food or have an excess of fat and sugar in their diet. That dysfunction is recorded in the DNA through epigenetic marks, so that if malnourished people have offspring, their children inherit an altered immune system (even after multiple generations). This altered immune system may then cause malnutrition even if children have an adequate diet.

"It's been thought for a long time that the immune system is driving pathology, but new experimental tools have made it possible to separate out the effects of the immune system from those of the diet alone," says Bourke. "There are new models for environmental enteric dysfunction in mice, a growing interest in microbiota and epigenetics--all of these studies show that the more we look into the immune system, the more it has a role to play in a really wide array of physiological systems. It doesn't just fight infection; it affects metabolism, neurological function, and growth, which are things that are also impaired in malnutrition."

Bourke imagines a future where clinicians could generate individualized immune readouts that can identify young people most susceptible to infection as a result of malnutrition. This could reduce the burden of a leading cause of child mortality by helping those who are most vulnerable get treated more often and sooner with targeted interventions.

Read more at Science Daily