Genes, ozone, and autism

A new analysis shows that individuals with high levels of genetic variation and elevated exposure to ozone in the environment are at an even higher risk for developing autism than would be expected by adding the two risk factors together. The study is the first to look at the combined effects of genome-wide genetic change and environmental risk factors for autism, and the first to identify an interaction between genes and environment that leads to an emergent increase in risk that would not be found by studying these factors independently. A paper describing the research appears online in the journal Autism Research.

“Autism, like most human diseases, is complex,” said Scott B. Selleck, professor of biochemistry and molecular biology at Penn State and one of the leaders of the research team. “There are probably hundreds, if not thousands, of genes involved and up until now — with very few exceptions — these have been studied independently of the environmental contributors to autism, which are real. Our team of researchers represents a merger of people with genetic expertise and environmental epidemiologists, allowing us for the first time to answer questions about how genetic and environmental risk factors for autism interact.”

The team looked at copy-number variation — deletions and duplications of repeated elements in the genome that lead to variation among individuals in the number of repeated elements — as a general measure of genetic variation and five types of air pollution — traffic-related air pollution, nitrogen oxides, two sizes of particulate matter, and ozone — in a large set of individuals with autism and a well-matched set of typically developing controls. The study participants — obtained through the Childhood Autism Risks from Genetics and Environment (CHARGE) Study, a population-based case-control study led by Irva Hertz-Picciotto, professor of epidemiology and chief of the Division of Environmental and Occupational Health at University of California Davis, and one of the leaders of the research team — includes cases and controls matched for age, sex, and geographic location. Each of 158 cases and 147 controls were genetically scored for genetic deletions, duplications, and total changes in copy number. Environmental exposures for each participant were determined based on residential histories using data from the U.S. Environmental Protection Agency (EPA) Air Quality System.

“This study used unique resources,” said Hertz-Picciotto. “By mapping the homes of the mothers during their pregnancies, we were able to estimate their levels of exposure to several types of air pollutants that are monitored by the U.S. EPA. This allowed us to examine differences between cases of autism and typically developing controls in both their prenatal pollutant exposure and their total load of extra or deleted genetic material.”

Evaluation of each of the risk factors showed that duplications, total copy-number variation, and particulate matter in the environment had the largest individual impact on risk for autism. However, when the researchers evaluated interactions among the various risk factors they saw a large effect of ozone among children with either duplications or total copy-number variation. Ozone on its own had very little effect on risk for autism, such that in studies that did not take interactions among risk factors into consideration, it may have been ignored. Interactions among the various other factors, even those with large individual effects, appeared to have very little effect on risk.

“This study showed the effect of a pollutant not previously associated with autism risk. This study may be one example of how taking genomic variation into account can help us identify new risk factors for autism,” said Heather Volk, assistant professor in the Department of Mental Health at the Johns Hopkins Bloomberg School of Public Health.

“If we just look at the raw numbers, before any statistical assessment, we see a ten-fold increase in the risk of autism for individuals in the top 25 percent for level of genetic variation and in the top 25 percent for exposure to ozone as compared to the individuals in the bottom 25 percent for each of these measures,” said Selleck. “This increase in risk is striking, but given what we know about the complexity of diseases like autism, perhaps not surprising. It demonstrates how important it is to consider different types of risk factors for disease together, even those with small individual effects.”

The researchers speculate that the large effect of the interaction between ozone exposure and copy-number variation could be the result of the fact that ozone is an oxidizing agent, and is known to produce reactive oxygen species, like peroxides, that cause cellular stress and can alter cell function in many ways. High levels of copy-number variation may indicate a compromised state that is primed for the type of damage that ozone can cause.

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Is it okay for children to count on their fingers?

Is it OK for children to count on their fingers? Generations of pupils have been discouraged by their teachers from using their hands when learning maths. But a new research article, published in Frontiers in Education shows using fingers may be a much more important part of maths learning than previously thought.

The article, by Professor Tim Jay of Sheffield Hallam University and independent researcher Dr Julie Betenson, confirms what parents have long felt instinctively — that the sorts of finger games children often play at home are central to their education.

The researchers worked with 137 primary pupils aged between six and seven. All the children were given different combinations of counting and number games to play — but only some were given exercises which involved finger-training.

Some pupils played games involving number symbols, such as dominoes, shut-the-box, or snakes and ladders.

Other pupils were asked to play finger games: such being asked to hold up a given number of fingers, or numbering fingers from 1 — 5 and then having to match one of them by touching it against the corresponding finger on the other hand, or tracing coloured lines using a particular finger.

Both these groups did a little better in maths tests than a third group of pupils who had simply had ‘business as usual’ with their teachers. But the group which did both the counting and the finger games fared significantly better.

“This study provides evidence that fingers provide children with a ‘bridge’ between different representations of numbers, which can be verbal, written or symbolic. Combined finger training and number games could be a useful tool for teachers to support children’s understanding of numbers,” Professor Jay said.

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Heavy-Drinking Mothers Linked to Their Child’s Path Toward the Justice System

This study investigated whether children whose mothers had an alcohol-related disorder would be at risk of early-life contact with the justice system, which can lead to many negative outcomes across an individual’s life span. Such outcomes can include repeated contact with the justice system, social disadvantages and marginalization, and mental-health and substance-use issues.

The study made use of linked administrative data from Western Australia. It used records of women who had a birth recorded on the Midwives Notification System between 1983 and 2007. The exposed cohort included mothers with an alcohol-related diagnosis, which served as a proxy for heavy drinking. A comparison group of mothers with no alcohol-related diagnoses was randomly selected, matching on maternal age within race and the year of the child’s birth. The study cohort included 10,211 exposed mothers and 47,688 comparison mothers. Child contact with the justice system was identified from Department of Corrective Services data — including those 10 years or older with a justice-system record for juveniles (10 — 17 years) and/or adults (18 years and older) from 1985 to 2011.

Children whose mothers had a maternal alcohol-related diagnosis had almost twice the odds of contact with the justice system as children whose mothers had no alcohol-related diagnosis. Additional risk was associated with being Indigenous and with markers of social disadvantage such as low socioeconomic status. Significant child-level factors associated with greater odds of justice-system contact included being male, having a mental-health diagnosis or child-protection contact, and academic failure. The authors suggest that these factors be considered in the development of targeted prevention programs.


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Journal Reference:

  1. Katherine Hafekost, David Lawrence, Colleen O’Leary, Carol Bower, James Semmens, Stephen R. Zubrick. Maternal Alcohol Use Disorder and Risk of Child Contact with the Justice System in Western Australia: A Population Cohort Record Linkage Study. Alcoholism: Clinical and Experimental Research, 2017; DOI: 10.1111/acer.13426

Cite This Page:

Research Society on Alcoholism. “Heavy-drinking mothers linked to their child’s path toward the justice system.” ScienceDaily. ScienceDaily, 22 June 2017. .

Research Society on Alcoholism. (2017, June 22). Heavy-drinking mothers linked to their child’s path toward the justice system. ScienceDaily. Retrieved June 23, 2017 from www.sciencedaily.com/releases/2017/06/170622182809.htm

Research Society on Alcoholism. “Heavy-drinking mothers linked to their child’s path toward the justice system.” ScienceDaily. www.sciencedaily.com/releases/2017/06/170622182809.htm (accessed June 23, 2017).

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Spinal cord injury: Using cortical targets to improve motor function

Monica A. Perez, P.T., Ph.D., Associate Professor, Department of Neurological Surgery and The Miami Project, and colleagues, recently published A novel cortical target to enhance hand motor output in humans with spinal cord injury in the June issue of Brain that provides the first evidence that cortical targets could represent a novel therapeutic site for improving motor function in humans paralyzed by spinal cord injury (SCI).

A main goal of rehabilitation strategies in humans with SCI is to strengthen transmission in spared neural networks. Although neuromodulatory strategies have targeted different sites within the central nervous system to restore motor function following SCI, the role of cortical targets remains poorly understood.

“I am excited to see that electrophysiology can be successfully used to guide interventions for recovery of function after spinal cord injury,” says Dr. Perez.

In this study, Drs. Perez, Jinyi Long, Ph.D., and Paolo Federico, Ph.D. used 180 pairs of noninvasive transcranial magnetic stimulation for 30 minutes over the hand representation of the primary motor cortex at an interstimulus interval mimicking the rhythmicity of descending late indirect (I) waves in corticospinal neurons (4.3 ms; late I-wave protocol) or at an interstimulus interval in-between I-waves (3.5 ms; control protocol) on separate days in a randomized order.

Late I-waves are thought to arise from trans-synaptic cortical inputs and have a crucial role in the recruitment of spinal motor neurons following SCI. The researchers found that the excitability of corticospinal projections to intrinsic finger muscles increased in SCI and uninjured participants after the late I-wave but not the control protocol for 30 to 60 minutes after the stimulation. Importantly, individuals with SCI were able to exert more force and electromyographic activity with finger muscles after the stimulation showing an enhanced ability to grasp small objects with their hands.

“This study is a major contribution to the realization of a powerful new class of rehabilitation therapies that can target beneficial plasticity to crucial sites in the nervous system. By taking advantage of recent scientific and technical advances, Dr. Perez’s group produced beneficial change in the cortical circuitry and spinal connections underlying voluntary movement,” says Dr. Jonathan R. Wolpaw, M.D. Director of the National Center for Adaptive Neurotechnologies Albany, New York.

“This carefully conducted study provides several pieces of important information in developing strategies to improve function following spinal cord injury. They provide further evidence demonstrating rather clearly, contrary to years of dogma, that positive functional plasticity potential persists within the sensorimotor system for years after a spinal injury,” says Dr. Reggie Edgerton, Ph.D. UCLA Brain Research Institute.

These results emphasize the need to develop new rehabilitation therapies based on mechanistic approaches to improve motor function in humans with paralysis due to spinal cord injury. Currently, Dr. Perez’ group is testing the effect of this intervention when given on consecutive days and in individuals with more severe muscle paralysis.

“What I find appealing about the work is that they exploit a basic characteristic of the human corticospinal neural circuit and designed a way to strengthen connections that does not depend on the person performing a motor task,” said John H. Martin, Ph.D., The City College of New York.

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Interventions to prevent cognitive decline, dementia

Cognitive training, blood pressure management for people with hypertension, and increased physical activity all show modest but inconclusive evidence that they can help prevent cognitive decline and dementia, but there is insufficient evidence to support a public health campaign encouraging their adoption, says a new report from the National Academies of Sciences, Engineering, and Medicine. Additional research is needed to further understand and gain confidence in their effectiveness, said the committee that conducted the study and wrote the report.

“There is good cause for hope that in the next several years much more will be known about how to prevent cognitive decline and dementia, as more clinical trial results become available and more evidence emerges,” said Alan I. Leshner, chair of the committee and CEO emeritus, American Association for the Advancement of Science. “Even though clinical trials have not conclusively supported the three interventions discussed in our report, the evidence is strong enough to suggest the public should at least have access to these results to help inform their decisions about how they can invest their time and resources to maintain brain health with aging.”

An earlier systematic review published in 2010 by the Agency for Healthcare Research and Quality (AHRQ) and an associated “state of the science” conference at the National Institutes of Health had concluded that there was insufficient evidence to make recommendations about any interventions to prevent cognitive decline and dementia. Since then, understanding of the pathological processes that result in dementia has advanced significantly, and a number of clinical trials of potential preventive interventions have been completed and published. In 2015, the National Institute on Aging (NIA) contracted with AHRQ to conduct another systematic review of the current evidence. NIA also asked the National Academies to convene an expert committee to help inform the design of the AHRQ review and then use the results to make recommendations to inform the development of public health messaging, as well as recommendations for future research. This report examines the most recent evidence on steps that can be taken to prevent, slow, or delay the onset of mild cognitive impairment and clinical Alzheimer’s-type dementia as well as steps that can delay or slow age-related cognitive decline.

Overall, the committee determined that despite an array of advances in understanding cognitive decline and dementia, the available evidence on interventions derived from randomized controlled trials — considered the gold standard of evidence — remains relatively limited and has significant shortcomings. Based on the totality of available evidence, however, the committee concluded that three classes of interventions can be described as supported by encouraging but inconclusive evidence. These interventions are:

cognitive training — which includes programs aimed at enhancing reasoning and problem solving, memory, and speed of processing — to delay or slow age-related cognitive decline. Such structured training exercises may or may not be computer-based. blood pressure management for people with hypertension — to prevent, delay, or slow clinical Alzheimer’s-type dementia. increased physical activity — to delay or slow age-related cognitive decline.

Cognitive training has been the object of considerable interest and debate in both the academic and commercial sectors, particularly within the last 15 years. Good evidence shows that cognitive training can improve performance on a trained task, at least in the short term. However, debate has centered on evidence for long-term benefits and whether training in one domain, such as processing speed, yields benefits in others, such as in memory and reasoning, and if this can translate to maintaining independence in instrumental activities of daily living, such as driving and remembering to take medications. Evidence from one randomized controlled trial suggests that cognitive training delivered over time and in an interactive context can improve long-term cognitive function as well as help maintain independence in instrumental activities of daily living for adults with normal cognition. However, results from other randomized controlled trials that tested cognitive training were mixed.

Managing blood pressure for people with hypertension, particularly during midlife — generally ages 35 to 65 years — is supported by encouraging but inconclusive evidence for preventing, delaying, and slowing clinical Alzheimer’s-type dementia, the committee said. The available evidence, together with the strong evidence for blood pressure management in preventing stroke and cardiovascular disease and the relative benefit/risk ratio of antihypertensive medications and lifestyle interventions, is sufficient to justify communication with the public regarding the use of blood pressure management, particularly during midlife, for preventing, delaying, and slowing clinical Alzheimer’s-type dementia, the report says.

It is well-documented that physical activity has many health benefits, and some of these benefits — such as stroke prevention — are causally related to brain health. The AHRQ systematic review found that the pattern of randomized controlled trials results across different types of physical activity interventions provides an indication of the effectiveness of increased physical activity in delaying or slowing age-related cognitive decline, although these results were not consistently positive. However, several other considerations led the committee to conclude that the evidence is sufficient to justify communicating to the public that increased physical activity for delaying or slowing age-related cognitive decline is supported by encouraging but inconclusive evidence.

None of the interventions evaluated in the AHRQ systematic review met the criteria for being supported by high-strength evidence, based on the quality of randomized controlled trials and the lack of consistently positive results across independent studies. This limitation suggests the need for additional research as well as methodological improvements in the future research. The National Institutes of Health and other interested organizations should support further research to strengthen the evidence base on cognitive training, blood pressure management, and increased physical activity, the committee said. Examples of research priorities for these three classes of interventions include evaluating the comparative effectiveness of different forms of cognitive training interventions; determining whether there are optimal blood pressure targets and approaches across different age ranges; and comparing the effects of different forms of physical activity.

When funding research on preventing cognitive decline and dementia, the National Institutes of Health and other interested organizations should identify individuals who are at higher risk of cognitive decline and dementia; increase participation of underrepresented populations; begin more interventions at younger ages and have longer follow-up periods; use consistent cognitive outcome measures across trials to enable pooling; integrate robust cognitive outcome measures into trials with other primary purposes; include biomarkers as intermediate outcomes; and conduct large trials designed to test the effectiveness of an intervention in broad, routine clinical practices or community settings.

Study links sleep patterns with pain persistence after pediatric surgery

About 20 percent of children develop persistent pain after surgery, and a new study published in The Journal of Pain showed that poorer night-time sleep quality was significantly associated with greater next-day pain intensity overfour months after surgery.  The Journal of Pain is published by the American Pain Society, www.americanpainsociety.org.

Researchers from the University of Washington and Seattle Children’s Hospital studied 66 children who had major surgery and examined the longitudinal sleep patterns over four months to assess the relationship between daily sleep and pain.  They hypothesized that poorer night-time sleep quality would be associated with greater pain intensity. 

In adults, the role of sleep disruption is considered a relevant predictor of acute as well as chronic post-surgical pain.  However, perioperative daily sleep patterns have not been longitudinally assessed in children, and the role of sleep in persistence of children’s pain after surgery has not been explored.

Results of the study showed, on average, children’s sleep duration and quality returned to baseline four months following surgery.  But at the individual level, significant temporal relationships were found between daily sleep and pain.

“Poor sleep quality predicted greater subsequent pain intensity the next day and our findings suggest that poor sleep quality may continue to influence the experience of post-surgical pain in children even four months after surgery,” said lead author Jennifer Rabbits, MB, ChB, Department of Anesthesiology at Seattle Children’s Hospital.

The authors concluded that improving sleep quality could be an important factor to reduce post-surgical pain and improve surgical recovery time in children.  

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UV-sensing protein in the brain of a marine annelid zooplankton

Researchers at Institute for Molecular Sciences reported that a photoreceptive protein expressed in the brain a marine annelid zooplankton (Platynereis dumerilii) is UV-sensitive. This work was carried out as a collaborative work of Drs. Hisao Tsukamoto and Yuji Furutani (Institute for Molecular Science) with Drs. Yoshihiro Kubo and I-Shan Chen (National Institute for Physiological Sciences). This study was published online in the Journal of Biological Chemistry on June 16, 2017.

Most animals use external light signals for vision and “non-visual” photoreceptive functions, such as regulation of circadian behaviors. In some cases, photoreceptor cells outside eyes are involved in non-visual photoreception. Previous studies have shown that larvae of the annelid Platynereis dumerilii (marine ragworm), which are studied as a zooplankton model, possess photoreceptor cells in the brain, and the cells regulate circadian swimming behaviors. Interestingly, the brain photoreceptor cells in Platynereis express an opsin that is closely related to visual pigments in our visual photoreceptor (rod and cone) cells. Zooplankton show a synchronized circadian movement known as diel vertical migration (DVM), moving upward in water at night and downward in daytime. DVM is probably the largest daily movement of biomass, comparable to human commuting. Since a major cause of DVM is to avoid damaging UV (ultra-violet) irradiation, light-dependent DVM regulation via the brain photoreceptor cells was suggested.

This study showed that the Platynereis opsin can receive and transmit UV signals. Unlike vertebrate visual opsins, the opsin can directly bind exogenous all-trans-retinal. This suggests that the opsin enables the brain photoreceptor cells to detect UV signals, even without the supply of 11-cis-retinal, which is specifically produced in eyes. Mutagenesis analyses identified that a single amino acid residue is responsible for not only UV sensing but also direct binding of exogenous all-trans-retinal. Thus, the single residue is essential for the opsin to achieve the characteristics suitable for UV reception in the brain. Taken together, the opsin possesses ideal properties enabling the brain photoreceptor cells in Platynereis to sense ambient UV signals.

As summarized above, this study revealed molecular basis of the opsin to function as a UV-sensor in the brain of the zooplankton model. Since detection of ambient UV signals should be necessary for DVM, the molecular properties of the opsin are helpful to understand the physiology, ecology and evolution of zooplankton species.

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Select memories can be erased, leaving others intact

Different types of memories stored in the same neuron of the marine snail Aplysia can be selectively erased, according to a new study by researchers at Columbia University Medical Center (CUMC) and McGill University and published today in Current Biology.

The findings suggest that it may be possible to develop drugs to delete memories that trigger anxiety and post-traumatic stress disorder (PTSD) without affecting other important memories of past events.

During emotional or traumatic events, multiple memories can become encoded, including memories of any incidental information that is present when the event occurs. In the case of a traumatic experience, the incidental, or neutral, information can trigger anxiety attacks long after the event has occurred, say the researchers.

“The example I like to give is, if you are walking in a high-crime area and you take a shortcut through a dark alley and get mugged, and then you happen to see a mailbox nearby, you might get really nervous when you want to mail something later on,” says Samuel Schacher, PhD, a professor of neuroscience in the Department of Psychiatry at CUMC and co-author of the paper. In the example, fear of dark alleys is an associative memory that provides important information — e.g., fear of dark alleys — based on a previous experience. Fear of mailboxes, however, is an incidental, non-associative memory that is not directly related to the traumatic event.

“One focus of our current research is to develop strategies to eliminate problematic non-associative memories that may become stamped on the brain during a traumatic experience without harming associative memories, which can help people make informed decisions in the future — like not taking shortcuts through dark alleys in high-crime areas,” Dr. Schacher adds.

Brains create long-term memories, in part, by increasing the strength of connections between neurons and maintaining those connections over time. Previous research suggested that increases in synaptic strength in creating associative and non-associative memories share common properties. This suggests that selectively eliminating non-associative synaptic memories would be impossible, because for any one neuron, a single mechanism would be responsible for maintaining all forms of synaptic memories.

The new study tested that hypothesis by stimulating two sensory neurons connected to a single motor neuron of the marine snail Aplysia; one sensory neuron was stimulated to induce an associative memory and the other to induce a non-associative memory.

By measuring the strength of each connection, the researchers found that the increase in the strength of each connection produced by the different stimuli was maintained by a different form of a Protein Kinase M (PKM) molecule (PKM Apl III for associative synaptic memory and PKM Apl I for non-associative). They found that each memory could be erased — without affecting the other — by blocking one of the PKM molecules.

In addition, they found that specific synaptic memories may also be erased by blocking the function of distinct variants of other molecules that either help produce PKMs or protect them from breaking down.

The researchers say that their results could be useful in understanding human memory because vertebrates have similar versions of the Aplysia PKM proteins that participate in the formation of long-term memories. In addition, the PKM-protecting protein KIBRA is expressed in humans, and mutations of this gene produce intellectual disability.

“Memory erasure has the potential to alleviate PTSD and anxiety disorders by removing the non-associative memory that causes the maladaptive physiological response,” says Jiangyuan Hu, PhD, an associate research scientist in the Department of Psychiatry at CUMC and co-author of the paper. “By isolating the exact molecules that maintain non-associative memory, we may be able to develop drugs that can treat anxiety without affecting the patient’s normal memory of past events.”

“Our study is a ‘proof of principle’ that presents an opportunity for developing strategies and perhaps therapies to address anxiety,” said Dr. Schacher. “For example, because memories are still likely to change immediately after recollection, a therapist may help to ‘rewrite’ a non-associative memory by administering a drug that inhibits the maintenance of non-associative memory.”

Future studies in preclinical models are needed to better understand how PKMs are produced and localized at the synapse before researchers can determine which drugs may weaken non-associative memories.

Rare cells are ‘window into the gut’ for the nervous system

Specialized cells in the gut sense potentially noxious chemicals and trigger electrical impulses in nearby nerve fibers, according to a new study led by UC San Francisco scientists. “These cells are sensors, like a window looking into the contents of the gut,” said James Bayrer, MD, PhD, an assistant professor of pediatrics at UCSF and one of the lead authors of the paper.

Using gut-mimicking “organoids” grown from mouse stem cells, the researchers showed how cells in the intestinal lining called enterochromaffin (EC) cells alert the nervous system to signs of trouble in the gut, from bacterial products to inflammatory food molecules.

The authors of the new study — published online in Cell on June 22, 2017 — said that understanding the role of EC cells in how the gut reacts, and overreacts, to chemical irritants could provide new approaches for treating gastrointestinal disorders such as irritable bowel syndrome (IBS).

With over 100 times the surface area of our skin, the gut is the body’s largest surface exposed to external substances. Though EC cells make up only one percent of the gut’s lining, they produce 90 percent of the body’s serotonin, a key signaling molecule, so scientists have long been curious about their functions. Serotonin is best known for mediating mood through its actions in the brain, but it has a very different role in the gut, where it is involved in gut contractions and gastric discomfort.

“There are so few of these cells, but they seem so powerful,” said Holly Ingraham, PhD, a UCSF professor of cellular and molecular pharmacology and co-senior author of the new paper. “People are very interested in understanding what these cells do with all that serotonin.”

EC cells are interspersed among other cells that make up the lining of the intestinal tract, on the surface of tiny, fingerlike structures called villi that project into the gut’s inside space. Within the villi, underneath the EC cells and other cells, are nerve fibers which sense the movement and contents of the gut and contribute to intestinal pain and discomfort. But precisely how these nerve fibers communicate with EC cells has been unclear.

In their new study, the researchers showed that EC cells integrate information about chemical irritants, bacterial compounds, and stress hormones in the gut, then use serotonin to pass that information on to the neighboring nerve cells, from which electrical impulses may travel throughout the gut’s nervous system and ultimately to the brain.

“People had suspected such a role for EC cells before, but this study is exciting because for the first time it gives us a rigorous handle on exactly how the gut talks to the nervous system,” said David Julius, PhD, a professor and chair of UCSF’s Department of Physiology and the study’s other senior author.

Cells Are Electrically Excited by Irritants

The collaboration at the heart of the new study was an unusual one for Ingraham and Julius, who are married but usually take different paths in their research.

Julius’s lab, which is focused on learning how the body’s pain sensors work using natural products like chili peppers, horseradish and snake venom, became interested in this new research direction after discovering that cells sensitive to a painful spider toxin were highly prevalent in the gut. Nicholas Bellono, PhD, a postdoctoral researcher in the lab and the other lead author on the paper, became fascinated by the way the gut’s lining, called the epithelium, appears to sense and react to what’s inside it.

“The nervous system, the immune system, the vasculature, everything converges in the epithelium,” said Bellono. He took particular interest in EC cells, wondering if the serotonin they release activated adjacent nerve fibers.

When Julius mentioned Bellono’s new interest to Ingraham, she suggested that Bellono work with Bayrer, a gastroenterologist who was leading efforts in her lab to study gut disorders using intestinal organoids, small clumps of cells grown from stem cells that can serve as models of the gut. For Bellono and Bayrer, organoids made the EC cells much easier to work with. “You can look in the dish and there’s a little intestine in there — it’s totally wild,” said Bellono.

The team tested the cells’ reactions to dozens of different molecules and found that three classes of molecules caused a change in voltage across the cell’s membranes. Intriguingly, the three types of molecules that triggered EC cells — bacterial byproducts called volatile fatty acids; a class of hormones called catecholamines (including dopamine, epinephrine and norepinephrine) that can signal stress in the gut; and a dietary irritant called AITC, which is responsible for garlic’s pungent flavor — have all previously been linked to IBS.

When the EC cells are excited by any of these molecules, they release serotonin into synapses with the nearby nerve fibers, acting much like other sensory organs, from taste buds to odor receptors. In tissue samples taken from mice, the team showed that this serotonin release triggered electrical impulses in nerve fibers, indicating the signal could move quickly throughout the gut.

“They’re actually electrically excitable,” said Julius, who also holds the Morris Herzstein Chair in Molecular Biology and Medicine at UCSF. “They kind of behave like neurons.”

Signals Could Cause Both Pain and Pooping

The intestines are unique among our organs in that many of the nerve signals that control them come not from the brain but from a network of nerves within the gut sometimes called “the second brain,” which helps carry out much of the organ’s routine contractions and digestive activities without the intervention of the brain itself.

The team thinks the nerve signals that originate with the EC cells can affect both networks, causing involuntary gut contractions or, if the signals reach the brain, what Ingraham described as a “gut ache.”

“Just like when we taste something foul and we try to get rid of it” through gagging, the gut may react to the foul “taste” of bacterial or irritating molecules by trying to push them out the other end, said Bayrer. “This could be a way of the gut sensing which populations of bacteria are around.”

The next step, said the researchers, is to study EC cells in organoids grown from human cells. Because mice and humans have different diets, our EC cells could be sensitive to entirely different molecules.

Targeting Cells Could Help Treat Irritable Bowel Syndrome

Though triggering the gut to push out unwanted chemicals and microbes is normally healthy, overreactions by EC cells and the nerve networks they trigger may cause problems like IBS. The team hopes that understanding what leads these cells to react to food and bacteria will aid the search for drugs that will prevent them from overreacting, perhaps by blocking the proteins that sense these molecules in the first place.

Intriguingly, clinicians already use SSRI’s (Selective Serotonin Reuptake Inhibitors), which affect serotonin levels, to treat IBS, suggesting there may be a link between the disease and the serotonin system. Bayrer, a pediatric gastroenterologist who works with children with IBS, hopes understanding EC cells and other gut sensors will help researchers understand and improve such treatments.

 

Elevated rate of autism symptoms found in children with Tourette syndrome

Around one in five children with Tourette syndrome, a neurological disorder characterized by involuntary movements and vocalizations, met criteria for autism in a study headed by UC San Francisco. But this prevalence may be more a reflection of similarity in symptoms than actual autism, according to the study’s researchers.

Researchers tested 535 children and adults with Tourette’s for autism, using a self-reporting test called the Social Responsiveness Scale. Among the 294 children tested, 22.8 percent reached the cutoff for autism, versus 8.7 percent of the 241 adults. In contrast, autism is estimated to affect between 0.3 and 2.9 percent of the general population, according to studies cited in the paper.

The Social Responsiveness Scale Second Edition is a 65-item quantitative measure of autism symptoms that assesses the ability to engage in “emotionally appropriate reciprocal social interactions.” It evaluates levels of social awareness, social cognition, social communication, social motivation, and restrictive interests and repetitive behavior. Its threshold for autism compares favorably with the diagnostic gold standard, the Autism Diagnostic Interview, the researchers noted.

The study is publishing on June 22, 2017, in the Journal of the American Academy of Child and Adolescent Psychiatry.

OCD, ADHD Frequent Co-Occurrences

The researchers wanted to examine autism symptoms in patients with Tourette’s, including those whose diagnosis was coupled with obsessive-compulsive disorder (OCD) or attention deficit hyperactivity disorder (ADHD), conditions that frequently co-occur. Tourette’s, OCD and ADHD have been shown to share common symptoms and genetic relationships in a recent study by the same researchers.

“Assessing autism symptom patterns in a large Tourette’s sample may be helpful in determining whether some of this overlap is due to symptoms found in both disorders, rather than an overlapping etiology,” said first author Sabrina Darrow, PhD, assistant professor in the department of psychiatry at UCSF.

“Our results suggest that although autism diagnoses were higher in individuals with Tourette’s, some of the increase may be due to autism-like symptoms, especially repetitive behaviors that are more strongly related to obsessive-compulsive disorder.”

The researchers found that the highest scores on the Social Responsiveness Scale, which met autism criteria, were found in participants with Tourette’s and either OCD or ADHD. Among those with Tourette’s who met the cutoff for autism, 83 percent also met criteria for OCD, the researchers found, noting that high scores were especially evident in the part of the autism test that measures restrictive interests and repetitive behavior.

Wide Gulf Between Adults, Kids with Autism Diagnosis.

A potentially compelling argument against the surprisingly high rates of autism found in this sample was the wide discrepancy between children and adults who met the diagnostic criteria. Tourette’s is usually diagnosed between the ages of 3 and 9; symptoms most often peak in the early teens and start to abate in the early twenties, with continued improvement in early adulthood.

“Children were more than twice as likely to meet the cutoff than adults, indicating that as tics recede, so do symptoms of autism. In contrast, autism is usually lifelong,” said Darrow.

“Previous studies have shown that children with mood and anxiety disorders also have higher rates of autism symptoms, based on the Social Responsiveness Scale,” said senior author Carol Mathews, MD, who did the research while a professor of psychiatry at UCSF. She currently is adjunct professor of psychiatry at UCSF and professor of psychiatry at the University of Florida in Gainesville.

Psychiatric Impairment Possible Factor in Diagnosis

“This suggests that some of the increase may reflect underlying psychiatric impairment rather than being specific for autism. Some of the children in the study probably have autism, others have symptoms that mimic autism, but are not really due to autism. These symptoms are called phenocopies.”

Tourette’s affects between one and 10 in 1,000 children according to the National Institutes of Health. Like autism, it is significantly more prevalent in males. Common tics include repetitive throat clearing, blinking or grimacing. Most people do not require medication to suppress their symptoms, but treatment may be recommended for co-occurring ADHD and OCD.

 

Starting school young can put child wellbeing at risk

New research has shown that the youngest pupils in each school year group could be at risk of worse mental health than their older classmates.

Starting school young is an exciting but sometimes challenging milestone for children and their families. Some children will be nearing their fifth birthday as they enter foundation classes while others will be only just four.

Now, a study led by the University of Exeter Medical School which investigated more than 2,000 children across 80 primary schools in Devon, has found that children who are younger than their peers when they start school are more likely to develop poorer mental health, as rated by parents and teachers. Overall the effect was small, however researchers believe the additional stress of keeping up with older peers could prove a “tipping point” for vulnerable children, such as those with learning difficulties or who were born prematurely.

The research team was supported by the National Institute for Health Research Public Health Research Programme and the Collaboration for Leadership in Applied Health Research and Care South West Peninsula (NIHR PenCLAHRC).

The research, published in the journal Child Care, Health and Development, could have implications on parents’ decisions on whether to defer their child’s school entry for a school year, permissible under guidance introduced in 2014.

The findings could also influence how teachers interact with younger children, particularly those with additional complex needs in the class, and on assessments and teaching and support structures within classrooms.

Anna Price, of the University of Exeter Medical School, was motivated to study the issue after home schooling her own April-born son, who has pre-existing learning difficulties, and was not ready to start school aged five. She said: “Using such a large dataset was a chance to explore what’s really happening in practice for children who start school at a young age. We found that children who started younger had slightly worse well-being- however, this effect was very small and unlikely to make a difference for most. The challenge to well-being of being young for your school year might however be one struggle too many for children who face other challenges to their mental health. Our findings can help guide parents and teachers in making decisions that best support the child.”

The researchers also explored the impact of starting school early on the child’s happiness levels and behaviour. In contrast to previous research, they found no significant impact on either. The research paper noted that the schools in the study had strong support in place, such as small group learning, which may have helped improve happiness and behaviour overall.

Professor Tamsin Ford, of the University of Exeter Medical School, oversaw the research. Professor Ford, a practising child psychiatrist, said: “Being relatively younger could be the tipping point for some, but certainly not all, children. For most it would just be something for teacher’s to be aware of but for children with other needs or who were born prematurely this difference could be significant. Awareness of this issue among teachers and educators means measures can be put in place that could help to mitigate this effect and get the best outcome for children.”

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Alzheimer’s disease study links brain health, physical activity

People at risk for Alzheimer’s disease who do more moderate-intensity physical activity, but not light-intensity physical activity, are more likely to have healthy patterns of glucose metabolism in their brain, according to a new UW-Madison study.

Results of the research were published online in Journal of Alzheimer’s Disease. Senior author Dr. Ozioma Okonkwo, assistant professor of medicine, is a researcher at the Wisconsin Alzheimer’s Disease Research Center and the Wisconsin Alzheimer’s Institute at the UW School of Medicine and Public Health. First author Ryan Dougherty is a graduate student studying under the direction of Dr. Dane B. Cook, professor of kinesiology and a co-author of the study, and Dr. Okonkwo. The research involved 93 members of the Wisconsin Registry for Alzheimer’s Prevention (WRAP), which with more than 1,500 registrants is the largest parental history Alzheimer’s risk study group in the world.

Researchers used accelerometers to measure the daily physical activity of participants, all of whom are in late middle-age and at high genetic risk for Alzheimer’s disease, but presently show no cognitive impairment. Activity levels were measured for one week, quantified, and analyzed. This approach allowed scientists to determine the amount of time each subject spent engaged in light, moderate, and vigorous levels of physical activity. Light physical activity is equivalent to walking slowly, while moderate is equivalent to a brisk walk and vigorous a strenuous run. Data on the intensities of physical activity were then statistically analyzed to determine how they corresponded with glucose metabolism — a measure of neuronal health and activity — in areas of the brain known to have depressed glucose metabolism in people with Alzheimer’s disease. To measure brain glucose metabolism, researchers used a specialized imaging technique called 18F-fluorodeoxyglucose positron emission tomography (FDG-PET).

Moderate physical activity was associated with healthier (greater levels of) glucose metabolism in all brain regions analyzed. Researchers noted a step-wise benefit: subjects who spent at least 68 minutes per day engaged in moderate physical activity showed better glucose metabolism profiles than those who spent less time.

“This study has implications for guiding exercise ‘prescriptions’ that could help protect the brain from Alzheimer’s disease,” said Dougherty. “While many people become discouraged about Alzheimer’s disease because they feel there’s little they can do to protect against it, these results suggest that engaging in moderate physical activity may slow down the progression of the disease.”

“Seeing a quantifiable connection between moderate physical activity and brain health is an exciting first step,” said Okonkwo. He explained that ongoing research is focusing on better elucidating the neuroprotective effect of exercise against Alzheimer’s disease.

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System detects, translates sarcasm on social media

Researchers in the Technion-Israel Institute of Technology Faculty of Industrial Engineering and Management have developed a system for interpreting sarcastic statements in social media. The system, developed by graduate student Lotam Peled, under the guidance of Assistant Professor Roi Reichart, is called Sarcasm SIGN (sarcasm Sentimental Interpretation GeNerator).

“There are a lot of systems designed to identify sarcasm, but this is the first that is able to interpret sarcasm in written text,” said Peled. “We hope in the future, it will help people with autism and Asperger’s, who have difficulty interpreting sarcasm, irony and humor.”

Based on machine translation, the new system turns sarcastic sentences into honest (non-sarcastic) ones. It will, for example, turn a sarcastic sentence such as, “The new ‘Fast and Furious’ movie is awesome. #sarcasm” into the honest sentence, “The new Fast and Furious movie is terrible.”

Despite the vast development in this field, and the successes of sentiment analysis applications on “social media intelligence,” existing applications do not know how to interpret sarcasm, where the writer writes the opposite of what (s)he actually means.

In order to teach the system to produce accurate interpretations, the researchers compiled a database of 3,000 sarcastic tweets that were tagged with #sarcasm, where each tweet was interpreted into a non-sarcastic expression by five human experts. In addition, the system was trained to identify words with strong sarcastic sentiments — for example, the word “best” in the tweet, “best day ever” — and to replace them with strong words that reveal the true meaning of the text. The system was examined by a number of (human) judges, who gave its interpretations high scores of fluency and adequacy, agreeing that in most cases it produced a semantically and linguistically correct sentence.

Automatic identification and analysis of sentiment in text is a very complex challenge being explored by many researchers around the world because of its commercial potential and scientific importance. Sentiment identification could be used in social, commercial, and other applications to improve communication between people and computers, and between social media users.

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Frequent sexual activity can boost brain power in older adults

More frequent sexual activity has been linked to improved brain function in older adults, according to a study by the universities of Coventry and Oxford.

Researchers found that people who engaged in more regular sexual activity scored higher on tests that measured their verbal fluency and their ability to visually perceive objects and the spaces between them.

The study, published today in The Journals of Gerontology, Series B: Psychological and Social Sciences, involved 73 people aged between 50 and 83.

Participants filled in a questionnaire on how often, on average, they had engaged in sexual activity over the past 12 months — whether that was never, monthly or weekly — as well as answering questions about their general health and lifestyle.

The 28 men and 45 women also took part in a standardized test, which is typically used to measure different patterns of brain function in older adults, focusing on attention, memory, fluency, language and visuospatial ability.

This included verbal fluency tests in which participants had 60 seconds to name as many animals as possible, and then to say as many words beginning with F as they could — tests which reflect higher cognitive abilities.

They also took part in tests to determine their visuospatial ability which included copying a complex design and drawing a clock face from memory.

It was these two sets of tests where participants who engaged in weekly sexual activity scored the most highly, with the verbal fluency tests showing the strongest effect.

The results suggested that frequency of sexual activity was not linked to attention, memory or language. In these tests, the participants performed just as well regardless of whether they reported weekly, monthly or no sexual activity.

This study expanded on previous research from 2016, which found that older adults who were sexually active scored higher on cognitive tests than those who were not sexually active.

But this time the research looked more specifically at the impact of the frequency of sexual activity (i.e. does it make a difference how often you engage in sexual activity) and also used a broader range of tests to investigate different areas of cognitive function.

The academics say further research could look at how biological elements, such as dopamine and oxytocin, could influence the relationship between sexual activity and brain function to give a fuller explanation of their findings.

Lead researcher Dr Hayley Wright, from Coventry University’s Centre for Research in Psychology, Behaviour and Achievement, said:

“We can only speculate whether this is driven by social or physical elements — but an area we would like to research further is the biological mechanisms that may influence this.

“Every time we do another piece of research we are getting a little bit closer to understanding why this association exists at all, what the underlying mechanisms are, and whether there is a ’cause and effect’ relationship between sexual activity and cognitive function in older people.

“People don’t like to think that older people have sex — but we need to challenge this conception at a societal level and look at what impact sexual activity can have on those aged 50 and over, beyond the known effects on sexual health and general wellbeing.”

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Adulthood wellbeing lower for single-parent kids

People who grew up in single-parent families have lower levels of wellbeing and life satisfaction in adulthood, according to new research by the University of Warwick.

Dr Sakari Lemola from Warwick’s Department of Psychology, and Dr David Richter from the German Institute for Economic Research, have discovered that individuals who were brought up by a single parent for their entire childhood earn on average 30% less and are more likely to be unemployed.

Furthermore, on average they were 9% less likely to be in a romantic relationship and had a smaller number of friends, according to the research.

In a study of over 24,000 adults aged 18-66, the researchers identified 641 individuals who spent their entire childhood with a single parent and 1539 who spent part of their childhood with a single parent.

The sample group was asked how satisfied they are with life in general, using an 11-point scale — ranging from zero (completely dissatisfied) to ten (completely satisfied). They were also asked who they lived with for the first fifteen years of their life.

The researchers analysed the participants’ annual income, number of visits to the doctor, level of social integration, and success in romantic relationships.

After accounting for childhood socio-economic circumstances, the differences in life-satisfaction were relatively small. Those who grew up with a single parent for their entire childhood were approximately 0.2 points lower on the scale ranging from 0 to 10 than those who were brought up by both parents — and 0.1 points lower than those who experienced parental separation during childhood.

“These findings suggest that both parents still provide important resources even when children have already grown up and left their parent’s home. During young adulthood these resources may include financial support as well as access to social networks, which is important to find a good job,” commented Dr Sakari Lemola.

“Children who had grown up with a single parent for their entire childhood are less likely to know their second parent well and to receive such support during adult life,” he continued.

“Thus, support from the state for those individuals who grew up in single-parent families should also target the life-stages after childhood and facilitate integration into adult life during important transitions such as from school to university or from education into the job market.”

Single parenthood is increasingly common in Western societies, with 20% of children in Germany and 24% in the UK currently being raised in single-parent households — more than 80% of those in households headed by single mothers.

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