Culture

TORONTO, May 5, 2018 - Selective serotonin reuptake (SSRI) antidepressant treatment during pregnancy is associated with better performance on a computerized task to measure cognitive skills in 12 year olds, according to a new study being presented during the Pediatric Academic Societies (PAS) 2018 Meeting.

This study, led by Dr. Sarah Hutchison and senior author, Dr. Tim Oberlander, investigates the complex relationships between pre-birth exposure to selective serotonin reuptake inhibitor (SSRI) antidepressants, and thinking and attention skills in 12-year-olds. Dr. Oberlander is a developmental pediatrician and investigator at BC Children's Hospital and BC Women's Hospital + Health Centre, and a professor in the UBC Department of Pediatrics. Dr. Hutchison is a UBC postdoctoral fellow at BC Children's.

Dr. Oberlander, in collaboration with Dr. Adele Diamond, UBC professor and a Canada Research Chair, followed 51 children from 26 weeks of pregnancy to 12 years of age. In this part of the longitudinal cohort study the investigators assessed mom's mood during and after pregnancy and the child's executive functions (EFs) at 12 years of age. EFs consist of a series of skills that help kids thrive in the classroom and workplace, including flexible, creative problem solving, the ability to focus and pay attention, and self-control.

SSRIs are a popular class of antidepressants commonly used to treat a mothers' mood disorder during pregnancy. They affect the brain's level of serotonin, a chemical that plays a critical role in the regulation of mood and attention.

Researchers found that children's performance varied depending on whether they were exposed to SSRIs before birth: Children with SSRI exposure had better EF skills, even when controlling for mother's mood during pregnancy and when the child was 12 years old. Interestingly, better EFs were also observed in the same children at 6 years (Weikum et al 2013). At 12 years, though (unlike at 6 years), differences in SSRI exposure while in utero and differences in the child's EFs did not vary with measures of the child's mood (anxiety or depression) or verbal ability.

"These are important early findings and further research is needed to examine whether 'better' cognitive skills in children with antidepressant exposure reflect a developmental advantage in some ways but also perhaps a risk in other ways, such as perhaps increased anxiety (Hanley et al, 2015)," said Dr. Oberlander. "Our findings when the children were 3 and 6 years of age indicated increased anxiety, though the absence of this at 12 years might indicate that as EFs improve further children are able to use them to help calm themselves."

At this time, researchers are continuing to study these outcomes in a larger cohort (n~=120 children) where they will be able to further examine links between EFs, mood and early development.

"The impact of prenatal antidepressant exposure is not a simple cause and effect," says Dr. Oberlander. "When it comes to assessing the long-term impact of SSRI exposure before birth, genes and family-life play a powerful role in influencing how a child will be affected."

"Depression during pregnancy and beyond is a major public health problem for mothers and their children," Dr. Oberlander added. "Non-treatment is never an option. It is really important that pregnant women discuss all treatment options with their physicians or midwives."

These findings build on Dr. Oberlander's broader research program, in collaboration with other researchers with the Brain Behavior and Development Research Theme at BC Children's, examining the developmental effects of maternal depression on babies and children. They also build on Dr. Diamond's research program, conducted in collaboration with other Neuroscience researchers at UBC and elsewhere, examining how EFs are affected by biological factors (such as genes and neurochemistry) and environmental ones (for example, impaired by stress or improved by interventions).

Dr. Hutchison will present the abstract, "Prenatal Serotonin Reuptake Inhibitor (SRI) Antidepressant Exposure Influences Executive Functions at 12 Years of Age," during the PAS 2018 Meeting on Sunday, May 6 at 5:45 p.m. EDT. Additional co-authors include Dr. Louise Mâsse, Dr. Ruth Grunau, Dr. Whitney Weikum, Ms. Ursula Brain and Mr. Cecil Chau.

TORONTO-(May 5, 2018) - Erythropoietin (EPO) helps to protect and repair vulnerable brains though it remains a mystery how the anemia drug does so. Genetic analyses conducted by a multi-institutional research team finds that EPO may work its neuroprotective magic by modifying genes essential for regulating growth and development of nervous tissue as well as genes that respond to inflammation and hypoxia. Findings from the pilot study will be presented during the Pediatric Academic Societies 2018 annual meeting.

"During the last trimester of pregnancy, the fetal brain undergoes tremendous growth. When infants are born weeks before their due dates, these newborns' developing brains are vulnerable to many potential insults as they are supported in the neonatal intensive care unit during this critical time," says An Massaro, M.D., an attending neonatologist at Children's National Health System and lead author of the research. "EPO, a cytokine that protects and repairs neurons, is a very promising therapeutic approach to support the developing brains of extremely low gestational age neonates."

The research team investigated whether micro-preemies treated with EPO had distinct DNA methylation profiles and related changes in expression of genes that regulate how the body responds to such environmental stressors as inflammation, hypoxia and oxidative stress. They also investigated changes in genes involved in glial differentiation and myelination, production of an insulating layer essential for a properly functioning nervous system. The genetic analyses are an offshoot of a large, randomized clinical trial of EPO to treat preterm infants born between 24 and 27 gestational weeks.

The DNA of 18 newborns enrolled in the clinical trial was isolated from specimens drawn within 24 hours of birth and at day 14 of life. Eleven newborns were treated with EPO; a seven-infant control group received placebo.

DNA methylation and whole transcriptome analyses identified 240 candidate differentially methylated regions and more than 50 associated genes that were expressed differentially in infants treated with EPO compared with the control group. Gene ontology testing further narrowed the list to five candidate genes that are essential for normal neurodevelopment and for repairing brain injury:

Neurogenin 1, a transcription factor that governs the progression of neurogenesis

FOS like 1, implicated in development of cognitive deficits after oxygen depravation (hypoxia)

Mitogen-activated protein kinase 8 interacting protein 2, encodes a scaffolding protein broadly expressed in the brain. Experimental models that lack this protein display autistic tendencies.

Resistance to inhibitors of cholinesterase 8 homolog A, an essential player in generating new brain cells

Major histocompatibility complex, class II, DR alpha, a central player in proper immune system function.

"These findings suggest that EPO's neuroprotective effect may be mediated by epigenetic regulation of genes involved in the development of the nervous system and that play pivotal roles in how the body responds to inflammation and hypoxia," Dr. Massaro says.

TORONTO, May 5, 2018 - Hospitals caring for children with serious, chronic illness are highly dependent on public payers, according to a new study. The research found that proposals to dramatically reduce federal expenditures on Medicaid and Children's Health Insurance Program (CHIP) could destabilize current specialty care referral networks serving all children, including the majority of privately-insured children in greatest need of high quality, specialized, pediatric care. Findings from the research will be presented during the Pediatric Academic Societies (PAS) 2018 Meeting in Toronto.

Although Medicaid and CHIP are directed at providing health services for low-income children, the potential impact of reduced Medicaid and CHIP spending on regionalized systems of hospital care for seriously ill children remains unexplored. The objectives of the study were to assess the role of Medicaid and CHIP in regional hospitals serving large numbers of seriously ill children; to assess the importance of these regional hospitals to privately-insured, seriously ill children; and to assess the characteristics of the hospitals with the highest patient volume and Medicaid and CHIP dependence.

Researchers conducted a retrospective analysis between the 2012 national KID inpatient database and the 2012 California confidential, unmasked Patient Discharge Database from the Office of Statewide Health Planning and Development. Public payers were defined as Medicaid and CHIP, and major pediatric hospitals as those with >500 discharges of children

Nationally, major pediatric hospitals reported over 50 percent of bed days covered by public payers with the 10 highest volume hospitals ranging from 36 percent to 100 percent. Similarly in California, 69 percent of bed days were covered by public payers with the six highest volume hospitals reporting >50 percent public payers. One in three privately-insured children were discharged from major hospitals with >50 percent public payers.

The characteristics of hospitals in the top quintile of Medicaid bed days and had >50 percent publicly insured discharges were 63 percent urban, most often in the south (36 percent) and least often in the northeast (12 percent), 21 percent urban teaching hospitals, and 70 percent children's hospitals.

Dr. Lisa Chamberlain, one of the authors of the study, will present the abstract, "Dependence of Privately-insured, Chronically Ill Children on Medicaid Reliant Hospitals," during the PAS 2018 Meeting on Monday, May 7 at 3:30 p.m. EDT. Reporters interested in an interview with Dr. Chamberlain should contact PAS2018@piercom.com.

Please note: Only the abstract is being presented at the meeting. In some cases, the researcher may have additional data to share with media.

The PAS 2018 Meeting, taking place in Toronto on May 5-8, 2018, brings together thousands of pediatric scientists and other health care providers to improve the health and well-being of children worldwide. For more information about the PAS 2018 Meeting, please visit http://www.pas-meeting.org.

TORONTO, May 5, 2018 - A new study examines the effectiveness of the ScreenQ, a measure of screen-based media use in children. Findings from the study will be presented during the Pediatric Academic Societies (PAS) 2018 Meeting.

"In a single generation, the explosion of screen-based media has transformed the experience of childhood, from TV and videos, to an unlimited range of content available at any time via portable devices that can be challenging to monitor," said Dr. John S. Hutton, one of the authors of the study. "The emergence of these technologies has far outpaced our ability to quantify its effects on child development, human relationships, learning and health, fueling controversies among parents, educators and clinical providers. The ScreenQ is a novel measure of screen-based media use in children intended for pediatric clinical use, incorporating evidence-based factors known to influence these effects, including access to screens, frequency and context of use (e.g., meals), content (e.g., violent versus educational) and co-viewing with grownup caregivers."

This study involved 27 healthy children from employee families at an academic medical center (15 boys, 12 girls; mean 57±7 months old, mid/high-SES). A 17-item version of the ScreenQ was developed applying a conceptual model of screen-based media use involving aspects cited in American Academy of Pediatrics (AAP) guidelines: access, frequency (e.g., age of use), content and interactivity (e.g., co-viewing). Responses were categorical, except for frequency, where numerical response was converted into a categorical score. Higher scores reflect greater risk. Validated measures were administered as criterion-referenced standards, including the EVT and PPVT (language), BRIEF-P (executive function), BASC (behavior), and StimQ-P READ home reading environment survey. Modern theory Rasch methods were used to evaluate items for smoothness, modality, difficulty, polarity, density and outliers. Preliminary indices of internal consistency were estimated using Cronbach's, and of validity using a Spearman-rho correlation coefficient with criterion-referenced standards (

The study found that applying these methods, the ScreenQ was reduced to 10 items (three access, two frequency, three content, two interactivity). The reduced version demonstrated strong internal consistency (Crohnbach's =0.63), good person- and item-level reliability, and variability in Logit endorsability. While non-significant, ScreenQ scores were negatively correlated with StimQ-P (-0.17), PPVT (-0.17), EVT (-0.17), and positively with BRIEF composite (0.20) and BASC (0.22) scaled scores. Kolmogorov-Smirnov tests revealed near-normality for ScreenQ scores (p=0.14), but not for StimQ-P (p=0.03).

Preliminary evidence suggests that the ScreenQ is an efficient, valid means to assess screen-based media use in children in the context of AAP guidelines and cognitive-behavioral risks, warranting further development.

A related study by Dr. Hutton, to be presented as a platform at the PAS 2018 Meeting, is the first to use magnetic resonance imaging (MRI) to explore the influence of story format (audio, illustrated, animated) on the engagement of brain networks supporting language, visual imagery and learning in preschool-age children.

AAP recommends that parents begin reading to their children as soon as possible after birth, and provide limits on screen-based media use. In addition to TV, screen-based story platforms with animated features are increasingly marketed to children, yet the influence of animation on brain development is unknown. The purpose of this study was to determine whether there were differences in the engagement of functional brain networks supporting narrative processing for stories presented in audio, illustrated and animated format.

Key findings suggest a "Goldilocks Effect," where audio may be "too cold" at this age, requiring more cognitive strain to process the story, animation "too hot," fast-moving media rendering imagination and network integration less necessary, and illustration "just right," limited visual scaffolding assisting the child while still encouraging active imagery and reflection.

"They underscore the appeal of illustrated books at this age, raise important questions about the influence of media on early brain development, and provide novel context for AAP reading and screen time recommendations," said Dr. Hutton.

Cold Spring Harbor, NY - During a stroke or an epileptic seizure, neurons in affected parts of the brain fire at an abnormally rapid rate. One byproduct of this condition is that the pH of the brain drops markedly, rendering the local environment inhospitably acidic.

Using a powerful microscopy method called cryo-EM, biologists at Cold Spring Harbor Laboratory (CSHL) have discovered how one key element of brain physiology, a docking port for excitatory neurotransmitters called the NMDA receptor, is able to function in this hostile environment.

A team led by CSHL Professor Hiro Furukawa has published high-resolution images of a variant of the NMDA receptor that is adapted to functioning at low pH. "We've known for at least 20 years that different types of NMDA receptors work distinctly, especially in an acidified environment created by seizure and stroke," says Furukawa. "Until now, we haven't understood the underlying molecular mechanism."

NMDA receptors sit on the membrane of excitatory neurons, where they form pores and control electrical signals by "gating" the flow of electrically charged atoms, or ions, in and out. NMDA receptors are active when the brain is learning and forming new memories. Malfunctions of the receptor are thought to be involved in a range of illnesses including neurodegenerative diseases, pain, depression and schizophrenia.

Furukawa's team shows how NMDA receptors can vary slightly in their protein makeup thanks to a cellular mechanism called alternative splicing--a process that enables a single gene to generate distinct variants of a single protein. One "splice variant" of the receptor that is present in the brain turns out to be less sensitive than other versions to an acidic environment.

The NMDA receptor is what scientists call a tetramer - think of it as a tube composed of four proteins that connects the inside of a neuron with the outside environment. The four proteins are intertwined in such a way that they leave an open space running through their center - the ion channel.

The four proteins of the receptor come in two sets of two - "subunits" called GluN1 and GluN2. Furukawa's team imaged a variant of the receptor in which a portion of the GluN1 subunit is altered slightly. This alteration changes the architecture of the receptor, by drawing the GluN1 and GluN2 subunits into a tighter embrace. This, in turn, alters an interface with a part of the larger structure where a pH sensor is located.

The result is that the entire receptor becomes less sensitive to changes in pH. "We've learned from nature how this receptor is able to remain intact and function when the environment turns hostile," says Furukawa. "Research like this informs efforts to create therapeutics that address malfunctions in this important receptor."

The most abundant molecule in cell membranes is the lipid phosphatidylcholine (PC, commonly known as lecithin); accordingly, the enzymes responsible for synthesizing it are essential. Research published in the May 4 issue of the Journal of Biological Chemistry used computer simulations to gain insights into how one of these enzymes activates and shuts off PC production. These results could help researchers understand why small changes in this enzyme can lead to conditions like blindness and dwarfism.

Rosemary Cornell, a professor of molecular biology and biochemistry at Simon Fraser University in Canada, studies the enzyme CTP:phosphocholine cytidylyltransferase, or CCT. CCT sets the rate of PC production in cells by binding to cell membranes with low PC content. When bound to membranes, the CCT enzyme changes shape in a way that allows it to carry out the key rate-limiting step in PC synthesis. When the amount of PC making up the membrane increases, the CCT falls off the membrane, and PC production ceases.

"The membrane is this big macromolecular array with lots of different molecules in it," Cornell said. "How does this enzyme recognize that 'Oh, I should slow down because the PC content of the membrane is getting too high?'"

Cornell and her project team - a collaboration with Peter Tieleman and graduate student, Mohsen Ramezanpour at the University of Calgary and Jaeyong Lee and Svetla Taneva, research associates at SFU - thought that the answer must have to do with the dynamic changes in shape that the enzyme undergoes when it binds to a membrane. But these changes are difficult to capture with traditional structural biology methods like x-ray crystallography, which take a static snapshot of molecules. Instead, the team used computational simulations of molecular dynamics, which use information about the forces between every individual atom in a molecule to calculate the trajectories of the enzyme's moving parts.

"What it looks like (when you visualize the output) is your big molecule dancing in front of your eyes," Cornell said. "We set up the molecular dynamics simulation not once, not twice, but 40 different (times). It took months and months just to do the computational parts and even more months trying to analyze the data afterward. We actually spent a lot of time once we got the data just looking on the screen at these dancing molecules."

The simulated dance of the CCT molecule showed that when the M-domain, the section of the enzyme that typically binds to the membrane, detaches from a membrane, it snags the active site of the enzyme, preventing it from carrying out its reaction. When the snagging segment was removed from the simulation, the team saw a dramatic bending motion in the docking site for the snagging element, and speculated that this bending would create a better enzyme active site for catalyzing the reaction when attached to a membrane. The team confirmed these mechanisms using biochemical laboratory experiments.

Interestingly, previous genetic studies had shown that mutations in the gene encoding CCT are responsible for rare conditions like spondylometaphyseal dysplasia with cone-rod dystrophy, which causes severe impairments in bone growth and vision, but it was unknown how these changes in the enzyme could lead to such dramatic consequences. Cornell hopes that understanding how the enzyme works could help researchers find out.

"If you have just one small change in CCT, then how is that going to make this whole process of synthesizing PC defective?" Cornell asks. "That's what we're studying right now."

People showing virtually no symptoms are likely the primary source of dengue fever, according to new research published in PLOS Pathogens. Nearly 400 million people each year are infected with dengue virus, which is transmitted through mosquitoes.

The study estimates that more than 80 percent of dengue virus infections are attributable to individuals with mild to no symptoms who do not seek treatment from a physician. The study also indicates that nearly a quarter of dengue virus transmission is the result of mosquitoes biting those already infected before the onset of symptoms. By the time those symptoms appear, the opportunity to prevent the virus from spreading has passed.

"Until a few years ago, it was assumed that individuals with mild to no symptoms contributed relatively little to dengue virus transmission," said Alex Perkins, Eck Family Assistant Professor of Biological Sciences at the University of Notre Dame and senior author on the study. "Our research reveals that people showing no symptoms of dengue virus infection are contributing much more than was previously recognized, so that we now have a better idea of the large extent to which they contribute to the spread of this disease."

Researchers at the University of Notre Dame used mathematical modeling to quantify what fraction of dengue virus infections might be caused by people whose illnesses were undetected by public health surveillance systems. Their work involved integrating data sets on the amount of virus in the blood during various stages of infection, the severity of symptoms in relation to previous infections and the proportion of infections resulting in clinical consultation.

The World Health Organization currently focuses disease surveillance efforts on detecting outbreaks, monitoring trends in the number of cases and assessing the possibility of outbreaks. This surveillance encompasses the monitoring of suspected and confirmed dengue cases.

"Unfortunately, based on our study, those who need to be targeted with interventions are either being identified after they have already contributed to transmission or are not being identified at all," said Perkins. "Our results indicate that it might be necessary to shift emphasis toward more proactive disease prevention strategies that do not rely as strongly on responding to detected cases."

The lead author on the study is Quirine ten Bosch, a former biological sciences doctoral student and graduate fellow of the Eck Institute for Global Health at Notre Dame. She is currently a postdoctoral scholar at Institut Pasteur in Paris. Perkins and ten Bosch are affiliated members of the Eck Institute for Global Health.

Stiffer breast tissue creates an environment more prone to cancer by enabling the disease to interfere with the surrounding healthy cells, according to a recent study published in Biomaterials.

Scientists studying tumor growth and metastasis at the University of Notre Dame fabricated a human tissue model to examine how cancer cells interact with connective tissue in the breast. The model allowed the team to control the stiffness of the tissue, mimicking both healthy and cancerous breast tissue structures. They found manipulation of fat cells to be stiffness-dependent.

"One of the interesting things we're looking at is how cancer interacts with surrounding cells and how it manipulates those cells to its own benefit," said Pinar Zorlutuna, assistant professor in the Department of Aerospace and Mechanical Engineering and the Harper Cancer Research Institute at the University of Notre Dame. "The goal of these tissue engineered cancer models is to mimic the physiological environment of the tumor, so we can use them as a platform to study breast cancer in the human tissue microenvironment."

Fat cells, collagen fibers and epithelial cells make up the microenvironment of breast tissue. Cancer typically appears around the epithelial cells. Previous studies looking at differences between healthy and cancerous tissue found that the cancerous tissue differed in stiffness. According to Zorlutuna's study, stiff tissue can present a microenvironment susceptible to tumor growth by enabling the cancer cells to modulate its surrounding connective tissue cells.

"If you have a stiffer environment, the cancer cell can do more manipulation of its immediate microenvironment," Zorlutuna said. "The model allowed us to study varying levels of stiffness in the tissue. In tissue with normal stiffness, the cancer cells did not interfere with the state of the surrounding stromal cells. In tests where the tissue was stiffer, the cancer halted the differentiation process of the surrounding fat stem cells, favoring a more stem cell-like state creating a microenvironment that favors a tumor to grow."

Researchers have typically conducted similar studies using animal models. While these tests can help advance an understanding of the disease, Zorlutuna said they could also pose a challenge.

"Animals and humans are quite different," she said. "If you're looking at tissue environment, mobility and the immune system, mouse models, for example, are as different to human models as the pancreas is to the lung."

Those models can also pose a challenge to drug discovery. A fraction of the drugs proven effective in mice actually makes it through clinical trials when tested on humans, Zorlutuna said. The results of this study could help make the case for tissue engineered human disease models to be used as part of a parallel approach to drug screening before administering those drugs in clinical trials.

University of Illinois at Chicago researchers have discovered a way turn pluripotent stem cells into atrial cells, which make up the upper chambers, or atria, of the heart. The discovery will enable them to better study atrial fibrillation, the most common heart rhythm disorder also known as AFib, which originates in the heart's atria.

As reported in the journal Stem Cell Reports, the researchers obtained blood cells from healthy volunteers, activated genes to make the cells pluripotent -- a type of stem cell that can become any cell type in the body -- and treated the cells with vitamin A.

These cells responded to electrical stimuli like atrial cells. The researchers say this is notable because stem cells typically default to ventricular cells, which make up the lower chambers, or ventricles, of the heart when they become heart cells.

"There is a fundamental gap in our understanding of AFib, in part, because the condition is challenging to study at a cellular level," said corresponding author Dr. Dawood Darbar, professor of medicine and cardiology in the UIC College of Medicine. "While science has provided much-needed insights into the causes of inherited arrhythmia syndromes that originate in the ventricles, thanks to the development of cellular models that act like ventricular cells, we have, until now, lacked fully-characterized cellular models of atrial-like stem cells."

"There are a select number of cell types that conduct electricity -- heart and brain cells are examples -- but even among heart cells how they conduct electricity varies," Darbar said. "This is the first time a study has shown that treating stem cells with vitamin A generates cells that are electrically like atrial cells."

The researchers hope that this fully-characterized atrial-like stem cell model will not only improve our understanding of the causes for AFib and discover new treatments, but will also enable us to test whether a patient, based on their genetic makeup, is likely to respond to a particular treatment.

"We believe this model will enable more in-depth research on the elusive causes of AFib and will facilitate a more 'personalized' approach to treating AFib in the future," Darbar said.

LA JOLLA, CA-- May 3, 2018 --You could say Hollis Cline's lab at The Scripps Research Institute is building better tadpoles.

To better understand how humans learn, Cline, PhD, Hahn Professor of Neuroscience and co-chair of the Department of Neuroscience, leads experiments designed to spark learning in tadpole brains. Over the years, her lab's work with tadpoles has shed light on neuroplasticity--how new experiences flood brain cells with proteins that fuel brain development and learning.

Now the lab's latest study, published in eLife, suggests a key to neuroplasticity is not just the presence of new proteins, but how the brain makes proteins in the first place. The research also points to a possible new role for proteins in sensory processing in some people with autism spectrum disorder.

"The idea that visual experience can influence how we make proteins is something brand new," Cline says. "This is interesting to think about because we live in a very busy sensory world."

The researchers used tadpoles that naturally have translucent skin--which makes them an excellent model for peering into the wirings of a living brain. The tadpoles were kept in the dark and then exposed to either ambient light (for the control group) or a screen with moving bars (simulating normal visual experience) for four hours.

Working closely with Professor John Yates, PhD, of the Scripps Research Department of Molecular Medicine, Cline's team measured changes in protein expression--the production of proteins in cells--before and after each experiment. They found that the expression of 83 proteins shifted either up or down in the experimental group.

Many of these were effector proteins--the proteins doing specific jobs in cells. But the team also spotted three outliers: proteins eIF3A, FUS and RPS17. These three are regulatory proteins, meaning they construct the machinery that makes the effector proteins further down the line. Cline was surprised. She and her colleagues always thought regulatory protein expression would hold steady even when visual experience varied.

"We just thought the regulatory machine would be just humming along," Cline says. "So, we were surprised to see them on our list. We thought, 'Is this accurate? Is this true?'"

It turned out that these regulatory proteins are essential for learning from visual experience. Cells are better at building connections and reinforcing learning when they synthesize these proteins at a certain rate during visual experience.

In fact, researchers could tag neurons with fluorescent proteins to see the physical signature that visual experience left in the brain. Thanks to eIF3A, FUS and RPS17, tadpoles had significant neuronal growth--seen in how their neurons sent out branch-like tendrils--after just four hours of visual experience.

Next, the scientists investigated whether changes in protein expression affected tadpole behavior. How important were these proteins for teaching tadpoles?

To find out, the researchers took advantage of a natural tadpole behavior: the instinct to avoid any large shape that may be a looming predator. The researchers had tadpoles swim above a screen that projected large, predator-like spots. Then they tracked whether a tadpole would turn to avoid the dark spots.

The tadpoles with exposure to visual experience did significantly better on the avoidance test than tadpoles in the control group. This suggests they had formed the neural circuits to better process visual information. Interestingly, tadpoles did not do as well on the test--even after exposure to visual experience--when they could not express all three key proteins (eIF3A, FUS and RPS17). This finding further confirmed the importance of the regulatory proteins in neuronal plasticity.

Finally, the researchers were curious whether the 83 total proteins they identified were expressed differently in human brain disorders, so they cross referenced their list with two databases--one of people with risk factors for autism spectrum disorders, and one with people with fragile X syndrome, which has similar characteristics as autism.

The results came as a surprise. Twenty-five percent of the proteins on the Scripps Research list overlapped with the database lists of genes thought to cause autism spectrum disorder and fragile X syndrome. That was a much bigger number than Cline expected, and it prompts new questions about what makes an autism "risk factor" actually risky.

Cline thinks mutations in regulatory proteins might keep some people from expressing the other proteins needed for processing sights, smells, textures, tastes and sounds. "This brings to mind a new dimension for understanding autism," Cline says.

Cline says future studies could focus on understanding all 83 synthesized proteins. She says the work has also made her consider the visual experience humans take in every day.

"It's fascinating to think about how sensory experience affects the brains of our children," says Cline. "We may wittingly or unwittingly affect how their brains develop."

In an amazing achievement akin to adding solar panels to your body, a Northeast sea slug sucks raw materials from algae to provide its lifetime supply of solar-powered energy, according to a study by Rutgers University-New Brunswick and other scientists.

"It's a remarkable feat because it's highly unusual for an animal to behave like a plant and survive solely on photosynthesis," said Debashish Bhattacharya, senior author of the study and distinguished professor in the Department of Biochemistry and Microbiology at Rutgers-New Brunswick. "The broader implication is in the field of artificial photosynthesis. That is, if we can figure out how the slug maintains stolen, isolated plastids to fix carbon without the plant nucleus, then maybe we can also harness isolated plastids for eternity as green machines to create bioproducts or energy. The existing paradigm is that to make green energy, we need the plant or alga to run the photosynthetic organelle, but the slug shows us that this does not have to be the case."

The sea slug Elysia chlorotica, a mollusk that can grow to more than 2 inches long, has been found in the intertidal zone between Nova Scotia, Canada, and Martha's Vineyard, Massachusetts, as well as in Florida. Juvenile sea slugs eat the nontoxic brown alga Vaucheria litorea and become photosynthetic - or solar-powered - after stealing millions of algal plastids, which are like tiny solar panels, and storing them in their gut lining, according to the study published online in the journal Molecular Biology and Evolution.

Photosynthesis is when algae and plants use sunlight to create chemical energy (sugars) from carbon dioxide and water. The brown alga's plastids are photosynthetic organelles (like the organs in animals and people) with chlorophyll, a green pigment that absorbs light.

This particular alga is an ideal food source because it does not have walls between adjoining cells in its body and is essentially a long tube loaded with nuclei and plastids, Bhattacharya said. "When the sea slug makes a hole in the outer cell wall, it can suck out the cell contents and gather all of the algal plastids at once," he said.

Based on studies of other sea slugs, some scientists have argued that they steal and store plastids as food to be digested during hard times, like camels that store fat in their humps, Bhattacharya said. This study showed that's not the case for solar-powered Elysia chlorotica.

"It has this remarkable ability to steal these algal plastids, stop feeding and survive off the photosynthesis from the algae for the next six to eight months," he said.

The team of Rutgers and other scientists used RNA sequencing (gene expression) to test their solar energy supply hypothesis. The data show that the slug responds actively to the stolen plastids by protecting them from digestion and turning on animal genes to utilize the algal photosynthetic products. Their findings mirror those found in corals that maintain dinoflagellates (also algae) - as intact cells and not stolen plastids - in symbiotic relationships.

Whereas Elysia chlorotica stores plastids, the algal nuclei that are also sucked in don't survive, and scientists still don't know how the sea slug maintains the plastids and photosynthesis for months without the nuclei that are normally needed to control their function, Bhattacharya said.

URBANA, Ill. - Diets rich in nuts, such as walnuts, have been shown to play a role in heart health and in reducing colorectal cancer. According to a new study from the University of Illinois, the way walnuts impact the gut microbiome--the collection of trillions of microbes or bacteria in the gastrointestinal tract--may be behind some of those health benefits.

Walnuts are just one in a line foods that contain dietary fiber and have interested scientists for their impact on the microbiome and health. Dietary fiber acts as a food source for gut microbiota, helping the bacteria to do their jobs--breaking down complex foods, providing us nutrients, or helping us feel full, for example.

Fruits, vegetables, whole grains, nuts, and legumes are important plant sources of dietary fiber. Eating a variety of these foods helps promote a diverse gut microbiota, which in turn helps to support health.

Findings from the study, published in The Journal of Nutrition, show that consuming walnuts not only impacted the gut microbiota and microbial derived secondary bile acids, but also reduced LDL-cholesterol levels in the adults participating in the study; good news for cardio, metabolic, and gastrointestinal health.

"We found that when you consume walnuts it increases microbes that produce butyrate, a beneficial metabolite for colonic health. So the interaction of walnuts with the microbiome is helping to produce some of those health effects," says Hannah Holscher, assistant professor of food science and human nutrition at U of I, and lead author of the study. "It is about getting to the 'black box' that is all the microbes in our GI tract to see how they are interfacing with the food we eat and having downstream health effects.

"Some of those health effects are hypothesized to be related to the metabolites bacteria produce," she adds.

For the controlled-feeding study, 18 healthy male and female adults consumed diets that either included 0 grams of walnuts or 42 grams--about a third cup or a palm-full of walnuts--for two, three-week periods. Fecal and blood samples were collected at the beginning and end of each period to assess secondary outcomes of the study, including effects of walnut consumption on fecal microbiota and bile acids and metabolic markers of health.

Walnut consumption resulted in higher relative abundance of three bacteria of interest: Faecalibacterium, Roseburia, and Clostridium.

"The microbes that increased in relative abundance in this walnut study are from one of the Clostridium clusters of microbes, and there's increased interest in those because they have the ability to make butyrate," Holscher says. "Unfortunately in this study we didn't measure butyrate, so we can't say that just because these microbes increased that butyrate did increase. We still need to answer that question.

"There is a lot of interest in Faecalibacterium because it has also been shown in animals to reduce inflammation. Animals with higher amounts also have better insulin sensitivity. There is also growing interest in Faecalibacterium as a potential probiotic bacteria, and so we are trying to follow up on foods that help support Faecalibacterium."

The findings also show, with walnut consumption, a reduction in secondary bile acids compared to the control. "Secondary bile acids have been shown to be higher in individuals with higher rates of colorectal cancer," Holscher explains. "Secondary bile acids can be damaging to cells within the GI tract, and microbes make those secondary bile acids. If we can reduce secondary bile acids in the gut, it may also help with human health."

Previous research that prompted this microbial research showed that the amount of energy (calories) derived from walnuts after we eat them is less than previously thought.

"When you do calculations to determine how much energy we predicted we would get from eating walnuts, it didn't line up with the energy that was absorbed," Holscher says. "You're really only absorbing around 80 percent of the energy from walnuts that labels say. That means that the microbes get access to that extra 20 percent of calories and the fats and fiber left in them, and so what happens then? Does it produce a positive health outcome, or a negative health outcome? Our study provides initial findings that suggest that the interactions of microbes with the undigested walnut components are producing positive outcomes.

"We need more research to look at additional microbial metabolites and how those are influencing health outcomes, instead of just characterizing the changes in the microbiome," Holscher says.

PHILADELPHIA - After eight years of failed treatment for persistent atrial fibrillation (AF), Janet Szilagyi, 78 of Clayton, New Jersey, became the first patient in the United States to undergo cardiac ablation - a procedure in which an electrophysiologist will scar or destroy tissue in the heart that's allowing incorrect electrical signals to cause an abnormal heart rhythm - using an intraoperative imaging and mapping system recently cleared by the Food and Drug Administration (FDA).

Szilagyi is one of the more than three million individuals in the United States who experience AF, a quivering or irregular heartbeat that can lead to a host of dangerous complications and everyday symptoms like shortness of breath, chest pains, and lightheadedness. Szilagyi had undergone several cardiac procedures and tried different medications to treat and/or control her AF, before coming to Penn Medicine in December 2017 to explore other interventions.

"When I was in atrial fibrillation, it was hard to breathe, and I couldn't walk from here to there without getting tired," said Szilagyi. "I'm usually pretty active; I try to walk every day, but I wasn't able to do that when I was feeling bad. I really wasn't myself." Szilagyi, about six weeks post-op, is home recovering, hoping to get back to her normal activities in the coming months.

"There were many areas of Janet's heart that required ablation, and having access to this new technology allowed us to see more of these regions that we would not have normally been able to, so we could fully address the areas of concerns," said Pasquale Santangeli, MD, an assistant professor of Cardiovascular Medicine, who performed the procedure. "Janet's procedure went well, and she is recovering nicely. I expect that with standard follow-up she will be able to return to normal life without severe threat of AF recurrence."

In October 2017, the system, AcQMap® High Resolution Imaging and Mapping System and the 3D Imaging and Mapping Catheter, received FDA clearance for patients with complex arrhythmias who may need a more extensive cardiac ablation procedure in order to treat the irregularities, based on successful European studies.

Santangeli along with David Callans, MD, associate director of Electrophysiology at Penn Medicine, who performed the country's second procedure with this new system just days later, said the new equipment has the potential to greatly improve treatment accuracy. "Preliminary data from European studies suggests that the success rates of ablation for patients with persistent AF have potential to climb by more than twenty-five percent, and even higher for paroxysmal (sporadic AF) patients," said Callans. "We see these as incredibly promising increases, as these are patients who often still experience symptoms of AF even after they've undergone similar cardiac procedures."

Current data shows that ablation procures are successful for patients with persistent AF about 50 to 55 percent of the time, and about 70 to 75 percent of the time in patients with paroxysmal AF. Researchers believe these numbers could increase to 75 percent and upwards of 85 percent, respectively, if the regions responsible for AF maintenance are adequately addressed with this new system.

Previous systems had only allowed physicians to see certain areas or angles of the heart, which proved challenging when trying to treat more complex cases of AF which require more sites to be ablated. With the new system, higher resolution mapping of the heart is available as it combines ultrasound technology with an ability to map every heartbeat to help pinpoint the cause and placement of each complex arrhythmia. Once an ablation treatment occurs in a specific area, physicians are then able to re-map the heart in seconds to see the effects of each single ablation in real-time. When repeated throughout the entirety of the ablation procedure, physicians can eliminate the arrhythmia-causing areas throughout the heart.

"As a next step, Penn Medicine researchers are exploring clinical trial possibilities, and hope to launch our own trials to evaluate the effectiveness of using this system for patients with complex arrhythmias here in the United States," said Callans.

ITHACA, N.Y. - College applicants and job hunters are often told to scour their networks for someone who could make a quick call or send an email on their behalf, telling the decision-maker a special applicant is heading their way.

But not much is known about whether and why these personal endorsements work. Do they get the applicant in the door? And once at the college or company, does the applicant benefit the organization they've tried so hard to join?

A Cornell University researcher and his colleague offer the first empirical evidence answering these questions. Personal endorsements give applicants a leg up on the competition, both in getting interviewed and admitted, according to their study of applicants to a university MBA program. Endorsed applicants also tend to support the university at higher rates by taking on leadership roles as students and giving more generous monetary donations as alumni. However, colleges and companies may be missing out on valuable talent if they accept only endorsed applicants, the researchers note in "Best in Class: The Returns on Application Endorsements in Higher Education," published in Administrative Science Quarterly.

"This research highlights how an endorser can have a large effect on who gets interviewed, and who gets admitted, into an MBA program," said co-author Ben A. Rissing, assistant professor of organizational behavior in Cornell's ILR School.

Rissing and his co-author, Emilio J. Castilla of the Massachusetts Institute of Technology, found that endorsed applicants were interviewed about 82 percent of the time, while those without endorsements scored an interview only 34 percent of the time. Among those who interviewed, endorsed applicants received offers to join the program 64 percent of the time, while those without endorsements got offers only 52 percent of the time. "These are big differences," Rissing said.

Researchers found that endorsed individuals were no more qualified than their non-endorsed counterparts, based on merit-based competency assessments conducted by admissions staff who didn't know the applicants' endorsement status. While endorsed applicants were sometimes seen as stronger ''on paper'' (after a review of their application materials), they generally scored worse during interviews than non-endorsed applicants. Further, students who were endorsed as applicants were neither better performers academically (in terms of awards or GPA) or on the job market after graduation (in terms of salary or signing bonuses).

That said, those who were endorsed as applicants did emerge as ''better citizens" (more likely to lead student clubs) and ''better alumni" (more likely to donate to the university, and notably, more likely to give large amounts) than those who had not been endorsed.

Endorsements do seem to identify individuals who will be committed to the organization. But they do not necessarily identify better-qualified candidates, Rissing said. "Organizations should go through their application process and ask, 'Are we selecting on applicant characteristics that are going to result in organizational members who are most desirable?'" he said. In selecting for qualified applicants and those who are community-minded, he said, "It's a question of how to balance the two of these considerations, so one doesn't overwhelm the other. Both have merits."

The study also raises concerns about inequality. For example, first-generation students, immigrants, and students without financial resources might not yet have contacts who are willing or able endorse them, Rissing said. "There are smart, qualified and community-minded individuals in all of these groups. Is their potential lack of awareness of these endorsement channels going to limit their opportunities?" he said. "Decision-makers must be attentive to the reality that access to these types of social connections, such as endorsements, are not ubiquitous."

A study of the microbiomes of wild gorillas and chimpanzees offers insights into the evolution of the human microbiome and might even have implications for human health. The research project was led by scientists at the Center for Infection and Immunity (CII) at Columbia University's Mailman School of Public Health. Findings appear in the journal Nature Communications.

The researchers used genetic sequencing to analyze fecal samples collected by the Wildlife Conservation Society (WCS) from wild African great apes living the Sangha region of the Republic of Congo over the course of three years. Their goal was to understand the mix of gut microbes living in gorillas and chimpanzees and compare them to those already documented in other non-human primates and human populations. They found that gorilla and chimpanzee microbiomes fluctuate with seasonal rainfall patterns and diet, switching markedly during the summer dry period when succulent fruits abound in their environment and make up a larger proportion of their diet, as opposed to their usual, more fiber-rich diet of leaves and bark.

These seasonal shifts in the microbiomes of gorillas and chimpanzees are similar to seasonal microbiome changes observed in the human Hadza hunter-gatherers from Tanzania, who also rely heavily on the seasonal availability of foods in their environment. Seasonal shifts in the microbiomes of human industrialized cultures, such as the United States, are likely less prevalent owing to reduced reliance on seasonally available foods and globalization of the food supply, as evident in any grocery store.

"While our human genomes share a great deal of similarity with those of our closest living relatives, our second genome (the microbiome) has some important distinctions, including reduced diversity and the absence of bacteria and archaea that appear to be important for fiber fermentation," says first author Allison L. Hicks, MS, a researcher at CII. "Understanding how these lost microbes influence health and disease will be an important area for future studies."

"We observed dramatic changes in the gorilla and chimpanzee microbiomes depending on seasons and what they are eating," says senior author Brent L. Williams, PhD, assistant professor of Epidemiology at CII. "Bacteria that help gorillas break down fibrous plants are replaced once a year by another group of bacteria that feed on the mucous layer in their gut during the months they are eating fruits.

"The fact that our microbiomes are so different from our nearest living evolutionary relatives says something about how much we've changed our diets, consuming more protein and animal fat at the expense of fiber," says Williams. "Many humans may be living in a constant state of fiber deficiency. Such a state may be promoting the growth of bacteria that degrade our protective mucous layer, which may have implications for intestinal inflammation, even colon cancer."

All great apes are endangered or critically endangered. Down to fewer than 500,000, their numbers have been reduced through deforestation-which destroys their habitat-and through hunting, including for meat. Even infectious disease is a major factor-as many as one-quarter of the world's gorilla population has died because of Ebola.

"We are losing biodiversity on a global scale," cautions co-author Sarah Olson, PhD, associate director of wildlife health at WCS. "In fact, our own human microbiome is not immune to this phenomenon. There is an ever growing need for conservation efforts to preserve environments that are vital to the health of animal populations."

"This study underscores the importance of a One Health framework in focusing not only on diseases but also on understanding more about normal physiology," said co-author W. Ian Lipkin, MD, John Snow Professor of Epidemiology and director of CII. "It also provides evidence to support the adage that you are what you eat."