Rainfall, brain infection linked in sub-Saharan Africa

The amount of rainfall affects the number of infant infections leading to hydrocephalus in Uganda, according to a team of researchers who are the first to demonstrate that these brain infections are linked to climate.

Hydrocephalus — literally “water on the brain” — is characterized by the buildup of the fluid that is normally within and surrounding the brain, leading to brain swelling. The swelling will cause brain damage or death if not treated. Even if treated, there is only a one-third chance of a child maintaining a normal life after post-infectious hydrocephalus develops, and that chance is dependent on whether the child has received the best treatment possible.

"The most common need for a child to require neurosurgery around the world is hydrocephalus," said Steven J. Schiff, the Brush Chair Professor of Engineering, director of the Penn State Center for Neural Engineering and a team member.

In sub-Saharan Africa, upward of 100,000 cases of post-infectious hydrocephalus a year are estimated to occur. The majority of these cases occur after a newborn has suffered from neonatal sepsis, a blood infection that occurs within the first four weeks of life, the researchers reported in a recent issue of the Journal of Neurosurgery: Pediatrics.

Benjamin C. Warf, associate professor of neurosurgery, Harvard Medical School, Boston Children’s Hospital, noticed that about three or four months after an infant in East Africa had an infection like neonatal sepsis, the child would often return to the clinic with a rapidly growing head — hydrocephalus. Schiff joined Warf to help figure out what caused this disease so frequently.

Schiff and colleagues tracked 696 hydrocephalus cases in Ugandan infants between the years 2000 and 2005. The researchers obtained localized rainfall data for the same time frame through NOAA (National Oceanic and Atmospheric Administration) weather satellites using the African Rainfall Estimation Algorithm developed at the U.S. NOAA Climate Prediction Center.

Uganda has two peak rainfall seasons, in spring and fall. By comparing the data from NOAA and the hydrocephalus cases, the researchers found that instances of the disorder rose significantly at four different times throughout the year — before and after the peak of each rainy season, when the amount of rainfall was at intermediate levels. In Uganda an intermediate rainfall is about 6 inches of rain per month.

Schiff and colleagues previously noted that different bacteria appear associated with post-infectious hydrocephalus at different seasons of the year. While the researchers have not yet characterized the full spectrum of bacteria causing hydrocephalus in so many infants, they note that environmental conditions affect conditions supporting bacterial growth, and that the amount of rain can quench bacterial infections. The moisture level clearly affects the number of cases of hydrocephalus in this region of East Africa.

"Hydrocephalus is the first major neurosurgical condition linked to climate," said Schiff, who is also professor of neurosurgery, engineering science and mechanics, and physics, and a faculty member of the Huck Institutes of the Life Sciences. "This means that a substantial component of these cases are almost certainly driven from the environmental conditions, and that means they are potentially preventable if we understand the routes and mechanisms of infection better."

Pioneering Research on Type 2 Diabetes

While legions of medical researchers have been looking to understand the genetic basis of disease and how mutations may affect human health, a group of biomedical researchers at UC Santa Barbara is studying the metabolism of cells and their surrounding tissue, to ferret out ways in which certain diseases begin. This approach, which includes computer modeling, can be applied to Type 2 diabetes, autoimmune diseases, and neurodegenerative diseases, among others.

Scientists at UCSB have published groundbreaking results of a study of Type 2 diabetes that point to changes in cellular metabolism as the triggering factor for the disease, rather than genetic predisposition. Type 2 diabetes is a chronic condition in which blood sugar or glucose levels are high. It affects a large and growing segment of the human population, especially among the obese. The team of scientists expects the discovery to become a basis for efforts to prevent and cure this disease.

The current work is based on a previous major finding by UCSB’s Jamey Marth, who determined the identity of the molecular building blocks needed in constructing the four types of macromolecules of all cells when he was based at the Howard Hughes Medical Institute in La Jolla in 2008. These include the innate, genetic macromolecules, such as nucleic acids (DNA and RNA) and their encoded proteins, and the acquired metabolic macromolecules known as glycans and lipids. Marth is a professor in the Department of Molecular, Cellular, and Developmental Biology and the Biomolecular Science and Engineering Program; and holds the John Carbon Chair in Biochemistry and Molecular Biology and the Duncan and Suzanne Mellichamp Chair in Systems Biology. He is also a professor with the Sanford-Burnham Medical Research Institute in La Jolla.

"By studying the four types of components that make up the cell, we can, for the first time, begin to understand what causes many of the common grievous diseases that exist in the absence of definable genetic variation, but, instead, are due to environmental and metabolic alterations of our cells," said Marth. UCSB is the only institution studying these four types of molecules in the cells while also using computational modeling to determine their functions in health and disease, according to Marth.

The new study, published in the December 27 issue of PLOS ONE, relies on computational systems biology modeling to understand the pathogenesis of Type 2 diabetes.

Professor Discovers New Information in the Understanding of Autism and Genetics

Research out of the George Washington University (GW), published in the journal Proceedings of the National Academy of Sciences (PNAS), reveals another piece of the puzzle in a genetic developmental disorder that causes behavioral diseases such as autism. Anthony-Samuel LaMantia, Ph.D., professor of pharmacology and physiology at the GW School of Medicine and Health Sciences (SMHS) and director of the GW Institute for Neuroscience, along with post-doctoral fellow Daniel Meechan, Ph.D. and Thomas Maynard, Ph.D., associate research professor of pharmacology and physiology at GW SMHS, authored the study titled “Cxcr4 regulation of interneuron migration is disrupted in 22q11.2 deletion syndrome.”

For the past nine years, LaMantia and his colleagues have been investigating how behavioral disorders such as autism, attention deficit hyperactivity disorder (ADHD), and schizophrenia arise during early brain development. His work published in PNAS focuses specifically on the effects diminished 22q11.2 gene dosage has on cortical circuit development.

This research shows for the first time that genetic lesions known to be associated with autism and other behavioral diseases disrupt cellular and molecular mechanisms that ensure normal development of a key type of cortical neuron: the interneuron. LaMantia and his colleagues had found previously that one type of cortical neuron, the projection neuron, is not generated in appropriate numbers during development in a mouse model of 22q11 Deletion Syndrome. In the current study published in PNAS, LaMantia found that interneurons, while made in the right numbers at their birthplace outside of the cortex, are not able to move properly into the cortex where they are needed to control cortical circuit activity. The research shows that the main reason they don’t move properly is due to diminished expression of activity of a key regulatory pathway for migration, the Cxcr4 cytokine receptor.

“This gives us two pieces of the puzzle for this genetic developmental disorder,” said LaMantia. “These two pieces tell us that in very early development, those with 22q11.2 deletion syndrome do not make enough cells in one case, and do not put the other cells in the right place. This occurs not because of some degenerative change, but because the mechanisms that make these cells and put them in the right place during the first step of development have gone awry due to mutation.”

The next step in LaMantia’s research is to probe further into the molecular mechanisms that disrupt the proliferation of projection neurons and migration of interneurons. “If we understand that better and understand its consequences, we can go about fixing it,” said LaMantia. “We want to understand why cortical circuits don’t get built properly due to the genetic deletion of chromosome 22.”

LaMantia recently received the latest installment of a 10-year RO1 grant from the National Institutes of Health and the Eunice Kennedy Shriver National Institute of Child Health & Human Development for his project, titled “Regulation of 22q11 Genes in Embryonic and Adult Forebrain.” This will allow him to further his research.

(Image: iStockphoto)

Dopamine-receptor gene variant linked to human longevity

A variant of a gene associated with active personality traits in humans seems to also be involved with living a longer life, UC Irvine and other researchers have found.

This derivative of a dopamine-receptor gene – called the DRD4 7R allele – appears in significantly higher rates in people more than 90 years old and is linked to lifespan increases in mouse studies.

Robert Moyzis, professor of biological chemistry at UC Irvine, and Dr. Nora Volkow, a psychiatrist who conducts research at the Brookhaven National Laboratory and also directs the National Institute on Drug Abuse, led a research effort that included data from the UC Irvine-led 90+ Study in Laguna Woods, Calif. Results appear online in The Journal of Neuroscience.

The variant gene is part of the dopamine system, which facilitates the transmission of signals among neurons and plays a major role in the brain network responsible for attention and reward-driven learning. The DRD4 7R allele blunts dopamine signaling, which enhances individuals’ reactivity to their environment.

People who carry this variant gene, Moyzis said, seem to be more motivated to pursue social, intellectual and physical activities. The variant is also linked to attention-deficit/hyperactivity disorder and addictive and risky behaviors.

“While the genetic variant may not directly influence longevity,” Moyzis said, “it is associated with personality traits that have been shown to be important for living a longer, healthier life. It’s been well documented that the more you’re involved with social and physical activities, the more likely you’ll live longer. It could be as simple as that.”

Numerous studies – including a number from the 90+ Study – have confirmed that being active is important for successful aging, and it may deter the advancement of neurodegenerative diseases, such as Alzheimer’s.

Prior molecular evolutionary research led by Moyzis and Chuansheng Chen, UC Irvine professor of psychology & social behavior, indicated that this “longevity allele” was selected for during the nomadic out-of-Africa human exodus more than 30,000 years ago.

In the new study, the UC Irvine team analyzed genetic samples from 310 participants in the 90+ Study. This “oldest-old” population had a 66 percent increase in individuals carrying the variant relative to a control group of 2,902 people between the ages of 7 and 45. The presence of the variant also was strongly correlated with higher levels of physical activity.

Next, Volkow, neuroscientist Panayotis Thanos and their colleagues at the Brookhaven National Laboratory found that mice without the variant had a 7 percent to 9.7 percent decrease in lifespan compared with those possessing the gene, even when raised in an enriched environment.

While it’s evident that the variant can contribute to longevity, Moyzis said further studies must take place to identify any immediate clinical benefits from the research. “However, it is clear that individuals with this gene variant are already more likely to be responding to the well-known medical adage to get more physical activity,” he added.

Your Brain on Big Bird: Sesame Street Helps to Reveal Patterns of Neural Development

Using brain scans of children and adults watching Sesame Street, cognitive scientists are learning how children’s brains change as they develop intellectual abilities like reading and math.

The novel use of brain imaging during everyday activities like watching TV, say the scientists, opens the door to studying other thought processes in naturalistic settings and may one day help to diagnose and treat learning disabilities.

Scientists are just beginning to use brain imaging to understand how humans process thought during real-life experiences. For example, researchers have compared scans of adults watching an entertaining movie to see if neural responses are similar across different individuals. “But this is the first study to use the method as a tool for understanding development,” says lead author Jessica Cantlon, an assistant professor in brain and cognitive sciences at the University of Rochester.

Eventually, that understanding may help pinpoint the cause when a child experiences difficulties mastering school work. “Psychologists have behavioral tests for trying to get the bottom of learning impairments, but these new imaging studies provide a totally independent source of information about children’s learning based on what’s happening in the brain,” says Cantlon.

The neuroimaging findings are detailed in a new study published Jan. 3 by the Public Library of Science’s open-access journal PLoS Biology, by Cantlon and her former research assistant Rosa Li, now a graduate student at Duke University.

The Nerve-Growth Factor: A New Tool for Manipulating Neurons

The human nervous system is a vast network of several billion neurons, or nerve cells, endowed with the remarkable ability to receive, store and transmit information. In order to communicate with one another and with non-neuronal cells the neurons rely on the long extensions called axons, which are somewhat analogous to electrically conducting wires. Unlike wires, however, the axons are fluid-filled cylindrical structures that not only transmit electrical signals but also ferry nutrients and other essential substances to and from the cell body. Many basic questions remain to be answered about the mechanisms governing the formation of this intricate cellular network. How do the nerve cells differentiate into thousands of different types? How do their axons establish specific connections (synapses) with other neurons and non-neuronal cells? And what is the nature of the chemical messages neurons send and receive once the synaptic connections are made?

This article will describe some major characteristics and effects of a protein called the nerve-growth factor (NGF), which has made it possible to induce and analyze under highly favorable conditions some crucial steps in the differentiation of neurons, such as the growth and maturation of axons and the synthesis and release of neurotransmitters: the bearers of the chemical messages. The discovery of NGF has also promoted an intensive search for other specific growth factors, leading to the isolation and characterization of a number of proteins with the ability to enhance the growth of different cell lines.

Continue reading

Bonobos will share with strangers before acquaintances

You’re standing in line somewhere and you decide to open a pack of gum. Do you share a piece with the coworker standing to one side of you, or with the stranger on the other?

Most humans would choose the person they know first, if they shared at all.

But bonobos, those notoriously frisky, ardently social great apes of the Congo, prefer to share with a stranger before sharing with an animal they know. In fact, a bonobo will invite a stranger to share a snack while leaving an acquaintance watching helplessly from behind a barrier.

"It seems kind of crazy to us, but bonobos prefer to share with strangers," said Brian Hare, a professor of evolutionary anthropology at Duke University. "They’re trying to extend their social network." And they apparently value that more than maintaining the friendships they already have.

To measure this willingness to share, Hare and graduate student Jingzhi Tan ran a series of experiments with bonobos living in the Lola ya Bonobo sanctuary in Kinshasa, Democratic Republic of Congo. The experiments involved piles of food and enclosures that the test subjects were able to unlock and open. Tan and Hare describe their work in a paper in the January 2, 2013 edition of PLOS ONE.

In the first series of experiments, a pile of food was placed in a central enclosure flanked by two enclosures, each of them holding another animal. The test subject had the knowledge and ability to open a door to either of the other chambers, or both. On one side was a bonobo they knew from their group (not necessarily a friend or family member) and in the other was a bonobo they had never really met, but had only seen at a distance.

Upon entering the chamber with the food, the test subjects could easily just sit down and consume it all themselves, or they could let in one or both of the other animals to share.

Nine of the 14 animals who went through this test released the stranger first. Two preferred their groupmates. Three showed no particular preference in repeated trials. The third animal was often let in on the treat as well, but more often it was the stranger, not the test subject, who opened the door for them.

Tan said that by letting the third animal into the enclosure, the stranger voluntarily outnumbered himself or herself with two bonobos who knew each other, which a chimpanzee would never do. In 51 trials of the experiment, there was never any aggression shown, although there was quite a bit of typical bonobo genital rubbing between the strangers.

To isolate how much motivation the animals receive from social interaction, the researchers ran a second set of experiments in which the subject animal wouldn’t receive any social contact with another animal. In the first of these experiments, the subjects couldn’t get any food for themselves regardless of whether they chose to open the door to allow the other animal to get some food. Nine out of ten animals shared with the stranger at least once.

In the final experiment without social contact, the subject animal was given access to the food in such a way that opening the door to share with the other animal would cost them some food. But they still wouldn’t have any social contact as a reward. In this instance, the animals chose not to share. “If they’re not going to see a social benefit, they won’t share,” Hare said.

This second test is similar to something called the dictator game in which humans are given the chance to share cash with a stranger, Hare said. Most people will share anonymously, but they share even more when they aren’t anonymous. Bonobos won’t share at all in the anonymous condition if it costs them food.

"They care about others," Hare said, but only in a sort of selfish way. "They’ll share when it’s a low-cost/low-benefit kind of situation. But when it’s a no-benefit situation, they won’t share. That’s different from a human playing the dictator game. You really have to care about others to give anonymously."

The findings, which Hare calls “one of the crazier things we’ve found” in more than a decade of bonobo research, form yet another distinction between bonobos and chimpanzees, our two closest relatives. “Chimps can’t do these tests, they’d be all over each other.”