Author: Nancy Fliesler

Science Seen: Worms give a clue to how the nervous system stays organized

nervous system tiling
Courtesy Candice Yip

To the eye, nervous systems look like a tangled mess of neurons and their tree-like branches known as dendrites, but it’s really organized chaos. How the system finds order has intrigued but eluded scientists. In the worm C. elegans, Max Heiman, PhD and graduate student Candice Yip found an elegant system to help explain how neurons each maintain their own space.

Normally, worms have just one neuron of a certain type on either side of their bodies. Yip did a “forward genetic screen” — mutating genes at random to find factors important for neuron wiring. One mutation caused the worm to grow not one set of neurons but five. By engineering the neurons to make a color-changing signal — as shown above — Yip showed that these extra neurons didn’t overlap with each other, but instead carved out discrete territories — a phenomenon known as tiling. How?

Acting on a hunch, Yip and Heiman, of Harvard Medical School and Boston Children’s Hospital’s Division of Genetics and Genomics, showed that C. elegans, faced with an increase in neurons, pressed a molecule called netrin into service to enforce boundaries between them. Netrin is better known for helping nerve fibers navigate to their destinations. When Yip took netrin out of action, the dendrites from the five neurons crossed the invisible borders and grew entangled.

The findings, published today in Cell Reports, could provide insight into neuropsychiatric diseases, believes Heiman, also part of Boston Children’s F.M. Kirby Neurobiology Center. “It’s fundamental to neuropsychiatric disease to make sure brain wiring goes right,” he says. “This is also story about how new features evolve, and how you can form something as complicated as a nervous system. There are pathways that bring everything into order.”

Read more in this feature from Harvard Medical School and learn more about Heiman’s research.

 

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An inner ear in a dish

lab-grown inner ear organs
Images courtesy Eri Hashino

Could regenerative techniques restore hearing or balance by replacing lost sensory cells in the inner ear? Lab-created inner-ear organs, described today in Nature Communications, could provide helpful three-dimensional models for testing potential therapies.

The lab-built sac-like structure above, about 1 millimeter in size, contains fully-formed balance organs resembling the utricle and saccule, which sense head orientation and movement and send impulses to the brain. The tiny organs were built from mouse embryonic stem cells in a 3-D tissue culture in work led by Jeffrey Holt, PhD, of the F.M. Kirby Neurobiology Center at Boston Children’s Hospital and Eri Hashino, PhD, of the University of Indiana.

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Science Seen: Poverty and accidental death, 1999-2012

Unintentional injuries are the fifth largest cause of death in the U.S., and these mortalities have been rising over the past decade. At the same time, more people are living in areas with high poverty levels. Are these trends connected?

An analysis published last week in PLOS One gives evidence that the answer is “yes.” Emergency medicine physician Eric Fleegler, MD, MPH, and colleagues crunched U.S. Census Bureau data against mortality data from the National Center for Health Statistics for 1999 to 2012 — providing resolution down to the county level.

Not only did fatalities increase in tandem with the level of poverty in a county, the study found, but this effect worsened over time, especially for deaths from certain causes such as poisonings, shown here. Read the details in our sister blog, Notes. (Interactive image: Erin Horan)

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Real-time influenza tracking with electronic health records

influenza tracking
Data captured from healthcare visits could be a tool for medical surveillance.

Early influenza detection and the ability to predict outbreaks are critical to public health. Reliable estimates of when influenza will peak can help drive proper timing of flu shots and prevent health systems from being blindsided by unexpected surges, as happened in the 2012-2013 flu season.

The Centers for Disease Control and Prevention collects accurate data, but with a time lag of one to two weeks. Google Flu Trends began offering real-time data in 2008, based on people’s Internet searches for flu-related terms. But it ultimately failed, at least in part because not everyone who searches “flu” is actually sick. As of last year, Google instead now sends its search data to scientists at the CDC, Columbia University and Boston Children’s Hospital.

Now, a Boston Children’s-led team demonstrates a more accurate way to pick up flu trends in near-real-time — at least a week ahead of the CDC — by harnessing data from electronic health records (EHRs).

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Medicine meets theater: Pediatrics training, parent practice, device innovation ‘on location’

medical simulation

Pediatric medicine just took a step for the better in Boston’s Longwood Medical Area with a new, expanded pediatric Simulation (SIM) Center — a dedicated space where doctors, nurses and other staff can rehearse tough medical situations or practice tricky or rare procedures in a clinical setting that looks and feels real.

But clinicians aren’t the only ones who will be using the new 4,000-square-foot facility, which incorporates real medical equipment, set design and special effects.

Families can get hands-on practice with medical equipment they’ll be using at home. Inventors and “hackers” can develop and test new devices or software platforms and see how they perform in a life-like clinical environment. Planned hacks, for example, will explore different medical and surgical applications for voice-activated and gesture-controlled devices.

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The face of telehealth: Serving children in health care “deserts”

pediatric telehealthAt least 15 million children reside in Health Professional Shortage Areas (HPSAs) that average fewer than one health professional for every 3,500 people. In these health care deserts, time and transportation barriers prevent even children with health insurance have trouble getting timely care, particularly specialty care. Children in poor, rural areas are most at risk.

So health problems fester and get worse — and more expensive when finally addressed.

Telehealth can solve many of these problems. Through remote video/voice/data connections, dermatologists can view images of rashes and moles sent by primary care providers; cardiologists can patch into local emergency rooms and listen to heart sounds and read EKG tracings; critical care physicians and neonatologists can see and hear newborns in distress, listen to lung sounds, read their vital signs and view images. They can advise local clinicians and guide them through next steps.

However, pediatric telehealth hasn’t been adopted as widely as it could be. A white paper presented by the Children’s Health Fund at a Congressional briefing last week enumerated the obstacles:

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Can we supercharge vaccines? Added compound boosts T-cell production

supercharged vaccines oxPAPCBridging our innate and adaptive immune systems, dendritic cells are sentinels that circulate in the body searching out microbes and activating T-cells to destroy the invaders. They do this by presenting bits of the microbes on their surface—explaining why they’re often called antigen-presenting cells.

Reporting in Science this week, researchers describe a way to push dendritic cells into a “hyperactive” state, supercharging their ability to rally T-cells.

The key player, a fatty chemical called oxPAPC, is naturally found in damaged tissues and atherosclerotic plaques. It selectively targets dendritic cells and could, the researchers believe, enhance people’s immunity to a wide range of infections.

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Arsenic and neural tube defects: Lessons from Bangladesh?

arsenic neural tube defects

Spina bifida and other neural tube defects have become fairly rare in the United States, thanks in part to folic acid added to foods and campaigns to get childbearing women to take folic acid. But in Bangladesh, spina bifida is a common occurrence on maternity wards; in fact, it is considered to be epidemic.

“No surveillance is done, so it’s not clear how many cases there are,” says Maitreyi Mazumdar, MD, MPH, a neurologist at Boston Children’s Hospital who conducts environmental health research. “Children may die in delivery, or they may die before seeing a surgeon.”

Although folic acid supplementation isn’t widespread in Bangladesh, Mazumdar thinks there is another factor in play: the country’s ongoing epidemic of arsenic poisoning.

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News Notes: Headlines in science and innovation

An occasional roundup of news items Vector finds noteworthy.

Zika’s surface in stunning detail; mosquito tactics

Zika virus
(Purdue University image/courtesy of Kuhn and Rossmann research groups)

We haven’t curbed the Zika epidemic yet. But cryo-electron microscopy — a newer, faster alternative to X-ray crystallography — at least reveals the structure of the virus, which has been linked to microcephaly (though not yet definitively). The anatomy of the virus’s projections gives clues to how the virus is able to attach to and infect cells, and could provide toeholds for developing antiviral treatments and vaccines. Read coverage in the Washington Post and see the full paper in Science.

Meanwhile, as The New York Times reports, scientists are coming together in an effort to control Zika by genetically manipulating the mosquito that spreads it, Aedes aegypti.

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Targeting synapse loss in Alzheimer’s to preserve cognition — before plaques appear

Alzheimer's microglia complement
Microglia (in red) consume synapses (in green) after mice are injected with the oligomeric form of beta-amyloid, before plaques appear in the brain. (Soyon Hong, Boston Children’s Hospital)

Currently, there are five FDA-approved drugs for Alzheimer’s disease, but these only boost cognition temporarily and don’t address the root causes of Alzheimer’s dementia. Many newer drugs in the pipeline seek to eliminate amyloid plaque deposits or reduce inflammation in the brain, but by the time this pathology is detectable, it’s unlikely medications can do much to slow the disease.

New research published in Science today suggests several ways that Alzheimer’s could be targeted much earlier to preserve cognitive function — before plaques or inflammation are evident.

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