Medical Terms, Facts, and etc.

Lungs are by most accounts mundane. Everybody has them, few give it much thought. But sequestered within darkness of the chest cavity, enveloping the fluttering heart, there’s a incredible wonder to this oddly inflatable organ.

Dissection is a destructive process. Rudely excised from membranous mooring and nourishing vessels, the deflated lungs appear little more than bloodied meat; amorphous and exposed…….until a breath of air unfurls its secret glory. 

Here, a set of cat lungs is inflated with a straw. Comprised of hundreds of millions of microscopic air sacks called aveoli, Mammalian lungs harbor air capacity that is difficult to believe unless seen. The color of the entire organ lightens into a soft pink, as each microscopic sac fills with air.

Pictures from The Resurrectionist by E.B. Hudspeth.

Trichobezoar removal surgery picture. (Trichobezoars or human hairballs are complications of trichophagia or eating of the hair)

The first systematic review of related research confirms a positive impact on cognitive function, but an inconsistent effect on mild cognitive impairment.

Look at what I’m saying: Engineers show brain depends on vision to hear

University of Utah bioengineers discovered our understanding of language may depend more heavily on vision than previously thought: under the right conditions, what you see can override what you hear. These findings suggest artificial hearing devices and speech-recognition software could benefit from a camera, not just a microphone.

“For the first time, we were able to link the auditory signal in the brain to what a person said they heard when what they actually heard was something different. We found vision is influencing the hearing part of the brain to change your perception of reality – and you can’t turn off the illusion,” says the new study’s first author, Elliot Smith, a bioengineering and neuroscience graduate student at the University of Utah. “People think there is this tight coupling between physical phenomena in the world around us and what we experience subjectively, and that is not the case.”

The brain considers both sight and sound when processing speech. However, if the two are slightly different, visual cues dominate sound. This phenomenon is named the McGurk effect for Scottish cognitive psychologist Harry McGurk, who pioneered studies on the link between hearing and vision in speech perception in the 1970s. The McGurk effect has been observed for decades. However, its origin has been elusive.

In the new study, which appears today in the journal PLOS ONE, the University of Utah team pinpointed the source of the McGurk effect by recording and analyzing brain signals in the temporal cortex, the region of the brain that typically processes sound.

Working with University of Utah bioengineer Bradley Greger and neurosurgeon Paul House, Smith recorded electrical signals from the brain surfaces of four severely epileptic adults (two male, two female) from Utah and Idaho. House placed three button-sized electrodes on the left, right or both brain hemispheres of each test subject, depending on where each patient’s seizures were thought to originate. The experiment was done on volunteers with severe epilepsy who were undergoing surgery to treat their epilepsy.

These four test subjects were then asked to watch and listen to videos focused on a person’s mouth as they said the syllables “ba,” “va,” “ga” and “tha.” Depending on which of three different videos were being watched, the patients had one of three possible experiences as they watched the syllables being mouthed:

– The motion of the mouth matched the sound. For example, the video showed “ba” and the audio sound also was “ba,” so the patients saw and heard “ba.”

– The motion of the mouth obviously did not match the corresponding sound, like a badly dubbed movie. For example, the video showed “ga” but the audio was “tha,” so the patients perceived this disconnect and correctly heard “tha.”

– The motion of the mouth only was mismatched slightly with the corresponding sound. For example, the video showed “ba” but the audio was “va,” and patients heard “ba” even though the sound really was “va.” This demonstrates the McGurk effect – vision overriding hearing.

By measuring the electrical signals in the brain while each video was being watched, Smith and Greger could pinpoint whether auditory or visual brain signals were being used to identify the syllable in each video. When the syllable being mouthed matched the sound or didn’t match at all, brain activity increased in correlation to the sound being watched. However, when the McGurk effect video was viewed, the activity pattern changed to resemble what the person saw, not what they heard. Statistical analyses confirmed the effect in all test subjects.

“We’ve shown neural signals in the brain that should be driven by sound are being overridden by visual cues that say, ‘Hear this!’” says Greger. “Your brain is essentially ignoring the physics of sound in the ear and following what’s happening through your vision.”

Greger was senior author of the study as an assistant professor of bioengineering at the University of Utah. He recently took a faculty position at Arizona State University.

To grow beyond the size of rice grain, tumors (yellow and red) must induce the growth of blood vessels (green-yellow). They secrete growth factors, such as VEGF, and they stop producing the anti-VEGF enzyme cGMP-dependent kinase (PKG). The construction of blood vessels is such an important step in tumorigenesis that numerous VEGF inhibitors have been approved as cancer treatments. However, whether these treatments have a long-term benefit for patients is still under debate.

A bundle of neurons suspended between two protein coated surfaces under scanning electron microscope.

Researchers discover a potential cause of autism

Key enzymes are found to have a ‘profound effect’ across dozens of genes linked to autism. The insight could help illuminate environmental factors behind autism spectrum disorder and contribute to a unified theory of how the disorder develops.

Problems with a key group of enzymes called topoisomerases can have profound effects on the genetic machinery behind brain development and potentially lead to autism spectrum disorder (ASD), according to research announced today in the journal Nature. Scientists at the University of North Carolina School of Medicine have described a finding that represents a significant advance in the hunt for environmental factors behind autism and lends new insights into the disorder’s genetic causes.

“Our study shows the magnitude of what can happen if topoisomerases are impaired,” said senior study author Mark Zylka, PhD, associate professor in the Neuroscience Center and the Department of Cell Biology and Physiology at UNC. “Inhibiting these enzymes has the potential to profoundly affect neurodevelopment — perhaps even more so than having a mutation in any one of the genes that have been linked to autism.”

The study could have important implications for ASD detection and prevention.

“This could point to an environmental component to autism,” said Zylka. “A temporary exposure to a topoisomerase inhibitor in utero has the potential to have a long-lasting effect on the brain, by affecting critical periods of brain development. ”

This study could also explain why some people with mutations in topoisomerases develop autism and other neurodevelopmental disorders.

Topiosomerases are enzymes found in all human cells. Their main function is to untangle DNA when it becomes overwound, a common occurrence that can interfere with key biological processes.

Most of the known topoisomerase-inhibiting chemicals are used as chemotherapy drugs. Zylka said his team is searching for other compounds that have similar effects in nerve cells. “If there are additional compounds like this in the environment, then it becomes important to identify them,” said Zylka. “That’s really motivating us to move quickly to identify other drugs or environmental compounds that have similar effects — so that pregnant women can avoid being exposed to these compounds.”

Zylka and his colleagues stumbled upon the discovery quite by accident while studying topotecan, a topoisomerase-inhibiting drug that is used in chemotherapy. Investigating the drug’s effects in mouse and human-derived nerve cells, they noticed that the drug tended to interfere with the proper functioning of genes that were exceptionally long — composed of many DNA base pairs. The group then made the serendipitous connection that many autism-linked genes are extremely long.

“That’s when we had the ‘Eureka moment,’” said Zylka. “We realized that a lot of the genes that were suppressed were incredibly long autism genes.”

Of the more than 300 genes that are linked to autism, nearly 50 were suppressed by topotecan. Suppressing that many genes across the board — even to a small extent — means a person who is exposed to a topoisomerase inhibitor during brain development could experience neurological effects equivalent to those seen in a person who gets ASD because of a single faulty gene.

The study’s findings could also help lead to a unified theory of how autism-linked genes work. About 20 percent of such genes are connected to synapses — the connections between brain cells. Another 20 percent are related to gene transcription — the process of translating genetic information into biological functions. Zylka said this study bridges those two groups, because it shows that having problems transcribing long synapse genes could impair a person’s ability to construct synapses.

30 August 2013

The Broken Heart

Rather than being a symbol of love, a heart should be the symbol of life. Its pump-action keeps us alive, and more than a quarter of all deaths in the UK are due to heart attacks and other circulatory diseases. This striking picture – a winner of this year’s British Heart Foundation Reflections of Research awards – is a three-dimensional view of an adult mouse heart, produced using a technique called optical projection tomography (OPT). Similar to the way that a CT scan uses layers of X-rays to build up a 3D image of the body, OPT builds up pictures with light beams. The technology gives researchers a new view of healthy and diseased hearts, exposing them in exquisite detail. It’s enabling scientists to measure the amount of damage heart muscles sustain after a heart attack, illuminating what goes wrong during heart disease and revealing ways to fix it.

Written by Kat Arney

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Dr Gillian Gray, Megan Swim and Harris Morrison

University of Edinburgh

Brains on Demand

Scientists Succeed in Growing Human Brain Tissue in “Test Tubes”

Complex human brain tissue has been successfully developed in a three-dimensional culture system established in an Austrian laboratory. The method described in the current issue of NATURE allows pluripotent stem cells to develop into cerebral organoids – or “mini brains” – that consist of several discrete brain regions. Instead of using so-called patterning growth factors to achieve this, scientists at the renowned Institute of Molecular Biotechnology (IMBA) of the Austrian Academy of Sciences (OeAW) fine-tuned growth conditions and provided a conducive environment. As a result, intrinsic cues from the stem cells guided the development towards different interdependent brain tissues. Using the “mini brains”, the scientists were also able to model the development of a human neuronal disorder and identify its origin – opening up routes to long hoped-for model systems of the human brain.

The development of the human brain remains one of the greatest mysteries in biology. Derived from a simple tissue, it develops into the most complex natural structure known to man. Studies of the human brain’s development and associated human disorders are extremely difficult, as no scientist has thus far successfully established a three-dimensional culture model of the developing brain as a whole. Now, a research group lead by Dr. Jürgen Knoblich at the Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA) has changed just that.

Brain Size Matters

Starting with established human embryonic stem cell lines and induced pluripotent stem (iPS) cells, the group identified growth conditions that aided the differentiation of the stem cells into several brain tissues. While using media for neuronal induction and differentiation, the group was able to avoid the use of patterning growth factor conditions, which are usually applied in order to generate specific cell identities from stem cells. Dr. Knoblich explains the new method: “We modified an established approach to generate so-called neuroectoderm, a cell layer from which the nervous system derives. Fragments of this tissue were then maintained in a 3D-culture and embedded in droplets of a specific gel that provided a scaffold for complex tissue growth. In order to enhance nutrient absorption, we later transferred the gel droplets to a spinning bioreactor. Within three to four weeks defined brain regions were formed.”

Already after 15 – 20 days, so-called “cerebral organoids” formed which consisted of continuous tissue (neuroepithelia) surrounding a fluid-filled cavity that was reminiscent of a cerebral ventricle. After 20 – 30 days, defined brain regions, including a cerebral cortex, retina, meninges as well as choroid plexus, developed. After two months, the mini brains reached a maximum size, but they could survive indefinitely (currently up to 10 months) in the spinning bioreactor. Further growth, however, was not achieved, most likely due to the lack of a circulation system and hence a lack of nutrients and oxygen at the core of the mini brains. 

Microcephaly in Mini Brains

The new method also offers great potential for establishing model systems for human brain disorders. Such models are urgently needed, as the commonly used animal models are of considerably lower complexity, and often do not adequately recapitulate the human disease. Knoblich’s group has now demonstrated that the mini brains offer great potential as a human model system by analysing the onset of microcephaly, a human genetic disorder in which brain size is significantly reduced. By generating iPS cells from skin tissue of a microcephaly patient, the scientists were able to grow mini brains affected by this disorder. As expected, the patient derived organoids grew to a lesser size. Further analysis led to a surprising finding: while the neuroepithilial tissue was smaller than in mini brains unaffected by the disorder, increased neuronal outgrowth could be observed. This lead to the hypothesis that, during brain development of patients with microcephaly, the neural differentiation happens prematurely at the expense of stem and progenitor cells which would otherwise contribute to a more pronounced growth in brain size. Further experiments also revealed that a change in the direction in which the stem cells divide might be causal for the disorder.

Heart disease is the leading cause of deaths worldwide, and atherosclerosis (the thickening of artery walls) is one of the precursors to a number of heart-related diseases. Atherosclerosis can result from smooth muscle cells migrating and proliferating to plaques on artery walls. These invading muscles cells differ from normal cells because of the unique polygonal geometry of their cell skeleton filament actin (in red). This “net” of actin helps to protect the invading cells while they move about.