Why Scientists Are Rooting For Mushrooms

(Image caption: A new technique called magnified analysis of proteome (MAP), developed at MIT, allows researchers to peer at molecules within cells or take a wider view of the long-range connections between neurons. Credit: Courtesy of the researchers)

Imaging the brain at multiple size scales

MIT researchers have developed a new technique for imaging brain tissue at multiple scales, allowing them to peer at molecules within cells or take a wider view of the long-range connections between neurons.

This technique, known as magnified analysis of proteome (MAP), should help scientists in their ongoing efforts to chart the connectivity and functions of neurons in the human brain, says Kwanghun Chung, the Samuel A. Goldblith Assistant Professor in the Departments of Chemical Engineering and Brain and Cognitive Sciences, and a member of MIT’s Institute for Medical Engineering and Science (IMES) and Picower Institute for Learning and Memory.

“We use a chemical process to make the whole brain size-adjustable, while preserving pretty much everything. We preserve the proteome (the collection of proteins found in a biological sample), we preserve nanoscopic details, and we also preserve brain-wide connectivity,” says Chung, the senior author of a paper describing the method in the July 25 issue of Nature Biotechnology.

The researchers also showed that the technique is applicable to other organs such as the heart, lungs, liver, and kidneys.

The paper’s lead authors are postdoc Taeyun Ku, graduate student Justin Swaney, and visiting scholar Jeong-Yoon Park.

Multiscale imaging

The new MAP technique builds on a tissue transformation method known as CLARITY, which Chung developed as a postdoc at Stanford University. CLARITY preserves cells and molecules in brain tissue and makes them transparent so the molecules inside the cell can be imaged in 3-D. In the new study, Chung sought a way to image the brain at multiple scales, within the same tissue sample.

“There is no effective technology that allows you to obtain this multilevel detail, from brain region connectivity all the way down to subcellular details, plus molecular information,” he says.

To achieve that, the researchers developed a method to reversibly expand tissue samples in a way that preserves nearly all of the proteins within the cells. Those proteins can then be labeled with fluorescent molecules and imaged.

The technique relies on flooding the brain tissue with acrylamide polymers, which can form a dense gel. In this case, the gel is 10 times denser than the one used for the CLARITY technique, which gives the sample much more stability. This stability allows the researchers to denature and dissociate the proteins inside the cells without destroying the structural integrity of the tissue sample.

Before denaturing the proteins, the researchers attach them to the gel using formaldehyde, as Chung did in the CLARITY method. Once the proteins are attached and denatured, the gel expands the tissue sample to four or five times its original size.

“It is reversible and you can do it many times,” Chung says. “You can then use off-the-shelf molecular markers like antibodies to label and visualize the distribution of all these preserved biomolecules.”

There are hundreds of thousands of commercially available antibodies that can be used to fluorescently tag specific proteins. In this study, the researchers imaged neuronal structures such as axons and synapses by labeling proteins found in those structures, and they also labeled proteins that allow them to distinguish neurons from glial cells.

“We can use these antibodies to visualize any target structures or molecules,” Chung says. “We can visualize different neuron types and their projections to see their connectivity. We can also visualize signaling molecules or functionally important proteins.”

High resolution

Once the tissue is expanded, the researchers can use any of several common microscopes to obtain images with a resolution as high as 60 nanometers — much better than the usual 200 to 250-nanometer limit of light microscopes, which are constrained by the wavelength of visible light. The researchers also demonstrated that this approach works with relatively large tissue samples, up to 2 millimeters thick.

“This is, as far as I know, the first demonstration of super-resolution proteomic imaging of millimeter-scale samples,” Chung says.

“This is an exciting advance for brain mapping, a technique that reveals the molecular and connectional architecture of the brain with unprecedented detail,” says Sebastian Seung, a professor of computer science at the Princeton Neuroscience Institute, who was not involved in the research.

Currently, efforts to map the connections of the human brain rely on electron microscopy, but Chung and colleagues demonstrated that the higher-resolution MAP imaging technique can trace those connections more accurately.

Chung’s lab is now working on speeding up the imaging and the image processing, which is challenging because there is so much data generated from imaging the expanded tissue samples.

“It’s already easier than other techniques because the process is really simple and you can use off-the-shelf molecular markers, but we are trying to make it even simpler,” Chung says.

More ‪#‎WorldChocolateDay‬ chemistry: this time with C&EN, looking at dark chocolate, milk chocolate, and white ‘chocolate’: ow.ly/ugB93021z64

This massive virus with its own immune system could hold the future of medicine

French researchers think they’ve found a giant virus big enough to house its own virus-killing devices using a system like CRISPR, and it could be a completely new form of life.

Called a mimivirus, it was first found growing in amoebae in a water tower. At four times the size of a typical virus, you can even see it under a light microscope

When the mimivirus encounters another virus, it stores some of the invader’s genetic material. That way, when it encounters the same kind of virus again, the MIMIVIRE system goes into gene-editing berserker mode, finding the key genes of the virus and cutting them to inert oblivion. This could have major applications.

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What Happens in the Brain During Unconsciousness?

Researchers are shining a light on the darkness of the unconscious brain. Three new studies add to the body of knowledge.

When patients undergo major surgery, they’re often put under anesthesia to allow the brain to be in an unconscious state.

But what’s happening in the brain during that time?

Three Michigan Medicine researchers are authors on three new articles from the Center for Consciousness Science exploring this question — specifically how brain networks fragment in association with a variety of unconsciousness states.

“These studies come from a long-standing hypothesis my colleagues and I have had regarding the essential characteristic of why we are conscious and how we become unconscious, based on patterns of information transfer in the brain,” says George A. Mashour, M.D., Ph.D., professor of anesthesiology, director of the Center for Consciousness Science and associate dean for clinical and translational research at the University of Michigan Medical School.

In the studies, the team not only explores how the brain networks fragment, but also how better to measure what is happening.

“We’ve been working for a decade to understand in a more refined way how the spatial and temporal aspects of brain function break down during unconsciousness, how we can measure that breakdown and the implications for information processing,” says UnCheol Lee, Ph.D., physicist, assistant professor of anesthesiology and associate director of the Center for Consciousness Science.

Examining different aspects of unconsciousness

The basis for the three studies, as well as other work from the Center for Consciousness Science, comes from a theory Mashour produced during his residency.

“I published a theoretical article when I was a resident in anesthesiology suggesting that anesthesia doesn’t work by turning the brain off, per se, but rather by isolating processes in certain areas of the brain,” Mashour says. “Instead of seeing a highly connected brain network, anesthesia results in an array of islands with isolated cognition and processing. We have taken this thought, as well as the work of others, and built upon it with our research.”

In the study in the Journal of Neuroscience, the team analyzed different areas of the brain during sedation, surgical anesthesia and a vegetative state.

“It’s often suggested that different areas of the brain that typically talk to one another get out of sync during unconsciousness,” says Anthony Hudetz, Ph.D., professor of anesthesiology, scientific director of the Center for Consciousness Science and senior author on the study. “We showed in the early stages of sedation, the information processing timeline gets much longer and local areas of the brain become more tightly connected within themselves. That tightening might lead to the inability to connect with distant areas.”

In the Frontiers in Human Neuroscience study, the team delved into how the brain integrates information and how it can be measured in the real world.

“We took a very complex computational task of measuring information integration in the brain and broke it down into a more manageable task,” says Lee, senior author on the study. “We demonstrated that as the brain gets more modular and has more local conversations, the measure of information integration starts to decrease. Essentially, we looked at how the brain network fragmentation was taking place and how to measure that fragmentation, which gives us the sense of why we lose consciousness.”

Finally, the latest article, in Trends in Neurosciences, aimed to take the team’s previous studies and other work on the subject of unconsciousness and put together a fuller picture.

“We examined unconsciousness across three different conditions: physiological, pharmacological and pathological,” says Mashour, lead author on the study. “We found that during unconsciousness, disrupted connectivity in the brain and greater modularity are creating an environment that is inhospitable to the kind of efficient information transfer that is required for consciousness.”

How these studies can help patients

The team members at the Center for Consciousness Science note that all of this work may help patients in the future.

“We’re looking for a better way to quantify the depth of anesthesia in the operating room and to assess consciousness in someone who has had a stroke or brain damage,” Hudetz says. “For example, we may assume that a patient is fully unconscious based on behavior, but in some cases consciousness can persist despite unresponsiveness.”

The team hopes this and future research could lead to therapeutic strategies for patients.

“We want to understand the communication breakdown that occurs in the brain during unconsciousness so we can precisely target or monitor these circuits to achieve safer anesthesia and restore these circuits to improve outcomes of coma,” Mashour says.

Hepatitis B in a Laboratory!! #serology #infection #liver #hepatitis #medicine #medstudent #medstudynotes #virus #medschool #microbiology #pathology https://www.instagram.com/p/BrIYa-LheyH/?utm_source=ig_tumblr_share&igshid=lqm0j92yobw0

Today is World Anaesthesia Day! Here’s a look at the chemistry behind a range of anaesthetics. More info here and here.

It’s nearly the season of the witch: time for some cauldron chemistry

Midwives and nurses sometimes came under suspicion because of their specialised knowledge and success - or failure - in treating those who were sick. These healing roles were traditionally taken on by women who, until around the turn of the nineteenth century, were excluded from formal medical training. However, many still practiced medicine in their homes and villages, and what they had learned came from shared knowledge and trial and error, rather than accepted official sources. A medical education might not have been a great help in any case. In the days before germ theory the causes of sickness and the reasons for recovery were not obvious. Any recoveries could be seen as miraculous … or the result of witchcraft.

Treating sickness and disease pre-germ theory was largely guesswork. All sorts of noxious compounds were administered to ailing individuals, and if they produced any effect on the body, be it vomiting, diarrhoea or sweating, it was seen as a good thing – and that was the practice of the so-called professionals. It is not hard to see how images of unofficial healers and herbalists (both men and women) stooping over boiling pots of herbs, roots and who-knows-what, could become a template for the image of a witch, especially when many of the concoctions they produced had such unpleasant effects on their patients.

Having said that, herbalists and traditional healers should not be dismissed as completely ignorant of the medical benefits of some of the plants and poultices they used. Some of the ingredients associated with traditional healing and witches’ potions have been found to be hugely beneficial to medicine once they have been isolated, tested and modified. Science has enabled us to identify the key components of some plants and test them to determine how and when they should be administered safely and effectively. Chemists have modified the structures of some of the compounds to reduce side-effects, make drugs more potent or lower their toxicity.

This year’s Halloween special wraps up the chemistry behind making a mummy: http://wp.me/p4aPLT-26m

NASA Just Found A Solar System With 7 Earth-Like Planets

Astronomers just announced a breaking discovery that has a monumental impact on life beyond Earth: A planetary system with a number of Earth-sized planets that could host liquid water and, thus, life.

Today, scientists working with telescopes at the European Southern Observatory and NASA announced a remarkable new discovery: An entire system of Earth-sized planets. If that’s not enough, the team asserts that the density measurements of the planets indicates that the six innermost are Earth-like rocky worlds.

And that’s just the beginning.

Three of the planets lie in the star’s habitable zone. If you aren’t familiar with the term, the habitable zone (also known as the “goldilocks zone”) is the region surrounding a star in which liquid water could theoretically exist. This means that all three of these alien worlds may have entire oceans of water, dramatically increasing the possibility of life. The other planets are less likely to host oceans of water, but the team states that liquid water is still a possibility on each of these worlds.

Summing the work, lead author Michaël Gillon notes that this solar system has the largest number of Earth-sized planets yet found and the largest number of worlds that could support liquid water: “This is an amazing planetary system — not only because we have found so many planets, but because they are all surprisingly similar in size to the Earth!”

Co-author Amaury Triaud notes that the star in this system is an “ultracool dwarf,” and he clarifies what this means in relation to the planets: “The energy output from dwarf stars like TRAPPIST-1 is much weaker than that of our Sun. Planets would need to be in far closer orbits than we see in the Solar System if there is to be surface water. Fortunately, it seems that this kind of compact configuration is just what we see around TRAPPIST-1.”

Continue Reading.