30 April 2013 Click Here for Video Clearing Your Mind Understanding how the brain works to produce behaviour is one of biology’s greatest challenges, and the sheer complexity and number of cells in vertebrate brains makes it difficult to get a close look. While most studies rely on painstakingly reconstructing 3D images from thin sections, a new technique allowing much thicker samples, even whole brains, to be observed in detail has recently been developed. Named CLARITY, the method uses a detergent to dissolve the cells’ fatty membranes, effectively making brain tissue transparent under the microscope. Researchers can then see deep inside the brain, identify particular cell types and track their connections. In the video, CLARITY has been used to image a mouse hippocampus, and different cell types have been labelled with fluorescent proteins. The technique has also been applied to human samples, opening up new possibilities for exploring both neural networks in healthy brains and the causes of neuronal diseases. Written by Emmanuelle Briolat — Karl Deisseroth Stanford University, USA Reprinted by permission from Macmillan Publishers Ltd: Nature Copyright 2013 Published in Nature
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30 April 2013 Click Here for Video

Clearing Your Mind

Understanding how the brain works to produce behaviour is one of biology’s greatest challenges, and the sheer complexity and number of cells in vertebrate brains makes it difficult to get a close look. While most studies rely on painstakingly reconstructing 3D images from thin sections, a new technique allowing much thicker samples, even whole brains, to be observed in detail has recently been developed. Named CLARITY, the method uses a detergent to dissolve the cells’ fatty membranes, effectively making brain tissue transparent under the microscope. Researchers can then see deep inside the brain, identify particular cell types and track their connections. In the video, CLARITY has been used to image a mouse hippocampus, and different cell types have been labelled with fluorescent proteins. The technique has also been applied to human samples, opening up new possibilities for exploring both neural networks in healthy brains and the causes of neuronal diseases.

Written by Emmanuelle Briolat

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Food for Thought Brains burn more energy than any other organ to produce and drive electrical signals along the filament-like brain cells that control everything from our breathing to our thoughts. In fact, neuroscientists estimate that 20% of our total energy budget is used just to keep our brains firing. And burning all that energy means brain cells need oxygen, and lots of it. A vast network of blood vessels (around 100,000 miles long) irrigates every nook of our brain ensuring it’s never starved of oxygen or nutrients. But there is still much to be learned about how vessels grow and form networks – a process called angiogenesis. Studying mouse brain (pictured), researchers have identified over 60 genes that could act as switches controlling the growth of vessels. In future, this could help stroke patients heal, or reversely, could be used to kill off brain tumours by stemming their blood supply. Written by Tristan Farrow — Ayşe N Başak, Boğaziçi University, Turkey Türker Kılıç, Marmara University, Turkey Originally published under Creative Commons Attribution License (CC-BY 2.0) Published in Vascular Cell 4:16
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Food for Thought

Brains burn more energy than any other organ to produce and drive electrical signals along the filament-like brain cells that control everything from our breathing to our thoughts. In fact, neuroscientists estimate that 20% of our total energy budget is used just to keep our brains firing. And burning all that energy means brain cells need oxygen, and lots of it. A vast network of blood vessels (around 100,000 miles long) irrigates every nook of our brain ensuring it’s never starved of oxygen or nutrients. But there is still much to be learned about how vessels grow and form networks – a process called angiogenesis. Studying mouse brain (pictured), researchers have identified over 60 genes that could act as switches controlling the growth of vessels. In future, this could help stroke patients heal, or reversely, could be used to kill off brain tumours by stemming their blood supply.

Written by Tristan Farrow

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Source: bpod.mrc.ac.uk

Uro Septic Cystitis is a cruel affliction. It has you crossing your legs desperate for a pee; and then when you go, it hurts like chilli in a wound. It’s an infection of the bladder – where urine is stored, until you’re prepared to release it – and is commonly caused by bacteria. Here E.coli bacteria (shown in yellow) are seen on a landscape of cells lining the bladder (shown in blue) where they are wreaking havoc. They are causing painful swelling and mucus secretion (strands shown in orange). Sometimes they irritate the bladder so much it bleeds and urine is coloured by red blood cells (disc-shapes seen on the left). Because they have a shorter and more easily infected urethra – the pipe leading from the bladder to the outside – women are more at risk. Drinking plenty of water can sometimes be enough to flush out a bladder infection, putting you back in control. Written by Lindsey Goff — Image provided courtesy of Science Photo Library Copyright Science Photo Library Any re-use of this image must be authorised by Science Photo Library
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Uro Septic

Cystitis is a cruel affliction. It has you crossing your legs desperate for a pee; and then when you go, it hurts like chilli in a wound. It’s an infection of the bladder – where urine is stored, until you’re prepared to release it – and is commonly caused by bacteria. Here E.coli bacteria (shown in yellow) are seen on a landscape of cells lining the bladder (shown in blue) where they are wreaking havoc. They are causing painful swelling and mucus secretion (strands shown in orange). Sometimes they irritate the bladder so much it bleeds and urine is coloured by red blood cells (disc-shapes seen on the left). Because they have a shorter and more easily infected urethra – the pipe leading from the bladder to the outside – women are more at risk. Drinking plenty of water can sometimes be enough to flush out a bladder infection, putting you back in control.

Written by Lindsey Goff

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Source: bpod.mrc.ac.uk

Bendy Bones We might think of cells as shapeless blobs, but just like us they have an internal skeleton that gives them structure and allows movement. Unlike our bones, however, which are rigid and immovable, the cell skeleton is a network of flexible cylinders calledmicrotubules. They can grow or shorten rapidly, bend and change position to sculpt the shape of the cell. In this human epithelial cell, the microtubule skeleton has been fluorescently labelled (the outline of the cell membrane can’t be seen). Using a new technique called scanning angle interference imaging scientists are now able to produce a reconstruction of the cell skeleton’s position in 3D space – the pattern of colours on the right indicates that the microtubules are curving away from us (close ones are falsely coloured green while those further away have been coloured red). Techniques like this allow tiny cell structures to be more accurately visualised. Written by Emma Stoye — Valerie Weaver Division of General Surgery, University of California, San Francisco, USA Reprinted by permission from Macmillan Publishers Ltd: Nature Methods Copyright 2012 Published in Nature Methods 9:825-827
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Bendy Bones

We might think of cells as shapeless blobs, but just like us they have an internal skeleton that gives them structure and allows movement. Unlike our bones, however, which are rigid and immovable, the cell skeleton is a network of flexible cylinders calledmicrotubules. They can grow or shorten rapidly, bend and change position to sculpt the shape of the cell. In this human epithelial cell, the microtubule skeleton has been fluorescently labelled (the outline of the cell membrane can’t be seen). Using a new technique called scanning angle interference imaging scientists are now able to produce a reconstruction of the cell skeleton’s position in 3D space – the pattern of colours on the right indicates that the microtubules are curving away from us (close ones are falsely coloured green while those further away have been coloured red). Techniques like this allow tiny cell structures to be more accurately visualised.

Written by Emma Stoye

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Source: bpod.mrc.ac.uk

Unravelling the Plumbing Most of us are familiar with the circulatory system, the internal ‘plumbing’ that directs blood around the body. But there’s another set of ‘pipes’ that shift fluid around inside us, called the lymphatic system. This network of vessels takes excess fluid away from our tissues and plays a vital role in shuttling immune cells around. This confocal microscope image shows a tightly intertwined network of developing lymphatic vessels (stained pink) against a backdrop of blood vessels (stained blue). The green patches among the lymphatic vessels highlight a protein called reelin, which first came to light in brain development research. Scientists have discovered that reelin also plays an important role in lymphatic vessel growth, helping the muscle and lining cells communicate with each other to create correctly-shaped vessels. Written by Kat Arney — Taija Makinen Cancer Research UK London Research Institute, UK Originally published under Creative Commons Attribution License (CC-BY-NC-SA 3.0) Published in Journal of Cell Biology 197(6): 837 
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Unravelling the Plumbing

Most of us are familiar with the circulatory system, the internal ‘plumbing’ that directs blood around the body. But there’s another set of ‘pipes’ that shift fluid around inside us, called the lymphatic system. This network of vessels takes excess fluid away from our tissues and plays a vital role in shuttling immune cells around. This confocal microscope image shows a tightly intertwined network of developing lymphatic vessels (stained pink) against a backdrop of blood vessels (stained blue). The green patches among the lymphatic vessels highlight a protein called reelin, which first came to light in brain development research. Scientists have discovered that reelin also plays an important role in lymphatic vessel growth, helping the muscle and lining cells communicate with each other to create correctly-shaped vessels.

Written by Kat Arney

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Source: bpod.mrc.ac.uk

Familiar Fungus The fungus pictured will be familiar to most women, if not by its scientific name, Candida albicans, then by its more common moniker, thrush. This little organism commonly causes vaginal infections. But it can also affect the mouth, especially in babies, elderly folk and the immunologically compromised such as people with HIV. Scientists have recently identified a crucial protein in the fungus that serves two opposing functions in such oral infections. It enables Candida to control the acidity of its environment, allowing fungal colonies to form the halo of hyphae (shown in white) necessary for penetrating the lining of the mouth. However, the protein also makes the fungus more susceptible to a natural salivary antiseptic, which in healthy people helps prevent infections from occurring in the first place. Written by Ruth Williams — François Mayer, Bernhard Hube, and Duncan Wilson Department of Microbial Pathogenicity Mechanisms, Hans-Knoell-Institute Originally published under Creative Commons (CC-BY 2.0) Published in PLoS Pathogens
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Familiar Fungus

The fungus pictured will be familiar to most women, if not by its scientific name, Candida albicans, then by its more common moniker, thrush. This little organism commonly causes vaginal infections. But it can also affect the mouth, especially in babies, elderly folk and the immunologically compromised such as people with HIV. Scientists have recently identified a crucial protein in the fungus that serves two opposing functions in such oral infections. It enables Candida to control the acidity of its environment, allowing fungal colonies to form the halo of hyphae (shown in white) necessary for penetrating the lining of the mouth. However, the protein also makes the fungus more susceptible to a natural salivary antiseptic, which in healthy people helps prevent infections from occurring in the first place.

Written by Ruth Williams

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Source: bpod.mrc.ac.uk

Know Your Enemy B cells are the weapons factories for our immune system. They produce antibodies, which lock on to a virus’s specific fingerprint, its antigen, marking it out for neutralisation by other immune cells. Here we see spleens from two different mice, where B cells are being ‘briefed’ on what their viral enemy looks like. The B cells (stained red) measure 1/2000 of a centimetre across and gather at hubs in the spleen. Here they are shown the virus’s antigen by specialised cells (stained blue). Only those B cells producing the most accurate antibodies survive this training and reproduce in large numbers (stained green). On the right we see the spleen of a mouse lacking a protein called Dicer, without which the B cells are unable to multiply. Written by John Ankers — Shengli Xu Bioprocessing Technology Institute, Singapore Courtesy American Society of Hematology Published in Blood 119(3) 767-776
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Know Your Enemy

B cells are the weapons factories for our immune system. They produce antibodies, which lock on to a virus’s specific fingerprint, its antigen, marking it out for neutralisation by other immune cells. Here we see spleens from two different mice, where B cells are being ‘briefed’ on what their viral enemy looks like. The B cells (stained red) measure 1/2000 of a centimetre across and gather at hubs in the spleen. Here they are shown the virus’s antigen by specialised cells (stained blue). Only those B cells producing the most accurate antibodies survive this training and reproduce in large numbers (stained green). On the right we see the spleen of a mouse lacking a protein called Dicer, without which the B cells are unable to multiply.

Written by John Ankers

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Source: bpod.mrc.ac.uk

Ageing Flies Flies, like humans, can show signs of brain degeneration as they reach old age. Affected insects possess gene mutations, which lead to shaking and difficulty walking as brain function is lost. By looking for early warning signs in the brains of these insects, scientists hope to improve early detection of human neurodegenerative diseases, such as Huntington’s and Parkinson’s. However, flies’ brains are delicate, and the traditional way of imaging them - preparing thin slices of the organ to view under a microscope – is laborious and requires great precision. Scientists have found a neat way to overcome this. By simply bleaching the fly’s dark pigmentation they can take images through the intact head (shown above) to the brain underneath. Written by Manisha Lalloo — Mary O’Connell Medical Research Council Human Genetics Unit, UK Originally published under Creative Commons (CC-BY 2.0) Published in PLoS One
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Ageing Flies

Flies, like humans, can show signs of brain degeneration as they reach old age. Affected insects possess gene mutations, which lead to shaking and difficulty walking as brain function is lost. By looking for early warning signs in the brains of these insects, scientists hope to improve early detection of human neurodegenerative diseases, such as Huntington’s and Parkinson’s. However, flies’ brains are delicate, and the traditional way of imaging them - preparing thin slices of the organ to view under a microscope – is laborious and requires great precision. Scientists have found a neat way to overcome this. By simply bleaching the fly’s dark pigmentation they can take images through the intact head (shown above) to the brain underneath.

Written by Manisha Lalloo

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Source: bpod.mrc.ac.uk

Brain Recipe Our brains contain billions of neurons – highly specialised, communicative cells – that are formed throughout life from less specialised precursors. A complex cocktail of signals drives this transition, and deciphering the recipe is no mean feat. Now researchers have identified one ingredient, a protein called activin, that appears key. In the lab, this dishful of precursor cells (stained red with blue nuclei) has been treated with activin, and after several days most have turned into mature neurons (stained green with blue nuclei). Modelling the developing brain in a dish highlights how different ‘ingredients’ can coax precursors to become different cell types. This will help scientists select the most suitable precursor cells for use in the regenerative medicine of the future – where cells grafted into a damaged brain could help repair or replace failing neurons. Written by Helen Pilcher — Charles Arber MRC Clinical Sciences Centre
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Brain Recipe

Our brains contain billions of neurons – highly specialised, communicative cells – that are formed throughout life from less specialised precursors. A complex cocktail of signals drives this transition, and deciphering the recipe is no mean feat. Now researchers have identified one ingredient, a protein called activin, that appears key. In the lab, this dishful of precursor cells (stained red with blue nuclei) has been treated with activin, and after several days most have turned into mature neurons (stained green with blue nuclei). Modelling the developing brain in a dish highlights how different ‘ingredients’ can coax precursors to become different cell types. This will help scientists select the most suitable precursor cells for use in the regenerative medicine of the future – where cells grafted into a damaged brain could help repair or replace failing neurons.

Written by Helen Pilcher

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Source: bpod.mrc.ac.uk

New Beats Skin and bones can heal themselves, but broken hearts are not so easily mended. Our heart is made up of two types of cells, fibroblasts for structure and muscle cells that do the beating. After a heart attack, muscle cells die and, in a struggle to repair the damage, fibroblasts multiply. But they make the heart tissue thicker and less flexible, imperilling the vital pump even further. Now, researchers studying mouse heart cells (pictured), have found that adding proteins which activate certain genes can turn fibroblasts into beating muscle cells (dyed red). What’s more, these converted cells integrate into existing heart muscle. And they form new junctions with existing cells (green bands), which means they can all beat in unison. This discovery brings hope for new ways to treat damaged hearts. Written by Sarah McLusky — Jose Cabrera Eric N. Olson, University of Texas Southwestern Medical Center Reprinted by permission from Macmillan Publishers Ltd: Nature, Copyright 2012 Published in Nature
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New Beats

Skin and bones can heal themselves, but broken hearts are not so easily mended. Our heart is made up of two types of cells, fibroblasts for structure and muscle cells that do the beating. After a heart attack, muscle cells die and, in a struggle to repair the damage, fibroblasts multiply. But they make the heart tissue thicker and less flexible, imperilling the vital pump even further. Now, researchers studying mouse heart cells (pictured), have found that adding proteins which activate certain genes can turn fibroblasts into beating muscle cells (dyed red). What’s more, these converted cells integrate into existing heart muscle. And they form new junctions with existing cells (green bands), which means they can all beat in unison. This discovery brings hope for new ways to treat damaged hearts.

Written by Sarah McLusky

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Source: bpod.mrc.ac.uk