Junction Box Millions of times a day we turn our thoughts into…

Junction Box

Millions of times a day we turn our thoughts into actions – at neuromuscular junctions where electrical signals from motor neurons feed into our muscles. Amyotrophic lateral sclerosis (ALS) gradually weakens these connections for thousands of people around the world – but here’s a vital step towards new treatments. Inside a sort of lab-in-a-box called a microfluidic device, a bundle of nerve cells (artificially-coloured green with nuclei in blue) is reaching out tiny finger-like neurites towards muscle cells (purple) – creating a living 3D model of a neuromuscular junction. The neurons are modified to be optogenetic – they respond to pulses of laser light by pulling at the muscle cells, revealing weaker forces in cells grown from ALS sufferers. The next job is to bathe the diseased cells in different combinations of drugs, looking for clues to restoring neuromuscular junctions to full strength, in the hope of treating ALS as well as other conditions affecting the nervous system.

Written by John Ankers

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Losing Contacts Like detectives piecing together the moments…

Losing Contacts

Like detectives piecing together the moments leading up to a crime, researchers have unpicked the events that result in the destruction of nerves in the muscle wasting disease amyotrophic lateral sclerosis (ALS). Connections between muscles and the nerves that stimulate them called neuromuscular junctions (NMJs) are lost early on in ALS. And in this study the team probed whether this is down to entire nerves suddenly dying or the dismantling of nerve branches along which the NMJs reside. They used fluorescent microscopy to repeatedly image the nerves, muscle fibres (pictured in red and green) and NMJs of normal (left) and ALS mice (right) revealing that NMJ loss was due to individual branches disassembling before total nerve degeneration. This presents a window of time, between the first signs of disease with NMJ loss and eventual nerve death, for targeting efforts to treat ALS.

Written by Lux Fatimathas

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Delivering Resistance Defeating infection can be tricky,…

Delivering Resistance

Defeating infection can be tricky, especially when the offending microorganisms band together to form a seemingly impenetrable biofilm. This is what the fungus Candida albicans does in humans, making treatment challenging. Researchers try to find a chink in their armour by imaging C. albicans biofilms using scanning electron microscopy. They noticed small spheres on the surface of C. albicans (cylindrical structure, pictured) and within the proteinaceous extracellular matrix (ECM) secreted by the fungus (mesh-like structure, pictured). The spheres resemble extracellular vesicles – sacs of cell contents important for inter-cell communication – and the matrix is thought to be what makes biofilms intractable. By creating C. albicans mutants that couldn’t produce extracellular vesicles the team found that the fungi still formed biofilms but lacked ECM and were now vulnerable to anti-fungal drugs. Extracellular vesicles therefore appear to be essential for delivering materials that comprise the ECM, making them ideal targets for new treatments.

Written by Lux Fatimathas

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