madame scientist's not-so-mad musings

Art or Science?

Are these pastel fractals the creation of an avant garde artist from some postmodern cubism movement?  You may be surprised to learn that these are high resolution images of bacterial populations growing on a petri dish!

◈ Bacterial Art: First, the familiar E. coli bacteria were genetically marked with differently colored fluorescent proteins before mixing together on an agar plate. Each rod-shaped bacterium grows by division to give a single file of cells that is sensitive to small mechanical forces from neighboring cells pushing and jostling against each other. The line of cells buckles in a way that is predicted by fractal mathematics.  As the bacteria grow to form a confluent film, jagged boundaries emerge between differently colored clonal lines. Zooming in, the patterns are self-similar, repeating at scales from millimeters to micrometers! Mutant bacteria that form spherical cells don’t produce these fractal patterns. 

◈ Form and Function: What do these beautiful images teach us? They help us understand how patterning happens on a nanoscale. In synthetic biology the goal is to engineer populations of cells to produce spatial patterns, synchronized signals and predictable behavior that can be simulated using simple, mathematically coded rules.  

◈ Life Imitates Art? Oscar Wilde reversed the conventional when he claimed that life imitates art far more than art imitates life. What do you think he meant by this? It seems to me that this bacterial fractal “art” perfectly illustrates John Berger’s definition of Cubism: “The metaphorical model of Cubism is the diagram: The diagram being a visible symbolic representation of invisible processes, forces, structures.”

Reference (and more beautiful images): http://data.plantsci.cam.ac.uk/Haseloff/resources/LabPapers/Rudge2013.pdf

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Fixing a Hole: Better (Spider) Web Design

⎈ From tiny webs like the one “repairing” a hole in a leaf seen in the image, to giant orbs spanning 25 meters across rivers and lakes, the architecture of spider webs can teach us a thing or two about engineering. After all, spiders have been spinning silk for 400 milion years and now number at least 41,000 species spread out over every continent, including Antarctica. Each spider produces many different types of silk covering a range of mechanical properties: from the steely dragline silk in the radial strands to sticky capture silk that forms concentric circles in the web. Yet, only few spider silks have been studied, mostly at random, sometimes simply from the researcher’s own backyard! 

⎈ Bioprospecting: By combining fields as diverse as natural history, ecology, taxonomy, behavior and biomaterial science, researchers found that the Darwin’s Bark Spider (Caerostris darwini), a giant Malagasy riverine orb-weaving spider, produces the toughest silk discovered to date. Outperforming steel and Kevlar, the radial web threads of this spider have unusual elasticity, absorbing more kinetic energy upon prey impact so that they stretch, instead of fracturing. This allows the spiders to occupy a new ecological niche- the flyways above rivers where they can catch unsuspecting insects and even small birds and bats. Don’t you agree that scientists should get out of their labs and explore new habitats as well?!

⎈ Biomimicry: In nature, tiny amounts of metals penetrate protein structures to change their properties. These “impurities” are found in jaws, claws and cuticles where they impart additional toughness to biological material. Inspired by nature, scientists purposefully introduced zinc, titanium or aluminum into spider dragline silks by using a multiple pulsed vapor-phase infiltration method. The resulting material was tougher and more stable to environmental damage. Now this is the stuff of Spider Man!    

Free Reads: New Opportunities for an Ancient Material (2010) Ometto and Kaplan. Science. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3136811/

Bioprospecting Finds the Toughest Biological Material: Extraordinary Silk from a Giant Riverine Orb Spider (2010). Agnarsson et al. PLOS ONE http://goo.gl/CcSMTd

The Beatles-Fixing a Hole: https://www.youtube.com/watch?v=j0I2ZrBuFdQ

Photo Credit: Bertrand Kulik 

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How to Boil Water

❉ In breaking news, scientists have figured out how to boil water – at least 3 times more efficiently and producing twice as much steam. Before you shake your fist at “wasteful research spending”, this isn’t really about your whistling tea kettle! 

❉ Phase change heat transfer processes (boiling, condensation) are a big part of everyday technology from water purification and HVAC units, power plants and cooling electronics.   When water boils, a thin layer of steam can coat the heated surface, insulating it and drastically cutting down on the efficient transfer of heat to liquid. This can lead to surface burnout and a destructive condition known as critical heat flux. What is needed is a surface that discourages the vapor from sticking and wicks in water to quickly re-wet the heated surface. To create a superhydrophilic wicking surface, Drexel University scientist Matthew McCarthy turned to biotemplating with….viruses! 

❉ The tobacco mosaic virus causes mottling of tobacco leaves, as its name implies, but is harmless to humans. It was the first virus ever to be discovered (in the late 1880’s) and is constructed simply of repeating units of a coat protein, wrapped around a single, helical strand of genetic material (RNA). A few tobacco plants can produce billions of virus particles, so it’s cheap to make. Dr. McCarthy tweaked the coat protein so it sticks to any engineered surface- from silicon to steel. After dunking the surface in a viral broth, nickel and palladium are added to grow a metallic grass. 

❉ The viral tendrils work like a wicking surface, drawing down water to replace what’s boiled away.  It’s the same idea behind thermal fabrics designed for athletes which draws moisture away from the body. They say a watched pot never boils. I’d volunteer to test a virally coated tea kettle, how about you? 

Waterproofin’ with Hydrophobin: This old post shows how a fungal spore protein can do the opposite, creating a superhydrophobic surface that repels water but allows gases to exchange. 

https://plus.google.com/u/0/+RajiniRao/posts/bf9gVFkaTxQ

News Story and Short Video: http://drexel.edu/now/archive/2015/March/TMV-heat-transfer/

Ref: M.M. Rahman, E. Ölçeroğlu, and M. McCarthy, “The Role of Wickability on the Critical Heat Flux of Structured Superhydrophilic Surfaces”, Langmuir 2014, 30 (37), pp 11225–11234.

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What Autism can Teach us about Brain Cancer

Glioblastoma multiforme, or GBM, is a deadly cancer with median survival of only 12-15 months. Recently, we found a gene that had been previously implicated in autism to also contribute to GBM. The gene NHE9 makes a protein that exchanges sodium ions for hydrogen ions (also called protons) across the boundaries of endosomes, hence it’s moniker “sodium-hydrogen exchanger”. But what are endosomes and why is the function of NHE9 important?

Highway Traffic: All cells contain many “cargo packages” surrounded by membranes, depicted in the expanded view as a blue compartment in the figure below. These so-called endosomes carry newly minted proteins to specific destinations throughout the cell and haul away old proteins for destruction. Key to their “shipping speed” is the level of acidity inside the endosomes. Acidity relates to the number of protons, which are controlled by balancing the activity of “pumps” that push protons into endosomes to increase their acidity with that of “leaks,” like the protein NHE9, that remove protons. 

There’s a Hole in the Bucket: You can think of endosomes as leaky buckets of water. Altering either the faucet or the leak rate can dramatically change the water level in the bucket. In autism, NHE9 is mutated and non-functional. In the absence of proton leak, the endosomes become too acidic and prematurely clear away important proteins on nerve ends, leading to neurological dysfunction. Helper cells called astrocytes cannot clear away neurotransmitter signals fast enough, and this leads to hyperexcitability or seizures associated with autism.

Too Much of a Good Thing: in contrast to autism, NHE9 is overactive in brain cancer, causing endosomes to leak too many protons and become too alkaline. This slows down the “shipping rate” of cancer-promoting cargo and leaves them on the cell surface for too long where they inappropriately prolong signals of growth and migration, the two main characteristics of invasive cancer cells. Fortunately, when the leak is plugged by inhibiting NHE9 with drugs, tumor growth is blocked. Currently, the drugs are not good enough to use on patients, so an important step going forward will be to discover better drugs that target NHE9. These could be used in combination with other drugs for treatment of this deadly disease. 

Paper: A leak pathway for luminal protons in endosomes drives oncogenic signalling in glioblastoma. Kondapalli et al. (2015) Nature Communications http://goo.gl/dAa5NG

Johns Hopkins News Story: http://goo.gl/XAsGDb

A Part of the Puzzle: NHE9 and Autism https://plus.google.com/u/0/+RajiniRao/posts/fsNzo1yKsQG

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Souring on Sweeteners: Why Diet Sugars Don’t Work

Sweet Serendipity: It was 1878, when a beaker of coal tar compounds boiled over in the chemistry laboratory of Ira Remsen at the newly founded Johns Hopkins University. Researcher Constantine Fahlberg cleaned up the mess, but later at dinner, his hands tasted surprisingly sweet as he put a piece of bread in his mouth. And this is how the first artificial sweetener was discovered! Named saccharin, it was 300 times sweeter than sugar. Soon, it was being prescribed to President Theodore Roosevelt, to counter his corpulence. More low-calorie sweeteners followed: sucralose, stevia and neotame, the last one being 10,000 times sweeter than table sugar. Today, 30% of adults and 15% of children in the U.S. consume low calorie sweeteners. A sweet deal, right?

Caloric Contradictions: Unfortunately, counterintuitive to expectations, studies show that people who consume large amounts of artificially sweetened drinks gain more weight and body fat compared to those who don’t. Could this be a case of reverse causation? Perhaps, increased body weight encourages people to turn to non-caloric sweeteners. However, this has been ruled out by (i) controlling for baseline body weight at the start of the study and by (ii) looking at weight changes in people who are not overweight to begin with. Another possibility is cognitive distortion: because non-caloric sweeteners are perceived to be healthy, we take that as permission to consume more high-calorie foods. Imaging studies of the human brain reveal a metabolic cause: unlike ordinary sugar, non-caloric sweeteners do not trigger the reward circuits that initiate satiety and fail to activate normal pathways of insulin release needed to deal with caloric loads. 

Diet to Diabetes: New research in both mice and humans showed that artificial sweeteners also change our gut microbiome, leading to glucose intolerance, the first step to diabetes. Surprisingly, if the feces from saccharin-fed mice was transplanted into mice whose guts were first cleared of bacteria by antibiotics, the sugar handling defect could be induced in the healthy mice. Oh, expletive!

The Archies sang, ♫ Oh honey, sugar, sugar..you are my candy girl and you’ve got me wanting you ♫

https://www.youtube.com/watch?v=0MiQzAo6Cp8

REF: Artificial sweeteners produce the counterintuitive effect of inducing metabolic derangements. Susanne Swithers (2013) http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3772345/

News Story & Link to Nature paper: http://www.nature.com/news/sugar-substitutes-linked-to-obesity-1.15938

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