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Rajini Rao

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Olympic Gold..or....Green?

♒ We know that green is Brazil's favorite color, and the Olympics are trying to Go Green for the environment, but even so, the overnight change in color of the Olympic swimming pool from an azure blue to murky green took scientists and sportsmen by surprise. While officials hastened to assure athletes that the green waters posed no health threat, the mystery caused much speculation. Caipirinha-flavored Soylent? Stiffed by Trump’s pool cleaning service? Who peed in the water?

♒ “Midafternoon, there was a sudden decrease in the alkalinity in the diving pool, and that’s the main reason the color changed,” said Mario Andrada, a Rio 2016 spokesman. So, the pool became more acidic. But acidic water is not green. There are two likely explanations: first, excess copper in the water can turn it green, but not murky. The latter is caused by a sudden and rapid growth of algae, triggered by the warm weather, lack of wind, insufficient chlorine and ineffective filters.

♒ Algal spores can enter the water inadvertently, carried by wind, rain and contaminated swimsuits. When the conditions are right, they can "bloom" overnight. Because these algae are visible only under the microscope, there must be millions of them in the water to change the pool color from blue to green. One way to deal with them, after normalizing the pH, is *superchlorination*—aka shocking them with high levels of chlorine. Not all the Olympians are complaining: Canadian divers said that the contrast with the sky helped them win the bronze.

♒ Pix: The Olympic diving pool on August 8 (left) and the Olympic diving pool on August 9 (right) Image: AP

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Project 523: From Chinese Secrets to Nobel Gold 

☯ On May 23, 1967 a secret military project was launched by the Chinese government. It was the height of the Vietnam war, and the communist north was losing more soldiers to the scourge of malaria than to the battlefield. An emergency plea was made to a powerful sympathizer, Chairman Mao Zedong, to find a cure. Code named Project 523 (after the date), more than 500 scientists were recruited from 60 military and civilian organizations, remarkably at the height of China's Cultural Revolution which closed universities and banished scientists and intellectuals. One group of scientists was tasked with searching through ancient Chinese records of herbal remedies.

☯ 39 year old phytochemist, Youyou Tu, was sent to the sweltering rain forests of Hainan, an island in southern China, where she witnessed the devastation of malaria first hand. By then, many ancient herbal compounds had been tested. The extract of quinghao (green-blue wormwood) appeared to be effective, but success was sporadic. Tu carefully read the recipe of 4th century writing of Ge Hong: qinghao, one bunch, take two sheng [2 × 0.2 l] of water for soaking it, wring it out, take the juice, ingest it in its entirety. Tu reasoned that extraction by boiling might destroy the active ingredient. So she tested a cold ether extract of the plant and it worked. She even voluntarily consumed the extract to make sure it was safe, then tested it on human patients. Her results were published anonymously in 1977. Today, 84 year old Youyou Tu received the Nobel Prize for Medicine, which she shared with two other scientists, an Irishman and Japanese, who worked on treatment of other parasitic diseases. 

☯ The success of artemisinin as a modern day miracle cure for Plasmodium falciparum malaria (spread by mosquitoes, and blamed annually for 1 million deaths world wide), rests on the breakthroughs of hundreds of scientists. Those who discovered a richer source of the drug in Artemisia annua grown in Sichuan province, those who purified the drug away from toxic contaminants, who solved the new and unusual chemical structure, synthesized better and safer derivatives for the treatment of malaria. While celebrating her success as the first Chinese woman to receive a Nobel in Medicine, let us not forget that Youyou Tu's Nobel represents an entire field of research. Tu herself is a modest individual who has drifted into obscurity despite receiving a Lasker Award, the so-called American Nobel, in 2011. At the time, she said, "I think the honor not only belongs to me but also to all Chinese scientists."

Project 523:
Nobel Press Release:
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The Greening of Greenhouse Gas

It's a Gas: Driving through the Western Ghat mountains along the continental edge of the Deccan Plateau, I was charmed by this vista of sculpted terraces with verdant blades of rice emerging from submerged paddy fields. Little did I know then that paddy fields generate 50-100 million tonnes of methane each year, a potent greenhouse gas with 25 times the heat trapping potential of carbon dioxide. Although the flooded fields keep weeds at bay, microbes harbored under the warm, waterlogged soil feed on organic matter exuded by roots, releasing methane and accounting for about 20% of human-related production. In China, farmers have begun draining fields mid-season to interrupt methanogenic bacteria. But India is still responsible for nearly a third of the methane emissions. 

It's Barley There: Now, thanks to genetic engineering, a new strain of rice yields more grain and produces less methane. Researchers spliced a gene from barley, encoding a master regulator (transcription factor) into rice. The gene, dubbed SUSIBA2 (acronym for "sugar signaling in barley 2") increases the output of sugar and starch in the seeds, leaves and shoots of the rice plant, leaving less biomass in the root. This strongly decreased the methanogenic bacteria in the rhizosphere, or region around the root. In a 3-year field trial, methane emissions fell by 90%.

Rice, Rice, Baby: The making of starch is under the direction of a set of genes which carry in front of them stretches of DNA sequences (promoters) known as sugar responsive elements or SURE. Aren't you loving the acronyms? When a little bit of sugar is made, SUSIBA2 is activated and it turns on genes that make even more sugar, to create a snowballing effect. The sugar is converted to starch, diverting carbon to the grains and away from the root, starving the methane producing bacteria of food. Now that's a sweet way to cool down our planet!

This work was a collaboration between scientists at Universities and non-profit research Institutes in Sweden, China and the US. The authors have no competing financial interests. 

Paper (paywalled): 


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Screws with a Twist

Secrets of the Silkworm: Did you know that the silkworm was domesticated in China over 5,000 years ago? Legend has it that the Empress Lei Zhu was drinking tea under a tree when a cocoon fell into the hot beverage, unraveling silken threads to reveal the Bombyx caterpillar within. Silk making was a deeply guarded secret until 550 AD, until Christian monks successfully smuggled silkworms out of China in a hollow stick and introduced them to the rest of the world. Today, there are thousands of genetically inbred and engineered strains, all completely dependent on humans for survival! 

From Steel to Silk: Fractured bones are often held in place by metal screws and plates until they heal. Removing the metal carries unnecessary risks, which can be averted using biocompatible materials that are naturally absorbed into the body over time. Silk is strong, stable to high heat of sterilization and can be fashioned into “self-tapping” surgical screws that have been successfully tested in rats. The silk screws are "radiolucent” or invisible to x-rays, allowing the fracture to be monitored post-operation, without the impedance of metal. Best of all, silk protein is digested by natural enzymes and resorbed into the body within 4-8 weeks. Researchers hope to use silk screws in facial fractures, which number in several hundred thousand each year. 

Bench to Body: (1) Fill test tube with silk solution then freeze dry. (2) Use scissors or a blender to cut into small pieces. (3) Dissolve pieces in 1,1,1,3,3,3 hexafluoro-2-propanol (HFIP) in a syringe. (4) Inject dissolved silk into bone plate or screw blank moulds. (5) Place molds in methanol for 3–4 days (to convert silk protein into β-sheets). (6) Remove and allow to dry (fume hood for 1 week then 60 °C oven for 5 days), then autoclave for stability. (8) Machine using a mill, lathe or die to obtain desired geometry. Almost DIY, right? :)

REF: Perrone et al., 2014 Nature Communications

+Gary Ray R describes a different kind of biodegradable screw made of an iron alloy-ceramic composite. This material could be used for shoulder surgeries and degrades at a slower rate over 1-2 years.

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Rajini Rao

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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.

News Story and Short Video:

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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Rajini Rao

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Gene Drives: Green Signal or Back Seat? 

What is the deadliest animal on earth? If you're thinking of the great white shark or a venomous snake, you could be wrong. Counting human deaths, it is the innocently named (Spanish for "little fly") mosquito. Millions, mostly children in third world countries, are killed or sickened each year by malaria, dengue, yellow fever and encephalitis caused by parasites and viruses that are transmitted by mosquito bites. This happens despite billions of dollars spent, years of research and potential cures ranging from vaccines and drugs to public health management. 

Stop or Go, that is the Question: Imagine if the mosquito could kill the parasite before it has the chance to spread to its human victims. For example, the mosquito could be engineered to make antibodies against Plasmodium, killing the parasite soon after it enters the mosquito after a blood meal. Just like a vaccination, nearly all mosquitoes would need to carry this new trait to be effective. There is a way to do this and it is not a new idea. What used to be theory, however, has just become a reality. A new paper published in the journal PNAS has now changed the question from Can we do this? to Should we do this?

What are Gene Drives?: Normally, the chance that any gene trait is passed from parent to offspring is 50%, since only one of a chromosome pair is inherited from that parent. But some selfish genes can copy themselves so that both chromosomes carry the trait, which now affects 100% offspring. A gene drive consists of DNA sequences that provides the technical ability to do this. With the new CRISPR/Cas9 tool that precisely cuts and inserts any gene of interest, the gene drive has become a reality. 

Can Gene Drives work on Humans? Gene drives work best in fast reproducing species, like mosquitoes, that can be released in large numbers. For this reason, they are not going to be effective in spreading inadvertently through humans, or even commercial crops and animals which are bred by controlled processes like artificial pollination and insemination.  

Gene Drives are Natural: For example, a gene called P element swept through all fruit flies in the wild, but is not found in lab strains that were isolated before it spread. 

Gene Drives can be Reversed: For each gene drive that spreads a trait, a reverse gene drive can undo the genetic changes in the original strain. Such reversal drives should be tested in advance, and could be released to stop the spread of any unintended consequences.

What else can Gene Drives do? Besides targeting mosquitoes, gene drives could be used to eradicate invasive species, or reverse resistance to herbicides and pesticides. 

Take the Poll: A public conversation based on sound scientific information, weighing pros and cons, must be the starting point for developing policy. Engineered mosquitoes that could rapidly spread in the wild and eradicate the malarial parasite have been made. Here is the question: Should we use Gene Drive engineered mosquitoes to fight Malaria? 

FAQ on Gene Drives:
Image: Matt Panuska
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Yes, release the engineered mozzies!
No, there may be unintended consequences
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Rajini Rao

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Herbal Cancer Cure: Weeding out the Hype

A recent G+ post ( claimed that artemisinin, derived from an ancient Chinese herb Artemisia annua, kills 98% of lung cancer cells in less than 16 hours. What's wrong with this claim?

◈ The comments fell into two categories: some outright disbelief If this is factual, it'd be amazing and More pseudoscience, Geesh! More common were conspiracy theories from the predictable, The W.H.O., F.D.A., C.D.C., etc. Can't patent it, so they can't make money off of it. to the bizarre, Funny thing is that the government gets their money off of cancer so I wonder if they'll make this illegal and claim it's got a side-effect that makes people experience what they would if they used Marijuana. Idk, but the government's gonna F it up somehow. Let's examine the claims and counterclaims. 

98% of cancer cells are killed by a culture dish! It's easy to kill cells in a dish -just ask my students :) These are in vitro findings. How about in vivo? Experiments done in rodents are indeed promising and have been reviewed and reported. Unfortunately, we scientists are excellent mouse doctors, and many drugs that cure cancer in mice under controlled, ideal lab conditions fail in the clinic. Does it work on humans? There are a few case reports of using artemisinin in humans. But, these are anecdotal and of limited use, since the patients were under chemotherapy anyway. What is needed are large scale randomized clinical trials with placebo controls to check if this herb is effective against cancers. Such trials cost a billion dollars and have not yet been done. 

Artemisinin has been safely tested in over 4000 patients...this claim from a doctor in a popular video ( probably refers to a Phase I trial where only safety is monitored. Notice the doctor does not say if the herb was effective against cancer in these 4000 patients. 

The FDA will never approve it....wrong, because it is already an FDA-approved antimalarial drug. In fact, artemisinin in combination with other drugs is the gold standard for treatment of Plasmodium falciparum malaria worldwide. The WHO has negotiated with Novartis and Sanofi-Aventis to obtain the drug at cost, with no profit. 

Bottom line: Both sets of comments are off the mark! The potential of artemisinin as a cancer chemotherapeutic should not be dismissed as pseudoscience until proven otherwise. As for the conspiracy theorists, they're just wrong.

Wiki: #OpenAccess REF: Anticancer Effect of AntiMalarial Artemisinin Compounds. (2015) Das, AK

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Affairs of the Heart: Dr. Helen Taussig 

❤  On a late November day in 1944, bright sunlight streamed upon the blue-tinged body of 18 month old Eileen Saxon, who was hovering near death. Born with a congenital heart defect that prevented her blood from being oxygenated by her lungs, she now weighed little more than 9 pounds. Across the ocean, World War II raged on, but at the +Johns Hopkins University hospital in Baltimore, another type of history was being made. Under the gaze of 706 doctors gathered around, Dr. Alfred Blalock meticulously rerouted an artery heading to the child's arm, back to the lungs giving the oxygen-starved blood a second chance of rejuvenation. The anesthesiologist cried out in astonishment as Eileen's lips turned from blue to a healthy red. That was the start of a successful procedure that would cure thousands of "blue babies" in the brand new era of heart surgery that followed. Today, we remember Dr. Helen Taussig, whose brilliant idea it was that set the stage.

❤ Born on this day, May 24, in 1898, Helen took medical classes at both Harvard and Boston Universities although neither would award her a degree because of her gender. Worse, she was forbidden to speak to her male colleagues in histology class because of fears that she would "contaminate" them. She completed her MD degree at Johns Hopkins and there, as a pediatric cardiologist did extensive work with anoxemia, or blue baby syndrome. She noticed that blue babies with an additional heart defect (called PDA) fared better, and that a shunt that mimicked PDA could be the solution. She pitched the idea of getting more blood to the lungs much "as a plumber changes pipes around" to surgeon Alfred Blalock and his technician Vivien Thomas. Thomas, a black man whose education did not go beyond high school, practiced the surgery in the animal lab and after modifying instruments for use in humans, coached Dr. Blalock through the first hundred surgeries in infants. In 1976, Hopkins awarded him an honorary doctorate. Sadly, little Eileen became cyanotic again in a few months and did not survive past 2 years even though other babies would go on to live healthy lives. Today, a modified version of the shunt is performed using a synthetic Gore-Tex graft (lower right image). 

¸¸.•*¨*•♫ Happy Birthday, Dr. Taussig!  

Image Note: Helen Taussig became deaf in later years, and actually used her fingers rather than a stethoscope to feel the rhythm of heartbeats.

#ScienceSunday   #STEMWomen  
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Dotting the I 

Colorful bindis are being handed out to tribal women in India by a philanthropic organization. When worn on the forehead, each dot delivers a daily dose of 100-150 micrograms of iodine (chemical symbol: I) which is absorbed by the skin. At least 70 million Indians suffer from iodine deficiency disorders. Sure, oral supplements or iodized salts are more efficient, but the tribal women won't take them. The bindis are a socially more acceptable, and creative, approach to dietary compliance! 

Bad Air: Iodine deficiencies were described by ancient Roman writers and medieval travelers, who would encounter entire villages in the Alps or southern Europe struck by cretinism.  Thought to be due to "bad air" or "stagnant water" in the mountains, we now know that dwarfism, deformed bones and intellectual disability are due to lack of iodine-rich thyroid hormone. Goiter belts characterized the more mildly afflicted inland regions of Europe and N. America, where populations were marked by enlarged thyroids and grossly swollen throats. Along the coast, however, wave action disperses natural iodine salts from sea water into the air, from where it enters our ecosystem. No wonder, sea air was recommended for recuperating invalids. 

The Rise and Fall of I: After the discovery of iodine in 1811, Lugol's solution (mostly potassium iodide, or KI) became the universal panacea of western medicine. Medical students were advised:

If ye don’t know where, what, and why 
Prescribe ye then K and I

But too much of a good thing led to the discovery that excess iodine actually blocked thyroid hormone production (known as Wolff-Chaikoff effect). Today, the Reference Daily Intake or RDI has decreased from 1 gram, to 150 micrograms, which many practitioners believe is too little. Proponents of iodine therapy point out the benefits in preventing breast cancer, skin disorders and more. For a fascinating history of the controversies and facts see the article in the reference. 


Video: Jeevan Bindi- The Life Saving Dot (1 min long)

Photo: Subir Basak

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Rajini Rao

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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.

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

The Beatles-Fixing a Hole:

Photo Credit: Bertrand Kulik 

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