❤ Happy (birthday) HIRL ❤

Happy (birthday) HIRL

A big thank you to all my friends, well-wishers and fellow incorrigibles for today’s extravaganza. How awesome to have not one, but a double-superhero hashtag #Wolverine2WonderWomanHappyBD accompanied by a #punderstorm and trending of my favorite #ScienceEveryday .  

This began with a mysterious package. I came home to find it partly open.

Husband: The calendar you ordered has arrived

Me: I didn’t order a calendar

Son: See, I told you it was from her G+ friends!

A few minutes later, my giggles over images of a moustachioed Freddie Mercury Buddhini Samarasinghe trying to break free with a pipette,  Wonder Woman Thomas Kang in drag, and variously exposed males ( Dan and Peter identities protected, you know who you are) force me to explain my (undeserved!) reputation as a connoisseur of men in kilts. Was it my imagination, or did my husband just pull his knees in a bit? 😉 Oh yes, my secret admirer Hugh Jackman (sadly, the secret part refers to his inexplicable ignorance of my existence), being devoured by cake queen Kimberly Chapman !

Then I had a most distinguished delivery man in the form of William McGarvey , who came bearing gifts of strawberries, chocolates, and a superb Pinot Noir. When I saw the card, I knew there had  been a whole lot of monkeying going around. Appropriately, I served Bill my last slice of banana bread.

Thank you all for making today, and everyday, so special!

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Decoding ENCODE

Decoding ENCODE

◑ Our HOA introduces you to the organization of our genome, from the structure of the gene to the relative abundance of coding vs non-coding DNA. Our panel of experts includes Ian Bosdet and Josh Witten along with the ScienceSunday team of Buddhini Samarasinghe, Scott Lewis and myself (in a sari!) discussing the much publicized ENCODE project along with the controversy it has generated.

Legoland: What do our genes have in common with Legos? Do we really have “junk” DNA? We try to avoid jargon and use simple diagrams to explain. If you have questions, I’m here to answer them. 

#ScienceEveryday  

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Bio-Nanowires Conduct Electricity

Bio-Nanowires Conduct Electricity

Imagine a conducting nanowire, only 3-5 nm wide but many thousand times longer, connecting a microbial community to form mini-power grids. Naturally occurring soil bacteria, such as Geobacter, use these conductive pili for long-range electron transport. How and why do they do this?

All living organisms respire. Our cells break down sugars to obtain energy by extracting electrons that are handed down a relay chain to oxygen, which becomes water. The proteins (cytochromes) that conduct electrons are aided by special metallic centers, studded with iron, so they can cycle between Fe2+ (ferrous) and Fe3+ (ferric) states that differ by one electron. Geobacter uses these cytochromes too, just as our cells do. But oxygen only made its debut a mere 2.4 billion years ago. Before that, ancient bacteria shuttled the electrons to other acceptors, such as sulfides, nitrates and Fe3+. When Geobacter is deprived of oxygen, it grows out long pili into mineral rich rocks and “breathes” iron (drawing on top right). The current is believed to pass between layers of bacteria (middle right image) across a distance of 12 millimetres, which may not seem large, but is 10,000 body lengths to bacteria!

But can proteins conduct current? Researchers knew that the pili were conductive, behaving like ohmic devices (image at bottom right). Although the pili were decorated with cytochromes, they were spaced too far apart to transfer electrons between their metallic centers. When the protein chains were mutated to replace a type of amino acid, the pili lost conductivity. These “aromatic” amino acids have pi-pi orbitals that may be conducting electrons.

Live Wires: Bacterial nanowires can be used in generating microbial energy cells, bioremediation of pollutants (like uranium), and in nano-manufacturing of a variety of devices. The main image shows bacteria growing on metal electrodes.

⚛ Ref: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3604773/

⚛ Sources: http://www.geobacter.org/Nanowires, http://goo.gl/E6Kpf , http://goo.gl/si6aH , http://goo.gl/T76L5

#ScienceEveryday when it’s not #ScienceSunday .

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Biological Bullets

Biological Bullets

Viral Payload: A rhabdovirus may be 150,000 times smaller than a 9 mm bullet, but it is just as deadly. A single strand of RNA self-assembles with a helical array of proteins, viewed in this 3D animation set to Mozart’s piano sonata in C-Major http://goo.gl/sRiwx. These viruses infect both plants and animals, and include the rabies causing virus that is transmitted to humans by bites. Watch a 3D model of a Rabies virus: http://goo.gl/z3Qx1

Silver Bullet? Researchers hope to exploit the cell-invading ability of viruses to destroy cancer cells. One favorite is the vesicular stomatitis virus (VSV) that infects horses and cattle, but causes only mild flu like symptoms in humans. Genetically crippled (“attenuated”) forms of VSV are safer to use and preferentially infect cancer cells by exploiting their altered signaling pathways. These oncolytic viruses hold the promise of a self-replicating biotherapy.

Image: Cryo-electron microscope image of a rhabdovirus. 

Ref: Self-organization of the vesicular stomatitis virus nucleocapsid into a bullet shape. Desfosses et al., 2013 Nat. Commun . http://goo.gl/xULA0

#ScienceEveryday   #viromania  

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Down Syndrome Day

Down Syndrome Day

Today, 3/21, is World Down Syndrome Day. Also known as Trisomy 21, because it involves three copies of chromosome 21 instead of the usual two (see image), Down syndrome is the most complex of genetic disorders that is compatible with survival (other trisomies are more common, but are lethal). Even Down syndrome is associated with ~50% lethality of embryos. In the US, 1 in 691 babies is born with Down syndrome.

Too much of a good thing: Anywhere from 300 to 500 genes have altered levels and function, resulting 80 or 90 possible symptoms and an instantly recognizable phenotype (physical appearance). For example, patients have a 1 in 5 chance of developing a hole in the heart, compared to an incidence of 1:10,000 in the normal population. Down syndrome is extraordinarily complex, and my friend and colleague Roger Reeves has dedicated his career to helping patients with his research.

Cerebellar size: Dr. Reeves showed that the reduced size of the cerebellum in patients was due to defects in the sonic hedgehog signaling pathway. Using a drug that activated this pathway, he was able to restore the number of cerebellar cells to normalcy in a mouse model of Down syndrome, pointing to a therapeutic potential for the central nervous system deficits in patients.

Tweaking circuits: In the hippocampus—that part of the brain that’s used to navigate landmarks and fix memories, Down syndrome patients show an excess of inhibitory pathways compared to excitatory ones. A drug that is already FDA-approved works wonders on mice with the equivalent of Down syndrome, restoring balance to their brain. This drug is now in clinical trials for  Down syndrome patients.

It’s not all bad: Research on Down syndrome has broad impact. For example, having three copies of a tumor suppressor gene means that patients have a 93% lower incidence of developing certain cancers. This insight could help treat cancers in the general population. Plus, as Roger likes to say, if you know anyone with Down syndrome, they tend to be pretty interesting individuals in their own right.

For more on Roger’s research: http://goo.gl/uSJWm

#ScienceEveryday #DownSyndrome  

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Meet the Erythrocyte

Meet the Erythrocyte

Red blood cells take up 45% of your blood volume and circulate about once in 20 seconds, carrying vital oxygen to every nook and cranny of your body. Did you know that ~2.4 million of these are produced each second? That’s because they have a short life span of only about 120 days.

Please squeeze me: The image shows a red blood cell squeezing through a tiny capillary: to accomplish this maneuver, the red cell sacrifices its nucleus and mitochondria to become a flexible, biconcave disk. In the inset, is a deformed red cell from a patient with sickle cell disease shown next to a normal cell. A single mutation in hemoglobin, the oxygen carrier of red blood cells, causes the proteins to clump giving the cells their characteristic sickle shape. The deformed cells block capillaries and burst more easily, surviving only 10-20 days. 

Heterozygote advantage: Given the severe health complications from sickle cell disease, why does the mutation persist in some populations? You might expect that negative selection against affected individuals would have eliminated the mutation. It turns out that carriers of the mutation (who have one normal copy and one mutated version of the gene), have mild sickling of their red blood cells which also makes them more resistant to infection by the malarial parasite. In fact, sickle cell disease is more common in areas where malaria is endemic. 

Another installment of an  #excyting  series on cells. This one is for Chad Haney who celebrates his birthday today and is my fellow conspirator in science outreach on Google Plus. Chad worked on generating a blood substitute as a graduate student. #HappyBirthdayChad   #HappyBirthdayMrMRI   #ScienceEveryday   #ScienceSunday  

Image: www.visualphotos.com

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My Day on the Hill

My Day on the Hill

This week, several hundred scientists – astronomers, chemists, biologists and engineers from across the nation, descended on Capitol Hill to lobby for science. We asked for sustained and predictable federal funds for scientific research. We voiced our worry that deep cuts in grants would destroy a generation of scientists: that research is not a faucet that can be turned on and off, because the well at the source dries up. We brought a personal face to the projects we were working on.

What did I learn? Our visit began with a briefing at the AAAS auditorium in Washington, DC. The Office of Science and Technology from the White House gave us the executive branch perspective by breaking down the budget into entitlements and discretionary spending, and showing us the thin slice of pie that went to Federal R&D. Then we got a Congressional perspective from both the House and Senate committees on Science, Space and Technology. These career administrators were scientists themselves, very much “on our side”. The next day was a blur of individual visits to offices of senators and congressmen from our states, efficiently organized by the Biophysical Society whom I was representing. The deal was that we spoke to staffers, and the staffers spoke to the elected members of Congress. We handed out folders full of statistics, talking points and projections. We shook hands, took pictures and exchanged cards.

Was it worth it? In the long run, yes. Maybe. Like the democratic process, visiting Congress is both our right and responsibility. I left with a better understanding of how Congress runs, and hopefully, made some contacts. It’s going to be easier to write to my elected representative the next time I’m called upon to lobby for science.

Was it fun? Definitely, this was an unforgettable experience. Senate offices are posh! Marbled halls, deep carpeting, brass-studded heavy doors. The House? Not so much. Congress is run by 20-30 somethings: smart but poorly paid, staffers put in long hours and typically don’t last more than a year. It was fun to spot faces: there was Sen. Barbara Boxer rushing past us, Rep. John Dingell leaning heavily on his cane, while another senator saw off some fund raisers at his door. 

#ScienceEveryday  

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Evolution of a Species

Evolution of a Species

Assortive Mating: The diversity of lifeforms on our planet is central to evolution. But how do new species form? A key step is assortive mating, when individuals use physical or vocal cues to choose mates that resemble themselves. Perhaps natural selection favors offspring from similar matings. Eventually, the populations diverge genetically to the extent that the hybrids are unfit, and separate species emerge.

Caught in the act? Take the curious case of the Australian Gouldian finch (Erythrura gouldiae). There are black and red head color morphs (see image) that prefer to mate with like types. This preference is genetic, as chicks reared by foster parents of different type still prefer to mate with their own head color morph. In fact, the head color and mating preference are tightly linked on the sex chromosome Z (males are ZZ and females are ZW in birds). This lack of “sexual imprinting” is unusual, since most birds get their cues from rearing parents.

Hybrid drama: Both head color types coexist in the same geographical area. Shrinking and unequal populations mean that mates of the same type can be hard to find (the bird is endangered). The birds seem to “make the best of a bad situation” and breed with different head color morphs anyway. But there is a steep price to pay : more than a third of the offspring die. The mortality rate is worse in female chicks, nearly half fail to survive. Curiously, the mothers seem to control for this by producing broods with more males. So, if they are tricked into thinking that their mate is of a different head color  (using bird make-up!) they produce biased broods! All of this suggests that the Gouldian finch may be in the process of splitting into species, unless it becomes extinct before then 😦

▪ Images (National Aquarium): http://aqua.org/explore/animals/gouldian-finch

▪ H/T Mindy Weisberger whose post on the phosphorescence beads marking the gouldian finch chick’s mouth (http://goo.gl/Zw8tv) set me off on this evolutionary hunt!

▪ Further readings by Sarah R. Pryke ▶ http://goo.gl/Tngj1

#ScienceEveryday  

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Fun with Furans: Making Flat Bread with Fenugreek

Fun with Furans: Making Flat Bread with Fenugreek

• The first reports of a strangely seductive aroma wafting over Manhattan and nearby New Jersey began in 2005. People smelled maple syrup, which got them fantasizing over pancakes and waffles. No doubt, the local Denny’s did brisk business. But there were enough calls to 311 to set the authorities sniffing. It was not until 2009, after the Department of Environmental Protection analyzed dozens of air samples and computed wind routes, that Mayor Bloomberg announced the mysterious source: a spice factory in New Jersey that processed fenugreek.

Sotolon, or more precisely 4,5-dimethyl-3-hydroxy-2[5H]-furanone, is an extremely strong aroma compound. In low concentrations, it smells like maple syrup, caramel or burnt sugar, and at high concentrations it evokes the smell of curry and spices. It is the major aroma and flavor component of fenugreek and lovage, but also flavors rum, white wine, aged sake and tobacco. Why you complain, New Yorkers?

• Remarkably, fenugreek (Trigonella foenum-graecum) is used three ways: as a spice, herb and vegetable. The yellowish cuboid seeds (methi) are roasted and widely used in Indian cooking, the dried leaves (kasuri methi) are used as herb, and the fresh leaves (methi) are cooked as greens. This time, I chopped the leaves up finely in my food processor and incorporated them into a verdant and pliant dough, to make methi parathas, a flaky, flat bread full of flavor.

Gene Mutations in the enzyme that breaks down branched chain amino acids result in sotolons accumulating in the urine. Maple syrup urine disease, (MSUD) is life threatening and is particularly prevalent in some ethnic groups (Old Order Mennonites).

Recipe: https://madamescientist.wordpress.com/2013/03/10/fun-with-furans-making-flat-bread-with-fenugreek/

MSUD: http://ghr.nlm.nih.gov/condition/maple-syrup-urine-disease

#ScienceSunday

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Fun With Furans: Making Flat Bread with Fenugreek

The first reports of a strangely seductive aroma wafting over Manhattan, Queens and nearby New Jersey began in 2005. People smelled maple syrup, which got them fantasizing over pancakes and waffles. No doubt, the local Denny’s did brisk business. But there were enough calls to 311 to set the authorities sniffing. It was not until 2009, after the Department of Environmental Protection analyzed dozens of air samples and computed wind routes, that Mayor Bloomberg announced the mysterious source: a spice factory in New Jersey that processed fenugreek.

Sotolon, or more precisely 4,5-dimethyl-3-hydroxy-2[5H]-furanone, is an extremely strong aroma compound. In low concentrations, it smells like maple syrup, caramel or burnt sugar, and at high concentrations it evokes the smell of curry and spices. It is the major aroma and flavor component of fenugreek and lovage, but also flavors rum, white wine, aged sake and tobacco. Why you complain, New Yorkers?

Remarkably, fenugreek (Trigonella foenum-graecum) is used three ways: as a spice, herb and vegetable. The yellowish cuboid seeds (methi) are roasted and widely used in Indian cooking, the dried leaves (kasuri methi) are used as herb, and the fresh leaves (methi) are cooked as greens (as in my recipe for Alu Methi). This time, I chopped the leaves up finely in my food processor and incorporated them into a verdant and pliant dough, to make methi parathas, a flaky, flat bread full of flavor.

Flat bread with fenugreek leaves (methi paratha), flavored by my favorite furan, sotolan

Flat bread with fenugreek leaves (methi paratha), flavored by my favorite furan, sotolan

  • For the dough, add 0.5 cup of chick pea flour (besan) to 2 cups of wheat flour (atta). You can omit the besan, but it imparts a distinctive texture and aroma that is irresistible. Add a tablespoon or two of vegetable oil when making the dough. Normally, I skip the oil when making ordinary Indian flat breads (chappatis), but it helps to have a softer dough when making the stuffed varieties.
  • Add a pinch of turmeric, chilli powder, cumin seeds and salt to taste. Chop up a green chilli or two if you want it hotter. I made the dough in the food processor, adding water slowly until the dough just began to form clumps. Turn out on the counter top, knead briefly and let it rest covered.

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Fenugreek leaves, washed and de-stemmed

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Make the dough with minced fenugreek, spices, whole wheat and chick pea flour. Let rest, covered, for half an hour.

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Roll out into a circle

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Spread a thin layer of oil on the surface

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Make a cut to the center, then roll dough around the cut end to form a cone

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Flatten the cone into a circle, in the palm of your hand. Note the concentric layers in the dough.

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Roll out the dough again. This time, the circle has concentric layers that make the paratha flaky.

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Cook on a hot griddle with a scant teaspoon of oil on each side until light brown spots appear

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Leftovers are delicious packed for lunch! I served the methi paratha with black eyed peas, roasted wedges of brussels sprouts with cumin seeds, topped off with a cranberry raisin relish. The green chilli is to get my endorphins going.

We were too hungry to wait for any more photos, so I’m sharing the left overs with you. I hope you enjoyed my favorite furan. Until next time, I’ll leave you with a substitute for the cheery yellow flowers of fenugreek and a walk down memory lane.

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Path leading from my conference in the village of Les Diablerets, tucked away in the Swiss Alps (banner picture).

Posted in FOOD, Herbs, Indian food, science, Uncategorized, Vegetarian | Tagged , , , , | 10 Comments