molecule of the day: milrinone

The molecule of the day is milrinone:

It's a drug that provides short-term benefits for heart transplant and heart failure patients by increasing heart contractility, but in the long-term it causes arrhythmia.  It inhibits type 3 phosphodiesterases (PDE3s).  Recent work suggests that its target in heart is probably the A isoform (PDE3A) (which is not that surprising given that it's PDE3A that's mostly expressed in heart muscle).

word of the day: inotropic

The word of the day is inotropic:

Etymology:  < German inotrop (T. W. Engelmann 1896, in Arch. f. ges. Physiol. LXII. 555): see ino- comb. form and -tropic comb. form.

Physiol.

Modifying the contractility of muscle. (OED)

"A positive inotropic cardiotonic agent with vasodilator properties."

 - PubChem entry on milrinone

word of the day: diamanté

The word of the day is diamanté:

Etymology:  French, past participle of diamanter to set with diamonds, to make shine like diamonds.

Material to which a sparkling effect is given by the use of paste brilliants, powdered glass or crystal, etc. Also attrib. (OED)

"In 'Country Girl', O'Brien uses the frame of memory to crop the commonplace out of life.  She loses her virginity in a field outside Dublin, but recalls 'the damp of the grass, a diamanté hair slide that I had lost, the peas that kept slipping off his fork.'"

 - Lauren Collins, "Ink: where she was from", 20 May 2013 The New Yorker

phrase of the day: wildcat strike

The phrase of the day is wildcat strike:


An employee work stoppage that is not authorized by the Labor Union to which the employees belong.  (legal-dictionary.thefreedictionary.com)


"On a later night, however, they return to lob Molotov cocktails, and a security guard is hurt; to avoid trouble, the friends take off for the summer break, hitching a ride to Italy with a revolutionary film collective in (of course) a VW van.  The sun glares, the strikes are wildcat, and the masses await enlightenment through cinema.  Bliss is it in that dawn to be alive."

 - Anthony Lane, "Battle weary: 'Iron Man 3' and 'Something in the Air'", 6 May 2013 The New Yorker

word of the day: fug

The word of the day is fug:

colloq. (orig dial. and School slang).

A thick, close, stuffy atmosphere, esp. that of a room overcrowded and with little or no ventilation. (OED)

"Instead, they exist in a constant fug that I took for cigarette smoke or tear gas, but that slowly resolves itself into a nimbus of ill-defined needs - a haze of becoming, with the foothills of adulthood starting to loom ahead."

 - Anthony Lane, "Battle weary: 'Iron Man 3' and 'Something in the Air'", 6 May 2013 The New Yorker

word of the day: logorrhea

The word of the day is logorrhea:

Etymology:  < Greek λόγος word + ῥοία flow, stream (probably after diarrhœa n.).

Excessive volubility accompanying some forms of mental illness; also gen., an excessive flow of words, prolixity.  (OED)

"To be honest, the film is a whiney and logorrheic mess until Stark, after a couple of misadventures, finds himself in Tennessee, just before Christmas, hauling a broken Iron Man suit through the snow like a toboggan."

 - Anthony Lane, "Battle weary: 'Iron Man 3' and 'Something in the Air'", 6 May 2013 The New Yorker

molecule of the day: benzopyrene

The molecule of the day is benzopyrene:

(PubChem)

It's a carcinogen found in tobacco smoke, among other things, and can be used to induce lung tumors in mice when injected into the peritoneal cavity (tummy), as in this paper, the star of today's Center for Metabolism and Obesity Research journal club.  One of the attendees described it as "that chickenwire compound".

I asked the presenter why, after injecting it into the peritoneal cavity, benzopyrene would cause tumors in the lung (after all, the paper uses a fancy aerosol device to deliver the 3-bromopyruvate (the chemical they were testing to see whether it prevented the tumors from forming), so why not use that to deliver the benzopyrene, too?  Wouldn't that be more relevant anyway for a carcinogen found in tobacco smoke?), and he thought that the authors were just looking at lung tumors and not really interested in any tumors that may or may not have formed in other parts of the body.  I guess intraperitoneal injection is the easiest way to deliver a drug to a mouse, and if it works to produce the desired lung tumors, then good enough?

Reading a bit more, I learned that benzopyrene is actually a "pro-carcinogen": after benzopyrene enters your body, you metabolize it into another molecule, 7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene:

which is the actual carcinogen.  It fits into the double helix of the DNA strand, which can cause the DNA to be copied incorrectly and introduce mutations, which can then cause cancer.

word of the day: cadre

The word of the day is cadre:

Etymology:  French cadre frame (e.g. of a picture), also used in sense ‘l'ensemble des officiers et sous-officiers d'une compagnie’ (Littré), < Italian quadro < Latin quadrum four-sided thing, square. 

 

1. A frame, framework; scheme.

2. Mil.a. The permanent establishment forming the framework or skeleton of a regiment, which is filled up by enlistment when required. Also of an R.A.F. squadron. Also attrib. 

b. The complement of officers of a regiment; the list or scheme of such officers.(After the Indian Mutiny, the cadres of Native Regiments which had been disbanded were kept in the Indian Army List for regulating promotions. In the parliamentary discussions about the amalgamation of the Indian with the British Army, the word was in constant use in this sense.)

 3.a. In Communist countries, a group of workers, etc., acting to promote the interests of the Communist Party; also, a member of such a group; = cell n.¹ 19.

b. In the People's Republic of China, an office-holder in a Party, governmental, or military organization; also more widely, one who holds a position, esp. in a local organization, school, etc. Also attrib., esp. as cadre school.  (OED)

"As the sharp end of a counter-insurgency strategy, McChrystal's approach resembled the C.I.A.'s Phoenix program during the Vietnam War, when the United States tried, and failed, to suppress the Vietcong by detaining and assassinating thousands of suspected militants and cadre leaders."

 - Steve Coll, "Remote control: our drone delusion", 6 May 2013 The New Yorker

word of the day: gravid

The word of the day is gravid:

Etymology:  < Latin gravidus, < gravis burdened, heavy (see grave adj.¹, grave n.¹ Compare French gravide.

Pregnant, heavy with young.

"Never fear.  I know the difference between
arteries and ardor, arbor and treed,
my bower and a weak-kneed need, a harbor
where one might moor tonight and a port worth
the oars' effort to come ashore for, a bit
part and the serpent's gravid apple."

 - Dora Malech, "To the you of ten years ago, now", 6 May 2013 The New Yorker

word of the day: fer-de-lance

The word of the day is fer-de-lance:


fer-de-lance, any of several extremely venomous snakes of the viper family (Viperidae) found in diverse habitats from cultivated lands to forests throughout tropical America and tropical Asia. (Britannica)


"The rain forests of Mosquitia, which span more than thirty-two thousand square miles of Honduras and Nicaragua, are among the densest and most inhospitable in the world.  'It's mountainous', Chris Begley, an archaeologist and expert on Honduras, told me recently.  'There's white water.  There are jumping vipers, coral snakes, fer-de-lance, stinging plants, and biting insects.  And then there are the illnesses - malaria, dengue fever, leishmaniasis, Chagas'."

 - Douglas Preston, "The El Dorado machine: a new scanner's rain-forest discoveries", 6 May 2013 The New Yorker


Shouldn't that be "fers-de-lance"?

word of the day: mishegoss

 The word of the day is mishegoss:

Etymology:  < Yiddish meshugas < Hebrew mĕšuggaʿaṯ , use as abstract noun of feminine of mĕšuggaʿ meshuga adj.(Show Less)

slang.

 

Esp. in Jewish usage: madness, craziness; nonsense, foolishness; (as a count noun) a foolish idea; a foible, an idiosyncracy.

"In 1983, around the time that Berman moved to Tuxedo Park, some of his former students received invitations to purchase 'a limited subscriber's edition of a monumental novel'.  It was Berman's magnum opus.  For many alumni, the book - a four-hundred-and-eighty-three-page volume, beautifully published by a former Berman student - is the only window they've had onto their mysterious teacher.  'His whole universe of mishegoss is in there - the art, the music, the literature, the sex', a college professor who has spent many years trying to figure out Berman says."

 - Marc Fisher, "The master: a charismatic teacher enthralled his students.  Was he abusing them?", 1 April 2013 The New Yorker

word of the day: halt

The word of the day is halt:

Etymology:  A Common Germanic adj.: Old English halt, healt = Old Frisian, Old Saxon halt (Middle Dutch halt, hout, Old High German, Middle High German halz, Old Norse haltr (Swedish, Danish halt), Gothic halt-s < Old Germanic *halt-oz.(Show Less)

arch. and literary.

Lame; crippled; limping. (OED)

"When I asked Berman, who is now seventy-eight, to talk with me, he wrote that he was 'very near death' and that he saw no point in meeting: 'All you would discover is a rather halt old man in deteriorating health.  What you most likely would not perceive is such a person who never in his long life intentionally injured anyone.'"

 - Marc Fisher, "The master: a charismatic teacher enthralled his students.  Was he abusing them?", 1 April 2013 The New Yorker

word of the day: humic

The word of the day is humic:

Etymology:  Latin humus ground, mould + -ic suffix. 

Of or pertaining to humus or mould; present in or of the nature of humus; rich in humus; also, formed or derived from plant remains. (OED)

"Patented Inhibitor Removal Technology eliminates humic substances and other PCR inhibitors."

 - product description for PowerSoil® DNA Isolation Kit from Mo Bio Laboratories, Inc.

“I didn’t hear about this experiment until I was a freshman at Brown”

At the Herbert Tabor Research Award Lecture at the American Society for Biochemistry and Molecular Biology meeting, in his talk “Chaperonin-mediated protein folding”, Prof. Arthur Horwich of Yale University and the Howard Hughes Medical Institute opened by regaling us with the story of the famous experiment by Christian Anfinsen.  The hypothesis was that all of the information required for a protein to fold into its three-dimensional shape was encoded in the amino acid sequence.  He tested the hypothesis by treating the protein with urea and beta-mercaptoethanol (BME), chemicals that cause the protein to unfold, then he slowly removed the urea and BME, and amazingly he recovered the protein’s activity, meaning that it had folded correctly.  This is amazing because the number of possible arrangements the protein could assume is huge, and yet it was able to find the right one.  The experiment is elegant, and it won a Nobel Prize in 1972.

It’s a common story to use when beginning a talk on protein folding, but I was more interested by what he said next: “I didn’t hear about this experiment until I was a freshman at Brown”, as if he had expected to have heard about it earlier.

I think this story illustrates the gulf between what scientists expect the public to know and what the public actually knows.  I went to an excellent high school, but my ninth-grade biology class didn’t really discuss biochemistry at a molecular level, and for pretty fair reasons: we didn’t have chemistry until tenth grade, so I’m not sure what would have been gained by talking about the fact that proteins are made of amino acids and the protein folding problem.  In Advanced Placement Chemistry in eleventh grade, we spent a good deal of time on intermolecular interactions, so we probably could have applied those principles to proteins, but it was a chemistry class, not a biochemistry class, so we didn’t.  So even as a definitely more-educated-in-chemistry-than-average student, I, as Prof. Horwich, entered college having never heard of the Anfinsen experiment, or indeed of protein folding.  We scientists would do well to remember that when trying to communicate with the public.

what is the best way to confront misogyny and racism?

Taking an (at least in my opinion) well-earned day recovering from EB2013 and SXMAR2013, I spent a good part of it looking over these entertaining blogs.

I'm a bit torn.  Racism and sexism (like other -isms, capitalism, socialism, etc.) are societal structures that have, over our lifetimes, been cultivated in every one of us (try the Harvard Implicit Association Tests if you haven't already).  I'm not convinced that labeling individuals as "racists" (so that you can then peace out on them) is productive: it implies that racism is something that can be isolated, and exists in some individuals, and not others, and all we have to do to solve racism is to stay away from those bad people.  I'm not the only person who thinks this: I've even heard the hypothesis that a good deal of the racial problems we continue to have in America today can be traced to the fact that Adventures of Huckleberry Finn (a book I love, by the way), which trades in the only-bad-people-are-racists view, is considered the definitive Great American Novel about race and is required reading in many schools, while Uncle Tom's Cabin (a book I haven't read, but this is how the hypothesis goes), which trades in the racism-is-a-structure view, is not.

On the other hand, I'm extremely sympathetic to the idea that denouncing racism and misogyny is more important than considering racists' and misogynists' feelings.  Racism and misogyny are much more offensive than being imperfectly polite while pointing out that people are being racist and misogynist.  And, to paraphrase Prof. Richard Dawkins, when someone calls you "shrill" (or the worse, more specifically misogynist words leveled at MTFOB), what they really mean is that they're unable to criticize the content of your message.

On the third hand: I think tone actually is really important when trying to communicate.  (I've been thinking about this more recently in the context of science communication: starting off with a I've-been-in-school-for-decades-and-know-more-than-you-mortals-ever-will is not a good strategy.)  I don't know if anyone has ever actually been persuaded to change their ways by statements like “FUCK YOU, you piece of shit racist"; maybe something like, "Hey, did you know the word 'gyp' comes from the word 'gypsie' and perpetuates negative stereotypes about certain groups of people being untrustworthy?  No?  But now you do, so now you know when you use that word you might offend people: maybe the word 'swindle' would better convey what you actually mean" would be more effective.  No one has ever regretted taking the high road.

But (and now we come to synthesis): I think it's extremely important not to let the perfect be the enemy of the good.  If someone says something racist or misogynist, I think the most important thing is to speak up: not just to let the person saying it know that that's not cool, but, more importantly, to signal to everyone else who heard that person say the racist or misogynist thing that you don't approve.  If you have to choose between letting the moment slip by because you can't think of the perfectly crafted message, or just spitting something out that, in hindsight, could have been better phrased, choose the latter.  It's pretty likely that the person you're speaking to will get nasty (no one likes being accused of being racist or misogynist), but this is noble work, and the more everyone speaks up, the more socially acceptable it will be and the easier it will be for everyone.

It just takes four words: "Hey, that's not cool."

"Alternative" career panel

Mid-day Saturday, I attended the American Society for Investigative Pathology's 13th Annual Workshop on Graduate Education in Pathology, "We can't all be PIs: preparing graduate students for alternative career paths".

I think panels like these are just wonderful (supporting evidence: this event was extremely well-attended), but I thought the title of the event could have been better.  It's true that we call can't be PIs (principle investigators, or the traditional science professor): in order for it to be sustainable, each PI would, over the course of his or her career, train exactly one replacement.  In fact, many more students and even postdocs are trained than faculty positions are available.  But then this is precisely why "alternative" is not a great word to use here.  People who end up as tenure-track faculty are, in fact, a tiny minority of science PhDs, so it's the academic track that really should be called "alternative".

But also: not everyone wants to be a PI, even if they could be one.  This can be hard for many scientists to imagine (even people who are not, themselves, PIs: I was once at a career fair where an industrial scientist justified his job as "well, being a professor is clearly the best job, but we can't all do that"), but, in fact, not everyone loves doing bench science.  Not everyone loves writing grants.  It's not just that we can't all be PIs: even if we could, not all science PhDs would be happy doing that.  In fact, I think the fact that these sorts of panels are, in my experience, always extremely well-attended, is itself evidence that these sorts of people pursuing PhDs in science, the sort who don't want to be professors, are not that uncommon.  There are many, many important ways science PhDs can contribute to society, but calling these careers "alternative" and saying "we can't all be PIs" doesn't do much to remove the stigma.

It was an admittedly small sample size, so I'm not sure what if anything we can conclude, but I did make the following observation.  The panel had four members, three female and one male.  All three female panel members mentioned that one major reason they chose their careers (over, say, the coveted "PI" role, or even an industrial bench science role) was "work-life balance".  Also, it turns out that all three of the female panelists were married to scientists, of the more "traditional" type (two faculty, one industrial).  Meanwhile, the one male panelist mentioned that after working for a year and a half at a law firm, he started law school at night, while still working full-time at the law firm, with three children.  I don't know what the male panelist's life partner does, but I suspect she's a housewife.

It made me wonder about the degree environment contributes to our "choices" when it comes to work-life balance.  The high school teacher panelist was clearly very happy with the career she had chosen.  But if she had a stay-at-home husband, she may have chosen differently, either because she would have more time to dedicate to a job that required more hours because she could rely on her husband to provide child care, or because she would need a job with a higher salary in order to support her family.  I've heard that the choice of a spouse is the single most important career decision you will make.  I do think one major challenge facing women in STEM [science, technology, engineering, and mathematics] (and, therefore, everyone) is the fact that women in STEM are more likely to have spouses in STEM than men in STEM are.  "Traditional" careers in STEM (like most careers) are still built on the model of employing a breadwinner who has a homemaker at home to take care of things.  This model is not sustainable.

The microbes within us

Shorter thoughts are going to Twitter, but this will be the first in a series of longer posts of thoughts from #EB2013:

Bright and early on Saturday morning I attended the symposium "Managing the microbiome in human GI disease" put on by the American Society for Nutrition.  (The Experimental Biology meeting is made up of six societies: the American Society for Biochemistry and Molecular Biology (the reason for which I was ostensibly attending), the American Society for Nutrition, the American Society for Investigative Pathology, the American Society for Pharmacology and Experimental Therapeutics, the American Association of Anatomists, and the American Physiological Society.  These societies are themselves integrative and interdisciplinary, so any given symposium title could be difficult to assign to which society was sponsoring it.)

The emphasis of the symposium was on inflammatory bowel disease, but as an aside the speakers mentioned recent work on the relationship between obesity and the microbes inhabiting our guts.  For example, you can transfer the bacteria from a fat mouse to a lean mouse, and the lean mouse will gain weight (without changing how much it eats or its physical activity).

I was reminded of this later in the week when I met a graduate student who was researching obesity, but felt that she should move to some other disease for her postdoc, where she could contribute more to potential therapeutics and actually helping patients, since obesity is "preventable".

It got me to thinking about the way that we teach metabolism to the medical students.  We teach them that "calories in - calories out = weight gain", which is true: if you eat less and exercise more, you will lose weight.

But it's also true that for every human cell in your body, there are ten bacterial cells.  Most of these bacteria live in your gut, eating the same food you eat.  The calories they consume and expend are crucially important for how many calories are left available to you .  (The agricultural industry certainly appreciates this fact: they treat their livestock with low doses of antibiotics not to prevent bacterial infection, but to make them gain weight.)  As a society we tend to blame obese patients for making bad choices, but it's not like I chose what kinds of bacteria are living in my gut.

We're just beginning to learn about how specifically our gut bacteria contribute to our metabolism, so maybe that's why we don't want to include that when we teach metabolism.  We're not at the stage where we can tell people to eat certain brands of yogurt to solve certain medical problems (although I do know a scientist who believes he has cured his lactose intolerance by eating yogurt and colonizing his GI tract with the appropriate strains).  But we do know that our microbial communities are extremely important, and I think we're doing our students a disservice when we don't tell them that.

new Twitter feed

Longer thoughts will continue to be posted here, but for microblogging please see my new Twitter feed @ElizabethJPetro .

(Thought I would prefer the term centi- or deciblogging: 1400-14,000 characters seems more realistic for blog posts than 140,000,000.)

letter to the LA Times: increased or reduced risk of transmission?

Here is the gist of a letter I wrote to the Los Angeles Times:


"Your 17 April 2013 article 'HIV concentrations in breast milk higher at earlier, abrupt weaning' states 'HIV-infected mothers who breast-fed exclusively longer than the first four months after birth had less risk of transmitting the virus to their babies through their milk, researchers said.'

"Here's what the Science Translational Medicine paper actually says about the risk of HIV transmission: 'Viewed from an intent-to-treat perspective, the risk of late postnatal transmission was 7.6% in the group randomized to stop breast-feeding at 4 months and 10.2% in the group randomized to continue breast-feeding (RH, 0.67; 95% CI, 0.39 to 1.15).'

"I.e., HIV-infected mothers who breast-fed exclusively longer than the first four months after birth had an increased risk of transmitting the virus to their babies through their milk."


It's true that HIV concentrations were higher in the milk collected at 4.5 months from the mothers who stopped breastfeeding at four months, but that milk was collected after the babies had stopped drinking it.   It's also true that adherence to the regimen was incomplete, which led to the "excess transmission risk" that the authors mentioned, but the fact remains that the risk was still lower in the group randomized to stop breastfeeding.

I think the culprit here is this sentence from the abstract: "This may explain the reduced risk of HIV-1 transmission associated with exclusive breast-feeding and why early weaning does not achieve the magnitude of HIV prevention predicted by models."  I think what the authors meant by "reduced" here is "reduced compared to what you would expect", but I can only come to that conclusion after having read the entire article.  STM is not an open-access journal: other readers of the LA Times (and, indeed, the science journalist that wrote the article) might not have the same opportunity I have.

word of the day: sui-generis

The word of the day is sui-generis:

Etymology:  Latin.

lit. Of one's or its own kind; peculiar. Also used attrib. †Also illiterately as n., a thing apart, an isolated specimen. (OED)

"But for the sheer density of material and effort, there is nothing like 'The Rose'.  You may not look at it so much as gawk at it, in the chapel-like black chamber, with dramatic lighting, that it commands in the show.  It strikes me as neither good art nor bad but a sui-generis folly that lends itself to mythic reflections."

 - Peter Schjeldahl, "Flower power: A Jay DeFeo retrospective", 18 March 2013 The New Yorker