Reap What You Sow

Sep 10 2014 Published by under [LifeTrajectories]

While in my fellowship, I became interested in the role of puberty and sex in the progression of kidney disease. I studied this and related sex differences in the renal responses for more than 20 years. Then the NIH would not, could not bring itself to fund my work. My spouse had a new job offer, and the writing on the wall was clear: I closed my lab and moved into full-time clinical medicine.

From this perspective, I can appreciate NPR's series on the state of NIH funding and folks quitting science. At least I knew my clinical skills made me employable, although at times I dream of running a distillery.

Of course, there is the additional irony of the NIH calling for more study of both sexes, even in basic science studies, earlier this year. Gee, exactly what I was doing that was not important enough to merit funding...and now you are issuing special calls for it. Any regrets, NIH?

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Messy, Complex? Math To Make It Simple: #xBio

Apr 30 2014 Published by under EB2014

A number of renal physiology presentations dealt with modeling of kidney functions. They featured Departments of Mathematics, something which I find a bit intimidating:

As usual, XKCD speaks truth

As usual, XKCD speaks truth

Structural organization of the renal medulla has a significant impact on oxygen distribution

Brendan Fry, Anita Layton

Duke University, Durham, NC

 

The first thing that caught my attention with this abstract was its medullary focus. Nephrologists and physiologists often give the medulla little love. It's not the part of the kidney that we biopsy (at least not what we want to get), and while it does a bunch of stuff for water and volume control, most folks only pay attention to their little piece of it.

AJP Renal 287:767, 2004

AJP Renal 287:767, 2004

So what does it take to model the structure of a kidney? Let's look at an example of a medullary reconstruction in the figure on the right. In this study by Pannabecker and Dantzler, segment-specific markers were used to reconstruct the medullary architecture on sections through the kidney. Cross-sectional photos were "assembled" into these tubular models going from corticomedullary junction (a) through the papilla (e). Red structures are descending thin limbs of the loop of Henle, while blue tubes represent collecting ducts.

And these are only two of the tubular structures that course through the medulla and give it a striped appearance.

So these sorts of studies give us a picture of the anatomic relationships within the medulla. Now we need to start adding what we know about functional relationships. For that, we will see the next figure from Lemley and Kriz.

Kidney Int 31:538, 1987

Kidney Int 31:538, 1987

In this cartoon (not as pithy as the XKCD one, huh?), some known transport properties of various segments gets thrown into the mix. This is, of course, one of the simplest diagrams from this paper.

So people have been doing this stuff for many years (that last paper is 26, the same age as my daughter). As time has passed, our understanding of both the structure and function of these areas of the medulla has improved, allowing a mathematical model to be created. The original model by Anita Layton is illustrated in the next figure. I will let you pull the paper if you want the key to the abbreviations.

AJP Renal 300:356, 2011

AJP Renal 300:356, 2011

In this version, certain assumptions were made about the regions in which these segments lie.

The new model adds to this 2011 version, with further refinements about the spatial relationships and how oxygen would traverse the interstitial goo at various levels. They hope to work further functions into their models in the near future, things like the nitric oxide system and acid-base handling.

I have not done this paper justice; I am merely an MD, at best a humble biologist. I can appreciate how an elegant model can direct new hypotheses and future experiments. I'm afraid, though, that when I model a kidney it will be something like my final figure...

Click for original source

Click for original source

 

 

 

 

 

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Kidney Physiology in People: xBio

Apr 29 2014 Published by under EB2014

Scientists do a lot of stuff to cells in culture and rodents in plastic boxes, but ultimately we often want to better understand the human condition. It's always exciting for me, as a medical doctor, to see the sorts of translational studies that bring concepts from bench to bedside, so to speak.

Improved survival at what cost?

Improved survival at what cost?

Prenatal steroid exposure promotes expression of renal injury indices in African American females

TanYa M. Gwathmey1, Mark C. Chappell1, Patricia A. Nixon2, Lisa K. Washburn3

1Hypertension and Vascular Research, Wake Forest School of Medicine, Winston-Salem, NC,2Health and Exercise Science, Wake Forest School of Medicine, Winston-Salem, NC,3Dept of Pediatrics, Wake Forest School of Medicine, Winston-Salem, NC

 

 

Peri- and neo-natologists have know for many years that term delivery is preceded by a burst of cortisol from the fetal adrenal glands. This surge of steroid produces an increase in surfactant production by the fetal lungs, making them ready for postnatal life. It may also help drive kidney maturation for the external world.

In the 1980s betamethasone, a pharmacologic glucocorticoid similar to cortisol, became standard treatment for preterm labor. Women who presented advanced in labor might not receive it, because it would not get to the fetus in time. Those who would likely keep the critter in utero for another day or two got the shot.

Full-term is 37-38 weeks of estimated gestational age (EGA), based on the time from the last menstrual cycle (depending on which classification system you use). Nephrogenesis is not complete in the human fetus until 36 weeks EGA, so anything done in pregnancy prior to that time may have a substantial impact on future kidney structure and function.

The present study examined measures of kidney function in 14-year-old African American girls with or without prenatal exposure to betamethasone. First question: why girls? Turns out the sample of boys in this cohort is insufficient for these sorts of comparisons.  The girls were classified in 3 groups: Full term; Preterm without betamethasone; and Preterm with betamethasone. Both preterm groups had similar degrees of prematurity, averaging 28 weeks EGA. All of these kids are fairly similar in many ways, and all have "normal" blood pressure; however, the preterm girls, both with and without betamethasone, trend higher within the normal range (reported at an earlier meeting).

A number of markers of kidney health were presented in the current poster:

  • 8-isoprostane, a marker of oxidative stress
  • Angiotensinogen, the precursor of angiotensin
  • Angiotensin II
  • Microalbuminuria

Premature girls showed higher levels of urinary angiotensinogen, angiotensin II, and microalbuminuria, with trends to higher levels with betamethasone exposure. Betamethasone exposure increased 8-isoprostane in the urine over full-term girls; preterm subjects without betamethasone exposure had levels intermediate to the other groups.

Obviously these results are not the startling, clear-cut, "eureka" differences that we are used to seeing in studies of models. The numbers are fairly low, with only 10-20 subjects per group. People are less enthusiastic about controlling other variables than our animal or cellular subjects. We do not yet have information on physical activity, body habitus, perinatal exposure to other drugs, and a million other variables that may affect renal health.

We also do not have a non-African-American control group. Blacks in this country have a disproportionate risk of prematurity as well as hypertension and chronic kidney disease. While these studies suggest that being born early and getting betamethasone are both bad for African American kidneys, we do not know if these factors are different for the white population.

Now, don't get me wrong. Betamethasone treatment has improved respiratory issues (along with administration of surfactant at birth), and a long-term risk of hypertension and kidney disease beats dying at birth of prematurity and respiratory distress. It is important that we recognize effects of these agents so we can come up with strategies to mitigate their consequences.

As always, further study is in order. And these investigators are on the case.

 

 

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Award-Worthy Renal Abstracts at #xBio

Apr 21 2014 Published by under EB2014

Pre- and post-doctoral researchers run the world of science. Sure, Principal Investigators get the credit, but our students and fellows actually perform the experiments and make the magic happen. At Experimental Biology each year (#xBio is the official hashtag), abstracts from trainees get considered for possible awards, with finalists judged on their presentations at the meeting.

Click to enlarge

Click to enlarge

All of the finalists will present poster versions of their work on Sunday, April 27, at the Renal Section's Posters and Professors Session. This event runs from 5:30 - 7:30 in Marina Ballroom DE of the San Diego Marriott Marquis & Marina (Level 3 of the South Tower; see the map). In addition to viewing some excellence science, you will get a chance to meet up-and-coming physiologists as well as hobnob with us more senior kidney folk.*

What if you can't make it Sunday evening? Below I have collected the information on the other presentations of the award-finalists' endeavors. Now you have no excuse for missing these amazing works of modern science!

 

 

 

Predoctoral Excellence in Renal Research Finalists

Gerasimova

University of California-San Diego & VA
What makes SGLT2 inhibition so effective in lowering blood glucose in diabetes?
Poster Sunday, 4/27:  689.5/A281
Platform Tuesday, 4/29: Room 25B, 9:00

Kasztan

Medical University of Gdansk
Mechanism of purinergic action on glomerular permeability for albumin
Poster Sunday, 4/27:  692.3/A319

Pollow

University of Arizona
T cell-dependent hypertension is attenuated in female mice during angiotensin II infusion
Poster Tuesday, 4/29: 1136.10/A751

Richards

University of Florida
Regulation of NCC and the WNK cascade by the circadian clock protein Per1 in murine distal convoluted tubule cells
Poster Tuesday, 4/29: 1109.5/A544
Platform Tuesday, 4/29: Room 22, 8:45

Rudemiller

Medical College of Wisconsin
Mutation of SH2B3 attenuates Dahl SS hypertension via inflammatory signaling
Poster Tuesday, 4/29: 1136.15/A756
Platform Tuesday, 4/29: Room 25B, 9:30

Postdoctoral Excellence in Renal Research Finalists

Ares

Henry Ford Health System
Fructose stimulates phosphorylation and trafficking of the Na/K/2Cl cotransporter in rat thick ascending limbs
Poster Tuesday, 4/29: 1109.2/A541
Platform Tuesday, 4/29: Room 22, 9:45

Collier

University of Iowa
Acid activates ENaC and enhances salt taste in human subjects
Poster Wednesday, 4/30: 1181.10/W354
Platform Wednesday, 4/30: Room 22, 12:15

Itani

Vanderbilt University
A potential role of memory T cells in hypertension
Poster Tuesday, 4/29: 1074.1/A76

Shepard

Johns Hopkins University School of Medicine
 Elucidating the role of a renal proximal tubule-specific olfactory receptor
Poster Monday, 4/28: 892.42/A456
Platform Monday, 4/28: Room 25B, 8:30

Wen

University of Nebraska Medical Center
Deficiency in NBCe2 causes distal renal tubular acidosis
Poster Monday, 4/28: 891.2/A413
Platform Monday, 4/28: Room 25B, 9:15

Or you can download a Printable File of these presentations in PDF format!

These works look absolutely amazing! All ten of these emerging scientists deserve congratulations, as well as our presence.

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*I will provide autographs upon request; no NSFW body parts, please!

 

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Countdown to #xBio 2014

Apr 11 2014 Published by under EB2014, Societies and Meetings

Two weeks from today I leave my home and head to glorious San Diego for Experimental Biology 2014, the annual gathering of the organizations that comprise the Federation of American Societies for Experimental Biology, AKA FASEB. My favorite of these groups, the American Physiological Society, once again asked me to blog the meeting. I have finally gathered scheduling information and abstracts to organize my activities.

I will be attending and summarizing Saturday's session on storytelling for scientists, presented by Randy Olson. He has followed that traditional career trajectory from tenured professor to film school, and he wrote two books about scientists and communication skills (or, more accurately, lack thereof). I heard him speak at a screening of his film, Flock of Dodos, a few years back. His latest book, written with Dorie Barton and Brian Palermo, is Connection: Hollywood Storytelling Meets Critical Thinking. I am looking forward to seeing how his message has morphed over time. Obviously, I love communications, so this session is right up my alley.

Saturday also starts more traditional fare, including the Cannon Memorial Lecture. James M. Anderson of the NIH will present his talk, The Contribution of Paracellular Transport to Epithelial Homeostasis. As someone who teaches renal pathophysiology, this topic will be relevant. Look for some live tweets during this session.

Of course I will also attend and discuss the Gottschalk Award Lecture for the Renal Physiology Section on Monday afternoon. Susan Wall of Emory University will present her work on The Role of Pendrin the the Pressor Response to Aldosterone.

I have selected a number of abstracts that interest me; next week I will contact authors about coverage, either through email interviews, conversations on site, or perhaps even videos of them at their posters. See something in the program you think I should explore? Drop me a line via twitter (@phlane) or email (pascalelane [at] gmail...you know the rest).

Be sure and follow me on twitter as well as @expbio, and track the official meeting hashtag (#xBio) while you're at it. You may not be gazing on San Diego harbor in the sunshine, but you can still get a feel for the science at the meeting.

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Give a Bit of Yourself

Feb 14 2014 Published by under Gadgets, gizmos

$299.95

The best Valentines are personal, especially if you are a Special Snowflake whose descendants will honor you in perpetuity. To this end, you can leave offspring born and unborn your DNA, preserved at room temperature for all time in the DNA Time Capsule:

This is the patented, triple-sealed time capsule that securely stores your genetic fingerprint for use by future generations. Preserving one's DNA in the present enables future scientific advances to reveal any predispositions to disease—currently undetectable by today's methods—a family's genetic makeup may bear. Dispensing with the need for long-term refrigerated storage in a lab, a chemical matrix of dissolvable compounds stabilizes DNA within a blood sample at room temperature (blood provides a higher quality and quantity of DNA than samples taken from cheek swabs), preserving the sample for over 100 years. A blood sample can be taken at your preferred medical facility or using the included kit. Once a sample is secured within the capsule, it can be stored within a home or bank lock box for decades until one's progeny submits it for genetic analysis.

Yup, for just under $300 you can leave your genetic code behind for at least a century! Now I am unclear on why your descendants would want to test your DNA rather than just doing their own ("Look Grandpa could have developed dementia if he hadn't been hit by that train!"). Maybe researchers might want to pinpoint when a mutation occurred in a kindred, but that would be for research not any practical benefit (that I can see) to your future relatives.

Maybe I am missing something that the good folks at Hammacher Schlemmer thought about, but I seriously doubt it. They just have a gizmo to sell, and they hope someone with $300 to spare will buy it.

Personally, I would rather have a giftcard for shoes.

Happy Valentines Day anyway!

 

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Art & Fashion, Meet Science

Feb 07 2014 Published by under Fashion (or not)

Loving this scarf.

Loving this scarf.

Are you looking for a gift for someone special? Valentines Day is next Friday, you know. If your sweetie wears scarves and loves science, you should give a sciencey scarf from Michelle Banks. Today I am wearing my latest acquisition, Portrait of a Human. Each panel on the 72 inch silk charmeuse scarf shows her rendition of a different cell from the human body.

Below is a better view of the details of the scarf; I wish this photo did justice to the vivid colors.

Click to enlarge

Click to enlarge

What could say "Be my valentine" better than a scarf with a normal ECG, Heartbeat? Neurons and various microbes also adorn silk in this Etsy shop. What if your sweetheart is not a biology junkie? No fears; Michelle produces other wonderful designs with an astronomical flare.

Of course, not all of the world can rock a scarf like yours truly; for the less fashion minded, original watercolors of various designs and other ornaments can be had.

So buzz on over the the Artologica Etsy Shop and buy a colorful piece for Valentines Day or some other occasion. You will not regret it!

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The Real Problem with Marie Curie

Nov 18 2013 Published by under [Science in Society]

So hot...like radioactive...

The internet went all a-twitter over the weekend about a video posted by Joe Hanson (@jtotheizzoe) in which he imagines the scientist bobble-heads in his collection joining him for Thanksgiving dinner. In it, the Einstein bobble-head repeatedly makes sexual advances toward the Curie figure, assaulting her at the end of the piece.  Certainly tasteless, even with bobble-heads, especially given recent events in the world of online science communication. Sophomoric? Certainly. Criminal? Hardly.

This video is part of Hanson's work for PBS Digital Studios, an ongoing series called It's Okay to be Smart. I am still unclear what this video had to do with Thanksgiving, being smart, or anything else, other than an excuse to play with bobble-heads. An apology eventually appeared, but the video remains on the internet. I wish PBS would take it down, but they haven't. There have been calls to fire Hanson. That seems a bit over-the-top to me, but then I watch Family Guy.

Then it came out that Joe Hanson will be moderating a session at Science Online in 2014. Moderaters were selected weeks ago; those in control could not have anticipated this unfortunate turn of events. At this point I tweeted a tongue-in-cheek suggestion that we dress up as Curie and beat the snot out of him at his session. I imagined a group of 20 bobble-head look-alikes coming at him...well, my attempt at humor also bombed. Repeated tweets have called for a serious, non-violent response.

It's kind of like TSA began running twitter: "Do not joke about weapons on the plane" or violence at the unconference.

What I would like to point out is the real problem here: Marie Curie is the only female bobble-head! In that setting, gender becomes the most obvious characteristic of the bobble-head. Why should the male bobble-heads consider her scientific accomplishments when she is merely the token woman? Clearly, her only raison d'etre must be her sex! In real life, such tokenism contibutes to an environment that permits marginalization of women (and other minorities) and likely contibutes to harassment. Does that excuse Einstein's douchebaggery? Hell no - dudes (even resin bobble-heads) should be able to keep their pants on and zipped! But the dynamics would have been different had Rosalind Franklin, Gerty Cori, and Linda Buck bobble-heads joined the party. Why can't I buy bobble-heads of these Nobel laureates? It's like Marie Curie is the only woman scientist ever!

So perhaps we should all step back and take a deep breath. We have an episode here that illustrates a lot of issues that lead to a hostile environment for women in science. No one has been physically harmed, although good taste was violated. Let's use this episode to learn and grow, rather than blame and shame.

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Why I Will Be There: #Scio14

Nov 15 2013 Published by under [Information&Communication]

Thursday I did something I have never done before; I sat at my computer waiting for 2:00 pm CST when I could start clicking the link for Science Online Together 2014. All went well for me, and I will be returning to Raleigh in February for another round of the unconference.

Some have recently made clear their intentions to not be at the upcoming gathering (see here and here). Several factors entered into my alternate decision.

I came to Science Online at a different point in my journey from many others. I had scaled the rarified heights of academia to become a tenured full professor. As I embarked on a new journey, to create a news magazine for the American Society of Nephrology, I needed to learn about new-fangled things like blogging and Facebook and Twitter. Science Online 2011, my virgin year, gave me insights into the interactions possible between academic and popular media, as well as the potential interplay of Web 2.0 content and the dead tree media of my youth. That was the last really "small" Science Online, with our venue at Sigma Xi bursting with energy. I felt like I met most of the attendees at some point in time, and I learned a lot that has been put to work in my professional life. Sessions on narrative structure and writing tools have enriched my work as well. I now give talks to faculty about ways to get writing done, much of which is information intially gathered via Science Online sessions. I have recruited several articles for ASN Kidney News from Science Online participants. The magazine also hires journalists for events, so some of these are paying gigs for the freelancers in the crowd!

I also have a guilty secret. One of the reasons I love academic medicine is my love of writing. Had I not been a doctor, I likely would have majored in English and ultimately gone on to an advanced writing degree of some sort. Most academics do not understand this attitude; they hate the writing, even while acknowledging its role in their success. Attending Science Online was like visiting the Mother Ship. All of these people who liked science and writing existed! I was not alone! I also love it now when my husband likes a book, and I can say I have met the author.

Like all meetings, Science Online is not just about work. Evenings include a lot of chatting and networking (and often drinking), just like those at my professional meetings. If anything, I attend more sessions at Science Online than at "real science" meetings, simply because the unconference venue is not adjacent to the hotel. Once you are there, you may as well be in a discussion session since you can't run back to your room and "work on your paper" (AKA chill out with Diet Coke and a novel or daytime TV).

This will be my fourth Science Online, and I see the meeting at a crossroads. First, the venue (North Carolina State University McKimmon Center) and participants expanded in 2012 and 2013. Many of these participants remain unfamiliar to me; the meeting has already crossed the "intimacy" line (and not in the slimey sense of the word; you know what I'm talking about). Also, last year the informal organizational group became a real entity with a dot-com web site. Spin-off conferences, in a variety of locales and on selected topics, sprung up in 2013 as well. The people and concept of Science Online are evolving, and growing pains are inevitable. Will Science Online become a more formal organization with a bigger, more professional conference? Or will it step back and downsize into several smaller gatherings in an attempt to maintain the "community" feel?

I do not know which way things will go, but I plan to make my opinions known. If things proceed in a direction I do not like, I may be writing one of those "Why I'm Not" posts next year. In the meantime, I know I have achieved things I would not have without the Science Online experience. I will be there in 2014, for the learning and the party - just like every other meeting I attend.

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Down with Glam; Up with Fast & Cheap

Apr 03 2013 Published by under Publication, Research issues

A lot of folks are trying to reinvent the way we share research. I cannot remember the last time I read a paper journal; even with traditional publishing models, the dead tree format ends up in the recycling. When I need to know something, I search online via PubMed or Google Scholar. Topics I want to keep up-to-date at all times have shared searches that update me periodically.

Some journals will now be online-only, either with a fairly traditional publishing model or a more liberal acceptance policy (PLoS One, for example). Platforms such as Figshare allow investigators to make raw data publicly available and citable, even if not included in the final paper for a study. Recently, Beyond the PDF 2 took place in Amsterdam where visionaries gathered to once again discuss the printing press of this century. More information can be found about this conference and conversation here.

PeerJAfter scanning this discussion, I began playing around with PeerJ. The model is intriguing; you pay a lifetime fee up front. You can freely pre-publish works (PeerJ PrePrints) and get public feedback . With a mouse-click, you can send your manuscript to peer review which will be based on scientific soundness of the research without attention to impact or "sex-appeal" factor of the work. The goal here is PLoS One without the high publication fees. For $99 you can become a basic lifetime member, able to submit unlimited public "pre-publications" and publish one peer-reviewed article for life. Of course, you will be expected to also review at least one article for life. All authors on the article must have memberships; if you wait until article acceptance to join, fees will be ~30% greater. Right now, content in PeerJ is limited to biomedical science and health issues. PeerJ only publishes research articles. Literature review articles, commentaries, case reports and other works may instead be submitted to PeerJ PrePrints.

My biggest concern took some digging about the web site:

PeerJ will be indexed in all major Abstracting & Indexing databases, including for example PubMed, PubMedCentral, GoogleScholar, and Microsoft Academic Search. We will also be applying for indexed status in services such as MedLine and Web of Science.

This model certainly has the right price; $99 runs less than the page fees for my last journal submission. As a senior professor, this site may be perfect for some of my less impressive results that I just want to get out there. When I was early in my career, PeerJ would have let me get some new data peer-reviewed and published and still make my grant deadline.

What other new-wave publishing services deserve exploration? Any Whizbangers have experience with PeerJ or similar platforms?

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