Archive for: April, 2012

A Brief Interlude

Apr 30 2012 Published by under Women in Medicine, Women in Science

First, a hearty thanks to all who read my posts from Experimental Biology. Blogging a meeting was a challenging yet fun experience. It enhanced my experience, and I hope it gave those "reading at home" some new information.

I flew home on Wednesday and went out again on Thursday for a committee meeting in Washington, DC, arriving back in Oklahoma on Friday about midnight. I am now covering the inpatient service until Thursday...when I leave town again.

I have another post or two from EB waiting for me to organize my material.

In the meantime, I finally solved a problem over on my site Academic Women for Equality Now. I wanted to share a 10+ MB PDF that contains women leadership scores for every college of medicine (COM) in the US. That file exceeds the upload/download capabilities of my web host. Today's post over there provides links to access the file in Google Docs. I hope you will all click on over and download the file. If you work at a COM in the book, please share it's status with your leadership. I hear a lot of COM deans et al state that their place is doing fine. They have female faculty and some in leadership positions. Until they see where each COM stands in relationship to the others in the country, they can't really know how they are doing.

Stay tuned; I will be back with more science and other stuff later in the week.

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So Long, #EB2012

Apr 25 2012 Published by under EB2012 Meeting, [Information&Communication]

So long, farewell, etc...

My suitcase lies open on the bed, awaiting the cooling process to make my hair iron packable. If I knew more physics, I might be able to discuss why this takes so long. Lucky for you, physics bored me.

I have material for at least two more posts that may happen soon, or they may wait until next week. Tomorrow I must jet off to a meeting in DC. I hate it when my day jobs interfere with le blogging.

I had a great time blogging Experimental Biology. I planned my meeting in more detail than I have since my very first conference in fellowship. I saw a greater breadth of sessions, took better notes, and synthesized my thoughts. I learned a hell of a lot this year. Even if I am not an official meeting blogger, I may start approaching conferences in this manner. I have always learned by organizing the information in writing. In college and medical school I used a typewriter; now my thoughts go out in the blogosphere or in my Dropbox. Same process, different tools.

Of course, I really enjoyed catching up with my IRL and OTI friends. You all know who you are. And even if I never accomplished anything else, I will leave behind a Storify of the taint talk.

They say it taint over (sorry, I had to go there) 'til the fat lady sings, and she is warming up for her farewell to #EB2012.

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#EB2012: Renal Section Honors

Apr 24 2012 Published by under EB2012 Meeting, [Biology&Environment]

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Di Feng makes an award-winning presentation

Every year the Renal Section of the American Physiological Society grants awards to undergraduate and post-doctoral trainees for work they submit and present at the meeting. A committee selects 5 finalists based on the abstract submitted, and their presentations are judged during the Posters and Professors Session that was held on Sunday, April 22.

Undergraduate Finalists

  • Justine Abais, Virginia Commonwealth University
  • Di Feng, Medical College of Wisconsin
  • Teresa Kennedy-Lydon, Roya Veterinary College
  • Jacob Richards, University of Floriday
  • Ryan Cornelius, University of Nebraska

The award went to Di Feng for her work :

Genetic regulation and functional relevance of the p67phox gene in salt-sensitive hypertension
Di Feng1, Chun Yang1, Jozef Lazar2, David Mattson1, Paul O'Connor1, Allen W. Cowley, Jr. 1,3. 1Physiology Department, 2Human and Molecular Genetics Center, 3Cardiovascular Center, Medical College of Wisconsin, Milwaukee, WI

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Feng receives her plaque while Jacob Richards looks on

A narrow region on rat Chr 13 was identified to harbor salt- sensitive genes. p67phox, a cytosolic subunit of NAD(P)H oxidase, is located in this region. We have previously found that on a high salt diet, the renal outer medulla (OM) of Dahl salt-sensitive (SS) rats exhibited higher levels of p67phox expression and NAD(P)H oxidase activity than salt-resistant congenic rats that contain the p67phox allele from the salt-resistant Brown Norway rat. We generated the first p67phox null mutant (p67phox-/-) SS rat in which we observed significantly reduced salt-sensitive hypertension. In our present study, we sequenced a 1650 bp promoter region and found that the SS allele of p67phox had a 204 bp deletion and four SNPs compared to the BN allele. The activity of the SS p67phox promoter was 1.7 fold higher than that of the BN p67phox promoter. We further characterized p67phox-/- rats and showed that they had a 40% reduction in OM H2O2 levels measured from interstitial fluid collected by microdialysis. Respiratory burst responses of peritoneal macrophages to phorbol 12-myristate 13-acetate were abolished in p67phox-/- rats. p67phox-/- rats also showed reduced renal injury, including reduced OM fibrosis, infiltrated T cells and macrophages, and glomerulosclerosis. These data provide new insights into the genetic regulation and functional relevance of p67phox in salt-sensitive hypertension. (HL-82798; HL-29587)

Postdoctoral finalists included:

  •  Krishna Boini, Virginia Commonwealth University
  • Richard Grimm, University of Mryland
  • Elena Mironova, University of Texas-San Antonio
  • Ann Riquier-Brison, University of Southern California
  • Ankita Roy, University of Pittsburgh
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Dr. Grimm gives me a guided tour of his work

Richard Grimm took home the award for this submission:

SPAK, OSR1 and Cab39/MO25 form an Interdependent Signaling system which Regulates Thiazide-Sensitive Salt- transport, Distal Tubule Mass and Blood Pressure
P Richard Grimm1, Tarvinder Taneja1, Jie Liu1, Richard Coleman1, Yang-Yi Chen1, Eric Delpire2, James B Wade1, Paul A Welling1. 1Physiology, University of Maryland School of Medicine, Baltimore, MD, 2Anesthesiology, Vanderbilt School of Medicine, Nashville, TN

STE20/SPS-1-related proline-alanine-rich protein kinase (SPAK) and, Oxidative Stress Related Kinase (OSR1), co-localize at the apical membrane of the Thick ascending Limb (TAL) and Distal Convoluted Tubule (DCT) and both regulate the potassium- dependent sodium-chloride co-transporter, NKCC2, thiazide- sensitive sodium-chloride cotransporter, NCC in vitro. Yet genetic ablation of SPAK in mice causes a salt-wasting nephropathy that is restricted to the DCT, reminiscent of Gitelman’s syndrome. Here, we explore why proper DCT function is especially SPAK- dependent. In the TAL of SPAK-/- mice, OSR1 and Cab39/MO25, a newly described OSR1/SPAK regulatory protein, remain at the apical membrane where they function with a compensatory increase in the AMP-activated kinase (AMPK) to hyper- phosphorylate NKCC2. By contrast, the OSR1/SPAK/M025 signal transduction apparatus is completely disrupted in the DCT. OSR1 and MO25 become largely displaced from the thiazide-sensitive sodium-chloride cotransporter, NCC, and the apical membrane. OSR1 redistributes to dense punctate structures within the cytoplasm. These changes are paralleled by a dramatic decrease in NCC abundance and phosphorylation. Without SPAK and the proper localization of OSR1 and MO25, phosphorylation- dependent regulation of NCC by dietary sodium restriction is lost. SPAK-/- mice also exhibit a decrease in the mass of the distal convoluted tubule, exclusive to DCT1. As a result of the interdependent nature of OSR1 and MO25 on SPAK in the DCT, SPAK-/- mice are highly sensitive to dietary salt-restriction, displaying prolonged negative sodium balance and hypotension.

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Dr. Grimm wins

 

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#EB2012: You Saw This One Coming

Apr 24 2012 Published by under EB2012 Meeting, [Biology&Environment]

On Monday, April 23, a symposium titled Impact of Environmental Estrogens and Androgens on Human and Animal Health and Reproductive Function convened at Experimental Biology. Hugh S. Taylor, MD of Yale presented an elegant talk on environmental estrogens and disorders of the reproductive tract. One point he made provided what I consider an elegant explanation for how exposure to diethylstilbestrol (DES) in utero could produce weird vaginal tumors many years down the line.

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Exposure to DES also produces abnormal reproductive anatomy at the histological level. Turns out normal mullerian development into the female reproductive organs depends on orderly segmental expression of Hox genes, which have estrogen-response elements. As shown in his talk (free full text here), DES exposure shift their expression segments posteriorly (see figure). This shift means that glandular cells normally confined to the uterus end up in the vagina. These cells seem more vulnerable to carcinogenic forces that the usual epithelial cells, and displacing them into the vagina offers them exposure to carcinogenic hits. Thus, these women end up with vaginal adenocarcinoma because they have "adeno" cells in their vaginas.

The other study that you may have heard about, especially if you follow me or @scicurious on twitter involves anogenital length and fetal androgen exposure. Yes, Sci had joined me in the session and we had a blast tweeting the taint! I have Storified the encounter below for posterity (Hey, Nobel Committee, why don't you have an award for meeting tweeting?).

[<a href="http://storify.com/PHLane/it-ain-t-nothing-else-it-tainttweets" target="_blank">View the story "It ain't nothing else...it #TaintTweets" on Storify</a>]

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#EB2012: A Pendrin for Your Thoughts

Apr 23 2012 Published by under EB2012 Meeting, [Biology&Environment]

Pendrin, also known as SLC26A4, is a luminal anion transporter. Anions, molecules with a negative charge, include chloride, bicarbonate, iodide, and others. The family of similar transporters (see figure) have some functional overlap, although knock-out studies confirm some individual transport specificities.

A child that lacks pendrin has Pendred Syndrome. This usually occurs as a monogenic recessive disorder (both parents have a mutation in the pendrin gene) although a few families have a digenic inheritance where the mutation occurs in a gene that controls the creation or function of pendrin. The major manifestation of the syndrome is progressive hearing loss; this syndrome may produce as much as 10% of congenital familial deafness. The syndrome also causes enlargement of portions of the inner ear and an enlarged thyroid gland (or goiter). The function of the thyroid remains normal, but it accumulates material and grows.

After Richard J. H. Smith reviewed the features and genetics of the syndrome, Philene Wangemann showed the role of pendrin in ear development in mice.

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Using conditional knock-outs of the gene, her group has established a critical 2-day period in gestation where lack of pendrin results in deafness. The mice also develop enlargement of the cochlea, just like humans. For her review on pendrin in ear development click here (PDF is free!).

So why does the thyroid enlarge in this syndrome? For those of you who are not endocrinologists (I may not be one, but I do sleep with one), thyroid hormone contains iodine.That's why a low iodine diet so profoundly affects growth and development (AKA cretinism). Since this family of transporters helps move iodine about, the thyroid can enlarge, even though its ability to make and release the hormone is intact. This topic was addressed by Peter Kopp.

Finally (saving the best for last?) Vladimir Pech reviewed the role of pendrin in blood pressure regulation. Pendrin resides in the type B intercalated cells of the cortical collecting duct where it exchanges chloride and bicarbonate between the lumen and the cell. Pendrin knock-out mice have normal blood pressures; however, during states where aldosterone would be activated (low sodium and low volume), pendrin mice are unable to conserve sodium as avidly as those with the transporter.

Huh? Most aldosterone-dependent sodium reabsorption occurs via the ENaC channel in the principal cell. How does a lack of pendrin tell another cell to behave differently? It does so by decreasing the activation of ENaC which requires a cleavage step to work. Perhaps this occurs via altered luminal pH or bicarbonate concentration, or some other signal that impairs the milieu for sodium channel activation. More to come; click here for a nice review (unfortunately not available freely online).

Ear and kidney abnormalities often occur together in children. Pendrin may provide one link to explain some of these issues.

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#EB2012: Competent or Not?

Apr 23 2012 Published by under [Education&Careers]

Bernard: Look at those chops

As we slipped into the lecture hall, a particularly fierce image glared at us from the screen. Claude Bernard's portrait greeted us to the lecture in his honor. The speaker, William Galey, took the podium, and proved that this visage was not necessary for teaching excellence.

Dr. Galey spent most of his career at the University of New Mexico and gave a wonderful history of its move to a case- or problem-based curriculum over the years. He also spoke of ongoing efforts to develop competencies for medical students and to drive our curricula in that direction. In his current position at Howard Hughes Medical Institute, he helped develop (with the Association of American Medical Colleges) a listing of competencies for students entering and graduation from medical school (available here).

My favorite part of his musings involved the central nature of physiology and medicine. Really, we need to start embroidering samplers with this quote:

Physiology is to medicine as physics is to engineering.

Later in the day, at What Do Competencies Have To Do With My Teaching? the audience got a more thorough look at the concept of competencies and their relationship to standards, objectives, goals, and assessment. Competencies first came about in graduate medical education, but now have extended into the pre-medical and medical curricula. Every objective and every assignment should be linked to achieving a particular necessary competency. Curriculum maps will make your head spin, but they can be quite valuable to identify gaps and other issues.

Competencies may soon be more as some groups work toward defining these skills for faculty. Particularly in academic medicine, new faculty often have minimal, if any, pedagogical training. Other skill gaps may present as well. As a person who works in faculty development, I appreciate these efforts so I can figure out what our faculty members may need.

Like it or not, we are educators. Even though our primary job may be research or patient care, at some point we will have to help train someone else. If we cannot say what they need to know, we cannot know if we succeed.

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#EB2012 #Navar: Reflections on the Work of a Lifetime

Apr 23 2012 Published by under EB2012 Meeting, [Biology&Environment]

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Dr. Navar and his entourage, pre-lecture

The final official event of Saturday actually provided the official opening of the meeting for the American Physiological Society (APS). Current president Joey Granger walked us through 125 years of the APS, including the founding of the umbrella organization FASEB (Federation of American Societies for Experimental Biology) 100 years ago. He then introduced the speaker, Gabby Navar, who presented his lifetime of work in renal physiology and the role of the kidney in hypertension (click here for more background).

Science takes place in baby-steps. Even a paper in a glamour journal with years of data, like a toddler's first efforts, is just as likely to lead to falling back on a full diaper as a movement forward. Take enough of these steps, and you can eventually get somewhere. You may always risk a trip and a fall, but with time you move forward.

Dr. Navar's contributions to science brought to mind two major observations. First, hypertension is not a disease. A disease has a cause and an effect. While the effect may be a single physiological measurement such as blood pressure, its causes clearly involve multiple genes and environmental factors. We should think of it as a syndrome.

Syndrome generally means a cluster of symptoms; the origins of the word signify concurrence. For example, a microangiopathic hemolytic anemia with kidney damage leads to a diagnosis of hemolytic uremic syndrome. This syndrome may be the result of several known diseases as well as some not yet characterized. I propose that hypertension, while not a cluster of abnormalities, is a syndrome in  a similar sense. Multiple diseases, defined and not, can cause high blood pressure as their sole manifestation.

The other point I considered overnight was how essential animal research has been in our advances in hypertension. We simply would not be able to tease out the complex relationships between neural, renal, and other mechanisms in blood pressure control without the use of animals.

Congratulations to Gabby Navar for a great talk and a good start to a great meeting.

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#EB2012 #apsACE: My First Storify

Apr 22 2012 Published by under EB2012 Meeting, [Biology&Environment]

I attended an excellent session on the need to increase transparency and public outreach in animal experimentation. I tweeted throughout the session, and I have assembled the highlights using Storify. I had hoped to include original observations from others in the room, but most of the other tweets were retweets of me (or the others tweeting forgot to use the hashtag).

I am reminded of the following facts:

  • People are programmed to want the world to make sense
  • Nature abhors a vacuum
  • If there is no story to make sense of something, people will supply their own
  • If you want the truth to be known, you should supply the story

Until scientists supply the stories to justify their research on both scientific and ethical grounds, people will remain suspicious of our intentions. We must reach out to the public and let them see and feel and hear our stories; not hide in a vivarium-bunker.

[<a href="http://storify.com/PHLane/apsace-public-outreach-and-animal-research-toolki" target="_blank">View the story "#apsACE Public Outreach and Animal Research: Toolkit for Investigators" on Storify</a>] 

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#EB2012 #apsComm: Using New Communication Tools

Apr 22 2012 Published by under EB2012 Meeting, [Information&Communication]

Yesterday, April 21, I had the pleasure of serving on a panel at Experimental Biology discussing the use of blogs and other social media to do public outreach. Yes, I got to be the old lady on the stage with Dr. Isis, Danielle Lee, and Jason Goldman at the session moderated by James Hicks. A good time was had by all (although Isis got a bit sweaty in her headdress replete with golden cobra) as we pontificated on our own uses of the brave new world of the internet. By unanimous request of the audience (OK, more like there were no objections) we have each agreed to share our slides on a number of platforms. I am also placing mine here.

Thus far many other sessions have addressed the use of these relatively new tools for communication. At their heart, Facebook, Twitter, and Blogs merely provide the latest pigment to spread on cave walls. Since the dawn of time humans have desired to tell their stories; these new media let us do it more widely and permanently than ever before.

The Animal Care and Experimentation Committee provided a Toolkit for Public Outreach (#apsACE) that addressed the need for transparency and engagement, rather than the bunker mentality that has prevailed at most institutions. Even this morning in accepting the Claude Bernard award, William Galey mentioned all the education resources available online. For today's students, access to information is not a problem. However, we must make sure that they learn to evaluate the reliability of information and sources before they use them in critical applications like patient care.

I ended my slides with a still from the movie Meet Me in Saint Louis. In its early scenes, a suitor calls the eldest sister, Rose, on that new-fangled invention, the telephone. A prolonged discussion ensues over whether or not a respectable girl should accept a proposal via an "invention". Similar attitudes toward the phone can be seen in the first season of Downton Abbey. All of the technology we use today was once considered radical, experimental, and unnecessary (I can remember when email elicited similar reactions to those about the phone). Social media will soon be just how we communicate, and we will move onto sessions on other cutting-edge topics, like flying cars or Star Trek transporter physiology.

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#EB2012: Physiology Education

Apr 22 2012 Published by under EB2012 Meeting

Dr. William (Bill) Galey will deliver The Claude Bernard Distinguished Lectureship of the APS Teaching of Physiology Section on Sunday, April 22, at 10:30 am in Room 27 of the San Diego Convention Center. If you tweet about the lecture, please use #Galey as your hashtag.

Bernard and the Lectureship

The Claude Bernard Distinguished Lectureship is awarded to an established investigator with a history of excellence in education who is making outstanding contributions to teaching and learning. This award is not restricted to APS members. The award is named for a 19th century French physiologist who pushed science and science education from “product” to “process” by incorporating experimentation, demonstration, and other activities.

Bill Galey

Dr. Galey

Born in Boise, Idaho, Bill Galey grew up on a small farm and was fascinated by the birth, growth, and death of the animals about him. He always wanted to know "how and why" things, such as plants and animals, and even machines, work the way they do. He decided to study science because of his interest in understanding how things work.

He was the first member of his family to attend college. He ultimately obtained a PhD from the University of Oregon.  After fellowship at Harvard and a brief period in the pharmaceutical industry, he joined the University Of New Mexico School Of Medicine where he conducted research and taught medical and graduate students. Bill was active in the development and implementation of problem based learning as well as numerous other educational innovations while a faculty member at New Mexico and was a founding member of IAMSE. Subsequently Dr Galey held various administrative positions including Associate Dean for Graduate Studies and Interim Dean for Research at UNMSOM before joining HHMI in 2002.

Dr. Galey is currently Director of Graduate and Medical Education Programs at Howard Hughes Medical Institute, running HHMI's programs to enhance biomedical science graduate education and scientific training of medical students. Among the programs under his directorship are HHMI's Medical Research Fellows Program and the HHMI-NIH Medical Research Scholars Program, which provide opportunities for medical students to engage in an intensive year of research. Dr. Galey was instrumental in developing and conducting the HHMI partnership with the Association of American Medical Colleges known as Scientific Foundations for Future Physicians (SFFP), which sets out the scientific competencies needed by physicians to practice medicine in the 21st century. Graduate education efforts under Galey's direction include the very successful Med into Grad Program, which supports efforts of graduate programs to graduate PhDs with a strong understanding of medicine. Dr. Galey's group also administers HHMI's Gilliam Fellowship Program, which provides predoctoral support to individuals committed to creating a more diverse professoriate. A new program known as the HHMI International Student Dissertation Research Fellowship Program is being initiated to support international graduate students during their dissertation research. Dr. Galey and his group also developed and conducted a highly successful partnership with the NIH to integrate graduate training in the physical and computational sciences with the biomedical sciences in a program known as Interfaces.

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