Wednesday, October 4, 2017

Biomolecule Imaging Pioneers Share Nobel Prize

Today, the Royal Swedish Academy of Sciences has decided to award the Nobel Prize in Chemistry 2017 to Jacques Dubochet (University of Lausanne, Switzerland) and Joachim Frank (Columbia University, New York, USA), and Richard Henderson (MRC Laboratory of Molecular Biology, Cambridge, UK). The award is given "for developing cryo-electron microscopy for the high-resolution structure determination of biomolecules in solution"

Cool microscope technology revolutionises biochemistry

We may soon have detailed images of life’s complex machineries in atomic resolution. The Nobel Prize in Chemistry 2017 is awarded to Jacques Dubochet, Joachim Frank and Richard Henderson for the development of cryo-electron microscopy, which both simplifies and improves the imaging of biomolecules. This method has moved biochemistry into a new era.

A picture is a key to understanding. Scientific breakthroughs often build upon the successful visualization of objects invisible to the human eye. However, biochemical maps have long been filled with blank spaces because the available technology has had difficulty generating images of much of life’s molecular machinery. Cryo-electron microscopy changes all of this. Researchers can now freeze biomolecules mid-movement and visualize processes they have never previously seen, which is decisive for both the basic understanding of life’s chemistry and for the development of pharmaceuticals.

Electron microscopes were long believed to only be suitable for imaging dead matter, because the powerful electron beam destroys biological material. But in 1990, Richard Henderson succeeded in using an electron microscope to generate a three-dimensional image of a protein at atomic resolution. This breakthrough proved the technology’s potential.

Joachim Frank made the technology generally applicable. Between 1975 and 1986 he developed an image processing method in which the electron microscope’s fuzzy two-dimensional images are analysed and merged to reveal a sharp three-dimensional structure.

Jacques Dubochet added water to electron microscopy. Liquid water evaporates in the electron microscope’s vacuum, which makes the biomolecules collapse. In the early 1980s, Dubochet succeeded in vitrifying water – he cooled water so rapidly that it solidified in its liquid form around a biological sample, allowing the biomolecules to retain their natural shape even in a vacuum.

Following these discoveries, the electron microscope’s every nut and bolt have been optimised. The desired atomic resolution was reached in 2013, and researchers can now routinely produce three-dimensional structures of biomolecules. In the past few years, scientific literature has been filled with images of everything from proteins that cause antibiotic resistance, to the surface of the Zika virus. Biochemistry is now facing an explosive development and is all set for an exciting future.

About the Nobel Laureates

Jacques Dubochet, born 1942 in Aigle, Switzerland. Ph.D. 1973, University of Geneva and University of Basel, Switzerland. Honorary Professor of Biophysics, University of Lausanne, Switzerland.

Joachim Frank, born 1940 in Siegen, Germany. Ph.D. 1970, Technical University of Munich, Germany. Professor of Biochemistry and Molecular Biophysics and of Biological Sciences, Columbia University, New York, USA.

Richard Henderson, born 1945 in Edinburgh, Scotland. Ph.D. 1969, Cambridge University, UK. Programme Leader, MRC Laboratory of Molecular Biology, Cambridge, UK.

What can we use from this in teaching undergraduate A&P?

  • If you talk about imaging molecules in your course, this could be a way to garner student interest—considering that this is a current and ongoing effort in science. I always have a brief "shape is important in biological chemistry and here's what we can see with current tools" because they're going to see all those little odd-shaped rutabaga blobs in illustrations in their textbooks.

  • If you bring up microscopy in your course, perhaps describing the types of microscopy, adding a bit of info on this could help show students that microscopy is still evolving—in exciting ways.

  • Consider using the annual Nobel Prize announcements as a springboard to discuss the process of scientific discovery. 

  • Consider mentioning the other major awards for scientific achievement and discuss what the judges seem to value most about scientific discoveries. The Nobel Prize is the one everyone has heard of, so it's a great place to start.

  • Use the Nobel Prizes (and other awards) over time as a way to keep students aware of the history of, and progress, of human biology. One could also address the global diversity of laureates.  Or the lack of other kinds of diversity among laureates.

Want to know more?

Popular Information 

Scientific Background


Image - 3D structures (pdf 1.4 MB)

Image - Blobology (pdf 8.5 MB)

Image - Dubochet's preparation method (948 kB)

Image - Frank's image analysis (pdf 1 MB)

Cool Animations (literally)

Structure and gating of the nuclear pore complex

Ion gating in the sarcoplasmic reticulum membrane

Antibody structure

Native LDL particles
  • Kumar V, Butcher S, Öörni K, Engelhardt P, Heikkonen J, Kaski K, Ala-Korpela M, Kovanen P

Changes in the water and ion contents of organelles during apoptosis
  • Nolin F, Michel J, Wortham L, Tchelidze P, Banchet V, Lalun N, Terryn C, Ploton D
Adapted from press release at
Click each image for its source/attribution

Monday, October 2, 2017

Nobel Prize for Biological Clock Mechanisms

The Nobel Assembly at Karolinska Institutet has today decided to award the 2017 Nobel Prize in Physiology or Medicine jointly to Jeffrey C. Hall, Michael Rosbash, and Michael W. Young for their discoveries of molecular mechanisms controlling the circadian rhythm.


Life on Earth is adapted to the rotation of our planet. For many years we have known that living organisms, including humans, have an internal, biological clock that helps them anticipate and adapt to the regular rhythm of the day. But how does this clock actually work? Jeffrey C. Hall, Michael Rosbash and Michael W. Young were able to peek inside our biological clock and elucidate its inner workings. Their discoveries explain how plants, animals and humans adapt their biological rhythm so that it is synchronized with the Earth's revolutions.

Using fruit flies as a model organism, this year's Nobel laureates isolated a gene that controls the normal daily biological rhythm. They showed that this gene encodes a protein that accumulates in the cell during the night, and is then degraded during the day. Subsequently, they identified additional protein components of this machinery, exposing the mechanism governing the self-sustaining clockwork inside the cell. We now recognize that biological clocks function by the same principles in cells of other multicellular organisms, including humans.

With exquisite precision, our inner clock adapts our physiology to the dramatically different phases of the day. The clock regulates critical functions such as behavior, hormone levels, sleep, body temperature and metabolism. Our wellbeing is affected when there is a temporary mismatch between our external environment and this internal biological clock, for example when we travel across several time zones and experience "jet lag". There are also indications that chronic misalignment between our lifestyle and the rhythm dictated by our inner timekeeper is associated with increased risk for various diseases.

Our inner clock

Most living organisms anticipate and adapt to daily changes in the environment. During the 18th century, the astronomer Jean Jacques d'Ortous de Mairan studied mimosa plants, and found that the leaves opened towards the sun during daytime and closed at dusk. He wondered what would happen if the plant was placed in constant darkness. He found that independent of daily sunlight the leaves continued to follow their normal daily oscillation (Figure 1). Plants seemed to have their own biological clock.

Other researchers found that not only plants, but also animals and humans, have a biological clock that helps to prepare our physiology for the fluctuations of the day. This regular adaptation is referred to as the circadian rhythm, originating from the Latin words circa meaning "around" and dies meaning "day". But just how our internal circadian biological clock worked remained a mystery.

Figure 1. An internal biological clock. The leaves of the mimosa plant open towards the sun during day but close at dusk (upper part). Jean Jacques d'Ortous de Mairan placed the plant in constant darkness (lower part) and found that the leaves continue to follow their normal daily rhythm, even without any fluctuations in daily light.

Identification of a clock gene

During the 1970's, Seymour Benzer and his student Ronald Konopka asked whether it would be possible to identify genes that control the circadian rhythm in fruit flies. They demonstrated that mutations in an unknown gene disrupted the circadian clock of flies. They named this gene period. But how could this gene influence the circadian rhythm?

This year's Nobel Laureates, who were also studying fruit flies, aimed to discover how the clock actually works. In 1984, Jeffrey Hall and Michael Rosbash, working in close collaboration at Brandeis University in Boston, and Michael Young at the Rockefeller University in New York, succeeded in isolating the period gene. Jeffrey Hall and Michael Rosbash then went on to discover that PER, the protein encoded by period, accumulated during the night and was degraded during the day. Thus, PER protein levels oscillate over a 24-hour cycle, in synchrony with the circadian rhythm.

A self-regulating clockwork mechanism

The next key goal was to understand how such circadian oscillations could be generated and sustained. Jeffrey Hall and Michael Rosbash hypothesized that the PER protein blocked the activity of the period gene. They reasoned that by an inhibitory feedback loop, PER protein could prevent its own synthesis and thereby regulate its own level in a continuous, cyclic rhythm (Figure 2A).

Figure 2B. A simplified illustration of the molecular components of the circadian clock.
Such a regulatory feedback mechanism explained how this oscillation of cellular protein levels emerged, but questions lingered. What controlled the frequency of the oscillations? Michael Young identified yet another gene, doubletime, encoding the DBT protein that delayed the accumulation of the PER protein. This provided insight into how an oscillation is adjusted to more closely match a 24-hour cycle.

The paradigm-shifting discoveries by the laureates established key mechanistic principles for the biological clock. During the following years other molecular components of the clockwork mechanism were elucidated, explaining its stability and function. For example, this year's laureates identified additional proteins required for the activation of the period gene, as well as for the mechanism by which light can synchronize the clock.

Keeping time on our human physiology

The biological clock is involved in many aspects of our complex physiology. We now know that all multicellular organisms, including humans, utilize a similar mechanism to control circadian rhythms. A large proportion of our genes are regulated by the biological clock and, consequently, a carefully calibrated circadian rhythm adapts our physiology to the different phases of the day (Figure 3). Since the seminal discoveries by the three laureates, circadian biology has developed into a vast and highly dynamic research field, with implications for our health and wellbeing.
Figure 3. The circadian clock anticipates and adapts our physiology to the different phases of the day. Our biological clock helps to regulate sleep patterns, feeding behavior, hormone release, blood pressure, and body temperature.

About the Nobel Laureates

Jeffrey C. Hall was born 1945 in New York, USA. He received his doctoral degree in 1971 at the University of Washington in Seattle and was a postdoctoral fellow at the California Institute of Technology in Pasadena from 1971 to 1973. He joined the faculty at Brandeis University in Waltham in 1974. In 2002, he became associated with University of Maine.

Michael Rosbash was born in 1944 in Kansas City, USA. He received his doctoral degree in 1970 at the Massachusetts Institute of Technology in Cambridge. During the following three years, he was a postdoctoral fellow at the University of Edinburgh in Scotland. Since 1974, he has been on faculty at Brandeis University in Waltham, USA.

Michael W. Young was born in 1949 in Miami, USA. He received his doctoral degree at the University of Texas in Austin in 1975. Between 1975 and 1977, he was a postdoctoral fellow at Stanford University in Palo Alto. From 1978, he has been on faculty at the Rockefeller University in New York.

What can we use from this in teaching undergraduate A&P?

  • When you discuss biological clocks and rhythms in your course, this could be a way to garner student interest—considering that this is a current and ongoing effort in science. I begin discussing this at the beginning of the course—when covering  homeostasis.

  • Consider using the annual Nobel Prize announcements as a springboard to discuss the process of scientific discovery. 

  • Consider mentioning the other major awards for scientific achievement and discuss what the judges seem to value most about scientific discoveries. The Nobel Prize is the one everyone has heard of, so it's a great place to start.

  • Use the Nobel Prizes (and other awards) over time as a way to keep students aware of the history of, and progress, of human biology. One could also address the global diversity of laureates.  Or the lack of other kinds of diversity among laureates.

  • The sources below are great places to find media for teaching and for great, pithy explanations of complex topics for a "beginner" audience like our A&P students.

  • Want to know more?

    Advanced information

    P-element transformation with period locus DNA restores rhythmicity to mutant, arrhythmic Drosophila melanogaster.

    • Zehring, W.A., Wheeler, D.A., Reddy, P., Konopka, R.J., Kyriacou, C.P., Rosbash, M., and Hall, J.C. (1984).  Cell 39, 369–376.

    Restoration of circadian behavioural rhythms by gene transfer in Drosophila. 

    • Bargiello, T.A., Jackson, F.R., and Young, M.W. (1984). Nature 312, 752–754.

    Antibodies to the period gene product of Drosophila reveal diverse tissue distribution and rhythmic changes in the visual system.

    • Siwicki, K.K., Eastman, C., Petersen, G., Rosbash, M., and Hall, J.C. (1988).  Neuron 1, 141–150.

    Feedback of the Drosophila period gene product on circadian cycling of its messenger RNA levels.

    • Hardin, P.E., Hall, J.C., and Rosbash, M. (1990).  Nature 343, 536–540.

    The period gene encodes a predominantly nuclear protein in adult Drosophila.

    • Liu, X., Zwiebel, L.J., Hinton, D., Benzer, S., Hall, J.C., and Rosbash, M. (1992).  J Neurosci 12, 2735–2744.

    Block in nuclear localization of period protein by a second clock mutation, timeless.

    • Vosshall, L.B., Price, J.L., Sehgal, A., Saez, L., and Young, M.W. (1994).  Science 263, 1606–1609.

    double-time is a novel Drosophila clock gene that regulates PERIOD protein accumulation. 

    • Price, J.L., Blau, J., Rothenfluh, A., Abodeely, M., Kloss, B., and Young, M.W. (1998). Cell 94, 83–95.

    Content: Adapted from press release at 
    Illustrations: © The Nobel Committee for Physiology or Medicine. Illustrator: Mattias Karlén

    Thursday, June 22, 2017

    Why You Want Your A&P Students to Fail

    I want my students to fail. Of course I don't want them to fail the course, but I do want to give them a lot of opportunities to get things wrong as they learn new facts, apply new knowledge, and build their conceptual frameworks.

    Learning scientists have plenty of research that shows that failing to get things right at first, then correcting one's thinking by relearning forgotten facts and applying knowledge in better ways, strengthens mastery. And it reinforces long-term memory of facts—and long-term memory of how to solve problems.

    So I give my A&P students a lot of opportunities to fail. So that they can stop failing and be more consistent in succeeding.

    One way I do that is by using clickers—a student response system—during lectures, labs, and discussion. I do assign "participation points" for answering questions using this system in class, but I do not assign points based on whether the answers were correct or incorrect. I want them take risks—to fail sometimes.

    By failing to get something right on a "clicker question," they wake up to where their deficiencies in learning are. Then we work together to correct their knowledge. It's more likely that when they encounter a similar challenge later on in my course, they'll be in a better position to succeed.

    I also give my students a lot of opportunity to fail in taking online tests. In my courses, I give a lot of online tests that act primarily as formative assessments. That is tests that help them gain knowledge at the beginning of their learning and tell them how they are doing—not tests that primarily evaluate if they've succeeded at the end of their learning process (summative testing). Most of my summative testing is instead done in written exams.

    My frequent online tests do have grade points associated with them, but because multiple attempts are allowed, they have a built-in formative component. Because the questions are randomly drawn from question sets containing many items, each test attempt has different items—but is testing the same set of learning objectives. Students fail, then fail again, then succeed in such tests.

    Because those online tests are cumulative—testing over all prior concepts—they get continuous practice in retrieving and applying concepts. And ongoing opportunities to fail—then succeed. By the time we get to their midterm and final exams, they are ready to succeed.

    But wait! There's more.

    I also require my student to take pretests before they begin their online testing. The pretests come before any learning activity in a new unit. Thus, they have an initial opportunity to fail—and fail miserably—by taking a test on a new set of topics that they may have never seen before. Learning research—and my own experience—shows that such pretests really prime student learning. Maybe a miserable failure at the start gets our brains into a mode that helps us really figure out how to avoid such failure again!

    I realize that it may seem counterintuitive for either teachers or learners to embrace failure as desirable. But considering how we really learn—by falling, then getting up and trying again—it makes a lot of sense. And the science of learning backs up this approach.

    What can we use from this in teaching undergraduate A&P?

    • Consider adding opportunities for students to fail early in their learning by using low-stakes or zero-stakes tests and quizzes.

    • Consider using clickers or mobile-based student response systems to embed questions in lectures, labs, group activities, and discussions.

    • Consider embedding quiz items in your pre-class "flipped" course materials.

    • Encourage students to test each other outside of class to give additional opportunities for failure. Flash cards, concept maps, and similar study activities also provide failure opportunities that enhance learning.

    Want to know more?

    Small Teaching: Everyday Lessons from the Science of Learning
    • James M. Lang, John Wiley & Sons, Feb 16, 2016 
    • Book that summarizes many different ideas about how to apply learning science to your courses, it gives practical advice and a lot of examples of how to do "small" things in your course to promote the kinds of failure that promote learning.

    Failure is an Option: Helping Students Learn from Mistakes
    • John Orlando, PhD, Faculty Focus, 
      May 16, 2011
    • Brief column on the value of failure as a teaching tool. And mentions the idea that even the toughest teacher can have a class full of "A students" when we let them fail, then succeed.

    What is the difference between formative and summative assessment?
    • Carnegie Mellon University (Eberly Center | Teaching Excellence & Educational Innovation), accessed June 15, 2017
    • Brief webpage contrasting formative and summative assessment.

    Testing as a Learning Tool | UPDATE
    • Kevin Patton, The A&P Professor blog, May 19, 2015
    • My most recent post that further explains the testing methods mentioned above. With links to additional resources.

    Cumulative Testing Enhances Learning
    • Kevin Patton, The A&P Professor blog, September 5, 2016
    • Briefly explains my use of cumulative testing in A&P courses. With links to additional resources.

    Student Response Systems: Trying Clickers in Your Course
    • Kevin Patton, The A&P Professor website, accessed June 16, 2017
    • My weminar on using clickers in the A&P course. With links to additional resources.
    Top photo: Sigurd Decroos
    Middle photo: ilker

    Thursday, May 4, 2017

    Reboot of The A&P Professor Website

    Next time you head over to the companion website for this blog at, you'll see a whole new website. Literally. The old website is enjoying a well-deserved rest on the beach of a sea of electrons, and a whole new—completely rebuilt—website has taken its place.

    Like rookie professors who replace veteran A&P professors, it still has a lot to learn. So I'm actively seeking your input on the kinds of things you'd like me to add or subtract from the website. Either comment on this blog post, or use the CONTACT form on the website.

    This new version of The A&P Professor retains a few of the design elements of the old one, like the Hip Logo. However, the website design is now "responsive" to allow resizing and rearrangement of page elements for easy viewing on any device—from desktop to pad to phone.

    I did a lot of pruning during the rebuild of The A&P Professor . I removed dated topics and book reviews, and the curated lists of websites and images. The latter just got out of hand for one guy with several "real" jobs, plus tending to a bunch of websites and blogs and a daily newsletter. When I started curating those collections, it was hard to find what we needed to teach A&P successfully—but now it's now much easier to find what you want on your own.

    The new website is now closely linked to another of my websites, the Lion Den. The Lion Den has also recently been rebuilt to focus entirely on the teaching and learning of human anatomy and physiology.

    So check out the Lion Den offerings as you explore the new The A&P Professor website! As always, I continue to appreciate your support!

    Thursday, April 20, 2017

    Huge Breakthrough in Human Anatomy & Physiology!

    This trend in misleading "click bait" headlines among science news outlets continues to spiral into infinity. Okay, "infinity" is an exaggeration, but apparently that's what it takes these days to get us reading the actual content of science articles. And a growing phenomenon is that the articles themselves include exaggerations within their content. That's the topic of my rant, er, post today.

    I've been thinking about this for a long while. I often discuss it in class with my students. Yesterday, I ran across a recent (January 2017) example of the perennial "scientists discover that the appendix has a function" headline: Your Appendix Might Serve an Important Biological Function After All 

    That example actually has a pretty good article about a study analyzing the evolutionary appearances and reappearances of the appendix in mammals and what that may tell us about this organ's function. But we already know enough about the functions of the vermiform appendix in humans that it's hardly true that its functions are completely unknown. The article clearly acknowledges that fact within the content, despite that attention-grabbing headline.

    Megakaryocyte producing platelets
    Another recent example was the round of excited shares on social media regarding the "discovery" that hematopoiesis (blood development) occurs in lung tissue. There were a lot of "wow, who knew?" tweets that week. Even from highly trained experts in A&P. But my Anatomy & Physiology textbook (p. 624) already has this information—and it surely cannot be the only textbook to do so.

    The journal article that prompted this wave of tweets and posts described some research in mice that expands our knowledge about this phenomenon—turns out that more is going in the lungs than we thought. The lungs may be the primary site for thrombopoiesis (platelet development), if human lungs work like mice lungs. But the fact that the lungs are sites of hematopoiesis—specifically platelet formation—is not new.

    I've shared these and other posts with exaggerated headlines myself—mostly on Twitter, Facebook, or my new daily newsletter from Nuzzel.

    However, I think it's way to easy to succumb to the excitement of a potential "new discovery" that turns out to be not new, or even a discovery, at all. As a blogger I know full well that exaggerated headlines get more "engagement", which leads to more "followers," which leads to better "brand recognition" and thus, more future "engagement." Who wants to spend time researching and writing when nobody is reading?

    But in science, maybe the public perception of how science works is better served by a more toned-down approach that recognizes what we already think we know, why we think we know it, and what any new studies can do to clarify, correct, or extend what we know.

    I know that none of us individuals can stop the tide of exaggerated science news headlines. I'm just using a platform I have to express my concern that we may be making a mistake by doing so. If everything is a "breakthrough" or even a "huge breakthrough," then maybe casual observers will miss those truly game-changing ideas when they come along.

    At least is something to keep in the back our minds and we do our daily scan of science new headlines.

    What can we use from this in teaching undergraduate A&P?

    • Consider challenging your student to find the first new "science discovers the function of the appendix" article or post of the semester. (or spleen or gallbladder or any organ).

    • Find some posts or articles that have exciting "new discovery" headlines and analyze them as a class. The may help us all learn better the critical analysis needed when reading science content.

    • Have a class discussion regarding the balance between the excitement of discovery that drives science and the exaggerations of discovery that may mislead.

    • Consider making sure that your students know that the appendix has functions (and that the lungs make platelets). Just in case they become science journalists.

    • Consider throwing out science journalism or science writing as career options. They already have an interest in human biology—and they may soon discover they don't like the career path they first chose, after all.

    Want to know more?

    Your Appendix Might Serve an Important Biological Function After All

    • BEC CREW Science Alert 10 JAN 2017
    • Article about an evolution study of the appendix in many organisms and how that may relate to the organ's function.

    An Unexpected New Lung Function Has Been Found - They Make Blood

    • This article, with the subtitle Things just got complicated, outlines the recent work done in mice to show that most platelets (not just some platelets) may form in lungs. 
    • BEC CREW Science Alert 24 MAR 2017
    Megakaryocyte image: A. Rad

    Thursday, February 9, 2017

    How Dietary Fiber Prevents Disease

    So why, exactly, is it that we should consume a lot of fiber in our diet to remain healthy? Are refined fiber supplements just as good as, say, an "apple a day?"

    Recently, an article in the journal Cell answer seems to verify some of the answers for us.

    As the paper cited below indicates, research seems to confirm that dietary fiber provides nutrients for the inhabitants of our intestinal microbiome.  When dietary fiber is missing, then the microbes undergo a shift in populations and start consuming our GI mucus as an alternate source of nutrition.  That, as you might guess, reduces the thickness of the protective mucus—hus increasing the likelihood that pathogens can more easily attack the intestinal lining. Ouch.

    Apparently, refined prebiotic fibers don't fix the problem.

    Here are some highlights of the research article (quoted from their online preview):

    • Characterized synthetic bacterial communities enable functional insights in vivo
    • Low-fiber diet promotes expansion and activity of colonic mucus-degrading bacteria
    • Purified prebiotic fibers do not alleviate degradation of the mucus layer
    • Fiber-deprived gut microbiota promotes aggressive colitis by an enteric pathogen

    Image for unlabelled figure

    What can we use from this in teaching undergraduate A&P?

    • When asked by students about dietary fiber, you have more information from which to draw an answer.
    • When discussing any of these topics, you'll now have a bit more to add to your story:
      • nutrition
      • function of mucus
      • the human microbial system (or specifically, the GI microbiome)
      • how pathogens cause disease (or specifically, GI disorders)

    Want to know more?

    Veggies and Intact Grains a Day Keep the Pathogens Away

    • Francesca S. Gazzaniga. Dennis L. Kasper. Cell. Available online 17 November 2016
    • Brief preview of the M. Desai article cited below.

    A Dietary Fiber-Deprived Gut Microbiota Degrades the Colonic Mucus Barrier and Enhances Pathogen Susceptibility

    • Mahesh S. Desai et al. Cell, Volume 167, Issue 5, 17 November 2016, Pages 1339-1353.e21
    • The detailed research article.

    Microbiome articles

    • Kevin Patton. The A&P Professor. Various dates.
    • Collection of previous posts on this topic from this blog.

    Photos: Youssef KH (top) Cell (bottom)

    Tuesday, January 31, 2017

    Pre-Tests as Student Success Tools

    I always thought of pre-testing as something you do before working on a unit of content, later followed up with a post-test. Comparing pre-test results with post-test results can then be used as part of the course assessment to find out what, if any, learning has happened. But that's no longer my first thought when I hear the term "pre-test."

    Several years ago, I ran across a news item that referred to a piece of learning science research that described another use for pre-testing. It showed that students who took a pre-test did better than students who did not take a pre-test. It showed, I think, that just the process of pre-testing primes student learning in a way that has a demonstrable and significant effect on student success.

    As with any new way of doing things that I discover, I had to let it percolate in the back of mind for a while. First, do I really believe it? Further research showed me that this was not a one-off experiment—it's been tested in both the lab and in the field with similar outcomes. Next, will it work in my courses? If so, how would I implement it? And the all-important question: would I have time to implement it? Would it then add extra effort and time to my workload every semester, in perpetuity?

    Well, I finally jumped in and tried it. I figured it could do no harm. And I found a way to do it without much effort—either in initially wedging it into my course or in maintaining it across all future courses.

    I'd already been using frequent online tests, each allowing multiple attempts, as a way for my students to prepare for their written exams. Each online test has a test bank of many more items than appear on any one attempt. Each test item is pulled from a group of items relating to the same learning outcome, so tests end up being different in every attempt. By using just a handful of items in each group, the odds quickly become astronomical that a student will get the same test twice—or get the same test as any other student in the course. Sort of like the classic type of slot machine.

    My existing online tests were already cumulative. They included test item groups from previous tests, so that students have continuing practice with concepts introduced throughout the course, as explained in my recent article, Cumulative Testing Enhances Learning

    What I did to make the pretests is simply go into my online test editor (Respondus) and make a copy of each online test. Then I removed the cumulative item groups from each test, leaving only the item groups that pertain to that particular unit of study. An easy and quick job in the test editor. Then I saved those as pre-tests and uploaded them to my learning management system (LMS). And set them up for ONE attempt only (not the usual three possible attempts).

    What?! Using the same test items as their "real" test? Isn't that just like handing them a list of answers? Glad you asked! Remember, the odds of anyone ever getting "the same test" again (or as anyone else gets) is astronomically low. What they get in the pre-test is a "version" of the real test, but not the actual test that individual will end up taking later.

    I then set up my LMS so that each pre-test opens about halfway through the preceding unit. Students can go into the LMS before their next unit to take the pre-test for the upcoming unit. I also set things up so that students do not have access to the course resources they need to get through the unit until after they submit the pre-test. For example, I use online Previews as part of my sorta-flipped format (I called it a half-flip with a quarter turn). If they don't take the pre-test first, then neither the Previews, nor anything else, will open up for them.

    Because the "locks" that unlock the other course resources give students incentive to do the pretests, I didn't need to assign grade points or deduct grade points if they didn't do it. My pre-tests do not impact the grade directly—only indirectly by enhancing student learning.

    I have been amazed at the results of that simple step. I noticed that class performance increased right away—and there has been no downward trend since then. So I guess I shoulda believed the research data when I first saw it, eh? 

    I think there are several things going on. For one, pre-tests give students an overview of what they'll be expected to solve at the end of the unit. And they'll get a chance to use what they know already to predict what might be a correct answer—with immediate feedback on where they predicted incorrectly. This prediction exercise can be a powerful learning strategy.

    Also, as they then struggle through the unit, they have in mind what they need to master if they're going to have a chance of passing the test. 

    Along the same lines, they gain some familiarity with the upcoming material. They'll have "seen this all before" even if they don't fully understand it. As we go through it all after the pre-test, students will have already walked through that neighborhood, so it's not so unfamiliar to them.

    I think pre-testing also shakes loose some prior learning. That is, students will recognize some basic principles and some patterns that they've seen before. I suggest that this stimulates their awareness of how things connect and thus gets them better prepared for their new learning.

    One last thing I want to mention: I now have another assessment tool that I can use to compare before-after data and get a sense of what my students have accomplished. Even better, I suppose, is that I added a column to their LMS gradebook that calculates their "gain" by providing the percentage by which they improved between the pre-test and the real test (post test). Individuals seeing that they learned a lot in each unit is a real motivator for continued hard work in the course.

    As with anything, there are potential pitfalls. The one that I didn't anticipate, but should have, is that the super-high-achievers will NOT want a "bad grade" anywhere in their gradebook. Even though students are EXPECTED TO FAIL the pre-test—and it isn't part of the course grade calculation. It's a mindset—it doesn't have to make sense.

    So I would have these high-achievers in my office the day after they took their pre-test and want me to go over every item with them. I'll bet their blood pressure wasn't normal that day, either—probably even worse the night before. The solution I found, which is not 100% effective, is to repeatedly remind students that they are expected to do poorly on the pre-tests. And that they should not struggle with it—just think a moment, then give your best guess and move on.

    Like any unfamiliar teaching strategy, pre-testing works best if you tell students how they will benefit.

    If any of you have experiences with pre-testing that you'd like to share, please comment at the blog site, in the form below this article.

    Want to know more?

    Testing in A&P Courses
    • Kevin Patton. The A&P Professor. Collection (various dates).
    • An assortment of brief articles on methods and issues regarding testing in the undergraduate A&P course.

    Cumulative Testing Enhances Learning
    • Kevin Patton. The A&P Professor. 5 Sep 2016.
    • Article on how cumulative testing can be used to promote long-term learning in A&P courses.

    The pretesting effect: Do unsuccessful retrieval attempts enhance learning?
    • Richland, Lindsey E.; Kornell, Nate; Kao, Liche Sean. Journal of Experimental Psychology: Applied, Vol 15(3), Sep 2009, 243-257. 
    • Research article describing experiments in pre-testing.

    Small Teaching: Everyday Lessons from the Science of Learning

    • James M. Lang. Jossey-Bass, San Francisco. 2016.
    • If you don't read anything else on teaching-learning this year, at least read this. Lang's clear writing, chunked into small chapters, reviews some of the major contemporary insights with practical "small" things you can do in your class to improve learning. Part I, Chapter 2, discusses pretesting.

    Monday, January 2, 2017

    Checkmarks Make Me Happy
    It's true. Like most of you, I have a long list of tasks that need to be done in any one day or week.

    I am pretty good about remembering what I have to get done by when, what I've already finished, and what has just been added to my plate. But my brain is not 100% reliable with that, so I make lists.

    Sometimes these are lists on my computer desktop or in my online Task List. But those are too easily hidden. I have to see them to be reminded. So I often make paper lists. There is something very satisfying about having the kinesthetic experience of physically ticking something off my list with my trusty green pen.

    I was talking about this last summer when I was presenting a bunch of practical tips to help textbook authors stay on track at the Textbook and Academic Authors conference. During the talk, my buddy Mike Kennamer tweeted, "'Checkmarks make me happy...' Kevin Patton". When I saw that tweet later in my Twitter feed, I chuckled that he took this out of the discussion—but I also realized how important a point that it is.

    Whether it's a textbook revision or a long semester of teaching A&P, those little surges of dopamine that happen when we can check something off our lists really do help keep us motivated.  Seeing the progress we are making as we add ticks to our checklists provides some additional satisfaction, which also helps keep us going.

    checklist with green checksAnd checklists also keep us from forgetting important things to do.

    In an online course I teach, it's easy to forget what needs to be graded each week because there are no stacks of tests or papers sitting there on my desk glaring at me. Those assignments are hidden away on a server somewhere and I need to intentionally call them up to grade them. So I need a checklist. the one pictured here lists grading duties organized by module (we have two-week modules A, B, C,...) and by week.

    Each Friday, during my scheduled grading session, I look at my checklist. I note that, even though it may not always feel like it, the trimester is actually progressing. And I see what I need to grade this week. And—hooray!—I get to check it off my list when I'm done. What a great way to start the weekend, eh?

    I recently posted my grading checklist in that online course. It's a bit late for this last term, but next time I teach the course, my students can print out my checklist to help them keep track of what they've submitted each week. Sure, they have a syllabus. Like they're going to use that to make their own list? Really? What planet do you live on?

    What can we use from this in teaching undergraduate A&P?

    • Grading checklists help us make sure that no graded assignments fall through the cracks.

    • Grading checklists provide happiness and motivation. At least a little.

    • Scheduled grading sessions help us keep up with our grading tasks, preventing them from piling up and disturbing our mental health.

    • We can share grading checklists (and an exhortation to use them) with students to help keep them on track—and stay motivated.

    Monday, November 28, 2016

    Sacral Efferent Pathways are Sympathetic, Not Parasympathetic

    A recent report in the journal Science proposed a big change in how we understand the sympathetic and parasympathetic pathways of the autonomic nervous system (ANS).

    In a nutshell, the new model stipulates that the outflow (efferent pathways) are divided into a cranial division and spinal division—not the craniosacral and thoracolumbar divisions that we learned (and that exist in all A&P textbooks):

    Current model:
    • Craniosacral division (parasympathetic outflow)
    • Thoracolumbar division (sympathetic outflow)
    New model:
    • Cranial division (parasympathetic outflow)
    • Spinal division (sympathetic outflow)
    The authors lay out embryological and genetic phenotype evidence to show that the sacral components of the ANS outflow pathways are similar to sympathetic thoracic pathways—not to cranial parasympathetic pathways as we have long supposed. 

    But wait, you say, what about the parasympathetic control of the genitals, rectum, bladder? What about, well, all kinds of things that now seem to unravel? I suggest reading the rather brief and plainly written article in Science for the full answer. 

    However, a few quick points may reduce your blood pressure a bit—and perhaps pique your interest.

    Quick points about the new ANS model

    • Thoracic and sacral pathways share common embryologic development by location and when looking at transcriptional markers associated with neurotransmitters that differ from the developmental pattern of cranial pathways.

    • Thoracic and sacral pathways have a ventral exit point from the spinal cord; cranial pathways have a dorsal exit point.

    • The pelvic ganglion has been considered a "mixed" sympathetic/parasympathetic ganglion because it receives fibers from both the upper lumbar and sacral segments. But if the sacral pathways are sympathetic, the pelvic ganglion is clearly a sympathetic ganglion (not mixed). 

    • Analyses of transcription factors show that cells of the pelvic ganglia resemble those sympathetic ganglia and do not resemble cells in cranial ganglia.

    • The supposed lumbar vs. sacral antagonism in the urinary bladder's detrusor muscle does not seem to hold up, with the lumbar inhibitory effects either not demonstrable in experiments or of questionable functional relevance.

    • The effects on vessel dilation in genitals can be explained as a "continuity of action—rather than antagonism"

    • The sacral pathway to the rectum seems to resemble sympathetic structure, not cranial (parasympathetic) structure.

    What can we use from this in teaching undergraduate A&P?

    • When covering the craniosacral/thoracolumbar scheme, consider mentioning this newly proposed model.

    • Consider using this scenario to illustrate the dynamic nature of science. Perhaps discuss that long-held dogma is occasionally challenged using newer methods and ways of thinking.

    • Consider discussing pros and cons of adopting the new model. For example, can evidence from mice extend to all vertebrates? Which is stronger, evidence for the current model or the new model? Which model is most useful in understanding principles of ANS regulation? A little critical thinking never hurt anyone (at least not much).

    Want to know more?

    The sacral autonomic outflow is sympathetic
    • I. Espinosa-Medina, O. Saha, F. Boismoreau, Z. Chettouh, F. Rossi, W. D. Richardson, J.-F. Brunet. Science  18 Nov 2016: Vol. 354, Issue 6314, pp. 893-897 DOI: 10.1126/science.aah5454
    • Peer-reviewed research report describing this discovery, Includes an updated version of the classic diagram of sympathetic and parasympathetic pathways.

    Neural circuitry gets rewired
    • Adameyko, I. Science 18 Nov 2016: Vol. 354, Issue 6314, pp. 833-834 DOI: 10.1126/science.aal2810
    • Companion article to the report cited above, stating that "This finding provokes a serious shift in textbook knowledge, and, as with any fundamental discovery, it brings important practical implications..." and goes on to mention of a few of the implications (e.g., how to treat bladder dysfunction).

    The Autonomic Nervous System. Part I.
    • John Newport Langley. W. Heffer & Sons Ltd., Cambridge, 1921.80pp.
    • Classic "primary source" that codified the modern concept of the ANS. 

    Gray's Anatomy ANS diagram
    • Henry Gray. 1918 (online edition at Bartleby)
    • Classic diagram by Henry Vandyke Carter of ANS pathways from an early edition of Gray's Anatomy.
    • or

    Wednesday, November 16, 2016

    Checking Our Attitudes About A&P Students "These Days"

    Ever been part of a conversation among faculty about "students these days" and how unmotivated they are, or how they lack the skills or knowledge that you'd like them to have? Yeah, me too.

    Today in my daily Nuzzel newsletter, I shared an excellent article from Faculty Focus that does a great job of exposing the dangers of such conversations. Dangers to students, dangers to our academic institutions, and dangers to ourselves as educators. Although the author, Maryellen Wiemer, admits that occasional venting to a trusted colleagues helps us put things in perspective, she also points out the many harms that outright chronic complaining can do.

    I'm not going to summarize that article here—it's best read in it's entirety. However, I'd like to add my two cents. After all, what's the good of having my own blog if I can't do that once in a while, eh?

    It took me decades of teaching in high school and college classrooms to fully realize what I think my role as an A&P professor should be. It's not solely to guide well-prepared, self-motivated, highly skilled students to the success that they can easily achieve without me. Sure, that's easy and mostly annoyance-free. But it can be awfully boring. What do they need me for, anyway?  Not much.

    I came to discover that what really rocks my boat as a professor is when I can help a struggling student achieve even a very small success. When I can help a learning-disabled student find ways to "get it" when studying those messy histology specimens. When I can help under-prepared students "catch up" and learn some effective study skills to continue keeping up. When I can get through to unfocused, unmotivated, immature students in some small way.

    We pay a lot of lip service to making our courses "student centered" and making carefully devised learning outcomes our primary goal, but we often just don't want to do the work—or put up with the frustrations—of really making that happen.

    It's when I finally started embracing those challenges and leaving aside my unhelpful judgments of "students these days" that I finally started truly and totally loving teaching my A&P students. I found that the more I connected with "problem students," the closer I got to finding the underlying reasons for their apparent lack of will or ability—and thus able to help them find appropriate strategies to succeed.

    Sometimes, sporadic attendance is more about serious family or health issues than it is about their attitude toward my course. Sometimes, their lack of focus in my class is more about neurological issues, personal emergencies outside the classroom, or side effects of an illness or therapy, than it is about them "not caring" about their learning. Sometimes, their lack of reading is more about dyslexia than it is about laziness.

    Sure, it's sometimes hard to face challenges. Otherwise, we wouldn't call them challenges, eh? But when I ask myself, "what kind of teacher do I want to be today?" the answer always comes back to, "the kind who is going to help even the most challenging students." And that makes all the difference.

    Want to know more?

    Ugly Consequences of Complaining about 'Students These Days'

    • Maryellen Weimer. Faculty Focus. 16 November 2016.
    • This is the article to which I refer in today's blog post.

    Photo: John Wisbey

    Monday, October 31, 2016

    Sex-Gender Differences in Medical Research

    We are only very slowly recognizing the many biological and medical differences between males and females (and masculine/feminine)—besides the obvious ones related to reproduction. There are divergent patterns in the anatomy and physiology of perhaps every body system. However, in medical research male and female subjects are often grouped together in a way that obscures those divergent patterns.

    Two "viewpoint" articles in the Journal of the American Medical Association (JAMA) today focus a light on this issue and point the way to improved—more clinically useful—medical research. Links to both articles are listed below.

    As one of the articles points out, women have been included in medical trials for only the past few decades. So there is still a lot of work to be done to shore up the database of male-female differences. But also a lot of work to be done in sorting out male-female patterns of health and disease. Then even more work in making this new knowledge part of the everyday practice medicine.

    Both articles are brief and relatively nontechnical, but when read together, they provide an important message for those of us teaching pre-clinical health professionals in A&P. That message is that we should consider introducing—then reinforcing—the notion of body-wide sex and gender differences.

    Both articles give examples of such differences, but many more are to be found elsewhere, as well. Not that we should teach every possible example in the undergraduate A&P course. However, the general concept of functional variation between males and females may be an important one to emphasize as a sub-theme in our story of the human body.

    What can we use from this in teaching undergraduate A&P? 

    • Consider making sex differences a sub-theme in your A&P course.
      • Occasionally point out examples of structural, functional, and clinical patterns of variation that differ between males and females.
        • Compare and contrast sex differences with other types of pattern variations.
        • Discuss "patterns of variability" in contrast to a strictly "binary" view.
      • Consider bringing up sex-difference research that is not yet fully supported.
        • Discuss whether more attention to sex differences across topics in scientific research might help advance this area of knowledge.
        • Discuss the opposing view that there are no clinically significant biological differences between males and females other than those related to reproduction.
      • Look for such examples in your textbook and other teaching/learning resources and point them out to your students.
      • Consider having a classroom or online discussion of this topic. 
      • Ask students to post links to articles that discuss male-female patterns of variation
        • Post to course discussion or course social media channel
        • Bring to class or email to instructor to share with class
        • Post on bulletin board

    • Bring up this issue when discussing how science is done.
      • Consider asking students what effects on public health a more thorough consideration of sex differences may produce.
      • Ask students to look at a study and ask whether sex differences were thoroughly accounted for in the methodology. Could this affect how the study is interpreted and applied in the clinic?

    Want to know more? 

    Consideration of Sex Differences in Medicine to Improve Health Care and Patient Outcomes

    • Marianne J. Legato, MD; Paula A. Johnson, MD, MPH; JoAnn E. Manson, MD, DrPH.
    • JAMA. Published online October 31, 2016. doi:10.1001/jama.2016.13995
    • One of the two articles cited in the post above.

    Reporting Sex, Gender, or Both in Clinical Research? 

    • Janine Austin Clayton, MD; Cara Tannenbaum, MD, MS
    • JAMA. Published online October 31, 2016. doi:10.1001/jama.2016.16405
    • One of the two articles cited in the post above.

    Let’s Talk About Sex…and Gender!

    • Amanda M. Rossi, PhD; Louise Pilote, MD, MPH, PhD
    • Circulation: Cardiovascular Quality and Outcomes. 2016; 9: S100-S101 doi: 10.1161/CIRCOUTCOMES.116.002660
    • Brief article that addresses the issue of terminology, specifically distinguishing between terms that address sex (male, female) and gender (masculine, feminine). Includes a solid list of references.
    Q-angle image: OpenStax College

    Monday, October 3, 2016

    Autophagy Discovery Garners Nobel Prize

    The Nobel Assembly at Karolinska Institutet has today decided to award the 2016 Nobel Prize in Physiology or Medicine to Yoshinori Ohsumi for his discoveries of mechanisms for autophagy.


    This year's Nobel Laureate discovered and elucidated mechanisms underlying autophagy, a fundamental process for degrading and recycling cellular components.

    The word autophagy (aw-toh-FAY-jee) originates from the Greek words auto-, meaning "self", and phagein, meaning "to eat". Thus, autophagy denotes "self eating".

    This concept emerged during the 1960's, when researchers first observed that the cell could destroy its own contents by enclosing it in membranes, forming sack-like vesicles that were transported to a recycling compartment, called the lysosome, for degradation.

    Difficulties in studying the phenomenon meant that little was known until, in a series of brilliant experiments in the early 1990's, Yoshinori Ohsumi used baker's yeast to identify genes essential for autophagy. He then went on to elucidate the underlying mechanisms for autophagy in yeast and showed that similar sophisticated machinery is used in our cells.

    Ohsumi's discoveries led to a new paradigm in our understanding of how the cell recycles its content. His discoveries opened the path to understanding the fundamental importance of autophagy in many physiological processes, such as in the adaptation to starvation or response to infection. Mutations in autophagy genes can cause disease, and the autophagic process is involved in several conditions including cancer and neurological disease.

    Degradation – a central function in all living cells

    In the mid 1950's scientists observed a new specialized cellular compartment, called an organelle, containing enzymes that digest proteins, carbohydrates and lipids. This specialized compartment is referred to as a "lysosome" and functions as a workstation for degradation of cellular constituents. The Belgian scientist Christian de Duve was awarded the Nobel Prize in Physiology or Medicine in 1974 for the discovery of the lysosome.

    New observations during the 1960's showed that large amounts of cellular content, and even whole organelles, could sometimes be found inside lysosomes. The cell therefore appeared to have a strategy for delivering large cargo to the lysosome. Further biochemical and microscopic analysis revealed a new type of vesicle transporting cellular cargo to the lysosome for degradation (Figure 1).

    Christian de Duve, the scientist behind the discovery of the lysosome, coined the term autophagy, "self-eating", to describe this process. The new vesicles were named autophagosomes.

    Figure 1: Autophagosome. Our cells have different specialized compartments. Lysosomes constitute one such compartment and contain enzymes for digestion of cellular contents. A new type of vesicle called autophagosome was observed within the cell. As the autophagosome forms, it engulfs cellular contents, such as damaged proteins and organelles. Finally, it fuses with the lysosome, where the contents are degraded into smaller constituents. This process provides the cell with nutrients and building blocks for renewal.

    During the 1970's and 1980's researchers focused on elucidating another system used to degrade proteins, namely the "proteasome". Within this research field Aaron Ciechanover, Avram Hershko and Irwin Rose were awarded the 2004 Nobel Prize in Chemistry for "the discovery of ubiquitin-mediated protein degradation". The proteasome efficiently degrades proteins one-by-one, but this mechanism did not explain how the cell got rid of larger protein complexes and worn-out organelles. Could the process of autophagy be the answer and, if so, what were the mechanisms?

    A groundbreaking experiment

    Yoshinori Ohsumi had been active in various research areas, but upon starting his own lab in 1988, he focused his efforts on protein degradation in the vacuole, an organelle that corresponds to the lysosome in human cells.

    Yeast cells are relatively easy to study and consequently they are often used as a model for human cells. They are particularly useful for the identification of genes that are important in complex cellular pathways. But Ohsumi faced a major challenge; yeast cells are small and their inner structures are not easily distinguished under the microscope and thus he was uncertain whether autophagy even existed in this organism.

    Ohsumi reasoned that if he could disrupt the degradation process in the vacuole while the process of autophagy was active, then autophagosomes should accumulate within the vacuole and become visible under the microscope. He therefore cultured mutated yeast lacking vacuolar degradation enzymes and simultaneously stimulated autophagy by starving the cells.

    The results were striking! Within hours, the vacuoles were filled with small vesicles that had not been degraded (Figure 2). The vesicles were autophagosomes and Ohsumi's experiment proved that authophagy exists in yeast cells. But even more importantly, he now had a method to identify and characterize key genes involved this process. This was a major break-through and Ohsumi published the results in 1992.

    Figure 2: Yeast. In yeast (left panel) a large compartment called the vacuole corresponds to the lysosome in mammalian cells. Ohsumi generated yeast lacking vacuolar degradation enzymes. When these yeast cells were starved, autophagosomes rapidly accumulated in the vacuole (middle panel). His experiment demonstrated that autophagy exists in yeast. As a next step, Ohsumi studied thousands of yeast mutants (right panel) and identified 15 genes that are essential for autophagy.

    Autophagy genes are discovered

    Ohsumi now took advantage of his engineered yeast strains in which autophagosomes accumulated during starvation. This accumulation should not occur if genes important for autophagy were inactivated. Ohsumi exposed the yeast cells to a chemical that randomly introduced mutations in many genes, and then he induced autophagy.

    His strategy worked! Within a year of his discovery of autophagy in yeast, Ohsumi had identified the first genes essential for autophagy. In his subsequent series of elegant studies, the proteins encoded by these genes were functionally characterized. The results showed that autophagy is controlled by a cascade of proteins and protein complexes, each regulating a distinct stage of autophagosome initiation and formation (Figure 3).

    Figure 3: Stages of autophagosome formation. Ohsumi studied the function of the proteins encoded by key autophagy genes. He delineated how stress signals initiate autophagy and the mechanism by which proteins and protein complexes promote distinct stages of autophagosome formation.

    Autophagy – an essential mechanism in our cells

    After the identification of the machinery for autophagy in yeast, a key question remained. Was there a corresponding mechanism to control this process in other organisms? Soon it became clear that virtually identical mechanisms operate in our own cells. The research tools required to investigate the importance of autophagy in humans were now available.

    Thanks to Ohsumi and others following in his footsteps, we now know that autophagy controls important physiological functions where cellular components need to be degraded and recycled.

    Autophagy can rapidly provide fuel for energy and building blocks for renewal of cellular components, and is therefore essential for the cellular response to starvation and other types of stress.

    After infection, autophagy can eliminate invading intracellular bacteria and viruses. Autophagy contributes to embryo development and cell differentiation. Cells also use autophagy to eliminate damaged proteins and organelles, a quality control mechanism that is critical for counteracting the negative consequences of aging.

    Disrupted autophagy has been linked to Parkinson's disease, type 2 diabetes and other disorders that appear in the elderly. Mutations in autophagy genes can cause genetic disease. Disturbances in the autophagic machinery have also been linked to cancer. Intense research is now ongoing to develop drugs that can target autophagy in various diseases.

    Autophagy has been known for over 50 years but its fundamental importance in physiology and medicine was only recognized after Yoshinori Ohsumi's paradigm-shifting research in the 1990's. For
    Yoshinori Ohsumi was born 1945 in Fukuoka, Japan. He received a Ph.D. from University of Tokyo in 1974. After spending three years at Rockefeller University, New York, USA, he returned to the University of Tokyo where he established his research group in 1988. He is since 2009 a professor at the Tokyo Institute of Technology.

    More background on the winner and the prize

    Yoshinori Ohsumi was born in Fukuoka, Japan, in 1945.  He is affiliated with the Tokyo Institute of Technology in Tokyo, Japan. His monetary award will be nearly one million dollars.

    The Nobel Assembly, consisting of 50 professors at Karolinska Institutet, awards the Nobel Prize in Physiology or Medicine. Its Nobel Committee evaluates the nominations. Since 1901 the Nobel Prize has been awarded to scientists who have made the most important discoveries for the benefit of mankind.his discoveries, he is awarded this year's Nobel Prize in physiology or medicine.

    Nobel Prize® is the registered trademark of the Nobel Foundation

    What can we use from this in teaching undergraduate A&P?

    • Consider using the Nobel Prizes as a discussion-starter in your class about 
      • How science influences society
      • How society influences science
      • How science progresses
      • Rewarding of science discoveries
      • What makes a discovery "important"

    • Relate this discovery to prior (or upcoming) discussions of 
      • Cell function
      • Organelle specialization
      • How cells handle protein
      • How autophagosomes work with lysosomes
      • Compare/contrast with phagocytosis
      • Compare/contrast with proteasome function and protein "quality control

    • Relate this discovery to the general idea of cellular mechanisms of disease
      • Consider taking this opportunity to emphasize "why we need to know all this" detail about cellular structure and function.

    Want to know more?

    Scientific Background Discoveries of Mechanisms for Autophagy

    • Larsson, N-G, Msucci, M. G. accessed 8 October 2016
    • A more advanced summary of the prizewinning discovery, including a handy glossary of terms.

    Honorary Professor Yoshinori Ohsumi wins Nobel Prize in Physiology or Medicine for 2016

    • Tokyo Tech News. 3 October 2016
    • Summary of biography and scientific work of the prizewinner.

    Autophagy in yeast demonstrated with proteinase-deficient mutants and conditions for its induction.

    • Takeshige, K., Baba, M., Tsuboi, S., Noda, T. and Ohsumi, Y. (1992). Journal of Cell Biology 119, 301-311
    • One of the scientific reports of the discovery.

    Isolation and characterization of autophagy-defective mutants of Saccharomyces cervisiae. 

    • Tsukada, M. and Ohsumi, Y. (1993). FEBS Letters 333, 169-17
    • One of the scientific reports of the discovery.

    A protein conjugation system essential for autophagy. 

    • Mizushima, N., Noda, T., Yoshimori, T., Tanaka, Y., Ishii, T., George, M.D., Klionsky, D.J., Ohsumi, M. and Ohsumi, Y. (1998). Nature 395, 395-398
    • One of the scientific reports of the discovery.

    A ubiquitin-like system mediates protein lipidation.

    • Ichimura, Y., Kirisako T., Takao, T., Satomi, Y., Shimonishi, Y., Ishihara, N., Mizushima, N., Tanida, I., Kominami, E., Ohsumi, M., Noda, T. and Ohsumi, Y. (2000).  Nature, 408, 488-492
    • One of the scientific reports of the discovery.

    Honoring the 2016 Nobel laureates with free access to selections of their research

    • Elisa Nelissen Elsevier Connect. October 3, 2016
    • This blog post provides links to download the most cited papers the laureates published with Elsevier, a major publisher of scientific journals and references.

    Hot Topic in Biochemistry: Role of Autophagy in Human Health and Disease
    • Sharon Tooze. YouTube 20 December 2011
    • Brief video of webcast presentation at the Biochemical Society Hot Topic event.

    Some content, including illustrations,
    is adapted from the press release
    and other resources at

    Monday, September 5, 2016

    Cumulative Testing Enhances Learning

    One of the most effective enhancements I've ever made to my human anatomy & physiology course was switching to cumulative testing. What I mean by that is instead of testing on each topic once, then moving on to a test on the next topic, I started testing my students on all the covered topics (thus far in the course) in each successive test.

    I've always had a comprehensive exam at the end of the course—and eventually added a comprehensive midterm exam, too. I found that adding that midterm helped my students relearn what they'd forgotten during the first half of the semester—making them better prepared for the comprehensive final. But not a whole lot better.

    As I got older and wiser—or at least grayer—and got more serious about seeking out solid research on how people actually learn new information and retain it for the long term, I realized that my thinking was sort of alongside the right track. But not fully on the right track. It finally dawned on me that I could not expect my students to really "get it" and "keep it" unless they were repeatedly challenged with a variety of test items that required them to dig back into their memories and drag out those "old" ideas from early in the course.

    Learning experts sometimes call this retrieval practice. The students practice retrieving their stored knowledge and skills. One of the key elements of using retrieval practice in learning is that it is most effective when it is spaced out over time. That is, it occurs after the brain has had time to do some forgetting.

    The "re-learning" and "re-remembering" that must happen after a spaced interval is one of the keys to getting it all solidly embedded into our memory. As my tai chi teacher always tells me, "you can't master it until you've forgotten it." The forgetting, making mistakes, and relearning also enhances our ability to get those concepts and skills back out of memory—thus enabling us to retrieve it when we need to apply it.

    Of course, most of the effort in getting my course on the right track in this regard was getting over that same old, often insurmountable, hurdle of taking a step outside of the "way we've always done it." This nearly universal mindset not only holds me back from trying new things—it encourages my colleagues and students to tell me how wrong I am when I do.

    After at least a year of self-doubt, I just forged ahead and tried it. Every one of my tests now includes test items from all previous topics. I told my students ahead of time why I was doing it and why. And guess what? They were okay with it! I didn't tell any of my colleagues what I was doing because, er, my internal voice was already telling me I was doing it all wrong.

    And you know what? Without changing much else in my course that semester, the comprehensive exam grades—and even the course grades—went up almost a whole letter grade on average. In other words, my course activities and testing covered the same content, at the same level of rigor, but my students were apparent much more successful in their ability to recall the information and skills they need to solve problems at the end of the course.

    This was about ten or so years ago, and I probably still have the numbers somewhere. I didn't do a statistical analysis and I didn't have a control group—unless you count sections of the course in previous semesters. But I didn't—and still don't—feel I really need that. My student grades that semester (and ever since) show a dramatic increase that I'm not willing to reverse.

    Looking back through the lens of 20/20 hindsight, I can see that this should have been plain to me all along. How can we expect anyone to learn something deeply and for the long term, if they only get one chance to have their knowledge and skills challenged? Only through repeated challenges can we master concepts at a level of usefulness.

    We expect our students to build a complete enough conceptual framework to see patterns and understand relationships among concepts. To really see the big picture. But do we give them enough practice to do that effectively? Or do we let them forget what they know and fail to give them those critical opportunities to relearn, thereby solidifying, key concepts?

    In my experience, cumulative testing is a valuable strategy to enhance learning in our courses.

    What can we use from this in teaching undergraduate A&P?

    • Adding items to every test that review all previous topics convert your testing strategy to cumulative testing. This may provide the repetitive, spaced retrieval practice that students need for learning for the long term.

    • Consider using a cumulative strategy for other forms of retrieval practice in your course. For example:
      • Quizzes
      • Clicker questions
      • Pre-lecture and pre-lab videos or reviews
      • Adaptive learning assignments
      • Homework/review assignments
      • In-class, small group reviews
      • Recommended study strategies for individuals and study groups

    Want to know more?

    The critical role of retrieval practice in long-term retention
    • Roediger H Butler A. Trends in Cognitive Sciences. 2011 vol: 15 (1) pp: 20-27. DOI: 10.1016/j.tics.2010.09.003
    • Scholarly review of the superiority of spaced retrieval practice over more traditional educational strategies.

    Make It Stick
    • Peter C. Brown, Henry L. Roediger, Mark A. McDaniel. Harvard University Press, Apr 14, 2014. 313 pages.
    • This is book written for the average teacher or student to help them understand what we now know about effective learning that may be different then the traditional approaches. You really need to read this book! It's well written, engaging, and has a wealth of great ideas.

    Photos: Bob Smith