Rita Levi-Montalcini, growth factor pioneer

Yesterday, the scientific community lost another of its great people, Rita Levi-Montalcini.

In The Human Body in Health & Disease and Structure & Function of the Body, I wrote this about Levi-Montalcini:

Rita Levi-Montalcini had just finished a medical degree in her native Italy when in 1938 the Fascist government under Mussolini barred all “non-Aryans” from working in academic and professional careers. Being Jewish, Levi-Montalcini was forced to move to Belgium to work. But when Belgium was about to be invaded by the Nazis, she decided to return home to Italy and work in secret. Her home laboratory was very crude, but in it she made some important discoveries about how the nervous system develops during embryonic development. After World War II, she was invited to Washington University in St. Louis to work. There, she discovered the existence of nerve growth factor (NGF), for which she later won the 1986 Nobel Prize. Her discovery of a chemical that regulates the growth of new nerves during early brain development has led to many different paths of investigation. For example, by learning more about growth regulators we now know more about how the nervous system develops, as well as other tissues, organs, and systems of the body.

Note that I put in a little plug for my hometown of St. Louis, where we continue to be proud of this remarkable woman and her pioneering work.

As I said in a recent post about the passing of transplant pioneer Joseph Murray, I think the occasional story of a pioneer in the history of human science adds a lot to the A&P course.  Such stories give a human dimension to the pursuit of science and provide the context needed for students to understand how we know what we know.  Levi-Montalcini's story gives us the further opportunities to weave into our courses the themes of global collaboration among the scientific community as the role of women in science.

Want to know more?

• Nobel Scientist Rita Levi-Montalcini Dies in Rome
• U.S. News & World Report online December 30, 2012
• [Plain-English obituary]
• http://my-ap.us/S1RKyW
  
  
• Oldest Nobel winner Rita Levi-Montalcini dies at 103
• Euronews at YouTube accessed 31 Dec 2012
• [Very brief video announcing the death and her contributions.]
• http://youtu.be/SXjt5GI5qEQ
  
  
• Nobel Lecture by Rita Levi-Montalcini 
• Media Player at Nobelprize.org
• [Full video (in English) of Nobel lecture by Rita Levi-Montalcini in which she fully credits "good luck"; 57 minutes]
• http://my-ap.us/Vf6sPz
  
  
• Rita Levi-Montalcini Interview
• Adam Smith, Editor-in-Chief of Nobelprize.org.
• Nobel Interview, November 2008
• [Video interview with Rita Levi-Montalcini, who talks about her daily work, why she had to make a laboratory in her bedroom to conduct research during World War II (3:06), the benefits of working in isolation (5:03), her post-war move to the United States (6:25), her work with Stanley Cohen and the discovery of nerve growth factor (7:15), the roles of intuition and chance in biological research (15:14), her current research (16:58), her advice to young scientists (17:41), and why this period of her life has been the best so far (28:10).]
• http://my-ap.us/Ug6gA5
  
  
• The Nobel Prize in Physiology or Medicine 1986 Press Release
• Nobelprize.org
• [Detailed news release that includes some simple diagrams that help illustrate the concepts involved.]
• http://my-ap.us/ZPyacv
  

• In Praise of Imperfection: My Life and Work

• Rita Levi-Montalcini
• Sloan Foundation Science Series, October 1989
• [Her autobiography]
• http://amzn.to/Wgjk7b

Related textbook content

• Anatomy & Physiology 8th ed.  p. 409, 1111-1113, A&P Connect: The Nobel Legacy my-ap.us/QZTbK1

• Essentials of Anatomy & Physiology p. 231-232, 241, 610-612 my-ap.us/SCfNlj  

• The Human Body in Health and Disease 5th ed. p. 236-237, 644-645, 658 my-ap.us/fNN00N 

• Structure & Function of the Body 14th ed. p. 168-169, 472-473 my-ap.us/X6QxqE

Photo: Presidenza della Repubblica Italiana

Help your students reduce test anxiety

Final exams are almost upon us. So last week, I posted an article on reducing test anxiety my blog The A&P Student

Recent research has revealed an easy and effective trick for reducing test anxiety.  Simply take about ten minutes before the start of your exam to have students journal their anxiety.

Research shows that if your students spend about ten minutes to write out (not just think about) their feelings at the moment, they’ll feel less anxious during the exam.  And because of that (the research shows) they will do better on the exam! 

On average, students that use this technique raise their grade and average of one whole letter grade.  So even if you think it’s silly—or a time waster—isn’t it worth trying?

Students in a research study reported that by writing out their feelings, they quickly got to a point of calm and confidence.  The writing somehow took the energy out of the anxiety and replaced nervousness with readiness. 

Don’t collect the writing, by the way.  Students must be confident that their writings are private for this to work.

Let me know if you try in your classroom and whether you were able to notice a difference.

Want to know more?

Read the story behind this trick:

Testing Anxiety: Researchers Find Solution To Help Students Cope
my-ap.us/TlD6Ba

And here’s the research behind the story:

Writing About Testing Worries Boosts Exam Performance in the Classroom
Gerardo Ramirez, Sian L. Beilock
Science 14 January 2011: Vol. 331 no. 6014 pp. 211-213 DOI: 10.1126/science.1199427
http://my-ap.us/XOQAJg

The related article from The A&P Student

Trick to reduce test anxiety
my-ap.us/Sl5T6j

Check out my advice on breathing to reduce test anxiety:

Don’t forget to breathe!
my-ap.us/dIdsS9

Some advice for A&P students on preparing well for exams:

Previous articles on exam strategies
my-ap.us/2CusmI

Brief video on preparing for exams
youtu.be/yrgNyDH3HrQ?hd=1

 

Photo by Josh Davis under CC license

Olfactory white

Here’s an interesting tidbit of current sensory research that you can drop into a discussion in your A&P course.

You know how mixing different colors (wavelengths) of light produces a non-color mixture we know as white color?  The mixture of wavelengths make it hard to make out any single wavelength.

You know how mixing different sounds (frequencies) produces a bland hiss we usually call white noise?  The mixture of sounds makes it hard to make out any single sound. So many people use it to block out annoying noises.

Well, researchers in Israel have come up with mixtures of different odorants that produce a bland—almost indescribable—odor that makes it virtually impossible to make out any single odor.  They have nicknamed it white smell or olfactory white.

What good is that, you ask?  If white noise can suppress unwanted noise, then maybe we can use white smell to block out unwanted odors.

That would have some benefit, I suppose, when trapped on an elevator with folks returning from their cigarette break.  I could have used it back in the day when I was a zookeeper, I guess.  But I’m thinking the really critical applications will be for handlers of cadaver dogs and others who routinely encounter really sickening smells.

It didn’t take long after arriving for work at the Elephant House to get used to the odor—we all adapt to it after a few minutes.  But after a disaster, when searchers find one decaying corpse, then find fresh air, then find more putrefied remains, any previous adaptation to the odor will have worn off.  White smell could be very valuable indeed.

Go ahead and wear that annoying cologne—we’re ready for you!

Want to know more?

New smell discovered, and it smells like ... well, who knows?Stephanie Pappas  Live Science on NBCnews.com updated 11/19/2012 6:19:55 PM ET[Brief article in plain English summarizes the significance of the discovery]
my-ap.us/ShV1rw

Perceptual convergence of multi-component mixtures in olfaction implies an olfactory white Tali Weiss et al.
Proceedings of the National Academy of Sciences of the United States PNAS Published online before print November 19, 2012, doi: 10.1073/pnas.1208110109
[Original research article]
my-ap.us/S35bL9

Joseph Murray, transplant pioneer

Yesterday, the scientific community lost a true pioneer . . . Joseph Murray, who pioneered skin grafting and developed the first successful organ transplant.  In 1954, he transplanted a kidney from one adult twin to his identical sibling.  He continued to pioneer transplant techniques that have saved countless lives.

In The Human Body in Health & Disease and Structure & Function of the Body, I wrote this about Murray:

"In the twentieth century, Joseph Murray . . . noticed that skin he grafted onto burned soldiers he treated during World War II would eventually be rejected by the body. After the war, Murray tried to understand the body’s immune reactions to transplanted tissues and his work led to the first successful kidney transplants. His breakthroughs in transplanting kidneys not only earned him a Nobel Prize in 1990, it also paved the way for all the different types of tissue and organ transplantation that we see today."

93-year-old Joseph E. Murray suffered a stroke on Thanksgiving day and died yesterday in Boston.

I think the occasional story of a pioneer in the history of human science adds a lot to the A&P course.  Such stories give a human dimension to the pursuit of science and provide the context needed for students to understand how we know what we know.

Today we have a sad but important occasion to bring up the amazing accomplishments of Joseph E. Murray with our students.

Want to know more?

• Joseph E. Murray, Transplant Doctor and Nobel Prize Winner, Dies at 93
• By CORNELIA DEAN
• The New York Times Published online: November 27, 2012
• [Obituary of Murray]
• my-ap.us/Tjwvn7

• Hope, Innovation: Remembering A Transplant Pioneer
• Renee Montagne
• National Public Radio (NPR) Morning Edition Broadcast/published online November 27, 2012
• [Renee Montagne talks with Dr. Atul Gawande about the life and work of Dr. Joseph E. Murray, who performed the first successful organ transplant in 1954. Murray died Monday at age 93.]
• Text my-ap.us/SbAjZ3
• Audio[4 min 15 sec] my-ap.us/QJLI5n

http://my-ap.us/QJLI5n

• Interview with Joseph E. Murray
• Nobel Web (nobelprize.org) Accessed 27 November 2012
• [Interview with Joseph E. Murray by Sten Orrenius at the meeting of Nobel Laureates in Lindau, Germany, June 2000. Joseph Murray talks about what led him into research; developing transplantation medicine (2:38); and whether breakthroughs in clinical research are often ignored by the Nobel Prize Committee (13:10).]
• my-ap.us/Y1v8Ro

• Nobel Lecture by Joseph E. Murray
• Nobel Web (nobelprize.org) Accessed 27 November 2012
• [Joseph E. Murray held his Nobel Lecture on 8 December 1990, at Karolinska Institutet, Stockholm. He was presented by Professor Hans Wigzell of the Karolinska Institutet.]
• my-ap.us/QomBDI

Related textbook content

• Anatomy & Physiology 8th ed.  p. 754, 767, 772-773, 996, A&P Connect: The Nobel Legacy my-ap.us/QZTbK1

• Essentials of Anatomy & Physiology p. 437 my-ap.us/SCfNlj  

• The Human Body in Health and Disease 5th ed. p. 94-95, 154 my-ap.us/fNN00N 

• Structure & Function of the Body 14th ed. p. 102 my-ap.us/X6QxqE

Brain injury in high-def with fiber tracking

U. PITTSBURGH (US) — New imaging technology will allow doctors to clearly see for the first time neural connections broken by traumatic brain injury.

Called High Definition Fiber Tracking [1], the technology shows injuries much like X-rays show a fractured bone, according to researchers from the University of Pittsburgh [2] in a report published online in the Journal of Neurosurgery [3].

In the report [4], the researchers describe the case of a 32-year-old man who wasn’t wearing a helmet when his all-terrain vehicle crashed. Initially, his CT scans showed bleeding and swelling on the right side of the brain, which controls left-sided body movement.





High definition fiber tracking reveals loss of fibers, or connections, on the injured right side (yellow) and the intact, undamaged left side (green). The patient was injured in an ATV accident and lost function in his left leg, arm, and hand. (Credit: Walt Schneider Laboratory)


High definition fiber-tracking map of a million brain fibers. (Credit: Walt Schneider Laboratory)
Straight from the Source


A week later, while the man was still in a coma, a conventional MRI scan showed brain bruising and swelling in the same area. When he awoke three weeks later, the man couldn’t move his left leg, arm and hand.

“There are about 1.7 million cases of TBI in the country each year, and all too often conventional scans show no injury or show improvement over time even though the patient continues to struggle,” says co-senior author and neurosurgeon David O. Okonkwo, associate professor in the neurological surgery department.

“Until now, we have had no objective way of identifying how the injury damaged the patient’s brain tissue, predicting how the patient would fare, or planning rehabilitation to maximize the recovery.”

HDFT might be able to provide those answers, says co-senior author Walter Schneider, professor of psychology, who led the team that developed the technology.

Data from sophisticated MRI scanners is processed through computer algorithms to reveal the wiring of the brain in vivid detail and to pinpoint breaks in the cables, called fiber tracts. Each tract contains millions of neuronal connections.

“In our experiments, HDFT has been able to identify disruptions in neural pathways with a clarity that no other method can see,” Schneider says. “With it, we can virtually dissect 40 major fiber tracts in the brain to find damaged areas and quantify the proportion of fibers lost relative to the uninjured side of the brain or to the brains of healthy individuals. Now, we can clearly see breaks and identify which parts of the brain have lost connections.”

HDFT scans of the study patient’s brain were performed four and 10 months after he was injured; he also had another scan performed with current state-of the-art diffusion tensor imaging (DTI), an imaging modality that collects data points from 51 directions, while HDFT is based on data from 257 directions. For the latter, the injury site was compared to the healthy side of his brain, as well as to HDFT brain scans from six healthy individuals.

Only the HDFT scan identified a lesion in a motor fiber pathway of the brain that correlated with the patient’s symptoms of left-sided weakness, including mostly intact fibers in the region controlling his left leg and extensive breaks in the region controlling his left hand. The patient eventually recovered movement in his left leg and arm by six months after the accident, but still could not use his wrist and fingers effectively 10 months later.

Memory loss, language problems, personality changes and other brain changes occur with TBI, which the researchers are exploring with HDFT in other research protocols.

University of Pittsburgh neurosurgeons also have used the technology to supplement conventional imaging, noted Robert Friedlander, professor and chair in the neurological surgery department, who was not involved with the study.

“I have used HDFT scans to map my approach to removing certain tumors and vascular abnormalities that lie in areas of the brain that cannot be reached without going through normal tissue,” he says.

“It shows me where significant functional pathways are relative to the lesion, so that I can make better decisions about which fiber tracts must be avoided and what might be an acceptable sacrifice to maintain the patient’s best quality of life after surgery.”

Okonkwo notes that the patient and his family were relieved to learn that there was evidence of brain damage to explain his ongoing difficulties. The team continues to evaluate and validate HDFT’s utility as a brain imaging tool, so it is not yet routinely available.

“We have been wowed by the detailed, meaningful images we can get with this technology,” Okonkwo says. “HDFT has the potential to be a game-changer in the way we handle TBI and other brain disorders.”

The study was funded by the Defense Advanced Research Projects Agency.

More news from the University of Pittsburgh: www.news.pitt.edu/ [5]

Article reprinted by CC license from Futurity.org: http://www.futurity.org
Posted By Anita Srikameswaran-Pittsburgh On March 2, 2012 @ 12:58 pm

URL to original article: http://www.futurity.org/top-stories/brain-injury-in-high-def-with-fiber-tracking/

URLs in this post:

[1] High Definition Fiber Tracking: http://schneiderlab.lrdc.pitt.edu/projects/tbi
[2] University of Pittsburgh: http://www.upmc.com/MediaRelations/NewsReleases/2012/Pages/High-Definition-Fiber-Tracking-Traumatic-Brain-Injury.aspx
[3] Journal of Neurosurgery: http://thejns.org/doi/abs/10.3171/2012.1.JNS111282?prevSearch=%255BFulltext%253A%2BOkonkwo%255D&searchHistoryKey=
[4] Read the original study: http://thejns.org/doi/abs/10.3171/2012.1.JNS111282?prevSearch=%255BFulltext%253A%2BOkonkwo%255D&searchHistoryKey=
[5] www.news.pitt.edu/: http://www.news.pitt.edu/

---------------------------------------------------------
Want to know more?

• Neuroscience: Making connections 
• J. Bardin Nature News & Comment 21 March 2012
• http://my-ap.us/REpcFs

Related textbook content

• Anatomy & Physiology 8th ed.  p. 420-453, 1142 my-ap.us/QZTbK1

• Essentials of Anatomy & Physiology p. 246-270 my-ap.us/SCfNlj  

• The Human Body in Health and Disease 5th ed. p. 246-254 my-ap.us/fNN00N 

• Structure & Function of the Body 14th ed. p. 176-187 my-ap.us/X6QxqE

New life science journal eLife publishes first articles

Most journals that publish the "big news" in life science breakthroughs, such as Nature and Science, carry with them big price tags for accessing the information they contain.  Unless your institution subscribes, that leaves most A&P professors out of the loop on the information we need to update our courses.  More importantly, it leaves us out of the loop of information that helps us keep the excitement of science alive in our courses.

The Public Library of Science (PLoS) began publishing FREE online science journals a few years ago, and now a new MAJOR free online journal dedicated specifically to the life sciences and biomedicine has emerged.  See my-ap.us/SqSOJM for more information

First announced in summer 2011, eLife is a researcher-led initiative for the best in science and science communication. Backed by the Howard Hughes Medical Institute, the Max Planck Society, and the Wellcome Trust, the initiative’s first aim is to launch an open-access journal for outstanding advances in life science and biomedicine, which is also a platform for experimentation and showcasing innovation in research communication.

The eLife journal Web site is set for launch by the end of 2012, but the first collection of articles was released October 15 – listed at the eLife Web site with the full content available at the online archive of the U.S. National Library of Medicine, PubMed Central (PMC), and its mirror sites including UKPMC.

According to Randy Schekman, the journal’s Editor-in-chief, “We see no reason to delay the availability of these discoveries. Our editors have identified them as important, inspiring contributions of the high caliber expected for eLife. So, while the launch of our own journal Web site isn’t expected until December, we will best serve our authors, and science, by just getting them out there.”

eLife’s initial collection of content includes these topics that may be of interest to A&P professors:

• A hormone involved in response to starvation that dramatically increases the lifespan of mice in which it is overexpressed, although further research into side effects is needed (Zhang et al.).  Information about this discovery will increase student interest in endocrine function, eh?


• A critical signaling molecule involved in the interaction between a species of single-celled organisms and bacteria – an important advance in efforts to understand the evolution of multicellularity (Alegado et al.).  I often discuss the implications of the serial endosymbiosis theory in my teaching of cell biology— I think this new information may play into that whole scenario.


• How cells cope with the stress of poorly folded proteins, and specifically how fission yeast deploys the same cellular machinery as other organisms but in an unusual and very different way (Kimmig et al.). I've mentioned the importance of understanding protein folding in A&P many times.

Links to the freely available full text for each article, plain-language summaries (the eLife digest), expert commentaries (Insights), and an editorial describing the motivations behind this move, are available at my-ap.us/U7OP25.  I think the eLife digest and the Insights are particularly useful for A&P professors and A&P students to use in expanding their understanding of human structure and function.

Want to know more?

For more information about eLife, visit my-ap.us/S5K9d3.

To sign up for free updates in the areas that interest you at my-ap.us/WToDyp

Content adapted from eLife press release 

New method to avoid mitochondrial disorders

A recent paper in Nature describes a new approach to avoiding inherited mitochondrial disorders.

Although identified as "germline gene therapy," in the title of the paper the method is a lot like cloning. The method calls for transferring a healthy nucleus out of an egg with mutant mitochondria, then transferring that nucleus to a healthy donor egg.

In this technique, scientists are not making a genetic copy of an individual as an cloning — but the technique is very similar. The whole idea of this is an interesting one to bring up in an A&P course when discussing the topic of mitochondrial inheritance. It not only emphasizes and clarifies the central idea of mitochondrial inheritance, it's also a good way to connect students to "what's going on right now" in the world of science. 

Among the links below I have included an article from Science News that does a great job of summarizing the new research and pointing out some of the ethical concerns that the method poses.

The article also contains a sidebar listing some of the mitochondrial diseases that might be avoided using the technique. That sidebar complements the coverage of mitochondrial inheritance found in my textbooks. 

Check out this video that demonstrates how the method is carried out in the lab.  You can use this video in your course!

Want to know more?

• Cloning-like method targets mitochondrial diseases: providing healthy ‘power plants’ in donor eggs appears feasible in humans
• Tina Hesman Saey Science News Web edition: October 24, 2012 Print edition: November 17, 2012; Vol.182 #10 (p. 5)
• A great feature article that summarizes the discovery in plain English.  Might be the best place to point your students if they want more information.
• my-ap.us/SEPeg5

• Towards germline gene therapy of inherited mitochondrial diseases. 
• M. Tachibana et al. Nature. Published online 24 Oct 2012 doi:10.1038/nature11647
• Abstract of original journal article describing the method. Includes images.
• my-ap.us/RwC2cf

Related articles

• Mitochondria Gone Bad | Genes & Cells | Science News my-ap.us/SyJGBk

• Embryo transfer technique could prevent maternally inherited diseases | Body & Brain | Science News my-ap.us/VjPGSR

• Mitochondrial DNA replacement successful in Rhesus monkeys | Genes & Cells | Science News my-ap.us/VInDbs

Related textbook content

• Anatomy & Physiology 8th ed.  p. 77, 1142 my-ap.us/QZTbK1

• Essentials of Anatomy & Physiology p.53 my-ap.us/SCfNlj  

• The Human Body in Health and Disease 5th ed. p. 45, 672, A-13 my-ap.us/fNN00N 

• Structure & Function of the Body 14th ed. p. 41-42 my-ap.us/X6QxqE

Here's a related image you can use in your course: my-ap.us/QZVNaH

G-protein coupled receptors

The Royal Swedish Academy of Sciences has decided to award the
Nobel Prize in Chemistry for 2012
to

Robert J. Lefkowitz
Howard Hughes Medical Institute and Duke University Medical Center, Durham, NC, USA

and

Brian K. Kobilka
Stanford University School of Medicine, Stanford, CA, USA

"for studies of G-protein–coupled receptors"


Smart receptors on cell surfaces

Your body is a fine-tuned system of interactions between billions of cells. Each cell has tiny receptors that enable it to sense its environment, so it can adapt to new situtations. Robert Lefkowitz and Brian Kobilka are awarded the 2012 Nobel Prize in Chemistry for groundbreaking discoveries that reveal the inner workings of an important family of such receptors: G-protein–coupled receptors (GPCRs).

For a long time, it remained a mystery how cells could sense their environment. Scientists knew that hormones such as adrenalin had powerful effects: increasing blood pressure and making the heart beat faster. They suspected that cell surfaces contained some kind of recipient for hormones. But what these receptors actually consisted of and how they worked remained obscured for most of the 20th Century.

Lefkowitz started to use radioactivity in 1968 in order to trace cells' receptors. He attached an iodine isotope to various hormones, and thanks to the radiation, he managed to unveil several receptors, among those a receptor for adrenalin: β-adrenergic receptor. His team of researchers extracted the receptor from its hiding place in the cell wall and gained an initial understanding of how it works.

The team achieved its next big step during the 1980s. The newly recruited Kobilka accepted the challenge to isolate the gene that codes for the β-adrenergic receptor from the gigantic human genome. His creative approach allowed him to attain his goal. When the researchers analyzed the gene, they discovered that the receptor was similar to one in the eye that captures light. They realized that there is a whole family of receptors that look alike and function in the same manner.

Today this family is referred to as G-protein–coupled receptors. About a thousand genes code for such receptors, for example, for light, flavour, odour, adrenalin, histamine, dopamine and serotonin. About half of all medications achieve their effect through G-protein–coupled receptors.

The studies by Lefkowitz and Kobilka are crucial for understanding how G-protein–coupled receptors function. Furthermore, in 2011, Kobilka achieved another break-through; he and his research team captured an image of the β-adrenergic receptor at the exact moment that it is activated by a hormone and sends a signal into the cell. This image is a molecular masterpiece--the result of decades of research.

Laureate's Links

Robert J. Lefkowitz, U.S. citizen. Born 1943 in New York, NY, USA. M.D. 1966 from Columbia University, New York, NY, USA.Investigator, Howard Hughes Medical Institute. James B. Duke Professor of Medicine, and Professor of Biochemistry, Duke University Medical Center, Durham, NC, USA.
lefkolab.org

Brian K. Kobilka, U.S. citizen. Born 1955 in Little Falls, MN, USA. M.D. 1981 from Yale University School of Medicine, New Haven, CT, USA. Professor of Medicine, and Professor of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA, USA.
med.stanford.edu/kobilkalab

Want to know more?

Popular Information
[A great synopsis, entitled "Cells and Sensibility," written for general reader and nicely illustrated.  This would make a great handout or reading assignment for your A&P class.]
my-ap.us/SLShCF

Scientific Background
[A more technical treatment of the discovery, but still accessible to advanced A&P students as well as A&P professors.  Includes extensive references.  Illustrated.]
my-ap.us/PnK4Fz

Adapted from my-ap.us/TwmIyd

Reprogramming cells to be pluripotent

The Nobel Assembly at Karolinska Institutet has today decided to award

The Nobel Prize in Physiology or Medicine 2012
jointly to

John B. Gurdon and Shinya Yamanaka
for the discovery that mature cells can be reprogrammed to become pluripotent

Summary
The Nobel Prize recognizes two scientists who discovered that mature, specialised cells can be reprogrammed to become immature cells capable of developing into all tissues of the body. Their findings have revolutionised our understanding of how cells and organisms develop.

John B. Gurdon discovered in 1962 that the specialisation of cells is reversible. In a classic experiment, he replaced the immature cell nucleus in an egg cell of a frog with the nucleus from a mature intestinal cell. This modified egg cell developed into a normal tadpole. The DNA of the mature cell still had all the information needed to develop all cells in the frog.

Shinya Yamanaka discovered more than 40 years later, in 2006, how intact mature cells in mice could be reprogrammed to become immature stem cells. Surprisingly, by introducing only a few genes, he could reprogram mature cells to become pluripotent stem cells, i.e. immature cells that are able to develop into all types of cells in the body.

These groundbreaking discoveries have completely changed our view of the development and cellular specialisation. We now understand that the mature cell does not have to be confined forever to its specialised state. Textbooks have been rewritten and new research fields have been established. By reprogramming human cells, scientists have created new opportunities to study diseases and develop methods for diagnosis and therapy.

Life – a journey towards increasing specialisation

All of us developed from fertilized egg cells. During the first days after conception, the embryo consists of immature cells, each of which is capable of developing into all the cell types that form the adult organism. Such cells are called pluripotent stem cells. With further development of the embryo, these cells give rise to nerve cells, muscle cells, liver cells and all other cell types - each of them specialised to carry out a specific task in the adult body. This journey from immature to specialised cell was previously considered to be unidirectional. It was thought that the cell changes in such a way during maturation that it would no longer be possible for it to return to an immature, pluripotent stage.

Frogs jump backwards in development

John B. Gurdon challenged the dogma that the specialised cell is irreversibly committed to its fate. He hypothesised that its genome might still contain all the information needed to drive its development into all the different cell types of an organism. In 1962, he tested this hypothesis by replacing the cell nucleus of a frog's egg cell with a nucleus from a mature, specialised cell derived from the intestine of a tadpole. The egg developed into a fully functional, cloned tadpole and subsequent repeats of the experiment yielded adult frogs. The nucleus of the mature cell had not lost its capacity to drive development to a fully functional organism.

Gurdon's landmark discovery was initially met with scepticism but became accepted when it had been confirmed by other scientists. It initiated intense research and the technique was further developed, leading eventually to the cloning of mammals. Gurdon's research taught us that the nucleus of a mature, specialized cell can be returned to an immature, pluripotent state. But his experiment involved the removal of cell nuclei with pipettes followed by their introduction into other cells. Would it ever be possible to turn an intact cell back into a pluripotent stem cell?

A roundtrip journey – mature cells return to a stem cell state

Shinya Yamanaka was able to answer this question in a scientific breakthrough more than 40 years after Gurdon´s discovery. His research concerned embryonal stem cells, i.e. pluripotent stem cells that are isolated from the embryo and cultured in the laboratory. Such stem cells were initially isolated from mice by Martin Evans (Nobel Prize 2007) and Yamanaka tried to find the genes that kept them immature. When several of these genes had been identified, he tested whether any of them could reprogram mature cells to become pluripotent stem cells.

Yamanaka and his co-workers introduced these genes, in different combinations, into mature cells from connective tissue, fibroblasts, and examined the results under the microscope. They finally found a combination that worked, and the recipe was surprisingly simple. By introducing four genes together, they could reprogram their fibroblasts into immature stem cells!

The resulting induced pluripotent stem cells (iPS cells) could develop into mature cell types such as fibroblasts, nerve cells and gut cells. The discovery that intact, mature cells could be reprogrammed into pluripotent stem cells was published in 2006 and was immediately considered a major breakthrough.

From surprising discovery to medical use

The discoveries of Gurdon and Yamanaka have shown that specialised cells can turn back the developmental clock under certain circumstances. Although their genome undergoes modifications during development, these modifications are not irreversible. We have obtained a new view of the development of cells and organisms.

Research during recent years has shown that iPS cells can give rise to all the different cell types of the body. These discoveries have also provided new tools for scientists around the world and led to remarkable progress in many areas of medicine. iPS cells can also be prepared from human cells.

For instance, skin cells can be obtained from patients with various diseases, reprogrammed, and examined in the laboratory to determine how they differ from cells of healthy individuals. Such cells constitute invaluable tools for understanding disease mechanisms and so provide new opportunities to develop medical therapies.

Sir John B. Gurdon was born in 1933 in Dippenhall, UK. He received his Doctorate from the University of Oxford in 1960 and was a postdoctoral fellow at California Institute of Technology. He joined Cambridge University, UK, in 1972 and has served as Professor of Cell Biology and Master of Magdalene College. Gurdon is currently at the Gurdon Institute in Cambridge.

Shinya Yamanaka was born in Osaka, Japan in 1962. He obtained his MD in 1987 at Kobe University and trained as an orthopaedic surgeon before switching to basic research. Yamanaka received his PhD at Osaka City University in 1993, after which he worked at the Gladstone Institute in San Francisco and Nara Institute of Science and Technology in Japan. Yamanaka is currently Professor at Kyoto University and also affiliated with the Gladstone Institute.

Key publications:

Gurdon, J.B. (1962). The developmental capacity of nuclei taken from intestinal epithelium cells of feeding tadpoles. Journal of Embryology and Experimental Morphology 10:622-640.

Takahashi, K., Yamanaka, S. (2006). Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126:663-676.

Link to a FREE handout you can use in your A&P class: my-ap.us/UNtV9i

Want to know more? Try my-ap.us/TbNCWG


Adapted from my-ap.us/TlWoqC

That junk is valuable!

During spring cleaning in my household, I'm often heard lamenting that yet another of my treasures has been deemed "junk" and hurled into the "it's outta here" box.  As we've been discovering in science, so-called "junk DNA" is also truly a treasure.

As scientists have been outlining for years, even before the start of the ENCODE project to explore the genome "within and between the genes," the noncoding regions of DNA contain important information that allows cells to regulate the activity of genes.

The ENCODE (Encyclopedia of DNA Elements) just announced the publication of 30 linked papers in Nature and other journals that give us the clearest picture yet of the critical roles played by noncoding DNA. 

The journal Nature has a great site that links many resources about these new discoveries in one nifty "dashboard."  Besides the 30 linked papers, you can access podcasts, news, comments, quick summaries of the ENCODE project, and more.  It's a great place to get up to speed on what's going on, so that we can be more informed about the current state of knowledge as we weave the genomic story into our A&P courses.

You might even find some resources that you can use directly in your course . . . or as supplemental activities.

Explore Nature's ENCODE site at my-ap.us/NatureENCODE

Doping. Again.

Most of us mention the concept of doping in our A&P courses because it's an ever present issue in our society and therefore a good way to help students apply their knowledge of human structure and function to practical scenarios.  As I've mentioned in previous posts, in Olympic years it becomes an even more potent way to draw students interest into the world of human A&P.

Once again, we're hearing doping stories in the news.  On the heels of continuing scandals in the sport of cycling, we are now hearing reports of doping in Olympic athletes.

As many longtime readers of this blog know, besides several blog articles, I have a resource page on doping for A&P teachers at my companion website The A&P Professor.

There is also a recent article in The Scientist outlining advances in detection of doping in athletes.  This article is not only informative for personal enjoyment of the current Olympic games--because we'll all be more knowledgeable--but it's a great resource to prepare for the student questions we'll be getting soon.  And in the near future.

Want to know more?

Anti-Doping Research Gets Creative: Scientists work hard to keep up with ever-evolving performance enhancement techniques that go undetected by existing tests.
Sabrina RichardsThe Scientist Online July 26, 2012
[Comprehensive, easy-to-follow article on the latest in anti-doping strategies. Might be good assigned reading for your course.]
my-ap.us/SXKHU0

Kevin's blog articles on doping
 . . . and how to use doping to illustrate A&P in your classroom
my-ap.us/aa3AjM

Resource page on doping at The A&P Professor website
my-ap.us/942vMZ

Andrew Huxley

A few weeks ago, science lost one of its greats . . . Andrew Fielding Huxley. 

As explained in my textbooks, "The British physiologist Andrew F. Huxley (born 1917) is  largely responsible for explaining how muscle fibers contract. After making pioneering discoveries in how nerves conduct impulses, a feat for which he shared the 1963 Nobel Prize in Medicine or Physiology, Huxley turned his attention to muscle fibers. It was he who in the 1950s proposed the sliding filament model, along with its mechanical explanation of muscle contraction."

Sometimes, our students don't fully appreciate that much of what we know about basic functions of the body have been discovered only within the last few decades.  They may not realize that people alive during their lifetimes were the ones who discovered central concepts of human structure and function, such as how nerves conduct action potentials and how muscle fibers contract.

The reason I include stories of Huxley and others in both my A&P textbooks and in my classroom discussions is that I think the story of science is important in gaining deep understanding of the concepts learned in A&P.  Learning "just the facts" devoid of their context and without any understanding of how we learned what we know does not give our students what they need to navigate the ongoing evolution of our scientific understanding of human A&P.

I also like to include stories of the people who helped shape our current understanding of the body's structure and function because it reveals the diversity of backgrounds, approaches, ethnic/national origins, gender, and age of the folks who have made striking discoveries and provided critical insights. I think that helps students understand that they, too, can play a role in the progress of science.

If you want to brush up on Huxley's role in the progress of science--so that you can perhaps drop it during your classroom discussions of nerve impulses and muscle contraction--check out the resources I have provided.

Want to know more?

Sir Andrew Huxley obituary: He shared the Nobel prize for unravelling the mechanism of the nerve impulse
Anthony Tucker   
guardian.co.uk, Thursday 31 May 2012 13.05 EDT
[Nice article summarizing the life and contributions of A. Huxley]
my-ap.us/O6jMUL   

Andrew Huxley, Nobel-Winning Physiologist, Dies at 94
By DENISE GELLENE
New York Times (online) June 4, 2012
[Another comprehensive obituary of Huxley]
my-ap.us/O7flW7

Click here for a photo you can use in your course.

Stem cells in the ovary

Beginning about 8 years ago, scientists began providing evidence that apparently overturns the dogma that adult ovaries do not contain stem cells capable of producing oocytes.  Jonathon Tilly found such cells first in mice, then later in middle-aged women. Other labs have replicated such findings.

However, a study by members of Kui Liu's lab published today disputes that the stem cells actually produce oocytes.  Needless to say, this is stirring up quite a bit of controversy.  Tilly believes Liu was looking at oocytes, not stem cells.  Liu doesn't agree.

What does this mean for the undergraduate A&P class?  I discuss the recent discoveries of stem cells in adult ovaries in my course.  I use it as an opportunity to point out that there is still much to learn about how the human body works . . . that we are continually surprised by new research findings.  This is part of a year-long subtext of "how science works."  I tell my A&P students that I'm telling them "the last, best story" about the human body.  But that my story changes from year to year as scientists tease out more information . . . and thus revise "the story."

How does this fit in?  Well, isn't this how science is supposed to work?  Wouldn't it seem logical that it is in the best interest of everyone to have vigorous debate and extensive re-examination before we throw out the last, best story in favor of a new version?

The first article below briefly summarizes the issues involved in today's publication.


Want to know more?

Ovarian Stem Cell Debate
Ed Yong
The Scientist (online) July 9, 2012
[Brief article discusses  that opinion is divided on a new paper showing that adult ovaries do not contain egg-making stem cells, contrary to two recent studies that appeared to overturn longstanding dogma.]
my-ap.us/Mf1Y5w

Experimental evidence showing that no mitotically active female germline progenitors exist in postnatal mouse ovaries
H. Zhang et al.
Proceedings of the National Academy of Sciences doi:10.1073/pnas.1206600109
[Recent paper disputing presence of stem cells in adult ovaries]
my-ap.us/RX4McG

Ovarian Stem Cells in Humans?
Sabrina Richards
The Scientist (online) February 27, 2012
[Brief summary of recent paper by Tilly's lab stating that adult human ovaries contain a population of stem cells capable of generating immature egg cells.]
my-ap.us/OWGY8G

Oocyte formation by mitotically active germ cells purified from ovaries of reproductive-age women
Y.A.R. White et al.
Nature Medicine 18:413–21, 2012.
[Original research paper by Tilly's lab showing presence of stem cells in human ovaries.]
my-ap.us/LFaYqX

The image above is copyright free and can be used in your course!

Want to fold some proteins?

In a previous post, I proposed that A&P students should be aware of the basic elements of protein folding.  To follow up, I'd like to mention a interesting phenomenon related to protein folding and "citizen science" using an online game called Foldit.  


The Foldit game is an online puzzle game in which anybody can try their hand and finding which way a given protein folds most efficiently.  Interestingly, this has proven to yield useful results for biochemists not obtainable by traditional methods.

You may want to mention the Foldit game to students.  I've already posted it at my blog The A&P Student.

Want to know more?

Online Gamers Achieve First Crowd-Sourced Redesign of Protein
Jessica Marshall & Nature magazine
Scientific American Online January 22, 2012
[Brief article about recent redesign of a protein by online gamers using Foldit. Original paper published in Nature Biotechnology]
my-ap.us/wRK2bV

Foldit Online Protein Puzzle
Scientific American Citizen Science accessed 23 January 2012
[Brief description of the online game Foldit and the goals of the project.]
my-ap.us/zIV75F

Foldit - Solve Puzzles for Science
[Direct link to portal for the game Foldit]
my-ap.us/wfRQPF

Why bother with protein folding?

For those of you who use (or refer to) my textbooks, you may notice that I've been gradually adding more and more coverage of protein folding to most of them. My newest text (due out in March) adds a bit more to the story. Why bother?  Isn't that way more than beginning students need to know for an A&P course preparing students for health careers?

I submit that beginning A&P students should know a bit about protein folding.

Knowing the very basic principles of protein folding help students visualize the complex shape of proteins.  That, in turn, helps them understand that "it's all about shape" when trying to understand how proteins like enzymes, receptors, and most other proteins work—proteins that they'll encounter many times throughout their A&P course and beyond. 

Besides that, protein folding has become a key concept in understanding not only how the body functions, but how to intervene therapeutically in important diseases.  If a class of therapy based on protein folding is now being developed, a class of therapy that many of our students will likely encounter in their professions, don't we owe it to them to cover the basic ideas of protein folding? 

This latest idea was brought up at a recent meeting of the American Society of Cell Biology (ASCB).  You may want to read the article below, which briefly summarizes some current work being done in developing drugs that affect protein folding systems.  None of the specific  information in the article would be appropriate for A&P students to learn.  But reading it will give the A&P professor better insights about why the concept of protein folding is important for students to learn.  And it gives you a chance to say, "I was just reading about how scientists are now developing drugs based on protein folding . . . " to get their attention in class!

Want to know more?

Protein Folding and Disease: The Path from Bench to Bedside
V. Glaser
Genetic Engineering & Biotechnology News 15 Jan 2012. Vol. 32, No. 2
[Brief, illustrated article that clearly summarizes some recent work in applying principles of protein folding to drug therapies.]
my-ap.us/wFh6F2

Protein folding animation
[Interesting Quicktime animation that shows a protein folding]
my-ap.us/xzWnW4

GCSF Protein Folding Illustration Movie
[Another animation, a bit more complex than the previous one.  Clearly shows different types of models used in most A&P textbooks.]
my-ap.us/xpSisS


The Three-Dimensional Structure of Proteins
[Narrated animation showing four levels of protein structure, including visualization of protein folding.]
my-ap.us/yAS2fr

Free book on heart function!

Besides free advice, The A&P Professor is also a big fan of free resources and references.  And here's a set of free resources that will help give you a new perspective on cardiovascular function, particularly the factors that affect cardiac output.

I was recently contacted by Doug Anderson, a relative of the late cardiac surgeon, educator, and inventor Robert M. Anderson.  Doug told me about their family's efforts to make Dr. Anderson's contributions to understanding cardiovascular function widely available to the educational community.

Besides a FREE downloadable textbook outlining an approach to understanding cardiovascular function that is different than what you might be used to, there is also a FREE video that summarizes Anderson's concepts.

The video features Anderson himself walking the viewer through the operation of an elegant pump that he designed and built for teaching purposes. For a deeper understanding of the fluid dynamics behind cardiac function, you should consider watching the video.

By the way, this textbook has a  Creative Commons license that allows you to use all or part of it FREE in your course!

Anderson with his circulation model 

If you are looking for a FREE "medical school lesson" on the factors that influence blood flow, then check out these resources:

Want to know more?



Free textbook

Gross Physiology of the Cardiovascular System
Robert M. Anderson
PDF (printable) my-ap.us/zGtqOa 
Kindle and ePub formats coming soon!

Free video

The Determinants of Cardiac Output
University of Arizona Health Sciences Center with Robert M. Anderson et. al.
Video my-ap.us/xT5dx9
Illustrated transcript my-ap.us/ywWcgL

Free website

Gross Physiology of the Cardiovascular System
Includes additional resources
cardiac-output.info

Anderson's approach is a bit different than what many of us are used to.  Tell me what you think!

Testing as a Learning Tool

Almost two years ago, I published an article about testing as a method of teaching in my blog The Electronic Professor. In the article, I shared my experience in using frequent online tests in my anatomy & physiology courses as a way to get students engaged with the material on an ongoing basis.

Almost a year later, research published in Science further supported this idea.  Not that I needed the support . . . my own experience over several years has confirmed for me that it works.  In fact, it works VERY well in enhancing student learning.  But as a scientist, a variety of independent confirmations of a topic is appreciated.

Of course, the concept of frequent, online formative testing (as opposed to summative testing) is not at all new.  But like a lot of breakthroughs in teaching and learning, it hasn't caught on with many professors "out in the trenches" yet.  But it's really worth taking a look at.

First, check out my article from 2009 to get an idea of what I'm talking about.

Teaching as Testing
Kevin Patton
The Electronic Professor. 27 Feb 2009.
[Article outlining my use of online, randomized formative tests in teaching A&P.]
my-ap.us/p3rM6B

Then check out the seminar that I gave on this topic a few years ago.

Seminar: Testing as Teaching
Kevin Patton
The A&P Professor. Accessed Jan 2012.
[Narrated presentation outlining a method to produce randomzed formative tests for A&P.]
my-ap.us/qtAclX

After that, take a look at the research published in Science a year ago.

To Really Learn, Quit Studying and Take a Test
Pam Belluck
The New York Times. 20 January 2011.
[Brief summary of the research, including a graph of the results.]
my-ap.us/yP6jZ0 

Retrieval Practice Produces More Learning than Elaborative Studying with Concept Mapping
J.D. Karpicke, J. R. Blunt
Science. Published Online January 20 2011. DOI: 10.1126/science.1199327
[Original research mentioned above.]
my-ap.us/yTr2b7

Academic integrity in the A&P course

How do you prevent cheating in your A&P class?  Or do you even think about it?

One of my favorite "teaching" books is What the Best College Teachers Do.  After examining diverse "master teachers," the author (Ken Bain) lists some of the characteristics most often seen in such individuals.  One of them is that master teachers do not fret much about cheating in their courses.  Instead, they seem to focus more on developing a culture in each learning community that naturally discourages dishonesty by building trust and integrity.

That revelation changed the way I look at cheating in my courses.  Rather than working hard at developing complex anti-cheating strategies, I work hard at educating my students about the value of academic integrity. Although one can never be absolutely certain of the extent of cheating in one's courses, the tools I do have available tell me that cheating is not a significant problem in my courses.

Of course, I do pay attention to setting things up in ways that discourage cheating, but I don't go overboard . . . and I don't worry about it.

How, exactly, do I promote academic integrity?  And what are some of the specific methods that I use to discourage cheating?   Those answers and more can be found in the resources below:

Want to know more?

Why be honest?
Kevin Patton
The A&P Student 5 January 2012
[Brief article for students.  Explains why they should want to be honest. You can link to this in your syllabus or course website.]
my-ap.us/zHHd7H

Academic Integrity
Kevin Patton
The A&P Professor accessed 5 January 2012
[Extended version of this article.  It also gives specific tips and examples, as well as free resources such as handouts, syllabus example, and PowerPoint slides.]
my-ap.us/xSDoxP

Free bookmarks for your students!

As you begin another term of A&P, don't forget to stock up on those FREE eyeball bookmarks for your students!

These unique "anatomically correct" first-day-of-class gifts for your students include information for your students on how to access my blog The A&P Student.  This blog has a continuously updated library of study tips for A&P, shortcuts, links to learning resources, and more.

These bookmarks are available in packs of 50 to qualified A&P instructors.  And if you act now, you'll also get some fun freebies for yourself!

Get your free bookmarks here: my-ap.us/99NNTx