Monday, October 26, 2009

Revisiting the spleen


I'll never forget that snowy day all those years ago when my friend Keith slammed his sled into a laundry pole and ruptured his spleen.  Perhaps as an expression of our shock and concern for him as he lay in his hospital bed after his splenectomy, we spent an afternoon wondering to each other, "what IS a spleen . . . and how can you live without one?" 

As we all know, the spleen has a number of functions including acting as a blood reservoir and as a site of lymphocyte development and activity.  Research published a few months ago has now expanded our understanding of this odd organ.

According to the new research, another function of the spleen is to serve as a reservoir of monocytes that can be called upon during tissue injury in other locations of the body.  The splenic monocytes, which far outnumber the monocytes circulating in the bloodstream, form clusters in the cords of red pulp just under the capsule (wall of the organ).  From there, they move in a group out of the spleen and to the site of injury.  There they help remove and repair damaged tissue. 


This is a FREE image (click for source).
You can use it in your course.



Want to know more?
Identification of Splenic Reservoir Monocytes and Their Deployments to Inflammatory Sites
Swirski, F. K. et al.
Science 31 July 2009: Vol. 325, no. 5940, pp. 612-616
DOI: 10.1126/science.1175202
[The original research article.  A particularly clear abstract.]

Dispensible But Not Irrelevant
Jia T. et al.
Science 31 July 2009: Vol. 325. no. 5940, pp. 549 - 550
DOI: 10.1126/science.1178329

[Editor's summary of the implications of the original research.  Full text version includes a great diagram of this newly discovered role of the spleen.]

Finally, the Spleen Gets Some Respect
N. Angier
The New York Times 3 August 2009
[Article summarizing the new findings.]

While we're on the subject of the spleen, have you seen the images of a pelvic spleen published recently in the New England Journal of Medicine?  The piece in the NEJM briefly documents the case of a rare condition in which the spleen my drop into the pelvic cavity when there is problem with the suspensory ligaments of the spleen.

Pelvic Spleen: Images in Clinical Medicine
Tseng and Chou
New England Journal of Medicine 361 (13): 1291, Figure 1
[Images.  Includes link to FREE PowerPoint slide for subscribers]


 For a few FREE images of the spleen, go to the Lymphatic Image Library at The A&P Professor website

Keeping time


Finally . . . a physiological explanation for why I have such hard time keeping time when trying to dance.  Any of you who have seen me on the dance floor at a Human Anatomy and Physiology Society (HAPS) conference know what I mean!

It turns out that there are time-keeping neurons in our brains.  Specifically in the prefrontal cortex and striatum of the cerebrum. Discovered recently in the brains of monkeys by researchers at MIT, these time-keeping neurons fire consistently at certain rhythms . . . thus helping our brains to figure out when things are happening.  This helps us with rhythmic activities, of course, but also with any number of tasks and memories that rely on knowing what came first, in what order, and so on. 

Researchers speculate that damage to these neurons, or damage to the mechanisms that read the timing pattern, may contribute to disorders (such as Parkinson Disease) that involve ill-timed movements and other functions.  And perhaps may explain why Kevin has a such a hard time dancing.

In their paper, researchers failed to speculate whether this is why A&P students know exactly when to start slamming their books shut moments before a class is scheduled to end.

Want to know more?

Neural representation of time in cortico-basal ganglia circuits
Jin, DZ et al.
Proceedings of the National Academy of Sciences, 22 Oct 2009


[Original research article]




Time-keeping Brain Neurons Discovered

Massachusetts Institute of Technology (2009, October 23).
[Press release summarizing the context of the discovery.]

Monday, October 19, 2009

Why the Golgi apparatus looks so funny


Did you ever wonder why the Golgi apparatus looks so odd, compared to other membranous organelles of the cell?  I mean, really, wouldn't you think that the forces causing other membrane-bound structures to form more of a globular shape would cause the cisternae (sacs) of the Golgi apparatus to be more, well, round?

A few days ago, the journal Cell published an article that answers that question . . . revealing an elegant mechanism resulting from the primary function of the Golgi apparatus.

As we know, the Golgi apparatus "processes and packages" proteins that arrive from the endoplasmic reticulum (ER) by way of ER vesicles. The central structure of the organelles is the Golgi stack or dictyosome, which resembles a stack of hollow pancakes. Vesicles pinch off of the first cisterna (cis face) and move to the next cisterna, then the next, and finally to the final cisterna (trans face).  Then a vesicle pinches off and moves to the plasma membrane, where it fuses and releases (secretes) it contents to the outside of the cell (exocytosis). Click here for a simplified video summary.

The new data suggest that the budding of vesicles and their movement toward the plasma membrane rely on the function of a protein called GOLPH3.  This tiny protein connects special phospholipid molecules [PtdIns(4)P] in the Golgi membrane to myoglobin molecules (MYO18A).  The myoglobin, in turn, is attached to F-actin filaments of cytoskeleton.  Well, you know what that means, right?  Yes . . . the myoglobin is a motor molecule that pulls the attached Golgi membrane along the F-actin filament, stretching it out into its familiar elongated shape.  Then thwap! . . . a vesicle pinches off and is carried away.

In short, the Golgi membranes flatten out because they are being pulled outward by the cytoskeleton in a process that produces budding of vesicles.  As simple as that!  Now, when you're describing this amazing little organelle in your A&P class, you have a new little twist to add to the story! 


By the way, the terms Golgi complex and Golgi apparatus, which are synonyms, are among the rare eponyms that appear in theTerminologia Histologica (TH). As you recall, the TH is the "official" list of microscopic anatomy terms produced by the FICAT (Federative International Committee on Anatomical Terminology).  It is named for its discoverer Camillo Golgi, who was ridiculed for believing it to be a distinct organelle.

(For a video on international terminology that you can share with students, go to http://www.youtube.com/watch?v=94PU6J3Y9mA)

Now for the next question to be answered . . . what mechanism pulled Golgi's mustache out into that crazy handlebar shape?
 
GOLPH3 bridges phosphatidylinositol-4-phosphate and actomyosin to stretch and shape the golgi to promote budding. 
Dippold, H.C. et al. 
Cell 139 (Oct. 16) 2009. 
DOI 10.1016/j.cell.2009.07.052
[The original paper. The "supplemental material" icludes a video showing the stretching of the Golgi]

Golgi's Job Stretches it Thin
Lisa Grossman
Science News October 19, 2009
[Summary article explains the context and importance of the discovery]

[For more FREE images of the Golgi apparatus, visit the FREE Image Library at The A&P Professor website.]

Flu facts . . . the basics about H1N1

The CDC tells us that there is widespread 2009 novel H1N1 influenza activity in 41 states and that the number of cases, hospitalizations, and deaths continue to increase.
 
Many of you have begun implementing strategies on your campus to minimize the spread of the flu, including self-isolation of faculty, staff, and students with flu-like symptoms.  The CDC suggests that nearly all flu cases right now are 2009 novel H1N1 infections.

Recently, I published a brief article in a publication called The Global Pages on my home campus that lays out the basic science needed to understand what's going on.  It's not a detailed report of the current status or all the complicated virology and epidemiology involved.  It's just a basic foundation of essential terms and key concepts about viruses, public health management, and this particular flu strain.  And why it's not really "swine flu" in the strictest sense, anyway.  It's directed at the average student (not particularly science students).


I'm sharing it because it may help you answer those inevitable questions that your students may have.  Feel free to share it with your students.

Novel H1N1--A Global Health Threat
Kevin Patton
The Global Pages Vol. 10 (No. 1) Fall 2009 St. Charles Community College
[A PDF-format handout that you can read and/or share with your students.  Click here for a SWF-format file that you can embed in a PowerPoint slide or a course web page.] 
 

Action potential in action


I recently found a really nice FREE animation of the action potential. It's from Harvard's outreach program and it does a great job of breaking down the essential processes of this hard-to-learn, hard-to-teach concept.

I've just added it to my own course outline so that my students can access it easily. One might also use it during class, or a tutoring session with students, to reinforce understanding of the action potential's mechanisms. Hmmm . . . this could also be a good thing to go through with my students in my A&P 1 Supplement course, eh?
Action Potential Animation
[Interactive animation]

Action Potential Video
[Another nice, animated explanation of the action potential]

Action Potential Diagram
[A free diagram of the action potential. Compares the ideal "schematic" to a recorded action potential.]

Monday, October 12, 2009

Virtual autopsies


Wow, this goes on my wish list for the holiday season. Take a look at the Virtual Autopsy system at visualiseringscenter.se

After scanning a body, users can manipulate the images on what my editor, Jeff Downing, calls "an iPhone on steroids." It's a big table-top, touch-screen monitor that shows high-resolution 3D images of the scanned body.

The creators tout their project as a potential solution to situations where traditional autopsies cannot be performed (for example, in areas where cultural taboos prohibit it). It can also be a complement to traditional autopsies because it can show things that may not be visible during the routine type of examination.

Besides the gee-whiz, ain't that cool factor you'll experience when you check it out, you may want to consider showing one of the FREE video clips to your students to show them what's happening out there on the cutting edge of anatomy applications. This might be a great bit to add to your "first lecture" dog-and-pony show to get your students engaged and excited about human A&P.

There are also some cool case study ideas included at the demo page.

If you get one of these things, let me know. I want to come and play with it!

Visual Analogy Guides


Well, it's "book order" time here at my college and I'm going to be recommending a series of student supplements for A&P that I've found to be really, really helpful. The Visual Analogy Guide series has been used by my students for a couple of years now and my students love them.

Created by my friend Paul Krieger at Grand Rapids Community College (GRCC), the Visual Analogy Guides really meet the students where they are at to help them master some of those little tricks for learning the core concepts of an A&P course.

Using his considerable skills as an illustrator and his great talent as a teacher, Paul has put together some great tools that help students focus their study time by using visual and kinesthetic processes to help them learn "the hard parts" of A&P.

Check out his video
, in which he explains how the Visual Analogy Guides work.

Wednesday, October 7, 2009

Ribosome scientists win 2009 Nobel Prize in Chemistry


EXTRA! EXTRA! This news just in from the Royal Swedish Academy of Sciences . . .

The 2009 Nobel Prize in Chemistry has been awarded jointly to


Venkatraman Ramakrishnan
MRC Laboratory of Molecular Biology, Cambridge,
United Kingdom

Thomas A. Steitz
Yale University, New Haven, CT, USA

Ada E. Yonath
Weizmann Institute of Science, Rehovot, Israel

"for studies of the structure and function of the ribosome"

As I've mentioned in yesterday's "extra edition" of The A&P Professor, as well as in previous posts, I love to tie major awards and other news about major discoveries in the recent history of science into what we are actually learning in A&P class. And the real people behind these discoveries.

Wow, this morning's announcement for the chemistry prize couldn't have been better timed. Not long ago we wrestled with the story of protein synthesis and my students slowly realized the critical role of the ribosome's structure in that story.

An understanding of the ribosome's innermost workings is important for a scientific understanding of life. This knowledge can be put to a practical and immediate use; many of today's antibiotics cure various diseases by blocking the function of bacterial ribosomes. Without functional ribosomes, bacteria cannot survive. This is why ribosomes are such an important target for new antibiotics.

This year's Nobel Laureates in Chemistry have all generated 3D models that show how different antibiotics bind to the ribosome. These models are now used by scientists in order to develop new antibiotics, directly assisting the saving of lives and decreasing humanity's suffering.

This gives us an opportunity to show how understanding the "basic science" that are teaching translates (ahem) into applications in "the real world."

Want to know more?

"Public" summary
[PDF article intended for the general reader; does a good job of recapping the role of the ribosome within the big picture of biology, includes some nice graphics that you can use in your class plus links for further reading]

Scientific Background
[PDF article directed at those of use with some science background; well-written summary of the ribosome and the evolution of scientific discovery leading to the awarding of this prize; includes some good graphics; comprehensive list of scientific references]


Other resources

Nobel's "useful links and further reading"

FREE image of ribosome's role in translation

FREE image of detailed ribosome structure

Additional FREE ribosome images

NOTE: I apologize to my email subscribers who received two posts yesterday instead of one. I've adjusted the timing so you should only get one delivery on these rare occasions when I have an "immediate" post to send to you.

{Some content of this post came from the Nobel organization}


Monday, October 5, 2009

2009 Nobel Prize in Physiology or Medicine

I love the sense of awe that I get on those brisk Monday mornings in October when NPR announces the first of the Nobel Prizes . . . the prize for Physiology or Medicine. I'm struck by the truly groundbreaking nature of the discoveries that win prizes. No less this year, with the prize going jointly to three U.S. scientists for the discovery of how chromosomes are protected by telomeres and the enzyme telomerase.

We've recently covered the whole molecular genetics/protein synthesis/cell life cycle suite in our A&P class . . . so my students will be ready to hear about the concepts for which the prize was awarded today. I like to show them that science is dynamic and evolving, with new discoveries made every day. These "big" announcements further underscore that what they are learning is fresh and relevant.

Hmmm . . . this gives me an idea for a bonus question on the midterm exam!

Today, I have a special longer post today, so that you can walk into the classroom TODAY ready to discuss what some of them may have already heard about. If you stick with me until the end, I have a link to an image that you can use TODAY in your class!

This year's Nobel Prize in Physiology or Medicine is awarded to three scientists who have solved a major problem in biology: how the chromosomes can be copied in a complete way during cell divisions and how they are protected against degradation. The Nobel Laureates have shown that the solution is to be found in the ends of the chromosomes – the telomeres – and in an enzyme that forms them – telomerase.

The long, thread-like DNA molecules that carry our genes are packed into chromosomes, the telomeres being the caps on their ends. Elizabeth Blackburn and Jack Szostak discovered that a unique DNA sequence in the telomeres protects the chromosomes from degradation. Carol Greider and Elizabeth Blackburn identified telomerase, the enzyme that makes telomere DNA. These discoveries explained how the ends of the chromosomes are protected by the telomeres and that they are built by telomerase.

If the telomeres are shortened, cells age. Conversely, if telomerase activity is high, telomere length is maintained, and cellular senescence is delayed. This is the case in cancer cells, which can be considered to have eternal life. Certain inherited diseases, in contrast, are characterized by a defective telomerase, resulting in damaged cells. The award of the Nobel Prize recognizes the discovery of a fundamental mechanism in the cell, a discovery that has stimulated the development of new therapeutic strategies.

The mysterious telomere

The chromosomes contain our genome in their DNA molecules. As early as the 1930s, Hermann Muller (Nobel Prize 1946) and Barbara McClintock (Nobel Prize 1983) had observed that the structures at the ends of the chromosomes, the so-called telomeres, seemed to prevent the chromosomes from attaching to each other. They suspected that the telomeres could have a protective role, but how they operate remained an enigma.

When scientists began to understand how genes are copied, in the 1950s, another problem presented itself. When a cell is about to divide, the DNA molecules, which contain the four bases that form the genetic code, are copied, base by base, by DNA polymerase enzymes. However, for one of the two DNA strands, a problem exists in that the very end of the strand cannot be copied. Therefore, the chromosomes should be shortened every time a cell divides – but in fact that is not usually the case (Fig 1).

Both these problems were solved when this year's Nobel Laureates discovered how the telomere functions and found the enzyme that copies it.

Telomere DNA protects the chromosomes

In the early phase of her research career, Elizabeth Blackburn mapped DNA sequences. When studying the chromosomes of Tetrahymena, a unicellular ciliate organism, she identified a DNA sequence that was repeated several times at the ends of the chromosomes. The function of this sequence, CCCCAA, was unclear. At the same time, Jack Szostak had made the observation that a linear DNA molecule, a type of minichromosome, is rapidly degraded when introduced into yeast cells.

Blackburn presented her results at a conference in 1980. They caught Jack Szostak's interest and he and Blackburn decided to perform an experiment that would cross the boundaries between very distant species (Fig 2). From the DNA of Tetrahymena, Blackburn isolated the CCCCAA sequence. Szostak coupled it to the minichromosomes and put them back into yeast cells. The results, which were published in 1982, were striking – the telomere DNA sequence protected the minichromosomes from degradation. As telomere DNA from one organism, Tetrahymena, protected chromosomes in an entirely different one, yeast, this demonstrated the existence of a previously unrecognized fundamental mechanism. Later on, it became evident that telomere DNA with its characteristic sequence is present in most plants and animals, from amoeba to man.


An enzyme that builds telomeres

Carol Greider, then a graduate student, and her supervisor Blackburn started to investigate if the formation of telomere DNA could be due to an unknown enzyme. On Christmas Day, 1984, Greider discovered signs of enzymatic activity in a cell extract. Greider and Blackburn named the enzyme telomerase, purified it, and showed that it consists of RNA as well as protein (Fig 3). The RNA component turned out to contain the CCCCAA sequence. It serves as the template when the telomere is built, while the protein component is required for the construction work, i.e. the enzymatic activity. Telomerase extends telomere DNA, providing a platform that enables DNA polymerases to copy the entire length of the chromosome without missing the very end portion.

Telomeres delay ageing of the cell

Scientists now began to investigate what roles the telomere might play in the cell. Szostak's group identified yeast cells with mutations that led to a gradual shortening of the telomeres. Such cells grew poorly and eventually stopped dividing. Blackburn and her co-workers made mutations in the RNA of the telomerase and observed similar effects in Tetrahymena. In both cases, this led to premature cellular aging – senescence. In contrast, functional telomeres instead prevent chromosomal damage and delay cellular senescence. Later on, Greider's group showed that the senescence of human cells is also delayed by telomerase. Research in this area has been intense and it is now known that the DNA sequence in the telomere attracts proteins that form a protective cap around the fragile ends of the DNA strands.

An important piece in the puzzle – human aging, cancer, and stem cells

These discoveries had a major impact within the scientific community. Many scientists speculated that telomere shortening could be the reason for aging, not only in the individual cells but also in the organism as a whole. But the aging process has turned out to be complex and it is now thought to depend on several different factors, the telomere being one of them. Research in this area remains intense.

Most normal cells do not divide frequently, therefore their chromosomes are not at risk of shortening and they do not require high telomerase activity. In contrast, cancer cells have the ability to divide infinitely and yet preserve their telomeres. How do they escape cellular senescence? One explanation became apparent with the finding that cancer cells often have increased telomerase activity. It was therefore proposed that cancer might be treated by eradicating telomerase. Several studies are underway in this area, including clinical trials evaluating vaccines directed against cells with elevated telomerase activity.

Some inherited diseases are now known to be caused by telomerase defects, including certain forms of congenital aplastic anemia, in which insufficient cell divisions in the stem cells of the bone marrow lead to severe anemia. Certain inherited diseases of the skin and the lungs are also caused by telomerase defects.

In conclusion, the discoveries by Blackburn, Greider and Szostak have added a new dimension to our understanding of the cell, shed light on disease mechanisms, and stimulated the development of potential new therapies.

Elizabeth H. Blackburn has US and Australian citizenship. She was born in 1948 in Hobart, Tasmania, Australia. After undergraduate studies at the University of Melbourne, she received her PhD in 1975 from the University of Cambridge, England, and was a postdoctoral researcher at Yale University, New Haven, USA. She was on the faculty at the University of California, Berkeley, and since 1990 has been professor of biology and physiology at the University of California, San Francisco.

Carol W. Greider is a US citizen and was born in 1961 in San Diego, California, USA. She studied at the University of California in Santa Barbara and in Berkeley, where she obtained her PhD in 1987 with Blackburn as her supervisor. After postdoctoral research at Cold Spring Harbor Laboratory, she was appointed professor in the department of molecular biology and genetics at Johns Hopkins University School of Medicine in Baltimore in 1997.

Jack W. Szostak is a US citizen. He was born in 1952 in London, UK and grew up in Canada. He studied at McGill University in Montreal and at Cornell University in Ithaca, New York, where he received his PhD in 1977. He has been at Harvard Medical School since 1979 and is currently professor of genetics at Massachusetts General Hospital in Boston. He is also affiliated with the Howard Hughes Medical Institute.

Want a high-resolution image that you can use in your class TODAY to illustrate the discovery for which today's Nobel Prize was given? Just click here.



Want to know more?

Video of the Nobel Prize announcement

Video of interview after the announcement explaining the story behind the discovery

Press Release on the award

[The above resources also have links to interviews with these Nobel laureates and photos of them and their work.]


Original Journal References:

Cloning yeast telomeres on linear plasmid vectors.
Szostak JW, Blackburn EH.
Cell 1982; 29:245-255.

Identification of a specific telomere terminal transferase activity in Tetrahymena extracts.
Greider CW, Blackburn EH.
Cell 1985; 43:405-13.

A telomeric sequence in the RNA of Tetrahymena telomerase required for telomere repeat synthesis.
Greider CW, Blackburn EH.
Nature 1989; 337:331-7.

[Some of the material in this article came from a press release from the Nobel organization.]

Sunday, October 4, 2009

FREE nerve signaling activity

The Nobel Prize site has a nice animated "game" that goes through the basics of nerve signaling.  It features explanatory text alongside some nifty, simplified diagrams that are animated.

The level of coverage may be sufficient for some courses . . . but if not, then it's a good preview or review, which will help students see how it all fits together.

Try it out at Nerve Signaling.

Here's a brief video introducing this FREE online activity for your students.



Keep up with this blog on your phone

The A&P Professor blog is now available on your mobile device!

Check it out at http://theapprofessor.mofuse.mobi/

Even if you prefer to view the blog at the Blogger interface or Facebook or the free email newsletter, you might find that being able to browse (or quickly find a reference) on your iPhone, BlackBerry, or other smartphone is a handy thing to be able to do.