Scientific Overlap

It recently came to my attention that a certain scientist had submitted identical proposals to two different funding sources at the same time. Submitting "overlapping" proposals to the same funding agency is prohibited by some (but not all?) funding agencies.

Scattering the same proposal among different programs in the hopes that one (or more) of them will fund the proposal might seem like an efficient strategy for the PI who invested a lot of time in a proposal, but this practice is prohibited for good reasons. Given the time and effort involved by funding agency employees, panel members, and reviewers to deal with the large number of submitted proposals, a prohibition on overlap makes sense

NIH outlines in detail the consequences of the simultaneous submission of proposals with scientific overlap. I did a rather quick search of the NSF website to try to find a similar document, but didn't find anything. It seems like there must be a policy, though, so maybe I just missed it.

Rejecting proposals for reasons of overlap is straightforward if the proposals are identical or even "essentially identical" (in the words of the NIH document). It might become more difficult to judge overlap when the definition is extended to proposals containing "similar" research, another term used in the NIH document, but I suppose experienced program directors know it (overlap) when they see it.

In the case to which I referred in the first sentence of this post, there was no administrative mechanism by which the "overlap" could have been detected if a reviewer had not been become aware of both proposals. I suppose there is a high probability of a reviewer's discovering overlap in cases in which the research is highly specialized and both funding programs use peer review. The same reviewer(s) are likely to be sent both proposals.

In the first sentence of this post, I used the vague term "funding source" deliberately so that I could consider the ethics and consequences of the following situations:

- Identical proposals are sent to different programs of one funding agency that specifically prohibits submission of overlapping proposals. This is clearly wrong and both proposals would be rejected

- Identical proposals are sent to different programs of a funding agency that does not have specific rules about overlap. Reviewers might balk at this (if the overlap is detected) because it is annoying and seems unethical, but if there are no rules against it, what's to stop a dual proposal submission?

- Identical proposals are sent to two completely different funding agencies, one or both of which may or may not have rules about overlapping proposals within each agency. Again, reviewers might balk at this, but is it wrong?

I have never attempted submission of overlapping proposals and am not really interested in doing so, though I'm not sure why not. There is something appealing about the general concept of sending a proposal out into a broad funding universe to see if anyone would like to give me money for my research. This would reduce the time spent trying to figure out to which one of several possible programs a proposal will be sent, a decision that may involve making likely unfounded assumptions about the scientific preferences and sanity levels of the program officers and hoping that an interdisciplinary proposal won't fall through the cracks between programs.

It does seem wrong, though. And speaking as someone who just reviewed quite a few proposals, I certainly don't want to see multiple versions of any of these, even the ones that were Very Good*.

* In NSF-speak, Very Good is not as good as Excellent but much better than Good, which is not good at all, except when compared to the dreaded Fair and Poor.

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Travelog Europe: Green Transportation

Throughout this month, I am highlighting my experiences in Europe and comparing and contrasting the wildlife and ecology of the Old World continent to my home continent of North America. However a recent radio story on NPR about urban cycling tapped me on the shoulder.
Is Biking Easier In New York? Ask The Bike Snob by Jo Ella Straley

I thought in line with my own and this blog's committment of Environmental Education and Awareness, and my theme of comparing and contrasting European and North American Urban Ecology, I am going to discuss Green Transportation.

Though I own a bike (a pretty cool one at that), I will admit to being slow when it comes to using it as my primary source of transportation. Why? Laziness. I'm not in good enough of shape to bike to my destination in a decent amount of time and still be energized enough to get my business done. Capacity. Motorized vehicles have better capacity to help me take care of errands while I am out - shopping, picking up something, picking up someone, etc.


But while in Europe, and most notably in the Netherlands, bikes where EVERYWHERE. Thousands of bikes parked in lots at the train station, at bus stations, the plazas, shopping areas. Everywhere. Most of the street traffic was of bikes and some places had dedicated bike lanes - for each direction of traffic. Not only was I impressed with the infrastructure dedicated to cycle traffic - lots, bike rails, and roads - I was most impressed with how my two main biking concerns were non-issues for the Dutch.

1. Laziness. People still seemed to get to wherever they needed to be in a reasonable amount of time using bikes. Plus, most people were in good shape - not alot of heavy people there. Nor were they thin and sickly, just in shape...and no one seemed to complain. Biking, walking, and the train were just very common ways of getting about town and the region.

2. Capacity. Much like a carpool, groups of people biked together - keeping each other company, conversing and travelling. Plus, most bikes had a cargo bench on the back and/or baskets in the front. People carried parcels, packages, and books in them. I also observed quite a few people riding shot gun. It may look easy, but it ain't. That's some serious core muscles being used to maintain your balance...and many people were not holding on to the driver.
I mean young and old alike were just chilling on the cargo bench. Moreover, cycling did not prohibit families from traveling together. It was not at all uncommon to see parents with babies and toddlers strapped into special seats at the handle bars or right behind the parent, which is another feat of strength. Sometimes children rode their bikes along side parents and siblings. But my favorite was the cargo bike, complete with belts for securing young ones.
(See the photo slide show at the end of the post.)

The NPR story - listen to the audio or read the transcript - reports that commuter cycling is growing in popularity and use in New York City. That's good. As New York goes, so does the rest of the nation, and I'm very proud of my region and it's bicycling advocacy programs. (Trailnet, St. Louis Regional Bicycle Federation). However, the story does make it very clear there are some cultural attitudes of Americans that makes us very distinct from our European counterparts.

1. Cycling is still largely regarded as a recreational activity. The movement for cycle-friendly streets and highways will have to overcome this perception before we will truly adopt cycling as utilitarian. And it is. It is a practical form of transportation - cheap, even with all of the bells, whistles, and safety gear. Maintenance is minimal and more cost-effective than an auto and no vehicle insurance is needed.

2. Bike theft is real problem, but not taken seriously the authorities. Having one's bike and gear stolen is a major financial burden, particularly for working-class urbanites who could really benefit the most from bike transportation. In the Netherlands, bikes were everywhere. People still locked their bikes, but there was no overwhelming concerns about theft. In fact, I noticed many bikes just parked on sidewalks not secured to a bike rack or post. At first I thought these bikes were unsecured, but in actuality they were self-locked, with a device sort of like the Club. It locks on the back wheel and prevents the wheel from spinning. Neat.

3. People are concerned about getting sweaty or getting stinky when they ride to work. I co-sign this concern. However, while I was in Europe, this concern didn't cross my mind. The Dutch biked everywhere and I don't remember my nose being assaulted. So, I think that is good news.

Finally, I noted that the auomoblile culture of Europe was greener than ours, too. Motorbikes and scooters, as well as fuel-efficient sub-compacts were common. Plus, I noted this sign for electric car recharging station in Paris near the Arc de Triomphe.

A Photo Essay Of European Transportation

View more presentations from Danielle Lee.

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Wordless Wednesday: Pesky Birds (Travelog Europe)

Urban Wildlife Sightings while I was in Europe. These three bird species are regarded as pest species in the United States. Like their American cousins, they are also well-adapted to live near people in urban settings, eating discarded food and crumbs and congregating near centers of people activity.

Young European Starling at the Schiphol Airport, Amsterdam, the Netherlands.

flock of pigeons in Rennes, France

A raven, Paris, France

A raven in a Sycamore tree, Paris France

Pigeons begging, Seine River, Paris, France

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Annoucement:

Tune into the Mario Armstrong radio program- Digital Spin - on WEAA 88.9 FM (Baltimore, MD), this Wednesday 6pm - 7pm CST/7p-8p EST.

Tune in and listen live online http://www.weaa.org/

I'll be discussing science blogging, including my recent 2009 Black Web Award for Best Science/Technology Blog and my bid to win the Blog Your Way to Antarctica Contest.

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Urban Wildlife Watch: Mimosa trees (Travelog Europe)

While in Europe for the professional science conference and holiday, I came across many plant, animal, and invertebrate species that I was familiar with in the States. Some of these species came from Europe and were brought to North America, some were taken from North America to Europe, and some were species from other parts of the world that were taken to both Europe and North America. Throughout the month of September I will showcase my pictures of these animals and botanicals and provide a little narrative comparing and contrasting the biodiversity of Europe and North America.

This is my first introduction - the Mimosa tree.

The Mimosa tree comes from the Mimosaceae family of trees and the Genus Albizia.

As I was taking a leisurely stroll on the off day of the IEC conference, I was so pleasantly surprised to see a Mimosa tree. I felt like I had bumped into an old friend in a strange place. I photographed the trees and the following dialogue played through my mind.

"My, fancy seeing you here. You're here on holiday in France, too."

To which the trees replied, "No, we live here. You must be mistaking us for our cousins who live everywhere".

You see, I know this tree, sometimes called the silk tree, because my paternal grandmother had a pink Mimosa tree in her backyard. I guess it still is there. I haven't stepped foot in that wondrous, awesome backyard - teeming with urban wildlife in a very, very long time. *Sigh* I digress. I remember this tree as magical. Shorter than the other trees in the yard, but much, much taller than me, this tree always provided a cool, shady spot in the backyard. Its pink, fluffy flowers just seemed to lie atop the bi-pinnately compound leaves in the canopy. As the flowers and seed pods died they gently fell to the ground as discarded husks and silk on the ground, clinging to nearby bushes and shrubs.

As a child (before I learned the details of tree and leaf anatomy) I noted that the leaves of this tree was different than the other trees in her backyard which included pecan trees, oak trees, and a mature apple tree. The leaves were sensitive to touch and would fold down. Plus, the leaf stem had additional, smaller stems attached on each side. The tender little leaflets, all in a row on each side of a thin stem could easily be rubbed off with a single swipe of a closed hand - which I often did. It didn't escape my attention that the naked stem was an ideal switch for my grandmother, so I often discarded the stems. But that is what a pinnately compound leaf is. It has several small leaflets lined up on a single stem. There are many different tree species that have these types of leaves. If you look closely, some of leaflets sprout out from the stem together in pairs, called opposite arrangement, and some of the leaflets are alternately arranged.

graphic courtesy of The Ohio State University Extension Bulletin

Leaf (and stem) arrangement is the first step in identifying trees, assuming you do not know the name of the tree in front of you. Using a field guide and dichotomous key, plus a keen sense of observation, you could identify most any tree you come across. But I will admit to you, I usually depend on my personal knowledge of one or two key features of the tree. As a result, I can only accurately identify a few species of trees. I know a Mimosa tree because of its pretty pink flowers and bi-pinnately compound leaves. However, I cannot identify this tree in the winter or early spring when these obvious characteristics are absent. Which brings me to my point. It's okay if you only know a few trees or animals by sight. As you see more and more of the plant (or animal), you'll begin notice seasonal changes and learn more about how to identify it from fewer characteristics.

Though I have seen the Mimosa tree in the United States and now in France, the tree species originally comes from Asia and the Middle East. It has been introduced to many different places all over the world with agreeable climates - warm weather and rainfall. It is regarded as an ornamental tree - one that has been cultivated and grown because it is beautiful and attractive. Yes, it still can do important jobs like provide food and shelter for animals and insects, but we plant it because it is pretty and provides shade to people. So, that may explain why I saw this tree at a park in Rennes, France - the War Veterans Memorial - and in my grandmother's backyard.

This particular tree has a support joint underneath.

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Now, it's your turn. Share your Urban Science Adventure Urban Wildlife Watch Story.

Have you ever seen this type of tree before?
Where had you become acquainted with this tree - a backyard, a park, during a vacation or visit somewhere?
What name was it called?
Do you know if someone planted the tree or was it always 'just there'?
What activities do you enjoy doing near or with this tree? relaxing in the shade, climbing, watching bees?

Write me and tell me all about your Urban Science Adventures! ©. Share pictures, too.

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New anti-cancer role for p53

I suppose that just about everyone knows of the important role the p53 protein plays in protecting cells from becoming cancerous. The protein was identified 30 years ago and its gene (TP53) cloned soon thereafter. What's not so widely known is just how complex the operation of p53 in protecting against cancer really is. And very recent research shows the complexity is even more than previously thought.

However, the complexity is to be expected, because evolution doesn't "design" cellular mechanisms to work in a straightforward way. The mechanisms are simply the result of about a billion years of trial and error. Being pretty and elegant was not a criterion for success.

Nature is "hairy", knowing nothing of Occam's Razor, and caring even less. Simplicity is for wimps.

But one thing is clear: p53 plays a large role in preventing, or at least suppressing, the development of cancer. In many types of cancer, p53 is found to have mutations more than 50% of the time. Even if p53 isn't mutated, cancer cells generally have other p53 abnormalities, such as low levels of the protein or the presence of various factors that interfere with its activity.

Until the latest research, there have been two principal ways known in which p53 works against cancer, and several additional minor ways. The two main ways p53 has been known to act are binding to DNA as a transcription factor, and binding directly to certain proteins. And each of these mechanisms can lead to either of two main types of tumor suppression: apoptosis (cell death) and temporary or permanent suspension of the cell cycle, which is the process a cell goes through in order to divide and proliferate.

P53 is primarily a transcription factor. In this role it is found in a cell nucleus and binds to various specific DNA gene promoter regions, in order to direct transcription of the associated gene – the first step in production of proteins from a gene.

The proteins that are expressed as a result of this p53 activity can play a part in either apopotosis or cell cycle control (as well as other functions not directly related to cancer – see here, here, here). Which function is invoked depends on the type of signal that activates the p53. Among the possible conditions that may be signaled are detection of correctable or uncorrectable damage to DNA and detection of chromosome telomeres that are too short.

In addition to binding to DNA as a transcription factor, p53 is also capable of binding directly to other proteins in order to control their behavior. Mainly these proteins are involved with apoptosis, such as members of the Bcl2 family.

P53 itself is actually a family of proteins – there are at least 9 different RNA transcripts that can be derived from the TP53 gene. But one thing that each of these family members have in common is a segment, called the DNA binding domain. It is this part of the p53 that is capable of binding to either DNA or other proteins. (In general, a protein domain is a more-or-less self-sufficient component of a protein. Often the same domain appears in different members of a family of proteins.)

One indication of the importance of this p53 domain is the fact that point mutations (errors involving only a single nucleotide pair) in the part of TP53 that code for the binding domain are the only type of point mutations of p53 that are commonly found in tumors. Errors that affect portions of p53 outside of the binding domain are not associated with cancer.

There's one more thing to note about p53's role as a transcription factor. Namely, the RNA that is transcribed under the direction of p53 is not always messenger RNA (mRNA) that will eventually code for the production of a protein. P53 can also initiate the transcription of genes that code for microRNA (miRNA), which is a single-stranded RNA molecule that's normally only 21 to 23 nucleotides in length. Over 500 different types of miRNA have been found in human cells.

MicroRNA is never translated into a protein. Instead, miRNA molecules regulate the translation of messenger RNA for many different proteins (by binding with the mRNA to prevent translation). It has been known for some time that p53 acts as a transcription factor for the miRNA family known as miR-34. It has also been learned that among the proteins regulated by miR-34 are some found in pathways that lead to apoptosis or cell cycle arrest. The net effect is that miR-34 has tumor-suppressing properties, so this is another way that p53, as a transcription factor, helps suppress tumors.

Many other miRNA molecules, on the other hand, are found at high levels in cancer cells. Such miRNAs most likely inhibit expression of tumor suppressing genes, whose proteins might otherwise control cell proliferation or migration. We've discussed a number of miRNAs associated with cancer, mostly of the sort that promote cancer, here and here.

Nevertheless, there are miRNAs besides miR-34 that have anti-cancer effects. Three in particular are miR-16-1, miR-143, and miR-145. It has been observed that these miRNAs, and several others, are found at higher levels in cells where p53 has been activated as a result of DNA damage. (Normally, p53 formed in non-cancer cells is either quickly degraded or else inhibited by certain proteins, especially MDM2, so as not to unnecessarily promote apoptosis or cell cycle arrest. The presence of DNA damage results in the removal of these inhibitions on p53.)

It therefore appears that p53 is doing something to help produce a number of miRNAs, some of which are tumor suppressors. The curious thing, though, is that it can be shown that p53 is not a transcription factor for the genes that encode these miRNAs.

So what is it that p53 is doing instead to help produce these miRNAs? New research published in the July 23, 2009 issue of Nature answers this question – and it uncovers an entirely new mechanism through which p53 (and its binding domain, in particular) acts as a tumor suppressor. Here's the research abstract:

Modulation of microRNA processing by p53

MicroRNAs (miRNAs) have emerged as key post-transcriptional regulators of gene expression, involved in diverse physiological and pathological processes. Although miRNAs can function as both tumour suppressors and oncogenes in tumour development, a widespread downregulation of miRNAs is commonly observed in human cancers and promotes cellular transformation and tumorigenesis. This indicates an inherent significance of small RNAs in tumour suppression. However, the connection between tumour suppressor networks and miRNA biogenesis machineries has not been investigated in depth. Here we show that a central tumour suppressor, p53, enhances the post-transcriptional maturation of several miRNAs with growth-suppressive function, including miR-16-1, miR-143 and miR-145, in response to DNA damage. ... These findings suggest that transcription-independent modulation of miRNA biogenesis is intrinsically embedded in a tumour suppressive program governed by p53. Our study reveals a previously unrecognized function of p53 in miRNA processing, which may underlie key aspects of cancer biology.

To understand what's going on, it's necessary to explain a few things about how miRNAs are produced. It's not a simple 1-step process of transcribing an miRNA gene into the final short piece of RNA.

There are, instead, three steps. The first step is transcription, done just as is done for any other gene. The RNA produced in this step is many nucleotides long, and is called the "primary transcript" or pri-miRNA. This pri-miRNA is then cut into smaller pieces having a hairpin shape, called pre-miRNA. The pre-miRNA, in turn, is further processed to produce the final "mature" miRNA.

The intermediate step that converts pri-miRNA to pre-miRNA is performed by a protein complex known as the "microprocessor complex" (having nothing to do with computers, of course). One of the key proteins in this complex is an enzyme called Drosha. The final step, which is performed by another enzyme called Dicer, splits the pre-miRNA apart to yield the mature miRNA.

The main contribution of p53 in this process is to facilitate the action of Drosha. It seems that, although Drosha can do the job by itself (since miRNAs are needed even if p53 isn't active), p53 helps by binding (via its binding domain) with parts of the microprocessor complex. This is indicated by the observation that mutations in the binding domain disable p53 binding to the complex, resulting in lower levels of miRNA production.

So there you have it: an essentially novel way that p53 acts as a tumor suppressor, by facilitating production, non-transcriptionally, of tumor-suppressing miRNAs.

Suzuki, H., Yamagata, K., Sugimoto, K., Iwamoto, T., Kato, S., & Miyazono, K. (2009). Modulation of microRNA processing by p53 Nature, 460 (7254), 529-533 DOI: 10.1038/nature08199

Further reading:

Protein plays three cancer-fighting roles (7/22/09) – Science News article on the research

Link between p53 and miRNA – editor's summary in Nature of the research

Cancer: Three birds with one stone (7/23/09) – Nature news article on the research

Tags: p53, microRNA, cancer

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Book Review: Puzzle of the Platypus

In fulfillment of my duties as a member of the Animal Behavior Society’s Outstanding Children’s Book Award committee I present one of the finalists for this year’s award.

Title: The Puzzle of the Platypus: And Other Explorations of Science in Action
Author: Jack Myers
Illustrator: John Rice
Publisher: Boyds Mills Press


It isn’t often that children get a chance to read fun stories about science and scientists. The scientific process can be hard to explain to students and it often they failed to comprehend how scientists follow their curiosity to solve problems and learn more about animals and nature. But I suppose it takes a scientist who appreciates the joys and challenge of science discovery to present these tales with wonder and creativity. Dr. Myers, a biologist and science writer, served as the science editor Highlights for Children Magazine writing numerous science stories for the periodical. This book is a collection of eleven of his most touching stories of animal behavior and science discovery. Each story is an account of current animal behavior research from science journals and text books translated into four-to-six page short articles with original illustrations for young readers. The introductory illustration for each story is a fun summary of the story with colorful accompanying illustrations that detail the work of the scientists. This book introduces readers to a variety of animals from around the world including hibernating polar bears, enigmatic platypuses, gregarious cliff swallows, clever crows, and deducing dolphins. For students who are warming to reading, this book offers short, yet engaging stories for active little minds who find it hard to read an entire book in one-sitting. Youth can revisit the book several times to enjoy the pictures, read the stories, and reflect on the scientific challenges and successes of each tale.

Ideal for students in grades 3-6 and great story-time book for younger students.

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And the winner is....

Thank you, Thank you, Thank you.

Plus a hearty Merci beau coup and Dank U from me to each of you - my blog readers and supportors. Against all odds, Urban Science Adventures! ©, the lone science blog in the slate of finalists for the 2009 Black Weblog Awards Best Science/Technology blog category, won the popular vote. The popular vote. That means I won because of you. Wow! I am honored and very, very happy.

This is how I feel..."I'm Nancy!" - super jubilant and excited.

The other contest, the Blog Your Way to Antarctica Contest, is still going on and I am need for your votes! The contest continues until September 30th!


Thanks again. Maybe I can announce another win at the end of the month with your help.

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