[Cool site] Biology.SE - the first 100 days

My preferred online place to exchange biology knowledge.

This is the most interesting Q&A site for biology researchers, academics, and students I stumbled upon so far. I'm really excited about it and since some increased participation is required to exit the beta stage, I'm inviting you to have a visit and consider joining.

Forget noncurated forums plenty of 'why my beta galactosidase assay does not work?' kind of questions. This is not a forum.
The day after tomorrow, Biology.StackExchange.com will cross its first 100 days of life, accumulating some 500 relevant questions and more interesting answers. Why it is so interesting? Because each answer is substantiated by references, so that it represents an useful piece of information rather than an opinion. Like any other stackexchange site, Biology.SE works on reputation: each user can vote up/down both the answers and the questions so that only interesting and useful content is selected and spam is virtually absent. In addition, the Q&A process is collaboratively written: similarly to a wiki, each answer/question can be edited by other users to improve the quality of the content. Under these inviting premises, I joined 50 days ago as user number 444 (this is my profile); today my overall impression is positive. Biology.SE is a nice site to vist for exchanging and increasing your academic knowledge about biological concepts, mechanisms and techniques. Bioinformatic questions are also accepted as long as they focus on the biological part of the subject. Otherwise, Biostar.stackexchange.com is the correct place to ask for the informatic part.

typical question asked on biology.stackexchange.com
This is a typical practical, answerable question example based on actual problems that you face asked at Biology.SE
Btw, this is my preferred question about even number of bases in the recognition site of restriction enzymes: it really shows how science works: from an odd observation, to documentation, hypothesis formulation, the research work done before asking the question, and the following interesting contributions from other users till the final analysis that clearly answer the question. Good job!

Other examples of answers I given, include sex dimorphism: whether testosterone increases female sex behaviour, I speculated what are the advantages of autocrine signaling and suggested about how to take photos of luciferase

Examples of questions I asked:
  • The number of mice on the Earth? I asked this question stimulated by some calculations by Carson Chow that would suggest (this is my interpretation) that if the mouse biomass is higher than the human biomass, mice will be more contributing to CO2 emissions than humans. (Well, looks like the mouse biomass is less, we are not excused!)
  • What is the total ATP cost for gene expression? I'm studying a transcription factor (PPARa) that promotes lipid metabolism in energy-demanding conditions, so I was wondering how much energy (ATP) it will cost to the cell to produce energy-harvesting proteins by a transcriptional mechanism (like the PPARa-mediated one). This is a sort of economy curiosity which goes beyond the literature I usually read: how much ATP should the cell spend to gain more ATP?
Look at the quality of the responses I got back: impossible to obtain these details and bibliographic references in classic forums, and distilling the same kind of knowledge from pubmed would have required me at least one week: here it was just matter of minutes, and it was more entertaining. Thus, in contrast to forums, if we stick to practical, scoped purposes, this could be an useful site if you are reviewing a manuscript and you are not confident with some parts, but I see also a good tool to broaden the impact of your grant application or PhD discussion. Otherwise, you can always indulge in the pure knowledge stream.

The site i currently receiving 250 visits/day that requires some work: to have a better impact, it could be good to exit the beta with some 1000-1500 visits, so have a look and exchange your knowledge.

[Interview] Sentinels for detection of estrogenic compounds

After a PhD in cellular and molecular medicine, Daniel Gorelick continued to study how steroid hormones affect development and behavior. He already wrote a guest post about enhancer discovery few years ago, and some days ago I had occasion to speak with him about his last paper. In a recent Endocrinology issue, Daniel describes a transgenic ERE-Luc zebrafish developed to visualize estrogen receptor activation. This is of extreme interest to me because I previously used an ERE-Luc mouse to study some pharmacological and nutritional aspects of ER activity. Here, I summarise part of the conversation with Daniel in an interview.

5 day old ERE-Luc transgenic Danio rerio incubated in water containing 100 μg/L estradiol have fluorescent liver (arrowheads), indicating that ERs are activated in the liver. Scale bar = 200 μm.
  #1 - Daniel, what prompted you to study steroid hormones like estrogens?
Steroid hormones are fascinating molecules. They regulate diverse cellular and physiological processes in different tissues throughout development and in adulthood. I was drawn to estrogens in particular because of their actions in the central nervous system. For decades scientists have recognized that estrogens affect the development of neuronal circuitry that regulates behaviors such as aggression and mating. There is increasing evidence that estrogens regulate cell proliferation and death in the brain, as well as more disparate processes like inflammation.

#2 - As a model, what are the advantages of zebrafish compared to mouse?
Zebrafish and mice models are two of many tools in the scientist's tool box. Every tool has unique advantages and limitations. Zebrafish embryos are transparent and develop externally, allowing scientists to observe development in live embryos from the moment of fertilization. It's difficult to perform similar observations in mice. For example, we were able to monitor estrogen receptor activation in live zebrafish embryos and larvae through 5 days post fertilization and identify a novel site of potential estrogen receptor activity in developing heart valves. Doing the comparable experiment in mice would be impossible. Zebrafish are small and reproduce easily, producing several hundred embryos from a single mating, compared with the dozen or so progeny from a typical mouse mating. These qualities make performing high-throughput chemical and mutagenesis screens straightforward and economical in zebrafish.

#3 - Today's scientists are used to genome-wide scenarios but are still focusing on single cells, at single time-points. Don't you feel alone in following one (reporter) gene in different organs at multiple time points?
As a graduate student I received good advice from my mentor: Don't worry about what other people are doing. We have a lot to learn about how estrogens influence development, and a good way to do that is to identify the tissues and cell types that respond to estrogens during embryogenesis and organ formation. I don't worry that many publications focus on genome-wide estrogen receptor binding (for example) in a single cell type at a single time-point. My guess is that interesting discoveries will be made using both approaches.

#4 - Let's talk about reporter design. You have chosen to combine five tandem consensus sequences: older approaches would have used a target gene promoter. What are the advantages of your design? Do you had difficulties in having the referee accepting this strategy?
The limitations of using a gene promoter is that the reporter can only monitor gene expression in tissues where that promoter is expressed. For example, the vitellogenin gene promoter responds to estrogen. Several labs have taken fragments of this promoter, placed them upstream of a reporter gene and generated transgenic zebrafish that report estrogen receptor activation. But this vitellogenin gene is only expressed in the liver, so you can't monitor estrogen receptor activity in other tissues, such as the heart or brain. Using tandem estrogen response elements without a promoter allowed us to monitor estrogen receptor transcriptional activation in every tissue, not just the liver. Luckily, several groups had pioneered this strategy previously in cultured cells and in mice so the journal referees had no trouble accepting this strategy.

#5 - Estrogens are quite active in the brain. Do you think that your model could help in coupling behavioral responses to specific maps of neuronal activation by estrogens?
I hope so! This is exactly one of the reasons why I generated the estrogen reporter zebrafish. We've done some studies in adult zebrafish demonstrating that we can detect estrogen-responsive cells in the brain. Correlating estrogen-response with a behavioral response, and comparing the number and type of estrogen-responsive cells in males versus females is proving to be more challenging that I originally thought. But I am optimistic that we will make some interesting observations in the future.

Original publication
Gorelick and Halpern, Visualization of Estrogen Receptor Transcriptional Activation in Zebrafish. Endocrinology 2011 vol. 152 no. 7 2690-2703.