Tuesday, August 30, 2011

new addition for the emergency reading list...

this is a case report, but the results are so dramatic I had to post it here: a prostate cancer patient with androgen independent disease failing docetaxel therapy had a PSA of 22ng/ml, and serum folate of 300nM. He revealed to his oncologist that he was taking a daily vitamin containing 400ug of folic acid, and in addition to B12 and porcine intrinsic factor, was taking methyl-folate (400ug per day). TWO WEEKS after dropping the vitamin supplements and avoiding the many foods fortified with folic acid, the patient's PSA began dropping, now at 2ng/ml - indicating a therapeutic response(!) - and now his serum folate is nearly 30-fold lower as well - read the whole report at

Saturday, August 27, 2011

Saturday's light reading....a novel pathway for DHT synthesis in humans?

Why Boys Will Be Boys: Two Pathways of Fetal Testicular Androgen Biosynthesis Are Needed for Male Sexual Differentiation
The American Journal of Human GeneticsVolume 89, Issue 212 August 2011Page 347
Christa E. Flück, Monika Meyer-Böni, Amit V. Pandey, Petra Kempná, Walter L. Miller, Eugen J. Schoenle, Anna Biason-Lauber
This paper demonstrates (once again) the value of studying marsupial systems - it turns out that humans, like marsupials and some rodents, are not only able to synthesize dihydrotestosterone from cholesterol without testosterone as an intermediate, but this alternative pathway is actually necessary for proper male this pathway active in adults, or in men with prostate cancer? and if the answer to those questions is YES, could this pathway be a new target for developing therapies against prostate cancer?   

Wednesday, August 24, 2011

Great new tools for literature searching

I just found out about these tools - they need to be played with a bit, but I already found a bunch of papers that I didn't know existed -- check them out:   (uses word clouds)   (gets pdfs)  (text similarities)  uses semantics (context/relationship significance)

and for fun, check out the plagiarism database, and see if you have been plagiarised - entire papers are copied according to this database, all too often (of course its easier to publish if you just copy other people's work)

and finally an online list of multiple useful sites:

5 SNPs predict prostate cancer mortality

In a nice study published by first authors Dan Lin and Liesel Fitzgerald in CEBP, polymorphisms in 5 genes were identified as being significantly associated with prostate cancer specific mortality - LEPR, CRY1, RNASEL, IL4, and ARVCF -- none of the SNPs interacted -- and none (except RNASEL) has been evaluated for prostate cancer before -- see it for yourself

Genetic Variants in the LEPR, CRY1, RNASEL, IL4, and ARVCF Genes Are Prognostic Markers of Prostate Cancer-Specific Mortality.

Lin DW, Fitzgerald LM, Fu R, Kwon EM, Zheng SL, Kolb S, Wiklund F, Stattin P, Isaacs WB, Xu J, Ostrander EA, Feng Z, Grönberg H, Stanford JL.

Friday, August 19, 2011

highly recommended reading...CNCing Is Believing!

Read the short perspective in today's Science Magazine, it is by Gregory A. Wray and discusses the potential contribution of conserved non-coding [aka "junk"] DNA between species - although this appears to be a discussion regarding speciation and evolutionary biology, the concepts can also be applied to carcinogenesis - tumor cell are constantly evolving in response to a changing environment - and it appears that these elements are able to control transcriptional regulation from a long distance...something to keep in mind perhaps...see the article at

Thursday, August 18, 2011

new addition for the emergency reading list...

Genes Dev. 2011 Aug 1;25(15):1583-8.

Polycomb eviction as a new distant enhancer function.

Vernimmen D, Lynch MD, De Gobbi M, Garrick D, Sharpe JA, Sloane-Stanley JA, Smith AJ, Higgs DR.



Remote distal enhancers may be located tens or thousands of kilobases away from their promoters. How they control gene expression is still poorly understood. Here, we analyze the influence of a remote enhancer on the balance between repression (Polycomb-PcG) and activation (Trithorax-TrxG) of a developmentally regulated gene associated with a CpG island. We reveal its essential, nonredundant role in clearing the PcG complex and H3K27me3 from the CpG island. In the absence of the enhancer, the H3K27me3 demethylase (JMJD3) is not recruited to the CpG island. We propose a new role of long-range regulatory elements in removing repressive PcG complexes.

oh my! reprogramming sex!

having grown up in the lab famous for helping to decipher the molecular genetics of sex-determination, this paper is super-cool -- previously, it was thought that SRY (sex-determining region on the Y) is the most important determinant of sexual differentiation, and that once decided, sexual fate was not able to be changed -- makes sense --  we don't want to have to change our wardrobe just because one of our genes shuts down transcription....anyway it turns out that in females, transcriptional silencing of FOXL2 results in reprogramming of ovarian granulosa cells, forming sertoli (testis!) cells -- now, as shown in a paper in nature by the Zarkower lab from U. Minnesota, adult sertoli cells from the testis can be reprogrammed to form granulosa cells, simply by loss of the transcription factor DMRT1!  Furthermore, after foxl2 is activated by loss of dmrt1, theca cells form and estrogen is produced, resulting in feminzation of the testis!  It is possible that capacity for such global reprogramming of cell fate is limited to the gonads, however it leaves me wondering whether there might be a similar transcription factor out there that could do the same for a cancer the paper by Matson et al.

New urine test for stratifying prostate cancer !

using TMPRSS2:ERG and PCA3 transcripts as targets, scientists were able to discriminate patients with a low likelihood of aggressive prostate cancer and therefore reducing the need for biopsies - and much more - read all about it in Science Translational Medicine, from Scott Tomlins and Arul Chinnaiyan and friends...

Wednesday, August 17, 2011

Looking for great tasting food that is actually healthy and fast?

Whip Up Your Own “Fast” Food at the AICR blog!

Time to register for the American Institute for Cancer Research Conference!

the focus this year is on diet, nutrition, and cancer stem cells -- get all the info at the AICR website!

changes in NIH study sections that affect urology!

Changes in study NIH sections: UKGD is becoming UGPP. The NIH Center for Scientific Review (CSR) has announced that beginning in October 2011, the new Urologic and Genitourinary Physiology and Pathology (UGPP) study section will replace the Urologic and Kidney Development and Genitourinary Diseases (UKGD) study section. The new study section will review applications concerning physiological and pathophysiological processes of the lower urinary tract, male reproductive organs, female pelvic floor, urolithiasis, and microbial infection and inflammation in the lower urinary tract. Normal and abnormal development of organs of the upper and lower genitourinary tract has been moved to KMBD which use to be CMBK. For more information, visit the following websites:

Tuesday, August 16, 2011

Interesting study on prostate cancer genomics from CSHL

collaboration between two gene mutants leads to lethal prostate cancer

How vampires find veins in the dark....

this one is especially for can read about it in Nature...

Keystone epigenomics and chromatin conference deadline coming up!

this conference is usually awesome, and definitely thought-provoking -- click here for the details...

nice review on the current state of immunotherapy for prostate cancer...

if you have access to clincal cancer research click here -

hydroxymethylcytosine - a simple primer

there's a nice summary of the latest DNA modification in a Biotechniques review - click here to see it!

interesting paper on the mechanism of x-inactivation...

Genetics. 2011 Aug 11. [Epub ahead of print]

A Boundary Element Between Tsix and Xist Binds the Chromatin Insulator Ctcf and Contributes to Initiation of X Chromosome Inactivation.

Spencer RJ, Del Rosario BC, Pinter SF, Lessing D, Sadreyev RI, Lee JT.


In mammals, X-chromosome inactivation (XCI) equalizes X-linked gene expression between XY males and XX females and is controlled by a specialized region known as the X-inactivation center (Xic). The Xic harbors two chromatin interaction domains, one centered around the noncoding Xist gene and the other around the antisense Tsix counterpart. Previous work demonstrated the existence of a chromatin transitional zone between the two domains. Here, we investigate the region and discover a conserved element, RS14, that presents a strong binding site for Ctcf protein. RS14 possesses insulatory function suggestive of a boundary element and is crucial for cell differentiation and growth. Knocking out RS14 results in compromised Xist induction and aberrant XCI in female cells. These data demonstrate that a junction element between Tsix and Xist contributes to the initiation of XCI.

Monday, August 8, 2011

Quantitating DNA methylation: traps for the unwary!

DNA methylation is rapidly becoming a useful biomarker  for diagnosis and prognosis of disease, as well as for predicting patient response to treatment.  However the gold standard for analyzing DNA methylation base-by-base, bisulfite sequencing, is time consuming and therefore not conducive for use in a molecular pathology lab.  Most labs get around this by using quantitative methylation-specific PCR, COBRA or pyrosequencing - however these techniques provide an average estimation of methylation levels at particular sites.  This would be OK if each allele were identically methylated; however as Thomas Mikesa, Ida Candiloro and Alex Dobrovic detail in a recent review, DNA methylation is frequently heterogeneous, and comprised of multiple "epialleles" - each with its' own specific methylation pattern.  In the review, Mikesa et al. critically assess the current techniques used to quantitate methylation in the context of epialleles, and provide a  novel methodology that could serve to solve this problem.  You can read the review for yourself, and best of all it is free!  Get it at the link below:

The implications of heterogeneous DNA methylation for the accurate quantification of methylation, by Mikesa et al.

Friday, August 5, 2011

now this is just really cool...

The Birth of Optogenetics

An account of the path to realizing tools for controlling brain circuits with light - see The Scientist

BioTechniques - Joe Wong, Man of Comedy and Science

BioTechniques - Joe Wong, Man of Comedy and Science

this is getting added to the emergency reading list...

Nat Struct Mol Biol. 2011 Jul 3;18(8):867-74. doi: 10.1038/nsmb.2084.

Genome-scale epigenetic reprogramming during epithelial-to-mesenchymal transition.

Friday's fun fact...

just published in Science magazine -- it seems that Google has changed how we remember things - read the article on line...

Finally, a mechanism for active DNA demethylation!

Tet-Mediated Formation of 5-Carboxylcytosine and Its Excision by TDG in Mammalian DNA see science magazine

Thursday, August 4, 2011

EpiGenie Stem Cell Epigenetics Review

EpiGenie Stem Cell Epigenetics Review

everything you always wanted to know about stem cell epigenetics!

Epigenetics Headlines for DNA Methylation, Chromatin, and Non-Coding RNA

Epigenetics Headlines for DNA Methylation, Chromatin, and Non-Coding RNA

a nice beginner's guide to ChIP...


Breaking news! How does the Debt Ceiling compromise affect NIH funding?

Last Monday, the senate signed on to the Debt Ceiling compromise that was the result of negotiations between the president and congress.  According to the deal, the government is able to increase borrowing up to more than $2 trillion dollars, and this will be accompanied by a combination of cuts to discretionary spending of a similar size spread over 10 years.  That leaves the FY2012 budget which begins on Sept. 1, 2011, with a cap on discretionary spending of $1.043 trillion (discretionary spending is appropriated, and includes funding for the NIH; mandatory spending is for entitlement programs, such as social security and medicare).  This cap will increase by around a couple of percentage points each year.  The good news is that this leaves more money for discretionary spending than was being considered by the house.  The bad news is that it doesn't look like funding research is going to get easier any time soon - not without a  miraculous recovery of the economy....

....and in case you missed it....
the house approved the FY12 DOD appropriations bill, by a vote of 331-83. No amendments were offered to reduce or eliminate CDMRP (Congressionally Directed Medical Research Program) funding!  As far as I can tell this should be able to make it through the senate and if that happens, start getting your preproposals ready people!

Wednesday, August 3, 2011

Free web-conference on epigenetics

Understanding the Role of Epigenetic Change in Gene Regulation - A Virtual Symposium from BioTechniques October 5, 2011: 11:00 AM - 12:30 PM EDT

Recently developed technologies and methods are impacting our understanding of the epigenetic code and the role that epigenetic changes play in the regulation of gene expression. This session examines the impact of histone/protein modifications and DNA methylation patterns on gene expression as well as the roles epigenetic modifications play in stem cell and cancer biology.

Keynote Address: • Brian Strahl, Associate Professor, University of North Carolina, Chapel Hill Dr. Strahl will present an overview of the latest research on histone modifications and the role these modifications play in gene regulation, placing this work in context with other recent advances in the field of epigenetics.

Session Speakers:
        • Mitchell Guttmann, Postdoctoral Fellow, Eric Lander Lab, MIT and Broad Institute, Cambridge, Massachusetts Dr. Guttmann will discuss recent findings on the roles large non-coding RNAs play in the regulation of gene expression and chromatin structure.
        • Donncha Dunican, Investigator Scientist, MRC Human Genetics Unit, Edinburgh, UK Dr. Dunican will discuss new approaches being used for the study of global DNA methylation patterns, chromatin structure, and gene regulation.

Free Event - Register Now to Reserve Your Place! click here