tag:blogger.com,1999:blog-90578866039312337172024-03-05T14:20:08.375-08:00Official O'Keefe Lab blog & (other) cool stuffHello! you have reached the official blog spot of our lab which is based at the University of Texas Health Science Center at San Antonio, Department of Urology - our main area of study is prostate cancer, nutrition, and epigenetics - but we also study changes in gene expression in benign-prostatic hyperplasia - we have made this blog so as we can share thoughts about the lab, papers that are just published and anything else remotely relevant at any time, and from anywhere!Denise S. O'Keefe, PhD.http://www.blogger.com/profile/10878930814538170550noreply@blogger.comBlogger114125tag:blogger.com,1999:blog-9057886603931233717.post-38327519204848257702015-02-10T07:21:00.001-08:002015-02-10T07:21:07.491-08:00Wow! So we've moved to sunny old south Texas!I admit it, it has been just over two years since I have written on this blog -- my last blog post was just before we headed out of the country to visit family -- then a whirlwind of actions which included the birth of one baby, and moving across the country to San Antonio, way down in south Texas -- I'm sorry but the winter of 2014 was as much as I could take in Pittsburgh - so here we are -- settling in and setting up the new labs -- I'm going to try and resurrect this blog, again posting what I think are interesting papers and info about our labs -- meanwhile, why have breakfast tacos been kept such a secret from the north? They could really use a little heat up there...hmmmm...Denise S. O'Keefe, PhD.http://www.blogger.com/profile/10878930814538170550noreply@blogger.com2tag:blogger.com,1999:blog-9057886603931233717.post-9074292889490490902012-09-12T07:47:00.001-07:002012-09-12T07:47:32.454-07:00AACR Progress against Cancer report now availableThe AACR is the American Association for Cancer Research - they have just published this comprehensive report on cancer - potential causes, including diet, environment and genetics - and how we are going in terms of treating patients and survivorship - it is free to down load so if you are interested, click <a href="http://www.aacr.org/home/public--media/science-policy--government-affairs/cancer-progress-report.aspx" target="_blank">here</a>Denise S. O'Keefe, PhD.http://www.blogger.com/profile/10878930814538170550noreply@blogger.com4tag:blogger.com,1999:blog-9057886603931233717.post-14592096194461405252012-09-07T11:11:00.001-07:002012-09-07T11:11:49.420-07:00Journal Impact Factors 2011I have updated the list for the journals that we are likely to publish in. Or at least would like to publish in....<br />
You can get to it by clicking <a href="http://okeefe-lab.blogspot.com/p/journal-impact-factors.html" target="_blank">here</a>Denise S. O'Keefe, PhD.http://www.blogger.com/profile/10878930814538170550noreply@blogger.com3tag:blogger.com,1999:blog-9057886603931233717.post-16360782987468993612012-09-06T11:41:00.000-07:002012-09-06T11:42:02.986-07:00Institute of Medicine: the U.S. wastes $750 billion on medical costs annuallyRead this stunning report regarding medical dollar spending in the U.S. In short, the non-government, IOM has concluded the as much as 30 cents of every medical dollar spent is wasted due to "unneeded care, byzantine paperwork, fraud and other waste" - every year - to use an analogy -" If banking worked like health care, ATM transactions would take days" you can read all about the report <a href="http://news.yahoo.com/report-us-health-care-system-wastes-750b-140106406.html" target="_blank">here </a>-Denise S. O'Keefe, PhD.http://www.blogger.com/profile/10878930814538170550noreply@blogger.com4tag:blogger.com,1999:blog-9057886603931233717.post-776270774502590382012-09-06T07:11:00.001-07:002012-09-06T07:11:26.624-07:00Activation of the Innate Anti-Viral Immune System in BPH - now published on-line!Allison's paper has just been published on-line in Genes & Immunity, prior to being published in the print version - if you have access, you can down-load the paper <a href="http://www.nature.com/gene/journal/vaop/ncurrent/full/gene201240a.html" target="_blank">here </a>- step by step, we're going to figure out what is going on in these patients...Denise S. O'Keefe, PhD.http://www.blogger.com/profile/10878930814538170550noreply@blogger.com0tag:blogger.com,1999:blog-9057886603931233717.post-87152564442725146202012-09-03T09:20:00.000-07:002012-09-03T09:20:28.789-07:00High serum folate levels in patients with prostate cancerI posted on this subject last year when our paper was published in The Prostate - it has subsequently been one of the most popular posts on the blog - because of that, I have updated the post to include a link to the original paper as it is now available free of charge - because this research was funded by the National Institutes of Health (and therefore you, the tax payer), it must be made available to the public one year after publication - click <a href="http://okeefe-lab.blogspot.com/2011/10/patients-with-high-serum-folate-levels.html">here </a>to read the updated post with the link to the pdf.Denise S. O'Keefe, PhD.http://www.blogger.com/profile/10878930814538170550noreply@blogger.com1tag:blogger.com,1999:blog-9057886603931233717.post-62506931863302999242012-08-31T06:47:00.000-07:002012-08-31T06:47:43.739-07:00Lupus: (aka SLE) an Autoimmune disease induced by DNA demethylationSince discovering that a friend had to quit her promising postgraduate degree at CMU because she had lupus, I have been interested in what could possibly cause such a debilitating downfall in such a young, healthy woman - as I read the scientific literature on the subject, it became clear that at the molecular level there is a methylation defect - that is there is demethylated DNA present in the patient --- we've seen demethylated DNA in several different disease states; Benign Prostatic Hyperplasia (our manuscript in press), cancer, and rheumatoid arthritis -- at a simplistic level, all these diseases have inflammation. Can demethylated DNA induce inflammation? Does how the cell see that inflammation differ depending on the type of cell or tissue, and the epigenetic background of the patient? I bet it does. I could theorize forever but as action speaks louder than words...here's a paper I found today which describes the development of a novel model for Lupus (as scientists we need realistic models to test potential mechanisms and treatments) - drug induced lupus can be induced by drugs that are known to inhibit DNA methylation, for example procainamide. This model extends those findings and will help to further our understanding of what treatments may, if any, be able to stop the disease from progressing. <br />
<br />
<div class="cit">
<a href="http://www.ncbi.nlm.nih.gov/pubmed/22933069#" role="button" title="Methods in molecular biology (Clifton, N.J.).">Methods Mol Biol.</a> 2012;900:169-80.</div>
<h3>
Murine models of lupus induced by hypomethylated T cells (DNA hypomethylation and lupus…).</h3>
<div class="auths">
Richardson B, Sawalha AH, Ray D, Yung R.</div>
<div class="aff">
<h3 class="label">
Source</h3>
University of Michigan and the Ann Arbor Veteran's Affairs Hospital, Ann Arbor, MI, USA, brichard@umich.edu.</div>
<div class="abstr">
<h3>
Abstract</h3>
CD4+
T cell DNA hypomethylation may contribute to the development of drug
induced and idiopathic human lupus. Inhibiting DNA methylation in mature
CD4+ T cells causes MHC-specific autoreactivity in vitro. The
lupus-inducing drugs hydralazine and procainamide also inhibit T cell
DNA methylation and induce autoreactivity, and T cells from patients
with active lupus have hypomethylated DNA and a similarly autoreactive T
cell subset. Further, T cells treated with DNA methylation inhibitors
demethylate the same sequences that demethylate in T cells from patients
with active lupus. The pathologic significance of the autoreactivity
induced by inhibiting T cell DNA methylation has been tested by treating
murine T cells in vitro with drugs which modify DNA methylation, then
injecting the cells into syngeneic female mice. Mice receiving CD4+ T
cells demethylated by a variety of agents including procainamide and
hydralazine develop a lupus-like disease. Further, transgenic mice with
an inducible T cell DNA methylation defect also develop lupus-like
autoimmunity. This chapter describes the protocols for inducing
autoreactivity in murine T cells in vitro and for inducing autoimmunity
in vivo using an adoptive transfer approach or transgenic animal models.</div>
<dl class="rprtid">
<dt>PMID:</dt>
<dd>22933069</dd><dd>[PubMed - in process] </dd></dl>
Denise S. O'Keefe, PhD.http://www.blogger.com/profile/10878930814538170550noreply@blogger.com4tag:blogger.com,1999:blog-9057886603931233717.post-78953473136293231022012-08-30T10:33:00.000-07:002012-08-30T10:34:04.204-07:00How to get your NIHRO1 grant renewed!Yikes! It's that time again...our once 5 year grant has 2 and a half years to go, time to think about renewal! What you say? But you're only half-way through - but think about it - the time from submission to actually getting the $ is 9 months! And that's assuming you get it funded the first time -- and usually, that's not a safe assumption to make, for anyone [OK good on you people who get everything you put in funded, I'm happy for you!] - as we probably are not the only people in this situation, I thought I would post this link to a very helpful website -- the NIH NIAID has a newsletter covering exactly these topics, and let's face it, if anyone is going to provide good advice, it's likely to be the NIH...read all about it <a href="http://www.niaid.nih.gov/researchfunding/newsletter/2012/Pages/0829.aspx#a00" target="_blank">here</a>.Denise S. O'Keefe, PhD.http://www.blogger.com/profile/10878930814538170550noreply@blogger.com0tag:blogger.com,1999:blog-9057886603931233717.post-25406122281644609092012-08-16T08:44:00.003-07:002012-08-16T08:44:50.883-07:00Congratulations Jenn!A big congrats to Jennifer Gregg in the lab, for placing second in the poster competition at the SBUR meeting in Baltimore over the weekend! Jenn's poster was regarding the mechanism by which PSMA increases uptake of monoglutamated folates - i.e. folic acid and methotrexate -- Congrats once again Jenn!<br />
<br />
<table align="center" cellpadding="0" cellspacing="0" class="tr-caption-container" style="margin-left: auto; margin-right: auto; text-align: center;"><tbody>
<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEi5CuVUPdFSOT3cH_dr0A-jWk_mcf-lp0PsWHJheObFTs8t91hYc48RNAe6XazUGQQxHMB8eYuE5ykl82zLW7cnpmH5SHgSWZK4IjfGz7SNVQBlUI0zLbzrj7U6JHgEEFQtU2y0av-EKHJ1/s1600/DSCF0153.JPG" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" height="240" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEi5CuVUPdFSOT3cH_dr0A-jWk_mcf-lp0PsWHJheObFTs8t91hYc48RNAe6XazUGQQxHMB8eYuE5ykl82zLW7cnpmH5SHgSWZK4IjfGz7SNVQBlUI0zLbzrj7U6JHgEEFQtU2y0av-EKHJ1/s320/DSCF0153.JPG" width="320" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">Jennifer Gregg, and her winning poster August 2012</td></tr>
</tbody></table>
<br />Denise S. O'Keefe, PhD.http://www.blogger.com/profile/10878930814538170550noreply@blogger.com0tag:blogger.com,1999:blog-9057886603931233717.post-5008654479455626002012-08-15T10:31:00.002-07:002012-08-15T10:31:36.341-07:00Activation of innate anti-viral immune response genes in symptomatic benign prostatic hyperplasiaA big CONGRATS to Allison Atwood-Madigan in the lab, the above paper has just been accepted for publication in Genes & Immunity (a Nature journal)! Bring on the celebratory laser-tag!Denise S. O'Keefe, PhD.http://www.blogger.com/profile/10878930814538170550noreply@blogger.com0tag:blogger.com,1999:blog-9057886603931233717.post-31986458503387064832012-08-10T07:56:00.000-07:002012-08-10T07:57:14.834-07:00Magical Beets?We all know you should eat your veggies, and here's another reason -- according to this paper by Hobbs et al., beets (called beetroot down under), pretty much instantly lower blood pressure after they are ingested! My hubby was so excited that he bought a dehydrator to start making beet-chips, which aren't too bad - but these veggies look great in salads or with a sunday roast -- <i>and</i>, unlike some food studies, you don't have to eat 50 beets to get the effect - just one 100g beet should do it! Try to beet that!<br />
<br />
<br />
<h1 style="background-color: white; border: 0px; font-family: arial, helvetica, clean, sans-serif; font: inherit; line-height: 1.125em; margin: 0.375em 0px; outline: 0px; padding: 0px; vertical-align: baseline;">
<a href="http://www.ncbi.nlm.nih.gov/pubmed/22414688" target="_blank">Blood pressure-lowering effects of <span class="highlight" style="border: 0px; font-size: 18px; font: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">beetroot</span> juice and novel <span class="highlight" style="border: 0px; font-size: 18px; font: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">beetroot</span>-enriched bread products in normotensive male subjects.</a></h1>
<div class="auths" style="background-color: white; border: 0px; font-family: arial, helvetica, clean, sans-serif; font: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">
<span style="color: #660066;"><span style="font: inherit;">Hobbs DA</span></span>, <span style="color: #660066;"><span style="font: inherit;">Kaffa N</span></span>, <span style="color: #660066;"><span style="font: inherit;">George TW</span></span>, <span style="color: #660066;"><span style="font: inherit;">Methven L</span></span>, <span style="color: #660066;"><span style="font: inherit;">Lovegrove JA</span></span>.</div>
<div class="aff" style="background-color: white; border: 0px; font-family: arial, helvetica, clean, sans-serif; font: inherit; line-height: 1.0915em; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">
<h3 class="label" style="border: 0px; color: #724128; font: inherit; height: 1px; left: -10000px; line-height: 1.2857; margin: 1.2856em 1em 0.6428em 0px; outline: 0px; overflow: hidden; padding: 0px; position: absolute; top: auto; vertical-align: baseline; width: 1px;">
Source</h3>
<div style="border: 0px; font: inherit; margin-bottom: 0.5em; margin-top: 0.5em; outline: 0px; padding: 0px; vertical-align: baseline;">
Hugh Sinclair Unit of Human Nutrition, Department of Food and Nutritional Sciences, School of Chemistry, Food and Pharmacy, The University of Reading, Whiteknights, PO Box 226, Reading, Berks RG6 6AP, UK.</div>
</div>
<div class="abstr" style="background-color: white; border: 0px; font-family: arial, helvetica, clean, sans-serif; font: inherit; line-height: 17px; margin: 1.2em auto auto; outline: 0px; padding: 0px; vertical-align: baseline;">
<h3 style="border: 0px; color: #985735; font: inherit; line-height: 1.2857; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">
Abstract</h3>
<div style="border: 0px; font: inherit; margin-bottom: 0.5em; outline: 0px; padding: 0px; vertical-align: baseline;">
A number of vegetables have a high nitrate content which after ingestion can be reduced to nitrite by oral bacteria, and further to vasoprotective NO endogenously. In the present study, two separate randomly controlled, single-blind, cross-over, postprandial studies were performed in normotensive volunteers. Ambulatory blood pressure (BP) was measured over a 24 h period following consumption of either four doses of <span class="highlight" style="border: 0px; font-size: 13px; font: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">beetroot</span> juice (BJ), 0, 100, 250 and 500 g (n 18), or three bread products, control bread (0 g <span class="highlight" style="border: 0px; font-size: 13px; font: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">beetroot</span>), red <span class="highlight" style="border: 0px; font-size: 13px; font: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">beetroot</span>- and white <span class="highlight" style="border: 0px; font-size: 13px; font: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">beetroot</span>-enriched breads (n 14). Total urinary nitrate/nitrite (NOx) was measured at baseline, and at 2, 4 and 24 h post-ingestion. BJ consumption significantly, and in a near dose-dependent manner, lowered systolic BP (SBP, P < 0·01) and diastolic BP (DBP, P < 0·001) over a period of 24 h, compared with water control. Furthermore, bread products enriched with 100 g red or white <span class="highlight" style="border: 0px; font-size: 13px; font: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">beetroot</span> lowered SBP and DBP over a period of 24 h (red <span class="highlight" style="border: 0px; font-size: 13px; font: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">beetroot</span>-enriched bread, P < 0·05), with no statistical differences between the varieties. Total urinary NOx significantly increased following the consumption of 100 g (P < 0·01), 250 g (P < 0·001) and 500 g BJ (P < 0·001) and after red <span class="highlight" style="border: 0px; font-size: 13px; font: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">beetroot</span>-enriched bread ingestion (P < 0·05), but did not reach significance for white <span class="highlight" style="border: 0px; font-size: 13px; font: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">beetroot</span>-enriched bread compared with the no-<span class="highlight" style="border: 0px; font-size: 13px; font: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">beetroot</span> condition. These studies demonstrated significant hypotensive effects of a low dose (100 g) of <span class="highlight" style="border: 0px; font-size: 13px; font: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;">beetroot</span> which was unaffected by processing or the presence of betacyanins. These data strengthen the evidence for cardioprotective BP-lowering effects of dietary nitrate-rich vegetables.</div>
</div>Denise S. O'Keefe, PhD.http://www.blogger.com/profile/10878930814538170550noreply@blogger.com0tag:blogger.com,1999:blog-9057886603931233717.post-19738572306032490702012-07-31T10:48:00.002-07:002012-07-31T10:48:36.105-07:00New study finds low levels of MLV GAG sequences in samples from CFS patientsJust spotted this today -- the authors appear to have carefully controlled for mouse contamination (using the mitochondrial DNA assay), and found that 2 of 12 CFS patient samples were positive for MLV-GAG region sequences...they were unable to find other genes related to MLVs...sound familiar? Again, if all these patients that come up negative for mouse DNA come up positive for MLV GAG -- but not for env or other genes...maybe people are looking for the wrong genes...the title of the paper is somewhat misleading but perhaps necessary to get it published "Xenotropic and polytropic murine leukemia virus-related sequences are not detected in the majority of patients with chronic fatigue syndrome", it is by an Italian group --Paolucci et al. and you can find it <a href="http://www.newmicrobiologica.org/PUB/allegati_pdf/2012/3/341.pdf" target="_blank">here</a><br />
<br />Denise S. O'Keefe, PhD.http://www.blogger.com/profile/10878930814538170550noreply@blogger.com20tag:blogger.com,1999:blog-9057886603931233717.post-61783732732744816532012-07-22T08:47:00.002-07:002012-07-22T08:47:10.010-07:00Congratulations Katy and Matt! The newest addition to the lab has (finally!) arrived!It is my absolute pleasure to welcome Samuel Steven Sobek into the world...born last night, July 21 - 21.25 inches and 8lbs 3oz (hey, I think that means I win the weight/length bet...!) -- Mom and Dad are ecstatic - Samuel was born the day after Katy uploaded all but one file to submit her first paper from her PhD studies -- so effectively she has given birth twice in the space of 24 hours!<br />
<br />
we look forward to meeting Samuel in person, and putting him to work at the bench :)Denise S. O'Keefe, PhD.http://www.blogger.com/profile/10878930814538170550noreply@blogger.com0tag:blogger.com,1999:blog-9057886603931233717.post-38780097423475103602012-07-20T08:13:00.001-07:002012-07-20T08:13:28.210-07:00PSMA as a therapeutic target for most cancers: one step closer to the clinicAs I mentioned previously, there's several papers that I want to blog about right now but I have been too busy writing grants and papers. But as another paper goes off today, I am going to write about this really awesome work that was published a couple of weeks ago by Sam Denmeade and John Isaacs, and their collaborators. Sam and John are at Hopkins, and have been working on targeting PSMA for a very long time - Let me digress for a minute and give some of the background - PSMA is an abbreviation for Prostate-Specific Membrane Antigen, but the term is somewhat a misnomer as it is expressed in a variety of tissues. The protein and the gene encoding it were identified in the lab of Skip Heston in 1993 -- who was at that time leading a lab at Memorial Sloan-Kettering Cancer Center. Skip was actually looking to use a bacterial glutamate carboxypeptidase to activate methotrexate triglutamate, a prodrug (meaning once the additional glutamates are removed, the drug will be active). I like to think of this story as a classic example as to how including the correct controls in an experiment, and being open to the unexpected, might lead to a serendipitous finding - in this case (as the story was told to me), the control cells (no bacterial glutamate carboxypeptidase added), unexpectedly died after addition of the prodrug. The cells were LNCaP, a prostate cancer cell line that, like most prostate cancer, expresses large amounts of PSMA. Together with John Pinto and apparently over a couple of beers, Skip figured out that PSMA was a glutamate carboxypeptidase itself, and in fact it is the previously sought-after folate hydrolase that removes glutamates from dietary folates so that they can be absorbed by the small intestine. Dean Bacich - at the time a postdoc in Skip's lab at Sloan made several types of PSMA transgenic mice - mice don't normally express PSMA in the prostate so Dean engineered the mice so that they expressed moderate levels (equivalent to humans) in the prostate epithelial cells. These mice got what is considered the precursor to prostate cancer, PIN, suggesting that PSMA expression can cause or promote cancer, and later he showed that if the mice lived as long as humans, it would have been cancer. David Silver and Sam Chang, both fellows at Sloan were the lead authors on papers showing the expression of PSMA on tumor-associated vasculature. This was really exciting because almost all tumors that we looked at expressed PSMA in the endothelial cells of the vasculature, and the one non malignant tumor we looked at, which from memory was a hemangioma, did not express it -- and so the idea of targeting PSMA in tumor-associated vasculature was born. Although he officially retired on July 1, Skip is now at the Cleveland Clinic and still working on targeting PSMA (the word retirement is not exactly in his vocabulary...but anyone who knows him won't be surprised about that). As Bob Silverman pointed out at Skip's "transition" party, there are currently 26 clinical trials registered that target PSMA either as a therapeutic or for imaging for prostate and kidney cancer. So back to the current work -- the major leaders of this study, Sam and John, are two of the guys whom I most respect as scientists. It seems to me that a lot of people are in this field for all the wrong reasons -- but these guys are genuinely driven to help people -- and are truly excited by science [I'm sorry but its almost impossible to stop John from talking about his and anybody else's research - not that that's a bad thing :) - we could use a lot more people like him around here!] -- their paper, published in Science Translational Medicine, is entitled <a href="http://stm.sciencemag.org/content/4/140/140ra86.short" target="_blank">"Engineering a Prostate-Specific Membrane Antigen Activated Tumor Endothelial Cell Prodrug for Cancer Therapy".</a> To summarize, they took a peptide that specifically binds to PSMA, and coupled it to the toxin thapsigargin (and called it G202). There are two major differences between this and other chemotherapeutic drugs; first, it targets the tumor vasculature, meaning the cells that supply the tumor with the nutrients it needs to grow. Secondly, the cells don't need to be dividing to be effected - most chemotherapies target some aspect of dividing cells, which is also why any other rapidly dividing cells, for example gut cells, are also targeted, leading to side-effects for the patient. They tested the drug in mice against a number of human cancers, and it caused regression while causing very little toxicity to the animals. The drug is now entering a phase I clinical trial. I highly recommend reading this paper - it may seem like a logical series of successful experiments, but it is really the culmination of nearly 20 years of work done by many dedicated scientists, whom I feel honored to be acquainted with.Denise S. O'Keefe, PhD.http://www.blogger.com/profile/10878930814538170550noreply@blogger.com1tag:blogger.com,1999:blog-9057886603931233717.post-9455689955380065682012-07-17T07:45:00.000-07:002012-07-17T07:45:54.277-07:00Another great link for scientists...Nature now has a new website to help you find antibodies against your target of interest... complete with an easy-to-use system that let's you compare demonstrated usefulness of the antibody...as we all know, just because the company says it works, doesn't actually mean that it does that well...you can get to the new site, called Antibodypedia, by clicking <a href="http://www.antibodypedia.com/" target="_blank">here</a><br />
<br />
Another great site, and my personal favorite, is this one, protein atlas -- it comes with actual pictures of antibodies used in immunohistochemistry of particular tissues, including normal samples and cancer. You can get there by clicking <a href="http://www.proteinatlas.org/" target="_blank">here </a><br />
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<br />Denise S. O'Keefe, PhD.http://www.blogger.com/profile/10878930814538170550noreply@blogger.com0tag:blogger.com,1999:blog-9057886603931233717.post-15699072139527432672012-07-10T08:54:00.001-07:002012-07-10T08:54:09.247-07:00Next gen sequencing reveals that Pre-XMRV-2 is part of an evolutionarily young clade and more issues with PCR amplification of MLV-related sequencesThere are a load of papers I'd love to blog about right now, but have been too busy writing grants to get them up -- this one however caught my eye today -- I think we have a lot of very interesting data yet to be revealed by next-gen sequencing - this paper, in Virus Research, compares pre-XMRV-2 sequences found in both wild-mice and inbred mouse populations. It also seems that despite the fact that the virus appears to be a polytropic non-ecotropic virus [thus can infect other wild mice], not all wild mice in the same geo area carry the virus (in this case, Germany), and phylogenetic analysis implies that the clade is evolutionarily young and wide-spread amongst M.m. domesticus. Also interesting is that the authors, Mayer et al., demonstrate the issues involved with PCR amplifying the gag region from these mice - and the utility of high throughput deep sequencing. If you have access to Virus Research, you can read all about it - click <a href="http://www.ncbi.nlm.nih.gov/pubmed/22771940" target="_blank">here </a>for the abstract -Denise S. O'Keefe, PhD.http://www.blogger.com/profile/10878930814538170550noreply@blogger.com14tag:blogger.com,1999:blog-9057886603931233717.post-82459244711432328132012-06-13T10:44:00.002-07:002012-06-13T10:44:58.449-07:00Cool Fast Fact!The gut microbiome, that is the microorganisms, "bugs" in the human gut, contribute 36% of the small molecules found in our blood stream. That's food for thought! To read more, pick up <a href="http://www.sciencemag.org/content/336/6086/1209.full" target="_blank">Leroy Hood's editorial</a> in this week's Science magazine --Denise S. O'Keefe, PhD.http://www.blogger.com/profile/10878930814538170550noreply@blogger.com1tag:blogger.com,1999:blog-9057886603931233717.post-82215870095508660972012-05-30T13:15:00.000-07:002012-05-30T13:15:10.967-07:00Yet another reason to drink coffee!Anyone that knows me knows that I have been called a bit of a coffee snob, as I like to roast my own beans at home...so I don't really need another reason to drink coffee - however I thought that I would mention the findings of this just-published study in New England Journal of Medicine, ominously titled "Association of Coffee Drinking with Total and Cause-Specific Mortality". I held my breath as I read that the study, carried out by the Epidemiology group at the National Institutes of Health, followed the health outcomes of nearly 230,000 men and 170,000 women aged 50-71 years of age. Those are some big numbers - over the period of the study, some 13 years, nearly 50,000 participants passed away. After adjusting for age, coffee drinkers were more likely to die! **stifle inward scream**. <i>However, </i>it turns out however, that coffee drinkers actually also include many more smokers than non-coffee drinkers - so after separating out the smokers, coffee drinkers actually have a significantly reduced risk of dying from heart disease, respiratory disease, stroke, injuries and accidents, diabetes, and infections, but not for deaths due to cancer. I know you want to know *how* much coffee had an effect - interestingly it was different for men and women - for men, the effect was evident at less than a cup a day, and maxed at 1 cup thru more than 6. For women, 2-3 cups produced an average 13% reduction in mortality, with protection maxing out at more than 6 cups per day (average 15% reduction). Apparently, it didn't matter if you drank mostly caffeinated, or decaf either -- but what I wonder is if there was also any relationship with use of sweetener (sugar or artificial) in the coffee. Anyhow, studies like this do still have limitations - people with existing cancer, heart disease or who had had a stroke at baseline were excluded, and coffee intake was reported once, at baseline. Nevertheless, I'm liking this data - if you have access to NEJM, you can read the paper, by Neal Freedman et al. <a href="http://www.nejm.org/doi/pdf/10.1056/NEJMoa1112010" target="_blank">here </a>--Denise S. O'Keefe, PhD.http://www.blogger.com/profile/10878930814538170550noreply@blogger.com1tag:blogger.com,1999:blog-9057886603931233717.post-34953467265664413412012-05-22T12:04:00.000-07:002012-05-22T12:04:16.570-07:00Novel MLV-GAG sequences detected in blood samples of ME/CFS patientsFrom the Hanson lab, this paper published today in PLoS ONE describes a study carried out with meticulous attention to detail and proper use of controls while analyzing ME/CFS patient samples for murine-leukemia related viruses. Although novel MLV-like GAG sequences were isolated and sequenced from the patient samples (as opposed to controls collected from the same sites) Lee et al. concludes that it is not possible to determine the origin of these sequences, although the samples were not contaminated with mouse DNA at a detectable level. First, bravo! to the Hanson group for being able to get anything published that might go against the current dogma regarding MLV-like viruses in human samples published -- I guarantee you that there are people with similar data whom don't want to torture themselves by attempting to publish. The fact is, that it seems somehow MLV-like nucleic acids somehow end up in patient samples quite a bit, albeit at exceedingly low levels. Theoretically, even if there was an MLV-type infection in a human, it would be rapidly eliminated (unless of course we don't know everything about the immune system yet). I wonder if it is possible that such viruses could hide somewhere in the body, not replicating much - perhaps killing host cells occasionally resulting in a release of (potentially degraded) viral nucleic acid that is ultimately detected in the blood stream. I haven't analyzed these sequences yet compared to those we have detected in tissue samples from BPH patients, but seeing as our sequences were recently published on the <a href="http://portal.uspto.gov/external/portal/!ut/p/c5/04_SB8K8xLLM9MSSzPy8xBz9CP0os3hff1NDc1NLYwN3SzcDA08PwyD_YF8zINcYKB-JW97AiCLdBgR0h4Nci992vPIGEHkDHMDRQN_PIz83VT9SP8ocpylGZvqROanpicmV-gW5oREGmQEZgY6KigBnIW_S/dl3/d3/L0lJSklna21DU1EhIS9JRGpBQU15QUJFUkNKRXFnLzRGR2dzbzBWdnphOUlBOW9JQSEhLzdfTU81MTc1OTMwRzlGMDBJSDFST1NNNjMwMjYvOnIzeEw0MjUwMDAxNi9zYS5nZXRCaWI!/" target="_blank">USPTO </a>website, someone else will probably try that. The link to the Hanson paper is <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0037482" target="_blank">here </a>--Denise S. O'Keefe, PhD.http://www.blogger.com/profile/10878930814538170550noreply@blogger.com58tag:blogger.com,1999:blog-9057886603931233717.post-39355866598397889692012-05-17T10:30:00.000-07:002012-05-17T10:30:40.764-07:00How YOU can help biomedical research in the U.S.!OK so for those fellow scientists out there that might read this blog, this is depressing - but we need to think about it now...it is more than likely that due to a failure of congress to agree on the budget, sequestration will kick in in January 2013. That means if you are lucky enough to have NIH funding, then you will likely suffer a cut of 7.3% of your yearly budget (as prices for everything we use in the lab increase) -- in addition, that will be on top of the already 17% cut from your budget (or more or less, depending on which part of NIH funds you) -- so how do you do the same for less and less each year? In my lab, we already started making most of our own kits, which takes extra time and has its own risks -- potentially diminishing productivity - but can save a lot of money -- we were able to cut about 20% of overall consumable costs this way, but now we are at the bare bones level - so if this cut comes in, the logical choice is to cut salaries - and that means jobs. We are not unique, this is going to affect everyone who is NIH funded, or funded by any other part of government. Furthermore, Dr. Collins, who is the NIH Director, testified to congress that if the "Budget Control Act" is implemented, then thousands of less grants will be able to be funded. That's more jobs gone. But this isn't just about jobs either, its about moving forward with research on cancer treatment and prevention- and every other disease - it's about making sure there is a reason for young people who are interested in science feel that there is a future career in scientific research - What can you do if you care about NIH funded research? Click on the link below, it will lead you to the American Association for Cancer Research website and from there you can contact your members in congress to let them know, they need to do whatever it takes to prevent forced sequestration - and pass a fair budget now! <a href="http://aacr.informz.net/aacr/archives/archive_2356391.html" target="_blank">Contact Congress now!</a>Denise S. O'Keefe, PhD.http://www.blogger.com/profile/10878930814538170550noreply@blogger.com0tag:blogger.com,1999:blog-9057886603931233717.post-8818425530365055272012-05-15T14:38:00.001-07:002012-05-15T14:38:39.397-07:00Supplements and Cancer Prevention: A Cautionary TaleCan there possibly be too much of a good thing? Supplements such as folic acid can be vital if your diet is deficient in folate (as most people's diets were prior to the mandated fortification of the US), especially if you are planning to have a child...and in the case of folate deficiency, it is clear that DNA is likely to become damaged, potentially causing tumors- but if it is so important to have enough, can having too much also be a problem? Read all about it at JNCI -<br />
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<a href="http://jnci.oxfordjournals.org/content/104/10/NP.6.full?etoc">http://jnci.oxfordjournals.org/content/104/10/NP.6.full?etoc</a>Denise S. O'Keefe, PhD.http://www.blogger.com/profile/10878930814538170550noreply@blogger.com3tag:blogger.com,1999:blog-9057886603931233717.post-68804084259167401782012-05-10T12:14:00.003-07:002012-05-10T12:16:27.644-07:00NAR list of useful databases 2012everything from the genome to the metabolome...if you can think it, there is probably a database for it - the journal Nucleic Acids Research has kindly put together a list of these sites -- access it <a href="http://www.oxfordjournals.org/nar/database/cat/10" target="_blank">here </a>--Denise S. O'Keefe, PhD.http://www.blogger.com/profile/10878930814538170550noreply@blogger.com0tag:blogger.com,1999:blog-9057886603931233717.post-79879336118781142892012-05-07T13:33:00.002-07:002012-05-07T13:33:59.525-07:00DNA methylation serves as a molecular memory for gene silencingIn this recent manuscript from JP Issa's group, DNA methylation of a CMV promoter driving GFP was examined - histone deacetylase inhibitors were able to reactivate the promoter, leading to GFP expression; however the promoter remained methylated. The inhibitors were effective for approximately two weeks, after which time the promoter became silent once again. Treatment with inhibitors of DNA methylation however, were able to induce permanent activation of the gene. These findings suggest that if this scenario is relevant to other promoters, it will be necessary to target DNA methylation when designing novel treatments as HDAC inhibitors are only able to temporarily "reset" chromatin. click <a href="http://www.ncbi.nlm.nih.gov/pubmed/22219169" target="_blank">here </a>to read it for yourself.Denise S. O'Keefe, PhD.http://www.blogger.com/profile/10878930814538170550noreply@blogger.com1tag:blogger.com,1999:blog-9057886603931233717.post-38239877408295247752012-05-02T07:19:00.003-07:002012-05-02T07:19:38.785-07:00Pittsburgh Chromatin Club Minisymposium<br />
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<u><span style="font-family: "Arial","sans-serif"; font-size: 11.0pt; mso-bidi-font-family: "Times New Roman"; mso-bidi-font-size: 10.0pt;">Session
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<span style="font-family: "Arial","sans-serif"; font-size: 11.0pt; mso-bidi-font-family: "Times New Roman"; mso-bidi-font-size: 10.0pt;">1:00 Dr.
Tony Schwacha, Department of Biological Sciences, University of Pittsburgh<o:p></o:p></span></div>
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<span style="font-family: "Arial","sans-serif"; font-size: 11.0pt; mso-bidi-font-family: "Times New Roman"; mso-bidi-font-size: 10.0pt;"> “The
Mcm2-7 helicase couples DNA replication to checkpoint control and sister
chromatid cohesion”<o:p></o:p></span></div>
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Nayak, Oesterreich Lab, Department of Pharmacology and Chemical Biology,
University of Pittsburgh School of Medicine, Magee Womens Research Institute<o:p></o:p></span></div>
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<span style="font-family: "Arial","sans-serif"; font-size: 11.0pt; mso-bidi-font-family: "Times New Roman"; mso-bidi-font-size: 10.0pt;"> “Epigenetic
regulation of histone variants—role in endocrine resistant breast cancer?”<o:p></o:p></span></div>
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<span style="font-family: "Arial","sans-serif"; font-size: 11.0pt; mso-bidi-font-family: "Times New Roman"; mso-bidi-font-size: 10.0pt;">2:00 Dr.
J. Richard Chaillet, Department of Microbiology and Molecular Genetics,
University of Pittsburgh School of Medicine, Magee Womens Research Institute<o:p></o:p></span></div>
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<span style="font-family: "Arial","sans-serif"; font-size: 11.0pt; mso-bidi-font-family: "Times New Roman"; mso-bidi-font-size: 10.0pt;"> “DNA
demethylation in plants and animals”<o:p></o:p></span></div>
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Yoel Sadovsky, Department of OBGYN and Reproductive Sciences, Magee Womens
Research Institute<o:p></o:p></span></div>
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<span style="font-family: "Arial","sans-serif"; font-size: 11.0pt; mso-bidi-font-family: "Times New Roman"; mso-bidi-font-size: 10.0pt;"> “Unprecedented
functions of placental microRNAs”<o:p></o:p></span></div>
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<span style="font-family: "Arial","sans-serif"; font-size: 11.0pt; mso-bidi-font-family: "Times New Roman"; mso-bidi-font-size: 10.0pt;">3:30 Dr.
Joe Martens, Department of Biological Sciences, University of Pittsburgh<o:p></o:p></span></div>
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<span style="font-family: "Arial","sans-serif"; font-size: 11.0pt; mso-bidi-font-family: "Times New Roman"; mso-bidi-font-size: 10.0pt;"> “Identification
of a new set of molecular tools to study transcription-dependent chromatin
dynamics”<o:p></o:p></span></div>
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<b><span style="font-family: "Arial","sans-serif"; font-size: 11.0pt; mso-bidi-font-family: "Times New Roman"; mso-bidi-font-size: 10.0pt;">4:00 </span></b><b><span style="font-family: "Arial","sans-serif"; font-size: 11.0pt; mso-bidi-font-family: "Times New Roman";">Dr. Vasily Studitsky, Professor,
Department of Pharmacology, UMDNJ-Robert Wood Johnson Medical School, Rutgers
University<o:p></o:p></span></b></div>
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<b><span style="font-family: "Arial","sans-serif"; font-size: 11.0pt; mso-bidi-font-family: "Times New Roman";"> “Mechanisms and regulation of
transcription in chromatin”<o:p></o:p></span></b></div>
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<span style="font-family: "Arial","sans-serif"; font-size: 11.0pt; mso-bidi-font-family: "Times New Roman"; mso-bidi-font-size: 10.0pt;">After
the final talk we will adjourn to the Church Brew Works, 3525 Liberty Avenue in
Bloomfield, for further discussions.<o:p></o:p></span></div>
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<span style="font-family: "Arial","sans-serif"; font-size: 11.0pt; mso-bidi-font-family: "Times New Roman"; mso-bidi-font-size: 10.0pt;">Please
email <a href="mailto:arndt@pitt.edu">arndt@pitt.edu</a> to be included on the
PCC email list.<o:p></o:p></span></div>
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<b><span style="font-family: "Arial","sans-serif"; mso-bidi-font-family: "Times New Roman";">Funding
generously provided by Abcam and the University of Pittsburgh<o:p></o:p></span></b></div>Denise S. O'Keefe, PhD.http://www.blogger.com/profile/10878930814538170550noreply@blogger.com0tag:blogger.com,1999:blog-9057886603931233717.post-37634697428943339732012-04-30T11:20:00.002-07:002012-04-30T11:21:00.045-07:00Activation of silenced tumor suppressor genes in prostate cancer cells by a novel energy restriction-mimetic agent.In this manuscript published in The Prostate, Ching-Shih Chen's group from Ohio State show that energy restriction (either by novel mimetics or 2-deoxyglucose), led to down-regulation of DNMT1 and 3A (DNA methyltransferases 1 and 3A) and subsequent reactivation of previously hypermethylated tumor suppressor genes - caloric restriction has been shown to suppress cancer in animal models, but these findings provide a novel mechanism for the effect -- read it for yourself at <a href="http://onlinelibrary.wiley.com/doi/10.1002/pros.22530/pdf">http://onlinelibrary.wiley.com/doi/10.1002/pros.22530/pdf</a>Denise S. O'Keefe, PhD.http://www.blogger.com/profile/10878930814538170550noreply@blogger.com0