Immortality Medicine

Comparison of heterologous xylose transporters in recombinant Saccharomyces cerevisiae

admin — Thu, 18 Mar 2010 04:12:03 +0000

Background:
Baker’s yeast (Saccharomyces cerevisiae) has been engineered for xylose utilization to enable production of fuel ethanol from lignocellulose raw material. One unresolved challenge is that S. cerevisiae lacks a dedicated transport system for pentose sugars, which means that xylose is transported by non-specific Hxt transporters with comparatively low transport rate and affinity for xylose.
Results:
In this study, we compared three heterologous xylose transporters that have recently been shown to improve xylose uptake under different experimental conditions. The transporters Gxf1, Sut1 and At5g59250 from Candida intermedia, Pichia stipitis and Arabidopsis thaliana, respectively, were expressed in isogenic strains of S. cerevisiae and the transport kinetics and utilization of xylose was evaluated. Expression of the Gxf1 and Sut1 transporters led to significantly increased affinity and transport rates of xylose. In batch cultivation at 4 g/L xylose concentration, improved transport kinetics led to a corresponding increase in xylose utilization, whereas no correlation could be demonstrated at xylose concentrations greater than 15 g/L. The relative contribution of native sugar transporters to the overall xylose transport capacity was also estimated during growth on glucose and xylose.
Conclusions:
Kinetic characterization and aerobic batch cultivation of strains expressing the Gxf1, Sut1 and At5g59250 transporters showed a direct relationship between transport kinetics and xylose growth. The Gxf1 transporter had the highest transport capacity and the highest xylose growth rate, followed by the Sut1 transporter. The range in which transport controlled the growth rate was determined to between 0 and 15 g/L xylose. The role of catabolite repression in regulation of native transporters was also confirmed by the observation that xylose transport by native S. cerevisiae transporters increased significantly during cultivation in xylose and at low glucose concentration.

Early Glance: Biotechnology companies (AP via Yahoo! Finance)

admin — Thu, 18 Mar 2010 04:12:02 +0000

NEW YORK (AP) — Shares of some top biotechnology companies are mixed at 10 a.m.: Amgen fell $.30 or .5 percent, to $57.12. Biogen Idec fell $.24 or .4 percent, to $59.49. Celgene rose $.57 or .9 percent, to $63.39. Gilead Sciences fell $.23 or .5 percent, to $47.24.

Gene Expression-Based Prognostic Signatures In Lung Cancer Not Ready For Clinical Use

admin — Thu, 18 Mar 2010 04:12:01 +0000

A review of published articles on gene expression-based prognostic signatures in lung cancer revealed little evidence that any of the signatures are ready for clinical use. Serious problems in the design and analysis of the studies were also found. The review was published online March 16, 2010 in the Journal of the National Cancer Institute…

Hand Bacteria May One Day Aid Forensic Identification, Study

admin — Thu, 18 Mar 2010 04:12:01 +0000

Next time you leave your computer station or close the lid of your laptop think about this: your mouse and keyboard are covered in hand bacteria that could be traced back to you, according to a new US study that suggests the unique bacterial communities we leave behind on objects we have handled may one day sit alongside DNA and fingerprints as part of the forensic tool…

How can MDVIP use Navigenics Test for Medicine?

admin — Thu, 18 Mar 2010 04:12:01 +0000

I have been harping on this say what you mean. Say what you do. Theme lately.

I am a board certified doctor who practices personalized medicine. I see patients and apply the principles or pharmacogenomics, risk prediction and prevention tailored to each individual patient. I do this by taking a 3 generation pedigree, using current clinical risk models and pharmacogenomic or other genetic tests when indicated. That’s me.

I have this nagging pain about MDVIP, Ed Goldman and Navigenics.

Some MDVIP members are using Navigenics tests for medical risk prediction. Navigenics is ok with this because hey, they’re doctors.

But I have a problem. The only terms of service I see here for Navigenics is listed and reads

The contents of our Site, including any risk estimates or other reports generated by the Services (collectively, “Your Report“) and any other information, data, analyses, editorial content, images, audio and video clips, hyperlinks and references (collectively, “Content“), are for informational purposes only and are not intended to substitute for professional medical advice, diagnosis, or treatment.

The part I want to focus on is “Are for informational purposes only and are not intended to substitute for professional medical advice, diagnosis or treatment”

It seems to me that this will be the more popular language in a Terms of Service for DTCG.

Notice that nowhere does it say, “This report is not intended to diagnose or treat”

I think that while it is nice to not say that, when in fact people are using it to diagnose, it is even goofier to say that it is not intended to substitute for a professional’s diagnosis. Ok, so are you saying

1. This is not to be used for diagnosis/medical advice

2. This is to be used for diagnosis, but the professional’s diagnosis trumps ours

3. This test is meant to be used by professionals to aid them in diagnosis and treatment

I am really confused here. Is this a medical test or not. Just come right out and say it!

The Sherpa Says: Say what you do, do what you say you do. Isn’t that what the Common Framework of Principles is About?

SNPs for breast cancer risk? It Depends.

admin — Thu, 18 Mar 2010 04:12:01 +0000

I hold in my hot little hands a copy of the NEJM, March 18th edition. In it there is an article which isn’t even released yet.

Entitled

“Performance of Common Genetic Variants in Breast-Cancer Risk Models”

Remember when we did this for heart disease risk? FAIL WHALE…..

Do you think it will happen again?

The Study

10 common genetic variants

I had to create a couple of pages on SNPedia for this list FYI…..

The Methods:

Cases and controls-WHI, ACS CPSII Nutrition Cohort, Nurses Health Study, Prostate/Lung/Colorectal/Ovarian Cancer Screening Trial, and Polish Breast Cancer Study.

Cases-Woman who had received diagnosis of invasive breast cancer.

Risk Models Used-A hybrid of the Gail model…..I.E. Not exactly the Gail Model.

1. First degree relatives with breast cancer

2. Age at Menarche

3. Age at first live birth

4. Number of Breast Biopsies

They acknowledge that they were unable to get atypical hyperplasia and Mammographic density. Both of which have improved Gail.

So, This Gail is a little hobbled and not the best predictive model…….

The studied models- 5 logistic regression models

I don’t have the supplementary tables and methods yet.

The nongenetic model-Gail Model

The Demographic/Genetic Variant Count Model-included number of alleles.

The Demographic/Genetic Individual Variant-Accounted for individual effects of each SNP

The Inclusive Model-Gail, Genetics Demographics

The Demographic Model

And Random….

When we do these sorts of statistical analyses we look for a couple of things.

A. Number of people reclassified and how?

B. The Area Under the ROC Curve

The AUC is a good way of seeing whether a model or test is worthless or useful. And how much MORE useful than another test.

Results-

1. The Inclusive Model Yielded and AUC of 61.8%

2. The Nongenetic Model yielded an AUC of 58%

3. The Genetic Individual Variant Yielded an AUC of 59.7%

4. The Genetic Variant Count Yielded an AUC of 58.8%

5. Breast Biopsy BY ITSELF Yielded an AUC of 56.2%

That is a 3.8% difference in Yield from Genes and without Genes integrated into the weaker Gail Model.

Lastly, they asked. Well, does this Inclusive Model do a good job of discrimination of High risk vs. low risk.

The Answer- It determines lower risk better than Gail. It does not determine higher risk better.

The authors of this study have stated that

“As in Diabetes and cardiovascular disease, the addition of the common SNPs added little to the predictive value of the clinical models. On the basis of theoretical models, Gail has shown that increases in the AUC similar to those observed here and not sufficiently large to improve meaningfully the identification of women who might benefit from tamoxifen prophylaxis or screening mammography”

Take Home

The addition of these factors only creates a minimal statistical increase that is of no useful clinical benefit.

The Sherpa Says: If the press says “gene tests fail to improve risk assessment” You can be assured that the DTCG industry is no longer the darlings. If instead they say “Improvement in risk model” well, then you have chance to woo them back! It Depends…….

GenVault Provides GenTegra(TM) DNA to Support Cardiovascular Genetic Testing at Berkeley HeartLab (redOrbit)

admin — Thu, 18 Mar 2010 04:11:59 +0000

CARLSBAD, Calif., March 17 /PRNewswire/ — GenVault Corporation today announced that Berkeley HeartLab, a subsidiary of Celera Corporation (Nasdaq: CRA), has adopted GenTegra DNA to preserve and store diagnostic samples for genetic testing related to the management of cardiovascular disease.

GenVault Provides GenTegra(TM) DNA to Support Cardiovascular Genetic Testing at Berkeley HeartLab (redOrbit)

admin — Thu, 18 Mar 2010 04:11:58 +0000

Pluripotent plasticity of stem cells and liver repopulation