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Sirt1 improves healthy ageing and protects from metabolic syndrome-associated cancer

Posted: May 3, 2010 at 5:50 am

FROM NATURE COMMUNICATIONS | for ARTICLE click here.

  • Daniel Herranz,

  • Maribel Muñoz-Martin,

  • Marta Cañamero,

  • Francisca Mulero,

  • Barbara Martinez-Pastor,

  • Oscar Fernandez-Capetillo

  • & Manuel Serrano

    • Abstract
    Genetic overexpression of protein deacetylase Sir2 increases longevity in a variety of lower organisms, and this has prompted interest in the effects of its closest mammalian homologue, Sirt1, on ageing and cancer. We have generated transgenic mice moderately overexpressing Sirt1 under its own regulatory elements (Sirt1-tg). Old Sirt1-tg mice present lower levels of DNA damage, decreased expression of the ageing-associated gene p16Ink4a, a better general health and fewer spontaneous carcinomas and sarcomas. These effects, however, were not sufficiently potent to affect longevity. To further extend these observations, we developed a metabolic syndrome-associated liver cancer model in which wild-type mice develop multiple carcinomas. Sirt1-tg mice show a reduced susceptibility to liver cancer and exhibit improved hepatic protection from both DNA damage and metabolic damage. Together, these results provide direct proof of the anti-ageing activity of Sirt1 in mammals and of its tumour suppression activity in ageing- and metabolic syndrome-associated cancer.

    Recommendation and review posted by G. Smith

    The Synaptic Leap Experiments on Reaction Attempts

    Posted: May 3, 2010 at 12:37 am

    Andrew Lang and I recently reported on the first edition of the Reaction Attempts book and database. Part of the motivation for this was to structure the experiments from the UsefulChem project in both a machine readable format and one that could be browsed as a physical copy. However, we also had in mind the easy integration of other open experiments, especially those labeled as “failed”, since these are unlikely to be found by searching conventional reaction archives.

    As a demonstration, we have added a series of experiments from The Synaptic Leap, which Michael Wolfle (working as a post-doc with Mat Todd) has posted. All of these reactions involve intermediates in the synthesis of praziquantel, which is a major focus of the Todd group. One group of these reactions involved the attempted synthesis of praziquanamine via a Pictet-Spengler cyclization. Most of these are failed attempts and one successful one.

    Adding these experiments to Reaction Attempts was very simple – since the minimum information required is the ChemSpiderIDs (CSIDs) of all the reactants and the product, which a hyperlink to more details. We also added a few more details provided by Michael – such as the solvent, reaction conditions and outcome.

    Andy has provided a simple mechanism to pull up all Reaction Attempts for a given reactant with the following url structure:

    http://showme.physics.drexel.edu/onsc/databook/ucdatabook.php?reactants=9099925

    The number at the end is the CSID for the reactant. Multiple reactants can be pulled from the database by adding more CSIDs separated by commas.

    Successful runs in Reaction Attempts are identified with a green check mark:


    Again the main idea here is not to exhaustively abstract all pertinent information for an experiment. Rather it is to connect up researchers who are working on similar reactions. Since it requires so little effort to come up with the minimum required information we are hoping to get contributions from other sources.

    We will focus next on coming up with more sophisticated ways to retrieve information – such as substructure searching or by reaction type, solvent, etc. We will also periodically publish hard copies of future Reaction Attempts editions.

    Recommendation and review posted by G. Smith

    Tiotropium for COPD: A good foundation therapy for most patients

    Posted: May 2, 2010 at 11:40 pm

    From a BMJ Editorial:

    Tiotropium is a once daily, inhaled, long acting anticholinergic drug (LAMA) that provides 24 hour improvement in airflow and hyperinflation in patients with chronic obstructive pulmonary disease (COPD).

    Clinical trials have consistently shown that these physiological effects translate into improvements in:

    – lung function
    – exercise tolerance
    – health related quality of life
    – fewer exacerbations

    References:

    Tiotropium and chronic obstructive pulmonary disease. BMJ, 2010.
    http://www.bmj.com/cgi/content/short/340/feb19_1/c833
    Image source: Wikipedia, public domain.

    Posted at Clinical Cases and Images. Stay updated and subscribe, follow us on Twitter and connect on Facebook.


    Recommendation and review posted by G. Smith

    CSC news links 2010-05-01

    Posted: May 2, 2010 at 8:16 am

    For links to recent news items, visit these [Twitter] or [FriendFeed] pages. Examples of two news items that have received attention:?

    Recommendation and review posted by Fredricko

    More about presentations at AACR10

    Posted: May 2, 2010 at 8:16 am

    Five presentations at the 101th annual meeting of the American Association of Cancer Research were highlighted a news release from Geron Corporation (dated March 3, 2010). One presentation that had an explicit focus on CSC was this poster:

    Imetelstat, a telomerase inhibitor in phase I trials in solid tumor and hematological malignancies, has broad activity against multiple types of cancer stem cells [Presentation Abstract].

    Also mentioned in the news release was an oral presentation by Jerry W Shay, given as part of the Major Symposium entitled: Role of Telomeres and Telomerase in Chromosomal Stability and Disease [Session Detail]. The presentation was:

    Role of telomerase in normal and neoplastic stem cells [Presentation Abstract].

    Another poster about the telomerase inhibitor imetelstat (GRN163L) was:

    Sensitivity and resistance of non-small cell lung cancer to the telomerase inhibitor imetelstat [Presentation Abstract].

    Comments: A search of the ClinicalTrials.gov database for GRN163L revealed 6 trials. Four were ongoing, but not recruiting participants. Two were still recruiting: 1) Safety and Dose Study of GRN163L Administered to Patients With Refractory or Relapsed Solid Tumor Malignancies; 2) A Study of GRN163L With Paclitaxel and Bevacizumab to Treat Patients With Locally Recurrent Or Metastatic Breast Cancer.

    An analogous search for imetelstat yielded the same 6 trials. All 6 trials have been sponsored by Geron Corporation.

    Recommendation and review posted by Fredricko

    Some nurses paid more than family doctors – CNN

    Posted: May 2, 2010 at 8:16 am

    Primary care doctors were offered an average base salary of $173,000 in 2009 compared to an average base salary of $189,000 offered to certified nurse anesthetists, or CRNAs.

    It’s the fourth year in a row that CRNAs were recruited at a higher pay than a family doctor.

    Comments from Google Buzz:

    Jeffrey Benabio, MD – And soon doctor of nursing programs will graduate nurses who call themselves “doctor” in clinic. Physicians have been asleep at the wheel.

    http://en.wikipedia.org/wiki/Doctorate_in_Nursing

    Francesco Diana – without words

    Anne Marie Cunningham – Both of these are very high salaries. As @scanman points out, they are unobtainable for most people working in health in India and countries. Can we tolerate such global inequality?

    How should salaries in any part of the world be determined? Are both these groups paid too much?

    At the moment there is a great deal of uncertainty on how the role of a doctor differs to the role of a nurse. Professor Alan Maynard suggests that professions are bad for healthcare. http://www.healthpolicyinsight.com/?q=node/458 What do you think?

    Image source: OpenClipArt.org, public domain.

    Posted at Clinical Cases and Images. Stay updated and subscribe, follow us on Twitter and connect on Facebook.


    Recommendation and review posted by G. Smith


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