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  • 1
    Publication Date: 2011-02-11
    Description: Telomere dysfunction activates p53-mediated cellular growth arrest, senescence and apoptosis to drive progressive atrophy and functional decline in high-turnover tissues. The broader adverse impact of telomere dysfunction across many tissues including more quiescent systems prompted transcriptomic network analyses to identify common mechanisms operative in haematopoietic stem cells, heart and liver. These unbiased studies revealed profound repression of peroxisome proliferator-activated receptor gamma, coactivator 1 alpha and beta (PGC-1alpha and PGC-1beta, also known as Ppargc1a and Ppargc1b, respectively) and the downstream network in mice null for either telomerase reverse transcriptase (Tert) or telomerase RNA component (Terc) genes. Consistent with PGCs as master regulators of mitochondrial physiology and metabolism, telomere dysfunction is associated with impaired mitochondrial biogenesis and function, decreased gluconeogenesis, cardiomyopathy, and increased reactive oxygen species. In the setting of telomere dysfunction, enforced Tert or PGC-1alpha expression or germline deletion of p53 (also known as Trp53) substantially restores PGC network expression, mitochondrial respiration, cardiac function and gluconeogenesis. We demonstrate that telomere dysfunction activates p53 which in turn binds and represses PGC-1alpha and PGC-1beta promoters, thereby forging a direct link between telomere and mitochondrial biology. We propose that this telomere-p53-PGC axis contributes to organ and metabolic failure and to diminishing organismal fitness in the setting of telomere dysfunction.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3741661/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3741661/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sahin, Ergun -- Colla, Simona -- Liesa, Marc -- Moslehi, Javid -- Muller, Florian L -- Guo, Mira -- Cooper, Marcus -- Kotton, Darrell -- Fabian, Attila J -- Walkey, Carl -- Maser, Richard S -- Tonon, Giovanni -- Foerster, Friedrich -- Xiong, Robert -- Wang, Y Alan -- Shukla, Sachet A -- Jaskelioff, Mariela -- Martin, Eric S -- Heffernan, Timothy P -- Protopopov, Alexei -- Ivanova, Elena -- Mahoney, John E -- Kost-Alimova, Maria -- Perry, Samuel R -- Bronson, Roderick -- Liao, Ronglih -- Mulligan, Richard -- Shirihai, Orian S -- Chin, Lynda -- DePinho, Ronald A -- P30 DK046200/DK/NIDDK NIH HHS/ -- P30DK079638/DK/NIDDK NIH HHS/ -- R01 CA084628/CA/NCI NIH HHS/ -- R01 DK035914/DK/NIDDK NIH HHS/ -- R01 DK056690/DK/NIDDK NIH HHS/ -- R01 DK063356/DK/NIDDK NIH HHS/ -- R01 DK089185/DK/NIDDK NIH HHS/ -- U24 DK-59635/DK/NIDDK NIH HHS/ -- England -- Nature. 2011 Feb 17;470(7334):359-65. doi: 10.1038/nature09787. Epub 2011 Feb 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Belfer Institute for Applied Cancer Science, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21307849" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphate/biosynthesis ; Aging/metabolism/pathology ; Animals ; Cardiomyopathies/chemically induced/metabolism/pathology/physiopathology ; Cell Proliferation ; DNA, Mitochondrial/analysis ; Doxorubicin/toxicity ; Gluconeogenesis ; Hematopoietic Stem Cells/metabolism/pathology ; Liver/cytology/metabolism ; Mice ; Mitochondria/*metabolism/*pathology ; Myocardium/cytology/metabolism ; RNA/genetics ; Reactive Oxygen Species/metabolism ; Telomerase/deficiency/genetics ; Telomere/enzymology/genetics/*metabolism/*pathology ; Transcription Factors/antagonists & inhibitors/metabolism ; Tumor Suppressor Protein p53/deficiency/genetics/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
    ISSN: 0277-5387
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford [u.a.] : International Union of Crystallography (IUCr)
    Acta crystallographica 51 (1995), S. 2263-2265 
    ISSN: 1600-5759
    Source: Crystallography Journals Online : IUCR Backfile Archive 1948-2001
    Topics: Chemistry and Pharmacology , Geosciences , Physics
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Oxford [u.a.] : International Union of Crystallography (IUCr)
    Acta crystallographica 51 (1995), S. 2484-2486 
    ISSN: 1600-5759
    Source: Crystallography Journals Online : IUCR Backfile Archive 1948-2001
    Topics: Chemistry and Pharmacology , Geosciences , Physics
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1745-4573
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Process Engineering, Biotechnology, Nutrition Technology
    Notes: This study evaluated the ability of the razor blade (RB) shearing method and various other instrumental shearing methods as a means for developing models to predict tenderness in broiler breast fillets. Breast fillets were subjected to either shear analysis (razor, Allo-Kramer or Warner-Bratzler) or sensory evaluation (trained descriptive or consumer). The relationships between the instrumental and the descriptive sensory attributes exhibited coefficients of determination of 0.53 〈 R2 〈 0.73 for initial hardness and chewdown hardness, while the relationships between the instrumental and the consumer sensory attributes of tenderness acceptability and intensity had coefficients of determination ranging between 0.71 〈 R2 〈 0.97. For both descriptive and consumer sensory analyses, the instrumental shear tests performed similarly for predicting the tenderness of cooked broiler breast meat. The RB shear test for assessing meat tenderness had advantages, in that no sample cutting or weighing was required to execute the test nor was it excessively destructive, as only a small incision was made in the sample.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1750-3841
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Process Engineering, Biotechnology, Nutrition Technology
    Notes: : This study was conducted to evaluate a new shearing method for the determination of poultry meat tenderness. Breast fillets were deboned at various postmortem times (0.25 to 24 h) to yield a vast array of tenderness levels. A trained descriptive panel was used to evaluate samples for attributes including initial hardness and chewdown hardness; instrumental measurements included Allo-Kramer (AK) and razor blade (RB) shear and laser sarcomere length determination. The RB shear method exhibited a higher correlation to sensory attributes than the AK method, suggesting that the new razor blade shear method is more advantageous in predicting poultry meat tenderness than the standard AK shear method. This new method not only has a higher sensory predictive value, but also requires shorter sample preparation time than the AK shear test because it is conducted on intact fillets.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1750-3841
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Process Engineering, Biotechnology, Nutrition Technology
    Notes: : A novel modeling technique named MARS (Multivariate Adaptive Regression Splines) can automate variable selection as well as model selection. The main purpose of this study was to apply MARS to consumer preference mapping using consumer test data for cheese sticks. The results show that MARS was capable of modeling consumer's preference patterns for cheese sticks. One distinct advantage of MARS in preference mapping is that it has the ability to model hedonic-scale response variables (such as overall acceptance, acceptance of appearance, flavor, and texture) from “Just About Right” (JAR) predictor variables (such as color, size, saltiness, breading, and cheese texture). In addition, MARS can reveal the underlying relationship between the predictors and the response in a piecewise regression function. This study shows that MARS has potential uncovering underlying patterns hidden in complex data.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1750-3841
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Process Engineering, Biotechnology, Nutrition Technology
    Notes: : This study was conducted to identify what constitutes consumer preference for and acceptance of white corn tortilla chips. Consumer overall acceptance of tortill chips was modeled by consumer data for acceptance of appearance, flavor, and texture and by descriptive sensory and/or instrumental data. Internal preference mapping (R2= 0.99) showed that flavor was the most important attribute to consumer overall acceptance followed by texture and appearance. The basic salt attribute and aftertaste attributes of salt, raw masa, and toasted grain aftertastes were important to consumer flavor acceptance, and the attributes of crispness, loose particles, hardness and oily/greasy film were responsible for consumer acceptance of texture. One appearance descriptive attribute (char marks) and 1 instrumental color measurement (a) were significantly related to consumer acceptance of appearance.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1750-3841
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Process Engineering, Biotechnology, Nutrition Technology
    Notes: : The effect of deformation (10% to 90%) and deformation rate (0.2 to 10 mm/s) on both maximum compression force and correlation between sensory and instrumental measurements of hardness were investigated for 26 commercial cheeses. Log-linear regression models were used to model the relationship between deformation rate and maximum compression force and fitted well to the relationship, indicating that maximum compression force is a log linear function of deformation rate. Deformation had a large effect on the correlation between sensory and instrumental hardness, while deformation rate had a small effect. The optimal deformation and deformation rate for the maximum correlation were 70% to 90% and 1.0 mm/s, respectively. This implies that an optimal combination of deformation and deformation rate can be used for maximizing the correlation between sensory and instrumental hardness for cheese products.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Oxford [u.a.] : International Union of Crystallography (IUCr)
    Acta crystallographica 51 (1995), S. 2258-2259 
    ISSN: 1600-5759
    Source: Crystallography Journals Online : IUCR Backfile Archive 1948-2001
    Topics: Chemistry and Pharmacology , Geosciences , Physics
    Type of Medium: Electronic Resource
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