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  • 1
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    Intestinal inflammation targets cancer-inducing activity of the microbiota (2012)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2012-08-21
    Description: Inflammation alters host physiology to promote cancer, as seen in colitis-associated colorectal cancer (CRC). Here, we identify the intestinal microbiota as a target of inflammation that affects the progression of CRC. High-throughput sequencing revealed that inflammation modifies gut microbial composition in colitis-susceptible interleukin-10-deficient (Il10(-/-)) mice. Monocolonization with the commensal Escherichia coli NC101 promoted invasive carcinoma in azoxymethane (AOM)-treated Il10(-/-) mice. Deletion of the polyketide synthase (pks) genotoxic island from E. coli NC101 decreased tumor multiplicity and invasion in AOM/Il10(-/-) mice, without altering intestinal inflammation. Mucosa-associated pks(+) E. coli were found in a significantly high percentage of inflammatory bowel disease and CRC patients. This suggests that in mice, colitis can promote tumorigenesis by altering microbial composition and inducing the expansion of microorganisms with genotoxic capabilities.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3645302/" 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/PMC3645302/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Arthur, Janelle C -- Perez-Chanona, Ernesto -- Muhlbauer, Marcus -- Tomkovich, Sarah -- Uronis, Joshua M -- Fan, Ting-Jia -- Campbell, Barry J -- Abujamel, Turki -- Dogan, Belgin -- Rogers, Arlin B -- Rhodes, Jonathan M -- Stintzi, Alain -- Simpson, Kenneth W -- Hansen, Jonathan J -- Keku, Temitope O -- Fodor, Anthony A -- Jobin, Christian -- MOP114872/Canadian Institutes of Health Research/Canada -- P30 CA016086/CA/NCI NIH HHS/ -- P30 DK034987/DK/NIDDK NIH HHS/ -- P40 R018603/PHS HHS/ -- R01 CA136887/CA/NCI NIH HHS/ -- R01 DK047700/DK/NIDDK NIH HHS/ -- R01 DK073338/DK/NIDDK NIH HHS/ -- R01 DK47700/DK/NIDDK NIH HHS/ -- R01 DK53347-11/DK/NIDDK NIH HHS/ -- R01 DK73338/DK/NIDDK NIH HHS/ -- T32 DK007737/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 2012 Oct 5;338(6103):120-3. doi: 10.1126/science.1224820. Epub 2012 Aug 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, Pharmacology and Immunology-Microbiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22903521" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Azoxymethane/toxicity ; Carcinogens/toxicity ; Carcinoma/chemically induced/*microbiology/pathology ; Cell Transformation, Neoplastic/genetics/pathology ; Colitis/*complications/genetics ; Colorectal Neoplasms/chemically induced/*microbiology/pathology ; *DNA Damage ; Escherichia coli/genetics/pathogenicity ; Interleukin-10/genetics ; Intestines/*microbiology/pathology ; Metagenome/genetics/*physiology ; Mice ; Mice, Mutant Strains ; Polyketide Synthases/genetics ; Sequence Deletion
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 2
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    Climate Sensitivity in the Anthropocene (2014)
    In:  CASI
    Details
    Publication Date: 2019-07-13
    Description: Climate sensitivity in its most basic form is defined as the equilibrium change in global surface temperature that occurs in response to a climate forcing, or externally imposed perturbation of the planetary energy balance. Within this general definition, several specific forms of climate sensitivity exist that differ in terms of the types of climate feedbacks they include. Based on evidence from Earth's history, we suggest here that the relevant form of climate sensitivity in the Anthropocene (e.g. from which to base future greenhouse gas (GHG) stabilization targets) is the Earth system sensitivity including fast feedbacks from changes in water vapour, natural aerosols, clouds and sea ice, slower surface albedo feedbacks from changes in continental ice sheets and vegetation, and climate-GHG feedbacks from changes in natural (land and ocean) carbon sinks. Traditionally, only fast feedbacks have been considered (with the other feedbacks either ignored or treated as forcing), which has led to estimates of the climate sensitivity for doubled CO2 concentrations of about 3 C. The 2CO2 Earth system sensitivity is higher than this, being approx. 4-6 C if the ice sheet/vegetation albedo feedback is included in addition to the fast feedbacks, and higher still if climate-GHG feedbacks are also included. The inclusion of climate-GHG feedbacks due to changes in the natural carbon sinks has the advantage of more directly linking anthropogenic GHG emissions with the ensuing global temperature increase, thus providing a truer indication of the climate sensitivity to human perturbations. The Earth system climate sensitivity is difficult to quantify due to the lack of palaeo-analogues for the present-day anthropogenic forcing, and the fact that ice sheet and climate-GHG feedbacks have yet to become globally significant in the Anthropocene. Furthermore, current models are unable to adequately simulate the physics of ice sheet decay and certain aspects of the natural carbon and nitrogen cycles. Obtaining quantitative estimates of the Earth system sensitivity is therefore a high priority for future work.
    Keywords: Meteorology and Climatology
    Type: GSFC-E-DAA-TN13916 , Quarterly Journal of the Royal Meteorological Society; 139; 674; 1121-1131
    Format: application/pdf
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  • 3
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    Making Sense of Palaeoclimate Sensitivity (2012)
    In:  CASI
    Details
    Publication Date: 2019-07-13
    Description: Many palaeoclimate studies have quantified pre-anthropogenic climate change to calculate climate sensitivity (equilibrium temperature change in response to radiative forcing change), but a lack of consistent methodologies produces a wide range of estimates and hinders comparability of results. Here we present a stricter approach, to improve intercomparison of palaeoclimate sensitivity estimates in a manner compatible with equilibrium projections for future climate change. Over the past 65 million years, this reveals a climate sensitivity (in K W1 m2) of 0.3-1.9 or 0.6-1.3 at 95% or 68% probability, respectively. The latter implies a warming of 2.2-4.8 K per doubling of atmospheric CO2, which agrees with IPCC estimates.
    Keywords: Meteorology and Climatology
    Type: GSFC-E-DAA-TN8833 , Nature; 491; 683-691
    Format: application/pdf
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