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  • 1
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    Chemoprevention of colorectal cancer by targeting APC-deficient cells for apoptosis (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-03-30
    Description: Cancer chemoprevention uses natural, synthetic, or biological substances to reverse, suppress, or prevent either the initial phase of carcinogenesis or the progression of neoplastic cells to cancer. It holds promise for overcoming problems associated with the treatment of late-stage cancers. However, the broad application of chemoprevention is compromised at present by limited effectiveness and potential toxicity. To overcome these challenges, here we developed a new chemoprevention approach that specifically targets premalignant tumour cells for apoptosis. We show that a deficiency in the adenomatous polyposis coli (APC) gene and subsequent activation of beta-catenin lead to the repression of cellular caspase-8 inhibitor c-FLIP (also known as CFLAR) expression through activation of c-Myc, and that all-trans-retinyl acetate (RAc) independently upregulates tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) death receptors and suppresses decoy receptors. Thus, the combination of TRAIL and RAc induces apoptosis in APC-deficient premalignant cells without affecting normal cells in vitro. In addition, we show that short-term and non-continuous TRAIL and RAc treatment induce apoptosis specifically in intestinal polyps, strongly inhibit tumour growth, and prolong survival in multiple intestinal neoplasms C57BL/6J-Apc(Min)/J (Apc(Min)) mice. With our approach, we further demonstrate that TRAIL and RAc induce significant cell death in human colon polyps, providing a potentially selective approach for colorectal cancer chemoprevention by targeting APC-deficient cells for apoptosis.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3425353/" 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/PMC3425353/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Ling -- Ren, Xiaoyang -- Alt, Eckhard -- Bai, Xiaowen -- Huang, Shaoyi -- Xu, Zhengming -- Lynch, Patrick M -- Moyer, Mary P -- Wen, Xian-Feng -- Wu, Xiangwei -- AI063063/AI/NIAID NIH HHS/ -- R01 AI063063/AI/NIAID NIH HHS/ -- England -- Nature. 2010 Apr 15;464(7291):1058-61. doi: 10.1038/nature08871. Epub 2010 Mar 28.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Head and Neck Surgery, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20348907" target="_blank"〉PubMed〈/a〉
    Keywords: Adenomatous Polyposis Coli Protein/*deficiency/genetics ; Animals ; Apoptosis/*drug effects ; CASP8 and FADD-Like Apoptosis Regulating Protein/metabolism ; Cell Proliferation/drug effects ; Colorectal Neoplasms/genetics/metabolism/*pathology/*prevention & control ; Gene Expression Regulation/drug effects ; Genes, APC ; Humans ; Intestinal Polyps/drug therapy/pathology ; Mice ; Mice, Inbred C57BL ; Precancerous Conditions/drug therapy/genetics/metabolism/pathology ; Proto-Oncogene Proteins c-myc/metabolism ; Receptors, TNF-Related Apoptosis-Inducing Ligand/metabolism ; Signal Transduction/drug effects ; Survival Rate ; TNF-Related Apoptosis-Inducing Ligand/administration & ; dosage/pharmacology/therapeutic use ; Time Factors ; Vitamin A/administration & dosage/*analogs & derivatives/pharmacology/therapeutic ; use ; beta Catenin/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 2
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    Systematic evaluation of antibody-mediated siRNA delivery using an industrial platform of THIOMAB-siRNA conjugates (2015)
    Oxford University Press
    Details
    Publication Date: 2015-01-24
    Description: Delivery of siRNA is a key hurdle to realizing the therapeutic promise of RNAi. By targeting internalizing cell surface antigens, antibody–siRNA complexes provide a possible solution. However, initial reports of antibody–siRNA complexes relied on non-specific charged interactions and have not been broadly applicable. To assess and improve this delivery method, we built on an industrial platform of therapeutic antibodies called THIOMABs, engineered to enable precise covalent coupling of siRNAs. We report that such coupling generates monomeric antibody–siRNA conjugates (ARCs) that retain antibody and siRNA activities. To broadly assess this technology, we generated a battery of THIOMABs against seven targets that use multiple internalization routes, enabling systematic manipulation of multiple parameters that impact delivery. We identify ARCs that induce targeted silencing in vitro and extend tests to target prostate carcinoma cells following systemic administration in mouse models. However, optimal silencing was restricted to specific conditions and only observed using a subset of ARCs. Trafficking studies point to ARC entrapment in endocytic compartments as a limiting factor, independent of the route of antigen internalization. Our broad characterization of multiple parameters using therapeutic-grade conjugate technology provides a thorough assessment of this delivery technology, highlighting both examples of success as well as remaining challenges.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 3
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    Underestimated effects of low temperature during early growing season on carbon sequestration of a subtropical coniferous plantation (2011)
    Copernicus
    Details
    Publication Date: 2011-02-15
    Description: The impact of air temperature in early months on the carbon sequestration of a subtropical coniferous plantation was discussed by analyzing the eddy flux observations at Qianyanzhou (QYZ) site located in southern China from 2003 to 2008. This site experienced two cold early growing seasons (with temperature anomalies of 2–5° C) in 2005 and 2008, and also a severe summer drought in 2003. Results indicated that the low air temperature from January to March was the major factor controlling the inter-annual variations in net carbon uptake at this site, rather than the previously thought summer drought. The accumulative air temperature from January to February showed high correlation (R2 = 0.970, p 〈 0.001) with the annual net ecosystem production (NEP). This was due to the controls of early-months temperature on the plant phenology developing and the growing season length at this subtropical site. The cold spring greatly shortened the growing season length and therefore reduced the carbon uptake period. The eddy flux observations showed a carbon loss of 4.04 g C m−2 per growing-season day at this coniferous forest site. On the other hand, the summer drought also reduced the net carbon uptake strength because the photosynthesis was more sensitive to water deficit stress than the ecosystem respiration. However, the impact of summer drought occurred within a relatively shorter period and the carbon sequestration went back to the normal level once the drought was relieved.
    Print ISSN: 1810-6277
    Electronic ISSN: 1810-6285
    Topics: Biology , Geosciences
    Published by Copernicus on behalf of European Geosciences Union.
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  • 4
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    Responses of soil microbial communities and enzyme activities to nitrogen and phosphorus additions in Chinese fir plantations of subtropical China (2015)
    Copernicus
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    Publication Date: 2015-07-08
    Description: Nitrogen (N) and phosphorus (P) additions to forest ecosystems are known to influence various above-ground properties, such as plant productivity and composition, and below-ground properties, such as soil nutrient cycling. However, our understanding of how soil microbial communities and their functions respond to nutrient additions in subtropical plantations is still not complete. In this study, we added N and P to Chinese fir plantations in subtropical China to examine how nutrient additions influenced soil microbial community composition and enzyme activities. The results showed that most soil microbial properties were responsive to N and/or P additions, but responses often varied depending on the nutrient added and the quantity added. For instance, there were more than 30 % greater increases in the activities of β-Glucosidase (βG) and N-acetyl-β-D-glucosaminidase (NAG) in the treatments that received nutrient additions compared to the control plot, whereas acid phosphatase (aP) activity was always higher (57 and 71 %, respectively) in the P treatment. N and P additions greatly enhanced the PLFA abundanceespecially in the N2P treatment, the bacterial PLFAs (bacPLFAs), fungal PLFAs (funPLFAs) and actinomycic PLFAs (actPLFAs) were about 2.5, 3 and 4 times higher, respectively, than in the CK. Soil enzyme activities were noticeably higher in November than in July, mainly due to seasonal differences in soil moisture content (SMC). βG or NAG activities were significantly and positively correlated with microbial PLFAs. There were also significant relationships between gram-positive (G+) bacteria and all three soil enzymes. These findings indicate that G+ bacteria is the most important microbial community in C, N, and P transformations in Chinese fir plantations, and that βG and NAG would be useful tools for assessing the biogeochemical transformation and metabolic activity of soil microbes. We recommend combined additions of N and P fertilizer to promote soil fertility and microbial activity in this kind of plantation.
    Print ISSN: 1810-6277
    Electronic ISSN: 1810-6285
    Topics: Biology , Geosciences
    Published by Copernicus on behalf of European Geosciences Union.
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  • 5
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    Underestimated effects of low temperature during early growing season on carbon sequestration of a subtropical coniferous plantation (2011)
    Copernicus
    Details
    Publication Date: 2011-06-23
    Description: The impact of air temperature in early growing season on the carbon sequestration of a subtropical coniferous plantation was discussed through analyzing the eddy flux observations at Qianyanzhou (QYZ) site in southern China from 2003 to 2008. This site experienced two cold early growing seasons (with temperature anomalies of 2–5 °C) in 2005 and 2008, and a severe summer drought in 2003. Results indicated that the low air temperature from January to March was the major factor controlling the inter-annual variations in net carbon uptake at this site, rather than the previously thought summer drought. The accumulative air temperature from January to February showed high correlation (R2=0.970, p
    Print ISSN: 1726-4170
    Electronic ISSN: 1726-4189
    Topics: Biology , Geosciences
    Published by Copernicus on behalf of European Geosciences Union.
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  • 6
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    Responses of soil microbial communities and enzyme activities to nitrogen and phosphorus additions in Chinese fir plantations of subtropical China (2015)
    Copernicus
    Details
    Publication Date: 2015-09-29
    Description: Nitrogen (N) and phosphorus (P) additions to forest ecosystems are known to influence various above-ground properties, such as plant productivity and composition, and below-ground properties, such as soil nutrient cycling. However, our understanding of how soil microbial communities and their functions respond to nutrient additions in subtropical plantations is still not complete. In this study, we added N and P to Chinese fir plantations in subtropical China to examine how nutrient additions influenced soil microbial community composition and enzyme activities. The results showed that most soil microbial properties were responsive to N and/or P additions, but responses often varied depending on the nutrient added and the quantity added. For instance, there were more than 30 % greater increases in the activities of β-glucosidase (βG) and N-acetyl-β-D-glucosaminidase (NAG) in the treatments that received nutrient additions compared to the control plot, whereas acid phosphatase (aP) activity was always higher (57 and 71 %, respectively) in the P treatment. N and P additions greatly enhanced the phospholipid fatty acids (PLFAs) abundance especially in the N2P (100 kg ha−1 yr−1 of N +50 kg ha−1 yr−1 of P) treatment; the bacterial PLFAs (bacPLFAs), fungal PLFAs (funPLFAs) and actinomycic PLFAs (actPLFAs) were about 2.5, 3 and 4 times higher, respectively, than in the CK (control). Soil enzyme activities were noticeably higher in November than in July, mainly due to seasonal differences in soil moisture content (SMC). βG or NAG activities were significantly and positively correlated with microbial PLFAs. These findings indicate that βG and NAG would be useful tools for assessing the biogeochemical transformation and metabolic activity of soil microbes. We recommend combined additions of N and P fertilizer to promote soil fertility and microbial activity in this kind of plantation.
    Print ISSN: 1726-4170
    Electronic ISSN: 1726-4189
    Topics: Biology , Geosciences
    Published by Copernicus on behalf of European Geosciences Union.
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  • 7
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    Ecosystem carbon exchange of a subtropical evergreen coniferous plantation subjected to seasonal drought, 2003–2007 (2009)
    Copernicus
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    Publication Date: 2009-09-02
    Description: The behavior of whole ecosystems in humid climate zone in response to drought is less well documented. Continuous measurements of carbon dioxide and water vapor exchange using the eddy covariance technique during 2003–2007 were made above a subtropical evergreen coniferous plantation in Southeast China. Seasonal distribution of precipitation and temperature was out of step during the summer, which resulted in droughts frequently. Gross ecosystem photosynthesis (GEP), ecosystem respiration (RE) and net ecosystem production (NEP) showed clear seasonality, with low rates during seasonal drought and in winter. The exponential response of monthly GEP and RE to air temperature provided us an implication that monthly NEP was less sensitive and only increased linearly. However, the function response of monthly NEP and its components (GEP and RE) disappeared under high temperature and low moisture. Monthly and year RE showed a linear and positive dependence on the corresponding GEP, with statistically significant. Annual NEP varied among years from 306 to 430 g C m−2 (mean 395, SD 50). Interannual variability in NEP was controlled primarily by air temperature and the ratio of precipitation and evapotranspiration that affected the RE/GEP ratio, which varied between 0.76 and 0.81 (mean 0.78, SD 0.02).
    Print ISSN: 1810-6277
    Electronic ISSN: 1810-6285
    Topics: Biology , Geosciences
    Published by Copernicus on behalf of European Geosciences Union.
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  • 8
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    Impact of cloudiness on net ecosystem exchange of carbon dioxide in different types of forest ecosystems in China (2009)
    Copernicus
    Details
    Publication Date: 2009-08-14
    Description: Clouds can significantly affect carbon uptake of forest ecosystems by affecting incoming solar radiation on the ground, temperature and other environmental factors. In this study, we analyzed the effects of cloudiness on the net ecosystem exchange of carbon dioxide (NEE) of a temperate broad-leaved Korean pine mixed forest at Changbaishan (CBS) and a subtropical evergreen broad-leaved forest at Dinghushan (DHS) of ChinaFLUX, based on the flux data obtained during June–August from 2003 to 2006. The results showed that the response of the NEE of forest ecosystem to photosynthetically active radiation (PAR) was different under clear sky and cloudy sky conditions, and this difference was not consistent between CBS and DHS. Compared with clear skies, light-saturated maximum photosynthetic rate (Pec,max) of CBS during mid-growing season (from June to August) was respectively enhanced by 34%, 25%, 4% and 11% on cloudy skies in 2003, 2004, 2005 and 2006; however, Pec,max of DHS was higher under clear skies than under cloudy skies from 2004 to 2006. NEE of forests at CBS reached its maximum when the clearness index (kt) was between 0.4 and 0.6, and the NEE decreased obviously when kt exceeded 0.6. Compare with CBS, although NEE of forest at DHS tended to the maximum when kt varied between 0.4 and 0.6, the NEE did not decrease noticeably when kt exceeded 0.6. The results indicated that cloudy sky conditions were more beneficial to carbon uptake for the temperate forest ecosystem rather than for the subtropical forest ecosystem. This is due to the fact that the non-saturating light conditions and increase of diffuse radiation were more beneficial to photosynthesis, and the reduced temperature was more conducive to decreasing the ecosystem respiration in temperate forest ecosystems under cloudy sky conditions. This phenomenon is important to evaluate carbon uptake of temperate forests under climate change conditions.
    Print ISSN: 1810-6277
    Electronic ISSN: 1810-6285
    Topics: Biology , Geosciences
    Published by Copernicus on behalf of European Geosciences Union.
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  • 9
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    Impact of cloudiness on net ecosystem exchange of carbon dioxide in different types of forest ecosystems in China (2010)
    Copernicus
    Details
    Publication Date: 2010-02-23
    Description: Clouds can significantly affect carbon exchange process between forest ecosystems and the atmosphere by influencing the quantity and quality of solar radiation received by ecosystem's surface and other environmental factors. In this study, we analyzed the effects of cloudiness on net ecosystem exchange of carbon dioxide (NEE) in a temperate broad-leaved Korean pine mixed forest at Changbaishan (CBS) and a subtropical evergreen broad-leaved forest at Dinghushan (DHS), based on the flux data obtained during June–August from 2003 to 2006. The results showed that the response of NEE of forest ecosystems to photosynthetically active radiation (PAR) differed under clear skies and cloudy skies. Compared with clear skies, the light-saturated maximum photosynthetic rate (Pec,max) at CBS under cloudy skies during mid-growing season (from June to August) increased by 34%, 25%, 4% and 11% in 2003, 2004, 2005 and 2006, respectively. In contrast, Pec,max of the forest ecosystem at DHS was higher under clear skies than under cloudy skies from 2004 to 2006. When the clearness index (kt) ranged between 0.4 and 0.6, the NEE reached its maximum at both CBS and DHS. However, the NEE decreased more dramatically at CBS than at DHS when kt exceeded 0.6. The results indicate that cloudy sky conditions are beneficial to net carbon uptake in the temperate forest ecosystem and the subtropical forest ecosystem. Under clear skies, vapor pressure deficit (VPD) and air temperature increased due to strong light. These environmental conditions led to greater decrease in gross ecosystem photosynthesis (GEP) and greater increase in ecosystem respiration (Re) at CBS than at DHS. As a result, clear sky conditions caused more reduction of NEE in the temperate forest ecosystem than in the subtropical forest ecosystem. The response of NEE of different forest ecosystems to the changes in cloudiness is an important factor that should be included in evaluating regional carbon budgets under climate change conditions.
    Print ISSN: 1726-4170
    Electronic ISSN: 1726-4189
    Topics: Biology , Geosciences
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  • 10
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    Evaluating calibration strategies for isotope ratio infrared spectroscopy for atmospheric 13CO2 / 12CO2 measurement (2013)
    Copernicus
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    Publication Date: 2013-06-05
    Description: Isotope ratio infrared spectroscopy (IRIS) provides an in situ technique for measuring δ13C in atmospheric CO2. A number of methods have been proposed for calibrating the IRIS measurements, but few studies have systematically evaluated their accuracy for atmospheric applications. In this study, we carried out laboratory and ambient measurements with two commercial IRIS analyzers and compared the accuracy of four calibration strategies. We found that calibration based on the 12C and 13C mixing ratios (Bowling et al., 2003) and on linear interpolation of the measured delta using the mixing ratio of the major isotopologue (Lee et al., 2005) yielded accuracy better than 0.06‰. Over a 7-day atmospheric measurement in Beijing, the two analyzers agreed to within −0.02 ± 0.18‰ after proper calibration. However, even after calibration the difference between the two analyzers showed a slight correlation with concentration, and this concentration dependence propagated through the Keeling analysis, resulting in a much larger difference of 2.44‰ for the Keeling intercept. The high sensitivity of the Keeling analysis to the concentration dependence underscores the challenge of IRIS for atmospheric research.
    Print ISSN: 1867-1381
    Electronic ISSN: 1867-8548
    Topics: Geosciences
    Published by Copernicus on behalf of European Geosciences Union.
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