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  • 1
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    TRAF3 enforces thymic cross-talk and development [Immunology] (2013)
    National Academy of Sciences
    Details
    Publication Date: 2013-12-25
    Description: Induction of self-tolerance in developing T cells depends on medullary thymic epithelial cells (mTECs), whose development, in turn, requires signals from single-positive (SP) thymocytes. Thus, the absence of SP thymocytes in Tcra−/− mice results in a profound deficiency in mTECs. Here, we have probed the mechanism that underlies this requirement...
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 2
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    DNA-damage-induced differentiation of leukaemic cells as an anti-cancer barrier (2014)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2014-08-01
    Description: Self-renewal is the hallmark feature both of normal stem cells and cancer stem cells. Since the regenerative capacity of normal haematopoietic stem cells is limited by the accumulation of reactive oxygen species and DNA double-strand breaks, we speculated that DNA damage might also constrain leukaemic self-renewal and malignant haematopoiesis. Here we show that the histone methyl-transferase MLL4, a suppressor of B-cell lymphoma, is required for stem-cell activity and an aggressive form of acute myeloid leukaemia harbouring the MLL-AF9 oncogene. Deletion of MLL4 enhances myelopoiesis and myeloid differentiation of leukaemic blasts, which protects mice from death related to acute myeloid leukaemia. MLL4 exerts its function by regulating transcriptional programs associated with the antioxidant response. Addition of reactive oxygen species scavengers or ectopic expression of FOXO3 protects MLL4(-/-) MLL-AF9 cells from DNA damage and inhibits myeloid maturation. Similar to MLL4 deficiency, loss of ATM or BRCA1 sensitizes transformed cells to differentiation, suggesting that myeloid differentiation is promoted by loss of genome integrity. Indeed, we show that restriction-enzyme-induced double-strand breaks are sufficient to induce differentiation of MLL-AF9 blasts, which requires cyclin-dependent kinase inhibitor p21(Cip1) (Cdkn1a) activity. In summary, we have uncovered an unexpected tumour-promoting role of genome guardians in enforcing the oncogene-induced differentiation blockade in acute myeloid leukaemia.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4410707/" 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/PMC4410707/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Santos, Margarida A -- Faryabi, Robert B -- Ergen, Aysegul V -- Day, Amanda M -- Malhowski, Amy -- Canela, Andres -- Onozawa, Masahiro -- Lee, Ji-Eun -- Callen, Elsa -- Gutierrez-Martinez, Paula -- Chen, Hua-Tang -- Wong, Nancy -- Finkel, Nadia -- Deshpande, Aniruddha -- Sharrow, Susan -- Rossi, Derrick J -- Ito, Keisuke -- Ge, Kai -- Aplan, Peter D -- Armstrong, Scott A -- Nussenzweig, Andre -- CA140575/CA/NCI NIH HHS/ -- CA66996/CA/NCI NIH HHS/ -- P30 CA008748/CA/NCI NIH HHS/ -- R00 CA139009/CA/NCI NIH HHS/ -- R01 DK098263/DK/NIDDK NIH HHS/ -- R01 DK100689/DK/NIDDK NIH HHS/ -- Intramural NIH HHS/ -- England -- Nature. 2014 Oct 2;514(7520):107-11. doi: 10.1038/nature13483. Epub 2014 Jul 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Genome Integrity, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. ; 1] Laboratory of Genome Integrity, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA [2]. ; The Genetics Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. ; Laboratory of Endocrinology and Receptor Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. ; 1] Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, Massachusetts 02115, USA [2] Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts 02138, USA. ; Human Oncology and Pathogenesis Program and Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA. ; Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. ; Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Departments of Cell Biology and Medicine, Albert Einstein Cancer Center, Albert Einstein College of Medicine, Bronx, New York 10461, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25079327" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Ataxia Telangiectasia Mutated Proteins/metabolism ; BRCA1 Protein/genetics/metabolism ; Cell Transformation, Neoplastic ; Cyclin-Dependent Kinase Inhibitor p21/metabolism ; DNA Breaks, Double-Stranded ; *DNA Damage ; DNA Repair ; Female ; Gene Expression Regulation, Neoplastic ; Genes, BRCA1 ; Hematopoietic Stem Cells/cytology/metabolism/pathology ; Histone-Lysine N-Methyltransferase/deficiency/genetics/metabolism ; Leukemia, Myeloid, Acute/*enzymology/*pathology ; Male ; Mice ; *Myelopoiesis ; Oncogene Proteins, Fusion/genetics/metabolism ; Reactive Oxygen Species/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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  • 3
    Electronic Resource
    Electronic Resource
    Effect of winter grazing date on yield components of Lolium perenne (L.)/Trifolium repens (L.) hill pasture (1991)
    Oxford, UK : Blackwell Publishing Ltd
    Grass and forage science 46 (1991), S. 0 
    Details
    ISSN: 1365-2494
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Perennial ryegrass/white clover pastures were grazed at different times in the winter to study the effect of time of grazing on subsequent plant growth. In 1983–84, 1984–85, and 1985–86, pastures were grazed to a residual of 400 kg dry matter ha-1 by sheep once in early December (D), January (J), February (F), March (M), or April (A) and compared with an ungrazed control (C). Rates of herbage accumulation on C in the winter were low, averaging 6, -9, and 2 kg dry matter ha-1 in December, January, and February, respectively. Little forage production occurred during the month immediately following winter grazing. Herbage accumulation rate then increased sufficiently to replace the forage removed from winter-grazed paddocks by early spring. By May, herbage mass on grazed treatments was similar to C except for D and A which averaged 20 and 47% less forage than C, respectively (P〈0·01). Herbage accumulation rates of D were unique among winter grazing treatments in never exceeding those of C. By May 1986, D yielded less perennial ryegrass compared with C (P〈0·05). Grazing reduced the number of leaves per ryegrass tiller for 1 to 2 months following grazing. By May, J, F and M had numerically more tillers m-2 and more leaves per tiller than C. Similar May yields of J, F, M, and C resulted from fewer but larger and slightly less leafy tillers of ungrazed compared with winter grazed plants.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2494.1991.tb02394.x
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  • 4
    Electronic Resource
    Electronic Resource
    Set stocking, rotational grazing and forward rotational grazing by sheep on western Oregon hill pastures (1984)
    Oxford, UK : Blackwell Publishing Ltd
    Grass and forage science 39 (1984), S. 0 
    Details
    ISSN: 1365-2494
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Data on sheep live weights, herbage standing crop and herbage quality are presented from a 3-year grazing management study comparing set stocking, four-paddock rotational grazing and four-paddock forward rotational grazing systems. In both rotational grazing and forward rotational grazing systems, sheep were sequentially moved from one paddock to the next every 5 days. Lambs were weaned at 12–15 weeks of age in the forward rotationally grazed system and from then on grazed one paddock ahead of the ewes. Herbage mass was consistently greater on the rotationally grazed system than on the set-stocked system, averaging 38.4% more herbage in 1978. 32.8% more in 1979 and 52.7% more in 1980. No differences were observed in ewe live weights at the end of the grazing year between the rotationally grazed and the set stocked systems. Live weights of rotationally grazed lambs were superior to set-stocked lambs only when herbage allowance was low; otherwise no difference existed between these two systems. The forward rotationally grazed lambs generally had lower liveweights than did the rotationally grazed lambs, perhaps due to weaning stress.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2494.1984.tb01704.x
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  • 5
    Electronic Resource
    Electronic Resource
    THE DISTRIBUTION OF SURFACE IgD ON B-LYMPHOCYTES OF MICE: TWO PARAMETERON CORRELATION WITH SURFACE IgM AND Ia (1982)
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 399 (1982), S. 0 
    Details
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1749-6632.1982.tb25674.x
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  • 6
    Electronic Resource
    Electronic Resource
    An Lyt differentiated thymocyte subpopulation detected by flow microfluorometry (1979)
    [s.l.] : Nature Publishing Group
    Nature 277 (1979), S. 478-480 
    Details
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] Fig. 1 Normal or cortisone-resistant thymocytes from 3-5-month C57BL/6 (B6) or appropriate B6/Ly congeneic mice were treated with anti-Lyt antisera and fluorescent goat anti-mouse immunoglobulin (Fl-GAMlg). CRT were obtained 36-40 h after intraperitoneal administration of 0.25 nig cortisone acetate ...
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1038/277478a0
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  • 7
    Electronic Resource
    Electronic Resource
    Tree planting pattern effects on forage production in a Douglas-fir agroforest (1991)
    Springer
    Agroforestry systems 16 (1991), S. 167-175 
    Details
    ISSN: 1572-9680
    Keywords: agrosilvopastoral ; sheep ; conifer ; clover ; competition
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract Resource sharing among agroforestry system components, as expressed by spatial patterns along interfaces between components, is a crucial factor in both understanding present systems and in designing new agroforestry applications. A study of the spatial pattern of forage production surrounding 9–10 year old Douglas-fir trees in a agrosilvopastoral plantation near Corvallis, Oregon, was conducted during 1988 and 1989. Transects of plots were clipped both between trees (tree/tree) and between trees and open pastures (tree/pasture). Best-fit regression models relating forage production to distance from trees (tree/tree R 2 = 0.87; and tree/pasture R 2 = 0.89) were combined into a single prediction model. Observed forage production increased rapidly with increasing distance from trees during the initial 4 m. Trees had little effect on forage production beyond 4.5 m (approximately 2 canopy diameters) from the nearest tree. Predictions of different combinations of tree density and planting pattern indicated a strong interaction between density and pattern with highly aggregated plantations better able to maintain forage production at high tree densities.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00129747
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  • 8
    Electronic Resource
    Electronic Resource
    Productivity of two Douglas fir/subclover/sheep agroforests compared to pasture and forest monocultures (1996)
    Springer
    Agroforestry systems 34 (1996), S. 305-313 
    Details
    ISSN: 1572-9680
    Keywords: spatial pattern ; silvopastoral ; intercropping ; polyculture ; Pseudotsuga menziesii ; Trifolium subterraneum
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract Resource sharing between tree and forage plant components in silvopastoral systems includes a complex set of facilitative and competitive interactions. To the extent that facilitation exceeds competition, agroforests are expected to outyield monocultures of their components. Pasture and Douglas fir (Pseudotsuga menziesii) tree production of young agroforests was compared to pasture and forest monocultures under both grid and cluster patterns of tree planting near Corvallis, Oregon, USA, during 1983–1987. The height and diameter growth of forest and agroforest trees was similar, regardless of tree planting pattern. Five-year average annual forage production was 6500, 5800, and 2800 kg ha−1 on pasture, agroforest, and forest plots, respectively. The total cumulative 1982–1987 above-ground phytomass yield of forage plus trees was similar for pasture and conventional grid forest monocultures. The total productivity of agroforests, however, was over 30% greater than either pasture or forest components grown in monoculture. Approximately 1.6 ha (0.96 ha forest + 0.64 ha pasture) of monocultures would be needed to equal the productivity of 1 ha of agroforest.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00046930
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  • 9
    Electronic Resource
    Electronic Resource
    Growth and yield of sorghum or cowpea in an agrisilviculture system in semiarid India (1998)
    Springer
    Agroforestry systems 42 (1998), S. 91-105 
    Details
    ISSN: 1572-9680
    Keywords: competition ; fertilization ; Leucaena leucocephala ; pruning ; Sorghum bicolor ; tree crop interactions ; Vigna unguiculata
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract This study was conducted near Hyderabad, India during 1991–1994 to quantify the effects of shoot pruning, fertilization, and root barriers around Leucaena leucocephala trees on intercropped sorghum(Sorghum bicolor) or cowpea (Vigna unguiculata) crop production under rainfed conditions. Crop plants grown with pruned trees attained higher dry matter and leaf area index than did those with unpruned trees. Two-year mean grain yields of sorghum with no root barriers were76% and 39% of pure crop yield (1553 kg ha–1)for pruned and unpruned trees, respectively. Corresponding values for cowpea were 49% and 26% of pure crop yield (1075 kgha–1). Sorghum or cowpea intercropped with trees responded to fertilizer application more strongly than did their respective pure crops, suggesting an increased need for fertilizer application in this agrisilviculture system over that currently used for pure crops. Impact of root barriers was small on either crop. Irrespective of root barriers, a high response to tree pruning suggested above ground competition for light dominated tree/crop interactions in this agrisilviculture system.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006147926915
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  • 10
    Electronic Resource
    Electronic Resource
    Direct impacts of sheep upon Douglas-fir trees in two agrosilvopastoral systems (1992)
    Springer
    Agroforestry systems 19 (1992), S. 223-232 
    Details
    ISSN: 1572-9680
    Keywords: agroforestry ; browsing ; debarking ; sheep ; deer ; Pseudotsuga menziesii
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract Livestock may provide important service and production functions in agroforestry systems. However, use of livestock in conifer/improved pasture agrosilvopastoral systems is currently limited by concerns about potential damage to trees by livestock. Effects of sheep grazing on Douglas-fir (Pseudotsuga menziesii) trees in two patterns of sheep/pasture/conifer agroforest (cluster and grid plantations) were studied from 4 years after planting (1983) until the first precommercial thinning at age 10 years (1988). Trees averaged over 1 m in height when grazing began in summer 1983. Some browsing of tree lateral branches by sheep occurred regardless of grazing season in 1983–1985. However, the 2 to 10% of current year's lateral branch growth removed by grazing sheep was too low to impact tree growth. Sheep removed the terminal leaders from only 3 to 9% of trees each year during 1983–1985. Most browsing of terminals occurred in the summer when other forages had become mature and were relatively unpalatable to sheep. Less than 13% of agroforest trees were debarked by sheep each year during 1983–1987. By the end of grazing in 1987, less than 8% of agroforest trees had sustained a level of debarking likely to impact future growth (〉50% of tree circumference debarked). Grazing had no discernible effect upon tree diameter or height in any year (P 〉 0.05). Total tree mortality attributable to sheep grazing during 1983–1987 was only 0.9%, including three trees girdled by sheep and two debarked trees which were subsequently attacked by insects. Overall, grazing had no detrimental impact on timber stand growth or mortality.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00118780
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