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  • 1
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    From noncoding variant to phenotype via SORT1 at the 1p13 cholesterol locus (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-08-06
    Description: Recent genome-wide association studies (GWASs) have identified a locus on chromosome 1p13 strongly associated with both plasma low-density lipoprotein cholesterol (LDL-C) and myocardial infarction (MI) in humans. Here we show through a series of studies in human cohorts and human-derived hepatocytes that a common noncoding polymorphism at the 1p13 locus, rs12740374, creates a C/EBP (CCAAT/enhancer binding protein) transcription factor binding site and alters the hepatic expression of the SORT1 gene. With small interfering RNA (siRNA) knockdown and viral overexpression in mouse liver, we demonstrate that Sort1 alters plasma LDL-C and very low-density lipoprotein (VLDL) particle levels by modulating hepatic VLDL secretion. Thus, we provide functional evidence for a novel regulatory pathway for lipoprotein metabolism and suggest that modulation of this pathway may alter risk for MI in humans. We also demonstrate that common noncoding DNA variants identified by GWASs can directly contribute to clinical phenotypes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3062476/" 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/PMC3062476/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Musunuru, Kiran -- Strong, Alanna -- Frank-Kamenetsky, Maria -- Lee, Noemi E -- Ahfeldt, Tim -- Sachs, Katherine V -- Li, Xiaoyu -- Li, Hui -- Kuperwasser, Nicolas -- Ruda, Vera M -- Pirruccello, James P -- Muchmore, Brian -- Prokunina-Olsson, Ludmila -- Hall, Jennifer L -- Schadt, Eric E -- Morales, Carlos R -- Lund-Katz, Sissel -- Phillips, Michael C -- Wong, Jamie -- Cantley, William -- Racie, Timothy -- Ejebe, Kenechi G -- Orho-Melander, Marju -- Melander, Olle -- Koteliansky, Victor -- Fitzgerald, Kevin -- Krauss, Ronald M -- Cowan, Chad A -- Kathiresan, Sekar -- Rader, Daniel J -- K99 HL098364/HL/NHLBI NIH HHS/ -- K99 HL098364-01/HL/NHLBI NIH HHS/ -- K99 HL098364-02/HL/NHLBI NIH HHS/ -- K99-HL098364/HL/NHLBI NIH HHS/ -- P01 HL059407/HL/NHLBI NIH HHS/ -- P01 HL059407-13/HL/NHLBI NIH HHS/ -- P01-HL059407/HL/NHLBI NIH HHS/ -- RC2 HL101864/HL/NHLBI NIH HHS/ -- RC2 HL101864-02/HL/NHLBI NIH HHS/ -- RC2-HL101864/HL/NHLBI NIH HHS/ -- T32 HL007954/HL/NHLBI NIH HHS/ -- T32 HL007954-10/HL/NHLBI NIH HHS/ -- U01 HL069757/HL/NHLBI NIH HHS/ -- U01 HL069757-09/HL/NHLBI NIH HHS/ -- U01-HL069757/HL/NHLBI NIH HHS/ -- Intramural NIH HHS/ -- England -- Nature. 2010 Aug 5;466(7307):714-9. doi: 10.1038/nature09266.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cardiovascular Research Center and Center for Human Genetic Research, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20686566" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Vesicular ; Transport/biosynthesis/deficiency/genetics/*metabolism ; Animals ; Base Sequence ; Binding Sites ; CCAAT-Enhancer-Binding Proteins/metabolism ; Cells, Cultured ; Cholesterol, LDL/blood/*metabolism ; Chromosomes, Human, Pair 1/*genetics ; Cohort Studies ; Coronary Artery Disease/blood/genetics ; Europe/ethnology ; Gene Expression Regulation ; Gene Knockdown Techniques ; Genetic Predisposition to Disease/*genetics ; Genome-Wide Association Study ; Haplotypes/genetics ; Hepatocytes/metabolism/secretion ; Humans ; Lipids/blood ; Lipoproteins, VLDL/blood/secretion ; Liver/cytology/metabolism/secretion ; Mice ; Myocardial Infarction/blood/genetics ; Phenotype ; Polymorphism, Single Nucleotide/*genetics ; Transcription, Genetic
    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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    Nuclear reprogramming of somatic cells after fusion with human embryonic stem cells (2005)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2005-08-27
    Description: We have explored the use of embryonic stem cells as an alternative to oocytes for reprogramming human somatic nuclei. Human embryonic stem (hES) cells were fused with human fibroblasts, resulting in hybrid cells that maintain a stable tetraploid DNA content and have morphology, growth rate, and antigen expression patterns characteristic of hES cells. Differentiation of hybrid cells in vitro and in vivo yielded cell types from each embryonic germ layer. Analysis of genome-wide transcriptional activity, reporter gene activation, allele-specific gene expression, and DNA methylation showed that the somatic genome was reprogrammed to an embryonic state. These results establish that hES cells can reprogram the transcriptional state of somatic nuclei and provide a system for investigating the underlying mechanisms.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cowan, Chad A -- Atienza, Jocelyn -- Melton, Douglas A -- Eggan, Kevin -- New York, N.Y. -- Science. 2005 Aug 26;309(5739):1369-73.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Harvard Stem Cell Institute, Department of Molecular and Cellular Biology, Harvard University, 7 Divinity Avenue, Cambridge, MA 02138, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16123299" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Animals ; Biomarkers/analysis ; Cell Cycle ; Cell Differentiation ; *Cell Fusion ; Cell Line ; Cell Nucleus/*physiology ; Cell Shape ; Cell Transplantation ; Chromosomes, Human/genetics ; Embryo, Mammalian/*cytology ; Epigenesis, Genetic ; Female ; Fibroblasts/cytology/*physiology ; Gene Expression Profiling ; Gene Expression Regulation, Developmental ; Humans ; Hybrid Cells/cytology/*physiology ; Male ; Mice ; Mice, Nude ; Phenotype ; Pluripotent Stem Cells/cytology/*physiology ; Polyploidy ; Teratoma/pathology ; Transcription, Genetic ; Transcriptional Activation ; Transfection
    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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  • 3
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    Identification of adult nephron progenitors capable of kidney regeneration in zebrafish (2011)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2011-01-29
    Description: Loss of kidney function underlies many renal diseases. Mammals can partly repair their nephrons (the functional units of the kidney), but cannot form new ones. By contrast, fish add nephrons throughout their lifespan and regenerate nephrons de novo after injury, providing a model for understanding how mammalian renal regeneration may be therapeutically activated. Here we trace the source of new nephrons in the adult zebrafish to small cellular aggregates containing nephron progenitors. Transplantation of single aggregates comprising 10-30 cells is sufficient to engraft adults and generate multiple nephrons. Serial transplantation experiments to test self-renewal revealed that nephron progenitors are long-lived and possess significant replicative potential, consistent with stem-cell activity. Transplantation of mixed nephron progenitors tagged with either green or red fluorescent proteins yielded some mosaic nephrons, indicating that multiple nephron progenitors contribute to a single nephron. Consistent with this, live imaging of nephron formation in transparent larvae showed that nephrogenic aggregates form by the coalescence of multiple cells and then differentiate into nephrons. Taken together, these data demonstrate that the zebrafish kidney probably contains self-renewing nephron stem/progenitor cells. The identification of these cells paves the way to isolating or engineering the equivalent cells in mammals and developing novel renal regenerative therapies.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3170921/" 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/PMC3170921/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Diep, Cuong Q -- Ma, Dongdong -- Deo, Rahul C -- Holm, Teresa M -- Naylor, Richard W -- Arora, Natasha -- Wingert, Rebecca A -- Bollig, Frank -- Djordjevic, Gordana -- Lichman, Benjamin -- Zhu, Hao -- Ikenaga, Takanori -- Ono, Fumihito -- Englert, Christoph -- Cowan, Chad A -- Hukriede, Neil A -- Handin, Robert I -- Davidson, Alan J -- K08 HL098361/HL/NHLBI NIH HHS/ -- K08 HL098361-01A1/HL/NHLBI NIH HHS/ -- K08 HL098361-02/HL/NHLBI NIH HHS/ -- P50DK074030/DK/NIDDK NIH HHS/ -- R01 DK069403/DK/NIDDK NIH HHS/ -- England -- Nature. 2011 Feb 3;470(7332):95-100. doi: 10.1038/nature09669. Epub 2011 Jan 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Regenerative Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21270795" target="_blank"〉PubMed〈/a〉
    Keywords: Aging/physiology ; Animals ; Animals, Genetically Modified ; Cell Proliferation ; Kidney/*cytology/*growth & development/injuries/metabolism ; Larva ; Models, Animal ; Nephrons/*cytology/growth & development ; Organogenesis ; Regeneration/*physiology ; Stem Cell Transplantation ; Stem Cells/*cytology ; Zebrafish/*growth & development
    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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  • 4
    Electronic Resource
    Electronic Resource
    Spatial and seasonal associations of benthic macroinvertebrates and detritus in an Alaskan subarctic stream (1984)
    Springer
    Polar biology 3 (1984), S. 211-215 
    Details
    ISSN: 1432-2056
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Seasonal and spatial patterns of benthic invertebrate abundance were examined in relation to benthic detritus in Monument Creek, an Alaskan subarctic stream. The total macroinvertebrate fauna showed a mid-summer low in abundance, increasing to seasonal highs in winter/early spring (November/May). Shredders were a small portion of the benthic fauna or leaf pack fauna in summer but increased rapidly (in biovolume) following autumnal leaf fall to dominate the fauna by early winter (October/November). Abundance was strongly correlated with quantity of detritus in the sample. Comparison of benthic macroinvertebrate densities from Alaskan streams with comparable data from temperate zone streams shows that Alaskan streams are similar to temperate zone streams in range of abundance. Each unit of benthic detritus in Monument Creek is associated with a relatively large number of small (low individual biomass) shredders compared to streams in temperate regions. Detrital resources in this subarctic stream were meager, compared to temperate streams, and appeared to strongly influence the spatial and temporal patterns of detritivores.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00292625
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  • 5
    Electronic Resource
    Electronic Resource
    Input and storage of benthic detritus in an Alaskan subarctic stream (1983)
    Springer
    Polar biology 2 (1983), S. 35-40 
    Details
    ISSN: 1432-2056
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Allochthonous leaf litter input and storage of benthic detritus were measured in Monument Creek, a second-order interior Alaskan stream. Litter input was very low, totaling 62.5 g ash-free dry weight (AFDW). m-2·y-2 in 1980. Peak input coincided with autumnal leaf fall. Benthic detritus storage was similarly low. CPOM (coarse particulate organic matter, 〉 1 mm) ranged from 2.8 to 28.9 g AFDW·m-2, peaking in mid-September. MPOM (medium particulate organic matter, 250 μm-1 mm) ranged from 3.7 to 10.9 g AFDW·m-2, peaking in May. SPOM (small particulate organic matter, 80–250 μm) ranged from 2.0 to 9.0 g AFDW·m-2 and also peaked in May. Compared to streams in temperate regions, Monument Creek is receiving and storing less energy from the surrounding forest.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00258283
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  • 6
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    Distant trophoblast enhancer for HLA-G expression [Immunology and Inflammation] (2016)
    National Academy of Sciences
    Details
    Publication Date: 2016-05-12
    Description: HLA-G, a nonclassical HLA molecule uniquely expressed in the placenta, is a central component of fetus-induced immune tolerance during pregnancy. The tissue-specific expression of HLA-G, however, remains poorly understood. Here, systematic interrogation of the HLA-G locus using massively parallel reporter assay (MPRA) uncovered a previously unidentified cis-regulatory element 12 kb...
    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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  • 7
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    STUDIES OF CHLOROPLAST DEVELOPMENT IN EUGLENA, VIII. CHLOROPLAST-ASSOCIATED DNA (1964)
    National Academy of Sciences
    Details
    Publication Date: 1964-11-01
    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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  • 8
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    Input and storage of benthic detritus in an Alaskan subarctic stream (1983)
    Springer
    Details
    Publication Date: 1983-06-01
    Print ISSN: 0722-4060
    Electronic ISSN: 1432-2056
    Topics: Biology
    Published by Springer
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  • 9
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    Spatial and seasonal associations of benthic macroinvertebrates and detritus in an Alaskan subarctic stream (1984)
    Springer
    Details
    Publication Date: 1984-11-01
    Print ISSN: 0722-4060
    Electronic ISSN: 1432-2056
    Topics: Biology
    Published by Springer
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  • 10
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    Autogenic dynamics in carbonate sedimentation; meter-scale, shallowing-upward cycles, Upper Cambrian, western Newfoundland, Canada (1996)
    American Journal of Science
    Details
    Publication Date: 1996-12-01
    Print ISSN: 0002-9599
    Electronic ISSN: 1945-452X
    Topics: Geosciences
    Published by American Journal of Science
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