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  • 1
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    Mice lacking a Myc enhancer that includes human SNP rs6983267 are resistant to intestinal tumors (2012)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2012-11-03
    Description: Multiple cancer-associated single-nucleotide polymorphisms (SNPs) have been mapped to conserved sequences within a 500-kilobase region upstream of the MYC oncogene on human chromosome 8q24. These SNPs may affect cancer development through altered regulation of MYC expression, but this hypothesis has been difficult to confirm. We generated mice deficient in Myc-335, a putative MYC regulatory element that contains rs6983267, a SNP accounting for more human cancer-related morbidity than any other genetic variant or mutation. In Myc-335 null mice, Myc transcripts were expressed in the intestinal crypts in a pattern similar to that in wild-type mice but at modestly reduced levels. The mutant mice displayed no overt phenotype but were markedly resistant to intestinal tumorigenesis induced by the APCmin mutation. These results establish that a cancer-associated SNP identified in human genome-wide association studies has a functional effect in vivo.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sur, Inderpreet Kaur -- Hallikas, Outi -- Vaharautio, Anna -- Yan, Jian -- Turunen, Mikko -- Enge, Martin -- Taipale, Minna -- Karhu, Auli -- Aaltonen, Lauri A -- Taipale, Jussi -- New York, N.Y. -- Science. 2012 Dec 7;338(6112):1360-3. doi: 10.1126/science.1228606. Epub 2012 Nov 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Science for Life Center, Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23118011" target="_blank"〉PubMed〈/a〉
    Keywords: Adenomatous Polyposis Coli/genetics/pathology ; Animals ; Cell Transformation, Neoplastic/*genetics ; Colon/metabolism/pathology ; Enhancer Elements, Genetic/*genetics ; Humans ; Ileum/metabolism/pathology ; Intestinal Neoplasms/*genetics/pathology ; Mice ; Mice, Mutant Strains ; Polymorphism, Single Nucleotide ; Proto-Oncogene Proteins c-myc/*genetics
    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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    El-Boustani et al. reply (2014)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2014-04-04
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉El-Boustani, Sami -- Wilson, Nathan R -- Runyan, Caroline A -- Sur, Mriganka -- England -- Nature. 2014 Apr 3;508(7494):E3-4. doi: 10.1038/nature13130.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Brain and Cognitive Sciences, Picower Institute for Learning and Memory, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24695315" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Neural Inhibition/*physiology ; Neural Pathways/*physiology ; Neurons/*physiology ; Visual Cortex/*cytology/*physiology
    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
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    Division and subtraction by distinct cortical inhibitory networks in vivo (2012)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2012-08-11
    Description: Brain circuits process information through specialized neuronal subclasses interacting within a network. Revealing their interplay requires activating specific cells while monitoring others in a functioning circuit. Here we use a new platform for two-way light-based circuit interrogation in visual cortex in vivo to show the computational implications of modulating different subclasses of inhibitory neurons during sensory processing. We find that soma-targeting, parvalbumin-expressing (PV) neurons principally divide responses but preserve stimulus selectivity, whereas dendrite-targeting, somatostatin-expressing (SOM) neurons principally subtract from excitatory responses and sharpen selectivity. Visualized in vivo cell-attached recordings show that division by PV neurons alters response gain, whereas subtraction by SOM neurons shifts response levels. Finally, stimulating identified neurons while scanning many target cells reveals that single PV and SOM neurons functionally impact only specific subsets of neurons in their projection fields. These findings provide direct evidence that inhibitory neuronal subclasses have distinct and complementary roles in cortical computations.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3653570/" 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/PMC3653570/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wilson, Nathan R -- Runyan, Caroline A -- Wang, Forea L -- Sur, Mriganka -- R01 EY007023/EY/NEI NIH HHS/ -- R01 EY018648/EY/NEI NIH HHS/ -- England -- Nature. 2012 Aug 16;488(7411):343-8. doi: 10.1038/nature11347.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Brain and Cognitive Sciences, Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22878717" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Dendrites/metabolism ; Electrophysiology ; Interneurons/physiology ; Mice ; Models, Neurological ; Neural Inhibition/*physiology ; Neural Pathways/*physiology ; Neurons/*physiology ; Parvalbumins/metabolism ; Somatostatin/metabolism ; Visual Cortex/*cytology/*physiology
    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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