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Institution

Harvard University

EducationCambridge, Massachusetts, United States
About: Harvard University is a(n) education organization based out in Cambridge, Massachusetts, United States. It is known for research contribution in the topic(s): Population & Cancer. The organization has 208150 authors who have published 530388 publication(s) receiving 38152182 citation(s). The organization is also known as: Harvard & University of Harvard.
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Journal ArticleDOI
01 Jan 2012-Nature Genetics
TL;DR: The combined analysis identified eight new T2D loci reaching genome-wide significance, which mapped in or near GLIS3, PEPD, FITM2-R3HDML-HNF4A, KCNK16, MAEA, GCC1-PAX4, PSMD6 and ZFAND3, which may regulate glucose-dependent insulin secretion in the pancreas.
Abstract: We conducted a three-stage genetic study to identify susceptibility loci for type 2 diabetes (T2D) in east Asian populations. We followed our stage 1 meta-analysis of eight T2D genome-wide association studies (6,952 cases with T2D and 11,865 controls) with a stage 2 in silico replication analysis (5,843 cases and 4,574 controls) and a stage 3 de novo replication analysis (12,284 cases and 13,172 controls). The combined analysis identified eight new T2D loci reaching genome-wide significance, which mapped in or near GLIS3, PEPD, FITM2-R3HDML-HNF4A, KCNK16, MAEA, GCC1-PAX4, PSMD6 and ZFAND3. GLIS3, which is involved in pancreatic beta cell development and insulin gene expression, is known for its association with fasting glucose levels. The evidence of an association with T2D for PEPD and HNF4A has been shown in previous studies. KCNK16 may regulate glucose-dependent insulin secretion in the pancreas. These findings, derived from an east Asian population, provide new perspectives on the etiology of T2D.

540 citations


Journal ArticleDOI
01 Jan 2009-Trends in Genetics
TL;DR: A thorough understanding of the co-evolution of these two cellular compartments will require carefully executed molecular studies combined with mathematical modeling.
Abstract: Increasing evidence indicates that tumor–stromal cell interactions have a crucial role in tumor initiation and progression. These interactions modify cellular compartments, leading to the co-evolution of tumor cells and their microenvironment. Although the importance of microenvironmental alterations in tumor development is recognized, the molecular mechanisms underlying these changes are only now beginning to be understood. Epigenetic and gene expression changes have consistently been reported in cancer-associated stromal cells and the influence of the host genotype on tumorigenesis is also well documented. However, the presence of clonally selected somatic genetic alterations within the tumor microenvironment has been controversial. A thorough understanding of the co-evolution of these two cellular compartments will require carefully executed molecular studies combined with mathematical modeling.

540 citations


Journal ArticleDOI
Vijay Yajnik1
01 Nov 2001-Gastroenterology

540 citations


Journal ArticleDOI
13 Dec 2002-Cell
TL;DR: It is proposed that fragile sites are unreplicated chromosomal regions resulting from stalled forks that escape the ATR replication checkpoint, and have important implications for understanding both the mechanism of fragile site instability and the consequences of stalled replication in mammalian cells.
Abstract: Conditions that partially inhibit DNA replication induce expression of common fragile sites. These sites form gaps and breaks on metaphase chromosomes and are deleted and rearranged in many tumors. Yet, the mechanism of fragile site expression has been elusive. We demonstrate that the replication checkpoint kinase ATR, but not ATM, is critical for maintenance of fragile site stability. ATR deficiency results in fragile site expression with and without addition of replication inhibitors. Thus, we propose that fragile sites are unreplicated chromosomal regions resulting from stalled forks that escape the ATR replication checkpoint. These findings have important implications for understanding both the mechanism of fragile site instability and the consequences of stalled replication in mammalian cells.

540 citations


Journal ArticleDOI
25 Sep 2014-Cell
Abstract: Pseudouridine is the most abundant RNA modification, yet except for a few well-studied cases, little is known about the modified positions and their function(s). Here, we develop Ψ-seq for transcriptome-wide quantitative mapping of pseudouridine. We validate Ψ-seq with spike-ins and de novo identification of previously reported positions and discover hundreds of unique sites in human and yeast mRNAs and snoRNAs. Perturbing pseudouridine synthases (PUS) uncovers which pseudouridine synthase modifies each site and their target sequence features. mRNA pseudouridinylation depends on both site-specific and snoRNA-guided pseudouridine synthases. Upon heat shock in yeast, Pus7p-mediated pseudouridylation is induced at >200 sites, and PUS7 deletion decreases the levels of otherwise pseudouridylated mRNA, suggesting a role in enhancing transcript stability. rRNA pseudouridine stoichiometries are conserved but reduced in cells from dyskeratosis congenita patients, where the PUS DKC1 is mutated. Our work identifies an enhanced, transcriptome-wide scope for pseudouridine and methods to dissect its underlying mechanisms and function.

539 citations


Authors

Showing all 208150 results

NameH-indexPapersCitations
Walter C. Willett3342399413322
Eric S. Lander301826525976
Robert Langer2812324326306
Meir J. Stampfer2771414283776
Ronald C. Kessler2741332328983
JoAnn E. Manson2701819258509
Albert Hofman2672530321405
Graham A. Colditz2611542256034
Frank B. Hu2501675253464
Bert Vogelstein247757332094
George M. Whitesides2401739269833
Paul M. Ridker2331242245097
Richard A. Flavell2311328205119
Eugene Braunwald2301711264576
Ralph B. D'Agostino2261287229636
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Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
2022294
202130,491
202029,817
201926,010
201823,929
201725,232

Top Attributes

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Institution's top 5 most impactful journals

Social Science Research Network

12.1K papers, 756.9K citations

The Astrophysical Journal

8.8K papers, 828.9K citations

bioRxiv

5.7K papers, 38.9K citations

Nature

4.9K papers, 1.7M citations