Institution
Virginia Commonwealth University
Education•Richmond, Virginia, United States•
About: Virginia Commonwealth University is a education organization based out in Richmond, Virginia, United States. It is known for research contribution in the topics: Population & Poison control. The organization has 23822 authors who have published 49587 publications receiving 1787046 citations. The organization is also known as: VCU.
Topics: Population, Poison control, Health care, Anxiety, Mental health
Papers published on a yearly basis
Papers
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TL;DR: Three of 10 children with lethal or severe osteogenesis imperfecta were found to have a recessive condition resulting in CRTAP deficiency, suggesting that prolyl 3-hydroxylation of type I collagen is important for bone formation.
Abstract: Classic osteogenesis imperfecta, an autosomal dominant disorder associated with osteoporosis and bone fragility, is caused by mutations in the genes for type I collagen. A recessive form of the disorder has long been suspected. Since the loss of cartilage-associated protein (CRTAP), which is required for post-translational prolyl 3-hydroxylation of collagen, causes severe osteoporosis in mice, we investigated whether CRTAP deficiency is associated with recessive osteogenesis imperfecta. Three of 10 children with lethal or severe osteogenesis imperfecta, who did not have a primary collagen defect yet had excess post-translational modification of collagen, were found to have a recessive condition resulting in CRTAP deficiency, suggesting that prolyl 3-hydroxylation of type I collagen is important for bone formation.
302 citations
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TL;DR: Together, these findings show the feasibility of genetic pleiotropy-informed methods to improve gene discovery in SCZ and BD and indicate overlapping genetic mechanisms between these two disorders.
Abstract: Several lines of evidence suggest that genome-wide association studies (GWAS) have the potential to explain more of the "missing heritability" of common complex phenotypes. However, reliable methods to identify a larger proportion of single nucleotide polymorphisms (SNPs) that impact disease risk are currently lacking. Here, we use a genetic pleiotropy-informed conditional false discovery rate (FDR) method on GWAS summary statistics data to identify new loci associated with schizophrenia (SCZ) and bipolar disorders (BD), two highly heritable disorders with significant missing heritability. Epidemiological and clinical evidence suggest similar disease characteristics and overlapping genes between SCZ and BD. Here, we computed conditional Q-Q curves of data from the Psychiatric Genome Consortium (SCZ; n = 9,379 cases and n = 7,736 controls; BD: n = 6,990 cases and n = 4,820 controls) to show enrichment of SNPs associated with SCZ as a function of association with BD and vice versa with a corresponding reduction in FDR. Applying the conditional FDR method, we identified 58 loci associated with SCZ and 35 loci associated with BD below the conditional FDR level of 0.05. Of these, 14 loci were associated with both SCZ and BD (conjunction FDR). Together, these findings show the feasibility of genetic pleiotropy-informed methods to improve gene discovery in SCZ and BD and indicate overlapping genetic mechanisms between these two disorders.
302 citations
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TL;DR: It is concluded that EMT is common in PTC invasion and that vimentin regulates thyroid cancer EMT in vitro, and that Vimentin was required both for the development and maintenance of a mesenchymal morphology and invasiveness in thyroid cancer cells.
Abstract: Papillary thyroid carcinomas (PTCs) that invade into local structures are associated with a poor prognosis, but the mechanisms for PTC invasion are incompletely defined, limiting the development of new therapies. To characterize biological processes involved in PTC invasion, we analyzed the gene expression profiles of microscopically dissected intratumoral samples from central and invasive regions of seven widely invasive PTCs and normal thyroid tissue by oligonucleotide microarray and performed confirmatory expression and functional studies. In comparison with the central regions of primary PTCs, the invasive fronts overexpressed TGF β, NFκB and integrin pathway members, and regulators of small G proteins and CDC42. Moreover, reduced levels of mRNAs encoding proteins involved in cell–cell adhesion and communication were identified, consistent with epithelial-to-mesenchymal transition (EMT). To confirm that aggressive PTCs were characterized by EMT, 34 additional PTCs were examined for expression of vimentin, a hallmark of EMT. Overexpression of vimentin was associated with PTC invasion and nodal metastasis. Functional, in vitro studies demonstrated that vimentin was required both for the development and maintenance of a mesenchymal morphology and invasiveness in thyroid cancer cells. We conclude that EMT is common in PTC invasion and that vimentin regulates thyroid cancer EMT in vitro.
302 citations
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TL;DR: Although both sphingosine kinase type 1 and type 2 can phosphorylate FTY720 with low efficiency, SphK2 is much more effective than SphK1 and may be the relevant enzyme that is responsible for in vivo phosphorylation of FTY 720.
302 citations
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TL;DR: The results indicate that Sam68 plays a role in the regulation of Bcl-x alternative splicing and that tyrosine phosphorylation of Sam68 by Src-like kinases can switch its role from proapoptotic to antiapoptosis in live cells.
Abstract: The RNA-binding protein Sam68 is involved in apoptosis, but its cellular mRNA targets and its mechanism of action remain unknown. We demonstrate that Sam68 binds the mRNA for Bcl-x and affects its alternative splicing. Depletion of Sam68 by RNA interference caused accumulation of antiapoptotic Bcl-x(L), whereas its up-regulation increased the levels of proapoptotic Bcl-x(s). Tyrosine phosphorylation of Sam68 by Fyn inverted this effect and favored the Bcl-x(L) splice site selection. A point mutation in the RNA-binding domain of Sam68 influenced its splicing activity and subnuclear localization. Moreover, coexpression of ASF/SF2 with Sam68, or fusion with an RS domain, counteracted Sam68 splicing activity toward Bcl-x. Finally, Sam68 interacted with heterogenous nuclear RNP (hnRNP) A1, and depletion of hnRNP A1 or mutations that impair this interaction attenuated Bcl-x(s) splicing. Our results indicate that Sam68 plays a role in the regulation of Bcl-x alternative splicing and that tyrosine phosphorylation of Sam68 by Src-like kinases can switch its role from proapoptotic to antiapoptotic in live cells.
302 citations
Authors
Showing all 24085 results
Name | H-index | Papers | Citations |
---|---|---|---|
Ronald C. Kessler | 274 | 1332 | 328983 |
Carlo M. Croce | 198 | 1135 | 189007 |
Nicholas G. Martin | 192 | 1770 | 161952 |
Michael Rutter | 188 | 676 | 151592 |
Kenneth S. Kendler | 177 | 1327 | 142251 |
Bernhard O. Palsson | 147 | 831 | 85051 |
Thomas J. Smith | 140 | 1775 | 113919 |
Ming T. Tsuang | 140 | 885 | 73865 |
Patrick F. Sullivan | 133 | 594 | 92298 |
Martin B. Keller | 131 | 541 | 65069 |
Michael E. Thase | 131 | 923 | 75995 |
Benjamin F. Cravatt | 131 | 666 | 61932 |
Jian Zhou | 128 | 3007 | 91402 |
Rena R. Wing | 128 | 649 | 67360 |
Linda R. Watkins | 127 | 519 | 56454 |