Institution
Loma Linda University
Education•Loma Linda, California, United States•
About: Loma Linda University is a education organization based out in Loma Linda, California, United States. It is known for research contribution in the topics: Population & Medicine. The organization has 9220 authors who have published 13485 publications receiving 447094 citations. The organization is also known as: University of Loma Linda.
Topics: Population, Medicine, Poison control, Transplantation, Health care
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TL;DR: It is demonstrated that 5mC and 5hmC in DNA are oxidized to 5-carboxylcytosine (5caC) by Tet dioxygenases in vitro and in cultured cells, suggesting that oxidation of 5m C by Tet proteins followed by TDG-mediated base excision of 5caC constitutes a pathway for active DNA demethylation.
Abstract: The prevalent DNA modification in higher organisms is the methylation of cytosine to 5-methylcytosine (5mC), which is partially converted to 5-hydroxymethylcytosine (5hmC) by the Tet (ten eleven translocation) family of dioxygenases. Despite their importance in epigenetic regulation, it is unclear how these cytosine modifications are reversed. Here, we demonstrate that 5mC and 5hmC in DNA are oxidized to 5-carboxylcytosine (5caC) by Tet dioxygenases in vitro and in cultured cells. 5caC is specifically recognized and excised by thymine-DNA glycosylase (TDG). Depletion of TDG in mouse embyronic stem cells leads to accumulation of 5caC to a readily detectable level. These data suggest that oxidation of 5mC by Tet proteins followed by TDG-mediated base excision of 5caC constitutes a pathway for active DNA demethylation.
2,408 citations
TL;DR: It is demonstrated that all three mouse Tet proteins (Tet1, Tet2 and Tet3) can also catalyse a similar reaction, uncover the enzymatic activity of the Tet proteins, and demonstrate a role for Tet1 in ES cell maintenance and inner cell mass cell specification.
Abstract: DNA methylation is one of the best-characterized epigenetic modifications. Although the enzymes that catalyse DNA methylation have been characterized, enzymes responsible for demethylation have been elusive. A recent study indicates that the human TET1 protein could catalyse the conversion of 5-methylcytosine (5mC) of DNA to 5-hydroxymethylcytosine (5hmC), raising the possibility that DNA demethylation may be a Tet1-mediated process. Here we extend this study by demonstrating that all three mouse Tet proteins (Tet1, Tet2 and Tet3) can also catalyse a similar reaction. Tet1 has an important role in mouse embryonic stem (ES) cell maintenance through maintaining the expression of Nanog in ES cells. Downregulation of Nanog via Tet1 knockdown correlates with methylation of the Nanog promoter, supporting a role for Tet1 in regulating DNA methylation status. Furthermore, knockdown of Tet1 in pre-implantation embryos results in a bias towards trophectoderm differentiation. Thus, our studies not only uncover the enzymatic activity of the Tet proteins, but also demonstrate a role for Tet1 in ES cell maintenance and inner cell mass cell specification.
2,364 citations
TL;DR: Of the many factors examined that might affect the relation between breast cancer risk and use of HRT, only a woman's weight and body-mass index had a material effect: the increase in the relative risk of breast cancer diagnosed in women using HRT and associated with long durations of use in current and recent users was greater for women of lower than of higher weight or body- mass index.
2,343 citations
National Institutes of Health1, Mayo Clinic2, Harvard University3, American Cancer Society4, University of Melbourne5, University of Cambridge6, University of California, Irvine7, Loma Linda University8, Johns Hopkins University9, University of Minnesota10, Cancer Council Victoria11, Karolinska Institutet12, City of Hope National Medical Center13, New York University14, University of Washington15, The Queen's Medical Center16
TL;DR: In white adults, overweight and obesity (and possibly underweight) are associated with increased all-cause mortality and the hazard ratios for the men were similar.
Abstract: BACKGROUND A high body-mass index (BMI, the weight in kilograms divided by the square of the height in meters) is associated with increased mortality from cardiovascular disease and certain cancers, but the precise relationship between BMI and all-cause mortality remains uncertain. METHODS We used Cox regression to estimate hazard ratios and 95% confidence intervals for an association between BMI and all-cause mortality, adjusting for age, study, physical activity, alcohol consumption, education, and marital status in pooled data from 19 prospective studies encompassing 1.46 million white adults, 19 to 84 years of age (median, 58). RESULTS The median baseline BMI was 26.2. During a median follow-up period of 10 years (range, 5 to 28), 160,087 deaths were identified. Among healthy participants who never smoked, there was a J-shaped relationship between BMI and all-cause mortality. With a BMI of 22.5 to 24.9 as the reference category, hazard ratios among women were 1.47 (95 percent confidence interval [CI], 1.33 to 1.62) for a BMI of 15.0 to 18.4; 1.14 (95% CI, 1.07 to 1.22) for a BMI of 18.5 to 19.9; 1.00 (95% CI, 0.96 to 1.04) for a BMI of 20.0 to 22.4; 1.13 (95% CI, 1.09 to 1.17) for a BMI of 25.0 to 29.9; 1.44 (95% CI, 1.38 to 1.50) for a BMI of 30.0 to 34.9; 1.88 (95% CI, 1.77 to 2.00) for a BMI of 35.0 to 39.9; and 2.51 (95% CI, 2.30 to 2.73) for a BMI of 40.0 to 49.9. In general, the hazard ratios for the men were similar. Hazard ratios for a BMI below 20.0 were attenuated with longer-term follow-up. CONCLUSIONS In white adults, overweight and obesity (and possibly underweight) are associated with increased all-cause mortality. All-cause mortality is generally lowest with a BMI of 20.0 to 24.9.
1,874 citations
TL;DR: Clinical manifestations such as fever, shortness of breath or dyspnea were associated with the progression of disease, and laboratory examination such as aspartate amino transferase(AST) > 40U/L, creatinine(Cr) ≥ 133mol/l, hypersensitive cardiac troponin I(hs-cTnI) > 28pg/mL, procalcitonin(PCT) > 0.5mg/L predicted the deterioration of disease.
1,743 citations
Authors
Showing all 9287 results
Name | H-index | Papers | Citations |
---|---|---|---|
Piet A. van den Brandt | 89 | 404 | 30237 |
David C. Nieman | 86 | 394 | 29712 |
Subburaman Mohan | 86 | 461 | 29023 |
John H. Zhang | 84 | 895 | 29976 |
John A. Jane | 84 | 451 | 30420 |
Bianca Weinstock-Guttman | 83 | 526 | 25870 |
Curt A. Sandman | 82 | 332 | 23863 |
Mohammed F. Saad | 81 | 168 | 26612 |
Jennifer B. Unger | 79 | 513 | 22614 |
Lonnie K. Zeltzer | 75 | 340 | 19391 |
Steven E. Wolf | 74 | 419 | 21329 |
Marcos Intaglietta | 72 | 412 | 17196 |
Elizabeth J. Perlman | 72 | 260 | 16621 |
Paola Romagnani | 71 | 223 | 17657 |
Robert G. Gish | 71 | 339 | 17401 |