Institution
Children's Hospital Oakland Research Institute
About: Children's Hospital Oakland Research Institute is a based out in . It is known for research contribution in the topics: Population & Human leukocyte antigen. The organization has 1568 authors who have published 2480 publications receiving 203418 citations.
Topics: Population, Human leukocyte antigen, Haplotype, Gene, Cholesterol
Papers published on a yearly basis
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TL;DR: Evidence is presented that vitamin D hormone (calcitriol) activates the transcription of the serotonin‐synthesizing gene tryptophan hydroxylase 2 (TPH2) in the brain at a vitamin D response element (VDRE) and represses thecription of TPH1 in tissues outside the blood‐brain barrier at a distinct VDRE.
Abstract: Serotonin and vitamin D have been proposed to play a role in autism; however, no causal mechanism has been established. Here, we present evidence that vitamin D hormone (calcitriol) activates the transcription of the serotonin-synthesizing gene tryptophan hydroxylase 2 (TPH2) in the brain at a vitamin D response element (VDRE) and represses the transcription of TPH1 in tissues outside the blood-brain barrier at a distinct VDRE. The proposed mechanism explains 4 major characteristics associated with autism: the low concentrations of serotonin in the brain and its elevated concentrations in tissues outside the blood-brain barrier; the low concentrations of the vitamin D hormone precursor 25-hydroxyvitamin D [25(OH)D3]; the high male prevalence of autism; and the presence of maternal antibodies against fetal brain tissue. Two peptide hormones, oxytocin and vasopressin, are also associated with autism and genes encoding the oxytocin-neurophysin I preproprotein, the oxytocin receptor, and the arginine vasopressin receptor contain VDREs for activation. Supplementation with vitamin D and tryptophan is a practical and affordable solution to help prevent autism and possibly ameliorate some symptoms of the disorder.
305 citations
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TL;DR: A 30-fold redundant human bacterial artificial chromosome (BAC) library with a large average insert size (178 kb) has been constructed to provide the intermediate substrate for the international genome sequencing effort.
Abstract: A 30-fold redundant human bacterial artificial chromosome (BAC) library with a large average insert size (178 kb) has been constructed to provide the intermediate substrate for the international genome sequencing effort. The DNA was obtained from a single anonymous volunteer, whose identity was protected through a double-blind donor selection protocol. DNA fragments were generated by partial digestion with EcoRI (library segments 1--4: 24-fold) and MboI (segment 5: sixfold) and cloned into the pBACe3.6 and pTARBAC1 vectors, respectively. The quality of the library was assessed by extensive analysis of 169 clones for rearrangements and artifacts. Eighteen BACs (11%) revealed minor insert rearrangements, and none was chimeric. This BAC library, designated as "RPCI-11," has been used widely as the central resource for insert-end sequencing, clone fingerprinting, high-throughput sequence analysis and as a source of mapped clones for diagnostic and functional studies.
305 citations
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TL;DR: A defect in the gene HSD11B1 encoding 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), a primary regulator of tissue-specific glucocorticoid bioavailability, is suggested and H6PDH is established as a potential factor in the pathogenesis of PCOS.
Abstract: In cortisone reductase deficiency (CRD), activation of cortisone to cortisol does not occur, resulting in adrenocorticotropin-mediated androgen excess and a phenotype resembling polycystic ovary syndrome (PCOS; refs. 1,2). This suggests a defect in the gene HSD11B1 encoding 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1), a primary regulator of tissue-specific glucocorticoid bioavailability. We identified intronic mutations in HSD11B1 that resulted in reduced gene transcription in three individuals with CRD. In vivo, 11beta-HSD1 catalyzes the reduction of cortisone to cortisol whereas purified enzyme acts as a dehydrogenase converting cortisol to cortisone. Oxo-reductase activity can be regained using a NADPH-regeneration system and the cytosolic enzyme glucose-6-phosphate dehydrogenase. But the catalytic domain of 11beta-HSD1 faces into the lumen of the endoplasmic reticulum (ER; ref. 6). We hypothesized that endolumenal hexose-6-phosphate dehydrogenase (H6PDH) regenerates NADPH in the ER, thereby influencing directionality of 11beta-HSD1 activity. Mutations in exon 5 of H6PD in individuals with CRD attenuated or abolished H6PDH activity. These individuals have mutations in both HSD11B1 and H6PD in a triallelic digenic model of inheritance, resulting in low 11beta-HSD1 expression and ER NADPH generation with loss of 11beta-HSD1 oxo-reductase activity. CRD defines a new ER-specific redox potential and establishes H6PDH as a potential factor in the pathogenesis of PCOS.
304 citations
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TL;DR: It is concluded that loss of phospholipid asymmetry may occur in small subpopulations of red cells and that fluorescently labeled annexin V can be used to quantify and isolate these cells.
302 citations
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TL;DR: The defined high fat diet can be used to study atherosclerosis in the mouse since it produces aortic lesions but reduces or eliminates other pathological changes such as gallstone formation and liver damage.
300 citations
Authors
Showing all 1568 results
Name | H-index | Papers | Citations |
---|---|---|---|
Frank B. Hu | 250 | 1675 | 253464 |
Bruce M. Psaty | 181 | 1205 | 138244 |
Bruce N. Ames | 158 | 506 | 129010 |
Rino Rappuoli | 132 | 816 | 64660 |
Robert S. Schwartz | 130 | 923 | 62624 |
Carlos López-Otín | 126 | 494 | 83933 |
Ronald M. Krauss | 120 | 438 | 77969 |
Robert S. Stern | 120 | 761 | 62834 |
Joan S. Brugge | 115 | 286 | 47965 |
Ewan Birney | 114 | 308 | 125382 |
Keith M. Sullivan | 105 | 447 | 39067 |
Bo Lönnerdal | 99 | 674 | 36297 |
Dennis E. Discher | 98 | 372 | 60060 |
Richard Reinhardt | 94 | 370 | 58076 |
Henry A. Erlich | 93 | 354 | 40295 |