Institution
Karolinska Institutet
Education•Stockholm, Sweden•
About: Karolinska Institutet is a education organization based out in Stockholm, Sweden. It is known for research contribution in the topics: Population & Poison control. The organization has 46212 authors who have published 121142 publications receiving 6008130 citations.
Topics: Population, Poison control, Cancer, Cohort study, Breast cancer
Papers published on a yearly basis
Papers
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TL;DR: The crystal structure analysis of horse liver alcohol dehydrogenase has been extended to 2.4 A resolution and the positions of the 374 amino acids in the polypeptide chain of each subunit are determined.
644 citations
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TL;DR: The definition of a specific caspase cleavage site in CK18 as a neo‐epitope can be used for quantification of apoptotic epithelial cells with immunocytochemical techniques and is applicable to both fresh and formalin‐fixed material.
Abstract: A neo-epitope in cytokeratin 18 (CK18) that becomes available at an early caspase cleavage event during apoptosis and is not detectable in vital epithelial cells is characterized. The monoclonal antibody M30, specific for this site, can be utilized specifically to recognize apoptotic cells, which show cytoplasmic cytokeratin filaments and aggregates after immunohistochemistry with M30, while viable and necrotic cells are negative. The number of cells recognized by the antibody increases after induction of apoptosis in exponentially growing epithelial cell lines and immunoreactivity is independent of the phosphorylation state of the cytokeratins. The generation of the M30 neo-epitope occurs early in the apoptotic cascade, before annexin V reactivity or positive DNA nick end labelling. In a flow cytometric assay, the majority of the M30-positive cells appear in the 'apoptotic' subG1 peak. Tests with synthetic peptides define positions 387-396 of CK18, with a liberated C-terminus at the caspase cleavage site DALD-S, as the ten-residue epitope of M30. This epitope starts at the end of coil 2 of the predicted CK18 structure, at a probable hinge region, compatible with the sensitivity to proteolytic cleavage. The definition of a specific caspase cleavage site in CK18 as a neo-epitope can be used for quantification of apoptotic epithelial cells with immunocytochemical techniques and is applicable to both fresh and formalin-fixed material.
644 citations
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TL;DR: There was a significant correlation between the concnetration of 5-HIAA and severity of depression in the lower, but not in the upper, mode, which suggests the existence of a biochemical subgroup of depressive disorder, characterized by a disturbance of serotonin turnover.
Abstract: The distribution of 5-hydroxyindoleacetic acid (5-HIAA) concentrations in the cerebrospinal fluid of 68 depressed patients was bimodal. Twenty-nine percent of the patients were in the lower mode, with a concentration of 5-HIAA below 15 nanograms per milliliter. Although there were no differences in overall severity of depression between the two modes, there was a significant correlation between the concnetration of 5-HIAA and severity of depression in the lower, but not in the upper, mode. The finding suggests the existence of a biochemical subgroup of depressive disorder, characterized by a disturbance of serotonin turnover.
644 citations
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Harvard University1, Broad Institute2, VU University Amsterdam3, University of Minnesota4, Hospital for Special Surgery5, University of Southern California6, University of Colorado Boulder7, Karolinska Institutet8, Uppsala University9, Stockholm School of Economics10, University of Queensland11, National Bureau of Economic Research12, Research Institute of Industrial Economics13, New York University14
TL;DR: Applying MTAG to summary statistics for depressive symptoms, neuroticism and subjective well-being increased discovery of associated loci as compared to single-trait analyses, yielding more informative bioinformatics analyses and increasing the variance explained by polygenic scores by approximately 25%, matching theoretical expectations.
Abstract: We introduce multi-trait analysis of GWAS (MTAG), a method for joint analysis of summary statistics from genome-wide association studies (GWAS) of different traits, possibly from overlapping samples. We apply MTAG to summary statistics for depressive symptoms (N eff = 354,862), neuroticism (N = 168,105), and subjective well-being (N = 388,538). As compared to the 32, 9, and 13 genome-wide significant loci identified in the single-trait GWAS (most of which are themselves novel), MTAG increases the number of associated loci to 64, 37, and 49, respectively. Moreover, association statistics from MTAG yield more informative bioinformatics analyses and increase the variance explained by polygenic scores by approximately 25%, matching theoretical expectations.
644 citations
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TL;DR: The findings do not support the hypothesis that AD reflects an accelerated aging process, and changes in saturated/polyunsaturated FA ratio are likely to influence cellular function, which in turn may cause certain neural deficiencies.
Abstract: The two major phospholipid classes, namely, phosphatidylethanolamines (PE) and phosphatidylcholines (PC), were studied in four different regions of human brain,i.e., in frontal gray matter, frontal white matter, hippocampus and in pons. The fatty acid (FA) compositions of these phospholipids were found to be specific for the different regions. PC contains mostly saturated and 18∶1 FA, while PE is rich in polyunsaturated FA. Aging has no influence on the FA compositions, while in Alzheimer’s disease (AD) PE is modified in all four regions, particularly in frontal gray matter and in hippocampus. The abundance of the major monounsaturated FA of PE, 18∶1, is not significantly altered in Alzheimer’s disease, but there is a substantial increase in the relative amounts of the saturated components 14∶0, 16∶0 and 18∶0. This is paralleled by a decrease in the polyunsaturated FA 20∶4, 22∶4 and 22∶6. It is not clear whether the changes observed are specific for AD. Changes in saturated/polyunsaturated FA ratio are likely to influence cellular function, which in turn may cause certain neural deficiencies. The findings do not support the hypothesis that AD reflects an accelerated aging process.
644 citations
Authors
Showing all 46522 results
Name | H-index | Papers | Citations |
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Meir J. Stampfer | 277 | 1414 | 283776 |
Albert Hofman | 267 | 2530 | 321405 |
Guido Kroemer | 236 | 1404 | 246571 |
Eric B. Rimm | 196 | 988 | 147119 |
Scott M. Grundy | 187 | 841 | 231821 |
Jing Wang | 184 | 4046 | 202769 |
Tadamitsu Kishimoto | 181 | 1067 | 130860 |
John Hardy | 177 | 1178 | 171694 |
Marc G. Caron | 173 | 674 | 99802 |
Ramachandran S. Vasan | 172 | 1100 | 138108 |
Adrian L. Harris | 170 | 1084 | 120365 |
Douglas F. Easton | 165 | 844 | 113809 |
Zulfiqar A Bhutta | 165 | 1231 | 169329 |
Judah Folkman | 165 | 499 | 148611 |
Ralph A. DeFronzo | 160 | 759 | 132993 |