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- Imanishi, T., et al.
(författare)
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Integrative annotation of 21,037 human genes validated by full-length cDNA clones
- 2004
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Ingår i: PLoS biology. - : Public Library of Science (PLoS). - 1544-9173 .- 1545-7885. ; 2:6, s. 856-875
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Tidskriftsartikel (refereegranskat)abstract
- The human genome sequence defines our inherent biological potential; the realization of the biology encoded therein requires knowledge of the function of each gene. Currently, our knowledge in this area is still limited. Several lines of investigation have been used to elucidate the structure and function of the genes in the human genome. Even so, gene prediction remains a difficult task, as the varieties of transcripts of a gene may vary to a great extent. We thus performed an exhaustive integrative characterization of 41,118 full-length cDNAs that capture the gene transcripts as complete functional cassettes, providing an unequivocal report of structural and functional diversity at the gene level. Our international collaboration has validated 21,037 human gene candidates by analysis of high-quality full-length cDNA clones through curation using unified criteria. This led to the identification of 5,155 new gene candidates. It also manifested the most reliable way to control the quality of the cDNA clones. We have developed a human gene database, called the H-Invitational Database (H-InvDB; http://www.h-invitational.jp/). It provides the following: integrative annotation of human genes, description of gene structures, details of novel alternative splicing isoforms, non-protein-coding RNAs, functional domains, subcellular localizations, metabolic pathways, predictions of protein three-dimensional structure, mapping of known single nucleotide polymorphisms (SNPs), identification of polymorphic microsatellite repeats within human genes, and comparative results with mouse full-length cDNAs. The H-InvDB analysis has shown that up to 4% of the human genome sequence (National Center for Biotechnology Information build 34 assembly) may contain misassembled or missing regions. We found that 6.5% of the human gene candidates (1,377 loci) did not have a good protein-coding open reading frame, of which 296 loci are strong candidates for non-protein-coding RNA genes. In addition, among 72,027 uniquely mapped SNPs and insertions/deletions localized within human genes, 13,215 nonsynonymous SNPs, 315 nonsense SNPs, and 452 indels occurred in coding regions. Together with 25 polymorphic microsatellite repeats present in coding regions, they may alter protein structure, causing phenotypic effects or resulting in disease. The H-InvDB platform represents a substantial contribution to resources needed for the exploration of human biology and pathology.
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| 2. |
- Kritikou, Joanna S, et al.
(författare)
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Constitutive activation of WASp leads to abnormal cytotoxic cells with increased granzyme B and degranulation response to target cells.
- 2021
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Ingår i: JCI insight. - : American Society for Clinical Investigation. - 2379-3708. ; 6:6
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Tidskriftsartikel (refereegranskat)abstract
- X-linked neutropenia (XLN) is caused by gain-of-function mutations in the actin regulator Wiskott-Aldrich Syndrome protein (WASp). XLN patients have reduced numbers of cytotoxic cells in peripheral blood; however, their capacity to kill tumor cells remains to be determined. Here, we examined NK and T cells from 2 patients with XLN harboring the activating WASpL270P mutation. XLN patient NK and T cells had increased granzyme B content and elevated degranulation and IFN-γ production when compared with healthy control cells. Murine WASpL272P NK and T cells formed stable synapses with YAC-1 tumor cells and anti-CD3/CD28-coated beads, respectively. WASpL272P mouse T cells had normal degranulation and cytokine response whereas WASpL272P NK cells showed an enhanced response. Imaging experiments revealed that while WASpL272P CD8+ T cells had increased accumulation of actin upon TCR activation, WASpL272P NK cells had normal actin accumulation at lytic synapses triggered through NKp46 signaling but had impaired response to lymphocyte function associated antigen-1 engagement. When compared with WT mice, WASpL272P mice showed reduced growth of B16 melanoma and increased capacity to reject MHC class I-deficient cells. Together, our data suggest that cytotoxic cells with constitutively active WASp have an increased capacity to respond to and kill tumor cells.
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| 3. |
- Chafik, L., et al.
(författare)
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Global linkages originating from decadal oceanic variability in the subpolar North Atlantic
- 2016
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Ingår i: Geophysical Research Letters. - 0094-8276 .- 1944-8007. ; 43:20, s. 10909-10919
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Tidskriftsartikel (refereegranskat)abstract
- The anomalous decadal warming of the subpolar North Atlantic Ocean (SPNA), and the northward spreading of this warm water, has been linked to rapid Arctic sea ice loss and more frequent cold European winters. Recently, variations in this heat transport have also been reported to covary with global warming slowdown/acceleration periods via a Pacific climate response. We here examine the role of SPNA temperature variability in this Atlantic-Pacific climate connectivity. We find that the evolution of ocean heat content anomalies from the subtropics to the subpolar region, likely due to ocean circulation changes, coincides with a basin-wide Atlantic warming/cooling. This induces an Atlantic-Pacific sea surface temperature seesaw, which in turn, strengthens/weakens the Walker circulation and amplifies the Pacific decadal variability that triggers pronounced global-scale atmospheric circulation anomalies. We conclude that the decadal oceanic variability in the SPNA is an essential component of the tropical interactions between the Atlantic and Pacific Oceans.
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| 9. |
- Hammarberg, T, et al.
(författare)
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Calcium binding to 5-lipoxygenase
- 2002
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Ingår i: Advances in experimental medicine and biology. - Boston, MA : Springer US. - 0065-2598. ; 507, s. 117-121
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Tidskriftsartikel (refereegranskat)
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