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- Tranvik, Lars J., et al.
(författare)
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Lakes and reservoirs as regulators of carbon cycling and climate
- 2009
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Ingår i: Limnology and Oceanography. - : Wiley. - 0024-3590 .- 1939-5590. ; 54:6:2, s. 2298-2314
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Forskningsöversikt (refereegranskat)abstract
- We explore the role of lakes in carbon cycling and global climate, examine the mechanisms influencing carbon pools and transformations in lakes, and discuss how the metabolism of carbon in the inland waters is likely to change in response to climate. Furthermore, we project changes as global climate change in the abundance and spatial distribution of lakes in the biosphere, and we revise the estimate for the global extent of carbon transformation in inland waters. This synthesis demonstrates that the global annual emissions of carbon dioxide from inland waters to the atmosphere are similar in magnitude to the carbon dioxide uptake by the oceans and that the global burial of organic carbon in inland water sediments exceeds organic carbon sequestration on the ocean floor. The role of inland waters in global carbon cycling and climate forcing may be changed by human activities, including construction of impoundments, which accumulate large amounts of carbon in sediments and emit large amounts of methane to the atmosphere. Methane emissions are also expected from lakes on melting permafrost. The synthesis presented here indicates that (1) inland waters constitute a significant component of the global carbon cycle, (2) their contribution to this cycle has significantly changed as a result of human activities, and (3) they will continue to change in response to future climate change causing decreased as well as increased abundance of lakes as well as increases in the number of aquatic impoundments.
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| 3. |
- Sevvana, Madhumati, et al.
(författare)
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Serendipitous Fatty Acid Binding Reveals the Structural Determinants for Ligand Recognition in Apolipoprotein M
- 2009
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Ingår i: Journal of Molecular Biology. - : Elsevier BV. - 1089-8638 .- 0022-2836. ; 393:4, s. 920-936
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Tidskriftsartikel (refereegranskat)abstract
- Apolipoprotein M (ApoM) is a 25-kDa HDL-associated apolipoprotein and a member of the lipocalin family of proteins. Mature apoM retains its signal peptide, which serves as a lipid anchor attaching apoM to the lipoproteins, thereby keeping it in the circulation. Studies in mice have suggested apoM to be antiatherogenic, but its physiological function is yet unknown. We have now determined the 1.95 angstrom resolution crystal structure of recombinant human apoM expressed in Escherichia coli and made the unexpected discovery that apoM, although refolded from inclusion bodies, was in complex with fatty acids containing 14, 16 or 18 carbon atoms. ApoM displays the typical lipocalin fold characterised by an eight-stranded antiparallel beta-barrel that encloses an internal ligand-binding pocket. The crystal structures of two different complexes provide a detailed picture of the ligand-binding determinants of apoM. Additional fatty acid- and lipid-binding studies with apoM and the mutants apoM(W47F) and apoM(W100F) showed that sphingosine-1-phosphate is able to displace the bound fatty acids and efficiently quenched the intrinsic fluorescence with an IC50 of 0.90 mu M. Whereas the fatty acids bound in the crystal structure could be a mere consequence of recombinant protein production, the observed binding of sphingosine-l-phosphate might provide a key to a better understanding of the physiological function of apoM. (C) 2009 Elsevier Ltd. All rights reserved.
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| 4. |
- Campistol, Josep M., et al.
(författare)
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Sirolimus therapy after early cyclosporine withdrawal reduces the risk for cancer in adult renal transplantation
- 2006
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Ingår i: Journal of the American Society of Nephrology. - 1046-6673 .- 1533-3450. ; 17:2, s. 581-589
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Tidskriftsartikel (refereegranskat)abstract
- Sirolimus (SRL) is a mammalian target of rapamycin inhibitor that, in contrast to cyclosporine (CsA), has been shown to inhibit rather than promote cancers in experimental models. At 3 mo +/- 2 wk after renal transplantation, 430 of 525 enrolled patients were randomly assigned to remain on SRL-CsA-steroids (ST) or to have CsA withdrawn and SRL troughs increased two-fold (SRL-ST). Median times to first skin and nonskin malignancies were compared between treatments using a survival analysis. Mean annualized rates of skin malignancy were calculated, and the relative risk was determined using a Poisson model. Malignancy-free survival rates for nonskin malignancies were compared using Kaplan-Meier estimates and the log-rank test. At 5 yr, the median time to a first skin carcinoma was delayed (491 versus 1126 d; log-rank test, P = 0.007), and the risk for an event was significantly lower with SRL-ST therapy (relative risk SRL-ST to SRL-CsA-ST 0.346; 95% confidence interval 0.227 to 0.526; P < 0.001, intention-to-treat analysis). The relative risks for both basal and squamous cell carcinomas were significantly reduced. Kaplan-Meier estimates of nonskin cancer were 9.6 versus 4.0% (SRL-CsA-ST versus SRL-ST; P = 0.032, intention-to-treat analysis). Nonskin cancers included those of the lung, larynx, oropharynx, kidney, gastrointestinal tract, prostate, breast, thyroid, and cervix as well as glioma, liposarcoma, astrocytoma, leukemia, lymphoma, and Kaposi's sarcoma. Patients who received SRL-based, calcineurin inhibitor-free therapy after CsA withdrawal at month 3 had a reduced incidence of both skin and nonskin malignancies at 5 yr after renal transplantation compared with those who received SRL therapy combined with CsA. Longer follow-up and additional trials are needed to confirm these promising results.
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| 5. |
- Clermont, Gilles, et al.
(författare)
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Bridging the gap between systems biology and medicine
- 2009
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Ingår i: Genome Medicine. - : Springer Science and Business Media LLC. - 1756-994X. ; 1:9
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Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT : Systems biology has matured considerably as a discipline over the last decade, yet some of the key challenges separating current research efforts in systems biology and clinically useful results are only now becoming apparent. As these gaps are better defined, the new discipline of systems medicine is emerging as a translational extension of systems biology. How is systems medicine defined? What are relevant ontologies for systems medicine? What are the key theoretic and methodologic challenges facing computational disease modeling? How are inaccurate and incomplete data, and uncertain biologic knowledge best synthesized in useful computational models? Does network analysis provide clinically useful insight? We discuss the outstanding difficulties in translating a rapidly growing body of data into knowledge usable at the bedside. Although core-specific challenges are best met by specialized groups, it appears fundamental that such efforts should be guided by a roadmap for systems medicine drafted by a coalition of scientists from the clinical, experimental, computational, and theoretic domains.
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