| 1. |
- Di Baldassarre, Giuliano, et al.
(författare)
-
Flood-plain mapping : a critical discussion of deterministic and probabilistic approaches
- 2010
-
Ingår i: Hydrological Sciences Journal. - : Informa UK Limited. - 0262-6667 .- 2150-3435. ; 55:3, s. 364-376
-
Tidskriftsartikel (refereegranskat)abstract
- Different methodologies for flood-plain mapping are analysed and discussed by comparing deterministic and probabilistic approaches using hydrodynamic numerical solutions. In order to facilitate the critical discussion, state-of-art techniques in the field of flood inundation modelling are applied to a specific test site (River Dee, UK). Specifically, different flood-plain maps are derived for this test site. A first map is built by applying an advanced deterministic approach: use of a fully two-dimensional finite element model (TELEMAC-2D), calibrated against a historical flood extent, to derive a 1-in-100 year flood inundation map. A second map is derived by using a probabilistic approach: use of a simple raster-based inundation model (LISFLOOD-FP) to derive an uncertain flood extent map predicting the 1-in-100 year event conditioned on the extent of the 2006 flood. The flood-plain maps are then compared and the advantages and disadvantages of the two different approaches are critically discussed.
|
|
| 2. |
- Graham, Lesley A, et al.
(författare)
-
Validation of Uromodulin as a Candidate Gene for Human Essential Hypertension
- 2014
-
Ingår i: Hypertension. - 0194-911X .- 1524-4563. ; 63:3, s. 551-558
-
Tidskriftsartikel (refereegranskat)abstract
- A recent genome-wide association study identified a locus on chromosome 16 in the promoter region of the uromodulin (UMOD) gene that is associated with hypertension. Here, we examined the hypertension signal with functional studies in Umod knockout (KO) mice. Systolic blood pressure was significantly lower in KO versus wild-type (WT) mice under basal conditions (KO: 116.6±0.3 mm Hg versus WT: 136.2±0.4 mm Hg; P<0.0001). Administration of 2% NaCl did not alter systolic blood pressure in KO mice, whereas it increased in WT mice by ≈33%, P<0.001. The average 24-hour urinary sodium excretion in the KO was greater than that of WT mice (P<0.001). Chronic renal function curves demonstrate a leftward shift in KO mice, suggesting that the relationship between UMOD and blood pressure is affected by sodium. Creatinine clearance was increased during salt loading with 2% NaCl in the KO mice, leading to augmented filtered Na(+) excretion and further Na(+) loss. The difference in sodium uptake that exists between WT and KO strains was explored at the molecular level. Urinary tumor necrosis factor-α levels were significantly higher in KO mice compared with WT mice (P<0.0001). Stimulation of primary thick ascending limb of the loop of Henle cells with exogenous tumor necrosis factor-α caused a reduction in NKCC2A expression (P<0.001) with a concurrent rise in the levels of UMOD mRNA (P<0.001). Collectively, we demonstrate that UMOD regulates sodium uptake in the thick ascending limb of the loop of Henle by modulating the effect of tumor necrosis factor-α on NKCC2A expression, making UMOD an important determinant of blood pressure control.
|
|
| 3. |
- Karlsson Söbirk, Sara, et al.
(författare)
-
Human Chemokines as Antimicrobial Peptides with Direct Parasiticidal Effect on Leishmania mexicana In Vitro.
- 2013
-
Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:3
-
Tidskriftsartikel (refereegranskat)abstract
- Chemokines and chemokine receptor-mediated effects are important mediators of the immunological response and cure in human leishmaniasis. However, in addition to their signalling properties for leukocytes, many chemokines have also been shown to act directly as antimicrobial peptides on bacteria and fungi. We screened ten human chemokines (CXCL2, CXCL6, CXCL8, CXCL9, CXCL10, CCL2, CCL3, CCL20, CCL27, CCL28) for antimicrobial effects on the promastigote form of the protozoan parasite Leishmania mexicana, and observed direct parasiticidal effects of several, CCL28 being the most potent. Damage to the plasma membrane integrity could be visualised by entrance of propidium iodide, as measured with flow cytometry, and by scanning electron microscopy, which showed morphological changes and aggregation of cells. The findings were in concordance with parasiticidal activity, measured by decreased mitochondrial activity in an MTT-assay. This is the first report of direct antimicrobial activity by chemokines on parasites. This component of immunity against Leishmania parasites identified here warrants further investigation that might lead to new insight in the mechanisms of human infection and/or new therapeutic approaches.
|
|
| 4. |
- Kõljalg, Urmas, et al.
(författare)
-
Towards a unified paradigm for sequence-based identification of fungi.
- 2013
-
Ingår i: Molecular ecology. - : Wiley. - 1365-294X .- 0962-1083. ; 22:21, s. 5271-7
-
Tidskriftsartikel (refereegranskat)abstract
- The nuclear ribosomal internal transcribed spacer (ITS) region is the formal fungal barcode and in most cases the marker of choice for the exploration of fungal diversity in environmental samples. Two problems are particularly acute in the pursuit of satisfactory taxonomic assignment of newly generated ITS sequences: (i) the lack of an inclusive, reliable public reference data set and (ii) the lack of means to refer to fungal species, for which no Latin name is available in a standardized stable way. Here, we report on progress in these regards through further development of the UNITE database (http://unite.ut.ee) for molecular identification of fungi. All fungal species represented by at least two ITS sequences in the international nucleotide sequence databases are now given a unique, stable name of the accession number type (e.g. Hymenoscyphus pseudoalbidus|GU586904|SH133781.05FU), and their taxonomic and ecological annotations were corrected as far as possible through a distributed, third-party annotation effort. We introduce the term 'species hypothesis' (SH) for the taxa discovered in clustering on different similarity thresholds (97-99%). An automatically or manually designated sequence is chosen to represent each such SH. These reference sequences are released (http://unite.ut.ee/repository.php) for use by the scientific community in, for example, local sequence similarity searches and in the QIIME pipeline. The system and the data will be updated automatically as the number of public fungal ITS sequences grows. We invite everybody in the position to improve the annotation or metadata associated with their particular fungal lineages of expertise to do so through the new Web-based sequence management system in UNITE.
|
|
| 5. |
|
|
| 6. |
- Moretti, Rocco, et al.
(författare)
-
Community-wide evaluation of methods for predicting the effect of mutations on protein-protein interactions
- 2013
-
Ingår i: Proteins. - : Wiley. - 0887-3585 .- 1097-0134. ; 81:11, s. 1980-1987
-
Tidskriftsartikel (refereegranskat)abstract
- Community-wide blind prediction experiments such as CAPRI and CASP provide an objective measure of the current state of predictive methodology. Here we describe a community-wide assessment of methods to predict the effects of mutations on protein-protein interactions. Twenty-two groups predicted the effects of comprehensive saturation mutagenesis for two designed influenza hemagglutinin binders and the results were compared with experimental yeast display enrichment data obtained using deep sequencing. The most successful methods explicitly considered the effects of mutation on monomer stability in addition to binding affinity, carried out explicit side-chain sampling and backbone relaxation, evaluated packing, electrostatic, and solvation effects, and correctly identified around a third of the beneficial mutations. Much room for improvement remains for even the best techniques, and large-scale fitness landscapes should continue to provide an excellent test bed for continued evaluation of both existing and new prediction methodologies. Proteins 2013; 81:1980-1987.
|
|
| 7. |
|
|
