| 1. |
- Cruz, Raquel, et al.
(author)
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Novel genes and sex differences in COVID-19 severity
- 2022
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In: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 31:22, s. 3789-3806
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Journal article (peer-reviewed)abstract
- Here, we describe the results of a genome-wide study conducted in 11 939 coronavirus disease 2019 (COVID-19) positive cases with an extensive clinical information that were recruited from 34 hospitals across Spain (SCOURGE consortium). In sex-disaggregated genome-wide association studies for COVID-19 hospitalization, genome-wide significance (P < 5 × 10−8) was crossed for variants in 3p21.31 and 21q22.11 loci only among males (P = 1.3 × 10−22 and P = 8.1 × 10−12, respectively), and for variants in 9q21.32 near TLE1 only among females (P = 4.4 × 10−8). In a second phase, results were combined with an independent Spanish cohort (1598 COVID-19 cases and 1068 population controls), revealing in the overall analysis two novel risk loci in 9p13.3 and 19q13.12, with fine-mapping prioritized variants functionally associated with AQP3 (P = 2.7 × 10−8) and ARHGAP33 (P = 1.3 × 10−8), respectively. The meta-analysis of both phases with four European studies stratified by sex from the Host Genetics Initiative (HGI) confirmed the association of the 3p21.31 and 21q22.11 loci predominantly in males and replicated a recently reported variant in 11p13 (ELF5, P = 4.1 × 10−8). Six of the COVID-19 HGI discovered loci were replicated and an HGI-based genetic risk score predicted the severity strata in SCOURGE. We also found more SNP-heritability and larger heritability differences by age (<60 or ≥60 years) among males than among females. Parallel genome-wide screening of inbreeding depression in SCOURGE also showed an effect of homozygosity in COVID-19 hospitalization and severity and this effect was stronger among older males. In summary, new candidate genes for COVID-19 severity and evidence supporting genetic disparities among sexes are provided.
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| 2. |
- Facchini, Maria Cristina, et al.
(author)
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Primary submicron marine aerosol dominated by insoluble organic colloids and aggregates
- 2008
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In: Geophysical Research Letters. - 0094-8276 .- 1944-8007. ; 35:17, s. L17814-
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Journal article (peer-reviewed)abstract
- The chemical properties of sea-spray aerosol particles produced by artificially generated bubbles using oceanic waters were investigated during a phytoplankton bloom in the North Atlantic. Spray particles exhibited a progressive increase in the organic matter ( OM) content from 3 +/- 0.4% up to 77 +/- 5% with decreasing particle diameter from 8 to 0.125 mu m. Submicron OM was almost entirely water insoluble (WIOM) and consisted of colloids and aggregates exuded by phytoplankton. Our observations indicate that size dependent transfer of sea water organic material to primary marine particles is mainly controlled by the solubility and surface tension properties of marine OM. The pattern of WIOM and sea-salt content in the different size intervals observed in bubble bursting experiments is similar to that measured in atmospheric marine aerosol samples collected during periods of high biological activity. The results point to a WIOM/sea-salt fingerprint associated with submicron primary marine aerosol production in biologically rich waters.
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| 3. |
- Kisiel, Marta, 1984-, et al.
(author)
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Evaluation of injectable constructs for bone repair with a subperiosteal cranial model in the rat
- 2013
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:8, s. e71683-
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Journal article (peer-reviewed)abstract
- While testing regenerative medicine strategies, the use of animal models that match the research questions and that are related to clinical translation is crucial. During the initial stage of evaluating new strategies for bone repair, the main goal is to state whether the strategies efficiently induce the formation of new bone tissue at an orthotopic site. Here, we present a subperiosteal model in rat calavria that allow the evaluation of a broad range of approaches including bone augmentation, replacement and regeneration. Easy and fast to perform, the model is minimally invasive and no defect are created. The procedure enables to evaluate the outcomes quantitatively using micro-computed tomography and qualitatively by histology and immunohistochemistry. For establishing the model, we used bone morphogenetic protein-2 as an osteoinductive factor and hyaluronic acid hydrogel as injectable biomaterial. We showed that this subperiosteal cranial model offers a minimally invasive and promising solution for a rapid evaluation of bone tissue engineering strategies, even for investigator with limited experience in orthopedic surgery. We believe that this approach could be a powerful platform for orthopedic research and regenerative medicine.
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| 4. |
- Kisiel, Marta, et al.
(author)
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Improving the osteogenic potential of BMP-2 with hyaluronic acid hydrogel modified with integrin-specific fibronectin fragment
- 2013
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In: Biomaterials. - : Elsevier BV. - 0142-9612 .- 1878-5905. ; 34:3, s. 704-712
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Journal article (peer-reviewed)abstract
- While human bone morphogenetic protein-2 (rhBMP-2) is a promising growth factor for bone regeneration, its clinical efficacy has recently shown to be below expectation. In order to improve the clinical translation of rhBMP-2, there exists strong motivation to engineer better delivery systems. Hyaluronic acid (HA) hydrogel is a suitable carrier for the delivery of rhBMP-2, but a major limitation of this scaffold is its low cell adhesive properties. In this study, we have determined whether covalent grafting of an integrin-specific ligands into HA hydrogel could improve cell attachment and further enhance the osteogenic potential of rhBMP-2. A structurally stabilized fibronectin (FN) fragment containing the major integrin-binding domain of full-length FN (FN III9 *-10) was engineered, in order to be incorporated into HA hydrogel. Compared to non-functionalized HA hydrogel, HA-FN hydrogel remarkably improved the capacity of the material to support mesenchymal stem cell attachment and spreading. In an ectopic bone formation model in the rat, delivery of rhBMP-2 with HA-FN hydrogel resulted in the formation of twice as much bone with better organization of collagen fibers compared to delivering the growth factor in non-functionalized HA hydrogel. This engineered hydrogel carrier for rhBMP-2 can be relevant in clinical bone repair.
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