| 1. |
- Cruz, Raquel, et al.
(författare)
-
Novel genes and sex differences in COVID-19 severity
- 2022
-
Ingår i: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 31:22, s. 3789-3806
-
Tidskriftsartikel (refereegranskat)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.
|
|
| 2. |
- Agelidis, Alex, et al.
(författare)
-
Disruption of innate defense responses by endoglycosidase HPSE promotes cell survival
- 2021
-
Ingår i: JCI Insight. - : American Society For Clinical Investigation. - 2379-3708. ; 6:7
-
Tidskriftsartikel (refereegranskat)abstract
- The drive to withstand environmental stresses and defend against invasion is a universal trait extant in all forms of life. While numerous canonical signaling cascades have been characterized in detail, it remains unclear how these pathways interface to generate coordinated responses to diverse stimuli. To dissect these connections, we followed heparanase (HPSE), a protein best known for its endoglycosidic activity at the extracellular matrix but recently recognized to drive various forms of late-stage disease through unknown mechanisms. Using herpes simplex virus-1 (HSV-1) infection as a model cellular perturbation, we demonstrate that HPSE acts beyond its established enzymatic role to restrict multiple forms of cell-intrinsic defense and facilitate host cell reprogramming by the invading pathogen. We reveal that cells devoid of HPSE are innately resistant to infection and counteract viral takeover through multiple amplified defense mechanisms. With a unique grasp of the fundamental processes of transcriptional regulation and cell death, HPSE represents a potent cellular intersection with broad therapeutic potential.
|
|
| 3. |
- Carlos Alcantara, Jose, et al.
(författare)
-
Biocomposites from Rice Straw Nanofibers: Morphology, Thermal and Mechanical Properties
- 2020
-
Ingår i: Materials. - : MDPI AG. - 1996-1944. ; 13:9
-
Tidskriftsartikel (refereegranskat)abstract
- Agricultural residues are major potential resources for biomass and for material production. In this work, rice straw residues were used to isolate cellulose nanofibers of different degree of oxidation. Firstly, bleached rice fibers were produced from the rice straw residues following chemical extraction and bleaching processes. Oxidation of rice fibers mediated by radical 2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPO) at pH 10 was then applied to extract rice cellulose nanofibers, with diameters of 3-11 nm from morphological analysis. The strengthening capacity of rice nanofibers was tested by casting nanocomposite films with poly(vinyl alcohol) polymer. The same formulations with eucalyptus nanofibers were produced as comparison. Their thermal and mechanical performance was evaluated using thermogravimetry, differential scanning calorimetry, dynamic mechanical analysis and tensile testing. The glass transition of nanocomposites was shifted to higher temperatures with respect to the pure polymer by the addition of rice cellulose nanofibers. Rice nanofibers also acted as a nucleating agent for the polymer matrix. More flexible eucalyptus nanofibers did not show these two phenomena on the matrix. Instead, both types of nanofibers gave similar stiffening (as Young's modulus) to the matrix reinforced up to 5 wt.%. The ultimate tensile strength of nanocomposite films revealed significant enhancing capacity for rice nanofibers, although this effect was somehow higher for eucalyptus nanofibers.
|
|
| 4. |
- Zhao, Evan Wenbo, et al.
(författare)
-
In situ NMR metrology reveals reaction mechanisms in redox flow batteries
- 2020
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 579:7798, s. 224-228
-
Tidskriftsartikel (refereegranskat)abstract
- Large-scale energy storage is becoming increasingly critical to balancing renewable energy production and consumption1. Organic redox flow batteries, made from inexpensive and sustainable redox-active materials, are promising storage technologies that are cheaper and less environmentally hazardous than vanadium-based batteries, but they have shorter lifetimes and lower energy density2,3. Thus, fundamental insight at the molecular level is required to improve performance4,5. Here we report two in situ nuclear magnetic resonance (NMR) methods of studying redox flow batteries, which are applied to two redox-active electrolytes: 2,6-dihydroxyanthraquinone (DHAQ) and 4,4′-((9,10-anthraquinone-2,6-diyl)dioxy) dibutyrate (DBEAQ). In the first method, we monitor the changes in the 1H NMR shift of the liquid electrolyte as it flows out of the electrochemical cell. In the second method, we observe the changes that occur simultaneously in the positive and negative electrodes in the full electrochemical cell. Using the bulk magnetization changes (observed via the 1H NMR shift of the water resonance) and the line broadening of the 1H shifts of the quinone resonances as a function of the state of charge, we measure the potential differences of the two single-electron couples, identify and quantify the rate of electron transfer between the reduced and oxidized species, and determine the extent of electron delocalization of the unpaired spins over the radical anions. These NMR techniques enable electrolyte decomposition and battery self-discharge to be explored in real time, and show that DHAQ is decomposed electrochemically via a reaction that can be minimized by limiting the voltage used on charging. We foresee applications of these NMR methods in understanding a wide range of redox processes in flow and other electrochemical systems.
|
|
