| 1. |
- Cruz, Raquel, et al.
(författare)
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Novel genes and sex differences in COVID-19 severity
- 2022
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Ingår i: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 31:22, s. 3789-3806
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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.
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| 2. |
- Akiyama, Kazunori, et al.
(författare)
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First Sagittarius A* Event Horizon Telescope Results. II. EHT and Multiwavelength Observations, Data Processing, and Calibration
- 2022
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Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 930:2
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Tidskriftsartikel (refereegranskat)abstract
- We present Event Horizon Telescope (EHT) 1.3 mm measurements of the radio source located at the position of the supermassive black hole Sagittarius A* (Sgr A*), collected during the 2017 April 5-11 campaign. The observations were carried out with eight facilities at six locations across the globe. Novel calibration methods are employed to account for Sgr A*'s flux variability. The majority of the 1.3 mm emission arises from horizon scales, where intrinsic structural source variability is detected on timescales of minutes to hours. The effects of interstellar scattering on the image and its variability are found to be subdominant to intrinsic source structure. The calibrated visibility amplitudes, particularly the locations of the visibility minima, are broadly consistent with a blurred ring with a diameter of similar to 50 mu as, as determined in later works in this series. Contemporaneous multiwavelength monitoring of Sgr A* was performed at 22, 43, and 86 GHz and at near-infrared and X-ray wavelengths. Several X-ray flares from Sgr A* are detected by Chandra, one at low significance jointly with Swift on 2017 April 7 and the other at higher significance jointly with NuSTAR on 2017 April 11. The brighter April 11 flare is not observed simultaneously by the EHT but is followed by a significant increase in millimeter flux variability immediately after the X-ray outburst, indicating a likely connection in the emission physics near the event horizon. We compare Sgr A*'s broadband flux during the EHT campaign to its historical spectral energy distribution and find that both the quiescent emission and flare emission are consistent with its long-term behavior.
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| 3. |
- Ferrando, Carlos, et al.
(författare)
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Effects of oxygen on post-surgical infections during an individualised perioperative open-lung ventilatory strategy : a randomised controlled trial
- 2020
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Ingår i: British Journal of Anaesthesia. - : ELSEVIER SCI LTD. - 0007-0912 .- 1471-6771. ; 124:1, s. 110-120
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Tidskriftsartikel (refereegranskat)abstract
- Background: We aimed to examine whether using a high fraction of inspired oxygen (FIO2) in the context of an individualised intra- and postoperative open-lung ventilation approach could decrease surgical site infection (SSI) in patients scheduled for abdominal surgery. Methods: We performed a multicentre, randomised controlled clinical trial in a network of 21 university hospitals from June 6, 2017 to July 19, 2018. Patients undergoing abdominal surgery were randomly assigned to receive a high (0.80) or conventional (0.3) FIO2 during the intraoperative period and during the first 3 postoperative hours. All patients were mechanically ventilated with an open-lung strategy, which included recruitment manoeuvres and individualised positive end-expiratory pressure for the best respiratory-system compliance, and individualised continuous postoperative airway pressure for adequate peripheral oxyhaemoglobin saturation. The primary outcome was the prevalence of SSI within the first 7 postoperative days. The secondary outcomes were composites of systemic complications, length of intensive care and hospital stay, and 6-month mortality. Results: We enrolled 740 subjects: 371 in the high FIO2 group and 369 in the low FIO2 group. Data from 717 subjects were available for final analysis. The rate of SSI during the first postoperative week did not differ between high (8.9%) and low (9.4%) FIO2 groups (relative risk [RR]: 0.94; 95% confidence interval [CI]: 0.59-1.50; P=0.90]). Secondary outcomes, such as atelectasis (7.7% vs 9.8%; RR: 0.77; 95% CI: 0.48-1.25; P=0.38) and myocardial ischaemia (0.6% [n=2] vs 0% [n=0]; P=0.47) did not differ between groups. Conclusions: An oxygenation strategy using high FIO2 compared with conventional FIO2 did not reduce postoperative SSIs in abdominal surgery. No differences in secondary outcomes or adverse events were found.
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| 4. |
- Aleix-Mata, Gael, et al.
(författare)
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Development and characterization of 15 novel polymorphic microsatellite loci for two important bot flies (Diptera, Oestridae) by next-generation sequencing
- 2020
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Ingår i: Parasitology Research. - : Springer Nature. - 0932-0113 .- 1432-1955. ; 119:9, s. 2829-2835
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Tidskriftsartikel (refereegranskat)abstract
- Cephenemyia stimulatorandOestrus ovisare two important parasitic bot flies (Oestridae) species causing myiasis, with a potential negative impact on the welfare of the host. Using next-generation sequencing approach and bioinformatics tools, a large panel of possible microsatellites loci was obtained in both species. Primer pairs were designed for 15 selected microsatellite loci inC. stimulatorand other 15 loci inO. ovisfor PCR amplification. Loci amplification and analysis were performed in four populations of each species. The results demonstrated that all selected loci were polymorphic, with the number of alleles ranging from 2 to 6 per locus inC. stimulatorand 3 to 13 per locus inO. ovis. This is the first time to describe these microsatellite loci forC. stimulatorandO. ovis. These two sets of microsatellite markers could be further used for biogeographic and population genetics studies.
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| 5. |
- Camacho, Juan Pedro M., et al.
(författare)
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Satellitome comparison of two oedipodine grasshoppers highlights the contingent nature of satellite DNA evolution
- 2022
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Ingår i: BMC Biology. - : Springer Nature. - 1741-7007. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe full catalog of satellite DNA (satDNA) within a same genome constitutes the satellitome. The Library Hypothesis predicts that satDNA in relative species reflects that in their common ancestor, but the evolutionary mechanisms and pathways of satDNA evolution have never been analyzed for full satellitomes. We compare here the satellitomes of two Oedipodine grasshoppers (Locusta migratoria and Oedaleus decorus) which shared their most recent common ancestor about 22.8 Ma ago.ResultsWe found that about one third of their satDNA families (near 60 in every species) showed sequence homology and were grouped into 12 orthologous superfamilies. The turnover rate of consensus sequences was extremely variable among the 20 orthologous family pairs analyzed in both species. The satDNAs shared by both species showed poor association with sequence signatures and motives frequently argued as functional, except for short inverted repeats allowing short dyad symmetries and non-B DNA conformations. Orthologous satDNAs frequently showed different FISH patterns at both intra- and interspecific levels. We defined indices of homogenization and degeneration and quantified the level of incomplete library sorting between species.ConclusionsOur analyses revealed that satDNA degenerates through point mutation and homogenizes through partial turnovers caused by massive tandem duplications (the so-called satDNA amplification). Remarkably, satDNA amplification increases homogenization, at intragenomic level, and diversification between species, thus constituting the basis for concerted evolution. We suggest a model of satDNA evolution by means of recursive cycles of amplification and degeneration, leading to mostly contingent evolutionary pathways where concerted evolution emerges promptly after lineages split.
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| 6. |
- Lourido, Lucia, et al.
(författare)
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Association of serum anti-centromere protein F antibodies with clinical response to infliximab in patients with rheumatoid arthritis : A prospective study
- 2020
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Ingår i: Seminars in Arthritis & Rheumatism. - : Elsevier BV. - 0049-0172 .- 1532-866X. ; 50:5, s. 1101-1108
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Tidskriftsartikel (refereegranskat)abstract
- Background: One-third of rheumatoid arthritis (RA) patients demonstrate no clinical improvement after receiving tumor necrosis factor inhibitors (TNFi). The presence of serum autoantibodies is a hallmark in RA and may provide information on future response to treatment. The aim of this prospective study was to search for novel serum autoantibodies useful to predict clinical response to TNFi. Methods: The autoantibody repertoire was profiled on RA patients treated with TNFi as a first line of biologic therapy (N= 185), who were recruited in three independent cohorts. The presence and levels of autoantibodies in serum at baseline were analysed in association with the clinical response after 24 weeks follow-up. A multiplex bead array built using antigens selected from an initial untargeted screening was employed to identify the autoantibodies on a discovery cohort (N= 50) and to verify and validate the results on verification (N= 61) and validation (N= 74) cohorts. Non-parametric tests, meta-analysis and Receiver Operating Curves (ROC) were performed in order to assess the clinical relevance of the observed findings. Results: Novel autoantibodies were associated with the clinical response to TNFi, showing different reactivity profiles among the different TNFi. The baseline levels of IgG antibodies against Centromere protein F (CENPF), a protein related to cell proliferation, were significantly (p <0.05) increased in responders (N=111) to infliximab (IFX) compared to non-responders (N= 44). The addition of anti-CENPF antibodies to demographic and clinical variables (age, sex, DAS28-ESR) resulted in the best model to discriminate responders, showing an area under the curve (AUC) of 0.756 (95% CI [0.639-0.874], p = 0.001). A further meta-analysis demonstrated the significant association of anti-CENPF levels with the patient's subsequent response to IFX, showing a standardized mean difference (SMD) of-0.65 (95% CI [-1.02;-0.27], p = 0.018). Conclusions: Our study reveals for the first time the potential of circulating anti-CENPF antibodies to predict the clinical response to IFX before starting the treatment. This finding could be potentially useful to guide therapeutic decisions and may lead to further studies focusing on the role of CENPF on RA pathology. (C) 2020 Elsevier Inc. All rights reserved.
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| 7. |
- Migueles, Jairo H., et al.
(författare)
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Effects of an Exercise Program on Cardiometabolic and Mental Health in Children With Overweight or Obesity A Secondary Analysis of a Randomized Clinical Trial
- 2023
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Ingår i: JAMA Network Open. - : AMER MEDICAL ASSOC. - 2574-3805. ; 6:7
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Tidskriftsartikel (refereegranskat)abstract
- Importance Childhood obesity is a risk factor associated with type 2 diabetes, cardiovascular disease, and mental disorders later in life. Investigation of the parallel effects of a defined exercise program on cardiometabolic and mental health in children with overweight or obesity may provide new insights on the potential benefits of exercise on overall health. Objective To investigate the effects of a 20-week exercise program on cardiometabolic and mental health in children with overweight or obesity. Design, Setting, and Participants This secondary analysis of a parallel-group randomized clinical trial was conducted in Granada, Spain, from November 1, 2014, to June 30, 2016. Data analyses were performed between February 1, 2020, and July 14, 2022. Children with overweight or obesity aged 8 to 11 years were eligible, and the study was performed in an out-of-school context. Intervention The exercise program included 3 to 5 sessions/wk (90 min/session) of aerobic plus resistance training for 20 weeks. The wait-list control group continued with their usual routines. Main Outcomes and Measures Cardiometabolic outcomes as specified in the trial protocol included body composition (fat mass, fat-free mass, and visceral adipose tissue), physical fitness (cardiorespiratory, speed-agility, and muscular), and traditional risk factors (waist circumference, blood lipid levels, glucose levels, insulin levels, and blood pressure). Cardiometabolic risk score (z score) was calculated based on age and sex reference values for levels of triglycerides, inverted high-density lipoprotein cholesterol, and glucose, the mean of systolic and diastolic blood pressure, and waist circumference. An additional cardiometabolic risk score also included cardiorespiratory fitness. Mental health outcomes included an array of psychological well-being and ill-being indicators. Results The 92 participants included in the per-protocol analyses (36 girls [39%] and 56 boys [61%]) had a mean (SD) age of 10.0 (1.1) years. The exercise program reduced the cardiometabolic risk score byapproximately0.38 (95% CI, -0.74 to -0.02) SDs; decreased low-density lipoprotein cholesterol level by -7.00 (95% CI, -14.27 to 0.37) mg/dL (to convert to mmol/L, multiply by 0.0259), body mass index (calculated as weight in kilograms divided by height in meters squared) by -0.59 (95% CI, -1.06 to -0.12), fat mass index by -0.67 (95% CI, -1.01 to -0.33), and visceral adipose tissue by -31.44 (95% CI, -58.99 to -3.90) g; and improved cardiorespiratory fitness by 2.75 (95% CI, 0.22-5.28) laps in the exercise group compared with the control group. No effects were observed on mental health outcomes. Conclusions and Relevance In this secondary analysis of a randomized clinical trial, an aerobic plus resistance exercise program improved cardiometabolic health in children with overweight or obesity but had no effect on mental health.
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| 8. |
- Navarro-Dominguez, Beatriz, et al.
(författare)
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Tandem Repeat DNA Provides Many Cytological Markers for Hybrid Zone Analysis in Two Subspecies of the Grasshopper Chorthippus parallelus
- 2023
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Ingår i: Genes. - : MDPI. - 2073-4425. ; 14:2
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Tidskriftsartikel (refereegranskat)abstract
- Recent advances in next generation sequencing (NGS) have greatly increased our understanding of non-coding tandem repeat (TR) DNA. Here we show how TR DNA can be useful for the study of hybrid zones (HZ), as it serves as a marker to identify introgression in areas where two biological entities come in contact. We used Illumina libraries to analyse two subspecies of the grasshopper Chorthippus parallelus, which currently form a HZ in the Pyrenees. We retrieved a total of 152 TR sequences, and used fluorescent in situ hybridization (FISH) to map 77 families in purebred individuals from both subspecies. Our analysis revealed 50 TR families that could serve as markers for analysis of this HZ, using FISH. Differential TR bands were unevenly distributed between chromosomes and subspecies. Some of these TR families yielded FISH bands in only one of the subspecies, suggesting the amplification of these TR families after the geographic separation of the subspecies in the Pleistocene. Our cytological analysis of two TR markers along a transect of the Pyrenean hybrid zone showed asymmetrical introgression of one subspecies into the other, consistent with previous findings using other markers. These results demonstrate the reliability of TR-band markers for hybrid zone studies.
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| 9. |
- Palacios-Gimenez, Octavio M., et al.
(författare)
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Eight Million Years of Satellite DNA Evolution in Grasshoppers of the Genus Schistocerca Illuminate the Ins and Outs of the Library Hypothesis
- 2020
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Ingår i: Genome Biology and Evolution. - : Oxford University Press (OUP). - 1759-6653. ; 12:3, s. 88-102
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Tidskriftsartikel (refereegranskat)abstract
- Satellite DNA (satDNA) is an abundant class of tandemly repeated noncoding sequences, showing high rate of change in sequence, abundance, and physical location. However, the mechanisms promoting these changes are still controversial. The library model was put forward to explain the conservation of some satDNAs for long periods, predicting that related species share a common collection of satDNAs, which mostly experience quantitative changes. Here, we tested the library model by analyzing three satDNAs in ten species of Schistocerca grasshoppers. This group represents a valuable material because it diversified during the last 7.9 Myr across the American continent from the African desert locust (Schistocerca gregaria), and this thus illuminates the direction of evolutionary changes. By combining bioinformatic and cytogenetic, we tested whether these three satDNA families found in S. gregaria are also present in nine American species, and whether differential gains and/or losses have occurred in the lineages. We found that the three satDNAs are present in all species but display remarkable interspecies differences in their abundance and sequences while being highly consistent with genus phylogeny. The number of chromosomal loci where satDNA is present was also consistent with phylogeny for two satDNA families but not for the other. Our results suggest eminently chance events for satDNA evolution. Several evolutionary trends clearly imply either massive amplifications or contractions, thus closely fitting the library model prediction that changes are mostly quantitative. Finally, we found that satDNA amplifications or contractions may influence the evolution of monomer consensus sequences and by chance playing a major role in driftlike dynamics.
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