| 1. |
|
|
| 2. |
- Wang, Z., et al.
(author)
-
Genome-wide association analyses of physical activity and sedentary behavior provide insights into underlying mechanisms and roles in disease prevention
- 2022
-
In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 54:9, s. 1332-1344
-
Journal article (peer-reviewed)abstract
- Although physical activity and sedentary behavior are moderately heritable, little is known about the mechanisms that influence these traits. Combining data for up to 703,901 individuals from 51 studies in a multi-ancestry meta-analysis of genome-wide association studies yields 99 loci that associate with self-reported moderate-to-vigorous intensity physical activity during leisure time (MVPA), leisure screen time (LST) and/or sedentary behavior at work. Loci associated with LST are enriched for genes whose expression in skeletal muscle is altered by resistance training. A missense variant in ACTN3 makes the alpha-actinin-3 filaments more flexible, resulting in lower maximal force in isolated type IIA muscle fibers, and possibly protection from exercise-induced muscle damage. Finally, Mendelian randomization analyses show that beneficial effects of lower LST and higher MVPA on several risk factors and diseases are mediated or confounded by body mass index (BMI). Our results provide insights into physical activity mechanisms and its role in disease prevention. Multi-ancestry meta-analyses of genome-wide association studies for self-reported physical activity during leisure time, leisure screen time, sedentary commuting and sedentary behavior at work identify 99 loci associated with at least one of these traits.
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
- Cebrian, Ariane V.S., et al.
(author)
-
Development of Conformable Substrates for OLEDs Using Highly Transparent Bacterial Cellulose Modified with Recycled Polystyrene
- 2022
-
In: Advanced Sustainable Systems. - : Wiley. - 2366-7486. ; 6:2
-
Journal article (peer-reviewed)abstract
- Bacterial cellulose (BC) is a biocompatible and nontoxic biopolymer that has been successfully used as a substrate for flexible organic light emitting diodes (OLEDs). Although BC membranes exhibit excellent mechanical properties and industrial scalability, they are semitransparent, which limits their performance. To improve the optical properties of BC membranes, methods such as the polymerization of different inorganic–organic hybrid materials and petrochemical derivative monomers have been considered; however, these methods require considerable time and effort. In this work, transparent BC membranes for conformable OLEDs substrates are fabricated by spray coating a solution of recycled petrochemical plastics, found in expanded foam package wastes, and d-limonene, which is a green solvent extracted from orange peels. This fabrication approach is highly scalable and can be considered a sustainable technique to develop high performance transparent substrates for photonic applications based on both recovered petrochemical polymers and naturally occurring biopolymers. In terms of the morphological and structural properties, the resulting transparent membranes exhibit a lower roughness than pristine BC. The resulting BC-PS composite is used as a substrate for OLED fabrication. The conformable OLEDs exhibit a current efficiency of up to 5 cd A−1 (16 000 cd m−2) and power density of ≈2.8 mW cm−2.
|
|
| 6. |
- de las Fuentes, Lisa, et al.
(author)
-
Gene-educational attainment interactions in a multi-ancestry genome-wide meta-analysis identify novel blood pressure loci
- 2021
-
In: Molecular Psychiatry. - : Springer Nature. - 1359-4184 .- 1476-5578. ; 26:6, s. 2111-2125
-
Journal article (peer-reviewed)abstract
- Educational attainment is widely used as a surrogate for socioeconomic status (SES). Low SES is a risk factor for hypertension and high blood pressure (BP). To identify novel BP loci, we performed multi-ancestry meta-analyses accounting for gene-educational attainment interactions using two variables, “Some College” (yes/no) and “Graduated College” (yes/no). Interactions were evaluated using both a 1 degree of freedom (DF) interaction term and a 2DF joint test of genetic and interaction effects. Analyses were performed for systolic BP, diastolic BP, mean arterial pressure, and pulse pressure. We pursued genome-wide interrogation in Stage 1 studies (N = 117 438) and follow-up on promising variants in Stage 2 studies (N = 293 787) in five ancestry groups. Through combined meta-analyses of Stages 1 and 2, we identified 84 known and 18 novel BP loci at genome-wide significance level (P < 5 × 10-8). Two novel loci were identified based on the 1DF test of interaction with educational attainment, while the remaining 16 loci were identified through the 2DF joint test of genetic and interaction effects. Ten novel loci were identified in individuals of African ancestry. Several novel loci show strong biological plausibility since they involve physiologic systems implicated in BP regulation. They include genes involved in the central nervous system-adrenal signaling axis (ZDHHC17, CADPS, PIK3C2G), vascular structure and function (GNB3, CDON), and renal function (HAS2 and HAS2-AS1, SLIT3). Collectively, these findings suggest a role of educational attainment or SES in further dissection of the genetic architecture of BP.
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
- Abejirinde, IOO, et al.
(author)
-
Strengthening capacity in hospitals to reduce perinatal morbidity and mortality through a codesigned intervention package: protocol for a realist evaluation as part of a stepped-wedge trial of the Action Leveraging Evidence to Reduce perinatal morTality and morbidity (ALERT) in sub-Saharan Africa project
- 2022
-
In: BMJ open. - : BMJ. - 2044-6055. ; 12:4, s. e057414-
-
Journal article (peer-reviewed)abstract
- Despite a strong evidence base for developing interventions to reduce child mortality and morbidity related to pregnancy and delivery, major knowledge–implementation gaps remain. The Action Leveraging Evidence to Reduce perinatal morTality and morbidity (ALERT) in sub-Saharan Africa project aims to overcome these gaps through strengthening the capacity of multidisciplinary teams that provide maternity care. The intervention includes competency-based midwife training, community engagement for study design, mentoring and quality improvement cycles. The realist process evaluation of ALERT aims at identifying and testing the causal pathway through which the intervention achieves its impact.Methods and analysisThis realist process evaluation complements the effectiveness evaluation and the economic evaluation of the ALERT intervention. Following the realist evaluation cycle, we will first elicit the initial programme theory on the basis of the ALERT theory of change, a review of the evidence on adoption and diffusion of innovations and the perspectives of the stakeholders. Second, we will use a multiple embedded case study design to empirically test the initial programme theory in two hospitals in each of the four intervention countries. Qualitative and quantitative data will be collected, using in-depth interviews with hospital staff and mothers, observations, patient exit interviews and (hospital) document reviews. Analysis will be guided by the Intervention-Actors-Context-Mechanism-Outcome configuration heuristic. We will use thematic coding to analyse the qualitative data. The quantitative data will be analysed descriptively and integrated in the analysis using a retroductive approach. Each case study will end with a refined programme theory (in-case analysis). Third, we will carry out a cross-case comparison within and between the four countries. Comparison between study countries should enable identifying relevant context factors that influence effectiveness and implementation, leading to a mid-range theory that may inform the scaling up the intervention.Ethics and disseminationIn developing this protocol, we paid specific attention to cultural sensitivity, the do no harm principle, confidentiality and non-attribution. We received ethical approval from the local and national institutional review boards in Tanzania, Uganda, Malawi, Benin, Sweden and Belgium. Written or verbal consent of respondents will be secured after explaining the purpose, potential benefits and potential harms of the study using an information sheet. The results will be disseminated through workshops with the hospital staff and national policymakers, and scientific publications and conferences.Trial registration numberPACTR202006793783148.
|
|
| 10. |
- Dicke, Sidney S., et al.
(author)
-
Metastable intermediate during hIAPP aggregation catalyzed by membranes as detected with 2D IR spectroscopy
- 2022
-
In: RSC CHEMICAL BIOLOGY. - : Royal Society of Chemistry (RSC). - 2633-0679. ; 3:7, s. 931-940
-
Journal article (peer-reviewed)abstract
- The aggregation of human islet amyloid polypeptide (hIAPP) into amyloid fibrils involves formation of oligomeric intermediates that are thought to be the cytotoxic species responsible for beta-cell dysfunction in type 2 diabetes. hIAPP oligomers permeating or disrupting the cellular membrane may be one mechanism of toxicity and so measuring the structural kinetics of aggregation in the presence of membranes is of much interest. In this study, we use 2D IR spectroscopy and (CO)-C-13-O-18 isotope labeling to study the secondary structure of the oligomeric intermediates formed in solution and in the presence of phospholipid vesicles at sites L12A13, L16V17, G24A25 and V32G33. Pairs of labels monitor the couplings between associated polypeptides and the dihedral angles between adjacent residues. In solution, the L12A13 residues form an oligomeric beta-sheet in addition to an alpha-helix whereas with the phospholipid vesicles they are alpha-helical throughout the aggregation process. In both solution and with DOPC vesicles, L16V17 and V32G33 have disordered structures until fibrils are formed. Similarly, under both conditions, G24A25 exhibits 3-state kinetics, created by an oligomeric intermediate with a well-defined beta-sheet structure. Amyloid fibril formation is often thought to involve intermediates with exceedingly low populations that are difficult to detect experimentally. These experiments establish that amyloid fibril formation of hIAPP when catalyzed by membranes includes a metastable intermediate and that this intermediate has a similar structure at G24A25 in the FGAIL region as the corresponding intermediate in solution, thought to be the toxic species.
|
|
