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| 6. |
- Bonham, LW, et al.
(författare)
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Genetic variation across RNA metabolism and cell death gene networks is implicated in the semantic variant of primary progressive aphasia
- 2019
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1, s. 10854-
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Tidskriftsartikel (refereegranskat)abstract
- The semantic variant of primary progressive aphasia (svPPA) is a clinical syndrome characterized by neurodegeneration and progressive loss of semantic knowledge. Unlike many other forms of frontotemporal lobar degeneration (FTLD), svPPA has a highly consistent underlying pathology composed of TDP-43 (a regulator of RNA and DNA transcription metabolism). Previous genetic studies of svPPA are limited by small sample sizes and a paucity of common risk variants. Despite this, svPPA’s relatively homogenous clinicopathologic phenotype makes it an ideal investigative model to examine genetic processes that may drive neurodegenerative disease. In this study, we used GWAS metadata, tissue samples from pathologically confirmed frontotemporal lobar degeneration, and in silico techniques to identify and characterize protein interaction networks associated with svPPA risk. We identified 64 svPPA risk genes that interact at the protein level. The protein pathways represented in this svPPA gene network are critical regulators of RNA metabolism and cell death, such as SMAD proteins and NOTCH1. Many of the genes in this network are involved in TDP-43 metabolism. Contrary to the conventional notion that svPPA is a clinical syndrome with few genetic risk factors, our analyses show that svPPA risk is complex and polygenic in nature. Risk for svPPA is likely driven by multiple common variants in genes interacting with TDP-43, along with cell death,x` working in combination to promote neurodegeneration.
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| 8. |
- Hibar, Derrek P., et al.
(författare)
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Novel genetic loci associated with hippocampal volume
- 2017
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (r(g) = -0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.
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| 9. |
- Thompson, Paul M., et al.
(författare)
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The ENIGMA Consortium : large-scale collaborative analyses of neuroimaging and genetic data
- 2014
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Ingår i: BRAIN IMAGING BEHAV. - : Springer Science and Business Media LLC. - 1931-7557 .- 1931-7565. ; 8:2, s. 153-182
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Tidskriftsartikel (refereegranskat)abstract
- The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, ENIGMA studies have analyzed neuroimaging data from over 12,826 subjects. In addition, data from 12,171 individuals were provided by the CHARGE consortium for replication of findings, in a total of 24,997 subjects. By meta-analyzing results from many sites, ENIGMA has detected factors that affect the brain that no individual site could detect on its own, and that require larger numbers of subjects than any individual neuroimaging study has currently collected. ENIGMA's first project was a genome-wide association study identifying common variants in the genome associated with hippocampal volume or intracranial volume. Continuing work is exploring genetic associations with subcortical volumes (ENIGMA2) and white matter microstructure (ENIGMA-DTI). Working groups also focus on understanding how schizophrenia, bipolar illness, major depression and attention deficit/hyperactivity disorder (ADHD) affect the brain. We review the current progress of the ENIGMA Consortium, along with challenges and unexpected discoveries made on the way.
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| 11. |
- Artigas Soler, María, et al.
(författare)
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Genome-wide association and large-scale follow up identifies 16 new loci influencing lung function.
- 2011
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 43:11, s. 1082-90
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Tidskriftsartikel (refereegranskat)abstract
- Pulmonary function measures reflect respiratory health and are used in the diagnosis of chronic obstructive pulmonary disease. We tested genome-wide association with forced expiratory volume in 1 second and the ratio of forced expiratory volume in 1 second to forced vital capacity in 48,201 individuals of European ancestry with follow up of the top associations in up to an additional 46,411 individuals. We identified new regions showing association (combined P < 5 × 10(-8)) with pulmonary function in or near MFAP2, TGFB2, HDAC4, RARB, MECOM (also known as EVI1), SPATA9, ARMC2, NCR3, ZKSCAN3, CDC123, C10orf11, LRP1, CCDC38, MMP15, CFDP1 and KCNE2. Identification of these 16 new loci may provide insight into the molecular mechanisms regulating pulmonary function and into molecular targets for future therapy to alleviate reduced lung function.
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| 12. |
- Loth, Daan W, et al.
(författare)
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Genome-wide association analysis identifies six new loci associated with forced vital capacity
- 2014
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 46, s. 669-677
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Tidskriftsartikel (refereegranskat)abstract
- Forced vital capacity (FVC), a spirometric measure of pulmonary function, reflects lung volume and is used to diagnose and monitor lung diseases. We performed genome-wide association study meta-analysis of FVC in 52,253 individuals from 26 studies and followed up the top associations in 32,917 additional individuals of European ancestry. We found six new regions associated at genome-wide significance (P < 5 × 10(-8)) with FVC in or near EFEMP1, BMP6, MIR129-2-HSD17B12, PRDM11, WWOX and KCNJ2. Two loci previously associated with spirometric measures (GSTCD and PTCH1) were related to FVC. Newly implicated regions were followed up in samples from African-American, Korean, Chinese and Hispanic individuals. We detected transcripts for all six newly implicated genes in human lung tissue. The new loci may inform mechanisms involved in lung development and the pathogenesis of restrictive lung disease.
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| 15. |
- Chen, J. Y., et al.
(författare)
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High-resolution 3D imaging uncovers organ-specific vascular control of tissue aging
- 2021
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Ingår i: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 7:6
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Tidskriftsartikel (refereegranskat)abstract
- Blood vessels provide supportive microenvironments for maintaining tissue functions. Age-associated vascular changes and their relation to tissue aging and pathology are poorly understood. Here, we perform 3D imaging of young and aging vascular beds. Multiple organs in mice and humans demonstrate an age-dependent decline in vessel density and pericyte numbers, while highly remodeling tissues such as skin preserve the vasculature. Vascular attrition precedes the appearance of cellular hallmarks of aging such as senescence. Endothelial VEGFR2 loss-of-function mice demonstrate that vascular perturbations are sufficient to stimulate cellular changes coupled with aging. Age-associated tissue-specific molecular changes in the endothelium drive vascular loss and dictate pericyte to fibroblast differentiation. Lineage tracing of perivascular cells with inducible PDGERB and NG2 Cre mouse lines demonstrated that increased pericyte to fibroblast differentiation distinguishes injury-induced organ fibrosis and zymosan-induced arthritis. To spur further discoveries, we provide a freely available resource with 3D vascular and tissue maps.
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| 16. |
- Ferrari, Raffaele, et al.
(författare)
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Frontotemporal dementia and its subtypes: a genome-wide association study.
- 2014
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Ingår i: Lancet Neurology. - 1474-4465. ; 13:7, s. 686-699
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Tidskriftsartikel (refereegranskat)abstract
- Frontotemporal dementia (FTD) is a complex disorder characterised by a broad range of clinical manifestations, differential pathological signatures, and genetic variability. Mutations in three genes-MAPT, GRN, and C9orf72-have been associated with FTD. We sought to identify novel genetic risk loci associated with the disorder.
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| 18. |
- Hancock, Dana B, et al.
(författare)
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Genome-Wide Joint Meta-Analysis of SNP and SNP-by-Smoking Interaction Identifies Novel Loci for Pulmonary Function
- 2012
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Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 8:12, s. e1003098-
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies have identified numerous genetic loci for spirometic measures of pulmonary function, forced expiratory volume in one second (FEV1), and its ratio to forced vital capacity (FEV1/FVC). Given that cigarette smoking adversely affects pulmonary function, we conducted genome-wide joint meta-analyses (JMA) of single nucleotide polymorphism (SNP) and SNP-by-smoking (ever-smoking or pack-years) associations on FEV1 and FEV1/FVC across 19 studies (total N = 50,047). We identified three novel loci not previously associated with pulmonary function. SNPs in or near DNER (smallest PJMA = 5.00×10−11), HLA-DQB1 and HLA-DQA2 (smallest PJMA = 4.35×10−9), and KCNJ2 and SOX9 (smallest PJMA = 1.28×10−8) were associated with FEV1/FVC or FEV1 in meta-analysis models including SNP main effects, smoking main effects, and SNP-by-smoking (ever-smoking or pack-years) interaction. The HLA region has been widely implicated for autoimmune and lung phenotypes, unlike the other novel loci, which have not been widely implicated. We evaluated DNER, KCNJ2, and SOX9 and found them to be expressed in human lung tissue. DNER and SOX9 further showed evidence of differential expression in human airway epithelium in smokers compared to non-smokers. Our findings demonstrated that joint testing of SNP and SNP-by-environment interaction identified novel loci associated with complex traits that are missed when considering only the genetic main effects.
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| 20. |
- Amaral, Andre F. S., et al.
(författare)
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Interaction between gas cooking and GSTM1 null genotype in bronchial responsiveness : results from the European Community Respiratory Health Survey
- 2014
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Ingår i: Thorax. - : BMJ. - 0040-6376 .- 1468-3296. ; 69:6, s. 558-564
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Tidskriftsartikel (refereegranskat)abstract
- Background Increased bronchial responsiveness is characteristic of asthma. Gas cooking, which is a major indoor source of the highly oxidant nitrogen dioxide, has been associated with respiratory symptoms and reduced lung function. However, little is known about the effect of gas cooking on bronchial responsiveness and on how this relationship may be modified by variants in the genes GSTM1, GSTT1 and GSTP1, which influence antioxidant defences. Methods The study was performed in subjects with forced expiratory volume in one second at least 70% of predicted who took part in the multicentre European Community Respiratory Health Survey, had bronchial responsiveness assessed by methacholine challenge and had been genotyped for GSTM1, GSTT1 and GSTP1-rs1695. Information on the use of gas for cooking was obtained from interviewer-led questionnaires. Effect modification by genotype on the association between the use of gas for cooking and bronchial responsiveness was assessed within each participating country, and estimates combined using meta-analysis. Results Overall, gas cooking, as compared with cooking with electricity, was not associated with bronchial responsiveness (beta=-0.08, 95% CI -0.40 to 0.25, p=0.648). However, GSTM1 significantly modified this effect (beta for interaction=-0.75, 95% CI - 1.16 to -0.33, p=4x10(-4)), with GSTM1 null subjects showing more responsiveness if they cooked with gas. No effect modification by GSTT1 or GSTP1-rs1695 genotypes was observed. Conclusions Increased bronchial responsiveness was associated with gas cooking among subjects with the GSTM1 null genotype. This may reflect the oxidant effects on the bronchi of exposure to nitrogen dioxide.
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| 21. |
- Anitha, K., et al.
(författare)
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Changes in structural attributes of plant communities along disturbance gradients in a dry deciduous forest of Western Ghats, India
- 2009
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Ingår i: Environmental Monitoring & Assessment. - : Springer Science and Business Media LLC. - 1573-2959 .- 0167-6369. ; 155:1-4, s. 393-405
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Tidskriftsartikel (refereegranskat)abstract
- Changes in tree and understory plant diversity and community composition in two sites at different disturbance levels were studied on the Anaikatty hills, Western Ghats. Systematic sampling using small scale permanent quadrates (50 x 20 m for trees, 5 x 5 m for shrubs/saplings, 1 x 1 m for herbs/seedlings) enumerated 3,376 individuals of trees (106 species), 8,599 of individuals shrubs (122 species) and 16,659 individuals of herbs (145 species). Among the two sites, species richness and diversity were highest for low disturbed stand (98 and 3.9, respectively) compared to high disturbed site (45 and 2.71, respectively). Result of cluster analysis showed that two distinct clusters were formed on the basis of disturbance of the area in concordance with our field observation. A total of 37 species were common to both sites, sixty one species exclusively found in low disturbed site and eight species were pertained to highly disturbed site. Mann-Whitney test based on Monte Carlo approximation at 95% confidence levels indicated that both populations were not entirely different. The clear difference was only observed for average basal area of trees, density of seedlings, number of species, density and diversity for shrubs and number of species and diversity for herb. The species composition were different in two stand i.e., Nothopegia racemosa-Albizia amara-Maba neilghrrensis in low disturbed stand and Albizia amara-Pleiospermium alatum-Bauhinia racemosa in high disturbed stand. The major disturbance factors identification using spearman rank correlation indicated that the disturbance in low disturbed habitats were mostly from past logging followed by cutting and illicit felling and grazing, while in high disturbed habitats, it was human presence, past logging and lopping and fuel wood collection.
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| 22. |
- Babu, Challa, et al.
(författare)
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Performance analysis of flat plate hybrid PV/thermal configurations
- 2022
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Ingår i: AIP Conference Proceedings. - : American Institute of Physics (AIP). - 9780735443570
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Konferensbidrag (refereegranskat)abstract
- In the recent times many hybrid renewable energy sources are developed. In that, hybrid PV/Thermal gains the more attention than other hybrid sources. In the present work, made a performance analysis of different PV/Thermal configurations. The flat plate configurations have the more feasibility for the domestic applications than the concentrated type. In this paper, liquid, air, nano fluid, phase change material and Thermoelectric generator type configurations are presented. The performance analysis of all configurations done with energy output generation and efficiency of the system.
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| 23. |
- Bakolis, I, et al.
(författare)
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Respiratory health and endotoxin : associations and modification by CD14/-260 genotype
- 2012
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Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 39:3, s. 573-581
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Tidskriftsartikel (refereegranskat)abstract
- Exposure to endotoxin has been associated with increased respiratory symptoms and decrements in lung function in occupational settings but little is known about health effects of domestic exposure in adults. We describe the association of respiratory disease, IgE sensitisation, bronchial reactivity and lung function with mattress endotoxin levels in adults and determine whether these associations are modified by polymorphisms in CD14.Endotoxin levels in mattress dust from a population based sample of 972 adults were measured. Associations were examined using generalized linear mixed models, adjusting for individual and household confounders. Effect modification of these associations by CD14/-260 (rs2569190) was assessed.Mattress endotoxin levels varied from 0.1 to 402.6 EU·mg(-1). Although there was no overall association of lung function with endotoxin exposure, there was evidence that the association of FEV1 and FVC with endotoxin was modified by CD14/-260 genotype (p for interaction 0.005 and 0.013 respectively). There was no evidence that symptoms, IgE sensitisation or bronchial reactivity was associated with mattress endotoxin levels.In this large epidemiological study of adults there was no evidence that mattress endotoxin level was associated with respiratory symptoms or IgE sensitisation but the association of lung function with endotoxin levels may be modified by CD14-genotype.
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| 25. |
- Glass, Daniel, et al.
(författare)
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Gene expression changes with age in skin, adipose tissue, blood and brain.
- 2013
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Ingår i: Genome Biology. - : Springer Science and Business Media LLC. - 1465-6906 .- 1474-760X. ; 14:7
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Previous studies have demonstrated that gene expression levels change with age. These changes are hypothesized to influence the aging rate of an individual. We analyzed gene expression changes with age in abdominal skin, subcutaneous adipose tissue and lymphoblastoid cell lines in 856 female twins in the age range of 39-85 years. Additionally, we investigated genotypic variants involved in genotype-by-age interactions to understand how the genomic regulation of gene expression alters with age.RESULTS: Using a linear mixed model, differential expression with age was identified in 1,672 genes in skin and 188 genes in adipose tissue. Only two genes expressed in lymphoblastoid cell lines showed significant changes with age. Genes significantly regulated by age were compared with expression profiles in 10 brain regions from 100 postmortem brains aged 16 to 83 years. We identified only one age-related gene common to the three tissues. There were 12 genes that showed differential expression with age in both skin and brain tissue and three common to adipose and brain tissues.CONCLUSIONS: Skin showed the most age-related gene expression changes of all the tissues investigated, with many of the genes being previously implicated in fatty acid metabolism, mitochondrial activity, cancer and splicing. A significant proportion of age-related changes in gene expression appear to be tissue-specific with only a few genes sharing an age effect in expression across tissues. More research is needed to improve our understanding of the genetic influences on aging and the relationship with age-related diseases.
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| 26. |
- Gomes, SC, et al.
(författare)
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Reboot surgery for chronic rhinosinusitis with nasal polyposis: recurrence and smell kinetics
- 2022
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Ingår i: European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery. - : Springer Science and Business Media LLC. - 1434-4726. ; 279:12, s. 5691-5699
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Tidskriftsartikel (refereegranskat)
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| 27. |
- Islavath, Nanaji, et al.
(författare)
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Effect of hole-transporting materials on the photovoltaic performance and stability of all-ambient-processed perovskite solar cells
- 2017
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Ingår i: Journal of Energy Chemistry. - : Elsevier BV. - 2095-4956 .- 2096-885X. ; 26:3, s. 584-591
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Tidskriftsartikel (refereegranskat)abstract
- High-efficiency perovskite solar cells (PSCs) reported hitherto have been mostly prepared in a moisture and oxygen-free glove-box atmosphere, which hampers upscaling and real-time performance assessment of this exciting photovoltaic technology. In this work, we have systematically studied the feasibility of all-ambient-processing of PSCs and evaluated their photovoltaic performance. It has been shown that phase-pure crystalline tetragonal MAPbI3 perovskite films are instantly formed in ambient air at room temperature by a two-step spin coating process, undermining the need for dry atmosphere and post-annealing. All-ambient-processed PSCs with a configuration of FTO/TiO2/MAPbI3/Spiro-OMeTAD/Au achieve open-circuit voltage (990 mV) and short-circuit current density (20.31 mA/cm2) comparable to those of best reported glove-box processed devices. Nevertheless, device power conversion efficiency is still constrained at 5% by the unusually low fill-factor of 0.25. Dark current–voltage characteristics reveal poor conductivity of hole-transporting layer caused by lack of oxidized spiro-OMeTAD species, resulting in high series-resistance and decreased fill-factor. The study also establishes that the above limitations can be readily overcome by employing an inorganic p-type semiconductor, copper thiocyanate, as ambient-processable hole-transporting layer to yield a fill-factor of 0.54 and a power conversion efficiency of 7.19%. The present findings can have important implications in industrially viable fabrication of large-area PSCs.The poor conductivity of ambient-processed spiro-OMeTAD HTM layer caused by lack of oxidation is identified as a major performance limiting factor and successfully overcome by replacing with stable inorganic CuSCN.
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| 28. |
- Muniz, Jorge, et al.
(författare)
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Challenges of Engineering Education 5.0 based on I4.0 Policies in Brazil, India, Japan, and Sweden
- 2022
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Ingår i: International Conference on Work Integrated Learning. - Trollhättan : University West. - 9789189325302 ; , s. 95-96
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: Industry and academia have placed increasing attention on implementing Industry 4.0 (I4.0) in the production ofgoods and services. Named as Industry 4.0 in Brazil, Made in India in India, Society 5.0 in Japan, andProduktion2030 in Sweden (Ribeiro et al., 2022). Hereafter, we apply I4.0 to simplify, which promises customizedproducts produced in smaller lots, and that repetitive manufacturing tasks can be automated very soon (Karre etal., 2017).Country policies play an important role in pushing different sectors of the economy, aligned as new with theregulatory framework of national and international trade, especially industrial (Aguinis et al., 2020). The implementation of I4.0 literature indicates different specificities in each country, including culture, R&D targets,education and vocational training, and their research opportunities related to how I4.0 affects workers (Jerman etal., 2020). The research-question is: How do different countries approach the opportunities and challenges of Engineering Education 4.0 through similar or different country policies?This study aims to discuss engineering education related to I4.0 policies. This discussion is based on policies fromBrazil, India, Japan, and Sweden related to education and workers 5.0, which include students and employees.Investigating how these countries are adjusting to I4.0 is relevant for national industrial sectors to wish to actefficiently in this new technological context. Industry 4.0 demands new professional skills and will impactemployment. It is noteworthy that this research is in line with the Sustainable Development Goals (SDGs) proposedby the United Nations (UN): Quality Education (SDG-4); o Decent Work and Economic Growth (SDG-8); andIndustry, Innovation, and Infrastructure (ODS-9) which seeks to promote inclusive and sustainableindustrialization and foster innovation. This research aims to contribute to sustainable o rganizational practices;formulation of public policies that alleviate social problems; guidance of professional curricula affected by I 4.0.Papers and Data Selection: A literature search was conducted in the Scopus database, which gathers some of the most important journalsrelated to manufacturing technologies with high impact factors, based on the PRISMA method, which refers to aminimum set of evidence-based items to report studies in systematic reviews and meta -analyses (MOHER et al.,2009). The paper set was assembled from the Scopus core collection, using the following search string: “industry4.0” OR “industry 5.0” AND “policies” AND ". The results were narrowed to texts in English, which yielded 1496papers. All titles and abstracts were read, which resulted in a set composed of 14 papers. We also use official documents relating to I4.0 raised from official government websites.Comparison of Countries’ Education policies and Industry 4.0: The literature addresses difficulties associated with the implementation of I4.0 in emerging economies (Dalagnore,2018; Hong and Muniz Jr., 2022). Not surprisingly, current literature I4.0 related to technology adoption is themost prevalent theme discussed from a hard, technology-oriented perspective rather than a people-oriented.Production systems are sociotechnical systems, with an explicit understanding that all systems involve ongoinginteractions between people and technology, and they are rapidly transforming virtually all areas of human life,work, and interaction.The European Commission’s (Breque et al., 2021) vision for ‘Industry 5.0’ proposes moves past a narrow andtraditional focus on technology-or economic enabled growth of the existing extractive, production andconsumption driven economic model to a more transformative view of growth that is focused on human progressand well-being based on reducing and shifting consumption to new forms of sustainable, circular and regenerativeeconomic value creation and equitable prosperity. This Human-centric production system design and managementapproach (Industry 5.0) is necessary to support skill development, learning, continuous improvement andcollaboration in the organization (Ribeiro et al., 2022).Conclusion: Brazil, India, Japan and Sweden create policies to support their own technological independence. All countriesindicate concern about education and development of skills related to I4.0.It can be concluded that the four countries studied from the perspective of Industry 4.0 an d Engineering Education4.0 are all embarking on their journeys towards increased digitalization in industry and society as a whole. Therealization of the human-centered Society 5.0 was realized and highlighted comparatively early for Japan, whereasin the Europe Union and thus in Sweden the focus of the importance of Industry 5.0 development in parallelIndustry 4.0 has risen up since year 2021.The results indicate that although there are many initiatives of meeting the needs for new competence andknowledge in the era of I4.0 to accommodate Engineering Education 4.0 there are still challenges for futureresearch to move forward in the nexus between I4.0 and I5.0. The result, of studying different countries'policies, highlights that it is imperative, when approaching novel technologies in I4.0 and designing Engineering Education 4.0, to in parallel consider technological implementations with the inclusion of I5.0 aspects and humancentric perspectives.
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| 33. |
- Repapi, Emmanouela, et al.
(författare)
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Genome-wide association study identifies five loci associated with lung function.
- 2010
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 42:1, s. 36-44
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Tidskriftsartikel (refereegranskat)abstract
- Pulmonary function measures are heritable traits that predict morbidity and mortality and define chronic obstructive pulmonary disease (COPD). We tested genome-wide association with forced expiratory volume in 1 s (FEV(1)) and the ratio of FEV(1) to forced vital capacity (FVC) in the SpiroMeta consortium (n = 20,288 individuals of European ancestry). We conducted a meta-analysis of top signals with data from direct genotyping (n < or = 32,184 additional individuals) and in silico summary association data from the CHARGE Consortium (n = 21,209) and the Health 2000 survey (n < or = 883). We confirmed the reported locus at 4q31 and identified associations with FEV(1) or FEV(1)/FVC and common variants at five additional loci: 2q35 in TNS1 (P = 1.11 x 10(-12)), 4q24 in GSTCD (2.18 x 10(-23)), 5q33 in HTR4 (P = 4.29 x 10(-9)), 6p21 in AGER (P = 3.07 x 10(-15)) and 15q23 in THSD4 (P = 7.24 x 10(-15)). mRNA analyses showed expression of TNS1, GSTCD, AGER, HTR4 and THSD4 in human lung tissue. These associations offer mechanistic insight into pulmonary function regulation and indicate potential targets for interventions to alleviate respiratory disease.
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| 34. |
- Shanmuga Rajan, K., et al.
(författare)
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Abundant and Altered Expression of PIWI-Interacting RNAs during Cardiac Hypertrophy
- 2016
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Ingår i: Heart, Lung and Circulation. - : ELSEVIER SCIENCE INC. - 1443-9506 .- 1444-2892. ; 25:10, s. 1013-1020
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Tidskriftsartikel (refereegranskat)abstract
- Background The discovery of PIWI-interacting RNAs (piRNAs) has fundamentally changed our understanding of post transcriptional regulation of transposons and other genes. Unlike miRNA and siRNA, the piRNAs are the most abundant but least studied RNA species in mammals. Although the expression of PIWI proteins and piRNAs has long been regarded as germline specific, increasing evidences suggest the expression of piRNAs in somatic cells. Methods In this study, the small RNA sequencing executed during induction of cardiac hypertrophy in both in vivo and in vitro conditions were annotated for the expression of piRNAs. The expression of piRNAs was validated by qPCR and RNA immunoprecipitation. In addition, the presence of piRNAs in circulation of myocardial infarction patients was studied by qPCR. Results We identified an abundant and altered expression of piRNAs during cardiac hypertrophy. The differentially expressed piRNAs was validated by qPCR and RNA immunoprecipitation. The significantly and differentially expressed piRNAs were predicted to target different retrotransposons and mRNAs in the rat genome. The detection of specific piRNA in serum of myocardial infarction patients suggests the potential of piRNA for diagnosis. Conclusion Overall this study is the first to provide a whole-genome analysis of the large repertoire of piRNAs in the cardiac system and this would pave a new path to understanding the molecular aetiology of piRNA and retrotransposons in the physiology and pathology of the cardiac system.
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| 35. |
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