| 1. |
- Kanai, M, et al.
(author)
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- 2023
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swepub:Mat__t
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| 2. |
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| 3. |
- Campbell, PJ, et al.
(author)
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Pan-cancer analysis of whole genomes
- 2020
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
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Journal article (peer-reviewed)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
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| 4. |
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| 5. |
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| 6. |
- Menden, MP, et al.
(author)
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Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen
- 2019
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 2674-
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Journal article (peer-reviewed)abstract
- The effectiveness of most cancer targeted therapies is short-lived. Tumors often develop resistance that might be overcome with drug combinations. However, the number of possible combinations is vast, necessitating data-driven approaches to find optimal patient-specific treatments. Here we report AstraZeneca’s large drug combination dataset, consisting of 11,576 experiments from 910 combinations across 85 molecularly characterized cancer cell lines, and results of a DREAM Challenge to evaluate computational strategies for predicting synergistic drug pairs and biomarkers. 160 teams participated to provide a comprehensive methodological development and benchmarking. Winning methods incorporate prior knowledge of drug-target interactions. Synergy is predicted with an accuracy matching biological replicates for >60% of combinations. However, 20% of drug combinations are poorly predicted by all methods. Genomic rationale for synergy predictions are identified, including ADAM17 inhibitor antagonism when combined with PIK3CB/D inhibition contrasting to synergy when combined with other PI3K-pathway inhibitors in PIK3CA mutant cells.
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| 7. |
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| 8. |
- Perez-Nadales, Elena, et al.
(author)
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Predictors of mortality in solid organ transplant recipients with bloodstream infections due to carbapenemase-producing Enterobacterales : The impact of cytomegalovirus disease and lymphopenia
- 2020
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In: American Journal of Transplantation. - : WILEY. - 1600-6135 .- 1600-6143. ; 20:6, s. 1629-1641
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Journal article (peer-reviewed)abstract
- Treatment of carbapenemase-producing Enterobacterales bloodstream infections in solid organ transplant recipients is challenging. The objective of this study was to develop a specific score to predict mortality in solid organ transplant recipients with carbapenemase-producing Enterobacterales bloodstream infections. A multinational, retrospective (2004-2016) cohort study (INCREMENT-SOT, ClinicalTrials.gov NCT02852902) was performed. The main outcome variable was 30-day all-cause mortality. The INCREMENT-SOT-CPE score was developed using logistic regression. The global cohort included 216 patients. The final logistic regression model included the following variables: INCREMENT-CPE mortality score >= 8 (8 points), no source control (3 points), inappropriate empirical therapy (2 points), cytomegalovirus disease (7 points), lymphopenia (4 points), and the interaction between INCREMENT-CPE score >= 8 and CMV disease (minus 7 points). This score showed an area under the receiver operating characteristic curve of 0.82 (95% confidence interval [CI] 0.76-0.88) and classified patients into 3 strata: 0-7 (low mortality), 8-11 (high mortality), and 12-17 (very-high mortality). We performed a stratified analysis of the effect of monotherapy vs combination therapy among 165 patients who received appropriate therapy. Monotherapy was associated with higher mortality only in the very-high (adjusted hazard ratio [HR] 2.82, 95% CI 1.13-7.06, P = .03) and high (HR 9.93, 95% CI 2.08-47.40, P = .004) mortality risk strata. A score-based algorithm is provided for therapy guidance.
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| 9. |
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| 10. |
- 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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| 11. |
- Mootha, VK, et al.
(author)
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PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes.
- 2003
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 34:3, s. 267-273
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Journal article (peer-reviewed)abstract
- DNA microarrays can be used to identify gene expression changes characteristic of human disease. This is challenging, however, when relevant differences are subtle at the level of individual genes. We introduce an analytical strategy, Gene Set Enrichment Analysis, designed to detect modest but coordinate changes in the expression of groups of functionally related genes. Using this approach, we identify a set of genes involved in oxidative phosphorylation whose expression is coordinately decreased in human diabetic muscle. Expression of these genes is high at sites of insulin-mediated glucose disposal, activated by PGC-1alpha and correlated with total-body aerobic capacity. Our results associate this gene set with clinically important variation in human metabolism and illustrate the value of pathway relationships in the analysis of genomic profiling experiments.
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| 12. |
- Rheinbay, E, et al.
(author)
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Analyses of non-coding somatic drivers in 2,658 cancer whole genomes
- 2020
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 102-
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Journal article (peer-reviewed)abstract
- The discovery of drivers of cancer has traditionally focused on protein-coding genes1–4. Here we present analyses of driver point mutations and structural variants in non-coding regions across 2,658 genomes from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium5 of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). For point mutations, we developed a statistically rigorous strategy for combining significance levels from multiple methods of driver discovery that overcomes the limitations of individual methods. For structural variants, we present two methods of driver discovery, and identify regions that are significantly affected by recurrent breakpoints and recurrent somatic juxtapositions. Our analyses confirm previously reported drivers6,7, raise doubts about others and identify novel candidates, including point mutations in the 5′ region of TP53, in the 3′ untranslated regions of NFKBIZ and TOB1, focal deletions in BRD4 and rearrangements in the loci of AKR1C genes. We show that although point mutations and structural variants that drive cancer are less frequent in non-coding genes and regulatory sequences than in protein-coding genes, additional examples of these drivers will be found as more cancer genomes become available.
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| 13. |
- Soininen, E.M., et al.
(author)
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Location of studies and evidence of effects of herbivory on Arctic vegetation: a systematic map
- 2021
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In: Environmental Evidence. - : BioMed Central (BMC). - 2047-2382. ; 10:1
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Journal article (peer-reviewed)abstract
- Background: Herbivores modify the structure and function of tundra ecosystems. Understanding their impacts is necessary to assess the responses of these ecosystems to ongoing environmental changes. However, the effects of herbivores on plants and ecosystem structure and function vary across the Arctic. Strong spatial variation in herbivore effects implies that the results of individual studies on herbivory depend on local conditions, i.e., their ecological context. An important first step in assessing whether generalizable conclusions can be produced is to identify the existing studies and assess how well they cover the underlying environmental conditions across the Arctic. This systematic map aims to identify the ecological contexts in which herbivore impacts on vegetation have been studied in the Arctic. Specifically, the primary question of the systematic map was: “What evidence exists on the effects of herbivores on Arctic vegetation?”.Methods: We used a published systematic map protocol to identify studies addressing the effects of herbivores on Arctic vegetation. We conducted searches for relevant literature in online databases, search engines and specialist websites. Literature was screened to identify eligible studies, defined as reporting primary data on herbivore impacts on Arctic plants and plant communities. We extracted information on variables that describe the ecological context of the studies, from the studies themselves and from geospatial data. We synthesized the findings narratively and created a Shiny App where the coded data are searchable and variables can be visually explored.Review findings: We identified 309 relevant articles with 662 studies (representing different ecological contexts or datasets within the same article). These studies addressed vertebrate herbivory seven times more often than invertebrate herbivory. Geographically, the largest cluster of studies was in Northern Fennoscandia. Warmer and wetter parts of the Arctic had the largest representation, as did coastal areas and areas where the increase in temperature has been moderate. In contrast, studies spanned the full range of ecological context variables describing Arctic vertebrate herbivore diversity and human population density and impact.Conclusions: The current evidence base might not be sufficient to understand the effects of herbivores on Arctic vegetation throughout the region, as we identified clear biases in the distribution of herbivore studies in the Arctic and a limited evidence base on invertebrate herbivory. In particular, the overrepresentation of studies in areas with moderate increases in temperature prevents robust generalizations about the effects of herbivores under different climatic scenarios.
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| 14. |
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| 15. |
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| 16. |
- Beal, Jacob, et al.
(author)
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Robust estimation of bacterial cell count from optical density
- 2020
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In: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Journal article (peer-reviewed)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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| 17. |
- Béquignon, Olivier J. M., et al.
(author)
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Collaborative SAR Modeling and Prospective In Vitro Validation of Oxidative Stress Activation in Human HepG2 Cells
- 2023
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In: Journal of Chemical Information and Modeling. - : American Chemical Society (ACS). - 1549-9596 .- 1549-960X. ; 63:17, s. 5433-5445
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Journal article (peer-reviewed)abstract
- Oxidative stress is the consequence of an abnormal increase of reactive oxygen species (ROS). ROS are generated mainly during the metabolism in both normal and pathological conditions as well as from exposure to xenobiotics. Xenobiotics can, on the one hand, disrupt molecular machinery involved in redox processes and, on the other hand, reduce the effectiveness of the antioxidant activity. Such dysregulation may lead to oxidative damage when combined with oxidative stress overpassing the cell capacity to detoxify ROS. In this work, a green fluorescent protein (GFP)-tagged nuclear factor erythroid 2-related factor 2 (NRF2)-regulated sulfiredoxin reporter (Srxn1-GFP) was used to measure the antioxidant response of HepG2 cells to a large series of drug and drug-like compounds (2230 compounds). These compounds were then classified as positive or negative depending on cellular response and distributed among different modeling groups to establish structure-activity relationship (SAR) models. A selection of models was used to prospectively predict oxidative stress induced by a new set of compounds subsequently experimentally tested to validate the model predictions. Altogether, this exercise exemplifies the different challenges of developing SAR models of a phenotypic cellular readout, model combination, chemical space selection, and results interpretation.
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| 18. |
- Carlevaro-Fita, J, et al.
(author)
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Cancer LncRNA Census reveals evidence for deep functional conservation of long noncoding RNAs in tumorigenesis
- 2020
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In: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1, s. 56-
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Journal article (peer-reviewed)abstract
- Long non-coding RNAs (lncRNAs) are a growing focus of cancer genomics studies, creating the need for a resource of lncRNAs with validated cancer roles. Furthermore, it remains debated whether mutated lncRNAs can drive tumorigenesis, and whether such functions could be conserved during evolution. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, we introduce the Cancer LncRNA Census (CLC), a compilation of 122 GENCODE lncRNAs with causal roles in cancer phenotypes. In contrast to existing databases, CLC requires strong functional or genetic evidence. CLC genes are enriched amongst driver genes predicted from somatic mutations, and display characteristic genomic features. Strikingly, CLC genes are enriched for driver mutations from unbiased, genome-wide transposon-mutagenesis screens in mice. We identified 10 tumour-causing mutations in orthologues of 8 lncRNAs, including LINC-PINT and NEAT1, but not MALAT1. Thus CLC represents a dataset of high-confidence cancer lncRNAs. Mutagenesis maps are a novel means for identifying deeply-conserved roles of lncRNAs in tumorigenesis.
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| 19. |
- Coll, M., et al.
(author)
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Towards Oxide Electronics: a Roadmap
- 2019
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In: Applied Surface Science. - : Elsevier BV. - 0169-4332 .- 1873-5584. ; 482, s. 1-93
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Journal article (peer-reviewed)abstract
- At the end of a rush lasting over half a century, in which CMOS technology has been experiencing a constant and breathtaking increase of device speed and density, Moore’s law is approaching the insurmountable barrier given by the ultimate atomic nature of matter. A major challenge for 21st century scientists is finding novel strategies, concepts and materials for replacing silicon-based CMOS semiconductor technologies and guaranteeing a continued and steady technological progress in next decades. Among the materials classes candidate to contribute to this momentous challenge, oxide films and heterostructures are a particularly appealing hunting ground. The vastity, intended in pure chemical terms, of this class of compounds, the complexity of their correlated behaviour, and the wealth of functional properties they display, has already made these systems the subject of choice, worldwide, of a strongly networked, dynamic and interdisciplinary research community. Oxide science and technology has been the target of a wide four-year project, named Towards Oxide-Based Electronics (TO-BE), that has been recently running in Europe and has involved as participants several hundred scientists from 29 EU countries. In this review and perspective paper, published as a final deliverable of the TO-BE Action, the opportunities of oxides as future electronic materials for Information and Communication Technologies ICT and Energy are discussed. The paper is organized as a set of contributions, all selected and ordered as individual building blocks of a wider general scheme. After a brief preface by the editors and an introductory contribution, two sections follow. The first is mainly devoted to providing a perspective on the latest theoretical and experimental methods that are employed to investigate oxides and to produce oxide-based films, heterostructures and devices. In the second, all contributions are dedicated to different specific fields of applications of oxide thin films and heterostructures, in sectors as data storage and computing, optics and plasmonics, magnonics, energy conversion and harvesting, and power electronics.
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| 20. |
- Galvan-Valencia, Oscar, et al.
(author)
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Associations of salivary aldosterone levels during pregnancy with maternal blood pressure and birth weight-for-gestational age in a Mexico City birth cohort
- 2024
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In: Journal of Perinatology. - : Springer Nature. - 0743-8346 .- 1476-5543. ; 44:5, s. 643-649
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Journal article (peer-reviewed)abstract
- ObjectiveTo determine associations of maternal salivary aldosterone with blood pressure (BP) in pregnancy and infant birth weight-for-gestational age (BWGA).MethodsWe measured maternal salivary aldosterone, BP and BWGA z-scores in 471 Mexico City pregnancy cohort participants and performed multivariable linear regression of BP and BWGA on log-aldosterone levels.ResultsLog-aldosterone was positively associated with diastolic BP (beta = 0.12 95% CI: 0.04, 0.21). There were no main effects of log-aldosterone on BWGA. However, we detected an interaction between log-aldosterone and BP in association with BWGA; higher log-aldosterone was associated with lower BWGA in the lowest (beta = -0.12, 95% CI: -0.26, 0.02) and highest (beta = -0.12, 95% CI: -0.29, 0.06) BP tertiles. In contrast, in the middle BP tertile the association was positive (beta = 0.09, 95% CI: -0.02, 0.20), p for interaction = 0.03.ConclusionHigher maternal salivary aldosterone is positively associated with diastolic BP and may affect fetal growth differently depending on concurrent maternal blood pressure.
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| 21. |
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| 22. |
- Levin-Schwartz, Yuri, et al.
(author)
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Exosomal miRNAs in urine associated with children's cardiorenal parameters : A cross-sectional study
- 2021
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In: Epigenetics. - : Future Medicine Ltd. - 1559-2294 .- 1559-2308. ; 13:7, s. 499-512
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Journal article (peer-reviewed)abstract
- Aims: The authors sought to examine associations between urinary exosomal miRNAs (exo-miRs), emerging biomarkers of renal health, and cardiorenal outcomes in early childhood. Materials & Methods: The authors extracted exo-miRs in urine from 88 healthy Mexican children aged 4-6 years. The authors measured associations between 193 exo-miRs and cardiorenal outcomes: systolic/diastolic blood pressure, estimated glomerular filtration rate and urinary sodium and potassium levels. The authors adjusted for age, sex, BMI, socioeconomic status, indoor tobacco smoke exposure and urine specific gravity. Results: Multiple exo-miRs were identified meeting a false discovery rate threshold of q < 0.1. Specifically, three exo-miRs had increased expression with urinary sodium, 17 with urinary sodium-to-potassium ratio and one with decreased estimated glomerular filtration rate. Conclusions: These results highlight urinary exo-miRs as early-life biomarkers of children's cardiorenal health.
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| 23. |
- ODonnell, Michael, et al.
(author)
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Registered Replication Report: Dijksterhuis and van Knippenberg (1998)
- 2018
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In: Perspectives on Psychological Science. - : SAGE PUBLICATIONS LTD. - 1745-6916 .- 1745-6924. ; 13:2, s. 268-294
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Journal article (peer-reviewed)abstract
- Dijksterhuis and van Knippenberg (1998) reported that participants primed with a category associated with intelligence (professor) subsequently performed 13% better on a trivia test than participants primed with a category associated with a lack of intelligence (soccer hooligans). In two unpublished replications of this study designed to verify the appropriate testing procedures, Dijksterhuis, van Knippenberg, and Holland observed a smaller difference between conditions (2%-3%) as well as a gender difference: Men showed the effect (9.3% and 7.6%), but women did not (0.3% and -0.3%). The procedure used in those replications served as the basis for this multilab Registered Replication Report. A total of 40 laboratories collected data for this project, and 23 of these laboratories met all inclusion criteria. Here we report the meta-analytic results for those 23 direct replications (total N = 4,493), which tested whether performance on a 30-item general-knowledge trivia task differed between these two priming conditions (results of supplementary analyses of the data from all 40 labs, N = 6,454, are also reported). We observed no overall difference in trivia performance between participants primed with the professor category and those primed with the hooligan category (0.14%) and no moderation by gender.
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| 24. |
- Padilla, P., et al.
(author)
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Glide Symmetry to Prevent the Lowest Stopband of Printed Corrugated Transmission Lines
- 2018
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In: IEEE Microwave and Wireless Components Letters. - : Institute of Electrical and Electronics Engineers Inc.. - 1531-1309 .- 1558-1764. ; 28:9, s. 750-752
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Journal article (peer-reviewed)abstract
- In this letter, we demonstrate that the dispersion properties of printed double-sided parallel-strip lines can be controlled by using glide symmetry. Glide symmetry is introduced in with corrugations in both strips of a double-sided line. We demonstrate that glide symmetry eliminates the stopband between first and second propagating modes and yields to a higher propagation constant, preserving its linearity, and the broadband nature of the underlying guiding technology. Thus, the glide-symmetric double-sided line can be designed to possess a high equivalent refractive index in an ultrawide range of frequencies. These exceptional properties have been numerically and experimentally validated. Finally, we demonstrate the possibilities of this technology with a specific design, a glide-symmetric double-sided parallel-strip line with filtering properties. Potential applications are low-dispersive leaky-wave antennas and electromechanical tunable phase shifters and filters.
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| 25. |
- Perez-Escobar, Oscar A., et al.
(author)
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The origin and speciation of orchids
- 2024
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In: NEW PHYTOLOGIST. - 0028-646X .- 1469-8137. ; 242:2, s. 700-716
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Journal article (peer-reviewed)abstract
- Orchids constitute one of the most spectacular radiations of flowering plants. However, their origin, spread across the globe, and hotspots of speciation remain uncertain due to the lack of an up-to-date phylogeographic analysis. We present a new Orchidaceae phylogeny based on combined high-throughput and Sanger sequencing data, covering all five subfamilies, 17/22 tribes, 40/49 subtribes, 285/736 genera, and c. 7% (1921) of the 29 524 accepted species, and use it to infer geographic range evolution, diversity, and speciation patterns by adding curated geographical distributions from the World Checklist of Vascular Plants. The orchids' most recent common ancestor is inferred to have lived in Late Cretaceous Laurasia. The modern range of Apostasioideae, which comprises two genera with 16 species from India to northern Australia, is interpreted as relictual, similar to that of numerous other groups that went extinct at higher latitudes following the global climate cooling during the Oligocene. Despite their ancient origin, modern orchid species diversity mainly originated over the last 5 Ma, with the highest speciation rates in Panama and Costa Rica. These results alter our understanding of the geographic origin of orchids, previously proposed as Australian, and pinpoint Central America as a region of recent, explosive speciation.
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| 26. |
- Reyna, Matthew A, et al.
(author)
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Pathway and network analysis of more than 2500 whole cancer genomes
- 2020
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11
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Journal article (peer-reviewed)abstract
- The catalog of cancer driver mutations in protein-coding genes has greatly expanded in the past decade. However, non-coding cancer driver mutations are less well-characterized and only a handful of recurrent non-coding mutations, most notably TERT promoter mutations, have been reported. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2658 cancer across 38 tumor types, we perform multi-faceted pathway and network analyses of non-coding mutations across 2583 whole cancer genomes from 27 tumor types compiled by the ICGC/TCGA PCAWG project that was motivated by the success of pathway and network analyses in prioritizing rare mutations in protein-coding genes. While few non-coding genomic elements are recurrently mutated in this cohort, we identify 93 genes harboring non-coding mutations that cluster into several modules of interacting proteins. Among these are promoter mutations associated with reduced mRNA expression in TP53, TLE4, and TCF4. We find that biological processes had variable proportions of coding and non-coding mutations, with chromatin remodeling and proliferation pathways altered primarily by coding mutations, while developmental pathways, including Wnt and Notch, altered by both coding and non-coding mutations. RNA splicing is primarily altered by non-coding mutations in this cohort, and samples containing non-coding mutations in well-known RNA splicing factors exhibit similar gene expression signatures as samples with coding mutations in these genes. These analyses contribute a new repertoire of possible cancer genes and mechanisms that are altered by non-coding mutations and offer insights into additional cancer vulnerabilities that can be investigated for potential therapeutic treatments.
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| 27. |
- Rosa, M. J., et al.
(author)
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Identifying critical windows of prenatal particulate matter (PM2.5) exposure and early childhood blood pressure
- 2020
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In: Environmental Research. - : Elsevier. - 0013-9351 .- 1096-0953. ; 182
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Journal article (peer-reviewed)abstract
- Background: Exposure to air pollution is associated with increased blood pressure (BP) in adults and children. Some evidence suggests that air pollution exposure during the prenatal period may contribute to adverse cardiorenal health later in life. Here we apply a distributed lag model (DLM) approach to identify critical windows that may underlie the association between prenatal particulate matter ≤ 2.5 μm in diameter (PM2.5) exposure and children's BP at ages 4–6 years. Methods: Participants included 537 mother-child dyads enrolled in the Programming Research in Obesity, GRowth Environment, and Social Stress (PROGRESS) longitudinal birth cohort study based in Mexico City. Prenatal daily PM2.5 exposure was estimated using a validated satellite-based spatio-temporal model and BP was measured using the automated Spacelabs system with a sized cuff. We used distributed lag models (DLMs) to examine associations between daily PM2.5 exposure and systolic and diastolic BP (SBP and DBP), adjusting for child's age, sex and BMI, as well as maternal education, preeclampsia and indoor smoking report during the second and third trimester, seasonality and average postnatal year 1 PM2.5 exposure. Results: We found that PM2.5 exposure between weeks 11–32 of gestation (days 80–226) was significantly associated with children's increased SBP. Similarly, PM2.5 exposure between weeks 9–25 of gestation (days 63–176) was significantly associated with increased DBP. To place this into context, a constant 10 μg/m3 increase in PM2.5 sustained throughout this critical window would predict a cumulative increase of 2.6 mmHg (CI: 0.5, 4.6) in SBP and 0.88 mmHg (CI: 0.1, 1.6) in DBP at ages 4–6 years. In a stratified analysis by sex, this association persisted in boys but not in girls. Conclusions: Second and third trimester PM2.5 exposure may increase children's BP in early life. Further work investigating PM2.5 exposure with BP trajectories later in childhood will be important to understanding cardiorenal trajectories that may predict adult disease. Our results underscore the importance of reducing air pollution exposure among susceptible populations, including pregnant women.
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| 28. |
- Thielke, M. W., et al.
(author)
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Full Lignin-Derived Electrospun Carbon Materials as Electrodes for Supercapacitors
- 2022
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In: Frontiers in Materials. - : Frontiers Media S.A.. - 2296-8016. ; 9
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Journal article (peer-reviewed)abstract
- In the search for more sustainable energy storage devices, biomass-derived materials have been widely researched as carbon source for electrode applications. Here we present the processing of high molecular lignin, an abundant carbon rich biopolymer and byproduct of the pulp and paper industry, into freestanding nonwoven carbon fiber (CNFs) electrodes by using electrospinning. It is worth mentioning that no petrol-derived polymers that are usually included in the electrospinning of lignin, were employed in this work, making these electrodes more sustainable than common lignin-derived carbon electrodes. The effect of the carbonization temperature and oxygen plasma treatment in the electrochemical performance of the CNFs as electrodes for supercapacitors was studied. The upscaling of the processing of lignin into carbon electrodes was also explored by comparing a standard electrospinning set up with a needleless electrospinning equipment that enabled faster and higher throughput. The electrochemical performance of the CNFs increased after plasma treatment of the surface and the electrodes prepared using the standard set up exhibited the highest activity, achieving specific capacitances of up to 103.6 F g−1. Copyright © 2022 Thielke, Lopez Guzman, Victoria Tafoya, García Tamayo, Castro Herazo, Hosseinaei and Sobrido.
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