SwePub
Sök i SwePub databas

  Extended search

Träfflista för sökning "WFRF:(Veronika R) "

Search: WFRF:(Veronika R)

  • Result 1-50 of 70
Sort/group result
   
EnumerationReferenceCoverFind
1.
  •  
2.
  •  
3.
  • Kattge, Jens, et al. (author)
  • TRY plant trait database - enhanced coverage and open access
  • 2020
  • In: Global Change Biology. - : Wiley-Blackwell. - 1354-1013 .- 1365-2486. ; 26:1, s. 119-188
  • Journal article (peer-reviewed)abstract
    • Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.
  •  
4.
  • Huyghe, Jeroen R, et al. (author)
  • Genetic architectures of proximal and distal colorectal cancer are partly distinct
  • 2021
  • In: Gut. - : BMJ Publishing Group Ltd. - 0017-5749 .- 1468-3288. ; 70:7, s. 1325-1334
  • Journal article (peer-reviewed)abstract
    • Objective: An understanding of the etiologic heterogeneity of colorectal cancer (CRC) is critical for improving precision prevention, including individualized screening recommendations and the discovery of novel drug targets and repurposable drug candidates for chemoprevention. Known differences in molecular characteristics and environmental risk factors among tumors arising in different locations of the colorectum suggest partly distinct mechanisms of carcinogenesis. The extent to which the contribution of inherited genetic risk factors for CRC differs by anatomical subsite of the primary tumor has not been examined.Design: To identify new anatomical subsite-specific risk loci, we performed genome-wide association study (GWAS) meta-analyses including data of 48 214 CRC cases and 64 159 controls of European ancestry. We characterised effect heterogeneity at CRC risk loci using multinomial modelling.Results: We identified 13 loci that reached genome-wide significance (p<5×10-8) and that were not reported by previous GWASs for overall CRC risk. Multiple lines of evidence support candidate genes at several of these loci. We detected substantial heterogeneity between anatomical subsites. Just over half (61) of 109 known and new risk variants showed no evidence for heterogeneity. In contrast, 22 variants showed association with distal CRC (including rectal cancer), but no evidence for association or an attenuated association with proximal CRC. For two loci, there was strong evidence for effects confined to proximal colon cancer.Conclusion: Genetic architectures of proximal and distal CRC are partly distinct. Studies of risk factors and mechanisms of carcinogenesis, and precision prevention strategies should take into consideration the anatomical subsite of the tumour.
  •  
5.
  • Huyghe, Jeroen R., et al. (author)
  • Discovery of common and rare genetic risk variants for colorectal cancer
  • 2019
  • In: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:1, s. 76-
  • Journal article (peer-reviewed)abstract
    • To further dissect the genetic architecture of colorectal cancer (CRC), we performed whole-genome sequencing of 1,439 cases and 720 controls, imputed discovered sequence variants and Haplotype Reference Consortium panel variants into genome-wide association study data, and tested for association in 34,869 cases and 29,051 controls. Findings were followed up in an additional 23,262 cases and 38,296 controls. We discovered a strongly protective 0.3% frequency variant signal at CHD1. In a combined meta-analysis of 125,478 individuals, we identified 40 new independent signals at P < 5 x 10(-8), bringing the number of known independent signals for CRC to similar to 100. New signals implicate lower-frequency variants, Kruppel-like factors, Hedgehog signaling, Hippo-YAP signaling, long noncoding RNAs and somatic drivers, and support a role for immune function. Heritability analyses suggest that CRC risk is highly polygenic, and larger, more comprehensive studies enabling rare variant analysis will improve understanding of biology underlying this risk and influence personalized screening strategies and drug development.
  •  
6.
  • Thomas, Minta, et al. (author)
  • Combining Asian and European genome-wide association studies of colorectal cancer improves risk prediction across racial and ethnic populations
  • 2023
  • In: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
  • Journal article (peer-reviewed)abstract
    • Polygenic risk scores (PRS) have great potential to guide precision colorectal cancer (CRC) prevention by identifying those at higher risk to undertake targeted screening. However, current PRS using European ancestry data have sub-optimal performance in non-European ancestry populations, limiting their utility among these populations. Towards addressing this deficiency, we expand PRS development for CRC by incorporating Asian ancestry data (21,731 cases; 47,444 controls) into European ancestry training datasets (78,473 cases; 107,143 controls). The AUC estimates (95% CI) of PRS are 0.63(0.62-0.64), 0.59(0.57-0.61), 0.62(0.60-0.63), and 0.65(0.63-0.66) in independent datasets including 1681-3651 cases and 8696-115,105 controls of Asian, Black/African American, Latinx/Hispanic, and non-Hispanic White, respectively. They are significantly better than the European-centric PRS in all four major US racial and ethnic groups (p-values < 0.05). Further inclusion of non-European ancestry populations, especially Black/African American and Latinx/Hispanic, is needed to improve the risk prediction and enhance equity in applying PRS in clinical practice.
  •  
7.
  • Chen, Zhishan, et al. (author)
  • Fine-mapping analysis including over 254 000 East Asian and European descendants identifies 136 putative colorectal cancer susceptibility genes
  • 2024
  • In: Nature Communications. - : Springer Nature. - 2041-1723. ; 15:1
  • Journal article (peer-reviewed)abstract
    • Genome-wide association studies (GWAS) have identified more than 200 common genetic variants independently associated with colorectal cancer (CRC) risk, but the causal variants and target genes are mostly unknown. We sought to fine-map all known CRC risk loci using GWAS data from 100,204 cases and 154,587 controls of East Asian and European ancestry. Our stepwise conditional analyses revealed 238 independent association signals of CRC risk, each with a set of credible causal variants (CCVs), of which 28 signals had a single CCV. Our cis-eQTL/mQTL and colocalization analyses using colorectal tissue-specific transcriptome and methylome data separately from 1299 and 321 individuals, along with functional genomic investigation, uncovered 136 putative CRC susceptibility genes, including 56 genes not previously reported. Analyses of single-cell RNA-seq data from colorectal tissues revealed 17 putative CRC susceptibility genes with distinct expression patterns in specific cell types. Analyses of whole exome sequencing data provided additional support for several target genes identified in this study as CRC susceptibility genes. Enrichment analyses of the 136 genes uncover pathways not previously linked to CRC risk. Our study substantially expanded association signals for CRC and provided additional insight into the biological mechanisms underlying CRC development.
  •  
8.
  • Lehtipalo, Katrianne, et al. (author)
  • Multicomponent new particle formation from sulfuric acid, ammonia, and biogenic vapors
  • 2018
  • In: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 4:12
  • Journal article (peer-reviewed)abstract
    • A major fraction of atmospheric aerosol particles, which affect both air quality and climate, form from gaseous precursors in the atmosphere. Highly oxygenated organic molecules (HOMs), formed by oxidation of biogenic volatile organic compounds, are known to participate in particle formation and growth. However, it is not well understood how they interact with atmospheric pollutants, such as nitrogen oxides (NOx) and sulfur oxides (SOx) from fossil fuel combustion, as well as ammonia (NH3) from livestock and fertilizers. Here, we show how NOx suppresses particle formation, while HOMs, sulfuric acid, and NH3 have a synergistic enhancing effect on particle formation. We postulate a novel mechanism, involving HOMs, sulfuric acid, and ammonia, which is able to closely reproduce observations of particle formation and growth in daytime boreal forest and similar environments. The findings elucidate the complex interactions between biogenic and anthropogenic vapors in the atmospheric aerosol system.
  •  
9.
  • Parma, Valentina, et al. (author)
  • More Than Smell—COVID-19 Is Associated With Severe Impairment of Smell, Taste, and Chemesthesis
  • 2020
  • In: Chemical Senses. - : Oxford University Press (OUP). - 0379-864X .- 1464-3553. ; 45:7, s. 609-622
  • Journal article (peer-reviewed)abstract
    • Recent anecdotal and scientific reports have provided evidence of a link between COVID-19 and chemosensory impairments, such as anosmia. However, these reports have downplayed or failed to distinguish potential effects on taste, ignored chemesthesis, and generally lacked quantitative measurements. Here, we report the development, implementation, and initial results of a multilingual, international questionnaire to assess self-reported quantity and quality of perception in 3 distinct chemosensory modalities (smell, taste, and chemesthesis) before and during COVID-19. In the first 11 days after questionnaire launch, 4039 participants (2913 women, 1118 men, and 8 others, aged 19–79) reported a COVID-19 diagnosis either via laboratory tests or clinical assessment. Importantly, smell, taste, and chemesthetic function were each significantly reduced compared to their status before the disease. Difference scores (maximum possible change ±100) revealed a mean reduction of smell (−79.7 ± 28.7, mean ± standard deviation), taste (−69.0 ± 32.6), and chemesthetic (−37.3 ± 36.2) function during COVID-19. Qualitative changes in olfactory ability (parosmia and phantosmia) were relatively rare and correlated with smell loss. Importantly, perceived nasal obstruction did not account for smell loss. Furthermore, chemosensory impairments were similar between participants in the laboratory test and clinical assessment groups. These results show that COVID-19-associated chemosensory impairment is not limited to smell but also affects taste and chemesthesis. The multimodal impact of COVID-19 and the lack of perceived nasal obstruction suggest that severe acute respiratory syndrome coronavirus strain 2 (SARS-CoV-2) infection may disrupt sensory-neural mechanisms.
  •  
10.
  • Rogelj, Joeri, et al. (author)
  • Mitigation pathways compatible with 1.5°C in the context of sustainable development
  • 2018
  • In: Global Warming of 1.5°C. An IPCC Special Report on the impacts of global warming of 1.5°C above pre-industrial levels and related global greenhouse gas emission pathways, in the context of strengthening the global response to the threat of climate change, sustainable development, and efforts to eradicate poverty. ; , s. 93-174
  • Book chapter (peer-reviewed)
  •  
11.
  • Thomas, Minta, et al. (author)
  • Genome-wide Modeling of Polygenic Risk Score in Colorectal Cancer Risk.
  • 2020
  • In: American Journal of Human Genetics. - Cambridge : Elsevier BV. - 0002-9297 .- 1537-6605. ; 107:3, s. 432-444
  • Journal article (peer-reviewed)abstract
    • Accurate colorectal cancer (CRC) risk prediction models are critical for identifying individuals at low and high risk of developing CRC, as they can then be offered targeted screening and interventions to address their risks of developing disease (if they are in a high-risk group) and avoid unnecessary screening and interventions (if they are in a low-risk group). As it is likely that thousands of genetic variants contribute to CRC risk, it is clinically important to investigate whether these genetic variants can be used jointly for CRC risk prediction. In this paper, we derived and compared different approaches to generating predictive polygenic risk scores (PRS) from genome-wide association studies (GWASs) including 55,105 CRC-affected case subjects and 65,079 control subjects of European ancestry. We built the PRS in three ways, using (1) 140 previously identified and validated CRC loci; (2) SNP selection based on linkage disequilibrium (LD) clumping followed by machine-learning approaches; and (3) LDpred, a Bayesian approach for genome-wide risk prediction. We tested the PRS in an independent cohort of 101,987 individuals with 1,699 CRC-affected case subjects. The discriminatory accuracy, calculated by the age- and sex-adjusted area under the receiver operating characteristics curve (AUC), was highest for the LDpred-derived PRS (AUC = 0.654) including nearly 1.2 M genetic variants (the proportion of causal genetic variants for CRC assumed to be 0.003), whereas the PRS of the 140 known variants identified from GWASs had the lowest AUC (AUC = 0.629). Based on the LDpred-derived PRS, we are able to identify 30% of individuals without a family history as having risk for CRC similar to those with a family history of CRC, whereas the PRS based on known GWAS variants identified only top 10% as having a similar relative risk. About 90% of these individuals have no family history and would have been considered average risk under current screening guidelines, but might benefit from earlier screening. The developed PRS offers a way for risk-stratified CRC screening and other targeted interventions.
  •  
12.
  • Thomas, Minta, et al. (author)
  • Response to Li and Hopper
  • 2021
  • In: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 108:3, s. 527-529
  • Journal article (peer-reviewed)
  •  
13.
  • Gorski, Mathias, et al. (author)
  • Meta-analysis uncovers genome-wide significant variants for rapid kidney function decline
  • 2021
  • In: Kidney International. - : Elsevier. - 0085-2538 .- 1523-1755. ; 99:4, s. 926-939
  • Journal article (peer-reviewed)abstract
    • Rapid decline of glomerular filtration rate estimated from creatinine (eGFRcrea) is associated with severe clinical endpoints. In contrast to cross-sectionally assessed eGFRcrea, the genetic basis for rapid eGFRcrea decline is largely unknown. To help define this, we meta-analyzed 42 genome-wide association studies from the Chronic Kidney Diseases Genetics Consortium and United Kingdom Biobank to identify genetic loci for rapid eGFRcrea decline. Two definitions of eGFRcrea decline were used: 3 mL/min/1.73m2/year or more ("Rapid3"; encompassing 34,874 cases, 107,090 controls) and eGFRcrea decline 25% or more and eGFRcrea under 60 mL/min/1.73m2 at follow-up among those with eGFRcrea 60 mL/min/1.73m2 or more at baseline ("CKDi25"; encompassing 19,901 cases, 175,244 controls). Seven independent variants were identified across six loci for Rapid3 and/or CKDi25: consisting of five variants at four loci with genome-wide significance (near UMOD-PDILT (2), PRKAG2, WDR72, OR2S2) and two variants among 265 known eGFRcrea variants (near GATM, LARP4B). All these loci were novel for Rapid3 and/or CKDi25 and our bioinformatic follow-up prioritized variants and genes underneath these loci. The OR2S2 locus is novel for any eGFRcrea trait including interesting candidates. For the five genome-wide significant lead variants, we found supporting effects for annual change in blood urea nitrogen or cystatin-based eGFR, but not for GATM or LARP4B. Individuals at high compared to those at low genetic risk (8-14 vs 0-5 adverse alleles) had a 1.20-fold increased risk of acute kidney injury (95% confidence interval 1.08-1.33). Thus, our identified loci for rapid kidney function decline may help prioritize therapeutic targets and identify mechanisms and individuals at risk for sustained deterioration of kidney function.
  •  
14.
  • Guo, Xingyi, et al. (author)
  • Identifying Novel Susceptibility Genes for Colorectal Cancer Risk From a Transcriptome-Wide Association Study of 125,478 Subjects
  • 2020
  • In: Gastroenterology. - : Elsevier. - 0016-5085 .- 1528-0012. ; 160:4, s. 1164-1178
  • Journal article (peer-reviewed)abstract
    • Background and Aims: Susceptibility genes and the underlying mechanisms for the majority of risk loci identified by genome-wide association studies (GWAS) for colorectal cancer (CRC) risk remain largely unknown. We conducted a transcriptome-wide association study (TWAS) to identify putative susceptibility genes.Methods: Gene-expression prediction models were built using transcriptome and genetic data from the 284 normal transverse colon tissues of European descendants from the Genotype-Tissue Expression (GTEx), and model performance was evaluated using data from The Cancer Genome Atlas (n = 355). We applied the gene-expression prediction models and GWAS data to evaluate associations of genetically predicted gene-expression with CRC risk in 58,131 CRC cases and 67,347 controls of European ancestry. Dual-luciferase reporter assays and knockdown experiments in CRC cells and tumor xenografts were conducted.Results: We identified 25 genes associated with CRC risk at a Bonferroni-corrected threshold of P < 9.1 × 10-6, including genes in 4 novel loci, PYGL (14q22.1), RPL28 (19q13.42), CAPN12 (19q13.2), MYH7B (20q11.22), and MAP1L3CA (20q11.22). In 9 known GWAS-identified loci, we uncovered 9 genes that have not been reported previously, whereas 4 genes remained statistically significant after adjusting for the lead risk variant of the locus. Through colocalization analysis in GWAS loci, we additionally identified 12 putative susceptibility genes that were supported by TWAS analysis at P < .01. We showed that risk allele of the lead risk variant rs1741640 affected the promoter activity of CABLES2. Knockdown experiments confirmed that CABLES2 plays a vital role in colorectal carcinogenesis.Conclusions: Our study reveals new putative susceptibility genes and provides new insight into the biological mechanisms underlying CRC development.
  •  
15.
  • Tran, Thao Thanh, et al. (author)
  • Inhibition of the master regulator of Listeria monocytogenes virulence enables bacterial clearance from spacious replication vacuoles in infected macrophages
  • 2022
  • In: PLoS Pathogens. - : Public Library Science. - 1553-7366 .- 1553-7374. ; 18:1
  • Journal article (peer-reviewed)abstract
    • A hallmark of Listeria (L.) monocytogenes pathogenesis is bacterial escape from maturing entry vacuoles, which is required for rapid bacterial replication in the host cell cytoplasm and cell-to-cell spread. The bacterial transcriptional activator PrfA controls expression of key virulence factors that enable exploitation of this intracellular niche. The transcriptional activity of PrfA within infected host cells is controlled by allosteric coactivation. Inhibitory occupation of the coactivator site has been shown to impair PrfA functions, but consequences of PrfA inhibition for L. monocytogenes infection and pathogenesis are unknown. Here we report the crystal structure of PrfA with a small molecule inhibitor occupying the coactivator site at 2.0 Å resolution. Using molecular imaging and infection studies in macrophages, we demonstrate that PrfA inhibition prevents the vacuolar escape of L. monocytogenes and enables extensive bacterial replication inside spacious vacuoles. In contrast to previously described spacious Listeria-containing vacuoles, which have been implicated in supporting chronic infection, PrfA inhibition facilitated progressive clearance of intracellular L. monocytogenes from spacious vacuoles through lysosomal degradation. Thus, inhibitory occupation of the PrfA coactivator site facilitates formation of a transient intravacuolar L. monocytogenes replication niche that licenses macrophages to effectively eliminate intracellular bacteria. Our findings encourage further exploration of PrfA as a potential target for antimicrobials and highlight that intra-vacuolar residence of L. monocytogenes in macrophages is not inevitably tied to bacterial persistence.
  •  
16.
  • Visvanathan, Kala, et al. (author)
  • Circulating vitamin D and breast cancer risk : an international pooling project of 17 cohorts
  • 2023
  • In: European Journal of Epidemiology. - : Springer Science+Business Media B.V.. - 0393-2990 .- 1573-7284. ; 38, s. 11-29
  • Journal article (peer-reviewed)abstract
    • Laboratory and animal research support a protective role for vitamin D in breast carcinogenesis, but epidemiologic studies have been inconclusive. To examine comprehensively the relationship of circulating 25-hydroxyvitamin D [25(OH)D] to subsequent breast cancer incidence, we harmonized and pooled participant-level data from 10 U.S. and 7 European prospective cohorts. Included were 10,484 invasive breast cancer cases and 12,953 matched controls. Median age (interdecile range) was 57 (42–68) years at blood collection and 63 (49–75) years at breast cancer diagnosis. Prediagnostic circulating 25(OH)D was either newly measured using a widely accepted immunoassay and laboratory or, if previously measured by the cohort, calibrated to this assay to permit using a common metric. Study-specific relative risks (RRs) for season-standardized 25(OH)D concentrations were estimated by conditional logistic regression and combined by random-effects models. Circulating 25(OH)D increased from a median of 22.6 nmol/L in consortium-wide decile 1 to 93.2 nmol/L in decile 10. Breast cancer risk in each decile was not statistically significantly different from risk in decile 5 in models adjusted for breast cancer risk factors, and no trend was apparent (P-trend = 0.64). Compared to women with sufficient 25(OH)D based on Institute of Medicine guidelines (50– < 62.5 nmol/L), RRs were not statistically significantly different at either low concentrations (< 20 nmol/L, 3% of controls) or high concentrations (100– < 125 nmol/L, 3% of controls; ≥ 125 nmol/L, 0.7% of controls). RR per 25 nmol/L increase in 25(OH)D was 0.99 [95% confidence intervaI (CI) 0.95–1.03]. Associations remained null across subgroups, including those defined by body mass index, physical activity, latitude, and season of blood collection. Although none of the associations by tumor characteristics reached statistical significance, suggestive inverse associations were seen for distant and triple negative tumors. Circulating 25(OH)D, comparably measured in 17 international cohorts and season-standardized, was not related to subsequent incidence of invasive breast cancer over a broad range in vitamin D status.
  •  
17.
  • Abulaiti, Yiming, et al. (author)
  • Search for strong gravity in multijet final states produced in pp collisions at root s=13 TeV using the ATLAS detector at the LHC
  • 2016
  • In: Journal of High Energy Physics (JHEP). - 1126-6708 .- 1029-8479. ; :3
  • Journal article (peer-reviewed)abstract
    • A search is conducted for new physics in multijet final states using 3.6 inverse femtobarns of data from proton-proton collisions at root s = 13TeV taken at the CERN Large Hadron Collider with the ATLAS detector. Events are selected containing at least three jets with scalar sum of jet transverse momenta (H-T) greater than 1TeV. No excess is seen at large H-T and limits are presented on new physics: models which produce final states containing at least three jets and having cross sections larger than 1.6 fb with H-T > 5.8TeV are excluded. Limits are also given in terms of new physics models of strong gravity that hypothesize additional space-time dimensions.
  •  
18.
  • Akhter, Shirin, et al. (author)
  • Cone-setting in spruce is regulated by conserved elements of the age-dependent flowering pathway
  • 2022
  • In: New Phytologist. - : Wiley. - 0028-646X .- 1469-8137. ; 236:5, s. 1951-1963
  • Journal article (peer-reviewed)abstract
    • Reproductive phase change is well characterized in angiosperm model species, but less studied in gymnosperms. We utilize the early cone-setting acrocona mutant to study reproductive phase change in the conifer Picea abies (Norway spruce), a gymnosperm. The acrocona mutant frequently initiates cone-like structures, called transition shoots, in positions where wild-type P. abies always produces vegetative shoots. We collect acrocona and wild-type samples, and RNA-sequence their messenger RNA (mRNA) and microRNA (miRNA) fractions. We establish gene expression patterns and then use allele-specific transcript assembly to identify mutations in acrocona. We genotype a segregating population of inbred acrocona trees. A member of the SQUAMOSA BINDING PROTEIN-LIKE (SPL) gene family, PaSPL1, is active in reproductive meristems, whereas two putative negative regulators of PaSPL1, miRNA156 and the conifer specific miRNA529, are upregulated in vegetative and transition shoot meristems. We identify a mutation in a putative miRNA156/529 binding site of the acrocona PaSPL1 allele and show that the mutation renders the acrocona allele tolerant to these miRNAs. We show co-segregation between the early cone-setting phenotype and trees homozygous for the acrocona mutation. In conclusion, we demonstrate evolutionary conservation of the age-dependent flowering pathway and involvement of this pathway in regulating reproductive phase change in the conifer P. abies. 
  •  
19.
  • Akhter, Shirin, et al. (author)
  • Transcriptome studies of the early cone-setting acrocona mutant provide evidence for a functional conservation of the age-dependent flowering pathway between angiosperms and gymnosperms.
  • Other publication (other academic/artistic)abstract
    • All seed plants go through a juvenile period before they initiate seed- and pollen-bearing organs and reproduce. Reproductive phase-change is well characterized in angiosperm model species, but much less well described in gymnosperms. Here, we utilize the early cone-setting acrocona mutant to study reproductive phase change in the conifer Picea abies; a representative of the gymnosperm lineage. The acrocona mutant frequently initiates cone-like structures, called transition shoots, in positions where wild-type P. abies always produces vegetative shoots. By sequence analysis of mRNA and microRNA transcripts, we demonstrate that orthologous components of the Age-dependent flowering pathway are active at the time of cone initiation. We show that a member of the SQUAMOSA BINDING PROTEIN-LIKE (SPL) gene family, PaSPL7, is active in reproductive meristems, whereas a putative negative regulator of PaSPL7, microRNA156 is upregulated in vegetative meristem. By allele-specific assembly, we also identify a short nucleotide polymorphism (SNP) in the miRNA156 binding of PaSPL7. By genotyping a segregating population of inbred acrocona trees, we show a clear co-segregation between the early cone-setting phenotype and trees homozygous for the SNP. Hence, the data presented demonstrate evolutionary conservation of the age-dependent flowering pathway and involvement of this pathway in regulating cone-setting in the conifer P. abies.
  •  
20.
  • Anandapadamanaban, Madhanagopal, et al. (author)
  • E3 ubiquitin-protein ligase TRIM21-mediated lysine capture by UBE2E1 reveals substrate-targeting mode of a ubiquitin-conjugating E2
  • 2019
  • In: Journal of Biological Chemistry. - : American Society for Biochemistry and Molecular Biology. - 0021-9258 .- 1083-351X. ; 294:30, s. 11404-11419
  • Journal article (peer-reviewed)abstract
    • The E3 ubiquitin-protein ligase TRIM21, of the RING-containing tripartite motif (TRIM) protein family, is a major autoantigen in autoimmune diseases and a modulator of innate immune signaling. Together with ubiquitin-conjugating enzyme E2 E1 (UBE2E1), TRIM21 acts both as an E3 ligase and as a substrate in autoubiquitination. We here report a 2.82-angstrom crystal structure of the human TRIM21 RING domain in complex with the human E2-conjugating UBE2E1 enzyme, in which a ubiquitin-targeted TRIM21 substrate lysine was captured in the UBE2E1 active site. The structure revealed that the direction of lysine entry is similar to that described for human proliferating cell nuclear antigen (PCNA), a small ubiquitin-like modifier (SUMO)-targeted substrate, and thus differs from the canonical SUMO-targeted substrate entry. In agreement, we found that critical UBE2E1 residues involved in the capture of the TRIM21 substrate lysine are conserved in ubiquitin-conjugating E2s, whereas residues critical for SUMOylation are not conserved. We noted that coordination of the acceptor lysine leads to remodeling of amino acid side-chain interactions between the UBE2E1 active site and the E2-E3 direct interface, including the so-called linchpin residue conserved in RING E3s and required for ubiquitination. The findings of our work support the notion that substrate lysine activation of an E2-E3-connecting allosteric path may trigger catalytic activity and contribute to the understanding of specific lysine targeting by ubiquitin-conjugating E2s.
  •  
21.
  • Bateman, Daniel R., et al. (author)
  • Agitation and impulsivity in mid and late life as possible riskmarkers for incident dementia
  • 2020
  • In: Alzheimer’s & Dementia. - : Elsevier. - 2352-8737. ; 6:1
  • Research review (peer-reviewed)abstract
    • To identify knowledge gaps regarding new-onset agitation and impulsivity prior to onsetof cognitive impairment or dementia the International Society to Advance Alzheimer’sResearch and Treatment Neuropsychiatric Syndromes (NPS) Professional InterestAreaconducted a scoping review. Extending a series of reviews exploring the pre-dementiarisk syndrome Mild Behavioral Impairment (MBI), we focused on late-onset agitationand impulsivity (the MBI impulse dyscontrol domain) and risk of incident cognitivedecline and dementia. This scoping review of agitation and impulsivity pre-dementiasyndromes summarizes the current biomedical literature in terms of epidemiology,diagnosis andmeasurement, neurobiology, neuroimaging, biomarkers, course and prognosis,treatment, and ongoing clinical trials. Validations for pre-dementia scales suchas the MBI Checklist, and incorporation into longitudinal and intervention trials, areneeded to better understand impulse dyscontrol as a risk factor for mild cognitiveimpairment and dementia.
  •  
22.
  • Bátori, Veronika, et al. (author)
  • Ethanol and Protein from Ethanol Plant By-Products Using Edible Fungi Neurospora intermedia and Aspergillus oryzae
  • 2015
  • In: BioMed Research International. - : Hindawi Limited. - 2314-6133 .- 2314-6141. ; 2015:nov23
  • Journal article (peer-reviewed)abstract
    • Feasible biorefineries for production of second-generation ethanol are difficult to establish due to the process complexity. An alternative is to partially include the process in the first-generation plants. Whole stillage, a by-product from dry-mill ethanol processes from grains, is mostly composed of undegraded bran and lignocelluloses can be used as a potential substrate for production of ethanol and feed proteins. Ethanol production and the proteins from the stillage were investigated using the edible fungi Neurospora intermedia and Aspergillus oryzae, respectively. N. intermedia produced 4.7 g/L ethanol from the stillage and increased to 8.7 g/L by adding 1 FPU of cellulase/g suspended solids. Saccharomyces cerevisiae produced 0.4 and 5.1 g/L ethanol, respectively. Under a two-stage cultivation with both fungi, up to 7.6 g/L of ethanol and 5.8 g/L of biomass containing 42% (w/w) crude protein were obtained. Both fungi degraded complex substrates including arabinan, glucan, mannan, and xylan where reductions of 91, 73, 38, and 89% (w/v) were achieved, respectively. The inclusion of the current process can lead to the production of 44,000 m(3) of ethanol (22% improvement), around 12,000 tons of protein-rich biomass for animal feed, and energy savings considering a typical facility producing 200,000 m(3) ethanol/year.
  •  
23.
  • Bátori, Veronika, 1980-, et al. (author)
  • Production of Pectin-Cellulose Biofilms: A New Approach for Citrus Waste Recycling
  • 2017
  • In: International Journal of Polymer Science. - : Hindawi Limited. - 1687-9422 .- 1687-9430. ; 2017, s. 1-9
  • Journal article (peer-reviewed)abstract
    • While citrus waste is abundantly generated, the disposal methods used today remain unsatisfactory: they can be deleterious for ruminants, can cause soil salinity, or are not economically feasible; yet citrus waste consists of various valuable polymers. This paper introduces a novel environmentally safe approach that utilizes citrus waste polymers as a biobased and biodegradable film, for example, for food packaging. Orange waste has been investigated for biofilm production, using the gelling ability of pectin and the strength of cellulosic fibres. A casting method was used to form a film from the previously washed, dried, and milled orange waste. Two film-drying methods, a laboratory oven and an incubator shaker, were compared. FE-SEM images confirmed a smoother film morphology when the incubator shaker was used for drying. The tensile strength of the films was 31.67 ± 4.21 and 34.76 ± 2.64 MPa, respectively, for the oven-dried and incubator-dried films, which is within the range of different commodity plastics. Additionally, biodegradability of the films was confirmed under anaerobic conditions. Films showed an opaque appearance with yellowish colour.
  •  
24.
  • Bátori, Veronika, 1980-, et al. (author)
  • Synthesis and characterization of maleic anhydride-grafted orange waste for potential use in biocomposites
  • 2018
  • In: BioResources. - : BioResources. - 1930-2126. ; 13:3, s. 4986-4997
  • Journal article (peer-reviewed)abstract
    • The purpose of the study was to develop a less hydrophilic, and therefore more useful, material from orange waste produced in large quantities by the food industry. A new derivative of industrial orange waste was synthesized via esterification with maleic anhydride. The reaction was confirmed via Fourier transform infrared spectroscopy (FTIR), and the degree of substitution of the hydroxyl groups was 0.39 ± 0.01, as determined by a back-titration method. A major change in physical structure was confirmed by scanning electron microscopy (SEM). The flake-like structure of orange waste changed to a sponge-like structure after the reaction, which involved an increased volume and a reduced density by approximately 40%. The sponge-like structure was represented as an agglomeration of particles with a low specific surface area of 2.18 m2/g and a mean pore diameter of 10.7 nm. Interestingly, the grafted orange waste seemed to become more hydrophobic, which was confirmed by a contact angle test; however, the material absorbed more water vapor. Thermogravimetric analysis (TGA) confirmed a thermally more uniform, though, less heat-resistant material. This work suggests a possible way of utilizing orange waste via synthesizing a renewable material with possible applications as a filler in biocomposites.
  •  
25.
  • Bátori, Veronika, 1980-, et al. (author)
  • The effect of glycerol, sugar and maleic anhydride on pectin-cellulose biofilms prepared from orange waste
  • 2019
  • In: Polymers. - : MDPI AG. - 2073-4360.
  • Journal article (peer-reviewed)abstract
    • This study was conducted to improve the properties of thin films prepared from orange waste by the solution casting method. The main focus was the elimination of holes in the film structure by establishing better cohesion between the major cellulosic and pectin fractions. For this, a previously developed method was improved first by the addition of sugar to promote pectin gelling, then by the addition of maleic anhydride. Principally, maleic anhydride was introduced to the films to induce cross-linking within the film structure. The effects of concentrations of sugar and glycerol as plasticizers and maleic anhydride as a cross-linking agent on the film characteristics were studied. Maleic anhydride improved the structure, resulting in a uniform film, and morphology studies showed better adhesion between components. However, it did not act as a cross-linking agent, but rather as a compatibilizer. The middle level (0.78%) of maleic anhydride content resulted in the highest tensile strength (26.65 ± 3.20 MPa) at low (7%) glycerol and high (14%) sugar levels and the highest elongation (28.48% ± 4.34%) at high sugar and glycerol levels. To achieve a uniform film surface with no holes present, only the lowest (0.39%) level of maleic anhydride was necessary. 
  •  
26.
  • Bernson, Elin, 1987, et al. (author)
  • Identification of Tissue-Resident Natural Killer and T Lymphocytes with Anti-Tumor Properties in Ascites of Ovarian Cancer Patients
  • 2023
  • In: Cancers. - 2072-6694. ; 15:13
  • Journal article (peer-reviewed)abstract
    • Simple Summary Ovarian cancer is the deadliest among gynecological cancers, and there is a huge demand for new treatments for these patients. Immunotherapy holds great potential in cancer treatment, but has not yet proven successful for the majority of ovarian cancer patients. To better understand the immunological landscape of the disease, we have characterized lymphocytes in patients with high-grade serous ovarian cancer. Natural killer cells and T cells are present in both primary tumors and in the metastasizing environment of ascites, a fluid in the abdominal cavity that is developed in many patients with ovarian cancer. Our data reveal that a large fraction of these natural killer cells and T cells express tissue-resident markers and the inhibitory receptor, NKG2A, and are able to kill ovarian cancer cells. In summary, we report a functional subset of lymphocytes that may be targeted in future immunotherapeutic approaches. Women with ovarian cancer have limited therapy options, with immunotherapy being unsatisfactory for a large group of patients. Tumor cells spread from the ovary or the fallopian tube into the abdominal cavity, which is commonly accompanied with massive ascites production. The ascites represents a unique peritoneal liquid tumor microenvironment with the presence of both tumor and immune cells, including cytotoxic lymphocytes. We characterized lymphocytes in ascites from patients with high-grade serous ovarian cancer. Our data reveal the presence of NK and CD8(+) T lymphocytes expressing CD103 and CD49a, which are markers of tissue residency. Moreover, these cells express high levels of the inhibitory NKG2A receptor, with the highest expression level detected on tissue-resident NK cells. Lymphocytes with these features were also present at the primary tumor site. Functional assays showed that tissue-resident NK cells in ascites are highly responsive towards ovarian tumor cells. Similar results were observed in an in vivo mouse model, in which tissue-resident NK and CD8(+) T cells were detected in the peritoneal fluid upon tumor growth. Together, our data reveal the presence of highly functional lymphocyte populations that may be targeted to improve immunotherapy for patients with ovarian cancer.
  •  
27.
  •  
28.
  • Borutinskaité, Veronika, et al. (author)
  • alpha-Dystrobrevin distribution and association with other proteins in human promyelocytic NB4 cells treated for granulocytic differentiation
  • 2011
  • In: MOLECULAR BIOLOGY REPORTS. - : Springer Science Business Media. - 0301-4851 .- 1573-4978. ; 38:5, s. 3001-3011
  • Journal article (peer-reviewed)abstract
    • Dystrobrevins (DBs) bind directly to dystrophin and are prominent components of the dystrophin-associated protein complex (DAPC) that links the cytoskeleton to the extracellular matrix. They are involved in brain development, synapse formation and plasticity, as well as water and ion homeostasis. However, the role of DB in non-muscular cells is not clear. In this study, we show that different alpha-dystrobrevin isoforms are present in promyelocytic leukemia (NB4) cells. Only the biggest alpha-dystrobrevin isoform (DB-alpha), which can be important for its function, was expressed in the membrane fraction of NB4 cells; the other alpha-DB isoforms were found in the hydrophilic cell fractions. Employing the immunoprecipitation and mass spectrometry, we identified novel alpha-DB-interacting proteins involved in cytoskeleton reorganization (actin, tropomyosin, gelsolin, tubulin) and signal transduction process (stathmin, prohibitin, RIBA) during proliferation and differentiation of NB4 cells. Our results suggest that alpha-DB isoforms play a central role in cytoskeleton reorganization via their multiple interactions with actin and actin-associating proteins and may participate in signal transduction process during NB4 cell granulocytic differentiation via directly and non directly associated proteins.
  •  
29.
  • Braem, Marieke G. M., et al. (author)
  • Multiple Miscarriages Are Associated with the Risk of Ovarian Cancer: Results from the European Prospective Investigation into Cancer and Nutrition
  • 2012
  • In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:5
  • Journal article (peer-reviewed)abstract
    • While the risk of ovarian cancer clearly reduces with each full-term pregnancy, the effect of incomplete pregnancies is unclear. We investigated whether incomplete pregnancies (miscarriages and induced abortions) are associated with risk of epithelial ovarian cancer. This observational study was carried out in female participants of the European Prospective Investigation into Cancer and Nutrition (EPIC). A total of 274,442 women were followed from 1992 until 2010. The baseline questionnaire elicited information on miscarriages and induced abortions, reproductive history, and lifestyle-related factors. During a median follow-up of 11.5 years, 1,035 women were diagnosed with incident epithelial ovarian cancer. Despite the lack of an overall association (ever vs. never), risk of ovarian cancer was higher among women with multiple incomplete pregnancies (HR >= 4vs.0: 1.74, 95% CI: 1.20-2.70; number of cases in this category: n = 23). This association was particularly evident for multiple miscarriages (HR >= 4vs.0: 1.99, 95% CI: 1.06-3.73; number of cases in this category: n = 10), with no significant association for multiple induced abortions (HR >= 4vs.0: 1.46, 95% CI: 0.68-3.14; number of cases in this category: n = 7). Our findings suggest that multiple miscarriages are associated with an increased risk of epithelial ovarian cancer, possibly through a shared cluster of etiological factors or a common underlying pathology. These findings should be interpreted with caution as this is the first study to show this association and given the small number of cases in the highest exposure categories.
  •  
30.
  • Catalano, Calogerina, et al. (author)
  • Epistatic effect of TLR3 and cGAS-STING-IKKε-TBK1-IFN signaling variants on colorectal cancer risk
  • 2020
  • In: Cancer Medicine. - : Wiley. - 2045-7634. ; 9:4, s. 1473-1484
  • Journal article (peer-reviewed)abstract
    • Objective: The TLR3/cGAS-STING-IFN signaling has recently been reported to be disturbed in colorectal cancer due to deregulated expression of the genes involved. Our study aimed to investigate the influence of potential regulatory variants in these genes on the risk of sporadic colorectal cancer (CRC) in a Czech cohort of 1424 CRC patients and 1114 healthy controls. Methods: The variants in the TLR3, CGAS, TMEM173, IKBKE, and TBK1 genes were selected using various online bioinformatic tools, such as UCSC browser, HaploReg, Regulome DB, Gtex Portal, SIFT, PolyPhen2, and miRNA prediction tools. Results: Logistic regression analysis adjusted for age and sex detected a nominal association between CRC risk and three variants, CGAS rs72960018 (OR: 1.68, 95% CI: 1.11-2.53, P-value =.01), CGAS rs9352000 (OR: 2.02, 95% CI: 1.07-3.84, P-value =.03) and TMEM173 rs13153461 (OR: 1.53, 95% CI: 1.03-2.27, P-value =.03). Their cumulative effect revealed a threefold increased CRC risk in carriers of 5-6 risk alleles compared to those with 0-2 risk alleles. Epistatic interactions between these genes and the previously genotyped IFNAR1, IFNAR2, IFNA, IFNB, IFNK, IFNW, IRF3, and IRF7 genes, were computed to test their effect on CRC risk. Overall, we obtained nine pair-wise interactions within and between the CGAS, TMEM173, IKBKE, and TBK1 genes. Two of them remained statistically significant after Bonferroni correction. Additional 52 interactions were observed when IFN variants were added to the analysis. Conclusions: Our data suggest that epistatic interactions and a high number of risk alleles may play an important role in CRC carcinogenesis, offering novel biological understanding for the CRC management.
  •  
31.
  • Catalano, Calogerina, et al. (author)
  • Investigation of single and synergic effects of NLRC5 and PD-L1 variants on the risk of colorectal cancer
  • 2018
  • In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 13:2
  • Journal article (peer-reviewed)abstract
    • Constitutive activation of interferon signaling pathways has been reported in colorectal cancer (CRC), leading to a strong CD8+ T cell response through stimulation of NLRC5 expression. Primed CD8+ T cell expansion, however, may be negatively regulated by PD-L1 expression. Additionally, aberrant PD-L1 expression enables cancer cells to escape the immune attack. Our study aimed to select potential regulatory variants in the NLRC5 and PD-L1 genes by using several online in silico tools, such as UCSC browser, HaploReg, Regulome DB, Gtex Portal, microRNA and transcription factor binding site prediction tools and to investigate their influence on CRC risk in a Czech cohort of 1424 CRC patients and 1114 healthy controls. Logistic regression analysis adjusted for age and gender reported a moderate association between rectal cancer risk and two NLRC5 SNPs, rs1684575 T>G (OR: 1.60, 95% CI: 1.13–2.27, recessive model) and rs3751710 (OR: 0.70, 95% CI: 0.51–0.96, dominant model). Given that a combination of genetic variants, rather than a single polymorphism, may explain better the genetic etiology of CRC, we studied the interplay between the variants within NLRC5, PD-L1 and the previously genotyped IFNGR1 and IFNGR2 variants, to evaluate their involvement in the risk of CRC development. Overall we obtained 18 pairwise interactions within and between the NLRC5 ad PD-L1 genes and 6 more when IFNGR variants were added. Thirteen out of the 24 interactions were below the threshold for the FDR calculated and controlled at an arbitrary level q*<0.10. Furthermore, the interaction IFNGR2 rs1059293 C>T—NLRC5 rs289747 G>A (P<0.0001) remained statistically significant even after Bonferroni correction. Our data suggest that not only a single genetic variant but also an interaction between two or more variants within genes involved in immune regulation may play important roles in the onset of CRC, providing therefore novel biological information, which could eventually improve CRC risk management but also PD-1-based immunotherapy in CRC.
  •  
32.
  • Catalano, Calogerina, et al. (author)
  • Short article : Influence of regulatory NLRC5 variants on colorectal cancer survival and 5-fluorouracil-based chemotherapy
  • 2018
  • In: European Journal of Gastroenterology and Hepatology. - 0954-691X. ; 30:8, s. 838-842
  • Journal article (peer-reviewed)abstract
    • Background NLRC5 is an interferon γ-inducible protein, which plays a role in immune surveillance with a potential influence on cancer survival. Objective We aimed to evaluate the effect of potential regulatory variants in NLRC5 on overall survival and survival after 5-fluorouracil (5-FU)-based therapy of colorectal cancer (CRC) patients. Patients and methods We carried out a case-only study in a Czech population of 589 cases; 232 received 5-FU-based therapy. Eleven variants within NLRC5 were selected using in-silico tools. Associations between polymorphisms and survival were assessed by Cox regression analysis adjusting for age at diagnosis, sex, and TNM stage. Survival curves were derived using the Kaplan-Meier method. Results Two variants showed a significant association with survival. All patients and metastasis-free patients at the time of diagnosis (pM0) who were homozygous carriers of the minor allele of rs27194 had a decreased overall survival (OS all and OS pM0) and event-free survival (EFS pM0) under a recessive model (OS all P=0.003, OS pM0 P=0.005, EFS pM0 P=0.01, respectively). OS was also decreased for all patients and for pM0 patients who carried at least one minor allele of rs289747 (OS all P=0.03 and OS pM0 P=0.003, respectively). Among CRC patients, who underwent a 5-FU-based adjuvant regimen, rs12445252 was associated with OS all, OS pM0 and EFS pM0, according to the dosage of the minor allele T (OS all P=0.0004, OS pM0 P=0.0001, EFS pM0 P=0.008, respectively). Conclusion Our results showed that polymorphisms in NLRC5 may be used as prognostic markers of survival of CRC patients, as well as for survival in response to 5-FU treatment.
  •  
33.
  • Chen, Gongbo, et al. (author)
  • Mortality risk attributable to wildfire-related PM2·5 pollution : a global time series study in 749 locations
  • 2021
  • In: The Lancet Planetary Health. - : Elsevier. - 2542-5196. ; 5:9, s. e579-e587
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Many regions of the world are now facing more frequent and unprecedentedly large wildfires. However, the association between wildfire-related PM2·5 and mortality has not been well characterised. We aimed to comprehensively assess the association between short-term exposure to wildfire-related PM2·5 and mortality across various regions of the world.METHODS: For this time series study, data on daily counts of deaths for all causes, cardiovascular causes, and respiratory causes were collected from 749 cities in 43 countries and regions during 2000-16. Daily concentrations of wildfire-related PM2·5 were estimated using the three-dimensional chemical transport model GEOS-Chem at a 0·25° × 0·25° resolution. The association between wildfire-related PM2·5 exposure and mortality was examined using a quasi-Poisson time series model in each city considering both the current-day and lag effects, and the effect estimates were then pooled using a random-effects meta-analysis. Based on these pooled effect estimates, the population attributable fraction and relative risk (RR) of annual mortality due to acute wildfire-related PM2·5 exposure was calculated.FINDINGS: 65·6 million all-cause deaths, 15·1 million cardiovascular deaths, and 6·8 million respiratory deaths were included in our analyses. The pooled RRs of mortality associated with each 10 μg/m3 increase in the 3-day moving average (lag 0-2 days) of wildfire-related PM2·5 exposure were 1·019 (95% CI 1·016-1·022) for all-cause mortality, 1·017 (1·012-1·021) for cardiovascular mortality, and 1·019 (1·013-1·025) for respiratory mortality. Overall, 0·62% (95% CI 0·48-0·75) of all-cause deaths, 0·55% (0·43-0·67) of cardiovascular deaths, and 0·64% (0·50-0·78) of respiratory deaths were annually attributable to the acute impacts of wildfire-related PM2·5 exposure during the study period.INTERPRETATION: Short-term exposure to wildfire-related PM2·5 was associated with increased risk of mortality. Urgent action is needed to reduce health risks from the increasing wildfires.
  •  
34.
  • Chen, Kai, et al. (author)
  • Ambient carbon monoxide and daily mortality: a global time-series study in 337 cities
  • 2021
  • In: The Lancet Planetary Health. - 2542-5196. ; 5:4, s. e191-e199
  • Journal article (peer-reviewed)abstract
    • Background: Epidemiological evidence on short-term association between ambient carbon monoxide (CO) and mortality is inconclusive and limited to single cities, regions, or countries. Generalisation of results from previous studies is hindered by potential publication bias and different modelling approaches. We therefore assessed the association between short-term exposure to ambient CO and daily mortality in a multicity, multicountry setting. Methods: We collected daily data on air pollution, meteorology, and total mortality from 337 cities in 18 countries or regions, covering various periods from 1979 to 2016. All included cities had at least 2 years of both CO and mortality data. We estimated city-specific associations using confounder-adjusted generalised additive models with a quasi-Poisson distribution, and then pooled the estimates, accounting for their statistical uncertainty, using a random-effects multilevel meta-analytical model. We also assessed the overall shape of the exposure–response curve and evaluated the possibility of a threshold below which health is not affected. Findings: Overall, a 1 mg/m3 increase in the average CO concentration of the previous day was associated with a 0·91% (95% CI 0·32–1·50) increase in daily total mortality. The pooled exposure–response curve showed a continuously elevated mortality risk with increasing CO concentrations, suggesting no threshold. The exposure–response curve was steeper at daily CO levels lower than 1 mg/m3, indicating greater risk of mortality per increment in CO exposure, and persisted at daily concentrations as low as 0·6 mg/m3 or less. The association remained similar after adjustment for ozone but was attenuated after adjustment for particulate matter or sulphur dioxide, or even reduced to null after adjustment for nitrogen dioxide. Interpretation: This international study is by far the largest epidemiological investigation on short-term CO-related mortality. We found significant associations between ambient CO and daily mortality, even at levels well below current air quality guidelines. Further studies are warranted to disentangle its independent effect from other traffic-related pollutants. Funding: EU Horizon 2020, UK Medical Research Council, and Natural Environment Research Council.
  •  
35.
  • Cimenci, Cagla Eren, et al. (author)
  • Combined Methylglyoxal Scavenger and Collagen Hydrogel Therapy Prevents Adverse Remodeling and Improves Cardiac Function Post-Myocardial Infarction
  • 2022
  • In: Advanced Functional Materials. - : WILEY-V C H VERLAG GMBH. - 1616-301X .- 1616-3028. ; 32:1
  • Journal article (peer-reviewed)abstract
    • Methylglyoxal (MG) is a highly reactive dicarbonyl and the main precursor of advanced glycation end-products (AGEs). After myocardial infarction (MI), MG-derived AGEs accumulate in the heart and contribute to adverse remodeling and loss of cardiac function. In this study, the flavonoid fisetin, a dicarbonyl scavenger, is used to reduce the negative effects of MG in the post-MI heart. A fisetin-loaded collagen type I hydrogel (fisetin-HG) is injected intramyocardially in mice at 3 h post-MI, and compared to fisetin-alone, hydrogel-alone, or saline treatment. Fisetin-HG treatment increases the level of glyoxalase-1 (the main MG-metabolizing enzyme), reduces MG-AGE accumulation, and decreases oxidative stress in the MI heart, which is associated with smaller scar size and improved cardiac function. Treatment with fisetin-HG also promotes neovascularization and increases the number of pro-healing macrophages in the infarct area, while reducing the number of pro-inflammatory macrophages. Taken together, the results demonstrate that the fisetin-collagen hydrogel therapy can reduce the accumulation and negative effects of MG post-MI. This therapy may be a promising approach to limit adverse cardiac remodeling, prevent damage, and preserve function of the infarcted heart.
  •  
36.
  • Dahm, Christina C., et al. (author)
  • Fatty acid patterns and risk of prostate cancer in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition
  • 2012
  • In: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165 .- 1938-3207. ; 96:6, s. 1354-1361
  • Journal article (peer-reviewed)abstract
    • Background: Fatty acids in blood may be related to the risk of prostate cancer, but epidemiologic evidence is inconsistent. Blood fatty acids are correlated through shared food sources and common endogenous desaturation and elongation pathways. Studies of individual fatty acids cannot take this into account, but pattern analysis can. Treelet transform (TT) is a novel method that uses data correlation structures to derive sparse factors that explain variation. Objective: The objective was to gain further insight in the association between plasma fatty acids and risk of prostate cancer by applying TT to take data correlations into account. Design: We reanalyzed previously published data from a case-control study of prostate cancer nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. TT was used to derive factors explaining the variation in 26 plasma phospholipid fatty acids of 962 incident prostate cancer cases matched to 1061 controls. Multiple imputation was used to deal with missing data in covariates. ORs of prostate cancer according to factor scores were determined by using multivariable conditional logistic regression. Results: Four simple factors explained 38% of the variation in plasma fatty acids. A high score on a factor reflecting a long-chain n-3 PUFA pattern was associated with greater risk of prostate cancer (OR for highest compared with lowest quintile: 1.36; 95% CI: 0.99, 1.86; P-trend = 0.041). Conclusion: Pattern analyses using TT groupings of correlated fatty acids indicate that intake or metabolism of long-chain n-3 PUFAs may be relevant to prostate cancer etiology. Am J Clin Nutr 2012;96:1354-61.
  •  
37.
  •  
38.
  • Gasparrini, Antonio, et al. (author)
  • Projections of temperature-related excess mortality under climate change scenarios
  • 2017
  • In: The Lancet Planetary Health. - 2542-5196. ; 1:9, s. e360-e367
  • Journal article (peer-reviewed)abstract
    • Background: Climate change can directly affect human health by varying exposure to non-optimal outdoor temperature. However, evidence on this direct impact at a global scale is limited, mainly due to issues in modelling and projecting complex and highly heterogeneous epidemiological relationships across different populations and climates.Methods: We collected observed daily time series of mean temperature and mortality counts for all causes or non-external causes only, in periods ranging from Jan 1, 1984, to Dec 31, 2015, from various locations across the globe through the Multi-Country Multi-City Collaborative Research Network. We estimated temperature-mortality relationships through a two-stage time series design. We generated current and future daily mean temperature series under four scenarios of climate change, determined by varying trajectories of greenhouse gas emissions, using five general circulation models. We projected excess mortality for cold and heat and their net change in 1990-2099 under each scenario of climate change, assuming no adaptation or population changes.Findings: Our dataset comprised 451 locations in 23 countries across nine regions of the world, including 85 879 895 deaths. Results indicate, on average, a net increase in temperature-related excess mortality under high-emission scenarios, although with important geographical differences. In temperate areas such as northern Europe, east Asia, and Australia, the less intense warming and large decrease in cold-related excess would induce a null or marginally negative net effect, with the net change in 2090-99 compared with 2010-19 ranging from -1·2% (empirical 95% CI -3·6 to 1·4) in Australia to -0·1% (-2·1 to 1·6) in east Asia under the highest emission scenario, although the decreasing trends would reverse during the course of the century. Conversely, warmer regions, such as the central and southern parts of America or Europe, and especially southeast Asia, would experience a sharp surge in heat-related impacts and extremely large net increases, with the net change at the end of the century ranging from 3·0% (-3·0 to 9·3) in Central America to 12·7% (-4·7 to 28·1) in southeast Asia under the highest emission scenario. Most of the health effects directly due to temperature increase could be avoided under scenarios involving mitigation strategies to limit emissions and further warming of the planet.Interpretation: This study shows the negative health impacts of climate change that, under high-emission scenarios, would disproportionately affect warmer and poorer regions of the world. Comparison with lower emission scenarios emphasises the importance of mitigation policies for limiting global warming and reducing the associated health risks.
  •  
39.
  • Golubinskaya, Veronika, 1974, et al. (author)
  • Bestrophin-3 Expression in a Subpopulation of Astrocytes in the Neonatal Brain After Hypoxic-Ischemic Injury
  • 2019
  • In: Frontiers in Physiology. - : Frontiers Media SA. - 1664-042X. ; 10
  • Journal article (peer-reviewed)abstract
    • Bestrophin-3, a potential candidate for a calcium-activated chloride channel, recently was suggested to have cell-protective functions. We studied the expression and alternative splicing of bestrophin-3 in neonatal mouse brain and after hypoxic-ischemic (HI) injury and in human neonatal brain samples. HI brain injury was induced in 9-day old mice by unilateral permanent common carotid artery occlusion in combination with exposure to 10% oxygen for 50 min. Endoplasmic reticulum stress was induced by thapsigargin treatment in primary culture of mouse brain astrocytes. We also investigated expression of bestrophin-3 protein in a sample of human neonatal brain tissue. Bestrophin-3 protein expression was detected with immunohistochemical methods and western blot; mRNA expression and splicing were analyzed by RT-PCR. HI induced a brain tissue infarct and a pronounced increase in the endoplasmic reticulum-associated marker CHOP. Three days after HI a population of astrocytes co-expressed bestrophin-3 and nestin in a penumbra-like area of the injured hemisphere. However, total levels of Bestrophin-3 protein in mouse cortex were reduced after injury. Mouse astrocytes in primary culture also expressed bestrophin-3 protein, the amount of which was reduced by endoplasmic reticulum stress. Bestrophin-3 protein was detected in astrocytes in the hippocampal region of the human neonatal brain which had patchy white matter gliosis and neuronal loss in the Sommer's sector of the Ammon's horn (CA1). Analysis of bestrophin-3 mRNA in mouse brain with and without injury showed the presence of two truncated spliced variants, but no full-length mRNA. Total amount of bestrophin-3 mRNA increased after HI, but showed only minor injury-related change. However, the splice variants of bestrophin-3 mRNA were differentially regulated after HI depending on the presence of tissue injury. Our results show that bestrophin-3 is expressed in neonatal mouse brain after injury and in the human neonatal brain with pathology. In mouse brain bestrophin-3 protein is upregulated in a specific astrocyte population after injury and is co-expressed with nestin. Splice variants of bestrophin-3 mRNA respond differently to HI, which might indicate their different roles in tissue injury.
  •  
40.
  • Gomez, Alberto, et al. (author)
  • Mechanically Powered Motion Imaging Phantoms: Proof of Concept
  • 2019
  • In: 2019 41ST ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY (EMBC). - : IEEE. - 9781538613115 - 9781538613122 ; , s. 2723-2726
  • Conference paper (peer-reviewed)abstract
    • Motion imaging phantoms are expensive, bulky and difficult to transport and set-up. The purpose of this paper is to demonstrate a simple approach to the design of multi-modality motion imaging phantoms that use mechanically stored energy to produce motion. We propose two phantom designs that use mainsprings and elastic bands to store energy. A rectangular piece was attached to an axle at the end of the transmission chain of each phantom, and underwent a rotary motion upon release of the mechanical motor. The phantoms were imaged with MRI and US, and the image sequences were embedded in a 1D non linear manifold (Laplacian Eigenmap) and the spectrogram of the embedding was used to derive the angular velocity over time. The derived velocities were consistent and reproducible within a small error. The proposed motion phantom concept showed great potential for the construction of simple and affordable motion phantoms.
  •  
41.
  • Grote, Verena A., et al. (author)
  • The associations of advanced glycation end products and its soluble receptor with pancreatic cancer risk: A case-control study within the prospective EPIC cohort
  • 2012
  • In: Cancer Epidemiology Biomarkers and Prevention. - 1055-9965 .- 1538-7755. ; 21:4, s. 619-628
  • Journal article (peer-reviewed)abstract
    • Background: Advanced glycation end products (AGE) and their receptors (RAGE) have been implicated in cancer development through their proinflammatory capabilities. However, prospective data on their association with cancer of specific sites, including pancreatic cancer, are limited. Methods: Prediagnostic blood levels of the AGE product Nε-(carboxymethyl)lysine (CML) and the endogenous secreted receptor for AGE (esRAGE) were measured using ELISA in 454 patients with exocrine pancreatic cancer and individually matched controls within the European Prospective Investigation into Cancer and Nutrition (EPIC). Pancreatic cancer risk was estimated by calculating ORs with corresponding 95% confidence intervals (CI). Results: Elevated CML levels tended to be associated with a reduction in pancreatic cancer risk [OR = 0.57 (95% CI, 0.32-1.01) comparing highest with lowest quintile), whereas no association was observed for esRAGE (OR = 0.98; 95% CI, 0.62-1.54). Adjustments for body mass index and smoking attenuated the inverse associations of CML with pancreatic cancer risk (OR = 0.78; 95% CI, 0.41-1.49). There was an inverse association between esRAGE and risk of pancreatic cancer for cases that were diagnosed within the first 2 years of follow-up [OR = 0.46 (95% CI, 0.22-0.96) for a doubling in concentration], whereas there was no association among those with a longer follow-up (OR = 1.11; 95% CI, 0.88-1.39; P interaction = 0.002). Conclusions and Impact: Our results do not provide evidence for an association of higher CML or lower esRAGE levels with risk of pancreatic cancer. The role of AGE/RAGE in pancreatic cancer would benefit from further investigations. ©2012 AACR.
  •  
42.
  • Huhn, Stefanie, et al. (author)
  • Coding variants in NOD-like receptors : An association study on risk and survival of colorectal cancer
  • 2018
  • In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 13:6
  • Journal article (peer-reviewed)abstract
    • Nod-like receptors (NLRs) are important innate pattern recognition receptors and regulators of inflammation or play a role during development. We systematically analysed 41 non-synonymous single nucleotide polymorphisms (SNPs) in 21 NLR genes in a Czech discovery cohort of sporadic colorectal cancer (CRC) (1237 cases, 787 controls) for their association with CRC risk and survival. Five SNPs were found to be associated with CRC risk and eight with survival at 5% significance level. In a replication analysis using data of two large genome-wide association studies (GWASs) from Germany (DACHS: 1798 cases and 1810 controls) and Scotland (2210 cases and 9350 controls) the associations found in the Czech discovery set were not confirmed. However, expression analysis in human gut-related tissues and immune cells revealed that the NLRs associated with CRC risk or survival in the discovery set were expressed in primary human colon or rectum cells, CRC tissue and/or cell lines, providing preliminary evidence for a potential involvement of NLRs in general in CRC development and/or progression. Most interesting was the finding that the enigmatic development-related NLRP5 (also known as MATER) was not expressed in normal colon tissue but in colon cancer tissue and cell lines. Future studies may show whether regulatory variants instead of coding variants might affect the expression of NLRs and contribute to CRC risk and survival.
  •  
43.
  • Janciauskiene, Sabina, et al. (author)
  • Indirect effect of alpha-1-antitrypsin on endotoxin-induced IL-1β secretion from human PBMCs
  • 2022
  • In: Frontiers in Pharmacology. - : Frontiers Media SA. - 1663-9812. ; 13
  • Journal article (peer-reviewed)abstract
    • Human alpha-1-antitrypsin (AAT) encoded by the SERPINA1 gene, is an acute phase glycoprotein that regulates inflammatory responses via both protease inhibitory and non-inhibitory activities. We previously reported that AAT controls ATP-induced IL-1β release from human mononuclear cells by stimulating the release of small bioactive molecules. In the current study, we aimed to elucidate the identity of these putative effectors released from human PBMCs in response to AAT, which may inhibit the LPS-induced release of IL-1β. We pre-incubated human PBMCs alone or with different preparations of AAT (4 mg/ml) for 30 min at 37°C, 5% CO2, and collected cell supernatants filtered through centrifugal filters (cutoff 3 kDa) to eliminate AAT and other high molecular weight substances. Supernatants passed through the filters were used to culture PBMCs isolated from the autologous or a heterologous donors with or without adding LPS (1 μg/ml) for 6 h. Unexpectedly, supernatants from PBMCs pre-incubated with AAT (Zemaira®), but not with other AAT preparations tested or with oxidized AAT (Zemaira®), lowered the LPS-induced release of IL-1β by about 25%–60% without affecting IL1B mRNA. The reversed-phase liquid chromatography coupled with mass spectrometry did not confirm the hypothesis that small pro-resolving lipid mediators released from PBMCs after exposure to AAT (Zemaira®) are responsible for lowering the LPS-induced IL-1β release. Distinctively from other AAT preparations, AAT (Zemaira®) and supernatants from PBMCs pre-treated with this protein contained high levels of total thiols. In line, mass spectrometry analysis revealed that AAT (Zemaira®) protein contains freer Cys232 than AAT (Prolastin®). Our data show that a free Cys232 in AAT is required for controlling LPS-induced IL-1β release from human PBMCs. Further studies characterizing AAT preparations used to treat patients with inherited AAT deficiency remains of clinical importance.
  •  
44.
  • Kirby, Andrew, et al. (author)
  • Mutations causing medullary cystic kidney disease type 1 lie in a large VNTR in MUC1 missed by massively parallel sequencing
  • 2013
  • In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:3, s. 299-303
  • Journal article (peer-reviewed)abstract
    • Although genetic lesions responsible for some mendelian disorders can be rapidly discovered through massively parallel sequencing of whole genomes or exomes, not all diseases readily yield to such efforts. We describe the illustrative case of the simple mendelian disorder medullary cystic kidney disease type 1 (MCKD1), mapped more than a decade ago to a 2-Mb region on chromosome 1. Ultimately, only by cloning, capillary sequencing and de novo assembly did we find that each of six families with MCKD1 harbors an equivalent but apparently independently arising mutation in sequence markedly under-represented in massively parallel sequencing data: the insertion of a single cytosine in one copy (but a different copy in each family) of the repeat unit comprising the extremely long (similar to 1.5-5 kb), GC-rich (>80%) coding variable-number tandem repeat (VNTR) sequence in the MUC1 gene encoding mucin 1. These results provide a cautionary tale about the challenges in identifying the genes responsible for mendelian, let alone more complex, disorders through massively parallel sequencing.
  •  
45.
  • Larsson, Rikard, et al. (author)
  • International growth through cooperation : Brand-driven strategies, leadership, and career development in Sweden.
  • 2003
  • In: Academy of Management Executive. - 0896-3789. ; 17:1, s. 7-21
  • Journal article (peer-reviewed)abstract
    • Corporate growth is often viewed as being either internally generated or externally achieved through mergers and acquisitions (M&As). During the last decade, strategic alliances have become an increasingly popular third alternative to either internal or acquired growth. Alliances can be cheaper, more flexible, and faster than internal or M&A growth. However, they suffer from a major drawback that makes many practitioners wary, namely the difficult issue of sharing control. One of the comparative strengths of Swedish corporate culture is the ability to cooperate laterally through sharing control. Several Swedish multinational corporations such as IKEA and H&M have turned this national trait into a successful strategic growth virtue. In this article, we discuss how some important Swedish organizational, leadership, brand, and career characteristics have been combined into a powerful international growth recipe. The Swedish "growth cocktail" of combining brand-driven, forward, internal growth with resource-saving supplier alliances with minimal loss of control can be deployed by other companies of different nationalities. These complementary forward and backward expansion forms can be enhanced through matching the external brand image and internal brand identity. Pluralistic career management is also essential to sustaining such international growth combinations
  •  
46.
  • Lazaryan, Aleksandr, et al. (author)
  • Impact of cytogenetic abnormalities on outcomes of adult Philadelphia-negative acute lymphoblastic leukemia after allogeneic hematopoietic stem cell transplantation : a study by the Acute Leukemia Working Committee of the Center for International Blood and Marrow Transplant Research
  • 2020
  • In: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 0390-6078 .- 1592-8721. ; 105:5, s. 1329-1338
  • Journal article (peer-reviewed)abstract
    • Cytogenetic risk stratification at diagnosis has long been one of the most useful tools to assess prognosis in acute lymphoblastic leukemia (ALL). To examine the prognostic impact of cytogenetic abnormalities on outcomes after allogeneic hematopoietic cell transplantation, we studied 1731 adults with Philadelphia-negative ALL in complete remission who underwent myeloablative or reduced intensity/non-myeloablative conditioning transplant from unrelated or matched sibling donors reported to the Center for International Blood and Marrow Transplant Research. A total of 632 patients had abnormal conventional metaphase cytogenetics. The leukemia-free survival and overall survival rates at 5 years after transplantation in patients with abnormal cytogenetics were 40% and 42%, respectively, which were similar to those in patients with a normal karyotype. Of the previously established cytogenetic risk classifications, modified Medical Research Council-Eastern Cooperative Oncology Group score was the only independent prognosticator of leukemia-free survival (P=0.03). In the multivariable analysis, monosomy 7 predicted post-transplant relapse [hazard ratio (HR)=2.11; 95% confidence interval (95% CI): 1.04-4.27] and treatment failure (HR=1.97; 95% CI: 1.20-3.24). Complex karyotype was prognostic for relapse (HR=1.69; 95% CI: 1.06-2.69), whereas t(8;14) predicted treatment failure (HR=2.85; 95% CI: 1.35-6.02) and overall mortality (HR=3.03; 95% CI: 1.44-6.41). This large study suggested a novel transplant-specific cytogenetic scheme with adverse [monosomy 7, complex karyotype, del(7q), t(8;14), t(11;19), del(7q), tetraploidy/near triploidy], intermediate (normal karyotype and all other abnormalities), and favorable (high hyperdiploidy) risks to prognosticate leukemia-free survival (P=0.02). Although some previously established high-risk Philadelphia-negative cytogenetic abnormalities in ALL can be overcome by transplantation, monosomy 7, complex karyotype, and t(8;14) continue to pose significant risks and yield inferior outcomes.
  •  
47.
  • Marks, David I, et al. (author)
  • Unrelated umbilical cord blood transplant for adult acute lymphoblastic leukemia in first and second complete remission : a comparison with allografts from adult unrelated donors.
  • 2014
  • In: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 0390-6078 .- 1592-8721. ; 99:2, s. 322-8
  • Journal article (peer-reviewed)abstract
    • Allogeneic hematopoietic cell transplantation has an established role in the treatment of adults with acute lymphoblastic leukemia whose survival when recipients of grafts from adult unrelated donors approaches that of recipients of grafts from sibling donors. Our aim was to determine the role of mismatched unrelated cord blood grafts in transplantation for 802 adults with acute lymphoblastic leukemia in first or second complete remission. Using Cox regression we compared outcomes after 116 mismatched single or double cord blood transplants, 546 peripheral blood progenitor cell transplants and 140 bone marrow transplants. The characteristics of the recipients and their diseases were similar except cord blood recipients were younger, more likely to be non-Caucasians and more likely to have a low white blood cell count at diagnosis. There were differences in donor-recipient human leukocyte antigen-match depending on the source of the graft. Most adult donor transplants were matched at the allele-level considering human leukocyte antigens-A, -B, -C and -DRB1. In contrast, most cord blood transplants were mismatched and considered antigen-level matching; 57% were mismatched at two loci and 29% at one locus whereas only 29% of adult donor transplants were mismatched at one locus and none at two loci. There were no differences in the 3-year probabilities of survival between recipients of cord blood (44%), matched adult donor (44%) and mismatched adult donor (43%) transplants. Cord blood transplants engrafted slower and were associated with less grade 2-4 acute but similar chronic graft-versus-host disease, relapse, and transplant-related mortality. The survival of cord blood graft recipients was similar to that of recipients of matched or mismatched unrelated adult donor grafts and so cord blood should be considered a valid alternative source of stem cells for adults with acute lymphoblastic leukemia in the absence of a matched unrelated adult donor.
  •  
48.
  • Mayer, Ludovic, et al. (author)
  • Widespread Pesticide Distribution in the European Atmosphere Questions their Degradability in Air
  • 2024
  • In: Environmental Science and Technology. - 0013-936X. ; 58:7, s. 3342-3352
  • Journal article (peer-reviewed)abstract
    • Risk assessment of pesticide impacts on remote ecosystems makes use of model-estimated degradation in air. Recent studies suggest these degradation rates to be overestimated, questioning current pesticide regulation. Here, we investigated the concentrations of 76 pesticides in Europe at 29 rural, coastal, mountain, and polar sites during the agricultural application season. Overall, 58 pesticides were observed in the European atmosphere. Low spatial variation of 7 pesticides suggests continental-scale atmospheric dispersal. Based on concentrations in free tropospheric air and at Arctic sites, 22 pesticides were identified to be prone to long-range atmospheric transport, which included 15 substances approved for agricultural use in Europe and 7 banned ones. Comparison between concentrations at remote sites and those found at pesticide source areas suggests long atmospheric lifetimes of atrazine, cyprodinil, spiroxamine, tebuconazole, terbuthylazine, and thiacloprid. In general, our findings suggest that atmospheric transport and persistence of pesticides have been underestimated and that their risk assessment needs to be improved.
  •  
49.
  • Metzler, Veronika M., et al. (author)
  • Androgen dependent mechanisms of pro-angiogenic networks in placental and tumor development
  • 2017
  • In: Placenta. - : W B SAUNDERS CO LTD. - 0143-4004 .- 1532-3102. ; 56, s. 79-85
  • Journal article (peer-reviewed)abstract
    • The placenta and tumors share important characteristics, including a requirement to establish effective angiogenesis. In the case of the placenta, optimal angiogenesis is required to sustain the blood flow required to maintain a successful pregnancy, whereas in tumors establishing new blood supplies is considered a key step in supporting metastases. Therefore the development of novel angiogenesis inhibitors has been an area of active research in oncology. A subset of the molecular processes regulating angiogenesis are well understood in the context of both early placentation and tumorigenesis. In this review we focus on the well-established role of androgen regulation of angiogenesis in cancer and relate these mechanisms to placental angiogenesis. The physiological actions of androgens are mediated by the androgen receptor (AR), a ligand dependent transcription factor. Androgens and the AR are essential for normal male embryonic development, puberty and lifelong health. Defects in androgen signalling are associated with a diverse range of clinical disorders in men and women including disorders of sex development (DSD), polycystic ovary syndrome in women and many cancers. We summarize the diverse molecular mechanisms of androgen regulation of angiogenesis and infer the potential significance of these pathways to normal and pathogenic placental function. Finally, we offer potential research applications of androgen-targeting molecules developed to treat cancer as investigative tools to help further delineate the role of androgen signalling in placental function and maternal and offspring health in animal models.
  •  
50.
  • Moiseev, Sergey, et al. (author)
  • Association of venous thromboembolic events with skin, pulmonary and kidney involvement in ANCA-associated vasculitis : A multinational study
  • 2021
  • In: Rheumatology. - : Oxford University Press (OUP). - 1462-0332 .- 1462-0324. ; 60:10, s. 4654-4661
  • Journal article (peer-reviewed)abstract
    • Objective: To investigate the occurrence of venous thromboembolic events (VTE) in a large cohort of patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) across the European Union, Turkey, Russia, UK and North America. Methods: Patients with a definite diagnosis of AAV who were followed for at least 3 months and had sufficient documentation were included. Data on VTE, including either deep vein thrombosis or pulmonary embolism, were collected retrospectively from tertiary vasculitis centres. Univariate and multivariate regression models were used to estimate odds ratios (ORs) and 95% CIs. Results: Over a median follow-up of 63 (interquartile range: 29, 101) months, VTE occurred in 278 (9.7%) of 2869 AAV patients with a similar frequency across different countries (from 6.3% to 13.7%), and AAV subtype [granulomatosis with polyangiitis: 9.8% (95% CI: 8.3, 11.6%); microscopic polyangiitis: 9.6% (95% CI: 7.9, 11.4%); and eosinophilic granulomatosis with polyangiitis: 9.8% (95% CI: 7.0, 13.3%)]. Most VTE (65.6%) were reported in the first-year post-diagnosis. Multiple factor logistic regression analysis adjusted for sex and age showed that skin (OR 1.71, 95% CI: 1.01, 2.92), pulmonary (OR 1.78, 95% CI: 1.04, 3.14) and kidney [eGFR 15-60 ml/min/1.73 m2, OR 2.86 (95% CI: 1.27, 6.47); eGFR <15 ml/min/1.73 m2, OR 6.71 (95% CI: 2.94, 15.33)] involvement were independent variables associated with a higher occurrence of VTE. Conclusion: Two-thirds of VTE occurred during the initial phase of active disease. We confirmed previous findings from smaller studies that a decrease in kidney function, skin involvement and pulmonary disease are independently associated with VTE.
  •  
Skapa referenser, mejla, bekava och länka
  • Result 1-50 of 70
Type of publication
journal article (63)
conference paper (2)
research review (2)
book chapter (2)
other publication (1)
Type of content
peer-reviewed (68)
other academic/artistic (2)
Author/Editor
Vodicka, Pavel (12)
Brenner, Hermann (10)
Chang-Claude, Jenny (9)
Gunter, Marc J. (9)
Hoffmeister, Michael (9)
Murphy, Neil (9)
show more...
Visvanathan, Kala (9)
Wolk, Alicja (8)
Berndt, Sonja I (8)
Giles, Graham G (8)
Bishop, D Timothy (8)
Casey, Graham (8)
Chan, Andrew T. (8)
Gruber, Stephen B. (8)
Gsur, Andrea (8)
Hampel, Heather (8)
Jenkins, Mark A. (8)
Keku, Temitope O. (8)
Li, Li (8)
Moreno, Victor (8)
Newcomb, Polly A. (8)
Platz, Elizabeth A. (8)
Potter, John D. (8)
Sakoda, Lori C. (8)
Schoen, Robert E. (8)
Slattery, Martha L. (8)
Ulrich, Cornelia M. (8)
van Guelpen, Bethany (8)
White, Emily (8)
Woods, Michael O. (8)
Hsu, Li (8)
Peters, Ulrike (8)
Campbell, Peter T. (8)
Lindblom, Annika (8)
Le Marchand, Loïc (8)
Boeing, Heiner (7)
Trichopoulou, Antoni ... (7)
Riboli, Elio (7)
Tangen, Catherine M (7)
Albanes, Demetrius (7)
Buchanan, Daniel D. (7)
Figueiredo, Jane C. (7)
Harrison, Tabitha A. (7)
Huyghe, Jeroen R. (7)
Su, Yu-Ru (7)
Wu, Anna H. (7)
Offit, Kenneth (7)
Pharoah, Paul D. P. (7)
Hayes, Richard B (7)
Bezieau, Stephane (7)
show less...
University
Umeå University (24)
Lund University (21)
Karolinska Institutet (18)
Uppsala University (16)
Stockholm University (8)
Swedish University of Agricultural Sciences (6)
show more...
University of Gothenburg (5)
Linköping University (5)
Kristianstad University College (4)
Jönköping University (4)
University of Borås (4)
Royal Institute of Technology (3)
Örebro University (3)
Karlstad University (1)
show less...
Language
English (70)
Research subject (UKÄ/SCB)
Medical and Health Sciences (44)
Natural sciences (19)
Social Sciences (8)
Engineering and Technology (3)
Agricultural Sciences (1)

Year

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

 
pil uppåt Close

Copy and save the link in order to return to this view