| 1. |
- 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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| 2. |
- Kehoe, Laura, et al.
(author)
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Make EU trade with Brazil sustainable
- 2019
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
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Journal article (other academic/artistic)
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| 3. |
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| 4. |
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| 5. |
- Abelev, Betty, et al.
(author)
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Long-range angular correlations on the near and away side in p-Pb collisions at root S-NN=5.02 TeV
- 2013
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In: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 719:1-3, s. 29-41
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Journal article (peer-reviewed)abstract
- Angular correlations between charged trigger and associated particles are measured by the ALICE detector in p-Pb collisions at a nucleon-nucleon centre-of-mass energy of 5.02 TeV for transverse momentum ranges within 0.5 < P-T,P-assoc < P-T,P-trig < 4 GeV/c. The correlations are measured over two units of pseudorapidity and full azimuthal angle in different intervals of event multiplicity, and expressed as associated yield per trigger particle. Two long-range ridge-like structures, one on the near side and one on the away side, are observed when the per-trigger yield obtained in low-multiplicity events is subtracted from the one in high-multiplicity events. The excess on the near-side is qualitatively similar to that recently reported by the CMS Collaboration, while the excess on the away-side is reported for the first time. The two-ridge structure projected onto azimuthal angle is quantified with the second and third Fourier coefficients as well as by near-side and away-side yields and widths. The yields on the near side and on the away side are equal within the uncertainties for all studied event multiplicity and p(T) bins, and the widths show no significant evolution with event multiplicity or p(T). These findings suggest that the near-side ridge is accompanied by an essentially identical away-side ridge. (c) 2013 CERN. Published by Elsevier B.V. All rights reserved.
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| 6. |
- Abelev, Betty, et al.
(author)
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Measurement of prompt J/psi and beauty hadron production cross sections at mid-rapidity in pp collisions at root s=7 TeV
- 2012
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In: Journal of High Energy Physics. - 1029-8479. ; :11
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Journal article (peer-reviewed)abstract
- The ALICE experiment at the LHC has studied J/psi production at mid-rapidity in pp collisions at root s = 7 TeV through its electron pair decay on a data sample corresponding to an integrated luminosity L-int = 5.6 nb(-1). The fraction of J/psi from the decay of long-lived beauty hadrons was determined for J/psi candidates with transverse momentum p(t) > 1,3 GeV/c and rapidity vertical bar y vertical bar < 0.9. The cross section for prompt J/psi mesons, i.e. directly produced J/psi and prompt decays of heavier charmonium states such as the psi(2S) and chi(c) resonances, is sigma(prompt J/psi) (p(t) > 1.3 GeV/c, vertical bar y vertical bar < 0.9) = 8.3 +/- 0.8(stat.) +/- 1.1 (syst.)(-1.4)(+1.5) (syst. pol.) mu b. The cross section for the production of b-hadrons decaying to J/psi with p(t) > 1.3 GeV/c and vertical bar y vertical bar < 0.9 is a sigma(J/psi <- hB) (p(t) > 1.3 GeV/c, vertical bar y vertical bar < 0.9) = 1.46 +/- 0.38 (stat.)(-0.32)(+0.26) (syst.) mu b. The results are compared to QCD model predictions. The shape of the p(t) and y distributions of b-quarks predicted by perturbative QCD model calculations are used to extrapolate the measured cross section to derive the b (b) over bar pair total cross section and d sigma/dy at mid-rapidity.
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| 7. |
- Abelev, Betty, et al.
(author)
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Underlying Event measurements in pp collisions at root s=0.9 and 7 TeV with the ALICE experiment at the LHC
- 2012
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In: Journal of High Energy Physics. - 1029-8479. ; :7
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Journal article (peer-reviewed)abstract
- We present measurements of Underlying Event observables in pp collisions at root s = 0 : 9 and 7 TeV. The analysis is performed as a function of the highest charged-particle transverse momentum p(T),L-T in the event. Different regions are defined with respect to the azimuthal direction of the leading (highest transverse momentum) track: Toward, Transverse and Away. The Toward and Away regions collect the fragmentation products of the hardest partonic interaction. The Transverse region is expected to be most sensitive to the Underlying Event activity. The study is performed with charged particles above three different p(T) thresholds: 0.15, 0.5 and 1.0 GeV/c. In the Transverse region we observe an increase in the multiplicity of a factor 2-3 between the lower and higher collision energies, depending on the track p(T) threshold considered. Data are compared to PYTHIA 6.4, PYTHIA 8.1 and PHOJET. On average, all models considered underestimate the multiplicity and summed p(T) in the Transverse region by about 10-30%.
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| 8. |
- Amare, Azmeraw T, et al.
(author)
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Association of Polygenic Score for Schizophrenia and HLA Antigen and Inflammation Genes With Response to Lithium in Bipolar Affective Disorder: A Genome-Wide Association Study.
- 2018
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In: JAMA psychiatry. - : American Medical Association (AMA). - 2168-6238 .- 2168-622X. ; 75:1, s. 65-74
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Journal article (peer-reviewed)abstract
- Lithium is a first-line mood stabilizer for the treatment of bipolar affective disorder (BPAD). However, the efficacy of lithium varies widely, with a nonresponse rate of up to 30%. Biological response markers are lacking. Genetic factors are thought to mediate treatment response to lithium, and there is a previously reported genetic overlap between BPAD and schizophrenia (SCZ).To test whether a polygenic score for SCZ is associated with treatment response to lithium in BPAD and to explore the potential molecular underpinnings of this association.A total of 2586 patients with BPAD who had undergone lithium treatment were genotyped and assessed for long-term response to treatment between 2008 and 2013. Weighted SCZ polygenic scores were computed at different P value thresholds using summary statistics from an international multicenter genome-wide association study (GWAS) of 36989 individuals with SCZ and genotype data from patients with BPAD from the Consortium on Lithium Genetics. For functional exploration, a cross-trait meta-GWAS and pathway analysis was performed, combining GWAS summary statistics on SCZ and response to treatment with lithium. Data analysis was performed from September 2016 to February 2017.Treatment response to lithium was defined on both the categorical and continuous scales using the Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder score. The effect measures include odds ratios and the proportion of variance explained.Of the 2586 patients in the study (mean [SD] age, 47.2 [13.9] years), 1478 were women and 1108 were men. The polygenic score for SCZ was inversely associated with lithium treatment response in the categorical outcome, at a threshold P<5×10-2. Patients with BPAD who had a low polygenic load for SCZ responded better to lithium, with odds ratios for lithium response ranging from 3.46 (95% CI, 1.42-8.41) at the first decile to 2.03 (95% CI, 0.86-4.81) at the ninth decile, compared with the patients in the 10th decile of SCZ risk. In the cross-trait meta-GWAS, 15 genetic loci that may have overlapping effects on lithium treatment response and susceptibility to SCZ were identified. Functional pathway and network analysis of these loci point to the HLA antigen complex and inflammatory cytokines.This study provides evidence for a negative association between high genetic loading for SCZ and poor response to lithium in patients with BPAD. These results suggest the potential for translational research aimed at personalized prescribing of lithium.
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| 9. |
- Burm, Rani, et al.
(author)
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Novel prime-boost immune-based therapy inhibiting both hepatitis B and D virus infections.
- 2023
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In: Gut. - : BMJ Publishing Group Ltd. - 0017-5749 .- 1468-3288. ; 72:6, s. 1186-1195
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Journal article (peer-reviewed)abstract
- OBJECTIVE: Chronic HBV/HDV infections are a major cause of liver cancer. Current treatments can only rarely eliminate HBV and HDV. Our previously developed preS1-HDAg immunotherapy could induce neutralising antibodies to HBV in vivo and raise HBV/HDV-specific T-cells. Here, we further investigate if a heterologous prime-boost strategy can circumvent T-cell tolerance and preclude HDV superinfection in vivo.DESIGN: A DNA prime-protein boost strategy was evaluated for immunogenicity in mice and rabbits. Its ability to circumvent T-cell tolerance was assessed in immunocompetent hepatitis B surface antigen (HBsAg)-transgenic mice. Neutralisation of HBV and HDV was evaluated both in vitro and in immunodeficient human-liver chimeric mice upon adoptive transfer.RESULTS: The prime-boost strategy elicits robust HBV/HDV-specific T-cells and preS1-antibodies that can effectively prevent HBV and HDV (co-)infection in vitro and in vivo. In a mouse model representing the chronic HBsAg carrier state, active immunisation primes high levels of preS1-antibodies and HDAg-specific T-cells. Moreover, transfer of vaccine-induced antibodies completely protects HBV-infected human-liver chimeric mice from HDV superinfection.CONCLUSION: The herein described preS1-HDAg immunotherapy is shown to be immunogenic and vaccine-induced antibodies are highly effective at preventing HBV and HDV (super)infection both in vitro and in vivo. Our vaccine can complement current and future therapies for the control of chronic HBV and HDV infection.
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| 10. |
- Calabrese, Claudia, et al.
(author)
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Genomic basis for RNA alterations in cancer
- 2020
-
In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 578:7793, s. 129-136
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Journal article (peer-reviewed)abstract
- Transcript alterations often result from somatic changes in cancer genomes1. Various forms of RNA alterations have been described in cancer, including overexpression2, altered splicing3 and gene fusions4; however, it is difficult to attribute these to underlying genomic changes owing to heterogeneity among patients and tumour types, and the relatively small cohorts of patients for whom samples have been analysed by both transcriptome and whole-genome sequencing. Here we present, to our knowledge, the most comprehensive catalogue of cancer-associated gene alterations to date, obtained by characterizing tumour transcriptomes from 1,188 donors of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA)5. Using matched whole-genome sequencing data, we associated several categories of RNA alterations with germline and somatic DNA alterations, and identified probable genetic mechanisms. Somatic copy-number alterations were the major drivers of variations in total gene and allele-specific expression. We identified 649 associations of somatic single-nucleotide variants with gene expression in cis, of which 68.4% involved associations with flanking non-coding regions of the gene. We found 1,900 splicing alterations associated with somatic mutations, including the formation of exons within introns in proximity to Alu elements. In addition, 82% of gene fusions were associated with structural variants, including 75 of a new class, termed 'bridged' fusions, in which a third genomic location bridges two genes. We observed transcriptomic alteration signatures that differ between cancer types and have associations with variations in DNA mutational signatures. This compendium of RNA alterations in the genomic context provides a rich resource for identifying genes and mechanisms that are functionally implicated in cancer.
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| 11. |
- Capodanno, Davide, et al.
(author)
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Bleeding avoidance strategies in percutaneous coronary intervention
- 2022
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In: Nature Reviews Cardiology. - : Springer Nature. - 1759-5002 .- 1759-5010. ; 19:2, s. 117-132
-
Journal article (peer-reviewed)abstract
- For many years, bleeding has been perceived as an unavoidable consequence of strategies aimed at reducing thrombotic complications in patients undergoing percutaneous coronary intervention (PCI). However, the paradigm has now shifted towards bleeding being recognized as a prognostically unfavourable event to the same extent as having a new or recurrent ischaemic or thrombotic complication. As such, in parallel with progress in device and drug development for PCI, there is clinical interest in developing strategies that maximize not only the efficacy but also the safety (for example, by minimizing bleeding) of any antithrombotic treatment or procedural aspect before, during or after PCI. In this Review, we discuss contemporary data and aspects of bleeding avoidance strategies in PCI, including risk stratification, timing of revascularization, pretreatment with antiplatelet agents, selection of vascular access, choice of coronary stents and antithrombotic treatment regimens.
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| 12. |
- Capodanno, Davide, et al.
(author)
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Trial Design Principles for Patients a High Bleeding Risk Undergoing PCI JACC Scientific Expert Panel
- 2020
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In: Journal of the American College of Cardiology. - : ELSEVIER SCIENCE INC. - 0735-1097 .- 1558-3597. ; 76:12, s. 1468-1483
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Journal article (peer-reviewed)abstract
- Investigating the balance of risk for thrombotic and bleeding events after percutaneous coronary intervention (PCI) is especially relevant for patients at high bleeding risk (HBR). The Academic Research Consortium for HBR recently proposed a consensus definition in an effort to standardize the patient population included in HBR trials. The aim of this consensus-based document, the second initiative from the Academic Research Consortium for HBR, is to propose recommendations to guide the design of clinical trials of devices and drugs in HBR patients undergoing PCI. The authors discuss the designs of trials in HBR patients undergoing PCI and various aspects of trial design specific to HBR patients, including target populations, intervention and control groups, primary and secondary outcomes, and timing of endpoint reporting. (C) 2020 by the American College of Cardiology Foundation.
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| 13. |
- Coombes, Brandon J, et al.
(author)
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Association of Attention-Deficit/Hyperactivity Disorder and Depression Polygenic Scores with Lithium Response: A Consortium for Lithium Genetics Study.
- 2021
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In: Complex psychiatry. - : S. Karger AG. - 2673-3005 .- 2673-298X. ; 7:3-4, s. 80-89
-
Journal article (peer-reviewed)abstract
- Response to lithium varies widely between individuals with bipolar disorder (BD). Polygenic risk scores (PRSs) can uncover pharmacogenomics effects and may help predict drug response. Patients (N = 2,510) with BD were assessed for long-term lithium response in the Consortium on Lithium Genetics using the Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder score. PRSs for attention-deficit/hyperactivity disorder (ADHD), major depressive disorder (MDD), and schizophrenia (SCZ) were computed using lassosum and in a model including all three PRSs and other covariates, and the PRS of ADHD (β = -0.14; 95% confidence interval [CI]: -0.24 to -0.03; p value = 0.010) and MDD (β = -0.16; 95% CI: -0.27 to -0.04; p value = 0.005) predicted worse quantitative lithium response. A higher SCZ PRS was associated with higher rates of medication nonadherence (OR = 1.61; 95% CI: 1.34-1.93; p value = 2e-7). This study indicates that genetic risk for ADHD and depression may influence lithium treatment response. Interestingly, a higher SCZ PRS was associated with poor adherence, which can negatively impact treatment response. Incorporating genetic risk of ADHD, depression, and SCZ in combination with clinical risk may lead to better clinical care for patients with BD.
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| 14. |
- D'Ascenzo, Fabrizio, et al.
(author)
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Incidence and predictors of coronary stent thrombosis : Evidence from an international collaborative meta-analysis including 30 studies, 221,066 patients, and 4276 thromboses
- 2013
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In: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 167:2, s. 575-584
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Journal article (peer-reviewed)abstract
- BACKGROUND:Stent thrombosis remains among the most feared complications of percutaneous coronary intervention (PCI) with stenting. However, data on its incidence and predictors are sparse and conflicting. We thus aimed to perform a collaborative systematic review on incidence and predictors of stent thrombosis.METHODS: PubMed was systematically searched for eligible studies from the drug-eluting stent (DES) era (1/2002-12/2010). Studies were selected if including ≥2000 patients undergoing stenting or reporting on ≥25 thromboses. Study features, patient characteristics, and incidence of stent thrombosis were abstracted and pooled, when appropriate, with random-effect methods (point estimate [95% confidence intervals]), and consistency of predictors was formally appraised.RESULTS:A total of 30 studies were identified (221,066 patients, 4276 thromboses), with DES used in 87%. After a median of 22months, definite, probable, or possible stent thrombosis had occurred in 2.4% (2.0%; 2.9%), with acute in 0.4% (0.2%; 0.6%), subacute in 1.1% (1.0%; 1.3%), late in 0.5% (0.4%; 0.6%), and very late in 0.6% (0.4%; 0.8%). Similar figures were computed for studies reporting only on DES. From a total of 47 candidate variables, definite/probable stent thrombosis was more commonly and consistently predicted by early antiplatelet therapy discontinuation, extent of coronary disease, and stent number/length, with acute coronary syndrome at admission, diabetes, smoking status, and bifurcation/ostial disease also proving frequent predictors, but less consistently.CONCLUSIONS:Despite numerous possible risk factors, the most common and consistent predictors of stent thrombosis are early antiplatelet therapy discontinuation, extent of coronary disease, and stent number/length.
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| 15. |
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| 16. |
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| 17. |
- Hou, Liping, et al.
(author)
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Genome-wide association study of 40,000 individuals identifies two novel loci associated with bipolar disorder.
- 2016
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In: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 0964-6906. ; 25:15, s. 3383-94
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Journal article (peer-reviewed)abstract
- Bipolar disorder (BD) is a genetically complex mental illness characterized by severe oscillations of mood and behavior. Genome-wide association studies (GWAS) have identified several risk loci that together account for a small portion of the heritability. To identify additional risk loci, we performed a two-stage meta-analysis of >9 million genetic variants in 9,784 bipolar disorder patients and 30,471 controls, the largest GWAS of BD to date. In this study, to increase power we used ∼2,000 lithium-treated cases with a long-term diagnosis of BD from the Consortium on Lithium Genetics, excess controls, and analytic methods optimized for markers on the X-chromosome. In addition to four known loci, results revealed genome-wide significant associations at two novel loci: an intergenic region on 9p21.3 (rs12553324, p=5.87×10(-9); odds ratio=1.12) and markers within ERBB2 (rs2517959, p=4.53×10(-9); odds ratio=1.13). No significant X-chromosome associations were detected and X-linked markers explained very little BD heritability. The results add to a growing list of common autosomal variants involved in BD and illustrate the power of comparing well-characterized cases to an excess of controls in GWAS.
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| 18. |
- Kalman, Janos L, et al.
(author)
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Investigating polygenic burden in age at disease onset in bipolar disorder: Findings from an international multicentric study.
- 2019
-
In: Bipolar disorders. - : Wiley. - 1399-5618 .- 1398-5647. ; 21:1, s. 68-75
-
Journal article (peer-reviewed)abstract
- Bipolar disorder (BD) with early disease onset is associated with an unfavorable clinical outcome and constitutes a clinically and biologically homogenous subgroup within the heterogeneous BD spectrum. Previous studies have found an accumulation of early age at onset (AAO) in BD families and have therefore hypothesized that there is a larger genetic contribution to the early-onset cases than to late onset BD. To investigate the genetic background of this subphenotype, we evaluated whether an increased polygenic burden of BD- and schizophrenia (SCZ)-associated risk variants is associated with an earlier AAO in BD patients.A total of 1995 BD type 1 patients from the Consortium of Lithium Genetics (ConLiGen), PsyCourse and Bonn-Mannheim samples were genotyped and their BD and SCZ polygenic risk scores (PRSs) were calculated using the summary statistics of the Psychiatric Genomics Consortium as a training data set. AAO was either separated into onset groups of clinical interest (childhood and adolescence [≤18years] vs adulthood [>18years]) or considered as a continuous measure. The associations between BD- and SCZ-PRSs and AAO were evaluated with regression models.BD- and SCZ-PRSs were not significantly associated with age at disease onset. Results remained the same when analyses were stratified by site of recruitment.The current study is the largest conducted so far to investigate the association between the cumulative BD and SCZ polygenic risk and AAO in BD patients. The reported negative results suggest that such a polygenic influence, if there is any, is not large, and highlight the importance of conducting further, larger scale studies to obtain more information on the genetic architecture of this clinically relevant phenotype.
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| 19. |
- Kelsoe, John, et al.
(author)
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Lithium Response in Bipolar Disorder is Associated with Focal Adhesion and PI3K-Akt Networks: A Multi-omics Replication Study.
- 2023
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In: Research square.
-
Other publication (other academic/artistic)abstract
- Lithium is the gold standard treatment for bipolar disorder (BD). However, its mechanism of action is incompletely understood, and prediction of treatment outcomes is limited. In our previous multi-omics study of the Pharmacogenomics of Bipolar Disorder (PGBD) sample combining transcriptomic and genomic data, we found that focal adhesion, the extracellular matrix (ECM), and PI3K-Akt signaling networks were associated with response to lithium. In this study, we replicated the results of our previous study using network propagation methods in a genome-wide association study of an independent sample of 2,039 patients from the International Consortium on Lithium Genetics (ConLiGen) study. We identified functional enrichment in focal adhesion and PI3K-Akt pathways, but we did not find an association with the ECM pathway. Our results suggest that deficits in the neuronal growth cone and PI3K-Akt signaling, but not in ECM proteins, may influence response to lithium in BD.
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| 20. |
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| 21. |
- Maravelia, Panagiota, et al.
(author)
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Blocking entry of hepatitis B and D viruses to hepatocytes as a novel immunotherapy for treating chronic infections
- 2021
-
In: Journal of Infectious Diseases. - : Oxford University Press. - 0022-1899 .- 1537-6613. ; 223:1, s. 128-138
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Chronic hepatitis B and D virus (HBV/HDV) infections can cause cancer. Current HBV therapy using nucleoside analogues (NAs) is life-long and reduces but does not eliminate the risk of cancer. A hallmark of chronic hepatitis B is a dysfunctional HBV-specific T cell response. We therefore designed an immunotherapy driven by naïve healthy T cells specific for the HDV antigen (HDAg) to bypass the need for HBV-specific T cells in order to prime PreS1-specific T cells and PreS1 antibodies blocking HBV entry.METHODS: Ten combinations of PreS1 and/or HDAg sequences were evaluated for induction of PreS1 antibodies and HBV- and HDV- specific T cells in vitro and in vivo. Neutralization of HBV by PreS1-specific murine and rabbit antibodies was evaluated in cell culture, and rabbit anti-PreS1 were tested for neutralization of HBV in mice repopulated with human hepatocytes.RESULTS: The best vaccine candidate induced T cells to PreS1 and HDAg, and PreS1 antibodies blocking HBV entry in vitro. Importantly, adoptive transfer of PreS1 antibodies prevented, or modulated, HBV infection after a subsequent challenge in humanized mice.CONCLUSION: We here describe a novel immunotherapy for chronic HBV/HDV that targets viral entry to complement NAs and coming therapies inhibiting viral maturation.
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| 22. |
- Niemiec, Maria Joanna, 1984-, et al.
(author)
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Dual transcriptome of the immediate neutrophil and Candida albicans interplay
- 2017
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In: BMC Genomics. - : Springer Science and Business Media LLC. - 1471-2164. ; 18
-
Journal article (peer-reviewed)abstract
- Background: Neutrophils are traditionally considered transcriptionally inactive. Compared to other immune cells, little is known about their transcriptional profile during interaction with pathogens. Methods: We analyzed the meta-transcriptome of the neutrophil-Candida albicans interplay and the transcriptome of C. albicans challenged with neutrophil extracellular traps (NETs) by RNA-Seq, considering yeast and hypha individually in each approach. Results: The neutrophil response to C. albicans yeast and hyphae was dominated by a morphotype-independent core response. However, 11 % of all differentially expressed genes were regulated in a specific manner when neutrophils encountered the hyphal form of C. albicans. While involving genes for transcriptional regulators, receptors, and cytokines, the neutrophil core response lacked typical antimicrobial effectors genes. Genes of the NOD-like receptor pathway, including NLRP3, were enriched. Neutrophil-and NET-provoked responses in C. albicans differed. At the same time, the Candida transcriptome upon neutrophil encounter and upon NET challenge included genes from various metabolic processes and indicate a mutual role of the regulators Tup1p, Efg1p, Hap43p, and Cap1p. Upon challenge with neutrophils and NETs, the overall Candida response was partially morphotype-specific. Yet again, actual oppositional regulation in yeasts and hyphae was only detected for the arginine metabolism in neutrophil-infecting C. albicans. Conclusions: Taken together, our study provides a comprehensive and quantitative transcript profile of the neutrophil-C. albicans interaction. By considering the two major appearances of both, neutrophils and C. albicans, our study reveals yet undescribed insights into this medically relevant encounter. Hence, our findings will facilitate future research and potentially inspire novel therapy developments.
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| 23. |
- Ou, Anna H., et al.
(author)
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Lithium response in bipolar disorder is associated with focal adhesion and PI3K-Akt networks: a multi-omics replication study
- 2024
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In: TRANSLATIONAL PSYCHIATRY. - 2158-3188. ; 14:1
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Journal article (peer-reviewed)abstract
- Lithium is the gold standard treatment for bipolar disorder (BD). However, its mechanism of action is incompletely understood, and prediction of treatment outcomes is limited. In our previous multi-omics study of the Pharmacogenomics of Bipolar Disorder (PGBD) sample combining transcriptomic and genomic data, we found that focal adhesion, the extracellular matrix (ECM), and PI3K-Akt signaling networks were associated with response to lithium. In this study, we replicated the results of our previous study using network propagation methods in a genome-wide association study of an independent sample of 2039 patients from the International Consortium on Lithium Genetics (ConLiGen) study. We identified functional enrichment in focal adhesion and PI3K-Akt pathways, but we did not find an association with the ECM pathway. Our results suggest that deficits in the neuronal growth cone and PI3K-Akt signaling, but not in ECM proteins, may influence response to lithium in BD.
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| 24. |
- Pascual, Didac, et al.
(author)
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The missing pieces for better future predictions in subarctic ecosystems: A Torneträsk case study
- 2021
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In: Ambio. - : Springer. - 0044-7447 .- 1654-7209. ; 50:2, s. 375-392
-
Research review (peer-reviewed)abstract
- Arctic and subarctic ecosystems are experiencing substantial changes in hydrology, vegetation, permafrost conditions, and carbon cycling, in response to climatic change and other anthropogenic drivers, and these changes are likely to continue over this century. The total magnitude of these changes results from multiple interactions among these drivers. Field measurements can address the overall responses to different changing drivers, but are less capable of quantifying the interactions among them. Currently, a comprehensive assessment of the drivers of ecosystem changes, and the magnitude of their direct and indirect impacts on subarctic ecosystems, is missing. The Torneträsk area, in the Swedish subarctic, has an unrivalled history of environmental observation over 100 years, and is one of the most studied sites in the Arctic. In this study, we summarize and rank the drivers of ecosystem change in the Torneträsk area, and propose research priorities identified, by expert assessment, to improve predictions of ecosystem changes. The research priorities identified include understanding impacts on ecosystems brought on by altered frequency and intensity of winter warming events, evapotranspiration rates, rainfall, duration of snow cover and lake-ice, changed soil moisture, and droughts. This case study can help us understand the ongoing ecosystem changes occurring in the Torneträsk area, and contribute to improve predictions of future ecosystem changes at a larger scale. This understanding will provide the basis for the future mitigation and adaptation plans needed in a changing climate.
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| 25. |
- Urban, Edward R., et al.
(author)
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The importance of bottom-up approaches to international cooperation in ocean science: The iron story
- 2020
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In: Oceanography. - : The Oceanography Society. - 1042-8275. ; 33, s. 11-15
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Journal article (other academic/artistic)abstract
- © 2020, Oceanography Society. All rights reserved. In the past decade, several international efforts developed to address urgent societal issues have been identified through, for example, the United Nations 2030 Agenda for Sustainable Development and its associated 17 Sustainable Development Goals and the United Nations Decade of Ocean Science for Sustainable Development (2021–2030). These worthy efforts will bring ocean science research to bear on problems that need attention in the short term. Yet, there is also a continuing need at the international level to support fundamental ocean science and solve methodological issues over the long term. While knowledge needs to be created before it can be applied, national and international science strategy documents often do not mention the need to maintain the health of the basic science enterprise. We argue that international organizations designed to create knowledge must be maintained and strengthened to inform decisions on how to allocate funding for generating knowledge about the ocean versus solving ocean problems. We use the ocean iron cycle as an example of the benefits of using such a “bottom-up” approach to knowledge generation.
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| 26. |
- Urban, Philip, et al.
(author)
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Defining High Bleeding Risk in Patients Undergoing Percutaneous Coronary Intervention : A Consensus Document From the Academic Research Consortium for High Bleeding Risk
- 2019
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In: Circulation. - : LIPPINCOTT WILLIAMS & WILKINS. - 0009-7322 .- 1524-4539. ; 140:3, s. 240-261
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Journal article (peer-reviewed)abstract
- Identification and management of patients at high bleeding risk undergoing percutaneous coronary intervention are of major importance, but a lack of standardization in defining this population limits trial design, data interpretation, and clinical decision-making. The Academic Research Consortium for High Bleeding Risk (ARC-HBR) is a collaboration among leading research organizations, regulatory authorities, and physician-scientists from the United States, Asia, and Europe focusing on percutaneous coronary intervention-related bleeding. Two meetings of the 31-member consortium were held in Washington, DC, in April 2018 and in Paris, France, in October 2018. These meetings were organized by the Cardiovascular European Research Center on behalf of the ARC-HBR group and included representatives of the US Food and Drug Administration and the Japanese Pharmaceuticals and Medical Devices Agency, as well as observers from the pharmaceutical and medical device industries. A consensus definition of patients at high bleeding risk was developed that was based on review of the available evidence. The definition is intended to provide consistency in defining this population for clinical trials and to complement clinical decision-making and regulatory review. The proposed ARC-HBR consensus document represents the first pragmatic approach to a consistent definition of high bleeding risk in clinical trials evaluating the safety and effectiveness of devices and drug regimens for patients undergoing percutaneous coronary intervention.
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| 27. |
- Urban, Philip, et al.
(author)
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Defining high bleeding risk in patients undergoing percutaneous coronary intervention : a consensus document from the Academic Research Consortium for High Bleeding Risk
- 2019
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In: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 40:31, s. 2632-2653
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Journal article (peer-reviewed)abstract
- Identification and management of patients at high bleeding risk undergoing percutaneous coronary intervention are of major importance, but a lack of standardization in defining this population limits trial design, data interpretation, and clinical decision-making. The Academic Research Consortium for High Bleeding Risk (ARC-HBR) is a collaboration among leading research organizations, regulatory authorities, and physician-scientists from the United States, Asia, and Europe focusing on percutaneous coronary intervention-related bleeding. Two meetings of the 31-member consortium were held in Washington, DC, in April 2018 and in Paris, France, in October 2018. These meetings were organized by the Cardiovascular European Research Center on behalf of the ARC-HBR group and included representatives of the US Food and Drug Administration and the Japanese Pharmaceuticals and Medical Devices Agency, as well as observers from the pharmaceutical and medical device industries. A consensus definition of patients at high bleeding risk was developed that was based on review of the available evidence. The definition is intended to provide consistency in defining this population for clinical trials and to complement clinical decision-making and regulatory review. The proposed ARC-HBR consensus document represents the first pragmatic approach to a consistent definition of high bleeding risk in clinical trials evaluating the safety and effectiveness of devices and drug regimens for patients undergoing percutaneous coronary intervention.
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| 28. |
- Wuensch, Urban, 1986, et al.
(author)
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Emerging patterns in the global distribution of dissolved organic matter fluorescence
- 2019
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In: Analytical Methods. - : Royal Society of Chemistry (RSC). - 1759-9679 .- 1759-9660. ; 11:7, s. 888-893
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Journal article (peer-reviewed)abstract
- The spectra responsible for natural dissolved organic matter (DOM) fluorescence in 90 peer-reviewed studies have been compared using new similarity metrics. Numerous spectra cluster in specific wavelength regions. The emerging patterns suggest that most fluorescence spectra are not tied to biogeochemical origin, but exist across a wide range of different environments.
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