| 1. |
- Campbell, PJ, et al.
(författare)
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Pan-cancer analysis of whole genomes
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
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Tidskriftsartikel (refereegranskat)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
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| 2. |
- Vergallo, A., et al.
(författare)
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Association of plasma YKL-40 with brain amyloid-β levels, memory performance, and sex in subjective memory complainers
- 2020
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Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580. ; 96, s. 22-32
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Tidskriftsartikel (refereegranskat)abstract
- Neuroinflammation, a key early pathomechanistic alteration of Alzheimer's disease, may represent either a detrimental or a compensatory mechanism or both (according to the disease stage). YKL-40, a glycoprotein highly expressed in differentiated glial cells, is a candidate biomarker for in vivo tracking neuroinflammation in humans. We performed a longitudinal study in a monocentric cohort of cognitively healthy individuals at risk for Alzheimer's disease exploring whether age, sex, and the apolipoprotein E ε4 allele affect plasma YKL-40 concentrations. We investigated whether YKL-40 is associated with brain amyloid-β (Aβ) deposition, neuronal activity, and neurodegeneration as assessed via neuroimaging biomarkers. Finally, we investigated whether YKL-40 may predict cognitive performance. We found an age-associated increase of YKL-40 and observed that men display higher concentrations than women, indicating a potential sexual dimorphism. Moreover, YKL-40 was positively associated with memory performance and negatively associated with brain Aβ deposition (but not with metabolic signal). Consistent with translational studies, our results suggest a potentially protective effect of glia on incipient brain Aβ accumulation and neuronal homeostasis. © 2020 Elsevier Inc.
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| 3. |
- Burrascano, S., et al.
(författare)
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Where are we now with European forest multi-taxon biodiversity and where can we head to?
- 2023
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Ingår i: Biological Conservation. - 0006-3207. ; 284
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Tidskriftsartikel (refereegranskat)abstract
- The European biodiversity and forest strategies rely on forest sustainable management (SFM) to conserve forest biodiversity. However, current sustainability assessments hardly account for direct biodiversity indicators. We focused on forest multi-taxon biodiversity to: i) gather and map the existing information; ii) identify knowledge and research gaps; iii) discuss its research potential. We established a research network to fit data on species, standing trees, lying deadwood and sampling unit description from 34 local datasets across 3591 sampling units. A total of 8724 species were represented, with the share of common and rare species varying across taxonomic classes: some included many species with several rare ones (e.g., Insecta); others (e.g., Bryopsida) were repre-sented by few common species. Tree-related structural attributes were sampled in a subset of sampling units (2889; 2356; 2309 and 1388 respectively for diameter, height, deadwood and microhabitats). Overall, multi-taxon studies are biased towards mature forests and may underrepresent the species related to other develop-mental phases. European forest compositional categories were all represented, but beech forests were over-represented as compared to thermophilous and boreal forests. Most sampling units (94%) were referred to a habitat type of conservation concern. Existing information may support European conservation and SFM stra-tegies in: (i) methodological harmonization and coordinated monitoring; (ii) definition and testing of SFM in-dicators and thresholds; (iii) data-driven assessment of the effects of environmental and management drivers on multi-taxon forest biological and functional diversity, (iv) multi-scale forest monitoring integrating in-situ and remotely sensed information.
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| 4. |
- Bruno, V., et al.
(författare)
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Low molecular weight heparin -induced miRNA changes in peripheral blood mononuclear cells in pregnancies with unexplained recurrent pregnancy loss
- 2022
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Ingår i: Journal of Reproductive Immunology. - : ELSEVIER IRELAND LTD. - 0165-0378 .- 1872-7603. ; 151
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Tidskriftsartikel (refereegranskat)abstract
- Unexplained recurrent pregnancy loss (uRPL) is a clinical condition for which there is a lack of evidenced-based therapies. However, in clinical practice, low molecular weight heparin (LMWH) has been widely used as an empirical therapy since immune effects have been hypothesized in modulating immune tolerance at the fetal maternal interface. Epigenetic mechanisms are involved in establishing of immune tolerance, at fetal-maternal interface. To investigate potential induced immune-epigenetic changes at maternal periphery level, which could reflect the maternal-fetal interface condition, seems to open up new therapeutical strategies, since microRNAs circulating in maternal plasma and in peripheral blood mononuclear cells (PBMCs) may be specific and sensitive immunological markers/predictors of adverse pregnancy outcomes such as RPL.Our aim in this pilot study is to evaluate potential LMWH effects on genes regulating immunological response key mechanisms related to maternal-fetal tolerance processes, by studying circulating miRNAs in maternal peripheral blood. We tested a panel of selected miRNAs on three groups: 18 healthy pregnant women, 20 pregnant women affected by uRPL, 18 pregnant women affected by uRPL, treated with LMWH. The majority of differentially expressed miRNAs (miR 374a-5p, 19a-3p, 30e-5p, 128-3p, 155-5p and 200c-3p) were found to be modulated by LMWH, which seems to have a positive function in RPL patients, by bringing patients values back to those comparable to the control ones. Selected microRNA panels would appear to be an effective clinical tool for uRPL diagnosis and management. LMWH-modified miRNA expression levels could be targets for immunotherapy, as LMWH would appear to restore physiological miRNA levels, which are dysregulated in uRPL.
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| 5. |
- Borozan, Ivan, et al.
(författare)
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Molecular and Pathology Features of Colorectal Tumors and Patient Outcomes Are Associated with Fusobacterium nucleatum and Its Subspecies animalis
- 2022
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 31:1, s. 210-220
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Tidskriftsartikel (refereegranskat)abstract
- Background: Fusobacterium nucleatum (F. nucleatum) activates oncogenic signaling pathways and induces inflammation to promote colorectal carcinogenesis.Methods: We characterized F. nucleatum and its subspecies in colorectal tumors and examined associations with tumor characteristics and colorectal cancer-specific survival. We conducted deep sequencing of nusA, nusG, and bacterial 16s rRNA genes in tumors from 1,994 patients with colorectal cancer and assessed associations between F. nucleatum presence and clinical characteristics, colorectal cancer-specific mortality, and somatic mutations.Results: F. nucleatum, which was present in 10.3% of tumors, was detected in a higher proportion of right-sided and advanced-stage tumors, particularly subspecies animalis. Presence of F. nucleatum was associated with higher colorectal cancer-specific mortality (HR, 1.97; P = 0.0004). This association was restricted to nonhypermutated, microsatellite-stable tumors (HR, 2.13; P = 0.0002) and those who received chemotherapy [HR, 1.92; confidence interval (CI), 1.07-3.45; P = 0.029). Only F. nucleatum subspecies animalis, the main subspecies detected (65.8%), was associated with colorectal cancer-specific mortality (HR, 2.16; P = 0.0016), subspecies vincentii and nucleatum were not (HR, 1.07; P = 0.86). Additional adjustment for tumor stage suggests that the effect of F. nucleatum on mortality is partly driven by a stage shift. Presence of F. nucleatum was associated with microsatellite instable tumors, tumors with POLE exonuclease domain mutations, and ERBB3 mutations, and suggestively associated with TP53 mutations.Conclusions: F. nucleatum, and particularly subspecies animalis, was associated with a higher colorectal cancer-specific mortality and specific somatic mutated genes.
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| 6. |
- Borsato, M., et al.
(författare)
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Unleashing the full power of LHCb to probe stealth new physics
- 2022
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Ingår i: Reports on Progress in Physics. - : IOP Publishing. - 0034-4885 .- 1361-6633. ; 85:2
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Tidskriftsartikel (refereegranskat)abstract
- In this paper, we describe the potential of the LHCb experiment to detect stealth physics. This refers to dynamics beyond the standard model that would elude searches that focus on energetic objects or precision measurements of known processes. Stealth signatures include long-lived particles and light resonances that are produced very rarely or together with overwhelming backgrounds. We will discuss why LHCb is equipped to discover this kind of physics at the Large Hadron Collider and provide examples of well-motivated theoretical models that can be probed with great detail at the experiment.
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| 7. |
- Pesce, S., et al.
(författare)
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miRNAs in NK Cell-Based Immune Responses and Cancer Immunotherapy
- 2020
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Ingår i: Frontiers in Cell and Developmental Biology. - : Frontiers Media SA. - 2296-634X. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- The incidence of certain forms of tumors has increased progressively in recent years and is expected to continue growing as life expectancy continues to increase. Tumor-infiltrating NK cells may contribute to develop an anti-tumor response. Optimized combinations of different cancer therapies, including NK cell-based approaches for targeting tumor cells, have the potential to open new avenues in cancer immunotherapy. Functional inhibitory receptors on NK cells are needed to prevent their attack on healthy cells. Nevertheless, disruption of inhibitory receptors function on NK cells increases the cytotoxic capacity of NK cells against cancer cells. MicroRNAs (miRNAs) are small non-coding RNA molecules that target mRNA and thus regulate the expression of genes involved in the development, maturation, and effector functions of NK cells. Therapeutic strategies that target the regulatory effects of miRNAs have the potential to improve the efficiency of cancer immunotherapy. Interestingly, emerging evidence points out that some miRNAs can, directly and indirectly, control the surface expression of immune checkpoints on NK cells or that of their ligands on tumor cells. This suggests a possible use of miRNAs in the context of anti-tumor therapy. This review provides the current overview of the connections between miRNAs and regulation of NK cell functions and discusses the potential of these miRNAs as innovative biomarkers/targets for cancer immunotherapy.
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| 8. |
- Verstraeten, A., et al.
(författare)
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Effects of tree pollen on throughfall element fluxes in European forests
- 2023
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Ingår i: Biogeochemistry. - Göteborg : Springer. - 0168-2563 .- 1573-515X. ; 165:3, s. 311-325
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Tidskriftsartikel (refereegranskat)abstract
- The effects of tree pollen on precipitation chemistry are not fully understood and this can lead to misinterpretations of element deposition in European forests. We investigated the relationship between forest throughfall (TF) element fluxes and the Seasonal Pollen Integral (SPIn) using linear mixed-effects modelling (LME). TF was measured in 1990-2018 during the main pollen season (MPS, arbitrary two months) in 61 managed, mostly pure, even-aged Fagus, Quercus, Pinus, and Picea stands which are part of the ICP Forests Level II network. The SPIn for the dominant tree genus was observed at 56 aerobiological monitoring stations in nearby cities. The net contribution of pollen was estimated as the TF flux in the MPS minus the fluxes in the preceding and succeeding months. In stands of Fagus and Picea, two genera that do not form large amounts of flowers every year, TF fluxes of potassium (K+), ammonium-nitrogen (NH4+-N), dissolved organic carbon (DOC), and dissolved organic nitrogen (DON) showed a positive relationship with SPIn. However- for Fagus- a negative relationship was found between TF nitrate-nitrogen (NO3--N) fluxes and SPIn. For Quercus and Pinus, two genera producing many flowers each year, SPIn displayed limited variability and no clear association with TF element fluxes. Overall, pollen contributed on average 4.1-10.6% of the annual TF fluxes of K+ > DOC > DON > NH4+--N with the highest contribution in Quercus > Fagus > Pinus > Picea stands. Tree pollen appears to affect TF inorganic nitrogen fluxes both qualitatively and quantitatively, acting as a source of NH4+--N and a sink of NO3--N. Pollen appears to play a more complex role in nutrient cycling than previously thought.
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| 9. |
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| 12. |
- Meredith, Sean J., et al.
(författare)
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Return to Sport After Anterior Cruciate Ligament Injury: Panther Symposium ACL Injury Return to Sport Consensus Group
- 2020
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Ingår i: Orthopaedic Journal of Sports Medicine. - : SAGE Publications. - 2325-9671. ; 8:6
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Tidskriftsartikel (refereegranskat)abstract
- Background: A precise and consistent definition of return to sport (RTS) after anterior cruciate ligament (ACL) injury is lacking, and there is controversy surrounding the process of returning patients to sport and their previous activity level. Purpose: The aim of the Panther Symposium ACL Injury Return to Sport Consensus Group was to provide a clear definition of RTS after ACL injury and a description of the RTS continuum as well as provide clinical guidance on RTS testing and decision-making. Study Design: Consensus statement. Methods: An international, multidisciplinary group of ACL experts convened as part of a consensus meeting. Consensus statements were developed using a modified Delphi method. Literature review was performed to report the supporting evidence. Results: Key points include that RTS is characterized by achievement of the preinjury level of sport and involves a criteria-based progression from return to participation to RTS and, ultimately, return to performance. Purely time-based RTS decision-making should be abandoned. Progression occurs along an RTS continuum, with decision-making by a multidisciplinary group that incorporates objective physical examination data and validated and peer-reviewed RTS tests, which should involve functional assessment as well as psychological readiness. Consideration should be given to biological healing, contextual factors, and concomitant injuries. Conclusion: The resultant consensus statements and scientific rationale aim to inform the reader of the complex process of RTS after ACL injury that occurs along a dynamic continuum. Research is needed to determine the ideal RTS test battery, the best implementation of psychological readiness testing, and methods for the biological assessment of healing and recovery.
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| 13. |
- Svantesson, Eleonor, et al.
(författare)
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Clinical Outcomes After Anterior Cruciate Ligament Injury: Panther Symposium ACL Injury Clinical Outcomes Consensus Group.
- 2020
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Ingår i: Orthopaedic journal of sports medicine. - 2325-9671. ; 8:7
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Tidskriftsartikel (refereegranskat)abstract
- A stringent outcome assessment is a key aspect of establishing evidence-based clinical guidelines for anterior cruciate ligament (ACL) injury treatment. To establish a standardized assessment of clinical outcome after ACL treatment, a consensus meeting including a multidisciplinary group of ACL experts was held at the ACL Consensus Meeting Panther Symposium, Pittsburgh, Pennsylvania, USA, in June 2019. The aim was to establish a consensus on what data should be reported when conducting an ACL outcome study, what specific outcome measurements should be used, and at what follow-up time those outcomes should be assessed. The group reached consensus on 9 statements by using a modified Delphi method. In general, outcomes after ACL treatment can be divided into 4 robust categories: early adverse events, patient-reported outcomes (PROs), ACL graft failure/recurrent ligament disruption, and clinical measures of knee function and structure. A comprehensive assessment after ACL treatment should aim to provide a complete overview of the treatment result, optimally including the various aspects of outcome categories. For most research questions, a minimum follow-up of 2 years with an optimal follow-up rate of 80% is necessary to achieve a comprehensive assessment. This should include clinical examination, any sustained reinjuries, validated knee-specific PROs, and health-related quality of life questionnaires. In the midterm to long-term follow-up, the presence of osteoarthritis should be evaluated. This consensus paper provides practical guidelines for how the aforementioned entities of outcomes should be reported and suggests the preferred tools for a reliable and valid assessment of outcome after ACL treatment.
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| 14. |
- Vahkal, B., et al.
(författare)
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Review of Methodological Approaches to Human Milk Small Extracellular Vesicle Proteomics
- 2021
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Ingår i: Biomolecules. - : MDPI AG. - 2218-273X. ; 11:6
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Tidskriftsartikel (refereegranskat)abstract
- Proteomics can map extracellular vesicles (EVs), including exosomes, across disease states between organisms and cell types. Due to the diverse origin and cargo of EVs, tailoring methodological and analytical techniques can support the reproducibility of results. Proteomics scans are sensitive to in-sample contaminants, which can be retained during EV isolation procedures. Contaminants can also arise from the biological origin of exosomes, such as the lipid-rich environment in human milk. Human milk (HM) EVs and exosomes are emerging as a research interest in health and disease, though the experimental characterization and functional assays remain varied. Past studies of HM EV proteomes have used data-dependent acquisition methods for protein detection, however, improvements in data independent acquisition could allow for previously undetected EV proteins to be identified by mass spectrometry. Depending on the research question, only a specific population of proteins can be compared and measured using isotope and other labelling techniques. In this review, we summarize published HM EV proteomics protocols and suggest a methodological workflow with the end-goal of effective and reproducible analysis of human milk EV proteomes.
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| 15. |
- Yakneen, S, et al.
(författare)
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Butler enables rapid cloud-based analysis of thousands of human genomes
- 2020
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Ingår i: Nature biotechnology. - : Springer Science and Business Media LLC. - 1546-1696 .- 1087-0156. ; 38:3, s. 288-
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Tidskriftsartikel (refereegranskat)abstract
- We present Butler, a computational tool that facilitates large-scale genomic analyses on public and academic clouds. Butler includes innovative anomaly detection and self-healing functions that improve the efficiency of data processing and analysis by 43% compared with current approaches. Butler enabled processing of a 725-terabyte cancer genome dataset from the Pan-Cancer Analysis of Whole Genomes (PCAWG) project in a time-efficient and uniform manner.
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| 16. |
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