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- Zaborowski, AM, et al.
(författare)
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Microsatellite instability in young patients with rectal cancer: molecular findings and treatment response
- 2022
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Ingår i: The British journal of surgery. - : Oxford University Press (OUP). - 1365-2168 .- 0007-1323. ; 109:3, s. 251-255
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Tidskriftsartikel (refereegranskat)abstract
- In this study of 400 patients with early-onset rectal cancer, 12.5 per cent demonstrated microsatellite instability (MSI). MSI was associated with a reduced likelihood of nodal positivity, an increased rate of pathological complete response, and improved disease-specific survival.
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| 9. |
- Abe, O, et al.
(författare)
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Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials
- 2005
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Ingår i: The Lancet. - 1474-547X. ; 365:9472, s. 1687-1717
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Tidskriftsartikel (refereegranskat)abstract
- Background Quinquennial overviews (1985-2000) of the randomised trials in early breast cancer have assessed the 5-year and 10-year effects of various systemic adjuvant therapies on breast cancer recurrence and survival. Here, we report the 10-year and 15-year effects. Methods Collaborative meta-analyses were undertaken of 194 unconfounded randomised trials of adjuvant chemotherapy or hormonal therapy that began by 1995. Many trials involved CMF (cyclophosphamide, methotrexate, fluorouracil), anthracycline-based combinations such as FAC (fluorouracil, doxombicin, cyclophosphamide) or FEC (fluorouracil, epirubicin, cyclophosphamide), tamoxifen, or ovarian suppression: none involved taxanes, trastuzumab, raloxifene, or modem aromatase inhibitors. Findings Allocation to about 6 months of anthracycline-based polychemotherapy (eg, with FAC or FEC) reduces the annual breast cancer death rate by about 38% (SE 5) for women younger than 50 years of age when diagnosed and by about 20% (SE 4) for those of age 50-69 years when diagnosed, largely irrespective of the use of tamoxifen and of oestrogen receptor (ER) status, nodal status, or other tumour characteristics. Such regimens are significantly (2p=0 . 0001 for recurrence, 2p<0 . 00001 for breast cancer mortality) more effective than CMF chemotherapy. Few women of age 70 years or older entered these chemotherapy trials. For ER-positive disease only, allocation to about 5 years of adjuvant tamoxifen reduces the annual breast cancer death rate by 31% (SE 3), largely irrespective of the use of chemotherapy and of age (<50, 50-69, &GE; 70 years), progesterone receptor status, or other tumour characteristics. 5 years is significantly (2p<0 . 00001 for recurrence, 2p=0 . 01 for breast cancer mortality) more effective than just 1-2 years of tamoxifen. For ER-positive tumours, the annual breast cancer mortality rates are similar during years 0-4 and 5-14, as are the proportional reductions in them by 5 years of tamoxifen, so the cumulative reduction in mortality is more than twice as big at 15 years as at 5 years after diagnosis. These results combine six meta-analyses: anthracycline-based versus no chemotherapy (8000 women); CMF-based versus no chemotherapy (14 000); anthracycline-based versus CMF-based chemotherapy (14 000); about 5 years of tamoxifen versus none (15 000); about 1-2 years of tamoxifen versus none (33 000); and about 5 years versus 1-2 years of tamoxifen (18 000). Finally, allocation to ovarian ablation or suppression (8000 women) also significantly reduces breast cancer mortality, but appears to do so only in the absence of other systemic treatments. For middle-aged women with ER-positive disease (the commonest type of breast cancer), the breast cancer mortality rate throughout the next 15 years would be approximately halved by 6 months of anthracycline-based chemotherapy (with a combination such as FAC or FEC) followed by 5 years of adjuvant tamoxifen. For, if mortality reductions of 38% (age <50 years) and 20% (age 50-69 years) from such chemotherapy were followed by a further reduction of 31% from tamoxifen in the risks that remain, the final mortality reductions would be 57% and 45%, respectively (and, the trial results could well have been somewhat stronger if there had been full compliance with the allocated treatments). Overall survival would be comparably improved, since these treatments have relatively small effects on mortality from the aggregate of all other causes. Interpretation Some of the widely practicable adjuvant drug treatments that were being tested in the 1980s, which substantially reduced 5-year recurrence rates (but had somewhat less effect on 5-year mortality rates), also substantially reduce 15-year mortality rates. Further improvements in long-term survival could well be available from newer drugs, or better use of older drugs.
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- Goubet, AG, et al.
(författare)
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Prolonged SARS-CoV-2 RNA virus shedding and lymphopenia are hallmarks of COVID-19 in cancer patients with poor prognosis
- 2021
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Ingår i: Cell death and differentiation. - : Springer Science and Business Media LLC. - 1476-5403 .- 1350-9047. ; 28:12, s. 3297-3315
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Tidskriftsartikel (refereegranskat)abstract
- Patients with cancer are at higher risk of severe coronavirus infectious disease 2019 (COVID-19), but the mechanisms underlying virus–host interactions during cancer therapies remain elusive. When comparing nasopharyngeal swabs from cancer and noncancer patients for RT-qPCR cycle thresholds measuring acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in 1063 patients (58% with cancer), we found that malignant disease favors the magnitude and duration of viral RNA shedding concomitant with prolonged serum elevations of type 1 IFN that anticorrelated with anti-RBD IgG antibodies. Cancer patients with a prolonged SARS-CoV-2 RNA detection exhibited the typical immunopathology of severe COVID-19 at the early phase of infection including circulation of immature neutrophils, depletion of nonconventional monocytes, and a general lymphopenia that, however, was accompanied by a rise in plasmablasts, activated follicular T-helper cells, and non-naive Granzyme B+FasL+, EomeshighTCF-1high, PD-1+CD8+ Tc1 cells. Virus-induced lymphopenia worsened cancer-associated lymphocyte loss, and low lymphocyte counts correlated with chronic SARS-CoV-2 RNA shedding, COVID-19 severity, and a higher risk of cancer-related death in the first and second surge of the pandemic. Lymphocyte loss correlated with significant changes in metabolites from the polyamine and biliary salt pathways as well as increased blood DNA from Enterobacteriaceae and Micrococcaceae gut family members in long-term viral carriers. We surmise that cancer therapies may exacerbate the paradoxical association between lymphopenia and COVID-19-related immunopathology, and that the prevention of COVID-19-induced lymphocyte loss may reduce cancer-associated death.
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- Tobias, Deirdre K, et al.
(författare)
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Second international consensus report on gaps and opportunities for the clinical translation of precision diabetes medicine
- 2023
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Ingår i: Nature Medicine. - 1546-170X. ; 29:10, s. 2438-2457
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Forskningsöversikt (refereegranskat)abstract
- Precision medicine is part of the logical evolution of contemporary evidence-based medicine that seeks to reduce errors and optimize outcomes when making medical decisions and health recommendations. Diabetes affects hundreds of millions of people worldwide, many of whom will develop life-threatening complications and die prematurely. Precision medicine can potentially address this enormous problem by accounting for heterogeneity in the etiology, clinical presentation and pathogenesis of common forms of diabetes and risks of complications. This second international consensus report on precision diabetes medicine summarizes the findings from a systematic evidence review across the key pillars of precision medicine (prevention, diagnosis, treatment, prognosis) in four recognized forms of diabetes (monogenic, gestational, type 1, type 2). These reviews address key questions about the translation of precision medicine research into practice. Although not complete, owing to the vast literature on this topic, they revealed opportunities for the immediate or near-term clinical implementation of precision diabetes medicine; furthermore, we expose important gaps in knowledge, focusing on the need to obtain new clinically relevant evidence. Gaps include the need for common standards for clinical readiness, including consideration of cost-effectiveness, health equity, predictive accuracy, liability and accessibility. Key milestones are outlined for the broad clinical implementation of precision diabetes medicine.
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| 23. |
- Adhikari, Subash, et al.
(författare)
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A high-stringency blueprint of the human proteome
- 2020
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
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Forskningsöversikt (refereegranskat)abstract
- The Human Proteome Organization (HUPO) launched the Human Proteome Project (HPP) in 2010, creating an international framework for global collaboration, data sharing, quality assurance and enhancing accurate annotation of the genome-encoded proteome. During the subsequent decade, the HPP established collaborations, developed guidelines and metrics, and undertook reanalysis of previously deposited community data, continuously increasing the coverage of the human proteome. On the occasion of the HPP’s tenth anniversary, we here report a 90.4% complete high-stringency human proteome blueprint. This knowledge is essential for discerning molecular processes in health and disease, as we demonstrate by highlighting potential roles the human proteome plays in our understanding, diagnosis and treatment of cancers, cardiovascular and infectious diseases.
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| 24. |
- Joseph, A, et al.
(författare)
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Metabolic features of cancer cells impact immunosurveillance
- 2021
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Ingår i: Journal for immunotherapy of cancer. - : BMJ. - 2051-1426. ; 9:6
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Tidskriftsartikel (refereegranskat)abstract
- Tumors rewire their metabolism to achieve robust anabolism and resistance against therapeutic interventions like cisplatin treatment. For example, a prolonged exposure to cisplatin causes downregulation of pyridoxal kinase (PDXK), the enzyme that generates the active vitamin B6, and upregulation of poly ADP-ribose (PAR) polymerase-1 (PARP1) activity that requires a supply of nicotinamide (vitamin B3) adenine dinucleotide. We investigated the impact of the levels of PDXK and PAR on the local immunosurveillance (ie, density of the antigen presenting cells and adaptive immune response by CD8 T lymphocytes) in two different tumor types.MethodsTumors from patients with locally advanced cervical carcinoma (LACC) and non-small cell lung cancer (NSCLC) were stained for PAR, PDXK, dendritic cell lysosomal associated membrane glycoprotein (DC-LAMP) and CD8 T cell infiltration. Their correlations and prognostic impact were assessed. Cisplatin-resistant NSCLC cell clones isolated from Lewis-lung cancer (LLC) cells were evaluated for PAR levels by immunoblot. Parental (PARlow) and cisplatin-resistant (PARhigh) clones were subcutaneously injected into the flank of C57BL/6 mice. Tumors were harvested to evaluate their immune infiltration by flow cytometry.ResultsThe infiltration of tumors by CD8 T and DC-LAMP+ cells was associated with a favorable overall survival in patients with LACC (p=0.006 and p=0.008, respectively) and NSCLC (p<0.001 for both CD8 T and DC-LAMP cells). We observed a positive correlation between PDXK expression and the infiltration by DC-LAMP (R=0.44, p=0.02 in LACC, R=0.14, p=0.057 in NSCLC), and a negative correlation between PAR levels and CD8 T lymphocytes (R=−0.39, p=0.034 in LACC, R=−0.18, p=0.017 in NSCLC). PARP1 is constitutively hyperactivated in cisplatin-resistant LLC cells manifesting elevated intracellular levels of poly(ADP-ribosyl)ated proteins (PARhigh). Tumors formed by such cancer cells injected into immunocompetent mice were scarcely infiltrated by CD8 T (p=0.028) and antigen presenting cells (p=0.086).ConclusionsOncometabolic features can impact local immunosurveillance, providing new functional links between cisplatin resistance and therapeutic failure.
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| 26. |
- Roach, J C, et al.
(författare)
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Genetic mapping at 3-kilobase resolution reveals inositol 1,4,5-triphosphate receptor 3 as a risk factor for type 1 diabetes in Sweden.
- 2006
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297. ; 79:4, s. 614-627
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Tidskriftsartikel (refereegranskat)abstract
- We mapped the genetic influences for type 1 diabetes (T1D), using 2,360 single-nucleotide polymorphism (SNP) markers in the 4.4-Mb human major histocompatibility complex (MHC) locus and the adjacent 493 kb centromeric to the MHC, initially in a survey of 363 Swedish T1D cases and controls. We confirmed prior studies showing association with T1D in the MHC, most significantly near HLA-DR/DQ. In the region centromeric to the MHC, we identified a peak of association within the inositol 1,4,5-triphosphate receptor 3 gene (ITPR3; formerly IP3R3). The most significant single SNP in this region was at the center of the ITPR3 peak of association (P=1.7×10−4 for the survey study). For validation, we typed an additional 761 Swedish individuals. The P value for association computed from all 1,124 individuals was 1.30×10−6 (recessive odds ratio 2.5; 95% confidence interval [CI] 1.7–3.9). The estimated population-attributable risk of 21.6% (95% CI 10.0%–31.0%) suggests that variation within ITPR3 reflects an important contribution to T1D in Sweden. Two-locus regression analysis supports an influence of ITPR3 variation on T1D that is distinct from that of any MHC class II gene.
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| 28. |
- Korth, F., et al.
(författare)
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Nitrate source identification in the Baltic Sea using its isotopic ratios in combination with a Bayesian isotope mixing model
- 2014
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Ingår i: Biogeosciences. - : Copernicus GmbH. - 1726-4170 .- 1726-4189. ; 11:17, s. 4913-4924
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Tidskriftsartikel (refereegranskat)abstract
- Nitrate (NO3-) is the major nutrient responsible for coastal eutrophication worldwide and its production is related to intensive food production and fossil-fuel combustion. In the Baltic Sea NO3- inputs have increased 4-fold over recent decades and now remain constantly high. NO3- source identification is therefore an important consideration in environmental management strategies. In this study focusing on the Baltic Sea, we used a method to estimate the proportional contributions of NO3- from atmospheric deposition, N-2 fixation, and runoff from pristine soils as well as from agricultural land. Our approach combines data on the dual isotopes of NO3- (delta N-15-NO3- and delta O-18-NO3-) in winter surface waters with a Bayesian isotope mixing model (Stable Isotope Analysis in R, SIAR). Based on data gathered from 47 sampling locations over the entire Baltic Sea, the majority of the NO3- in the southern Baltic was shown to derive from runoff from agricultural land (33-100 %), whereas in the northern Baltic, i.e. the Gulf of Bothnia, NO3- originates from nitrification in pristine soils (34-100 %). Atmospheric deposition accounts for only a small percentage of NO3- levels in the Baltic Sea, except for contributions from northern rivers, where the levels of atmospheric NO3- are higher. An additional important source in the central Baltic Sea is N-2 fixation by diazotrophs, which contributes 49-65% of the overall NO3- pool at this site. The results obtained with this method are in good agreement with source estimates based upon delta N-15 values in sediments and a three-dimensional ecosystem model, ERGOM. We suggest that this approach can be easily modified to determine NO3- sources in other marginal seas or larger near-coastal areas where NO3- is abundant in winter surface waters when fractionation processes are minor.
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| 29. |
- Maziarz, M., et al.
(författare)
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The association between the PTPN22 1858C > T variant and type 1 diabetes depends on HLA risk and GAD65 autoantibodies
- 2010
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Ingår i: Genes and Immunity. - : Springer Science and Business Media LLC. - 1476-5470 .- 1466-4879. ; 11:5, s. 406-415
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Tidskriftsartikel (refereegranskat)abstract
- The single nucleotide polymorphism 1858C> T in the PTPN22 gene is associated with type 1 diabetes (T1D) in several populations. Earlier reports have suggested that the association may be modified by human leukocyte antigen (HLA), as well as by islet autoantibodies. In a large case-control study of Swedish incident T1D patients and controls, 0-34 years of age, we tested whether the odds ratio (OR) measure of association was dependent on HLA or autoantibodies against the islet autoantigens glutamic acid decarboxylase 65 kDa autoantibodies (GADA), insulin, islet antigen-2, or islet cell. The association between the carrier status of 1858C> T allele in PTPN22 (PTPN22(CT + TT)) and T1D was modified by HLA. In addition, in GADA-positive T1D, the OR was 2.83 (2.00, 3.99), whereas in GADA-negative T1D, the OR was 1.41 (0.98, 2.04) (P for comparison = 0.007). The OR of association between PTPN22(CT + TT) and GADA-positive T1D declined with increasing HLA-risk category from 6.12 to 1.54 (P = 0.003); no such change was detected in GADA-negative T1D (P = 0.722) (P for comparison = 0.001). However, the absolute difference in risk between PTPN22(CC) and PTPN22(CT + TT) subjects with high-risk HLA was five times higher than that for subjects with low-risk HLA. We hypothesize that the altered T-cell function because of the PTPN22(1858C> T) polymorphism is exclusively associated with GADA-positive T1D at diagnosis. Genes and Immunity (2010) 11, 406-415; doi: 10.1038/gene.2010.12; published online 6 May 2010
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| 30. |
- Rocha, Juan C., et al.
(författare)
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Toward understanding the dynamics of land change in Latin America : potential utility of a resilience approach for building archetypes of land-systems change
- 2019
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Ingår i: Ecology and Society. - 1708-3087. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- Climate change, financial shocks, and fluctuations in international trade are some of the reasons why resilience is increasingly invoked in discussions about land-use policy. However, resilience assessments come with the challenge of operationalization, upscaling their conclusions while considering the context-specific nature of land-use dynamics and the common lack of long-term data. We revisit the approach of system archetypes for identifying resilience surrogates and apply it to land-use systems using seven case studies spread across Latin America. The approach relies on expert knowledge and literature-based characterizations of key processes and patterns of land-use change synthesized in a data template. These narrative accounts are then used to guide development of causal networks, from which potential surrogates for resilience are identified. This initial test of the method shows that deforestation, international trade, technological improvements, and conservation initiatives are key drivers of land-use change, and that rural migration, leasing and land pricing, conflicts in property rights, and international spillovers are common causal pathways that underlie land-use transitions. Our study demonstrates how archetypes can help to differentiate what is generic from context dependant. They help identify common causal pathways and leverage points across cases to further elucidate how policies work and where, as well as what policy lessons might transfer across heterogeneous settings.
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| 31. |
- Shao, WG, et al.
(författare)
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The SysteMHC Atlas project
- 2018
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Ingår i: Nucleic acids research. - : Oxford University Press (OUP). - 1362-4962 .- 0305-1048. ; 46:D1, s. D1237-D1247
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Tidskriftsartikel (refereegranskat)
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| 32. |
- Shin, J. H., et al.
(författare)
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IA-2 autoantibodies in incident type I diabetes patients are associated with a polyadenylation signal polymorphism in GIMAP5
- 2007
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Ingår i: Genes Immun. - : Springer Science and Business Media LLC. - 1466-4879 .- 1476-5470. ; 8:6, s. 503-12
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Tidskriftsartikel (refereegranskat)abstract
- In a large case-control study of Swedish incident type I diabetes patients and controls, 0-34 years of age, we tested the hypothesis that the GIMAP5 gene, a key genetic factor for lymphopenia in spontaneous BioBreeding rat diabetes, is associated with type I diabetes; with islet autoantibodies in incident type I diabetes patients or with age at clinical onset in incident type I diabetes patients. Initial scans of allelic association were followed by more detailed logistic regression modeling that adjusted for known type I diabetes risk factors and potential confounding variables. The single nucleotide polymorphism (SNP) rs6598, located in a polyadenylation signal of GIMAP5, was associated with the presence of significant levels of IA-2 autoantibodies in the type I diabetes patients. Patients with the minor allele A of rs6598 had an increased prevalence of IA-2 autoantibody levels compared to patients without the minor allele (OR=2.2; Bonferroni-corrected P=0.003), after adjusting for age at clinical onset (P=8.0 x 10(-13)) and the numbers of HLA-DQ A1*0501-B1*0201 haplotypes (P=2.4 x 10(-5)) and DQ A1*0301-B1*0302 haplotypes (P=0.002). GIMAP5 polymorphism was not associated with type I diabetes or with GAD65 or insulin autoantibodies, ICA, or age at clinical onset in patients. These data suggest that the GIMAP5 gene is associated with islet autoimmunity in type I diabetes and add to recent findings implicating the same SNP in another autoimmune disease.
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| 35. |
- Ashwood, C., et al.
(författare)
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Proceedings of the EuBIC-MS 2020 Developers’ Meeting
- 2020
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Ingår i: EuPA Open Proteomics. - : Elsevier B.V.. - 2212-9685. ; 24, s. 1-6
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Tidskriftsartikel (refereegranskat)abstract
- The 2020 European Bioinformatics Community for Mass Spectrometry (EuBIC-MS) Developers’ meeting was held from January 13th to January 17th 2020 in Nyborg, Denmark. Among the participants were scientists as well as developers working in the field of computational mass spectrometry (MS) and proteomics. The 4-day program was split between introductory keynote lectures and parallel hackathon sessions. During the latter, the participants developed bioinformatics tools and resources addressing outstanding needs in the community. The hackathons allowed less experienced participants to learn from more advanced computational MS experts, and to actively contribute to highly relevant research projects. We successfully produced several new tools that will be useful to the proteomics community by improving data analysis as well as facilitating future research. All keynote recordings are available on https://doi.org/10.5281/zenodo.3890181.
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| 36. |
- Bailey-Wilson, Joan E, et al.
(författare)
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Analysis of Xq27-28 linkage in the international consortium for prostate cancer genetics (ICPCG) families
- 2012
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Ingår i: BMC Medical Genetics. - London : BioMed Central. - 1471-2350. ; 13, s. 46-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Genetic variants are likely to contribute to a portion of prostate cancer risk. Full elucidation of the genetic etiology of prostate cancer is difficult because of incomplete penetrance and genetic and phenotypic heterogeneity. Current evidence suggests that genetic linkage to prostate cancer has been found on several chromosomes including the X; however, identification of causative genes has been elusive.Methods: Parametric and non-parametric linkage analyses were performed using 26 microsatellite markers in each of 11 groups of multiple-case prostate cancer families from the International Consortium for Prostate Cancer Genetics (ICPCG). Meta-analyses of the resultant family-specific linkage statistics across the entire 1,323 families and in several predefined subsets were then performed.Results: Meta-analyses of linkage statistics resulted in a maximum parametric heterogeneity lod score (HLOD) of 1.28, and an allele-sharing lod score (LOD) of 2.0 in favor of linkage to Xq27-q28 at 138 cM. In subset analyses, families with average age at onset less than 65 years exhibited a maximum HLOD of 1.8 (at 138 cM) versus a maximum regional HLOD of only 0.32 in families with average age at onset of 65 years or older. Surprisingly, the subset of families with only 2-3 affected men and some evidence of male-to-male transmission of prostate cancer gave the strongest evidence of linkage to the region (HLOD = 3.24, 134 cM). For this subset, the HLOD was slightly increased (HLOD = 3.47 at 134 cM) when families used in the original published report of linkage to Xq27-28 were excluded.Conclusions: Although there was not strong support for linkage to the Xq27-28 region in the complete set of families, the subset of families with earlier age at onset exhibited more evidence of linkage than families with later onset of disease. A subset of families with 2-3 affected individuals and with some evidence of male to male disease transmission showed stronger linkage signals. Our results suggest that the genetic basis for prostate cancer in our families is much more complex than a single susceptibility locus on the X chromosome, and that future explorations of the Xq27-28 region should focus on the subset of families identified here with the strongest evidence of linkage to this region.
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| 37. |
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| 38. |
- Christensen, G Bryce, et al.
(författare)
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Genome-wide linkage analysis of 1,233 prostate cancer pedigrees from the International Consortium for prostate cancer Genetics using novel sumLINK and sumLOD analyses.
- 2010
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Ingår i: The Prostate. - : Wiley. - 0270-4137 .- 1097-0045. ; 70, s. 735-744
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Prostate cancer (PC) is generally believed to have a strong inherited component, but the search for susceptibility genes has been hindered by the effects of genetic heterogeneity. The recently developed sumLINK and sumLOD statistics are powerful tools for linkage analysis in the presence of heterogeneity. METHODS: We performed a secondary analysis of 1,233 PC pedigrees from the International Consortium for Prostate Cancer Genetics (ICPCG) using two novel statistics, the sumLINK and sumLOD. For both statistics, dominant and recessive genetic models were considered. False discovery rate (FDR) analysis was conducted to assess the effects of multiple testing. RESULTS: Our analysis identified significant linkage evidence at chromosome 22q12, confirming previous findings by the initial conventional analyses of the same ICPCG data. Twelve other regions were identified with genome-wide suggestive evidence for linkage. Seven regions (1q23, 5q11, 5q35, 6p21, 8q12, 11q13, 20p11-q11) are near loci previously identified in the initial ICPCG pooled data analysis or the subset of aggressive PC pedigrees. Three other regions (1p12, 8p23, 19q13) confirm loci reported by others, and two (2p24, 6q27) are novel susceptibility loci. FDR testing indicates that over 70% of these results are likely true positive findings. Statistical recombinant mapping narrowed regions to an average of 9 cM. CONCLUSIONS: Our results represent genomic regions with the greatest consistency of positive linkage evidence across a very large collection of high-risk PC pedigrees using new statistical tests that deal powerfully with heterogeneity. These regions are excellent candidates for further study to identify PC predisposition genes. Prostate (c) 2010 Wiley-Liss, Inc.
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| 39. |
- Deutsch, Eric W., et al.
(författare)
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Expanding the Use of Spectral Libraries in Proteomics
- 2018
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 17:12, s. 4051-4060
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Tidskriftsartikel (refereegranskat)abstract
- The 2017 Dagstuhl Seminar on Computational Proteomics provided an opportunity for a broad discussion on ABSTRACT: The 2017 Dagstuhl Seminar on Computational the current state and future directions of the generation and use of peptide tandem mass spectrometry spectral libraries. Their use in proteomics is growing slowly, but there are multiple challenges in the field that must be addressed to further increase the adoption of spectral libraries and related techniques. The primary bottlenecks are the paucity of high quality and comprehensive libraries and the general difficulty of adopting spectral library searching into existing workflows. There are several existing spectral library formats, but none captures a satisfactory level of metadata; therefore, a logical next improvement is to design a more advanced, Proteomics Standards Initiative-approved spectral library format that can encode all of the desired metadata. The group discussed a series of metadata requirements organized into three designations of completeness or quality, tentatively dubbed bronze, silver, and gold. The metadata can be organized at four different levels of granularity: at the collection (library) level, at the individual entry (peptide ion) level, at the peak (fragment ion) level, and at the peak annotation level. Strategies for encoding mass modifications in a consistent manner and the requirement for encoding high-quality and commonly seen but as-yet-unidentified spectra were discussed. The group also discussed related topics, including strategies for comparing two spectra, techniques for generating representative spectra for a library, approaches for selection of optimal signature ions for targeted workflows, and issues surrounding the merging of two or more libraries into one. We present here a review of this field and the challenges that the community must address in order to accelerate the adoption of spectral libraries in routine analysis of proteomics datasets.
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| 40. |
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| 41. |
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| 42. |
- Galluzzi, L, et al.
(författare)
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Consensus guidelines for the definition, detection and interpretation of immunogenic cell death
- 2020
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Ingår i: Journal for immunotherapy of cancer. - : BMJ. - 2051-1426. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Cells succumbing to stress via regulated cell death (RCD) can initiate an adaptive immune response associated with immunological memory, provided they display sufficient antigenicity and adjuvanticity. Moreover, multiple intracellular and microenvironmental features determine the propensity of RCD to drive adaptive immunity. Here, we provide an updated operational definition of immunogenic cell death (ICD), discuss the key factors that dictate the ability of dying cells to drive an adaptive immune response, summarize experimental assays that are currently available for the assessment of ICD in vitro and in vivo, and formulate guidelines for their interpretation.
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| 43. |
- Gephart, Jessica A., et al.
(författare)
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The 'seafood gap' in the food-water nexus literature-issues surrounding freshwater use in seafood production chains
- 2017
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Ingår i: Advances in Water Resources. - : Elsevier BV. - 0309-1708 .- 1872-9657. ; 110, s. 505-514
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Tidskriftsartikel (refereegranskat)abstract
- Freshwater use for food production is projected to increase substantially in the coming decades with population growth, changing demographics, and shifting diets. Ensuring joint food-water security has prompted efforts to quantify freshwater use for different food products and production methods. However, few analyses quantify freshwater use for seafood production, and those that do use inconsistent water accounting. This inhibits water use comparisons among seafood products or between seafood and agricultural/livestock products. This 'seafood gap' in the food-water nexus literature will become increasingly problematic as seafood consumption is growing globally and aquaculture is one of the fastest growing animal food sectors in the world. Therefore, the present study 1) reviews freshwater use concepts as they relate to seafood production; 2) provides three cases to highlight the particular water use concerns for aquaculture, and; 3) outlines future directions to integrate seafood into the broader food-water nexus discussion. By revisiting water use concepts through a focus on seafood production systems, we highlight the key water use processes that should be considered for seafood production and offer a fresh perspective on the analysis of freshwater use in food systems more broadly. This is an open access article under the CC BY-NC-ND license.
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| 46. |
- Harrison, Dick, et al.
(författare)
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Sverige i andra världskriget
- 2010
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Ingår i: Om Tyskland segrat - 53 alternativa scenarier. - 9789185183999 ; , s. 291-314
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 47. |
- Horvatovich, Peter, et al.
(författare)
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Quest for Missing Proteins : Update 2015 on Chromosome-Centric Human Proteome Project
- 2015
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 14:9, s. 3415-3431
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- This paper summarizes the recent activities of the Chromosome-Centric Human Proteome Project (C-HPP) consortium, which develops new technologies to identify yet-to-be annotated proteins (termed "missing proteins") in biological samples that lack sufficient experimental evidence at the protein level for confident protein identification. The C-HPP also aims to identify new protein forms that may be caused by genetic variability, post-translational modifications, and alternative splicing. Proteogenomic data integration forms the basis of the C-HPP's activities; therefore, we have summarized some of the key approaches and their roles in the project. We present new analytical technologies that improve the chemical space and lower detection limits coupled to bioinformatics tools and some publicly available resources that can be used to improve data analysis or support the development of analytical assays. Most of this paper's content has been compiled from posters, slides, and discussions presented in the series of C-HPP workshops held during 2014. All data (posters, presentations) used are available at the C-HPP Wild (http://c-hpp.webhosting.rug.nl/) and in the Supporting Information.
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| 48. |
- Humborg, Christoph, et al.
(författare)
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Sea-air exchange patterns along the central and outer East Siberian Arctic Shelf as inferred from continuous CO2, stable isotope, and bulk chemistry measurements
- 2017
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Ingår i: Global Biogeochemical Cycles. - 0886-6236 .- 1944-9224. ; 31:7, s. 1173-1191
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Tidskriftsartikel (refereegranskat)abstract
- This large-scale quasi-synoptic study gives a comprehensive picture of sea-air CO 2 fluxes during the melt season in the central and outer Laptev Sea (LS) and East Siberian Sea (ESS). During a 7 week cruise we compiled a continuous record of both surface water and air CO 2 concentrations, in total 76,892 measurements. Overall, the central and outer parts of the ESAS constituted a sink for CO 2 , and we estimate a median uptake of 9.4 g C m -2 yr -1 or 6.6 Tg C yr -1 . Our results suggest that while the ESS and shelf break waters adjacent to the LS and ESS are net autotrophic systems, the LS is a net heterotrophic system. CO 2 sea-air fluxes for the LS were 4.7 g C m -2 yr -1 , and for the ESS we estimate an uptake of 7.2 g C m -2 yr -1 . Isotopic composition of dissolved inorganic carbon (δ 13 C DIC and δ 13 C CO2 ) in the water column indicates that the LS is depleted in δ 13 C DIC compared to the Arctic Ocean (ArcO) and ESS with an offset of 0.5‰ which can be explained by mixing of δ 13 C DIC -depleted riverine waters and 4.0 Tg yr -1 respiration of OC ter ; only a minor part (0.72 Tg yr -1 ) of this respired OC ter is exchanged with the atmosphere. Property-mixing diagrams of total organic carbon and isotope ratio (δ 13 C SPE-DOC ) versus dissolved organic carbon (DOC) concentration diagram indicate conservative and nonconservative mixing in the LS and ESS, respectively. We suggest land-derived particulate organic carbon from coastal erosion as an additional significant source for the depleted δ 13 C DIC .
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| 49. |
- Lane, Lydie, et al.
(författare)
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Metrics for the Human Proteome Project 2013-2014 and Strategies for Finding Missing Proteins
- 2014
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 13:1, s. 15-20
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Tidskriftsartikel (refereegranskat)abstract
- One year ago the Human Proteome Project (HPP) leadership designated the baseline metrics for the Human Proteome Project to be based on neXtProt with a total of 13 664 proteins validated at protein evidence level 1 (PE1) by mass spectrometry, antibody-capture, Edman sequencing, or 3D structures. Corresponding chromosome-specific data were provided from PeptideAtlas, GPMdb, and Human Protein Atlas. This year, the neXtProt total is 15 646 and the other resources, which are inputs to neXtProt, have high-quality identifications and additional annotations for 14 012 in PeptideAtlas, 14 869 in GPMdb, and 10 976 in HPA. We propose to remove 638 genes from the denominator that are "uncertain" or "dubious" in Ensembl, UniProt/SwissProt, and neXtProt. That leaves 3844 "missing proteins", currently having no or inadequate documentation, to be found from a new denominator of 19 490 protein-coding genes. We present those tabulations and web links and discuss current strategies to find the missing proteins.
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| 50. |
- Lenz, Tobias L., et al.
(författare)
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Widespread non-additive and interaction effects within HLA loci modulate the risk of autoimmune diseases
- 2015
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Ingår i: Nature Genetics. - : Macmillan Publishers Ltd.. - 1061-4036 .- 1546-1718. ; 47:9, s. 1085-1090
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Tidskriftsartikel (refereegranskat)abstract
- Human leukocyte antigen (HLA) genes confer substantial risk for autoimmune diseases on a log-additive scale. Here we speculated that differences in autoantigen-binding repertoires between a heterozygote's two expressed HLA variants might result in additional non-additive risk effects. We tested the non-additive disease contributions of classical HLA alleles in patients and matched controls for five common autoimmune diseases: rheumatoid arthritis (n(cases) = 5,337), type 1 diabetes (T1D; n(cases) = 5,567), psoriasis vulgaris (n(cases) = 3,089), idiopathic achalasia (n(cases) = 727) and celiac disease (ncases = 11,115). In four of the five diseases, we observed highly significant, non-additive dominance effects (rheumatoid arthritis, P = 2.5 x 10(-12); T1D, P = 2.4 x 10(-10); psoriasis, P = 5.9 x 10(-6); celiac disease, P = 1.2 x 10(-87)). In three of these diseases, the non-additive dominance effects were explained by interactions between specific classical HLA alleles (rheumatoid arthritis, P = 1.8 x 10(-3); T1D, P = 8.6 x 10(-27); celiac disease, P = 6.0 x 10(-100)). These interactions generally increased disease risk and explained moderate but significant fractions of phenotypic variance (rheumatoid arthritis, 1.4%; T1D, 4.0%; celiac disease, 4.1%) beyond a simple additive model.
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