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| 5. |
- Veronese, N., et al.
(författare)
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Inverse relationship between body mass index and mortality in older nursing home residents : a meta-analysis of 19,538 elderly subjects
- 2015
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Ingår i: Obesity Reviews. - : Wiley. - 1467-7881 .- 1467-789X. ; 16:11, s. 1001-1015
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Forskningsöversikt (refereegranskat)abstract
- Body mass index (BMI) and mortality in old adults from the general population have been related in a U-shaped or J-shaped curve. However, limited information is available for elderly nursing home populations, particularly about specific cause of death. A systematic PubMed/EMBASE/CINAHL/SCOPUS search until 31 May 2014 without language restrictions was conducted. As no published study reported mortality in standard BMI groups (<18.5, 18.5-24.9, 25-29.9, 30kg/m(2)), the most adjusted hazard ratios (HRs) according to a pre-defined list of covariates were obtained from authors and pooled by random-effect model across each BMI category. Out of 342 hits, 20 studies including 19,538 older nursing home residents with 5,223 deaths during a median of 2 years of follow-up were meta-analysed. Compared with normal weight, all-cause mortality HRs were 1.41 (95% CI=1.26-1.58) for underweight, 0.85 (95% CI=0.73-0.99) for overweight and 0.74 (95% CI=0.57-0.96) for obesity. Underweight was a risk factor for higher mortality caused by infections (HR=1.65 [95% CI=1.13-2.40]). RR results corroborated primary HR results, with additionally lower infection-related mortality in overweight and obese than in normal-weight individuals. Like in the general population, underweight is a risk factor for mortality in old nursing home residents. However, uniquely, not only overweight but also obesity is protective, which has relevant nutritional goal implications in this population/setting.
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| 6. |
- Braekeveldt, N., et al.
(författare)
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Patient-Derived Xenograft Models Reveal Intratumor Heterogeneity and Temporal Stability in Neuroblastoma
- 2018
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Ingår i: Cancer Research. - 0008-5472. ; 78:20, s. 5958-5969
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Tidskriftsartikel (refereegranskat)abstract
- Patient-derived xenografts (PDX) and the Avatar, a single PDX mirroring an individual patient, are emerging tools in preclinical cancer research. However, the consequences of intratumor heterogeneity for PDX modeling of biomarkers, target identification, and treatment decisions remain under-explored. In this study, we undertook serial passaging and comprehensive molecular analysis of neuroblastoma orthotopic PDXs, which revealed strong intrinsic genetic, transcriptional, and phenotypic stability for more than 2 years. The PDXs showed preserved neuroblastoma-associated gene signatures that correlated with poor clinical outcome in a large cohort of patients with neuroblastoma. Furthermore, we captured spatial intratumor heterogeneity using ten PDXs from a single high-risk patient tumor. We observed diverse growth rates, transcriptional, proteomic, and phosphoproteomic profiles. PDX-derived transcriptional profiles were associated with diverse clinical characteristics in patients with high-risk neuroblastoma. These data suggest that high-risk neuroblastoma contains elements of both temporal stability and spatial intratumor heterogeneity, the latter of which complicates clinical translation of personalized PDX-Avatar studies into preclinical cancer research. Significance: These findings underpin the complexity of PDX modeling as a means to advance translational applications against neuroblastoma. (C) 2018 AACR.
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- de Ávila, Renato Ivan, et al.
(författare)
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A proteomics dataset capturing myeloid cell responses upon cellular exposure to fungicides, adjuvants and fungicide formulations
- 2023
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Ingår i: Data in Brief. - : Elsevier BV. - 2352-3409. ; 46
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Tidskriftsartikel (refereegranskat)abstract
- Dendritic cells are the sentinels of the immune system, linking the innate and adaptive immune response. Myeloid and dendritic cell models have been successfully used in in vitro approaches to predict adverse outcomes such as skin sensitization. We here exposed a well-characterized human dendritic cell-like cell line to agricultural chemicals, including fungicide formulations, active ingredients, adjuvants and defined mixtures for 24 h to profile induced changes on protein levels. Cell pellets were harvested and prepared for bottom-up label-free analysis with peptide separation on an EASY-nano LC system 1200 coupled online with a QExactive HF-X mass spectrometer with data-dependent acquisition (DDA). The raw data files and processed quantitative data have been deposited to ProteomeXchange with the data identification number PXD034624 and are described here. The data in this article may serve as a resource for researchers interested in e.g. human toxicology, immunology, cell biology and pharmacology.
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| 15. |
- de Ávila, Renato Ivan, et al.
(författare)
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Adjuvants in fungicide formulations can be skin sensitizers and cause different types of cell stress responses
- 2022
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Ingår i: Toxicology Reports. - : Elsevier BV. - 2214-7500. ; 9, s. 2030-2041
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Tidskriftsartikel (refereegranskat)abstract
- New approaches based on -omics technologies can identify biomarkers and processes regulated in response to xenobiotics, and thus support toxicological risk assessments. This is vital to meet the challenges associated with “cocktail effects”, i.e. combination effects of chemicals present simultaneously in a product, our environment, and/or our body. For plant protection products (PPPs), investigations largely focus on active ingredients such as herbicides and fungicides. In this study, we have analyzed agricultural chemicals, two surfactants (poly(oxy-1,2-ethanediyl), alpha-sulfo-omega-[2,4,6-tris(1-phenylethyl)phenoxy]-, ammonium salt, POL; N,N-dimethylcapramide, NND), and one preservative, 1,2-benzisothiazol-3(2 H)-one (BEN) used as adjuvants in PPPs, and further three fungicide PPPs, Proline EC 250, Shirlan, Folicur Xpert, containing the adjuvants, and other major individual constituents (fluazinam (FLU), prothioconazole (PRO), tebuconazole (TEB)) as well as defined mixtures (“mixes”) thereof using several in vitro approaches. All investigated single agricultural chemicals were predicted as skin sensitizers using an in vitro transcriptomic assay based on a dendritic cell model. For selected chemicals and mixes, also skin sensitization potency was predicted. The preservative BEN induced significant changes in cytokine secretion and dendritic cell activation marker CD86 expression. The surfactant NND changed cytokine secretion only and the POL only affected CD86 expression. Proteomic analyses revealed unique response profiles for all adjuvants, an oxidative stress pattern response in BEN-treated cells, and differentially abundant proteins associated with cholesterol homeostasis in response to POL. In summary, we find responses to agricultural chemicals and products consistent with the dendritic cell model reacting to chemical exposure with oxidative stress, ER stress, effects on autophagy, and metabolic changes especially related to cholesterol homeostasis. After exposure to certain mixes, novel proteins or transcripts were differentially expressed and these were not detected for any single constituents, supporting the occurrence of cocktail effects. This indicates that all chemicals in a PPP can contribute to the toxicity profile of a PPP, including their skin sensitizing/immunotoxic properties.
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| 16. |
- Deutsch, Eric W., et al.
(författare)
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TraML: a standard format for exchange of selected reaction monitoring transition lists
- 2012
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Ingår i: Molecular & Cellular Proteomics. - 1535-9484. ; 11:4, s. 111-015040
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Tidskriftsartikel (refereegranskat)abstract
- Abstract in UndeterminedTargeted proteomics via selected reaction monitoring (SRM) is a powerful mass spectrometric technique affording higher dynamic range, increased specificity and lower limits of detection than other shotgun mass spectrometry methods when applied to proteome analyses. However, it involves selective measurement of predetermined analytes, which requires more preparation in the form of selecting appropriate signatures for the proteins and peptides that are to be targeted. There is a growing number of software programs and resources for selecting optimal transitions and the instrument settings used for the detection and quantification of the targeted peptides, but the exchange of this information is hindered by a lack of a standard format. We have developed a new standardized format, called TraML, for encoding transition lists and associated metadata. In addition to introducing the TraML format, we demonstrate several implementations across the community, and provide semantic validators, extensive documentation, and multiple example instances to demonstrate correctly written documents. Widespread use of TraML will facilitate the exchange of transitions, reduce time spent handling incompatible list formats, increase the reusability of previously optimized transitions, and thus accelerate the widespread adoption of targeted proteomics via SRM.
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| 17. |
- Douglas, S Kevin, et al.
(författare)
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Reliability and validity evaluation of the psychopathy checklist: Screening version (PCL : SV) in Swedish correctional and forensic psychiatric samples
- 2005
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Ingår i: Assessment. - : SAGE Publications. - 1552-3489 .- 1073-1911. ; 12:2, s. 145-161
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Tidskriftsartikel (refereegranskat)abstract
- This study evaluated the structural reliability, construct-related validity, and cultural validity generalization of the Hare Psychopathy Checklist: Screening Version (PCL:SV) in a sample of more than 560 male and female Swedish forensic psychiatric treatment patients, forensic evaluation patients, and criminal offenders. Structural reliability was excellent for most indices. PCL:SV scores were higher for males than females for total and Part 1 scores (interpersonal/affective features) but not for Part 2 (behavioral features). With some exceptions, PCL:SV scores were meaningfully related to aggression to others, a measure of risk for violence, substance use problems, personality disorder (positive), and psychosis (negative). Correlations between PCL:SV and aggression were larger for females than males, although the difference was smaller when personality disorder was held constant. The structural reliability and pattern of validity coefficients were comparable in these Swedish samples to other non-North American samples. Implications for the cross-cultural manifestation and correlates of psychopathy are discussed.
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| 21. |
- Levander, S, et al.
(författare)
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Immune-mediated effects targeting hepatitis C virus in a syngeneic replicon cell transplantation mouse model
- 2018
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Ingår i: Gut. - : BMJ. - 1468-3288 .- 0017-5749. ; 67:8, s. 1525-1535
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Tidskriftsartikel (refereegranskat)abstract
- HCV is characterised by its ability to establish chronic infection in hepatocytes and to replicate in the presence of an inflammation. We mimicked this situation in vivo in immune-competent mice by syngeneic transplantation of HCV replicon-containing mouse hepatoma cells.DesignA total of 5 million H-2b positive Hep56.1D cells, carrying a subgenomic genotype (gt) 2a replicon (HCV replicon cells) or stably expressing comparable levels of the HCV NS3/4A protease/helicase complex (NS3/4A hepatoma cells), were injected subcutaneously into syngeneic H-2b-restricted mice. Kinetics of tumour growth, HCV RNA replication levels and HCV-specific immune responses were monitored. For immune monitoring, new H-2b-restricted cytotoxic T cell epitopes within the gt2a NS3/4A region were mapped. Immune mice were generated by DNA-based vaccination.ResultsHCV replicon and NS3/4A hepatoma cells generated solid tumours in vivo. Similar to what is seen in human HCV infection did HCV RNA replicate in the presence of inflammation. NS3/4A-specific CD8+ T cells seemed to transiently reduce HCV RNA levels. Both CD4+ and CD8+ T cells were required for protection against tumour growth. Vaccine-induced NS3/4A(gt2a)-specific T cells protected against HCV replicon tumours in wild-type, but not in HCV NS3/4A(gt1a)-transgenic mice with dysfunctional HCV-specific T cells. Importantly, as in human HCV infection, HCV replicon cells neither primed nor boosted a strong NS3/4A-specific T cell response.ConclusionSyngeneic transplantation of mouse HCV replicon cells into immune-competent animals mirrors many in vivo events in humans. This system is versatile and can be applied to any genetically modified H-2b-restricted mouse strain.
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| 22. |
- Lindberg, Tim, et al.
(författare)
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An integrated transcriptomic- and proteomic-based approach to evaluate the human skin sensitization potential of glyphosate and its commercial agrochemical formulations
- 2020
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Ingår i: Journal of Proteomics. - : Elsevier BV. - 1874-3919 .- 1876-7737. ; 217
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Tidskriftsartikel (refereegranskat)abstract
- We investigated the skin sensitization hazard of glyphosate, the surfactant polyethylated tallow amine (POEA) and two commercial glyphosate-containing formulations using different omics-technologies based on a human dendritic cell (DC)-like cell line. First, the GARD™skin assay, investigating changes in the expression of 200 transcripts upon cell exposure to xenobiotics, was used for skin sensitization prediction. POEA and the formulations were classified as skin sensitizers while glyphosate alone was classified as a non-sensitizer. Interestingly, the mixture of POEA together with glyphosate displayed a similar sensitizing prediction as POEA alone, indicating that glyphosate likely does not increase the sensitizing capacity when associated with POEA. Moreover, mass spectrometry analysis identified differentially regulated protein groups and predicted molecular pathways based on a proteomic approach in response to cell exposures with glyphosate, POEA and the glyphosate-containing formulations. Based on the protein expression data, predicted pathways were linked to immunologically relevant events and regulated proteins further to cholesterol biosynthesis and homeostasis as well as to autophagy, identifying novel aspects of DC responses after exposure to xenobiotics. In summary, we here present an integrative analysis involving advanced technologies to elucidate the molecular mechanisms behind DC activation in the skin sensitization process triggered by the investigated agrochemical materials. Significance: The use of glyphosate has increased worldwide, and much effort has been made to improve risk assessments and to further elucidate the mechanisms behind any potential human health hazard of this chemical and its agrochemical formulations. In this context, omics-based techniques can provide a multiparametric approach, including several biomarkers, to expand the mechanistic knowledge of xenobiotics-induced toxicity. Based on this, we performed the integration of GARD™skin and proteomic data to elucidate the skin sensitization hazard of POEA, glyphosate and its two commercial mixtures, and to investigate cellular responses more in detail on protein level. The proteomic data indicate the regulation of immune response-related pathways and proteins associated with cholesterol biosynthesis and homeostasis as well as to autophagy, identifying novel aspects of DC responses after exposure to xenobiotics. Therefore, our data show the applicability of a multiparametric integrated approach for the mechanism-based hazard evaluation of xenobiotics, eventually complementing decision making in the holistic risk assessment of chemicals regarding their allergenic potential in humans.
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- Rojas-Macias, Miguel A., 1979, et al.
(författare)
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Towards a standardized bioinformatics infrastructure for N- and O-glycomics
- 2019
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- The mass spectrometry (MS)-based analysis of free polysaccharides and glycans released from proteins, lipids and proteoglycans increasingly relies on databases and software. Here, we review progress in the bioinformatics analysis of protein-released N- and O-linked glycans (N-and O-glycomics) and propose an e-infrastructure to overcome current deficits in data and experimental transparency. This workflow enables the standardized submission of MS-based glycomics information into the public repository UniCarb-DR. It implements the MIRAGE (Minimum Requirement for A Glycomics Experiment) reporting guidelines, storage of unprocessed MS data in the GlycoPOST repository and glycan structure registration using the GlyTouCan registry, thereby supporting the development and extension of a glycan structure knowledgebase.
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| 28. |
- Santesson, Sabina, et al.
(författare)
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Airborne chemistry coupled to Raman spectroscopy
- 2003
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Ingår i: Analytical Chemistry. - : American Chemical Society (ACS). - 1520-6882 .- 0003-2700. ; 75:9, s. 2177-2180
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Tidskriftsartikel (refereegranskat)abstract
- In this paper, the use of airborne chemistry (acoustically levitated drops) in combination with Raman spectroscopy is explored. We report herein the first Raman studies of crystallization processes in levitated drops and the first demonstration of surface-enhanced Raman scattering (SERS) detection in this medium. Crystallization studies on the model compounds benzamide and indomethacin resulted in the formation of two crystal modifications for each compound, suggesting that this methodology may be useful for investigation of polymorphs. SERS detection resulted in a signal enhancement of 27 000 for benzoic acid and 11 000 for rhodamine 6-G. The preliminary results presented here clearly indicate that several important applications of the combination between Raman spectroscopy and acoustic drop levitation can be expected in the future.
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| 29. |
- Strand, Susanne, et al.
(författare)
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Clinical and risk management facotrs in risk prediction of mentally disordered offenders - More important than historical data? : A retrospective study of 40 mentally disordered offenders assessed with the HCR-20 violence risk assessment scheme
- 1999
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Ingår i: Legal and Criminological Psychology. - : Wiley. - 1355-3259 .- 2044-8333. ; 4:1, s. 67-76
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Tidskriftsartikel (refereegranskat)abstract
- Purpose. The predictive validity of the risk prediction instrument HCR-20 was studied. Methods. Two matched groups of discharged forensic psychiatric patients, one who had recidivated into violent criminality and the other not, were assessed with the HCR-20. This was done retrospective and blind to the outcome. Results. The results show an overall high predictive validity (AUC = .80). However, historical data had none, or a low, validity while clinical and risk management data had a very high validity. Conclusions. One of the most interesting findings in this study is that clinical and risk management factors came out as more predictive of future violence than historical factors, which is very much contrary to findings in past research. We think that one has to bear in mind that both clinical and risk management factors are heavily influenced by historical information. Thus, historical data are probably as important as is generally shown in follow-up studies of violence in various offender groups. However, using the HCR-20, which allows systematic and reliable coding of clinical and risk management factors, seems to make it possible to use these factors more successfully than has been hitherto possible.
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| 34. |
- Willforss, J, et al.
(författare)
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Interactive proteogenomic exploration of response to Fusarium head blight in oat varieties with different resistance
- 2020
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Ingår i: Journal of Proteomics. - : Elsevier BV. - 1874-3919 .- 1876-7737. ; 218, s. 103688-103688
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Tidskriftsartikel (refereegranskat)abstract
- Fusarium species are cereal pathogens that cause the Fusarium Head Blight (FHB) disease. FHB can reduce yield, cause mycotoxin accumulation in the grain and reduce germination efficiency of the harvested seeds. Understanding the biochemical interactions between the host plants and the pathogen is crucial for controlling the disease and for the development of cultivars with improved tolerance to FHB. Here, we studied morphological and proteomic differences between the susceptible oat variety Belinda and the more resistant variety Argamak using variety-specific transcriptome assemblies as references. Measurements of deoxynivalenol toxin levels confirmed the partial resistance in Argamak and the susceptibility in Belinda. To jointly investigate the proteomics- and sequence data, we developed an RShiny-based interface for interactive exploration of the dataset using univariate and multivariate statistics. When applying this interface to the dataset, quantitative protein differences between Belinda and Argamak were detected, and eighteen peptides were found uniquely in Argamak during infection, among them several lipoxygenases. Such proteins can be developed as markers for Fusarium resistance breeding. In conclusion, this study provides the first proteogenomic insight on molecular Fusarium-oat interactions at both morphological and molecular levels and the data are openly available through an interactive interface for further inspection. SIGNIFICANCE: Fusarium head blight causes widespread damage to crops, and chronic and acute toxicity to human and livestock due to the accumulation of toxins during infection. In the present study, two oat varieties with differing resistance were challenged with Fusarium to understand the disease better, and studied both at morphological and molecular levels, identifying proteins which could play a role in the defense mechanism. Furthermore, a proteogenomics approach allows joint profiling of expression and sequence level differences to identify potentially functionally differing mutations. Here such analysis is made openly available through an interactive interface which allows other scientists to draw further findings from the data. This study may both serve as a basis for understanding oat disease response and developing breeding markers for Fusarium resistant oat and future proteogenomic studies using the interactive approach described.
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| 35. |
- Willforss, J., et al.
(författare)
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Stable bull fertility protein markers in seminal plasma
- 2021
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Ingår i: Journal of Proteomics. - : Elsevier BV. - 1874-3919 .- 1876-7737. ; 236
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Tidskriftsartikel (refereegranskat)abstract
- Bull fertility is an important trait in breeding as the semen of one bull can, potentially, be used to perform thousands of inseminations. The high number of inseminations needed to obtain reliable measures from Non-Return Rates to oestrus creates difficulties in assessing fertility accurately. Improving molecular knowledge of seminal properties may provide ways to facilitate selection of bulls with good semen quality. In this study, liquid chromatography mass spectrometry (LC-MS/MS) was used to analyze the protein content from the seminal plasma of 20 bulls with Non-Return Rates between 35 and 60%, sampled across three seasons. Overall, 1343 proteins were identified and proteins with consistent correlation to fertility across multiple seasons found. From these, nine protein groups had a significant Pearson correlation (p < 0.1) with fertility in all three seasons and 34 protein groups had a similar correlation in at least two seasons. Among notable proteins showing a high and consistent correlation across seasons were Osteopontin, a lipase (LIPA) and N-acetylglucosamine-1phosphotransferase subunit gamma. Three proteins were combined in a multiple linear regression to predict fertility (r = 0.81). These sets of proteins represent potential markers, which could be used by the breeding industry to phenotype bull fertility. Significance: The ability of bull spermatozoa to fertilize oocytes is crucial for breeding efficiency. However, the reliability of this trait from field measures is relatively low and the prediction of fertility given by conventional methods to evaluate sperm quality is currently not very accurate. In this work, we identify sets of proteins in bull seminal plasma from repeated samples collected at different times of the year that correlate to fertility in a consistent way. We combined these individual proteins to build a molecular signature predictive of fertility. This study provides an overview of proteins linked to fertility in seminal plasma, thereby increasing knowledge of the bull seminal plasma proteome. Protein signatures from the latter, potentially related to fertility, may be of use to predict fertility for individual bulls.
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