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Sökning: WFRF:(Levander E)

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  • Veronese, N., et al. (författare)
  • Inverse relationship between body mass index and mortality in older nursing home residents : a meta-analysis of 19,538 elderly subjects
  • 2015
  • Ingår i: Obesity Reviews. - : Wiley. - 1467-7881 .- 1467-789X. ; 16:11, s. 1001-1015
  • 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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  • Bengtsson, Therese, et al. (författare)
  • Proteomics and transcriptomics of the BABA-induced resistance response in potato using a novel functional annotation approach
  • 2014
  • Ingår i: BMC Genomics. - : Springer Science and Business Media LLC. - 1471-2164. ; 15
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Induced resistance (IR) can be part of a sustainable plant protection strategy against important plant diseases. beta-aminobutyric acid (BABA) can induce resistance in a wide range of plants against several types of pathogens, including potato infected with Phytophthora infestans. However, the molecular mechanisms behind this are unclear and seem to be dependent on the system studied. To elucidate the defence responses activated by BABA in potato, a genome-wide transcript microarray analysis in combination with label-free quantitative proteomics analysis of the apoplast secretome were performed two days after treatment of the leaf canopy with BABA at two concentrations, 1 and 10 mM. Results: Over 5000 transcripts were differentially expressed and over 90 secretome proteins changed in abundance indicating a massive activation of defence mechanisms with 10 mM BABA, the concentration effective against late blight disease. To aid analysis, we present a more comprehensive functional annotation of the microarray probes and gene models by retrieving information from orthologous gene families across 26 sequenced plant genomes. The new annotation provided GO terms to 8616 previously un-annotated probes. Conclusions: BABA at 10 mM affected several processes related to plant hormones and amino acid metabolism. A major accumulation of PR proteins was also evident, and in the mevalonate pathway, genes involved in sterol biosynthesis were down-regulated, whereas several enzymes involved in the sesquiterpene phytoalexin biosynthesis were up-regulated. Interestingly, abscisic acid (ABA) responsive genes were not as clearly regulated by BABA in potato as previously reported in Arabidopsis. Together these findings provide candidates and markers for improved resistance in potato, one of the most important crops in the world.
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  • Burra, Dharani, et al. (författare)
  • Phosphite-induced changes of the transcriptome and secretome in Solanum tuberosum leading to resistance against Phytophthora infestans
  • 2014
  • Ingår i: BMC Plant Biology. - : Springer Science and Business Media LLC. - 1471-2229. ; 14
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Potato late blight caused by the oomycete pathogen Phytophthora infestans can lead to immense yield loss. We investigated the transcriptome of Solanum tubersoum (cv. Desiree) and characterized the secretome by quantitative proteomics after foliar application of the protective agent phosphite. We also studied the distribution of phosphite in planta after application and tested transgenic potato lines with impaired in salicylic and jasmonic acid signaling. Results: Phosphite had a rapid and transient effect on the transcriptome, with a clear response 3 h after treatment. Strikingly this effect lasted less than 24 h, whereas protection was observed throughout all time points tested. In contrast, 67 secretome proteins predominantly associated with cell-wall processes and defense changed in abundance at 48 h after treatment. Transcripts associated with defense, wounding, and oxidative stress constituted the core of the phosphite response. We also observed changes in primary metabolism and cell wall-related processes. These changes were shown not to be due to phosphate depletion or acidification caused by phosphite treatment. Of the phosphite-regulated transcripts 40% also changed with beta-aminobutyric acid (BABA) as an elicitor, while the defence gene PR1 was only up-regulated by BABA. Although phosphite was shown to be distributed in planta to parts not directly exposed to phosphite, no protection in leaves without direct foliar application was observed. Furthermore, the analysis of transgenic potato lines indicated that the phosphite-mediated resistance was independent of the plant hormones salicylic and jasmonic acid. Conclusions: Our study suggests that a rapid phosphite-triggered response is important to confer long-lasting resistance against P. infestans and gives molecular understanding of its successful field applications.
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  • Eisenacher, Martin, et al. (författare)
  • Proteomics Data Collection - 2nd ProDaC Workshop 5 October 2007, Seoul, Korea
  • 2008
  • Ingår i: Proteomics. - : Wiley. - 1615-9861 .- 1615-9853. ; 8:7, s. 1326-1330
  • Tidskriftsartikel (refereegranskat)abstract
    • Proteomics Data Collection (ProDaC) is an EU-funded Coordination Action within the 6th framework programme. It aims to simplify the publication, dissemination and utilization of proteomics data by establishing standards that will support broad data collection from the research community. As a part of ProDaC, regular workshops are organized on a half-yearly basis to enable communication and discussion of the involved partners and to report on project progress. After the kick-off meeting (October 2006) in Long Beach, CA, USA and the 1st workshop in Lyon, France (April 2007), the 2nd ProDaC workshop took place at the COEX InterContinental Hotel in Seoul, Korea, on 5th October 2007, shortly before the HUPO World Congress. The progress achieved within the first year was presented by the leaders of the work packages. Additionally, a Journal's representative talked about his experiences and future plans concerning Proteomics standards; and two further external speakers presented their research related to data handling and Proteomics repositories.
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  • Eisenacher, Martin, et al. (författare)
  • Proteomics data collection--4th ProDaC workshop 15 August 2008, Amsterdam, The Netherlands
  • 2009
  • Ingår i: Proteomics. - : Wiley. - 1615-9861 .- 1615-9853. ; 9:2, s. 218-222
  • Tidskriftsartikel (refereegranskat)abstract
    • ProDaC (Proteomics Data Collection), a Coordination Action within the 6th EU framework programme, was created to support the collection, distribution and public availability of data from proteomics experiments. Within the consortium standards are created and maintained enabling an extensive data collection within the proteomics community. Important elements of ProDaC are workshops held twice a year to allow communication between the ProDaC partners and to report the ongoing progress. The most recent assembly was the 4th ProDaC workshop on August 15th, 2008, in Amsterdam, The Netherlands. It took place directly before the 7th HUPO Annual World Congress (Human Proteome Organisation). Work package coordinators and partners presented the progress achieved since the last meeting. Additionally, an EU official presented funding opportunities for proteomics in the next EU framework programme and five external speakers presented talks about their work in relation to ProDaC.
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  • Levander, Sten, et al. (författare)
  • Costs of schizophrenia during five years
  • 2007
  • Ingår i: Schizophrenia Bulletin. - : Oxford University Press (OUP). - 1745-1701 .- 0586-7614. ; 33:2, s. 485-485
  • Konferensbidrag (refereegranskat)
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  • Lindblad, O, et al. (författare)
  • Aberrant activation of the PI3K/mTOR pathway promotes resistance to sorafenib in AML
  • 2016
  • Ingår i: Oncogene. - : Springer Science and Business Media LLC. - 1476-5594 .- 0950-9232. ; 35:39, s. 5119-5131
  • Tidskriftsartikel (refereegranskat)abstract
    • Therapy directed against oncogenic FLT3 has been shown to induce response in patients with acute myeloid leukemia (AML), but these responses are almost always transient. To address the mechanism of FLT3 inhibitor resistance, we generated two resistant AML cell lines by sustained treatment with the FLT3 inhibitor sorafenib. Parental cell lines carry the FLT3-ITD (tandem duplication) mutation and are highly responsive to FLT3 inhibitors, whereas resistant cell lines display resistance to multiple FLT3 inhibitors. Sanger sequencing and protein mass-spectrometry did not identify any acquired mutations in FLT3 in the resistant cells. Moreover, sorafenib treatment effectively blocked FLT3 activation in resistant cells, whereas it was unable to block colony formation or cell survival, suggesting that the resistant cells are no longer FLT3 dependent. Gene expression analysis of sensitive and resistant cell lines, as well as of blasts from patients with sorafenib-resistant AML, suggested an enrichment of the PI3K/mTOR pathway in the resistant phenotype, which was further supported by next-generation sequencing and phospho-specific-antibody array analysis. Furthermore, a selective PI3K/mTOR inhibitor, gedatolisib, efficiently blocked proliferation, colony and tumor formation, and induced apoptosis in resistant cell lines. Gedatolisib significantly extended survival of mice in a sorafenib-resistant AML patient-derived xenograft model. Taken together, our data suggest that aberrant activation of the PI3K/mTOR pathway in FLT3-ITD-dependent AML results in resistance to drugs targeting FLT3.Oncogene advance online publication, 21 March 2016; doi:10.1038/onc.2016.41.
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  • Lindstrom, E, et al. (författare)
  • Costs of schizophrenia during five years
  • 2007
  • Ingår i: Acta Psychiatrica Scandinavica. - : Wiley. - 1600-0447 .- 0001-690X. ; 116:S435, s. 33-40
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To explore the direct and Indirect costs in a cohort of 225 risperidone-treated patients with schizophrenia followed up annually during 5 years. Method: Data on costs for medication, hospitalization, sheltered living and productivity losses, as well as degree of social isolation, were collected. Results: The direct costs were dominated by hospitalization and sheltered living expenses, while drug costs only represented 7% of the direct costs. Indirect costs represented 43% of the total costs during the 5 years. About 12% worked full-time, and 12% worked part-time, implying large productivity losses. As a consequence of the national mental health care reform, a substantial shift of costs from hospital care to sheltered living took place on the national level, but the reduction of hospital days for the study patients over time was much larger suggesting that the switch from first to second generation compounds was therapeutically successful. A high degree of social isolation was seen, with more than 20% being completely without social contacts and 30% seeing friends/relatives less often than once a week. Conclusion: The economic costs of schizophrenia are high and driven by the need for assisted living and hospitalizations, together with productivity losses. In addition, the intangible costs, such as social contacts, are also high.
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  • Mayer, Gerhard, et al. (författare)
  • The HUPO proteomics standards initiative-mass spectrometry controlled vocabulary
  • 2013
  • Ingår i: Database: the journal of biological databases and curation. - : Oxford University Press (OUP). - 1758-0463. ; , s. 009-009
  • Tidskriftsartikel (refereegranskat)abstract
    • Controlled vocabularies (CVs), i.e. a collection of predefined terms describing a modeling domain, used for the semantic annotation of data, and ontologies are used in structured data formats and databases to avoid inconsistencies in annotation, to have a unique (and preferably short) accession number and to give researchers and computer algorithms the possibility for more expressive semantic annotation of data. The Human Proteome Organization (HUPO)-Proteomics Standards Initiative (PSI) makes extensive use of ontologies/CVs in their data formats. The PSI-Mass Spectrometry (MS) CV contains all the terms used in the PSI MS-related data standards. The CV contains a logical hierarchical structure to ensure ease of maintenance and the development of software that makes use of complex semantics. The CV contains terms required for a complete description of an MS analysis pipeline used in proteomics, including sample labeling, digestion enzymes, instrumentation parts and parameters, software used for identification and quantification of peptides/proteins and the parameters and scores used to determine their significance. Owing to the range of topics covered by the CV, collaborative development across several PSI working groups, including proteomics research groups, instrument manufacturers and software vendors, was necessary. In this article, we describe the overall structure of the CV, the process by which it has been developed and is maintained and the dependencies on other ontologies.
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  • Nielsen, R. E., et al. (författare)
  • Effects of sertindole on cognition in clozapine-treated schizophrenia patients
  • 2012
  • Ingår i: Acta Psychiatrica Scandinavica. - : Wiley-Blackwell. - 0001-690X .- 1600-0447. ; 126:1, s. 31-39
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To assess the cognitive effects of sertindole augmentation in clozapine-treated patients diagnosed with schizophrenia. Cognition is secondary outcome of the trial. Method: A 12-week, double-blinded, randomized, placebo-controlled, augmentation study of patients treated with clozapine. Participants were randomized 1:1 to receive 16 mg of sertindole or placebo as adjunctive treatment to clozapine. Results: Participants displayed substantial cognitive deficits, ranging from 1.6 standard deviation below norms at baseline to more than three standard deviations on tests of response readiness and focused attention. There were no significant differences between sertindole augmentation and placebo groups at study end. Correlation analysis of Positive and Negative Syndrome (PANSS) subscales, Global Assessment of Functioning subscale (GAF-F) and Clinical Global Impression (CGI) with 20 neurocognitive indices was conducted, but no significant correlations were found. Second, we tested change from baseline to endpoint for the PANSS, GAF-F, and CGI, vs. the concomitant changes in cognitive test performance, and found no significant correlations. Conclusion: The clozapine-treated patients displayed marked cognitive deficits at baseline. Adding sertindole did not improve or worsen cognitive functioning, which is in line with previous negative studies of the effect on cognition of augmenting clozapine treatment with another antipsychotic drug.
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  • Nielsen, R E, et al. (författare)
  • Second-generation antipsychotic effect on cognition in patients with schizophrenia : a meta-analysis of randomized clinical trials
  • 2015
  • Ingår i: Acta Psychiatrica Scandinavica. - : John Wiley & Sons. - 0001-690X .- 1600-0447. ; 131:3, s. 185-196
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective To investigate the effect of second-generation antipsychotics on cognitive function in patients diagnosed with schizophrenia or schizoaffective disorder. Method Multiple-treatments meta-analysis model. Results On cognitive composite score, sertindole was superior to clozapine, effect size (ES) 0.87; 95% CI: 0.12–1.63, quetiapine, ES 0.75; 95% CI: 0.00–1.49, and first-generation antipsychotics (FGAs), ES 0.89; 95% CI: 0.14–1.64. Analyses on each cognitive domain showed clozapine, ES 0.37; 95% CI: 0.00–0.74, olanzapine, ES 0.31; 95%CI: 0.02–0.59, quetiapine, ES 0.34; 95% CI: 0.03–0.64, and FGAs, ES 0.51; 95% CI: 0.18–0.83 performing poorer on verbal working memory than ziprasidone, as well as FGAs performing poorer than risperidone, ES 0.31; 95% CI: 0.04–0.58. On executive function, sertindole performed better than clozapine, ES 0.82; 95% CI: 0.06–1.58, olanzapine, ES 0.81; 95% CI: 0.07–1.55, quetiapine, ES 0.76; 95% CI: 0.02–1.51, ziprasidone, ES 0.90; 95% CI: 0.14–1.67, and FGAs, ES 0.83; 95% CI: 0.08–1.58. On processing speed, FGAs performed poorer than sertindole, ES 0.97; 95% CI: 0.02–1.91, and quetiapine, ES 0.36; 95% CI: 0.01–0.72. On long-term verbal working memory, clozapine performed poorer than olanzapine, ES 0.41; 95% CI: 0.06–0.76. On verbal fluency, FGAs performed poorer than olanzapine, ES 0.26; 95% CI: 0.01–0.50, and clozapine, ES 0.44; 95% CI: 0.06–0.81. Lastly, FGAs, ES 0.41; 95% CI: 0.04–0.78, and clozapine, ES 0.44; 95% CI: 0.05–0.83, performed poorer on visuospatial skill compared to olanzapine. Conclusion The meta-analysis was able to detect some trends in the data analyzed, but did not show any drug having a uniform positive cognitive profile.
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  • Redéen, Stefan, 1961-, et al. (författare)
  • Reliability of diagnostic tests for Helicobacter pylori infection
  • 2011
  • Ingår i: Gastroenterology Research and Practice. - : Hindawi. - 1687-6121 .- 1687-630X. ; 2011:940650
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Helicobacter pylori (H.pylori) infection is very common worldwide. A reliable diagnosis is crucial for patients with H.pylori related diseases. At follow-up it is important to confirm that eradication therapy has been successful. There is no established gold standard for the diagnosis of H.pylori infection. Material and Methods: A sample of 304 volunteers from the general population was screened for H.pylori infection with serology, 13C-urea breath test (UBT), rapid urease test (RUT) on fresh biopsy, culture from biopsy and histological examination. Each method was tested against the other methods (except serology) taken together as gold standard. Result: The sensitivity was 0.99 for serology 0.92 for UBT, 0.96 for RUT, 0.99 for culture and 0.95 for histological examination. Corresponding specificities were 0.82, 0.94, 0.93, 0.90 and 0.92, respectively. The accuracy was 0.86 for serology, 0.94 for UBT, 0.94 for RUT, 0.93 for culture and 0.93 for histology. There was a strong correlation between the results of UBT and histological scores for H.pylori colonization as well as between the results of UBT and the scores of RUT. Conclusion: There were only minor differences in accuracy between three invasive tests for H.pylori infection in this population. RUT may be recommended as first choice since a result is obtained within hours. The accuracy of UBT was comparable to the invasive tests and it is recommended for situations when endoscopy is not needed.
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  • Siino, Valentina, et al. (författare)
  • Plasma proteome profiling of healthy individuals across the life span in a Sicilian cohort with long-lived individuals
  • 2022
  • Ingår i: Aging Cell. - : Wiley. - 1474-9718 .- 1474-9726. ; 21:9
  • Tidskriftsartikel (refereegranskat)abstract
    • The study of healthy human aging is important for shedding light on the molecular mechanisms behind aging to promote well-being and to possibly predict and/or avoid the development of age-related disorders such as atherosclerosis and diabetes. Herein, we have employed an untargeted mass spectrometry-based approach to study age-related protein changes in a healthy Sicilian plasma cohort including long-lived individuals. This approach confirmed some of the previously known proteins correlated with age including fibulin-1, dystroglycan, and gamma-glutamyl hydrolase. Furthermore, our findings include novel proteins that correlate with age and/or with location and uric acid, which could represent a unique signature for healthy aging.
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  • Willforss, J, et al. (författare)
  • Interactive proteogenomic exploration of response to Fusarium head blight in oat varieties with different resistance
  • 2020
  • Ingår i: Journal of Proteomics. - : Elsevier BV. - 1874-3919 .- 1876-7737. ; 218, s. 103688-103688
  • 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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