| 51. |
- Bos, Isabelle, et al.
(author)
-
The frequency and influence of dementia risk factors in prodromal Alzheimer's disease
- 2017
-
In: Neurobiology of Aging. - : Elsevier. - 0197-4580 .- 1558-1497. ; 56, s. 33-40
-
Journal article (peer-reviewed)abstract
- We investigated whether dementia risk factors were associated with prodromal Alzheimer's disease (AD) according to the International Working Group-2 and National Institute of Aging-Alzheimer's Association criteria, and with cognitive decline. A total of 1394 subjects with mild cognitive impairment from 14 different studies were classified according to these research criteria, based on cognitive performance and biomarkers. We compared the frequency of 10 risk factors between the subgroups, and used Cox-regression to examine the effect of risk factors on cognitive decline. Depression, obesity, and hypercholesterolemia occurred more often in individuals with low-AD-likelihood, compared with those with a high-AD-likelihood. Only alcohol use increased the risk of cognitive decline, regardless of AD pathology. These results suggest that traditional risk factors for AD are not associated with prodromal AD or with progression to dementia, among subjects with mild cognitive impairment. Future studies should validate these findings and determine whether risk factors might be of influence at an earlier stage (i.e., preclinical) of AD.
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| 52. |
- Edwards, Kieron D., et al.
(author)
-
Circadian clock components control daily growth activities by modulating cytokinin levels and cell division-associated gene expression in Populus trees
- 2018
-
In: Plant, Cell and Environment. - : John Wiley & Sons. - 0140-7791 .- 1365-3040. ; 41:6, s. 1468-1482
-
Journal article (peer-reviewed)abstract
- Trees are carbon dioxide sinks and major producers of terrestrial biomass with distinct seasonal growth patterns. Circadian clocks enable the coordination of physiological and biochemical temporal activities, optimally regulating multiple traits including growth. To dissect the clock's role in growth, we analysed Populus tremula x P. tremuloides trees with impaired clock function due to down-regulation of central clock components. late elongated hypocotyl (lhy-10) trees, in which expression of LHY1 and LHY2 is reduced by RNAi, have a short free-running period and show disrupted temporal regulation of gene expression and reduced growth, producing 30-40% less biomass than wild-type trees. Genes important in growth regulation were expressed with an earlier phase in lhy-10, and CYCLIN D3 expression was misaligned and arrhythmic. Levels of cytokinins were lower in lhy-10 trees, which also showed a change in the time of peak expression of genes associated with cell division and growth. However, auxin levels were not altered in lhy-10 trees, and the size of the lignification zone in the stem showed a relative increase. The reduced growth rate and anatomical features of lhy-10 trees were mainly caused by misregulation of cell division, which may have resulted from impaired clock function.
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| 53. |
- Karnkowska, Anna, et al.
(author)
-
The Oxymonad Genome Displays Canonical Eukaryotic Complexity in the Absence of a Mitochondrion
- 2019
-
In: Molecular biology and evolution. - : OXFORD UNIV PRESS. - 0737-4038 .- 1537-1719. ; 36:10, s. 2292-2312
-
Journal article (peer-reviewed)abstract
- The discovery that the protist Monocercomonoides exilis completely lacks mitochondria demonstrates that these organelles are not absolutely essential to eukaryotic cells. However, the degree to which the metabolism and cellular systems of this organism have adapted to the loss of mitochondria is unknown. Here, we report an extensive analysis of the M. exilis genome to address this question. Unexpectedly, we find that M. exilis genome structure and content is similar in complexity to other eukaryotes and less "reduced" than genomes of some other protists from the Metamonada group to which it belongs. Furthermore, the predicted cytoskeletal systems, the organization of endomembrane systems, and biosynthetic pathways also display canonical eukaryotic complexity. The only apparent preadaptation that permitted the loss of mitochondria was the acquisition of the SUF system for Fe-S cluster assembly and the loss of glycine cleavage system. Changes in other systems, including in amino acid metabolism and oxidative stress response, were coincident with the loss of mitochondria but are likely adaptations to the microaerophilic and endobiotic niche rather than the mitochondrial loss per se. Apart from the lack of mitochondria and peroxisomes, we show that M. exilis is a fully elaborated eukaryotic cell that is a promising model system in which eukaryotic cell biology can be investigated in the absence of mitochondria.
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| 54. |
- Kloth, Karen J., et al.
(author)
-
PECTIN ACETYLESTERASE9 Affects the Transcriptome and Metabolome and Delays Aphid Feeding1[OPEN]
- 2019
-
In: Plant Physiology. - Rockville : American Society of Plant Biologists. - 0032-0889 .- 1532-2548. ; 181:4, s. 1704-1720
-
Journal article (peer-reviewed)abstract
- The plant cell wall plays an important role in damage-associated molecular pattern-induced resistance to pathogens and herbivorous insects. Our current understanding of cell wall-mediated resistance is largely based on the degree of pectin methylesterification. However, little is known about the role of pectin acetylesterification in plant immunity. This study describes how one pectin-modifying enzyme, PECTIN ACETYLESTERASE 9 (PAE9), affects the Arabidopsis (Arabidopsis thaliana) transcriptome, secondary metabolome, and aphid performance. Electro-penetration graphs showed that Myzus persicae aphids established phloem feeding earlier on pae9 mutants. Whole-genome transcriptome analysis revealed a set of 56 differentially expressed genes (DEGs) between uninfested pae9-2 mutants and wild-type plants. The majority of the DEGs were enriched for biotic stress responses and down-regulated in the pae9-2 mutant, including PAD3 and IGMT2, involved in camalexin and indole glucosinolate biosynthesis, respectively. Relative quantification of more than 100 secondary metabolites revealed decreased levels of several compounds, including camalexin and oxylipins, in two independent pae9 mutants. In addition, absolute quantification of phytohormones showed that jasmonic acid (JA), jasmonoyl-Ile, salicylic acid, abscisic acid, and indole-3-acetic acid were compromised due to PAE9 loss of function. After aphid infestation, however, pae9 mutants increased their levels of camalexin, glucosinolates, and JA, and no long-term effects were observed on aphid fitness. Overall, these data show that PAE9 is required for constitutive up-regulation of defense-related compounds, but that it is not required for aphid-induced defenses. The signatures of phenolic antioxidants, phytoprostanes, and oxidative stress-related transcripts indicate that the processes underlying PAE9 activity involve oxidation-reduction reactions. PECTIN ACETYLESTERASE9 is involved in the accumulation of jasmonic acid, camalexin and antioxidants, and delays establishment of aphid phloem feeding, but is not required for aphid-induced defenses.
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| 55. |
- Marschall, Tobias, et al.
(author)
-
Computational pan-genomics : status, promises and challenges
- 2018
-
In: Briefings in Bioinformatics. - : Oxford University Press (OUP). - 1467-5463 .- 1477-4054. ; 19:1, s. 118-135
-
Journal article (peer-reviewed)abstract
- Many disciplines, from human genetics and oncology to plant breeding, microbiology and virology, commonly face the challenge of analyzing rapidly increasing numbers of genomes. In case of Homo sapiens, the number of sequenced genomes will approach hundreds of thousands in the next few years. Simply scaling up established bioinformatics pipelines will not be sufficient for leveraging the full potential of such rich genomic data sets. Instead, novel, qualitatively different computational methods and paradigms are needed. We will witness the rapid extension of computational pan-genomics, a new sub-area of research in computational biology. In this article, we generalize existing definitions and understand a pan-genome as any collection of genomic sequences to be analyzed jointly or to be used as a reference. We examine already available approaches to construct and use pan-genomes, discuss the potential benefits of future technologies and methodologies and review open challenges from the vantage point of the above-mentioned biological disciplines. As a prominent example for a computational paradigm shift, we particularly highlight the transition from the representation of reference genomes as strings to representations as graphs. We outline how this and other challenges from different application domains translate into common computational problems, point out relevant bioinformatics techniques and identify open problems in computer science. With this review, we aim to increase awareness that a joint approach to computational pan-genomics can help address many of the problems currently faced in various domains.
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| 56. |
- Molnar, Miklos Z, et al.
(author)
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Association of incident obstructive sleep apnoea with outcomes in a large cohort of US veterans
- 2015
-
In: Thorax. - : BMJ. - 0040-6376 .- 1468-3296. ; 70:9, s. 888-895
-
Journal article (peer-reviewed)abstract
- RATIONALE: There is a paucity of large cohort studies examining the association of obstructive sleep apnoea (OSA) with clinical outcomes including all-cause mortality, coronary heart disease (CHD), strokes and chronic kidney disease (CKD).OBJECTIVES: We hypothesised that a diagnosis of incident OSA is associated with higher risks of these adverse clinical outcomes.METHODS, MEASUREMENTS: In a nationally representative cohort of over 3 million (n=3 079 514) US veterans (93% male) with baseline estimated glomerular filtration rate (eGFR)≥60 mL/min/1.73 m(2), we examined the association between the diagnosis of incident OSA, treated and untreated with CPAP, and: (1) all-cause mortality, (2) incident CHD, (3) incident strokes, (4)incident CKD defined as eGFR<60 mL/min/1.73 m(2), and (5) slopes of eGFR.MAIN RESULTS: Compared with OSA-negative patients, untreated and treated OSA was associated with 86% higher mortality risk, (adjusted HR and 95% CI 1.86 (1.81 to 1.91) and 35% (1.35 (1.21 to 1.51)), respectively. Similarly, untreated and treated OSA was associated with 3.5 times (3.54 (3.40 to 3.69)) and 3 times (3.06 (2.62 to 3.56)) higher risk of incident CHD; 3.5 times higher risk of incident strokes (3.48 (3.28 to 3.64) and 3.50 (2.92 to 4.19)) for untreated and treated OSA, respectively. The risk of incident CKD was also significantly higher in untreated (2.27 (2.19 to 2.36)) and treated (2.79 (2.48 to 3.13)) patients with OSA. The median (IQR) of the eGFR slope was -0.41 (-2.01 to 0.99), -0.61 (-2.69 to 0.93) and -0.87 (-3.00 to 0.70) mL/min/1.73 m(2) in OSA-negative patients, untreated OSA-positive patients and treated OSA-positive patients, respectively.CONCLUSIONS: In this large and contemporary cohort of more than 3 million US veterans, a diagnosis of incident OSA was associated with higher mortality, incident CHD, stroke and CKD and with faster kidney function decline.
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| 57. |
- Muscas, Giuseppe, et al.
(author)
-
The interplay between single particle anisotropy and interparticle interactions in ensembles of magnetic nanoparticles
- 2018
-
In: Physical Chemistry, Chemical Physics - PCCP. - : Royal Society of Chemistry. - 1463-9076 .- 1463-9084. ; 20, s. 28634-28643
-
Journal article (peer-reviewed)abstract
- This paper aims to analyze the competition of single particle anisotropy and interparticle interactions in nanoparticle ensembles using a random anisotropy model. The model is first applied to ideal systems of non-interacting and strongly dipolar interacting ensembles of maghemite nanoparticles. The investigation is then extended to more complex systems of pure cobalt ferrite CoFe2O4 (CFO) and mixed cobalt-nickel ferrite (Co,Ni)Fe2O4 (CNFO) nanoparticles. Both samples were synthetized by the polyol process and exhibit the same particle size (D-TEM approximate to 5 nm), but with different interparticle interaction strengths and single particle anisotropy. The implementation of the random anisotropy model allows investigation of the influence of single particle anisotropy and interparticle interactions, and sheds light on their complex interplay as well as on their individual contribution. This analysis is of fundamental importance in order to understand the physics of these systems and to develop technological applications based on concentrated magnetic nanoparticles, where single and collective behaviors coexist.
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| 58. |
- Novak, Iona, et al.
(author)
-
Early, Accurate Diagnosis and Early Intervention in Cerebral Palsy : Advances in Diagnosis and Treatment
- 2017
-
In: JAMA pediatrics. - : American Medical Association. - 2168-6203 .- 2168-6211. ; 171:9, s. 897-907
-
Research review (peer-reviewed)abstract
- Importance: Cerebral palsy describes the most common physical disability in childhood and occurs in 1 in 500 live births. Historically, the diagnosis has been made between age 12 and 24 months but now can be made before 6 months' corrected age.Objectives: To systematically review best available evidence for early, accurate diagnosis of cerebral palsy and to summarize best available evidence about cerebral palsy-specific early intervention that should follow early diagnosis to optimize neuroplasticity and function.Evidence Review: This study systematically searched the literature about early diagnosis of cerebral palsy in MEDLINE (1956-2016), EMBASE (1980-2016), CINAHL (1983-2016), and the Cochrane Library (1988-2016) and by hand searching. Search terms included cerebral palsy, diagnosis, detection, prediction, identification, predictive validity, accuracy, sensitivity, and specificity. The study included systematic reviews with or without meta-analyses, criteria of diagnostic accuracy, and evidence-based clinical guidelines. Findings are reported according to the PRISMA statement, and recommendations are reported according to the Appraisal of Guidelines, Research and Evaluation (AGREE) II instrument.Findings: Six systematic reviews and 2 evidence-based clinical guidelines met inclusion criteria. All included articles had high methodological Quality Assessment of Diagnostic Accuracy Studies (QUADAS) ratings. In infants, clinical signs and symptoms of cerebral palsy emerge and evolve before age 2 years; therefore, a combination of standardized tools should be used to predict risk in conjunction with clinical history. Before 5 months' corrected age, the most predictive tools for detecting risk are term-age magnetic resonance imaging (86%-89% sensitivity), the Prechtl Qualitative Assessment of General Movements (98% sensitivity), and the Hammersmith Infant Neurological Examination (90% sensitivity). After 5 months' corrected age, the most predictive tools for detecting risk are magnetic resonance imaging (86%-89% sensitivity) (where safe and feasible), the Hammersmith Infant Neurological Examination (90% sensitivity), and the Developmental Assessment of Young Children (83% C index). Topography and severity of cerebral palsy are more difficult to ascertain in infancy, and magnetic resonance imaging and the Hammersmith Infant Neurological Examination may be helpful in assisting clinical decisions. In high-income countries, 2 in 3 individuals with cerebral palsy will walk, 3 in 4 will talk, and 1 in 2 will have normal intelligence.Conclusions and Relevance: Early diagnosis begins with a medical history and involves using neuroimaging, standardized neurological, and standardized motor assessments that indicate congruent abnormal findings indicative of cerebral palsy. Clinicians should understand the importance of prompt referral to diagnostic-specific early intervention to optimize infant motor and cognitive plasticity, prevent secondary complications, and enhance caregiver well-being.
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| 59. |
- Paulus, A, et al.
(author)
-
Coinhibition of the deubiquitinating enzymes, USP14 and UCHL5, with VLX1570 is lethal to ibrutinib- or bortezomib-resistant Waldenstrom macroglobulinemia tumor cells
- 2016
-
In: Blood cancer journal. - : Springer Science and Business Media LLC. - 2044-5385. ; 6:11, s. e492-
-
Journal article (peer-reviewed)abstract
- The survival of Waldenstrom macroglobulinemia (WM) tumor cells hinges on aberrant B-cell receptor (BCR) and MYD88 signaling. WM cells upregulate the proteasome function to sustain the BCR-driven growth while maintaining homeostasis. Clinically, two treatment strategies are used to disrupt these complementary yet mutually exclusive WM survival pathways via ibrutinib (targets BTK/MYD88 node) and bortezomib (targets 20 S proteasome). Despite the success of both agents, WM patients eventually become refractory to treatment, highlighting the adaptive plasticity of WM cells and underscoring the need for development of new therapeutics. Here we provide a comprehensive preclinical report on the anti-WM activity of VLX1570, a novel small-molecule inhibitor of the deubiquitinating enzymes (DUBs), ubiquitin-specific protease 14 (USP14) and ubiquitin carboxyl-terminal hydrolase isozyme L5 (UCHL5). Both DUBs reside in the 19 S proteasome cap and their inhibition by VLX1570 results in rapid and tumor-specific apoptosis in bortezomib- or ibrutinib-resistant WM cells. Notably, treatment of WM cells with VLX1570 downregulated BCR-associated elements BTK, MYD88, NFATC, NF-κB and CXCR4, the latter whose dysregulated function is linked to ibrutinib resistance. VLX1570 administered to WM-xenografted mice resulted in decreased tumor burden and prolonged survival (P=0.0008) compared with vehicle-treated mice. Overall, our report demonstrates significant value in targeting USP14/UCHL5 with VLX1570 in drug-resistant WM and carries a high potential for clinical translation.
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| 60. |
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| 61. |
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| 62. |
- Polzer, S., et al.
(author)
-
Structure-based constitutive model can accurately predict planar biaxial properties of aortic wall tissue
- 2015
-
In: Acta Biomaterialia. - : Elsevier BV. - 1742-7061 .- 1878-7568. ; 14, s. 133-145
-
Journal article (peer-reviewed)abstract
- Structure-based constitutive models might help in exploring mechanisms by which arterial wall histology is linked to wall mechanics. This study aims to validate a recently proposed structure-based constitutive model. Specifically, the model's ability to predict mechanical biaxial response of porcine aortic tissue with predefined collagen structure was tested. Histological slices from porcine thoracic aorta wall (n = 9) were automatically processed to quantify the collagen fiber organization, and mechanical testing identified the non-linear properties of the wall samples (n = 18) over a wide range of biaxial stretches. Histological and mechanical experimental data were used to identify the model parameters of a recently proposed multi-scale constitutive description for arterial layers. The model predictive capability was tested with respect to interpolation and extrapolation. Collagen in the media was predominantly aligned in circumferential direction (planar von Mises distribution with concentration parameter b(M) = 1.03 +/- 0.23), and its coherence decreased gradually from the luminal to the abluminal tissue layers (inner media, b = 1.54 +/- 0.40; outer media, b = 0.72 +/- 0.20). In contrast, the collagen in the adventitia was aligned almost isotropically (b(A) = 0.27 +/- 0.11), and no features, such as families of coherent fibers, were identified. The applied constitutive model captured the aorta biaxial properties accurately (coefficient of determination R-2 = 0.95 +/- 0.03) over the entire range of biaxial deformations and with physically meaningful model parameters. Good predictive properties, well outside the parameter identification space, were observed (R-2 = 0.92 +/- 0.04). Multi-scale constitutive models equipped with realistic micro-histological data can predict macroscopic non-linear aorta wall properties. Collagen largely defines already low strain properties of media, which explains the origin of wall anisotropy seen at this strain level. The structure and mechanical properties of adventitia are well designed to protect the media from axial and circumferential overloads.
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| 63. |
- Pramanick, A., et al.
(author)
-
Stabilization of Polar Nanoregions in Pb-free Ferroelectrics
- 2018
-
In: Physical Review Letters. - 0031-9007. ; 120:20
-
Journal article (peer-reviewed)abstract
- The formation of polar nanoregions through solid-solution additions is known to enhance significantly the functional properties of ferroelectric materials. Despite considerable progress in characterizing the microscopic behavior of polar nanoregions (PNR), understanding their real-space atomic structure and dynamics of their formation remains a considerable challenge. Here, using the method of dynamic pair distribution function, we provide direct insights into the role of solid-solution additions towards the stabilization of polar nanoregions in the Pb-free ferroelectric of Ba(Zr,Ti)O3. It is shown that for an optimum level of substitution of Ti by larger Zr ions, the dynamics of atomic displacements for ferroelectric polarization are slowed sufficiently below THz frequencies, which leads to increased local correlation among dipoles within PNRs. The dynamic pair distribution function technique demonstrates a unique capability to obtain insights into locally correlated atomic dynamics in disordered materials, including new Pb-free ferroelectrics, which is necessary to understand and control their functional properties.
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| 64. |
- Smolčić, Vernesa, et al.
(author)
-
The XXL Survey: XI. ATCA 2.1 GHz continuum observations?
- 2016
-
In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 592:Art. no A10
-
Research review (peer-reviewed)abstract
- We present 2.1 GHz imaging with the Australia Telescope Compact Array (ATCA) of a 6.5 deg2 region within the XXM-Newton XXL South field using a band of 1.1-3.1 GHz.We achieve an angular resolution of 4:7″ × 4:2″ in the final radio continuum map with a median rms noise level of 50 μJy/beam. We identify 1389 radio sources in the field with peak S=N ≥ 5 and present the catalogue of observed parameters. We find that 305 sources are resolved, of which 77 consist of multiple radio components. These number counts are in agreement with those found for the COSMOS-VLA 1.4 GHz survey. We derive spectral indices by a comparison with the Sydney University Molongolo Sky Survey (SUMSS) 843MHz data. We find an average spectral index of -0:78 and a scatter of 0.28, in line with expectations. This pilot survey was conducted in preparation for a larger ATCA program to observe the full 25 deg2 southern XXL field. When complete, the survey will provide a unique resource of sensitive, wide-field radio continuum imaging with complementary X-ray data in the field. This will facilitate studies of the physical mechanisms of radio-loud and radio-quiet AGNs and galaxy clusters, and the role they play in galaxy evolution. The source catalogue is publicly available online via the XXL Master Catalogue browser and the Centre de Données astronomiques de Strasbourg (CDS).
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| 65. |
- Smolcic, V., et al.
(author)
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The XXL Survey: XXIX. GMRT 610 MHz continuum observations
- 2018
-
In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 620
-
Journal article (peer-reviewed)abstract
- We present the 25 square-degree GMRT-XXL-N 610 MHz radio continuum survey, conducted at 50 cm wavelength with the Giant Metrewave Radio Telescope (GMRT) towards the XXL Northern field (XXL-N). We combined previously published observations of the XMM-Large Scale Structure (XMM-LSS) field, located in the central part of XXL-N, with newly conducted observations towards the remaining XXL-N area, and imaged the combined data-set using the Source Peeling and Atmospheric Modeling (SPAM) pipeline. The final mosaic encompasses a total area of 30:4 square degrees, with rms <150 μJy beam-1 over 60% of the area. The rms achieved in the inner 9.6 square degree area, enclosing the XMM-LSS field, is about 200 μJy beam-1, while that over the outer 12.66 square degree area (which excludes the noisy edges) is about 45 μJy beam-1. The resolution of the final mosaic is 6.5 arcsec. We present a catalogue of 5434 sources detected at ≥7 × rms. We verify, and correct the reliability of, the catalog in terms of astrometry, flux, and false detection rate. Making use of the (to date) deepest radio continuum survey over a relatively large (2 square degree) field, complete at the flux levels probed by the GMRT-XXL-N survey, we also assess the survey's incompleteness as a function of flux density. The radio continuum sensitivity reached over a large field with a wealth of multi-wavelength data available makes the GMRTXXL- N 610 MHz survey an important asset for studying the physical properties, environments and cosmic evolution of radio sources, in particular radio-selected active galactic nuclei (AGN).
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| 66. |
- Vizcaíno, Juan Antonio, et al.
(author)
-
A community proposal to integrate proteomics activities in ELIXIR
- 2017
-
In: F1000Research. - : F1000 Research Ltd. - 2046-1402. ; 6
-
Journal article (peer-reviewed)abstract
- Computational approaches have been major drivers behind the progress of proteomics in recent years. The aim of this white paper is to provide a framework for integrating computational proteomics into ELIXIR in the near future, and thus to broaden the portfolio of omics technologies supported by this European distributed infrastructure. This white paper is the direct result of a strategy meeting on 'The Future of Proteomics in ELIXIR' that took place in March 2017 in Tübingen (Germany), and involved representatives of eleven ELIXIR nodes. These discussions led to a list of priority areas in computational proteomics that would complement existing activities and close gaps in the portfolio of tools and services offered by ELIXIR so far. We provide some suggestions on how these activities could be integrated into ELIXIR's existing platforms, and how it could lead to a new ELIXIR use case in proteomics. We also highlight connections to the related field of metabolomics, where similar activities are ongoing. This white paper could thus serve as a starting point for the integration of computational proteomics into ELIXIR. Over the next few months we will be working closely with all stakeholders involved, and in particular with other representatives of the proteomics community, to further refine this paper.
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| 67. |
- Westwood, Sarah, et al.
(author)
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The influence of insulin resistance on cerebrospinal fluid and plasma biomarkers of Alzheimer's pathology.
- 2017
-
In: Alzheimer's research & therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 9:1
-
Journal article (peer-reviewed)abstract
- Insulin resistance (IR) has previously been associated with an increased risk of developing Alzheimer's disease (AD), although the relationship between IR and AD is not yet clear. Here, we examined the influence of IR on AD using plasma and cerebrospinal fluid (CSF) biomarkers related to IR and AD in cognitively healthy men. We also aimedto characterise the shared protein signatures between IR and AD.Fifty-eight cognitively healthy men, 28 IR and 30 non-IR (age and APOE ε4 matched), were drawn from the Metabolic Syndrome in Men study in Kuopio, Finland. CSF AD biomarkers (amyloid β-peptide (Aβ), total tau and tau phosphorylated at the Thr181 epitope) were examined with respect to IR. Targeted proteomics using ELISA and Luminex xMAP assays were performed to assess the influence of IR on previously identified CSF and plasma protein biomarker candidates of AD pathology. Furthermore, CSF and plasma SOMAscan was performed to discover proteins that associate with IR and CSF AD biomarkers.CSF AD biomarkers did not differ between IR and non-IR groups, although plasma insulin correlated with CSF Aβ/tau across the whole cohort. In total, 200 CSF and 487 plasma proteins were differentially expressed between IR and non-IR subjects, and significantly enriched pathways, many of which have been previously implicated in AD, were identified. CSF and plasma proteins significantly associated with CSF AD biomarkers were also discovered, and those sensitive to both IR and AD were identified.These data indicate that IR is not directly related to the level of CSF AD pathology in cognitively healthy men. Proteins that associated with both AD and IR are potential markers indicative of shared pathology.
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| 68. |
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