36 research outputs found
Iterative Dynamic Programming : An Efficient Method for the Validation of Power Flow Control Strategies
A Compact Quadrupole-Orbitrap Mass Spectrometer with FAIMS Interface Improves Proteome Coverage in Short LC Gradients
Protein aggregation capture on microparticles enables multi-purpose proteomics sample preparation
SPIN enables high throughput species identification of archaeological bone by proteomics
Species determination based on genetic evidence is an indispensable tool in archaeology,
forensics, ecology, and food authentication. Most available analytical approaches involve
compromises with regard to the number of detectable species, high cost due to low
throughput, or a labor-intensive manual process. Here, we introduce “Species by Proteome
INvestigation” (SPIN), a shotgun proteomics workflow for analyzing archaeological bone
capable of querying over 150 mammalian species by liquid chromatography-tandem mass
spectrometry (LC-MS/MS). Rapid peptide chromatography and data-independent acquisition
(DIA) with throughput of 200 samples per day reduce expensive MS time, whereas
streamlined sample preparation and automated data interpretation save labor costs. We
confirm the successful classification of known reference bones, including domestic species
and great apes, beyond the taxonomic resolution of the conventional peptide mass fingerprinting (PMF)-based Zooarchaeology by Mass Spectrometry (ZooMS) method. In a blinded
study of degraded Iron-Age material from Scandinavia, SPIN produces reproducible results
between replicates, which are consistent with morphological analysis. Finally, we demonstrate the high throughput capabilities of the method in a high-degradation context by
analyzing more than two hundred Middle and Upper Palaeolithic bones from Southern European sites with late Neanderthal occupation. While this initial study is focused on modern
and archaeological mammalian bone, SPIN will be open and expandable to other biological
tissues and taxa.info:eu-repo/semantics/publishedVersio
Genetic Evidence Implicates the Immune System and Cholesterol Metabolism in the Aetiology of Alzheimer's Disease
Background
1Late Onset Alzheimer's disease (LOAD) is the leading cause of dementia. Recent large genome-wide association studies (GWAS) identified the first strongly supported LOAD susceptibility genes since the discovery of the involvement of APOE in the early 1990s. We have now exploited these GWAS datasets to uncover key LOAD pathophysiological processes.
Methodology
We applied a recently developed tool for mining GWAS data for biologically meaningful information to a LOAD GWAS dataset. The principal findings were then tested in an independent GWAS dataset.
Principal Findings
We found a significant overrepresentation of association signals in pathways related to cholesterol metabolism and the immune response in both of the two largest genome-wide association studies for LOAD.
Significance
Processes related to cholesterol metabolism and the innate immune response have previously been implicated by pathological and epidemiological studies of Alzheimer's disease, but it has been unclear whether those findings reflected primary aetiological events or consequences of the disease process. Our independent evidence from two large studies now demonstrates that these processes are aetiologically relevant, and suggests that they may be suitable targets for novel and existing therapeutic approaches
Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease
We sought to identify new susceptibility loci for Alzheimer's disease through a staged association study (GERAD+) and by testing suggestive loci reported by the Alzheimer's Disease Genetic Consortium (ADGC) in a companion paper. We undertook a combined analysis of four genome-wide association datasets (stage 1) and identified ten newly associated variants with P ≤ 1 × 10−5. We tested these variants for association in an independent sample (stage 2). Three SNPs at two loci replicated and showed evidence for association in a further sample (stage 3). Meta-analyses of all data provided compelling evidence that ABCA7 (rs3764650, meta P = 4.5 × 10−17; including ADGC data, meta P = 5.0 × 10−21) and the MS4A gene cluster (rs610932, meta P = 1.8 × 10−14; including ADGC data, meta P = 1.2 × 10−16) are new Alzheimer's disease susceptibility loci. We also found independent evidence for association for three loci reported by the ADGC, which, when combined, showed genome-wide significance: CD2AP (GERAD+, P = 8.0 × 10−4; including ADGC data, meta P = 8.6 × 10−9), CD33 (GERAD+, P = 2.2 × 10−4; including ADGC data, meta P = 1.6 × 10−9) and EPHA1 (GERAD+, P = 3.4 × 10−4; including ADGC data, meta P = 6.0 × 10−10)
Correction: genetic evidence implicates the immune system and cholesterol metabolism in the aetiology of Alzheimer's disease.
[This corrects the article on p. e13950 in vol. 5.].
Background: Late Onset Alzheimer's disease (LOAD) is the leading cause of dementia. Recent large genome-wide association studies (GWAS) identified the first strongly supported LOAD susceptibility genes since the discovery of the involvement of APOE in the early 1990s. We have now exploited these GWAS datasets to uncover key LOAD pathophysiological processes.
Methodology: We applied a recently developed tool for mining GWAS data for biologically meaningful information to a LOAD GWAS dataset. The principal findings were then tested in an independent GWAS dataset.
Principal Findings: We found a significant overrepresentation of association signals in pathways related to cholesterol metabolism and the immune response in both of the two largest genome-wide association studies for LOAD.
Significance: Processes related to cholesterol metabolism and the innate immune response have previously been implicated by pathological and epidemiological studies of Alzheimer's disease, but it has been unclear whether those findings reflected primary aetiological events or consequences of the disease process. Our independent evidence from two large studies now demonstrates that these processes are aetiologically relevant, and suggests that they may be suitable targets for novel and existing therapeutic approaches
Comparison of Electrical Contacting Techniques to Carbon Fiber Reinforced Plastics for Self-Strain-Sensing Applications
The electrical conductivity of carbon fibers can be used to enable the design of intrinsically smart carbon fiber reinforced plastics (CFRPs). Resistance and impedance measurements of the structural material itself can then be used to measure physical stimuli such as strain or damage without requiring a dedicated sensor to be installed. Measuring the resistance with high precision requires good electrical contact between the measurement equipment and the conductive carbon fibers. In the literature, many different combinations of surface contacting material and surface preparation procedures are used, but only seldomly compared to one another. This article aims to compare frequently used electrical contact methods by analyzing their contact resistance to a pultruded CFRP rod. Furthermore, this study explores the change of contact resistance with increasing mechanical strain. The results show that contact resistance is highly dependent on both the material used for contacting the fibers as well as the surface preparation technique. From the combinations analyzed in this article, the electrodeposition in combination with a surface treatment using concentrated sulphuric acid shows the most promising results
Comparison of Electrical Contacting Techniques to Carbon Fiber Reinforced Plastics for Self-Strain-Sensing Applications
The electrical conductivity of carbon fibers can be used to enable the design of intrinsically smart carbon fiber reinforced plastics (CFRPs). Resistance and impedance measurements of the structural material itself can then be used to measure physical stimuli such as strain or damage without requiring a dedicated sensor to be installed. Measuring the resistance with high precision requires good electrical contact between the measurement equipment and the conductive carbon fibers. In the literature, many different combinations of surface contacting material and surface preparation procedures are used, but only seldomly compared to one another. This article aims to compare frequently used electrical contact methods by analyzing their contact resistance to a pultruded CFRP rod. Furthermore, this study explores the change of contact resistance with increasing mechanical strain. The results show that contact resistance is highly dependent on both the material used for contacting the fibers as well as the surface preparation technique. From the combinations analyzed in this article, the electrodeposition in combination with a surface treatment using concentrated sulphuric acid shows the most promising results