304 research outputs found
MetaboLab - advanced NMR data processing and analysis for metabolomics
Background\ud
Despite wide-spread use of Nuclear Magnetic Resonance (NMR) in metabolomics for the analysis of biological samples there is a lack of graphically driven, publicly available software to process large one and two-dimensional NMR data sets for statistical analysis.\ud
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Results\ud
Here we present MetaboLab, a MATLAB based software package that facilitates NMR data processing by providing automated algorithms for processing series of spectra in a reproducible fashion. A graphical user interface provides easy access to all steps of data processing via a script builder to generate MATLAB scripts, providing an option to alter code manually. The analysis of two-dimensional spectra (1H,13C-HSQC spectra) is facilitated by the use of a spectral library derived from publicly available databases which can be extended readily. The software allows to display specific metabolites in small regions of interest where signals can be picked. To facilitate the analysis of series of two-dimensional spectra, different spectra can be overlaid and assignments can be transferred between spectra. The software includes mechanisms to account for overlapping signals by highlighting neighboring and ambiguous assignments.\ud
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Conclusions\ud
The MetaboLab software is an integrated software package for NMR data processing and analysis, closely linked to the previously developed NMRLab software. It includes tools for batch processing and gives access to a wealth of algorithms available in the MATLAB framework. Algorithms within MetaboLab help to optimize the flow of metabolomics data preparation for statistical analysis. The combination of an intuitive graphical user interface along with advanced data processing algorithms facilitates the use of MetaboLab in a broader metabolomics context.\ud
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New light valve based in photoinduced space charge fields in BSO-crystals
The combined photoelectric and electrooptic properties of the BSO-crystal lead to a new possibility of realizing a real time spatial light modulator. Under certain geometrical conditions the crystal becomes birefringent in dependence on the local illuminance. Together with a suitable polarizer setup the crystal works as well as an incoherent to coherent converter as for contrast inversion
A spatial light modulator using BSO crystals
The combined use of the photoelectric and electro-optic properties of the Bi12SiO20 (BSO)-crystal leads to a new possibility of realizing a spatial light modulator. Under certain geometrical conditions, which will be discussed, it is possible to realize, that the BSO-crystal becomes birefringent depending on the local illuminance; the physical connection between the distributions of birefringence and illuminance will be shown. The BSO-crystal combined with a polarizer setup works as a spatial light modulator or as an incoherent to coherent converter
Synovial cell metabolism and chronic inflammation in rheumatoid arthritis
Metabolomic studies of body fluids show that immune-mediated inflammatory diseases such as rheumatoid arthritis (RA) are associated with metabolic disruption. This is likely to reflect the increased bioenergetic and biosynthetic demands of sustained inflammation and changes to nutrient and oxygen availability in damaged tissue. The synovial membrane lining layer is the principle site of inflammation in RA. Here the resident cells are the fibroblast-like synoviocytes (FLS) and the synovial tissue macrophages (STM), which are transformed toward overproduction of enzymes which degrade cartilage and bone, and cytokines which promote immune cell infiltration. Recent studies have shown metabolic changes in both FLS and macrophages from RA patients and these may be therapeutically targetable. However, as the origins and subset specific functions of synoviocytes are poorly understood and the signaling modules which control metabolic deviation in RA synovial cells are yet to be explored, significant additional research is needed to translate these findings toward clinical application. Furthermore, in many inflamed tissues, different cell types can forge metabolic collaborations through solute carriers (SLC) in their membranes, to meet a high demand for energy or biomolecules. Such relationships are likely to exist in the synovium and are yet to be explored. Finally, it is not yet known whether metabolic change is a consequence of disease or if primary changes to cellular metabolism might underlie or contribute to early stage disease pathogenesis. This article collates what is known about metabolism in synovial tissue cells and highlights future research directions in this area
A Novel Autosomal Recessive GJA1 Missense Mutation Linked to Craniometaphyseal Dysplasia
Craniometaphyseal dysplasia (CMD) is a rare sclerosing skeletal disorder with progressive hyperostosis of craniofacial bones. CMD can be inherited in an autosomal dominant (AD) trait or occur after de novo mutations in the pyrophosphate transporter ANKH. Although the autosomal recessive (AR)form of CMD had been mapped to 6q21-22 the mutation has been elusive. In this study, we performed whole-exome sequencing for one subject with AR CMD and identified a novel missense mutation (c.716G>A, p.Arg239Gln) in the C-terminus of the gap junction
protein alpha-1 (GJA1) coding for connexin 43 (Cx43). We confirmed this mutation in 6 individuals from 3 additional families. The homozygous mutation cosegregated only with affected family members. Connexin 43 is a major component of gap junctions in osteoblasts, osteocytes, osteoclasts and chondrocytes. Gap junctions are responsible
for the diffusion of low molecular weight molecules between cells. Mutations in Cx43 cause several dominant and recessive disorders involving developmental abnormalities of bone such as dominant and recessive oculodentodigital dysplasia (ODDD; MIM #164200, 257850) and isolated syndactyly type III (MIM #186100), the characteristic digital anomaly in ODDD. However, characteristic ocular and dental features of ODDD as well as syndactyly are absent in
patients with the recessive Arg239Gln Cx43 mutation. Bone remodeling mechanisms disrupted by this novel Cx43 mutation remain to be elucidated
Real-time measurements in optical metrology
Methods as well as recording materials for real-time measurements were discussed. Electrooptical crystals can be used for nearly realtime contactless measuring techniques. The BSO was found appropriate for real-time holographic interferometry, contour line display and for deformation, displacement and vibration analysis. Furthermore, for real-time speckle photography the BSO was found to be very useful. For noise and vibration analysis of oscillating objects such as rotating car tyres, gearing boxes, turbines blades, a vibrometer based on Doppler shift measuring principles was found to be useful, leading to an amplitude and frequency analysis. For the analyse of rotating objects an image derotator is frequently used for compensation of the rotation. In optical metrology real-time methods will be useful for the engineer in future
Glutamine-Derived Aspartate Biosynthesis in Cancer Cells: Role of Mitochondrial Transporters and New Therapeutic Perspectives
Aspartate has a central role in cancer cell metabolism. Aspartate cytosolic availability is crucial for protein and nucleotide biosynthesis as well as for redox homeostasis. Since tumor cells display poor aspartate uptake from the external environment, most of the cellular pool of aspar-tate derives from mitochondrial catabolism of glutamine. At least four transporters are involved in this metabolic pathway: the glutamine (SLC1A5_var), the aspartate/glutamate (AGC), the as-partate/phosphate (uncoupling protein 2, UCP2), and the glutamate (GC) carriers, the last three belonging to the mitochondrial carrier family (MCF). The loss of one of these transporters causes a paucity of cytosolic aspartate and an arrest of cell proliferation in many different cancer types. The aim of this review is to clarify why different cancers have varying dependencies on metabolite transporters to support cytosolic glutamine-derived aspartate availability. Dissecting the precise metabolic routes that glutamine undergoes in specific tumor types is of upmost importance as it promises to unveil the best metabolic target for therapeutic intervention
Grundlagenuntersuchung, Entwicklung und Erprobung optischer Sensoren für die Qualitätssicherung und zum Einsatz an Montagerobotern in der flexiblen Montage : Teilprojekt A4
Die dreidimensionale berührungslose Objektvermessung ist eine zentrale Sensoraufgabe in der industriellen Montage und Qualitätssicherung. Hierfür geeignet sind optische Triangulationsverfahren, die sich im Vergleich zu anderen Verfahren durch hohe relative Distanz- und Lateralauflösung sowie geringen apparativen Aufwand auszeichnen
Hypoxia Triggers Major Metabolic Changes in AML Cells without Altering Indomethacin-Induced TCA Cycle Deregulation
Metabolic Signatures of Lung Cancer in Biofluids: NMR-Based Metabonomics of Blood Plasma
In this work, the variations in the metabolic profile of blood plasma from lung cancer patients and healthy controls were investigated through NMR-based metabonomics, to assess the potential of this approach for lung cancer screening and diagnosis. PLS-DA modeling of CPMG spectra from plasma, subjected to Monte Carlo Cross Validation, allowed cancer patients to be discriminated from controls with sensitivity and specificity levels of about 90%. Relatively lower HDL and higher VLDL + LDL in the patients' plasma, together with increased lactate and pyruvate and decreased levels of glucose, citrate, formate, acetate, several amino acids (alanine, glutamine, histidine, tyrosine, valine), and methanol, could be detected. These changes were found to be present at initial disease stages and could be related to known cancer biochemical hallmarks, such as enhanced glycolysis, glutaminolysis, and gluconeogenesis, together with suppressed Krebs cycle and reduced lipid catabolism, thus supporting the hypothesis of a systemic metabolic signature for lung cancer. Despite the possible confounding influence of age, smoking habits, and other uncontrolled factors, these results indicate that NMR-based metabonomics of blood plasma can be useful as a screening tool to identify suspicious cases for subsequent, more specific radiological tests, thus contributing to improved disease management.ERDF - Competitive Factors Thematic Operational ProgrammeFCT/PTDC/ QUI/68017/2006FCOMP-01-0124-FEDER-007439SFRH/BD/ 63430/2009National UNESCO Committee - L'Oréal Medals of Honor for Women in Science 200Portuguese National NMR Network - RNRM
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