244 research outputs found
Zyklen in den Differenzen tĂ€glicher mittlerer WasserstĂ€nde zwischen nördlichen und sĂŒdlichen Ostseepegeln
Protein-observed 19F NMR of LecA from Pseudomonas aeruginosa
The carbohydrate-binding protein LecA (PA-IL) from Pseudomonas aeruginosa plays an important
role in the formation of biofilms in chronic infections. Development of inhibitors to disrupt LecAmediated biofilms is desired but it is limited to carbohydrate-based ligands. Moreover, discovery
of drug-like ligands for LecA is challenging because of its weak affinities. Therefore, we established
a protein-observed 19F (PrOF) nuclear magnetic resonance (NMR) to probe ligand binding to LecA.
LecA was labeled with 5-fluoroindole to incorporate 5-fluorotryptophanes and the resonances were
assigned by site-directed mutagenesis. This incorporation did not disrupt LecA preference for
natural ligands, Ca2+ and D-galactose (D-Gal). Following NMR perturbation of W42, which is located
in the carbohydrate-binding region of LecA, allowed to monitor binding of low-affinity ligands such
as N-acetyl D-galactosamine (D-GalNAc, Kd = 780 ± 97 ΌM). Moreover, PrOF NMR titration with
glycomimetic of LecA p-nitrophenyl ÎČ-D-galactoside (pNPGal, Kd = 54 ± 6 ÎŒM) demonstrated a
6-fold improved binding of D-Gal proving this approach to be valuable for ligand design in future
drug discovery campaigns that aim to generate inhibitors of LecA
Electronic properties of curved few-layers graphene: a geometrical approach
We show the presence of non-relativistic L\'evy-Leblond fermions in flat
three- and four-layers graphene with AB stacking, extending the results
obtained in [Curvatronics2017] for bilayer graphene. When the layer is curved
we obtain a set of equations for Galilean fermions that are a variation of
those of L\'evy-Leblond with a well defined combination of pseudospin, and that
admit L\'evy-Leblond spinors as solutions in an approriate limit. The local
energy of such Galilean fermions is sensitive to the intrinsic curvature of the
surface. We discuss the relationship between two-dimensional pseudospin,
labelling layer degrees of freedom, and the different energy bands. For
L\'evy-Leblond fermions an interpretation is given in terms of massless
fermions in an effective 4D spacetime, and in this case the pseudospin is
related to four dimensional chirality. A non-zero energy band gap between
conduction and valence electronic bands is obtained for surfaces with positive
curvature.Comment: 16 pages, 4 figures. Matches the published version. Refined theory
that describes the unique combination of isospin states ocurring in curved
bilayer graphene sheet
Discovery of food identity markers by metabolomics and machine learning technology
Verification of food authenticity establishes consumer trust in food ingredients and components of processed food. Next to genetic or protein markers, chemicals are unique identifiers of food components. Non-targeted metabolomics is ideally suited to screen food markers when coupled to efficient data analysis. This study explored feasibility of random forest (RF) machine learning, specifically its inherent feature extraction for non-targeted metabolic marker discovery. The distinction of chia, linseed, and sesame that have gained attention as âsuperfoodsâ served as test case. Chemical fractions of non-processed seeds and of wheat cookies with seed ingredients were profiled. RF technology classified original seeds unambiguously but appeared overdesigned for material with unique secondary metabolites, like sesamol or rosmarinic acid in the Lamiaceae, chia. Most unique metabolites were diluted or lost during cookie production but RF technology classified the presence of the seed ingredients in cookies with 6.7% overall error and revealed food processing markers, like 4-hydroxybenzaldehyde for chia and succinic acid monomethylester for linseed additions. RF based feature extraction was adequate for difficult classifications but marker selection should not be without human supervision. Combination with alternative data analysis technologies is advised and further testing of a wide range of seeds and food processing methods.Fil: Erban, Alexander. Max-Planck-Institute of Molecular Plant Physiology. Department of Molecular Physiology; AlemaniaFil: Fehrle, Ines. Max-Planck-Institute of Molecular Plant Physiology. Department of Molecular Physiology; AlemaniaFil: Martinez-Seidel, Federico. Max-Planck-Institute of Molecular Plant Physiology. Department of Molecular Physiology; AlemaniaFil: Brigante, Federico IvĂĄn. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - CĂłrdoba. Instituto de Ciencia y TecnologĂa de Alimentos CĂłrdoba. Universidad Nacional de CĂłrdoba. Facultad de Ciencias QuĂmicas. Instituto de Ciencia y TecnologĂa de Alimentos CĂłrdoba; ArgentinaFil: Lucini Mas, AgustĂn. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - CĂłrdoba. Instituto de Ciencia y TecnologĂa de Alimentos CĂłrdoba. Universidad Nacional de CĂłrdoba. Facultad de Ciencias QuĂmicas. Instituto de Ciencia y TecnologĂa de Alimentos CĂłrdoba; ArgentinaFil: Baroni, MarĂa VerĂłnica. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - CĂłrdoba. Instituto de Ciencia y TecnologĂa de Alimentos CĂłrdoba. Universidad Nacional de CĂłrdoba. Facultad de Ciencias QuĂmicas. Instituto de Ciencia y TecnologĂa de Alimentos CĂłrdoba; ArgentinaFil: Wunderlin, Daniel Alberto. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - CĂłrdoba. Instituto de Ciencia y TecnologĂa de Alimentos CĂłrdoba. Universidad Nacional de CĂłrdoba. Facultad de Ciencias QuĂmicas. Instituto de Ciencia y TecnologĂa de Alimentos CĂłrdoba; ArgentinaFil: Kopka, Joachim. Max-Planck-Institute of Molecular Plant Physiology. Department of Molecular Physiology; Alemani
Eignung der instrumentellen Analytik fĂŒr die Unterscheidung von ökologisch und konventionell gefarmtem Speisefisch bei verschiedenen Spezies einschlieĂlich verarbeiteter Produkte
Die aufgrund der Begrenzung natĂŒrlicher Ressourcen wachsende Bedeutung der Aquakultur fĂŒr die Produktion von Speisefisch erfordert geeignete Instrumente zur RĂŒckverfolgbarkeit von Fischereierzeugnissen. Dies gilt insbesondere im Hinblick auf die zum 01.07.2010 in Kraft getretene ergĂ€nzende Ăko-Verordnung (EG) 710/2009 bezĂŒglich der Produktion von Tieren in ökologischer Aquakultur. Um dem potenziellen Risiko der Falschdeklaration konventioneller Produkte als Bio-Ware zu begegnen, untersuchte das Vorhaben die Eignung etablierter Methoden der instrumentellen Analytik fĂŒr die Authentifizierung von Fischereierzeugnissen aus ökologischer Aquakultur.
Exemplarisch wurden Bachforellen, Pangasius, Doraden sowie Garnelen analysiert, die innerhalb von 18 Monaten wiederholt aus mehreren ökologisch und konventionell arbeitenden Betrieben beschafft wurden. ZusÀtzlich wurden verarbeitete Produkte (gerÀuchert, gebeizt) aus Lachs und Bachforelle untersucht sowie FÀnge aus wild lebenden BestÀnden von Doraden, Garnelen und Lachs in die Differenzierung einbezogen. Nach Speziesidentifizierung der insgesamt 320 Fischereierzeugnisse erfolgte die Bestimmung des Carotinoidmusters (Lachs, Bachforelle, Garnele), der FettsÀuren (FS) sowie der stabilen Isotope (SI) von Kohlenstoff und Stickstoff.
Zur Differenzierung der drei Aufwuchsformen (ökologisch, konventionell, wild) wurden sowohl einzelne Parameter als auch durch multivariate Tests (Partial Least Squares Discriminant Analysis) ermittelte Kombinationen betrachtet. FĂŒr jede Tierart wurden â meist spezifische â Unterscheidungskriterien ermittelt, die mit Ausnahme von Garnelen eine weitreichende Authentifizierung von Bio-Produkten erlaubten. Aufgrund der potenziell hohen VariabilitĂ€t der Futterzusammensetzung ist eine Festlegung starrer Grenzwerte fĂŒr einzelne Parameter nicht praktikabel. Nach Demonstration der prinzipiellen Eignung vor allem der FS- und SI-Analytik zur Bestimmung der Produktionsweise sollten in der Praxis der LebensmittelĂŒberwachung jeweils empirische Schwellenwerte oder auch abweichende Kombinationen von Variablen ermittelt und verwendet werden. Der Einsatz der Verfahren kann durch Steigerung des Verbrauchervertrauens ein gesundes Wachstum der ökologischen Aquakultur unterstĂŒtzen
Data Harmonisation Put into Practice by the HUMBOLDT Project
Data harmonisation is a key prerequisite for an efficient and meaningful combination of heterogeneous information in cross-border applications and spatial data infrastructures. This is also the main objective of the INSPIRE Directive which has entered its implementation phase. Data Specifications for INSPIRE Annex I data themes have been published containing harmonised, pan-European data models and a number of other requirements. Data providers across Europe face the challenge of transforming their legacy data to comply with these Data Specifications. This paper presents results of the European project HUMBOLDT. Data harmonisation requirements identified in nine scenarios covering a wide range of application domains and using heterogeneous data from a number of European countries are illustrated. Processes required to achieve data harmonisation are described from an application point of view. The open-source software framework for data harmonisation and services integration developed in the project is introduced and its use in two application scenarios is demonstrated
Can Exercise Enhance the Efficacy of Checkpoint Inhibition by Modulating Anti-Tumor Immunity?
Immune checkpoint inhibition (ICI) has revolutionized cancer therapy. However, response to ICI is often limited to selected subsets of patients or not durable. Tumors that are non-responsive to checkpoint inhibition are characterized by low anti-tumoral immune cell infiltration and a highly immunosuppressive tumor microenvironment. Exercise is known to promote immune cell circulation and improve immunosurveillance. Results of recent studies indicate that physical activity can induce mobilization and redistribution of immune cells towards the tumor microenvironment (TME) and therefore enhance anti-tumor immunity. This suggests a favorable impact of exercise on the efficacy of ICI. Our review delivers insight into possible molecular mechanisms of the crosstalk between muscle, tumor, and immune cells. It summarizes current data on exercise-induced effects on anti-tumor immunity and ICI in mice and men. We consider preclinical and clinical study design challenges and discuss the role of cancer type, exercise frequency, intensity, time, and type (FITT) and immune sensitivity as critical factors for exercise-induced impact on cancer immunosurveillance
In renal cell carcinoma the PTEN splice variant PTEN-Î shows similar function as the tumor suppressor PTEN itself
BACKGROUND:
Loss of PTEN is involved in tumor progression of several tumor entities including renal cell carcinoma (RCC). During the translation process PTEN generates a number of splice variants, including PTEN-Î. We analyzed the impact of PTEN-Î in RCC progression.
METHODS:
In specimens of RCC patients the expression of PTEN-Î and PTEN was quantified. The PTEN expressing RCC cell line A498 and the PTEN deficient 786-O cell line were stably transfected with the PTEN-Î or PTEN transcript. In Caki-1 cells that highly express PTEN-Î, this isoform was knocked down by siRNA. Cell migration, adhesion, apoptosis and signaling pathways activities were consequently analyzed in vitro.
RESULTS:
Patients with a higher PTEN-Î expression had a longer lymph node metastasis free and overall survival. In RCC specimens, the PTEN-Î expression correlated with the PTEN expression. PTEN-Î as well as PTEN induced a reduced migration when using extracellular matrix (ECM) compounds as chemotaxins. This effect was confirmed by knockdown of PTEN-Î, inducing an enhanced migration. Likewise a decreased adhesion on these ECM components could be shown in PTEN-Î and PTEN transfected cells. The apoptosis rate was slightly increased by PTEN-Î. In a phospho-kinase array and Western blot analyses a consequently reduced activity of AKT, p38 and JNK could be shown.
CONCLUSIONS:
We could show that the PTEN splice variant PTEN-Î acts similar to PTEN in a tumor suppressive manner, suggesting synergistic effects of the two isoforms. The impact of PTEN-Î in context of tumor progression should thus be taken into account when generating new therapeutic options targeting PTEN signaling in RCC
Entwicklung von Methoden zum Nachweis von ökologisch erzeugten Produkten am Beispiel der Lachszucht
Zur Zeit stehen der LebensmittelĂŒberwachung keine analytischen Methoden zur VerfĂŒgung mit denen Deklarationen wie âBio-Fischâ, âBio-Lachsâ oder âOrganic Salmonâ am Erzeugnis ĂŒberprĂŒft werden können. Das Ziel dieses Projektes bestand in der Entwicklung von objektiven, praxistauglichen Analysenverfahren zur Identifizierung von Lachserzeugnissen aus der ökologischen Aquakultur.
Die VerfĂŒgbarkeit solcher Verfahren ermöglicht einen verbesserten Verbraucherschutz und eine StĂ€rkung des redlichen Handels. Es kann aber auch der Tierschutz von den Ergebnissen des Projektes profitieren, wenn man berĂŒcksichtigt, dass die ökologische Aquakultur eine artgerechte Haltung der Fische besonders fördern soll.
In einem umfangreichen Untersuchungsprogramm wurden biologische und chemische Methoden, sowie ganzheitliche Verfahren eingesetzt. Zum Vergleich wurden auch Wildlachse und einige Lachsfutter analysiert. Probenziehungen fanden in den Jahren 2002 und 2003 statt; der Ăkolachs und Wildlachs stammte aus Irland, Farmlachse hoher QualitĂ€t wurden aus Irland und Norwegen bezogen. Insgesamt wurden 100 Lachsproben analysiert.
Folgende Methoden kamen u.a. zum Einsatz: Beurteilung des Ausgangsmaterials (Aussehen, Kondition der Lachse), DNA Analyse, Bildverarbeitung (Muskelstruktur), Aromaprofil Bestimmung, Messung der Gehalte an EiweiĂ und Fett, Bestimmung von Stoffwechselprodukten und Stressparametern, Stabil-Isotopen-Analyse (15-N, 13-C), Bestimmung der Astaxanthin-Isomere und Canthaxanthingehalte, Bestimmung von organischen und anorganischen RĂŒckstĂ€nden.
Aus den vielfĂ€ltigen Ergebnissen ist zu schlieĂen, dass Ăko- und Farmlachs sich in Aussehen, Zusammensetzung (z.B. im Fettgehalt) und Schadstoffgehalten generell nicht unterscheiden. Nur mit Hilfe einer Methode, der Bestimmung der Astaxanthin-Isomere, konnte der Ăkolachs aus Irland sicher identifiziert werden
Strong Expression of Chemokine Receptor CXCR4 by Renal Cell Carcinoma Correlates with Advanced Disease
Diverse chemokines and their receptors have been associated with tumor growth, tumor dissemination, and local immune escape. In different tumor entities, the level of chemokine receptor CXCR4 expression has been linked with tumor progression and decreased survival. The aim of this study was to evaluate the influence of CXCR4 expression on the progression of human renal cell carcinoma. CXCR4 expression of renal cell carcinoma was assessed by immunohistochemistry in 113 patients. Intensity of CXCR4 expression was correlated with both tumor and patient characteristics. Human renal cell carcinoma revealed variable intensities of CXCR4 expression. Strong CXCR4 expression of renal cell carcinoma was significantly associated with advanced T-status (P = .039), tumor dedifferentiation (P = .0005), and low hemoglobin (P = .039). In summary, strong CXCR4 expression was significantly associated with advanced dedifferentiated renal cell carcinoma
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