Glutathione Metabolism in Renal Cell Carcinoma Progression and Implications for Therapies

A significantly increased level of the reactive oxygen species (ROS) scavenger glutathione (GSH) has been identified as a hallmark of renal cell carcinoma (RCC). The proposed mechanism for increased GSH levels is to counteract damaging ROS to sustain the viability and growth of the malignancy. Here, we review the current knowledge about the three main RCC subtypes, namely clear cell RCC (ccRCC), papillary RCC (pRCC), and chromophobe RCC (chRCC), at the genetic, transcript, protein, and metabolite level and highlight their mutual influence on GSH metabolism. A further discussion addresses the question of how the manipulation of GSH levels can be exploited as a potential treatment strategy for RCC

Acylcarnitine profiling by low-resolution LC-MS

Acylcarnitines are fatty acyl esters of L-carnitine and facilitate the entry of long-chain fatty acids into mitochondria via the carnitine shuttle, where they are metabolized via ß-oxidation. Alterations of acylcarnitine species can be diagnostic for fatty acid oxidation disorders and organic aciduria and are thus frequently used to screen newborns. Only a subfraction of all known acylcarnitines is thereby monitored and quantified. Therefore, a method for the simultaneous fast and robust detection of all known acylcarnitines was developed using a single concise liquid chromatography mass spectrometry (LC-MS) approach. Derivatization by 3-nitrophenylhydrazine increased the signal intensity of the acylcarnitines and a linear elution from a reversed phase column was observed that was dependent on the length of the carbon chain. This allowed a precise prediction of the exact elution time for each acylcarnitine class, which depended solely on the chemical nature of the carbon chain. This method can be further used to screen for yet unknown acylcarnitine species and adds a layer of confidence for their correct identification. Altogether 123 acylcarnitines species were used to establish a targeted low-resolution LC-MS method. The method was applied to acylcarnitine profiling in several mouse tissues and fluids, in order to identify large differences in the quantity and composition of acylcarnitines

The effects of arbuscular mycorrhizal fungi (AMF) and Rhizophagus irregularis on soil microorganisms assessed by metatranscriptomics and metaproteomics

Arbuscular mycorrhizal fungi (AMF) form symbioses with approximately 80% of plant species and potentially benefit their hosts (e.g. nutrient acquisition) and the soil environment (e.g. soil aggregation). AMF also affect soil microbiota and soil multifunctionality. We manipulated AMF presence (via inoculation of non-sterile soil with Rhizophagus irregularis and using a hyphal compartment design) and used RNA-seq and metaproteomics to assess AMF roles in soil. The results indicated that AMF drove an active soil microbial community expressing transcripts and proteins related to nine metabolic functions, including the metabolism of C and N. We suggest two possible mechanisms: 1) the AMF hyphae produce exudates that select a beneficial community, or, 2) the hyphae compete with other soil microbes for available nutrients and consequently induce the community to mineralize nutrients from soil organic matter. We also identified candidate proteins that are potentially related to soil aggregation, such as Lpt and HSP60. Our results bridge microbial ecology and ecosystem functioning. We show that the AMF hyphosphere contains an active community related to soil respiration and nutrient cycling, thus potentially improving nutrient mineralization from soil organic matter and nutrient supply to the plants

Daten-basierter Service-Nutzen entlang der Customer Journey

Der Begriff Digitalisierung ist omnipräsent und wird besonders auch im Kundendienst als unerlässliches Mittel für die Zukunftstauglichkeit betrachtet. Jedoch zielt dies zu oft vor allem auf betriebliche Effizienzsteigerung ab. Durch Automatisierung im Kundendienst soll der Personalaufwand reduziert werden

Wie sich die Dienstleistungswirtschaft durch Daten wandelt

Dieses Werk ist lizenziert unter einer Creative Commons Namensnennung 3.0 Schweiz Lizenz (http://creativecommons.org/licenses/by/3.0/ch/

Simulation based case studies for management training in the fields of production and supply chain Management

It is well known that interactive learning is much more efficient than classical learning with textbooks. With the broad propagation of computers, new opportunities for computer-based interactive learning are available. In particular, simulation based learning allows the student to learn based on experience. In economic and technical environments, where complex systems comprise numerous decision variables, conducting experiments can provide a deeper insights and an intuitive understanding to the student. In the present paper, a newly developed environment for computer-based interactive learning in the fields of production and supply chain training is described. The different steps from the evaluation of an appropriate electronic platform to the development of eight different case studies for the students are explained. The environment now provides an easily applicable and ready-to-use solution for university teachers and their students

Mutual Zonated Interactions of Wnt and Hh Signaling Are Orchestrating the Metabolism of the Adult Liver in Mice and Human

The Hedgehog (Hh) and Wnt/β-Catenin (Wnt) cascades are morphogen pathways whose pronounced influence on adult liver metabolism has been identified in recent years. How both pathways communicate and control liver metabolic functions are largely unknown. Detecting core components of Wnt and Hh signaling and mathematical modeling showed that both pathways in healthy liver act largely complementary to each other in the pericentral (Wnt) and the periportal zone (Hh) and communicate mainly by mutual repression. The Wnt/Hh module inversely controls the spatiotemporal operation of various liver metabolic pathways, as revealed by transcriptome, proteome, and metabolome analyses. Shifting the balance to Wnt (activation) or Hh (inhibition) causes pericentralization and periportalization of liver functions, respectively. Thus, homeostasis of the Wnt/Hh module is essential for maintaining proper liver metabolism and to avoid the development of certain metabolic diseases. With caution due to minor species-specific differences, these conclusions may hold for human liver as well

Serial interactome capture of the human cell nucleus

Novel RNA-guided cellular functions are paralleled by an increasing number of RNA-binding proteins (RBPs). Here we present ‘serial RNA interactome capture’ (serIC), a multiple purification procedure of ultraviolet-crosslinked poly(A)–RNA–protein complexes that enables global RBP detection with high specificity. We apply serIC to the nuclei of proliferating K562 cells to obtain the first human nuclear RNA interactome. The domain composition of the 382 identified nuclear RBPs markedly differs from previous IC experiments, including few factors without known RNA-binding domains that are in good agreement with computationally predicted RNA binding. serIC extends the number of DNA–RNA-binding proteins (DRBPs), and reveals a network of RBPs involved in p53 signalling and double-strand break repair. serIC is an effective tool to couple global RBP capture with additional selection or labelling steps for specific detection of highly purified RBPs

Protein sets define disease states and predict in vivo effects of drug treatment

Gaining understanding of common complex diseases and their treatments are the main drivers for life sciences. As we show here, comprehensive protein set analyses offer new opportunities to decipher functional molecular networks of diseases and assess the efficacy and side-effects of treatments in vivo. Using mass spectrometry, we quantitatively detected several thousand proteins and observed significant changes in protein pathway (dys-) regulated in diet-induced obesity mice. Analysis of the expression and posttranslational modifications of proteins in various peripheral metabolic target tissues including adipose, heart and liver tissue generated functional insights in the regulation of cell and tissue homeostasis during high fat diet and medication with two anti-diabetic compounds. Protein set analyses singled out pathways for functional characterization, and indicated for example early on potential cardiovascular complication of the diabetes drug rosiglitazone. In vivo protein set detection can provide new avenues for monitoring complex disease processes, and for evaluating preclinical drug candidates