Background and aims: Tumour necrosis factor α (TNF-α) induction of nuclear factor κB (NFκB) activation plays a major role in the pathogenesis of inflammatory bowel disease (IBD). Trefoil factor ...family peptides TFF1, TFF2, and TFF3 exert protective, curative, and tumour suppressive functions in the gastrointestinal tract. In this study, we investigated effects of the TNF-α/NFκB regulatory pathway by TNF-α on expression of TFFs. Methods: After TNF-α stimulation, expression of TFF genes was analysed by quantitative real time polymerase chain reaction and by reporter gene assays in the gastrointestinal tumour cell lines HT-29 and KATO III. Additionally, NFκB subunits and a constitutive repressive form of inhibitory factor κB (IκB) were transiently coexpressed. In vivo, morphological changes and expression of TFF3, mucins, and NFκB were monitored by immunohistochemistry in a rat model of 2,4,6-trinitrobenzene sulphonic acid induced colitis. Results: TNF-α stimulation evoked up to 10-fold reduction of TFF3 expression in the colon tumour cell line HT-29. Downregulation of reporter gene transcription of TFF3 was observed with both TNF-α and NFκB, and was reversible by IκB. In vivo, the increase in epithelial expression of NFκB coincided with reduced TFF3 expression during the acute phase of experimental colitis. Conclusions: Downregulation of intestinal trefoil factor TFF3 is caused by repression of transcription through TNF-α and NFκB activation in vitro. In IBD, perpetual activation of NFκB activity may contribute to ulceration and decreased wound healing through reduced TFF3.
For successful implementation of sustainability in industry robust assessments of products and processes are necessary that quantify environmental aspects under consideration of costs. The ...sustainability needs of companies vary greatly according to region, sector and stakeholder. BASF has developed a toolbox for eco-efficiency assessments that addresses the broad range of in-house and external needs, allowing flexibility while ensuring that relevant and sufficient environmental impact is covered to support decision-making based on quantified sustainability assessments. The toolbox is based on standard practices for life cycle assessment to support strategic decisions, product development and marketing. Environmental impact assessment follows ISO 14040 and 14044. Impacts are aggregated to an overall environmental impact. Life cycle costs are similarly determined and may be combined with environmental impact to an overall Eco-Efficiency Portfolio and Eco-Efficiency Index. The relevance check ensures inclusion of main impact categories and coverage of sufficient environmental impacts. A peer-reviewed case study on the treatment of flowback from fracturing operations demonstrates the applicability of the Eco-Efficiency Analysis. Deposition of flowback in existing hydrocarbon-containing reservoirs was compared with treatment in preparation for disposal to a municipal waste water treatment plant. The Reservoir option is more eco-efficient both at low and high flowback volumes. Disadvantages of the waste water treatment option include the greenhouse gas emissions associated with the high energy needed for the removal of dissolved solids from the flowback. The relevance check shows that climate change is the dominant environmental impact, but photochemical ozone formation, acidification, freshwater eutrophication, human toxicity and resource depletion (mineral & fossil) are significant as well.
Purpose
Modern, personalized treatment concepts in oncology require an interdisciplinary and multiprofessional collaboration. In addition to its relevance in patient care, interdisciplinary ...collaboration is also becoming increasingly important in clinical research as well as medical education and resident training in oncology.
Methods
Between November 2021 and March 2022, an online survey was conducted among German early career research groups, represented by Young Oncologists United (YOU). The aim was to identify the status and need for interdisciplinarity at clinic, educational, and research levels.
Results
A total of 294 participants completed the questionnaire in full. 90.7% of the respondents fully or predominantly agreed with the statement that interdisciplinary work plays a major role in their daily clinical work. 78.9% wished for more interdisciplinary collaboration. Of the 49.7% of participants who have never participated in an interdisciplinary research project, 80.1% said they would like to participate in such a study project in the future. Lack of time resources, too much organizational effort, and possible political conflicts between institutions were identified as factors that make practical implementation difficult. 74.1% declared their willingness to become active in an oncology early career research group.
Conclusion
Interdisciplinary collaboration has become increasingly important in oncology. Networks that span different disciplines could help to promote interdisciplinary research projects among young scientists and improve exchange in professional practice and education with the implication of improved patient care.
The influence of stoichiometry on the elastic modulus of eight-functional end-linked poly(dimethylsiloxane) (PDMS) networks was investigated by extensional rheometry with extensions up to more than ...100%, and the stress−strain relation was found to be almost lineara characteristic property for a network structure with an eight-functional cross-linker. The experimental data were compared to a stochastic model taking into account entanglements and to Monte Carlo simulations. The Mooney−Rivlin model was furthermore used to fit the data, and the dependency of C 1 and C 2 parameters on the stoichiometric ratio was investigated in order to clarify especially the influence of trapped entanglements acting either as chemical cross-links or as sliding links. It was found that including a locking factor dividing trapped entanglements into locked entanglements and slip-links could explain our data obtained for the Mooney−Rivlin constants. It was furthermore found that trapped entanglements dominate when there is an excess of cross-linker, ensuring that all long difunctional DMS chains are bound to the infinite network in both ends.
Zusammenfassung
Jeder Zehnte der über 65-Jährigen in der westlichen Welt wird von Vorhofflimmern betroffen sein. Wichtigstes Ziel bei Patienten mit Vorhofflimmern ist die Verhinderung ...thrombembolischer Komplikationen durch eine suffiziente und am Risikoprofil (CHA
2
DS
2
-Vasc-Score) des Patienten ausgerichtete Antikoagulation sowie die Behandlung zusätzlicher kardiovaskulärer Erkrankungen. Der Leidensdruck bestimmt das weitere Therapiekonzept. Dabei kann der/die behandelnde Arzt/Ärztin eine frequenzkontrollierende Strategie mit einer maximalen Ruheherzfrequenz von 110/min und/oder rhythmuserhaltende Methoden wie Kardioversion, Antiarrhythmika und Katheterablation einsetzen, um die Symptome des Patienten zu mindern. Inwiefern der Erhalt des Sinusrhythmus bei Vorhofflimmerpatienten die Prognose verbessert, wird in laufenden Studien derzeit untersucht.
In western countries one in ten of elderly persons (> 65 years old) will develop atrial fibrillation. The main goal in atrial fibrillation therapy is the prophylaxis of thromboembolic complications ...through anticoagulation according to the individual risk profile (CHA2DS2-Vasc score) of patients and treatment of cardiovascular comorbidities. Symptoms during atrial fibrillation guide the further therapeutic concept. Doctors can deploy a rate control strategy with a heart rate at rest less than 110/min and/or a rhythm control strategy with cardioversion, antiarrhythmic drugs and catheter ablation to alleviate complaints. To what extent maintaining the sinus rhythm improves the prognosis of atrial fibrillation patients is part of ongoing trials.
Synopsis
Objective
Organotypic skin models are powerful tools for research in development, ageing and diseases. They have become more and more complex with the use of multiple cell types. This ...requires a culture medium adapted to optimize the development of such in vitro skin. Foetal bovine serum (FBS) is the most complete supplement in existence at the moment, providing at once growth factors, vitamins, hormones and other circulating compounds. However, this cocktail suffers from batch variability and its animal origin is ethically questionable. More importantly, its biological activities may interfere with the study of certain signalling pathways. Here, we present a strategy for constructing an epidermal equivalent using a defined culture medium without serum.
Methods
An epidermal equivalent was constructed with primary human keratinocytes cultured using an insulin–transferrin–selenium (ITS) medium. Determination of steady‐state gene expression levels and the immunohistological characterization of keratinocyte markers were performed to compare the ITS medium condition with a reference model, where keratinocytes were co‐cultured with fibroblasts in the presence of FBS.
Results
The data show that the ITS medium promoted the expression of keratinocyte proliferation and differentiation markers at the protein and transcript levels in a similar way to that of the reference model.
Conclusion
We show that culture using the ITS medium appears as a viable replacement for FBS in the construction of epidermal equivalents, opening the way to signal transduction studies.
Résumé
Objectif
Les modèles de peaux reconstruites sont des outils performants pour l'étude des mécanismes mis en jeu au cours du développement, du vieillissement et de pathologies. Ces modèles ont connu diverses adaptations et perfectionnements avec notamment l'implémentation de plusieurs types cellulaires. Pour répondre aux contraintes du développement d'une peau reconstruite in vitro, le milieu de culture nécessite d'être réfléchi avec soin. Le facteur le plus répandu est le sérum de veau fœtal (SVF) qui présente la composition la plus complète et permet d'apporter en une fois les facteurs de croissance, les vitamines, les hormones et d'autres éléments circulant. Cependant sa composition varie d'un lot à l'autre au détriment de la reproductibilité expérimentale, et son origine animale peut poser des problèmes éthiques. De plus, ses activités biologiques peuvent le rendre incompatible avec l'étude de certaines voies de signalisation. Dans cette étude, nous présentons une stratégie d'épiderme reconstruit élaboré à partir d'un milieu défini sans sérum.
Methodes
Nous avons élaboré un épiderme reconstruit à partir de kératinocytes humains primaires cultivés dans un milieu supplémenté avec le cocktail Insuline‐Transferrine‐Sélénium (ITS). Nous avons ensuite comparé notre modèle de référence, une co‐culture de kératinocytes et de fibroblastes en milieu supplémenté en SVF, avec ce nouveau modèle et attesté de sa légitimité en déterminant l'expression de marqueurs caractéristiques des kératinocytes par PCR en temps réel et par immunofluorescence.
Resultats
Les résultats montrent que le cocktail ITS engendre des profils d'expression des marqueurs de prolifération et de différenciation, aux niveaux transcriptomique et protéique, similaires au milieu avec SVF.
Conclusion
Nous avons démontré que le milieu supplémenté en ITS est une alternative valable à l'utilisation de SVF dans l'élaboration de modèles d'épidermes reconstruits, ouvrant ainsi le chemin vers l'étude des voies de signalisation.
We developed a serum and fibroblasts free epidermis model. By using the ITS cocktail on keratinocytes, we could obtain a fully differentiated epidermis, which might be used for signaling studies.
In a visionary work published in 1971, Albert Szent-Györgyi predicted that crystalline interfacial water layers would play a fundamental role in biological processes and evolution. However, ...interfacial water layers are so sensitive to observation that they have never been imaged on relevant surfaces, so far. Here we show that crystalline interfacial water layers prevail at room temperature on both hydrophilic and hydrophobic surfaces − in ambient air and subaquatically. We probe the interfacial water layers by monitoring the resonance frequency responses of quartz crystal microbalance sensors to their irradiation with 633 and 670 nm lasers. Our results are consistent with the fractional picture of confined water, previously explored by atomic force microscopy, near-field scanning optical microscopy, and atomic force acoustic microscopy. Since we provide both structural information and quantitative data on the thickness of interfacial water layers, our approach promises progress in biomedicine and life sciences.
Recently several cDNAs have been described encoding lysyl oxidase-like proteins. Their deduced amino acid sequences are characterized by a strong similarity in the C-terminal region, corresponding to ...the lysyl oxidase family catalytic domain, and by marked differences in the N-terminal regions. Different biological functions have been described for lysyl oxidases in addition to their traditionally assumed cross-linking role. To answer the question of whether these different functions are carried out by different lysyl oxidases, purified and active forms of these enzymes are required. At present only the classical form of lysyl oxidase has been purified and characterized. The purpose of this study was to isolate and characterize the lysyl oxidase-like protein. In view of the strong sequence homology with the C-terminal domain of other lysyl oxidases, we chose to purify the protein from bovine aorta using antibodies specific to the N-terminal domain of the proenzyme. We have isolated a 56-kDa protein identified by amino acid sequencing as the bovine lysyl oxidase-like precursor, which is cleaved at the Arg-Arg-Arg sequence at positions 89-91 by a furin-like activity, as revealed after deblocking of the N-terminal residue. The immunopurified protein was largely inactive, but further processing in vitro by bone morphogenetic protein-1 led to an enzyme that was active on elastin and collagen substrates.
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