Pancreatic cancer is still a dismal disease. The high mortality rate is mainly caused by the lack of highly sensitive and specific diagnostic tools, and most of the patients are diagnosed in an advanced and incurable stage. Knowledge about precursor lesions for pancreatic cancer has grown significantly over the last decade, and nowadays we know that mainly three lesions (PanIN, and IPMN, MCN) are responsible for the development of pancreatic cancer. The early detection of these lesions is still challenging but provides the chance to cure patients before they might get an invasive pancreatic carcinoma. This paper focuses on PanIN, IPMN, and MCN lesions and reviews the current level of knowledge and clinical measures.

The two related putative cytochrome c oxidase (COX) assembly factors HCC1 and HCC2 from Arabidopsis thaliana are Homologs of the yeast Copper Chaperones Sco1p and Sco2p. The hcc1 null mutation was previously shown to be embryo lethal while the disruption of the HCC2 gene function had no obvious effect on plant development, but increased the expression of stress-responsive genes. Both HCC1 and HCC2 contain a thioredoxin domain, but only HCC1 carries a Cu-binding motif also found in Sco1p and Sco2p. In order to investigate the physiological implications suggested by this difference, various hcc1 and hcc2 mutants were generated and analyzed. The lethality of the hcc1 knockout mutation was rescued by complementation with the HCC1 gene under the control of the embryo-specific promoter ABSCISIC ACID INSENSITIVE 3. However, the complemented seedlings did not grow into mature plants, underscoring the general importance of HCC1 for plant growth. The HCC2 homolog was shown to localize to mitochondria like HCC1, yet the function of HCC2 is evidently different, because two hcc2 knockout lines developed normally and exhibited only mild growth suppression compared with the wild type (WT). However, hcc2 knockouts were more sensitive to UV-B treatment than the WT. Complementation of the hcc2 knockout with HCC2 rescued the UV-B-sensitive phenotype. In agreement with this, exposure of wild-type plants to UV-B led to an increase of HCC2 transcripts. In order to corroborate a function of HCC1 and HCC2 in COX biogenesis, COX activity of hcc1 and hcc2 mutants was compared. While the loss of HCC2 function had no significant effect on COX activity, the disruption of one HCC1 gene copy was enough to suppress respiration by more than half compared with the WT. Therefore, we conclude that HCC1 is essential for COX function, most likely by delivering Cu to the catalytic center. HCC2, on the other hand, seems to be involved directly or indirectly in UV-B-stress responses.

Background: Replacement of dysfunctional β-cells in the islets of Langerhans by transdifferentiation of pancreatic acinar cells has been proposed as a regenerative therapy for diabetes. Adult acinar cells spontaneously revert to a multipotent state upon tissue dissociation in vitro and can be stimulated to redifferentiate into β-cells. Despite accumulating evidence that contact-mediated signals are involved, the mechanisms regulating acinar-to-islet cell transdifferentiation remain poorly understood. Results: In this study, we propose that the crosstalk between two contact-mediated signaling mechanisms, lateral inhibition and lateral stabilization, controls cell fate stability and transdifferentiation of pancreatic cells. Analysis of a mathematical model combining gene regulation with contact-mediated signaling reveals the multistability of acinar and islet cell fates. Inhibition of one or both modes of signaling results in transdifferentiation from the acinar to the islet cell fate, either by dedifferentiation to a multipotent state or by direct lineage switching. Conclusions: This study provides a theoretical framework to understand the role of contact-mediated signaling in pancreatic cell fate control that may help to improve acinar-to-islet cell transdifferentiation strategies for β-cell neogenesis.

Determination of cell signalling behaviour is crucial for understanding the physiological response to a specific stimulus or drug treatment. Current approaches for large-scale data analysis do not effectively incorporate critical topological information provided by the signalling network. We herein describe a novel model- and data-driven hybrid approach, or signal transduction score flow algorithm, which allows quantitative visualization of cyclic cell signalling pathways that lead to ultimate cell responses such as survival, migration or death. This score flow algorithm translates signalling pathways as a directed graph and maps experimental data, including negative and positive feedbacks, onto gene nodes as scores, which then computationally traverse the signalling pathway until a pre-defined biological target response is attained. Initially, experimental data-driven enrichment scores of the genes were computed in a pathway, then a heuristic approach was applied using the gene score partition as a solution for protein node stoichiometry during dynamic scoring of the pathway of interest. Incorporation of a score partition during the signal flow and cyclic feedback loops in the signalling pathway significantly improves the usefulness of this model, as compared to other approaches. Evaluation of the score flow algorithm using both transcriptome and ChIP-seq data-generated signalling pathways showed good correlation with expected cellular behaviour on both KEGG and manually generated pathways. Implementation of the algorithm as a Cytoscape plug-in allows interactive visualization and analysis of KEGG pathways as well as user-generated and curated Cytoscape pathways. Moreover, the algorithm accurately predicts gene-level and global impacts of single or multiple in silico gene knockouts. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

This article provides an overview of the first BioASQ challenge, a competition on large-scale biomedical semantic indexing and question answering (QA), which took place between March and September 2013. BioASQ assesses the ability of systems to semantically index very large numbers of biomedical scientific articles, and to return concise and user-understandable answers to given natural language questions by combining information from biomedical articles and ontologies.

Sogar eine vegetarische Ernährung führt durch den Konsum von Milchprodukten zum Schlachten der nicht mehr produktiven oder ausselektierten Milchkühe sowie der männlichen Nachkommen. Eine Rinderhaltung ohne Schlachtung (ROS) wäre (für Lakto-Vegetarier) hier ein Ausweg. Es wurden narrative und semi-strukturierte Interviews mit Tierhaltern der 5 hier dargestellten Fallbeispiele mit qualitativen Methoden der interpretativen Sozialforschung (Grounded Theory, Biographieforschung und sequentielle Feinanalyse) erhoben und untersucht. Die 5 Fallbeispiele wurden anhand biographischer Entwicklungen, ihrer Ethik und ihrem Tierhaltungssystem sowie anhand ihrer Konventionen verglichen. Der Fallvergleich ergab 5 Grundsätze des Care-Systems einer ROS: 1. Universal, 2. Bedingungslos, 3. Das ganze Leben betreffend - „a lifetime of Care“, 4. Familisierend, 5. Präventiv. Das Agrar-System der Fallbeispiele wurde in drei Betriebsstile differenziert: Reine Sanctuaries (Lebens-/Gnadenhof), Landwirtschaftliche Sanctuaries und Vegetarische Rinderhaltung/Milcherzeugung. Das Care- und das Agrar-System ergeben zusammen ein Agrar-Care-System. Kernelemente des Agrar-Systems der 4 hier untersuchten europäischen Betriebe sind u.a. ein hohes durchschnittliches Abgangsalter der Kühe von 12,5 Jahren und der Ochsen von 10 Jahren, stabile Herden, insg. vielfältige Dungnutzung, eine weitgehend muttergebundene Kälberaufzucht und partielle Ochsenanspannung. Bei dem dritten Fallbeispiel beträgt die Dauer der Laktationen durchschnittlich 2,8 Jahre und es werden dabei 9.055 kg pro Laktation ermolken. Bei Kühen mit sehr langen Laktationen sinken vom ca. 4.-6. Jahr die Leistungen nicht mehr und sind persistent. Die Milchkühe sind für 3,4 Jahre (als Mittel der beiden melkenden Betriebe) „in Rente". Der kostendeckende Milcherlös liegt bei ca. 2,95 bis 3,05 EUR pro kg Milch. Eine gemolkene Kuh trägt dabei die Kosten von 0,63 Kühen „in Rente" sowie von 1,48 Ochsen. Milch und Dung wären hier Beiprodukte des Tierlebens. / Even a vegetarian nutrition, through consumption of milk products, leads to the slaughtering of dairy cows that are no longer productive or have been sorted out, and of their male offspring. A cattle husbandry without slaughtering (here ‘CWS’) could be a solution (for lacto-vegetarians). Narrative and semi-structured interviews with the heads of animal husbandry in a total of five cases have been carried out and reviewed using qualitative methods of interpretive social research (Grounded Theory, biography research and detailed sequential analysis). In a case comparison, the five cases have been compared to each other in terms of their biographical developments, their ethics and their animal husbandry systems and also in terms of their conventions. The following five principles for a care system in CWS were derived: Universality, Unconditionality, A lifetime of care, Familialisation and Prevention. The agri-system of the case studies has been differentiated into three styles of farming: Pure sanctuary, agricultural sanctuary and vegetarian cattle husbandry. The combination of the agri- and care-system becomes the agri-care-system. Core elements of the agricultural system of CWS and of the 4 European farms are: a high average dying age which is 12.5 years for cows and 10 years for oxen, novel dung products, mostly rearing calves with the dam and on some farms the use of oxen for traction. In regard to the third case study, the average duration of lactation is 2.8 years, generating about 9,055 kg milk per lactation cycle. The dairy cows "retire" for a period of 3.4 years as a mean of the two milking case studies. In cows with very long lactation cycles, the milk yield, instead of decreasing from the 4th to the 6th year, rather seems to be constant during this period. The cost-covering milk revenue would be about 2,95 up to 3,05 EUR per kg. Each milked cow carries the cost of ca. 0,63 "retired" cows and 1,48 oxen. Milk and dung are the by-product of the animal life.