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MicroRNAs (miRNAs) are short, noncoding RNAs that regulate gene expression by suppressing mRNA translation and reducing mRNA stability. A miRNA can potentially bind many mRNAs, thereby affecting the expression of oncogenes and tumor suppressor genes as well as the activity of whole pathways. The promise of miRNA therapeutics in cancer is to harness this evolutionarily conserved mechanism for the coordinated regulation of gene expression, and thus restoring a normal cell phenotype. However, the promiscuous binding of miRNAs can provoke unwanted off-target effects, which are usually caused by high-dose single-miRNA treatments. Thus, it is desirable to develop miRNA therapeutics with increased specificity and efficacy. To achieve that, we propose the concept of miRNA cooperativity in order to exert synergistic repression on target genes, thus lowering the required total amount of miRNAs. We first review miRNA therapies in clinical application. Next, we summarize the knowledge on the molecular mechanism and biological function of miRNA cooperativity and discuss its application in cancer therapies. We then propose and discuss a systems biology approach to investigate miRNA cooperativity for the clinical setting. Altogether, we point out the potential of miRNA cooperativity to reduce off-target effects and to complement conventional, targeted, or immune-based therapies for cancer.

Die in Amerika heimische Kolumbianische Zwergwasserlinse (Wolffia columbiana) tritt neuerdings in Europa als Neophyt auf und konnte in Niedersachsen zum ersten Mal im Jahr 2016 nachgewiesen werden. Im Hintergrund stehen die für den Naturschutz relevanten Fragen, wie viele vermeintliche Vorkommen von Wolffia arrhiza in Wirklichkeit Wolffia columbiana repräsentieren und ob dieser Neophyt die heimische und gefährdete Art Wolffia arrhiza verdrängen kann., Columbian Watermeal (Wolffia columbiana), which is native to the Americas, is now emerging as an alien species in Europe and was recorded in 2016 for the first time in Lower Saxony (Germany). In the background, the questions of nature conservation are, how many occurrences of assumed Wolffia arrhiza are in reality Wolffia columbiana, and whether this neophyte could displace the indig-enous and endangered species Wolffia arrhiza.

Die aus Amerika stammende, neophytische Kolumbianische Zwergwasserlinse Wolffia columbiana wurde in Europa erstmals im Jahr 2013 in Deutschland und den Niederlanden nachgewiesen. Daraufhin wurden weitere 11 Freilandvorkommen von Wolffia aus Deutschland (Nordrhein-Westfalen, Hessen und Rheinland-Pfalz), den Niederlanden und Polen überprüft. Bei 10 der insgesamt 13 untersuchten Proben handelte es sich um Wolffia columbiana, darunter alle 8 bislang untersuchten Vorkommen aus Deutschland. Lediglich bei 3 Freilandproben aus den Niederlanden und Polen handelte es sich um die einheimische Wolffia arrhiza. Der Neophyt scheint also durchaus weiter verbreitet zu sein als gedacht. Die Unterscheidung beider Arten ist nicht ganz leicht, die Unterscheidungsmerkmale werden vorgestellt. Die Vorkommen von Wolffia in Europa sollten überprüft werden, um zu klären, wie viele Vorkommen von Wolffia arrhiza es überhaupt noch gibt, und bei wie vielen Vorkommen es sich tatsächlich um die neophytische Wolffia columbiana oder andere neophytische Wolffia-Arten handelt. The watermeal Wolffia columbiana is native to the Americas. In 2013, the first 2 occurrences of Wolffia columbiana were recorded in Germany and the Netherlands. Consequently, 11 further occurrences of Wolffia from Germany (North Rhine-Westphalia, Hesse and Rhineland-Palatinate), the Netherlands and Poland were examined. Of a total of 13 samples, all 8 samples from Germany and 2 from the Netherlands turned out to be Wolffia columbiana. Only 3 samples from the Netherlands and from Poland were identified as the native Wolffia arrhiza. Thus the alien species seems to be more widespread than previously thought. Since the differentiation of both species is not easy, the distinguishing features are presented. Other occurrences of Wolffia in Europe should be assessed in order to identify how many of them are populations of the non-native Wolffia columbiana or other non-native Wolffia species.

Um den Stand der gegenwärtigen Verbreitung der drei in der Ufervegetation des Niederrheins vorkommenden Cuscuta-Arten C. lupuliformis KROCKER, C. europaea L. und C. gronovii WILLD. festzustellen, wurde eine Kartierung beider Rheinufer zwischen Monheim-Baumberg (Kr. Mettmann) und der niederländischen Grenze durchgeführt. Cuscuta europaea und Cuscuta lupuliformis sind im gesamten Rheinverlauf häufig zu finden, wobei letztere Art die Prallufer des Rheins bevorzugt. Die seltenere Art Cuscuta gronovii konnte an vier Fundorten nachgewiesen werden. Des Weiteren wurde die soziologische Eingliederung der Cuscuta-Arten in der Ufervegetation untersucht. Die Auswertung von insgesamt 112 Vegetationsaufnahmen ergab, daß sich Cuscuta lupuliformis und Cuscuta europaea aus vegetationskundlicher Sicht deutlich unterscheiden. Vom Cuscuto europaeae-Calystegietum Tx. 1947 wurde deswegen ein Cuscuto lupuliformis-Rubetum caesii ass. nov. abgegliedert und neu beschrieben. The present distribution of Cuscuta lupuliformis KROCKER, Cuscuta europaea L. and Cuscuta gronovii WILLD. on the banks of the lower Rhine (Germany) was recorded between Monheim-Baumberg (near Düsseldorf) and the Dutch border. Both Cuscuta europaea and Cuscuta lupuliformis are very common in the area investigated, the latter preferring the outer bends of the river. The rare species Cuscuta gronovii was recorded at four sites. The sociological integration of the Cuscuta species into the bank vegetation was also examined. Evaluation of, in total, 112 relevés showed Cuscuta europaea and Cuscuta lupuliformis preferring different communities. Therefore, the Cuscuto lupuliformis-Rubetum caesii ass. nov. was described and distinguished from the Cuscuto europaeae-Calystegietum Tx. 1947.

Pie chart illustrating enriched biological processes of upregulated genes in the aCaB derived cardiomyocytes. The chart presents the enriched GO superclasses. (DOC 26 kb)

A comparison of experiments without (A) and with (B) bias correction performed with the help of Cufflinks2. The dots represent the dependency of the log ratio of two FPKM values (M) and their mean average (A). The MA plot is a common method to investigate the biases of datasets [53]. (PPTX 236 kb)

Benchmarking results of TRAPLINE performed on a public Galaxy server and on a local desktop PC (based on computing speed). (DOC 31 kb)

Exemplarily results of protein-protein interaction prediction, splice variants and multi promoter regions. (DOC 37 kb)

Example for DAVID functional gene annotation clustering of significantly differentially expressed genes from aCaBs and EBs. (DOC 48 kb)

Performance comparison of TRAPLINE vs other tools. (DOC 28 kb)

TRAPLINE manual: Step by Step instructions for the usage. (DOC 35 kb)