Probiotic treatment reduces appetite and glucose level in the zebrafish model.

The gut microbiota regulates metabolic pathways that modulate the physiological state of hunger or satiety. Nutrients in the gut stimulate the release of several appetite modulators acting at central and peripheral levels to mediate appetite and glucose metabolism. After an eight-day exposure of zebrafish larvae to probiotic Lactobacillus rhamnosus, high-throughput sequence analysis evidenced the ability of the probiotic to modulate the microbial composition of the gastrointestinal tract. These changes were associated with a down-regulation and up-regulation of larval orexigenic and anorexigenic genes, respectively, an up-regulation of genes related to glucose level reduction and concomitantly reduced appetite and body glucose level. BODIPY-FL-pentanoic-acid staining revealed higher short chain fatty acids levels in the intestine of treated larvae. These results underline the capability of the probiotic to modulate the gut microbiota community and provides insight into how the probiotic interacts to regulate a novel gene network involved in glucose metabolism and appetite control, suggesting a possible role for L. rhamnosus in the treatment of impaired glucose tolerance and food intake disorders by gut microbiota manipulation

Gefechtsfeld der Elb-Armee bei Münchengrätz, 28. Juni 1866

aufgenommen im August 1866 von Gnügge, Hauptmann im Westfälischen Feld Art. Regt. No. 7Nordnordost-orientiertMit Geländeschraffuren[Karten zum preuss.- oesterr. Krieg von 1866

Dbf4-dependent kinase promotes cell cycle controlled resection of DNA double-strand breaks and repair by homologous recombination

DNA double-strand breaks (DSBs) can be repaired by several pathways. In eukaryotes, DSB repair pathway choice occurs at the level of DNA end resection and is controlled by the cell cycle. Upon cell cycle-dependent activation, cyclin-dependent kinases (CDKs) phosphorylate resection proteins and thereby stimulate end resection and repair by homologous recombination (HR). However, inability of CDK phospho-mimetic mutants to bypass this cell cycle regulation, suggests that additional cell cycle regulators may be important. Here, we identify Dbf4-dependent kinase (DDK) as a second major cell cycle regulator of DNA end resection. Using inducible genetic and chemical inhibition of DDK in budding yeast and human cells, we show that end resection and HR require activation by DDK. Mechanistically, DDK phosphorylates at least two resection nucleases in budding yeast: the Mre11 activator Sae2, which promotes resection initiation, as well as the Dna2 nuclease, which promotes resection elongation. Notably, synthetic activation of DDK allows limited resection and HR in G1 cells, suggesting that DDK is a key component of DSB repair pathway selection.ISSN:2041-172

A Cyber-Physical Platform for Model Calibration

25 pages, 8 figuresSynthetic biology has so far made limited use of mathematical models, mostly because their inference has been traditionally perceived as expensive and/or difficult. We have recently demonstrated how in silico simulations and in vitro/vivo experiments can be integrated to develop a cyber-physical platform that automates model calibration and leads to saving 60–80% of the effort. In this book chapter, we illustrate the protocol used to attain such results. By providing a comprehensive list of steps and pointing the reader to the code we use to operate our platform, we aim at providing synthetic biologists with an additional tool to accelerate the pace at which the field progresses toward applicationsN