Engineering microbialm phenotypes through rewiring of genetic networks

The ability to program cellular behaviour is a major goal of synthetic biology, with applications in health, agriculture and chemicals production. Despite efforts to build ‘orthogonal’ systems, interactions between engineered genetic circuits and the endogenous regulatory network of a host cell can have a significant impact on desired functionality. We have developed a strategy to rewire the endogenous cellular regulatory network of yeast to enhance compatibility with synthetic protein and metabolite production. We found that introducing novel connections in the cellular regulatory network enabled us to increase the production of heterologous proteins and metabolites. This strategy is demonstrated in yeast strains that show significantly enhanced heterologous protein expression and higher titers of terpenoid production. Specifically, we found that the addition of transcriptional regulation between free radical induced signalling and nitrogen regulation provided robust improvement of protein production. Assessment of rewired networks revealed the importance of key topological features such as high betweenness centrality. The generation of rewired transcriptional networks, selection for specific phenotypes, and analysis of resulting library members is a powerful tool for engineering cellular behavior and may enable improved integration of heterologous protein and metabolite pathways

The making of an entertainment revolution: How the TV format trade became a global industry

From its humble origins in the 1950s, the TV format industry has become a global trade worth billions of Euros per year. Few viewers are aware that their favourite shows may be local adaptations but formats represent a significant percentage of European broadcasting schedules in access prime time and prime time. Formatted brands exist in all TV genres and reach almost every country in the world. This article defends the thesis that the format business turned into a global industry in the late 1990s. Before this turning point, the few formatted programmes were most likely American game shows that travelled slowly and to a limited number of territories. Following an overview of this early period, this article examines the convergence of factors that created a world format market. These include the emergence of four exceptional formats (Who Wants to Be a Millionaire?, Survivor, Big Brother and Idols), the formation of a programming market, the rise of the independent production sector, and the globalization of information flows within the TV industry

Improved survival in patients with peritoneal metastases from colorectal cancer: a preliminary study

Patients with peritoneal or local metastases from colorectal cancer have a poor prognosis. However, aggressive treatments by debulking surgery and infusional intraperitoneal (i.p.) chemotherapy have been tried and appear to benefit selected patients. We assayed the effects of debulking surgery and i.p. chemotherapy with respect to survival and compared the results with matched control patients treated by intravenous (i.v.) chemotherapy. In all, 18 patients with peritoneal and/or local metastases from colorectal adenocarcinoma underwent debulking surgery followed by 5-fluorouracil (5-FU) 550 mg m(-2) day(-1) i.p. and leucovorin (LV) 60 mg m(-2) day(-1) i.v. The chemotherapy was started the day after surgery and was given daily for 6 days and repeated monthly for totally eight courses. The control patients, matched for age, gender, performance status and metastatic site, were randomly selected from controlled clinical chemotherapy trials and treated with i.v. 5-FU+LV or i.v. methotrexate+5-FU+LV. There was no treatment-related mortality. The median survival among i.p. patients was 32 months compared to 14 months in the control group. In all, 11 patients who underwent macroscopically radical surgery had a longer survival than those who were not radically operated (P=0.02). These results indicate that patients with peritoneal metastases and/or locally advanced cancers but without distant metastases may benefit from cytoreductive surgery combined with i.p. chemotherapy