Heterologous synthesis of geranyllinalool,a diterpenol plant product,in the cyanobacterium Synechocystis

Cyanobacteria are industrially robust photosynthetic microorganisms that can be genetically programmed to synthesize commodity products for domestic and industrial consumption. In the present work, Synechocystis was endowed with the synthesis of the plant secondary metabolite geranyllinalool, a diterpene alcohol of commercial interest. Total average yields of 360 μg of geranyllinalool per gram of dry cell weight were obtained in the course of a 48-h cultivation period. Geranyllinalool was primarily sequestered inside the transformant cells, corresponding to 60–70% of the total heterologous product, instead of being entirely exuded, as the case is with shorter heterologous terpene hydrocarbons. Extraction of geranyllinalool necessitated disruption of the cells in order to release and isolate this chemical product. Moreover, geranyllinalool accumulation in the cells caused a mild inhibitory effect on cell fitness and biomass growth rate, such that the duplication time of Synechocystis transformants was 1.4-fold longer than that of the control. The remaining 30–40% of the geranyllinalool product was found to float on the surface of sealed transformant cultures, where it was siphoned off by applying a hydrophobic overlayer, with no need to disrupt the cells in this case. Concluding, the work extended efforts to heterologously produce terpene and terpenol products in cyanobacteria, and addressed possibilities and constrains inherent to this production system.

     

A Generalized Estimator of the Attributable Benefit of an Optimal Treatment Regime

Summary For many diseases where there are several treatment options often there is no consensus on the best treatment to give individual patients. In such cases, it may be necessary to define a strategy for treatment assignment; that is, an algorithm that dictates the treatment an individual should receive based on their measured characteristics. Such a strategy or algorithm is also referred to as a treatment regime. The optimal treatment regime is the strategy that would provide the most public health benefit by minimizing as many poor outcomes as possible. Using a measure that is a generalization of attributable risk (AR) and notions of potential outcomes, we derive an estimator for the proportion of events that could have been prevented had the optimal treatment regime been implemented. Traditional AR studies look at the added risk that can be attributed to exposure of some contaminant; here we will instead study the benefit that can be attributed to using the optimal treatment strategy. We will show how regression models can be used to estimate the optimal treatment strategy and the attributable benefit of that strategy. We also derive the large sample properties of this estimator. As a motivating example, we will apply our methods to an observational study of 3856 patients treated at the Duke University Medical Center with prior coronary artery bypass graft surgery and further heart‐related problems requiring a catheterization. The patients may be treated with either medical therapy alone or a combination of medical therapy and percutaneous coronary intervention without a general consensus on which is the best treatment for individual patients.     

Hotspots of endemic terrestrial invertebrates in southern Greece

In the present paper we identify biodiversity hotspots of endemic terrestrial invertebrates in southern Greece, using four different criteria and five taxonomic groups. The hotspots identification procedure was facilitated by the use of the MapInfoPro G.I.S. software. We mapped the known distribution of 424 endemic species on a digital map of southern Greece in 548 10 × 10 km² grids. The total number of registrations (records per grid) is 3826 in 465 grids. Registrations are unevenly distributed in the five sub-regions of the study area, a fact that results from both the unequal collecting effort applied in each sub-region and their different levels of endemism. We first identified the hotspots for each individual taxonomic group, and then for the total species pool. Finally, we analyzed the species saturation pattern in order to find the minimum number of grids needed for the inclusion of 85% of the total number of species. The most important hotspots are mostly at the higher mountains of the study area, especially on Taygetos and Idi Mts. We also give a brief evaluation of the performance of the four criteria used in the case of endemic species analyses.