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Background Recording and analyzing microbial growth is a routine task in the life sciences. Microplate readers that record dozens to hundreds of growth curves simultaneously are increasingly used for this task raising the demand for their rapid and reliable analysis. Results Here, we present Dashing Growth Curves, an interactive web application ( http://dashing-growth-curves.ethz.ch/ ) that enables researchers to quickly visualize and analyze growth curves without the requirement for coding knowledge and independent of operating system. Growth curves can be fitted with parametric and non-parametric models or manually. The application extracts maximum growth rates as well as other features such as lag time, length of exponential growth phase and maximum population size among others. Furthermore, Dashing Growth Curves automatically groups replicate samples and generates downloadable summary plots for of all growth parameters. Conclusions Dashing Growth Curves is an open-source web application that reduces the time required to analyze microbial growth curves from hours to minutes.

Methanol is a liquid with high energy storage capacity that holds promise as an alternative substrate to replace sugars in the biotechnology industry. It can be produced from CO 2 or methane and its use does not compete with food and animal feed production. However, there are currently only limited biotechnological options for the valorization of methanol, which hinders its widespread adoption. Here, we report the conversion of the industrial platform organism Escherichia coli into a synthetic methylotroph that assimilates methanol via the energy efficient ribulose monophosphate cycle. Methylotrophy is achieved after evolution of a methanol-dependent E . coli strain over 250 generations in continuous chemostat culture. We demonstrate growth on methanol and biomass formation exclusively from the one-carbon source by 13 C isotopic tracer analysis. In line with computational modeling, the methylotrophic E. coli strain optimizes methanol oxidation by upregulation of an improved methanol dehydrogenase, increasing ribulose monophosphate cycle activity, channeling carbon flux through the Entner-Doudoroff pathway and downregulating tricarboxylic acid cycle enzymes. En route towards sustainable bioproduction processes, our work lays the foundation for the efficient utilization of methanol as the dominant carbon and energy resource. Using one carbon compounds as feedstock is a promising approach in abating climate change. Here, the authors report the conversion of E. coli into a synthetic methylotroph that assimilates methanol via the ribulose monophosphate cycle and a set of distinctive mutations.

Drug-induced QT prolongation (diLQTS), and subsequent risk of torsade de pointes, is a major concern with use of many medications, including for non-cardiac conditions. The possibility that genetic risk, in the form of polygenic risk scores (PGS), could be integrated into prediction of risk of diLQTS has great potential, although it is unknown how genetic risk is related to clinical risk factors as might be applied in clinical decision-making. In this study, we examined the PGS for QT interval in 2500 subjects exposed to a known QT-prolonging drug on prolongation of the QT interval over 500ms on subsequent ECG using electronic health record data. We found that the normalized QT PGS was higher in cases than controls (0.212±0.954 vs. -0.0270±1.003, P = 0.0002), with an unadjusted odds ratio of 1.34 (95%CI 1.17–1.53, P<0.001) for association with diLQTS. When included with age and clinical predictors of QT prolongation, we found that the PGS for QT interval provided independent risk prediction for diLQTS, in which the interaction for high-risk diagnosis or with certain high-risk medications (amiodarone, sotalol, and dofetilide) was not significant, indicating that genetic risk did not modify the effect of other risk factors on risk of diLQTS. We found that a high-risk cutoff (QT PGS ≥ 2 standard deviations above mean), but not a low-risk cutoff, was associated with risk of diLQTS after adjustment for clinical factors, and provided one method of integration based on the decision-tree framework. In conclusion, we found that PGS for QT interval is an independent predictor of diLQTS, but that in contrast to existing theories about repolarization reserve as a mechanism of increasing risk, the effect is independent of other clinical risk factors. More work is needed for external validation in clinical decision-making, as well as defining the mechanism through which genes that increase QT interval are associated with risk of diLQTS.

\"Family therapy trainees are inundated with a multitude of family therapy theories. They also have difficulty shifting from an individualistic view to one of seeing interactions and systems. How do therapists hone their own methods with all of these choices? And how do they learn how to best treat families with all of the focus being taken away from their clients and redirected instead on processes? Perhaps most importantly, how can they learn through an inductive process of exploring what has occurred during the therapeutic session? Veteran therapist and founder of Structural Family Therapy, Salvador Minuchin, goes back to basics with his two co-authors Michael D. Reiter and Charmaine Borda in The Craft of Family Therapy. In this book they teach readers basic communication and family therapy skills using some of Dr. Minuchin's most interesting and illuminating cases. Not only do readers re-learn basic techniques, such as reframing and joining, but they are treated to an in-depth commentary on each case, with Dr. Minuchin emphasizing the techniques he uses that allow him to refocus attention from the Identifying Patient to the family as a whole. The book ends with three supervision transcripts from Dr. Minuchin's students, whose commentary illuminates the struggles, fears, and insecurities that new family therapists face and how they can overcome them. Each of these chapters ends with a consultation interview that Dr. Minuchin conducted with each supervisees case family.\"-- Provided by publisher.

Cannabis sativa L. has been cultivated and used around the globe for its medicinal properties for millennia 1 . Some cannabinoids, the hallmark constituents of Cannabis , and their analogues have been investigated extensively for their potential medical applications 2 . Certain cannabinoid formulations have been approved as prescription drugs in several countries for the treatment of a range of human ailments 3 . However, the study and medicinal use of cannabinoids has been hampered by the legal scheduling of Cannabis , the low in planta abundances of nearly all of the dozens of known cannabinoids 4 , and their structural complexity, which limits bulk chemical synthesis. Here we report the complete biosynthesis of the major cannabinoids cannabigerolic acid, Δ 9 -tetrahydrocannabinolic acid, cannabidiolic acid, Δ 9 -tetrahydrocannabivarinic acid and cannabidivarinic acid in Saccharomyces cerevisiae , from the simple sugar galactose. To accomplish this, we engineered the native mevalonate pathway to provide a high flux of geranyl pyrophosphate and introduced a heterologous, multi-organism-derived hexanoyl-CoA biosynthetic pathway 5 . We also introduced the Cannabis genes that encode the enzymes involved in the biosynthesis of olivetolic acid 6 , as well as the gene for a previously undiscovered enzyme with geranylpyrophosphate:olivetolate geranyltransferase activity and the genes for corresponding cannabinoid synthases 7 , 8 . Furthermore, we established a biosynthetic approach that harnessed the promiscuity of several pathway genes to produce cannabinoid analogues. Feeding different fatty acids to our engineered strains yielded cannabinoid analogues with modifications in the part of the molecule that is known to alter receptor binding affinity and potency 9 . We also demonstrated that our biological system could be complemented by simple synthetic chemistry to further expand the accessible chemical space. Our work presents a platform for the production of natural and unnatural cannabinoids that will allow for more rigorous study of these compounds and could be used in the development of treatments for a variety of human health problems. Genetic engineering of yeast enables the production of cannabinoids and cannabinoid analogues from the simple sugar galactose, without the need to cultivate Cannabis .

Methanol is a biotechnologically promising substitute for food and feed substrates since it can be produced renewably from electricity, water and CO 2 . Although progress has been made towards establishing Escherichia coli as a platform organism for methanol conversion via the energy efficient ribulose monophosphate (RuMP) cycle, engineering strains that rely solely on methanol as a carbon source remains challenging. Here, we apply flux balance analysis to comprehensively identify methanol-dependent strains with high potential for adaptive laboratory evolution. We further investigate two out of 1200 candidate strains, one with a deletion of fructose-1,6-bisphosphatase ( fbp ) and another with triosephosphate isomerase ( tpiA ) deleted. In contrast to previous reported methanol-dependent strains, both feature a complete RuMP cycle and incorporate methanol to a high degree, with up to 31 and 99% fractional incorporation into RuMP cycle metabolites. These strains represent ideal starting points for evolution towards a fully methylotrophic lifestyle. The engineering of methanol-dependent growth in Escherichia coli is challenging. Here, the authors predict and experimentally validate methanol-dependent strains with a complete RuMP cycle and high potential for the development of a methylotrophic platform organism.

Methanol synthesized from captured greenhouse gases is an emerging renewable feedstock with great potential for bioproduction. Recent research has raised the prospect of methanol bioconversion to value-added products using synthetic methylotrophic Escherichia coli , as its metabolism can be rewired to enable growth solely on the reduced one-carbon compound. Here we describe the generation of an E. coli strain that grows on methanol at a doubling time of 4.3 h—comparable to many natural methylotrophs. To establish bioproduction from methanol using this synthetic chassis, we demonstrate biosynthesis from four metabolic nodes from which numerous bioproducts can be derived: lactic acid from pyruvate, polyhydroxybutyrate from acetyl coenzyme A, itaconic acid from the tricarboxylic acid cycle and p -aminobenzoic acid from the chorismate pathway. In a step towards carbon-negative chemicals and valorizing greenhouse gases, our work brings synthetic methylotrophy in E. coli within reach of industrial applications. Synthetic methylotrophic organisms provide potential for valorization of greenhouse gas-derived methanol. Here an Escherichia coli strain is generated that reaches a similar growth rate on methanol to many natural methylotrophs and is capable of producing chemicals from this carbon source.