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Forestry companies have invested in genetic improvement to increase wood production in a shorter amount of time. Thus, studies are needed to compare the properties of clonal and seminal wood materials. The objective of this study was to analyze physical and mechanical properties of Tectona grandis from clonal (C1 and C2) and seminal (S) origin and evaluate the yield and quality of sawn wood subjected to outdoor and oven drying. Genetic material was collected from six, 15-year-old trees. Clone C2 presented the lowest amount of bark, and 51 % heartwood up to half the commercial height, while the heartwood of C1 and S went up to 25 % of the height. The three materials did not differ statistically for maximum angular deviation, pith eccentricity, basic density, Janka hardness, anisotropy, commercial income of sawn wood and the presence of knots. After the drying processes, the bowing and crooking indexes were less than 5 mm.m-1, however, the seminal material showed a higher cracking incidence after outdoor and oven drying. In conclusion, the wood properties of the three materials are similar. In addition, the oven drying process is recommended., Las empresas forestales han invertido en mejoramiento genético para aumentar la producción de madera en menos tiempo. Por tanto, se necesitan estudios para comparar las propiedades de los materiales de madera clonales y seminales. El objetivo de este estudio fue analizar las propiedades físicas y mecánicas de Tectona grandis de origen clonal (C1 y C2) y seminal (S) y evaluar el rendimiento y calidad de la madera aserrada sometida a secado al aire libre y al horno. Se recolectó material genético de seis árboles de 15 años. El clon C2 presentó la menor cantidad de corteza, y un 51 % de duramen hasta la mitad de la altura comercial, mientras que el duramen de C1 y S llegó hasta un 25 % de la altura. Los tres materiales no difirieron estadísticamente en cuanto a desviación angular máxima, excentricidad de la médula, densidad básica, dureza Janka, anisotropía, ingreso comercial de la madera aserrada y presencia de nudos. Luego de los procesos de secado, los índices de arqueamiento y torcedura fueron menores a 5 mm.m-1, sin embargo, el material seminal presentó una mayor incidencia de agrietamiento luego del secado al aire libre y al horno. En conclusión, las propiedades de la madera de los tres materiales son similares. Además, se recomienda el proceso de secado en horno

Forestry companies have invested in genetic improvement to increase wood production in a shorter amount of time. Thus, studies are needed to compare the properties of clonal and seminal wood materials. The objective of this study was to analyze physical and mechanical properties of Tectona grandis from clonal (C1 and C2) and seminal (S) origin and evaluate the yield and quality of sawn wood subjected to outdoor and oven drying. Genetic material was collected from six, 15-year-old trees. Clone C2 presented the lowest amount of bark, and 51 % heartwood up to half the commercial height, while the heartwood of C1 and S went up to 25 % of the height. The three materials did not differ statistically for maximum angular deviation, pith eccentricity, basic density, Janka hardness, anisotropy, commercial income of sawn wood and the presence of knots. After the drying processes, the bowing and crooking indexes were less than 5 mm.m-1, however, the seminal material showed a higher cracking incidence after outdoor and oven drying. In conclusion, the wood properties of the three materials are similar. In addition, the oven drying process is recommended., Las empresas forestales han invertido en mejoramiento genético para aumentar la producción de madera en menos tiempo. Por tanto, se necesitan estudios para comparar las propiedades de los materiales de madera clonales y seminales. El objetivo de este estudio fue analizar las propiedades físicas y mecánicas de Tectona grandis de origen clonal (C1 y C2) y seminal (S) y evaluar el rendimiento y calidad de la madera aserrada sometida a secado al aire libre y al horno. Se recolectó material genético de seis árboles de 15 años. El clon C2 presentó la menor cantidad de corteza, y un 51 % de duramen hasta la mitad de la altura comercial, mientras que el duramen de C1 y S llegó hasta un 25 % de la altura. Los tres materiales no difirieron estadísticamente en cuanto a desviación angular máxima, excentricidad de la médula, densidad básica, dureza Janka, anisotropía, ingreso comercial de la madera aserrada y presencia de nudos. Luego de los procesos de secado, los índices de arqueamiento y torcedura fueron menores a 5 mm.m-1, sin embargo, el material seminal presentó una mayor incidencia de agrietamiento luego del secado al aire libre y al horno. En conclusión, las propiedades de la madera de los tres materiales son similares. Además, se recomienda el proceso de secado en horno

Base editors are a new family of programmable genome editing tools that fuse ssDNA (single stranded DNA) modifying enzymes to catalytically inactive CRISPR-associated (Cas) endonucleases to induce highly efficient single base changes. With dozens of base editors now reported, it is apparent that these tools are highly modular; many combinations of ssDNA modifying enzymes and Cas proteins have resulted in a variety of base editors, each with its own unique properties and potential uses. In this perspective, we describe currently available base editors, highlighting their modular nature and describing the various options available for each component. Furthermore, we briefly discuss applications in synthetic biology and genome engineering where base editors have presented unique advantages over alternative techniques.

Base editors are a new family of programmable genome editing tools that fuse ssDNA (single stranded DNA) modifying enzymes to catalytically inactive CRISPR-associated (Cas) endonucleases to induce highly efficient single base changes. With dozens of base editors now reported, it is apparent that these tools are highly modular; many combinations of ssDNA modifying enzymes and Cas proteins have resulted in a variety of base editors, each with its own unique properties and potential uses. In this perspective, we describe currently available base editors, highlighting their modular nature and describing the various options available for each component. Furthermore, we briefly discuss applications in synthetic biology and genome engineering where base editors have presented unique advantages over alternative techniques.

Increasing evidence supports a close relationship between Ras-ERK1/2 activation in the striatum and L-DOPA-induced dyskinesia (LID). ERK1/2 activation by L-DOPA takes place through the crosstalk between D1R/AC/PKA/DARPP-32 pathway and NMDA/Ras pathway. Compelling genetic and pharmacological evidence indicates that Ras-ERK1/2 inhibition prevents LID onset and may even revert already established dyskinetic symptoms. However, it is currently unclear whether exacerbation of Ras-ERK1/2 activity in the striatum may further aggravate dyskinesia in experimental animal models. Here we took advantage of two genetic models in which Ras-ERK1/2 signaling is hyperactivated, the Nf1+/− mice, in which the Ras inhibitor neurofibromin is reduced, and the Ras-GRF1 overexpressing (Ras-GRF1 OE) transgenic mice in which a specific neuronal activator of Ras is enhanced. Nf1+/− and Ras-GRF1 OE mice were unilaterally lesioned with 6-OHDA and treated with an escalating L-DOPA dosing regimen. In addition, a subset of Nf1+/− hemi-parkinsonian animals was also co-treated with the Ras inhibitor lovastatin. Our results revealed that Nf1+/− and Ras-GRF1 OE mice displayed similar dyskinetic symptoms to their wild-type counterparts. This observation was confirmed by the lack of differences between mutant and wild-type mice in striatal molecular changes associated to LID (i.e., FosB, and pERK1/2 expression). Interestingly, attenuation of Ras activity with lovastatin does not weaken dyskinetic symptoms in Nf1+/− mice. Altogether, these data suggest that ERK1/2-signaling activation in dyskinetic animals is maximal and does not require further genetic enhancement in the upstream Ras pathway. However, our data also demonstrate that such a genetic enhancement may reduce the efficacy of anti-dyskinetic drugs like lovastatin

The fascinating progress of genetics has led to great achievements in the modern, medical, and nonmedical sciences. Genetic engineering is used in many fields, among which human enhancement is one of the most controversial. Most bioethicists agree on the definition of human enhancement as a physical, cognitive, or moral improvement. Genetic enhancement refers to the introduction of the changes into a genome or epigenome intended to improve nonpathological human traits. It is expected that implementation of genetic enhancement will be reached through the discovery of markers in enhancement related genes, such as athletic performance- or aging-related genes, but also through the development of approaches characteristic for personalized medicine, such as gene enhancement, molecular-targeted enhancement, and cellular enhancement. However, we should be aware that genetic enhancement creates significant ethical and regulatory challenges. Prompt and thorough discussion between liberal eugenicists and bioconservatives is indispensable, because genetics is moving extremely fast toward human genetic enhancement.

Monoterpenes (C10 isoprenoids) are the main components of essential oils and are possible precursors for many commodity chemicals and high energy density fuels. Monoterpenes are synthesized from geranyl diphosphate (GPP), which is also the precursor for the biosynthesis of farnesyl diphosphate (FPP). FPP biosynthesis diverts the carbon flux from monoterpene production to C15 products and quinone biosynthesis. In this study, we tested a chromosomal mutation of Escherichia coli's native FPP synthase (IspA) to improve GPP availability for the production of monoterpenes using a heterologous mevalonate pathway. Monoterpene production at high levels required not only optimization of GPP production but also a basal level of FPP to maintain growth. The optimized strains produced two jet fuel precursor monoterpenoids 1,8-cineole and linalool at the titer of 653 mg/L and 505 mg/L, respectively, in batch cultures with 1% glucose. The engineered strains developed in this work provide useful resources for the production of high-value monoterpenes. Biotechnol. Bioeng. 2017;114: 1703-1712. © 2017 Wiley Periodicals, Inc.

Monoterpenes (C10 isoprenoids) are the main components of essential oils and are possible precursors for many commodity chemicals and high energy density fuels. Monoterpenes are synthesized from geranyl diphosphate (GPP), which is also the precursor for the biosynthesis of farnesyl diphosphate (FPP). FPP biosynthesis diverts the carbon flux from monoterpene production to C15 products and quinone biosynthesis. In this study, we tested a chromosomal mutation of Escherichia coli's native FPP synthase (IspA) to improve GPP availability for the production of monoterpenes using a heterologous mevalonate pathway. Monoterpene production at high levels required not only optimization of GPP production but also a basal level of FPP to maintain growth. The optimized strains produced two jet fuel precursor monoterpenoids 1,8-cineole and linalool at the titer of 653 mg/L and 505 mg/L, respectively, in batch cultures with 1% glucose. The engineered strains developed in this work provide useful resources for the production of high-value monoterpenes. Biotechnol. Bioeng. 2017;114: 1703-1712. © 2017 Wiley Periodicals, Inc.

The nutritional value of Brassica seed meals is reduced by the presence of glucosinolates, which are toxic compounds involved in plant defense. Mutation of the genes encoding two glucosinolate transporters (GTRs) eliminated glucosinolates from Arabidopsis thaliana seeds, but translation of loss-of-function phenotypes into Brassica crops is challenging because Brassica is polyploid. We mutated one of seven and four of 12 GTR orthologs and reduced glucosinolate levels in seeds by 60-70% in two different Brassica species (Brassica rapa and Brassica juncea). Reduction in seed glucosinolates was stably inherited over multiple generations and maintained in field trials of two mutant populations at three locations. Successful translation of the gtr loss-of-function phenotype from model plant to two Brassica crops suggests that our transport engineering approach could be broadly applied to reduce seed glucosinolate content in other oilseed crops, such as Camelina sativa or Crambe abyssinica.

One of the key drivers for successful metabolic engineering in microbes is the efficacy by which genomes can be edited. As such there are many methods to choose from when aiming to modify genomes, especially those of model organisms like yeast and bacteria. In recent years, clustered regularly interspaced palindromic repeats (CRISPR) and its associated proteins (Cas) have become the method of choice for precision genome engineering in many organisms due to their orthogonality, versatility and efficacy. Here we review the strategies adopted for implementation of RNA-guided CRISPR/Cas9 genome editing with special emphasis on their application for metabolic engineering of yeast and bacteria. Also, examples of how nuclease-deficient Cas9 has been applied for RNA-guided transcriptional regulation of target genes will be reviewed, as well as tools available for computer-aided design of guide-RNAs will be highlighted. Finally, this review will provide a perspective on the immediate challenges and opportunities foreseen by the use of CRISPR/Cas9 genome engineering and regulation in the context of metabolic engineering.

The fermentation of simple sugars to ethanol has been the most successful biofuel process to displace fossil fuel consumption worldwide thus far. However, the physical properties of ethanol and automotive components limit its application in most cases to 10-15 vol% blends with conventional gasoline. Fermentative co-production of ethanol and acetone coupled with a catalytic alkylation reaction could enable the production of gasoline blendstocks enriched in higher-chain oxygenates. Here we demonstrate a synthetic pathway for the production of acetone through the mevalonate precursor hydroxymethylglutaryl-CoA. Expression of this pathway in various strains of Escherichia coli resulted in the co-production of acetone and ethanol. Metabolic engineering and control of the environmental conditions for microbial growth resulted in controllable acetone and ethanol production with ethanol:acetone molar ratios ranging from 0.7:1 to 10.0:1. Specifically, use of gluconic acid as a substrate increased production of acetone and balanced the redox state of the system, predictively reducing the molar ethanol:acetone ratio. Increases in ethanol production and the molar ethanol:acetone ratio were achieved by co-expression of the aldehyde/alcohol dehydrogenase (AdhE) from E. coli MG1655 and by co-expression of pyruvate decarboxylase (Pdc) and alcohol dehydrogenase (AdhB) from Z. mobilis. Controlling the fermentation aeration rate and pH in a bioreactor raised the acetone titer to 5.1 g L(-1) , similar to that obtained with wild-type Clostridium acetobutylicum. Optimizing the metabolic pathway, the selection of host strain, and the physiological conditions employed for host growth together improved acetone titers over 35-fold (0.14-5.1 g/L). Finally, chemical catalysis was used to upgrade the co-produced ethanol and acetone at both low and high molar ratios to higher-chain oxygenates for gasoline and jet fuel applications. Biotechnol. Bioeng. 2016;113: 2079-2087. © 2016 Wiley Periodicals

El aumento genético en el rendimiento deportivo parece inevitable y por lo tanto, es necesario establecer criterios racionales sobre el dopaje genético. Una estrategia para establecer estos parámetros normativos es atender a dos criterios: la extensión de los efectos del tratamiento y el tipo de intervención genética. Habiendo examinado estas posibilidades de modificación genética en relación con el deporte se pueden sugerir algunas conclusiones: 1) Mejora somática Intervenciones: su aplicación en el deporte podría calificarse como legítima. 2) modificaciones somáticas transhumanas: su aplicación en el deporte podría calificarse de ilegítima por el principio de igualdad entre competidores; 3) Mejoras en las líneas germinales e intervenciones transhumanas en líneas germinales: ambos casos se verían afectados por el principio de daño., The genetic enhancement in the sport performance seems unavoidable and therefore, it is necessary establish rational criteria on genetic doping. A strategy to establish these normative parameters is to attend to two criteria: the extension of the effects of the treatment and the type of genetic intervention.Having examined these possibilities for genetic modification in relation with sport some conclusions can be suggested: 1) Somatic enhancement interventions: their application in sport could be qualified as legitimate. 2) Somatic transhuman modifications: their application in sport could be qualified as ilegitimate by the principle of equality between competitors; 3) Germline enhancements and transhuman germline interventions: both cases would be affected by the harm principle

El aumento genético en el rendimiento deportivo parece inevitable y por lo tanto, es necesario establecer criterios racionales sobre el dopaje genético. Una estrategia para establecer estos parámetros normativos es atender a dos criterios: la extensión de los efectos del tratamiento y el tipo de intervención genética. Habiendo examinado estas posibilidades de modificación genética en relación con el deporte se pueden sugerir algunas conclusiones: 1) Mejora somática Intervenciones: su aplicación en el deporte podría calificarse como legítima. 2) modificaciones somáticas transhumanas: su aplicación en el deporte podría calificarse de ilegítima por el principio de igualdad entre competidores; 3) Mejoras en las líneas germinales e intervenciones transhumanas en líneas germinales: ambos casos se verían afectados por el principio de daño., The genetic enhancement in the sport performance seems unavoidable and therefore, it is necessary establish rational criteria on genetic doping. A strategy to establish these normative parameters is to attend to two criteria: the extension of the effects of the treatment and the type of genetic intervention.Having examined these possibilities for genetic modification in relation with sport some conclusions can be suggested: 1) Somatic enhancement interventions: their application in sport could be qualified as legitimate. 2) Somatic transhuman modifications: their application in sport could be qualified as ilegitimate by the principle of equality between competitors; 3) Germline enhancements and transhuman germline interventions: both cases would be affected by the harm principle

The fermentation of simple sugars to ethanol has been the most successful biofuel process to displace fossil fuel consumption worldwide thus far. However, the physical properties of ethanol and automotive components limit its application in most cases to 10-15 vol% blends with conventional gasoline. Fermentative co-production of ethanol and acetone coupled with a catalytic alkylation reaction could enable the production of gasoline blendstocks enriched in higher-chain oxygenates. Here we demonstrate a synthetic pathway for the production of acetone through the mevalonate precursor hydroxymethylglutaryl-CoA. Expression of this pathway in various strains of Escherichia coli resulted in the co-production of acetone and ethanol. Metabolic engineering and control of the environmental conditions for microbial growth resulted in controllable acetone and ethanol production with ethanol:acetone molar ratios ranging from 0.7:1 to 10.0:1. Specifically, use of gluconic acid as a substrate increased production of acetone and balanced the redox state of the system, predictively reducing the molar ethanol:acetone ratio. Increases in ethanol production and the molar ethanol:acetone ratio were achieved by co-expression of the aldehyde/alcohol dehydrogenase (AdhE) from E. coli MG1655 and by co-expression of pyruvate decarboxylase (Pdc) and alcohol dehydrogenase (AdhB) from Z. mobilis. Controlling the fermentation aeration rate and pH in a bioreactor raised the acetone titer to 5.1 g L(-1) , similar to that obtained with wild-type Clostridium acetobutylicum. Optimizing the metabolic pathway, the selection of host strain, and the physiological conditions employed for host growth together improved acetone titers over 35-fold (0.14-5.1 g/L). Finally, chemical catalysis was used to upgrade the co-produced ethanol and acetone at both low and high molar ratios to higher-chain oxygenates for gasoline and jet fuel applications. Biotechnol. Bioeng. 2016;113: 2079-2087. © 2016 Wiley Periodicals

One of the key drivers for successful metabolic engineering in microbes is the efficacy by which genomes can be edited. As such there are many methods to choose from when aiming to modify genomes, especially those of model organisms like yeast and bacteria. In recent years, clustered regularly interspaced palindromic repeats (CRISPR) and its associated proteins (Cas) have become the method of choice for precision genome engineering in many organisms due to their orthogonality, versatility and efficacy. Here we review the strategies adopted for implementation of RNA-guided CRISPR/Cas9 genome editing with special emphasis on their application for metabolic engineering of yeast and bacteria. Also, examples of how nuclease-deficient Cas9 has been applied for RNA-guided transcriptional regulation of target genes will be reviewed, as well as tools available for computer-aided design of guide-RNAs will be highlighted. Finally, this review will provide a perspective on the immediate challenges and opportunities foreseen by the use of CRISPR/Cas9 genome engineering and regulation in the context of metabolic engineering.

El aumento genético en el rendimiento deportivo parece inevitable y por lo tanto, es necesario establecer criterios racionales sobre el dopaje genético. Una estrategia para establecer estos parámetros normativos es atender a dos criterios: la extensión de los efectos del tratamiento y el tipo de intervención genética. Habiendo examinado estas posibilidades de modificación genética en relación con el deporte se pueden sugerir algunas conclusiones: 1) Mejora somática Intervenciones: su aplicación en el deporte podría calificarse como legítima. 2) modificaciones somáticas transhumanas: su aplicación en el deporte podría calificarse de ilegítima por el principio de igualdad entre competidores; 3) Mejoras en las líneas germinales e intervenciones transhumanas en líneas germinales: ambos casos se verían afectados por el principio de daño., The genetic enhancement in the sport performance seems unavoidable and therefore, it is necessary establish rational criteria on genetic doping. A strategy to establish these normative parameters is to attend to two criteria: the extension of the effects of the treatment and the type of genetic intervention.Having examined these possibilities for genetic modification in relation with sport some conclusions can be suggested: 1) Somatic enhancement interventions: their application in sport could be qualified as legitimate. 2) Somatic transhuman modifications: their application in sport could be qualified as ilegitimate by the principle of equality between competitors; 3) Germline enhancements and transhuman germline interventions: both cases would be affected by the harm principle

El aumento genético en el rendimiento deportivo parece inevitable y por lo tanto, es necesario establecer criterios racionales sobre el dopaje genético. Una estrategia para establecer estos parámetros normativos es atender a dos criterios: la extensión de los efectos del tratamiento y el tipo de intervención genética. Habiendo examinado estas posibilidades de modificación genética en relación con el deporte se pueden sugerir algunas conclusiones: 1) Mejora somática Intervenciones: su aplicación en el deporte podría calificarse como legítima. 2) modificaciones somáticas transhumanas: su aplicación en el deporte podría calificarse de ilegítima por el principio de igualdad entre competidores; 3) Mejoras en las líneas germinales e intervenciones transhumanas en líneas germinales: ambos casos se verían afectados por el principio de daño., The genetic enhancement in the sport performance seems unavoidable and therefore, it is necessary establish rational criteria on genetic doping. A strategy to establish these normative parameters is to attend to two criteria: the extension of the effects of the treatment and the type of genetic intervention.Having examined these possibilities for genetic modification in relation with sport some conclusions can be suggested: 1) Somatic enhancement interventions: their application in sport could be qualified as legitimate. 2) Somatic transhuman modifications: their application in sport could be qualified as ilegitimate by the principle of equality between competitors; 3) Germline enhancements and transhuman germline interventions: both cases would be affected by the harm principle

El aumento genético en el rendimiento deportivo parece inevitable y por lo tanto, es necesario establecer criterios racionales sobre el dopaje genético. Una estrategia para establecer estos parámetros normativos es atender a dos criterios: la extensión de los efectos del tratamiento y el tipo de intervención genética. Habiendo examinado estas posibilidades de modificación genética en relación con el deporte se pueden sugerir algunas conclusiones: 1) Mejora somática Intervenciones: su aplicación en el deporte podría calificarse como legítima. 2) modificaciones somáticas transhumanas: su aplicación en el deporte podría calificarse de ilegítima por el principio de igualdad entre competidores; 3) Mejoras en las líneas germinales e intervenciones transhumanas en líneas germinales: ambos casos se verían afectados por el principio de daño., The genetic enhancement in the sport performance seems unavoidable and therefore, it is necessary establish rational criteria on genetic doping. A strategy to establish these normative parameters is to attend to two criteria: the extension of the effects of the treatment and the type of genetic intervention.Having examined these possibilities for genetic modification in relation with sport some conclusions can be suggested: 1) Somatic enhancement interventions: their application in sport could be qualified as legitimate. 2) Somatic transhuman modifications: their application in sport could be qualified as ilegitimate by the principle of equality between competitors; 3) Germline enhancements and transhuman germline interventions: both cases would be affected by the harm principle

Transgenic microalgae have the potential to impact many diverse biotechnological industries including energy, human and animal nutrition, pharmaceuticals, health and beauty, and specialty chemicals. However, major obstacles to sophisticated genetic and metabolic engineering in algae have been the lack of well-characterized transformation vectors to direct engineered gene products to specific subcellular locations, and the inability to robustly express multiple nuclear-encoded transgenes within a single cell. Here we validate a set of genetic tools that enable protein targeting to distinct subcellular locations, and present two complementary methods for multigene engineering in the eukaryotic green microalga Chlamydomonas reinhardtii. The tools described here will enable advanced metabolic and genetic engineering to promote microalgae biotechnology and product commercialization.

Transgenic microalgae have the potential to impact many diverse biotechnological industries including energy, human and animal nutrition, pharmaceuticals, health and beauty, and specialty chemicals. However, major obstacles to sophisticated genetic and metabolic engineering in algae have been the lack of well-characterized transformation vectors to direct engineered gene products to specific subcellular locations, and the inability to robustly express multiple nuclear-encoded transgenes within a single cell. Here we validate a set of genetic tools that enable protein targeting to distinct subcellular locations, and present two complementary methods for multigene engineering in the eukaryotic green microalga Chlamydomonas reinhardtii. The tools described here will enable advanced metabolic and genetic engineering to promote microalgae biotechnology and product commercialization.

Advances in synthetic biology and metabolic engineering have enabled the construction of novel biological routes to valuable chemicals using suitable microbial hosts. Aldehydes serve as chemical feedstocks in the synthesis of rubbers, plastics, and other larger molecules. Microbial production of alkanes is dependent on the formation of a fatty aldehyde intermediate which is converted to an alkane by an aldehyde deformylating oxygenase (ADO). However, microbial hosts such as Escherichia coli are plagued by many highly active endogenous aldehyde reductases (ALRs) that convert aldehydes to alcohols, which greatly complicates strain engineering for aldehyde and alkane production. It has been shown that the endogenous ALR activity outcompetes the ADO enzyme for fatty aldehyde substrate. The large degree of ALR redundancy coupled with an incomplete database of ALRs represents a significant obstacle in engineering E. coli for either aldehyde or alkane production. In this study, we identified 44 ALR candidates encoded in the E. coli genome using bioinformatics tools, and undertook a comprehensive screening by measuring the ability of these enzymes to produce isobutanol. From the pool of 44 candidates, we found five new ALRs using this screening method (YahK, DkgA, GldA, YbbO, and YghA). Combined deletions of all 13 known ALRs resulted in a 90-99% reduction in endogenous ALR activity for a wide range of aldehyde substrates (C2-C12). Elucidation of the ALRs found in E. coli could guide one in reducing competing alcohol formation during alkane or aldehyde production.

This work addresses the debate mounted in the last decade on the subject of improvement in its different variations. There is astriking lack of consensus when it comes to defining the concept and the need to permit or prohibit such practices. The only pointon which there is widespread agreement is the need to block improvements that involve health hazards, thereby postponing thedebate based on arguments that go beyond the mere risk to physical wellbeing. Thus, it seems as though scientific criteria are whatdetermines the fate of social behavior. In this sense, the category of medicalization will allow for accommodating a critique of contemporarysociety and the hegemony of the medical-scientific vision., O presente trabalho aborda o debate que vem sendo dado na última década a respeito do tema do melhoramento em suas diferentesvariantes. Salienta o escasso consenso na hora de definir o conceito e respeito da necessidade de permitir ou proibir essas práticas. Oúnico ponto de amplo acordo é a necessidade de não admitir melhoramentos que impliquem riscos para a saúde, adiando o debatebaseado em argumentos que superem o mero perigo para a saúde física. Dessa maneira, pareceria que os critérios científicos são osque determinam o destino dos comportamentos sociais. Nesse sentido, a categoria de medicalização permitirá incorporar a crítica àsociedade contemporânea e à hegemonia da visão médico-científica., DOI: 10.5294/pebi.2013.17.1.5 El presente trabajo aborda el debate que se ha dado en la última década a propósito del tema del mejoramiento en sus diferentesvariantes. Sobresale el escaso consenso a la hora de definir el concepto y respecto de la necesidad de permitir o prohibir estas prácticas.El único punto de amplio acuerdo es la necesidad de no admitir mejoramientos que impliquen riesgos para la salud, aplazandoel debate basado en argumentos que superen el mero peligro para la salud física. De esta manera, parecería que los criterios científicosson los que determinan el destino de los comportamientos sociales. En este sentido, la categoría de medicalización permitiráincorporar la crítica a la sociedad contemporánea y a la hegemonía de la visión médico-científica. DOI: 10.5294/pebi.2013.17.1.5

This thesis is an analysis of the relationship between the concepts of chance, choice and responsibility in Michael Sandel’s “The Case against Perfection” (2007). Sandel predicts that if genetic enhancements were introduced in the society, the social meaning of these concepts would change significantly and social solidarity would vanish. He argues that that if people were able to control their genome and the element of chance in the genetic lottery would be replaced with choice, individuals could be held responsible for their deficiencies. Thus, the societal motivation to share our wealth with the disadvantaged would be eroded. However, the philosophical premises in Sandel’s argument remain obscure. Therefore, a new means for the philosophical assessment of Sandel’s argument is introduced in my thesis. The method for the analysis is to examine the premises in Sandel’s argument by comparing it to responsibility-sensitive egalitarian theories and their critique. The central literature used in the analysis is Sandel’s “Liberalism and the Limits of Justice” (1982) and “Democracy’s Discontent: America in Search of a Public Philosophy” (1996). The examination of responsibility-sensitive egalitarianism is based on Ronald Dworkin’s article “What is Equality? Part 2: Equality of Resources” (1981) and contrasted to John Rawls’ “A Theory of Justice” (1971), and the critique of responsibility-sensitive egalitarianism is derived from Samuel Scheffler’s article “What is Egalitarianism?” (2003). I suggest that Sandel’s argument is based on the principle of responsibility of the responsibility-sensitive egalitarian theories: unequal outcomes are just if they arise from factors for which individuals can properly be held responsible and are otherwise unjust. As Sandel’s argument entails this principle, the critique of the principle of responsibility can be applied to it. I conclude that due to extensive critique posed to the principle of responsibility, Sandel’s prediction about the, Pro gradu – tutkielmani käsittelee sattuman, valinnan ja vastuun käsitteiden välistä suhdetta Michael Sandelin teoksessa ”The Case Against Perfection” (2007). Sandelin mukaan geneettisen parantelun käyttöönottaminen yhteiskunnassa muuttaisi merkittävästi näiden käsitteiden sosiaalista merkitystä ja poistaisi yhteiskunnallisen solidaarisuuden. Sandel väittää, että jos ihmiset voisivat kontrolloida perimäänsä ja geneettisen lottoarvonnan sattumanvaraisuus korvautuisi valinnoilla, yksilöä voitaisiin pitää vastuussa hänen vajaavaisuuksistaan. Seurauksena olisi, että sosiaalinen motivaatio jakaa vaurautta huono-osaisten kanssa heikentyisi merkittävästi. Ongelmallista on kuitenkin se, että Sandelin argumentin filosofiset lähtökohdat jäävät epäselviksi. Tämän vuoksi aion tutkielmassani nostaa esiin uuden tarkastelukeinon Sandelin argumentin filosofista arviointia varten. Tutkielmani metodina on tarkastella Sandelin argumentin filosofisia lähtökohtia vertaamalla sitä vastuu-sensitiivisiin egalitaarisiin teorioihin ja niiden kritiikkiin. Analyysin keskeistä lähdekirjallisuutta ovat Sandelin “Liberalism and the Limits of Justice” (1982) ja “Democracy’s Discontent: America in Search of a Public Philosophy” (1996). Vastuu-sensitiivisen egalitarismin tarkastelu perustuu Ronald Dworkinin artikkeliin ”What is Equality? Part 2: Equality of Resources” (1981) ja sitä verrataan John Rawlsin teokseen “A Theory of Justice” (1971), ja vastuu-sensitiivisen egalitarismin kritiikki juontuu Samuel Schefflerin artikkelista ”What is Egalitarianism?” (2003). Totean pro gradu -työssäni, että Sandelin argumentti perustuu vastuu-sensitiivisen egalitarismin vastuuperiaatteeseen: epätasa-arvon voidaan katsoa olevan oikeutettua, mikäli se on peräisin seikoista joista yksilöä voidaan pitää vastuullisena, mutta muissa tapauksissa se on epäoikeutettua. Koska Sandelin argumentti sisältää tämän periaatteen, myös vastuuperiaatteen kritiikki on sovellettavissa siihen. Tutkielmani johtopäätöksenä esitän että

Aspergillus terreus is successfully used for industrial production of itaconic acid. The acid is formed from cis-aconitate, an intermediate of the tricarboxylic (TCA) cycle, by catalytic action of cis-aconitate decarboxylase. It could be assumed that strong anaplerotic reactions that replenish the pool of the TCA cycle intermediates would enhance the synthesis and excretion rate of itaconic acid. In the phylogenetic close relative Aspergillus niger, upregulated metabolic flux through glycolysis has been described that acted as a strong anaplerotic reaction. Deregulated glycolytic flux was caused by posttranslational modification of 6-phosphofructo-1-kinase (PFK1) that resulted in formation of a highly active, citrate inhibition-resistant shorter form of the enzyme. In order to avoid complex posttranslational modification, the native A. niger pfkA gene has been modified to encode for an active shorter PFK1 fragment. By the insertion of the modified A. niger pfkA genes into the A. terreus strain, increased specific productivities of itaconic acid and final yields were documented by transformants in respect to the parental strain. On the other hand, growth rate of all transformants remained suppressed which is due to the low initial pH value of the medium, one of the prerequisites for the accumulation of itaconic acid by A. terreus mycelium. © 2010 Springer-Verlag.

In this paper I argue that the widespread use of liberal eugenics  would establish a biopolitical horizon for class conflict.  In the course of my discussion, I examine Foucault’s discussion of the origins of class racism in Society Must Be Defended.  I then turn to an examination of how a widespread use of genetic engineering could aggravate class divisions and produce new forms of class racism.  I conclude the essay with an overview of the political options which are available to opponents of liberal eugenics.

The following essay was written by a sophomore undergraduate student majoring in Bioengineering at the University of Maryland, Mr. Zachary Russ. Mr. Russ was one of 174 students who submitted a 1000–1200 word essay to the 4th Annual Bioethics Contest sponsored by the Institute of Biological Engineering (IBE). A group of professionals in Biological Engineering assessed and ranked the essays in a blinded process. Five semi-finalists were invited to present their essays at a session at the annual meeting of IBE in Santa Clara, CA on March 21, 2009. Five judges scored all the presentation at the annual meeting and selected Mr. Russ's contribution as the overall winner (1st Place).

An experiment was conducted to evaluate feeding transgenic corn containing the cry34Ab1 and cry35Ab1 genes from a Bacillus thuringiensis strain and the phosphinothricin acetyltransferase (pat) gene from Streptomyces viridochromogenes to finishing cattle compared with nontransgenic corn. Expression of the cry34Ab1 and cry35Ab1 genes confers resistance to corn rootworms, and the pat gene confers tolerance to herbicides containing glufosinate-ammonium. Sixty crossbred steers (396 kg) were individually fed either transgenic corn (DAS-59122-7; 59122), a near-isogenic, nontransgenic control (Control), and a conventional, nontransgenic corn for 109 d to evaluate nutritional equivalency (20 steers/treatment). The corn was coarsely rolled (geometric mean diameter = 4,200 μm) and treatments were offered in the finishing diet at 82% of diet DM. Gain (P = 0.38) and G:F (P = 0.80) were similar between 59122 and Control with a tendency for a difference in DMI (P = 0.08). When adjusted using the statistical analysis of false discovery rate, DMI, ADG, and G:F were not different between Control and 59122 (P > 0.33). No differences were observed between Control and 59122 for HCW, marbling score, LM area, fat depth, or calculated USDA YG (P > 0.12). The genetically modified corn DAS-59122-7 was nutritionally equivalent to a near-isogenic control when fed to finishing steers. Feeding corn grain containing these transgenic traits did not influence steer performance or carcass quality.

The study analyzes the ethical implications of human gene transfer technology for enhancement. Although human gene transfer technology is widely accepted on therapeutic grounds the non-therapeutic use of gene transfer technology remains to be a gray zone for moral deliberation. The present discussion addresses several ethical issues concerning the impacts of human gene transfer technology on individuals, the society, and future people. Accordingly, the study examines major ethical issues concerning the use of human gene transfer technology in general and genetic enhancement in particular, and reliability of the putative demarcation between therapy and enhancement, and further proposes ethical guidelines for non-therapeutic application of human gene transfer technology. A special attention is given to three major ethical issues, such as our obligation to future generations, problems concerning justice, fairness, and equality, and the problem of uncertainty.

In this thesis I argue against the use of genetic technologies to enhance human cognitive capacities. More specifically, I respond to Nick Bostrom and Toby Ord's "Reversal Test", which they use to argue in favour of genetic cognitive enhancement. The Reversal Test is a burden of proof challenge designed to diagnose status quo bias in arguments against enhancement. By noting that most of those who oppose raising intelligence would also oppose lowering intelligence, the Reversal Test puts the onus on opponents of enhancement to explain why both increases and decreases in our cognitive capacity would be worse than the status quo (our current level of intelligence). Bostrom and Ord claim that if no good reasons can be provided, this indicates that the opposition to enhancement is influenced by status quo bias. Since cognitive biases cannot provide a moral reason against enhancement, opposition to genetic cognitive enhancement shown to be affected by status quo bias can accordingly be discounted. The aim of my thesis, then, is to overcome the Reversal Test' s burden of proof challenge by showing that my reasons for opposing cognitive enhancement are not influenced by status quo bias. However, I do not argue that enhanced intelligence could not be beneficial to the individual. Instead, I claim that the probable unequal distribution of enhancements between the best- and worst-off would be likely to cause serious injustices to those who are unable to afford them.

The study analyzes the ethical implications of human gene transfer technology for enhancement. Although human gene transfer technology is widely accepted on therapeutic grounds the non-therapeutic use of gene transfer technology remains to be a gray zone for moral deliberation. The present discussion addresses several ethical issues concerning the impacts of human gene transfer technology on individuals, the society, and future people. Accordingly, the study examines major ethical issues concerning the use of human gene transfer technology in general and genetic enhancement in particular, and reliability of the putative demarcation between therapy and enhancement, and further proposes ethical guidelines for non-therapeutic application of human gene transfer technology. A special attention is given to three major ethical issues, such as our obligation to future generations, problems concerning justice, fairness, and equality, and the problem of uncertainty.

In this thesis I argue against the use of genetic technologies to enhance human cognitive capacities. More specifically, I respond to Nick Bostrom and Toby Ord's "Reversal Test", which they use to argue in favour of genetic cognitive enhancement. The Reversal Test is a burden of proof challenge designed to diagnose status quo bias in arguments against enhancement. By noting that most of those who oppose raising intelligence would also oppose lowering intelligence, the Reversal Test puts the onus on opponents of enhancement to explain why both increases and decreases in our cognitive capacity would be worse than the status quo (our current level of intelligence). Bostrom and Ord claim that if no good reasons can be provided, this indicates that the opposition to enhancement is influenced by status quo bias. Since cognitive biases cannot provide a moral reason against enhancement, opposition to genetic cognitive enhancement shown to be affected by status quo bias can accordingly be discounted. The aim of my thesis, then, is to overcome the Reversal Test' s burden of proof challenge by showing that my reasons for opposing cognitive enhancement are not influenced by status quo bias. However, I do not argue that enhanced intelligence could not be beneficial to the individual. Instead, I claim that the probable unequal distribution of enhancements between the best- and worst-off would be likely to cause serious injustices to those who are unable to afford them.

In this thesis I argue against the use of genetic technologies to enhance human cognitive capacities. More specifically, I respond to Nick Bostrom and Toby Ord's "Reversal Test", which they use to argue in favour of genetic cognitive enhancement. The Reversal Test is a burden of proof challenge designed to diagnose status quo bias in arguments against enhancement. By noting that most of those who oppose raising intelligence would also oppose lowering intelligence, the Reversal Test puts the onus on opponents of enhancement to explain why both increases and decreases in our cognitive capacity would be worse than the status quo (our current level of intelligence). Bostrom and Ord claim that if no good reasons can be provided, this indicates that the opposition to enhancement is influenced by status quo bias. Since cognitive biases cannot provide a moral reason against enhancement, opposition to genetic cognitive enhancement shown to be affected by status quo bias can accordingly be discounted. The aim of my thesis, then, is to overcome the Reversal Test' s burden of proof challenge by showing that my reasons for opposing cognitive enhancement are not influenced by status quo bias. However, I do not argue that enhanced intelligence could not be beneficial to the individual. Instead, I claim that the probable unequal distribution of enhancements between the best- and worst-off would be likely to cause serious injustices to those who are unable to afford them.

In this thesis I argue against the use of genetic technologies to enhance human cognitive capacities. More specifically, I respond to Nick Bostrom and Toby Ord's "Reversal Test", which they use to argue in favour of genetic cognitive enhancement. The Reversal Test is a burden of proof challenge designed to diagnose status quo bias in arguments against enhancement. By noting that most of those who oppose raising intelligence would also oppose lowering intelligence, the Reversal Test puts the onus on opponents of enhancement to explain why both increases and decreases in our cognitive capacity would be worse than the status quo (our current level of intelligence). Bostrom and Ord claim that if no good reasons can be provided, this indicates that the opposition to enhancement is influenced by status quo bias. Since cognitive biases cannot provide a moral reason against enhancement, opposition to genetic cognitive enhancement shown to be affected by status quo bias can accordingly be discounted. The aim of my thesis, then, is to overcome the Reversal Test' s burden of proof challenge by showing that my reasons for opposing cognitive enhancement are not influenced by status quo bias. However, I do not argue that enhanced intelligence could not be beneficial to the individual. Instead, I claim that the probable unequal distribution of enhancements between the best- and worst-off would be likely to cause serious injustices to those who are unable to afford them.

In this thesis I argue against the use of genetic technologies to enhance human cognitive capacities. More specifically, I respond to Nick Bostrom and Toby Ord's "Reversal Test", which they use to argue in favour of genetic cognitive enhancement. The Reversal Test is a burden of proof challenge designed to diagnose status quo bias in arguments against enhancement. By noting that most of those who oppose raising intelligence would also oppose lowering intelligence, the Reversal Test puts the onus on opponents of enhancement to explain why both increases and decreases in our cognitive capacity would be worse than the status quo (our current level of intelligence). Bostrom and Ord claim that if no good reasons can be provided, this indicates that the opposition to enhancement is influenced by status quo bias. Since cognitive biases cannot provide a moral reason against enhancement, opposition to genetic cognitive enhancement shown to be affected by status quo bias can accordingly be discounted. The aim of my thesis, then, is to overcome the Reversal Test' s burden of proof challenge by showing that my reasons for opposing cognitive enhancement are not influenced by status quo bias. However, I do not argue that enhanced intelligence could not be beneficial to the individual. Instead, I claim that the probable unequal distribution of enhancements between the best- and worst-off would be likely to cause serious injustices to those who are unable to afford them.

Actually possible and conceivable future uses of preimplantation genetic diagnosis (PGD) and germ-line genetic intervention in assisted reproduction seem to offer increasing possibilities of choosing the kind of persons that will be brought to existence. Many are troubled by the idea of these technologies being used for enhancement purposes. How can we make sense of this worry? Why are our thoughts about therapeutic genetic interventions and non-genetic enhancement (for instance education) not accompanied by the same intuitive uneasiness? I argue that the concepts of autonomy and freedom of choice, typically invoked to delimit the morally acceptable uses of reproductive technologies, cannot fully answer these questions. Instead, I suggest that an alternative answer might begin with reflections on the notion of interfering with nature. Drawing on Martin Heidegger's critique of modern technology and Hans Jonas's moral philosophy, I outline an argument that attempts to capture what might be particularly troubling about the idea of "designing" future persons. At the core of the argument is the suggestion that enhancing selections and modifications on embryos might be bound up with an instrumentalising, non-responsive perspective on the future persons into which they are intended to grow. © Springer Science+Business Media, LLC 2007.

Implant ethics is defined here as the study of ethical aspects of the lasting introduction of technological devices into the human body. Whereas technological implants relieve us of some of the ethical problems connected with transplantation, other difficulties arise that are in need of careful analysis. A systematic approach to implant ethics is proposed. The major specific problems are identified as those concerning end of life issues (turning off devices), enhancement of human capabilities beyond normal levels, mental changes and personal identity, and cultural effects., QC 20100525

Proteolysis is one of the reasons for poor production of recombinant proteins in Escherichia coli. Important properties of E. coli proteases, which are relevant for the production of recombinant proteins, are reviewed. Furthermore, various strategies to control the proteolysis of the recombinant proteins are presented. These strategies for control of proteolysis can be applied on various stages of the process: design of more stable protein, a modification of the host cell in respect to proteolytic activity, optimisation of cultivation and downstream processing. However, before implementing these measures the proteolysis rate should be measured in order to calculate a potential benefit of reduced proteolysis rate., QC 20141215

The nucleotide sequences of several animal, plant and bacterial genomes are now known, but the functions of many of the proteins that they are predicted to encode remain unclear. RNA interference is a gene-silencing technology that is being used successfully to investigate gene function in several organisms - for example, Caenorhabditis elegans. We discuss here that RNA-induced gene silencing approaches are also likely to be effective for investigating plant gene function in a high-throughput, genome-wide manner.

Traditional anti-icing agents are either propylene or ethylene glycol. Glycols are effective in lowering the freezing point of water mixtures by the phenomenon of freezing point depression based solely on the molal concentration. The key environmental concerns with respect to use of ice control fluids are BOD loading and toxicity (human/mammalian and aquatic) resulting in extensive costs associated with the collection and cleanup associated with their use. For example, at Griffith AFB, NY, the use of glycols as a deicing fluid for aircraft has resulted in ground water cleanup programs costing over $8.2M. Additionally, an Air Force policy has been issued banning future purchase of ethylene glycol. Glycol based anti-icing agents are effective in lowering the freezing point of water mixtures by the phenomenon of freezing point depression. The magnitude of the freezing point depression of a given material is dependent on the amount of the material (solute), present in the solution (water) but not on its nature, and therefore freezing point depression is called a colligative property, denoting depending on the collection.