Engineered reversal of the β-oxidation cycle for the synthesis of fuels and chemicals

Advanced (long-chain) fuels and chemicals are generated from short-chain metabolic intermediates through pathways that require carbon-chain elongation. The condensation reactions mediating this carbon-carbon bond formation can be catalysed by enzymes from the thiolase superfamily, including β-ketoacyl-acyl-carrier protein (ACP) synthases, polyketide synthases, 3-hydroxy-3-methylglutaryl-CoA synthases, and biosynthetic thiolases. Pathways involving these enzymes have been exploited for fuel and chemical production, with fatty-acid biosynthesis (β-ketoacyl-ACP synthases) attracting the most attention in recent years. Degradative thiolases, which are part of the thiolase superfamily and naturally function in the β-oxidation of fatty acids, can also operate in the synthetic direction and thus enable carbon-chain elongation. Here we demonstrate that a functional reversal of the β-oxidation cycle can be used as a metabolic platform for the synthesis of alcohols and carboxylic acids with various chain lengths and functionalities. This pathway operates with coenzyme A (CoA) thioester intermediates and directly uses acetyl-CoA for acyl-chain elongation (rather than first requiring ATP-dependent activation to malonyl-CoA), characteristics that enable product synthesis at maximum carbon and energy efficiency. The reversal of the β-oxidation cycle was engineered in Escherichia coli and used in combination with endogenous dehydrogenases and thioesterases to synthesize n-alcohols, fatty acids and 3-hydroxy-, 3-keto- and trans-Δ(2)-carboxylic acids. The superior nature of the engineered pathway was demonstrated by producing higher-chain linear n-alcohols (C?≥?4) and extracellular long-chain fatty acids (C?>?10) at higher efficiency than previously reported. The ubiquitous nature of β-oxidation, aldehyde/alcohol dehydrogenase and thioesterase enzymes has the potential to enable the efficient synthesis of these products in other industrial organisms.     

Basketball scoring in NBA games: An example of complexity

Abstract Scoring in a basketball game is a highly dynamic, non-linear process. NBA teams try to be more and more competitive each season. For instance, they incorporate into their rosters the best players in the world. This and other mechanisms concur to make the scoring process in NBA games exciting and rarely predictable. This paper is to study the behavior of timing and scoring in basketball games. The authors analyze all the games in five NBA regular seasons (2005–06, 2006–07, 2007–08, 2008–09, 2009–10), for a total of 6150 games. Scoring does not behave uniformly; therefore, the authors also analyze the distributions of the differences in points in the basketball games. To further analyze the behavior of the tail of the distribution, the authors also carry out a semilog-plot and a log-log plot to verify whether this trend approaches a Poisson distribution or a PL. This paper reveals different areas of behavior related to the score, with specific instances of time that could be considered tipping points of the game. The presence of these critical points suggests that there are phase transitions where the dynamic scoring of the games varies significantly.     

Range Extension and Channel Capacity Increase in Impulse-Radio Ultra-Wideband Communications

We theoretically analyze the channel capacity of a 5th-order Gaussian pulse-based ultra-wideband (UWB) system and experimentally demonstrate 2 Gbit/s UWB-over-fiber transmission systems incorporating wireless transmission. Both electrical and photonic UWB pulse generation methods are employed and its performance is compared. By utilizing optimum UWB pulse design and employing a digital signal processing (DSP) receiver, a bit-error-rate above the forward error correction (FEC) limit for 8 meters of wireless ...     

Biodiversity loss and its impact on humanity

The most unique feature of Earth is the existence of life, and the most extraordinary feature of life is its diversity. Approximately 9 million types of plants, animals, protists and fungi inhabit the Earth. So, too, do 7 billion people. Two decades ago, at the first Earth Summit, the vast majority of the world's nations declared that human actions were dismantling the Earth's ecosystems, eliminating genes, species and biological traits at an alarming rate. This observation led to the question of how such loss of biological diversity will alter the functioning of ecosystems and their ability to provide society with the goods and services needed to prosper.     

Live imaging of stem cell and progeny behaviour in physiological hair-follicle regeneration

Tissue development and regeneration depend on cell-cell interactions and signals that target stem cells and their immediate progeny. However, the cellular behaviours that lead to a properly regenerated tissue are not well understood. Using a new, non-invasive, intravital two-photon imaging approach we study physiological hair-follicle regeneration over time in live mice. By these means we have monitored the behaviour of epithelial stem cells and their progeny during physiological hair regeneration and addressed how the mesenchyme influences their behaviour. Consistent with earlier studies, stem cells are quiescent during the initial stages of hair regeneration, whereas the progeny are more actively dividing. Moreover, stem cell progeny divisions are spatially organized within follicles. In addition to cell divisions, coordinated cell movements of the progeny allow the rapid expansion of the hair follicle. Finally, we show the requirement of the mesenchyme for hair regeneration through targeted cell ablation and long-term tracking of live hair follicles. Thus, we have established an in vivo approach that has led to the direct observation of cellular mechanisms of growth regulation within the hair follicle and that has enabled us to precisely investigate functional requirements of hair-follicle components during the process of physiological regeneration.     

Genetic variation in DLG5 is associated with inflammatory bowel disease

Crohn disease and ulcerative colitis are two subphenotypes of inflammatory bowel disease (IBD), a complex disorder resulting from gene-environment interaction. We refined our previously defined linkage region for IBD on chromosome 10q23 and used positional cloning to identify genetic variants in DLG5 associated with IBD. DLG5 encodes a scaffolding protein involved in the maintenance of epithelial integrity. We identified two distinct haplotypes with a replicable distortion in transmission (P = 0.000023 and P = 0.004 for association with IBD, P = 0.00012 and P = 0.04 for association with Crohn disease). One of the risk-associated DLG5 haplotypes is distinguished from the common haplotype by a nonsynonymous single-nucleotide polymorphism 113G-->A, resulting in the amino acid substitution R30Q in the DUF622 domain of DLG5. This mutation probably impedes scaffolding of DLG5. We stratified the study sample according to the presence of risk-associated CARD15 variants to study potential gene-gene interaction. We found a significant difference in association of the 113A DLG5 variant with Crohn disease in affected individuals carrying the risk-associated CARD15 alleles versus those carrying non-risk-associated CARD15 alleles. This is suggestive of a complex pattern of gene-gene interaction between DLG5 and CARD15, reflecting the complex nature of polygenic diseases. Further functional studies will evaluate the biological significance of DLG5 variants.     

The liver blood flow after local X-irradiation

Zusammenfassung Mit Hilfe der Clearance von kolloidalem Radiogold, der Leber- und Milzspeicherung wurde die Durchblutung der Leber nach lokaler Bestrahlung der Leberregion bestimmt. Im Anschluss an 500, 1000 oder 2000 R wurde eine Verminderung der Leberdurchblutung festgestellt. Eine Restitutio ad integrum wurde dosisunabhängig 3–4 Tage post irritationem beobachtet.