Characteristic Evolution and Matching

I review the development of numerical evolution codes for general relativity based upon the characteristic initial value problem. Progress in characteristic evolution is traced from the early stage of 1D feasibility studies to 2D axisymmetric codes that accurately simulate the oscillations and gravitational collapse of relativistic stars and to current 3D codes that provide pieces of a binary black hole spacetime. Cauchy codes have now been successful at simulating all aspects of the binary black hole problem inside an artificially constructed outer boundary. A prime application of characteristic evolution is to extend such simulations to null infinity where the waveform from the binary inspiral and merger can be unambiguously computed. This has now been accomplished by Cauchy-characteristic extraction, where data for the characteristic evolution is supplied by Cauchy data on an extraction worldtube inside the artificial outer boundary. The ultimate application of characteristic evolution is to eliminate the role of this outer boundary by constructing a global solution via Cauchy-characteristic matching. Progress in this direction is discussed.Comment: New version to appear in Living Reviews 2012. arXiv admin note: updated version of arXiv:gr-qc/050809

Biotechnological production of γ-decalactone, a peach like aroma, by Yarrowia lipolytica

The request for new flavourings increases every year. Consumer perception that everything natural is better is causing an increase demand for natural aroma additives. Biotechnology has become a way to get natural products. γ-Decalactone is a peach-like aroma widely used in dairy products, beverages and others food industries. In more recent years, more and more studies and industrial processes were endorsed to cost-effect this compound production. One of the best-known methods to produce -decalactone is from ricinoleic acid catalyzed by Yarrowia lipolytica, a generally regarded as safe status yeast. As yet, several factors affecting -decalactone production remain to be fully understood and optimized. In this review, we focus on the aromatic compound -decalactone and its production by Y. lipolytica. The metabolic pathway of lactone production and degradation are addressed. Critical analysis of novel strategies of bioprocess engineering, metabolic and genetic engineering and other strategies for the enhancement of the aroma productivity are presented.This study was supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UID/BIO/04469/2013 unit and COMPETE 2020 (POCI-01-0145-FEDER-006684)

Cloning and characterization of a 9-lipoxygenase gene induced by pathogen attack from Nicotiana benthamiana for biotechnological application

<p>Abstract</p> <p>Background</p> <p>Plant lipoxygenases (LOXs) have been proposed to form biologically active compounds both during normal developmental stages such as germination or growth as well as during responses to environmental stress such as wounding or pathogen attack. In our previous study, we found that enzyme activity of endogenous 9-LOX in <it>Nicotiana benthamiana </it>was highly induced by agroinfiltration using a tobacco mosaic virus (TMV) based vector system.</p> <p>Results</p> <p>A <it>LOX </it>gene which is expressed after treatment of the viral vectors was isolated from <it>Nicotiana benthamiana</it>. As the encoded LOX has a high amino acid identity to other 9-LOX proteins, the gene was named as <it>Nb-9-LOX</it>. It was heterologously expressed in yeast cells and its enzymatic activity was characterized. The yeast cells expressed large quantities of stable 9-LOX (0.9 U ml^-1cell cultures) which can oxygenate linoleic acid resulting in high yields (18 μmol ml^-1cell cultures) of hydroperoxy fatty acid. The product specificity of Nb-9-LOX was examined by incubation of linoleic acid and Nb-9-LOX in combination with a 13-hydroperoxide lyase from watermelon (Cl-13-HPL) or a 9/13-hydroperoxide lyase from melon (Cm-9/13-HPL) and by LC-MS analysis. The result showed that Nb-9-LOX possesses both 9- and 13-LOX specificity, with high predominance for the 9-LOX function. The combination of recombinant Nb-9-LOX and recombinant Cm-9/13-HPL produced large amounts of C₉-aldehydes (3.3 μmol mg^-1crude protein). The yield of C₉-aldehydes from linoleic acid was 64%.</p> <p>Conclusion</p> <p>The yeast expressed Nb-9-LOX can be used to produce C₉-aldehydes on a large scale in combination with a <it>HPL </it>gene with 9-HPL function, or to effectively produce 9-hydroxy-10(<it>E</it>),12(<it>Z</it>)-octadecadienoic acid in a biocatalytic process in combination with cysteine as a mild reducing agent.</p

Selected heterozygosity at cis-regulatory sequences increases the expression homogeneity of a cell population in humans

Background: Examples of heterozygote advantage in humans are scarce and limited to protein-coding sequences. Here, we attempt a genome-wide functional inference of advantageous heterozygosity at cis-regulatory regions. Results: The single-nucleotide polymorphisms bearing the signatures of balancing selection are enriched in active cis-regulatory regions of immune cells and epithelial cells, the latter of which provide barrier function and innate immunity. Examples associated with ancient trans-specific balancing selection are also discovered. Allelic imbalance in chromatin accessibility and divergence in transcription factor motif sequences indicate that these balanced polymorphisms cause distinct regulatory variation. However, a majority of these variants show no association with the expression level of the target gene. Instead, single-cell experimental data for gene expression and chromatin accessibility demonstrate that heterozygous sequences can lower cell-to-cell variability in proportion to selection strengths. This negative correlation is more pronounced for highly expressed genes and consistently observed when using different data and methods. Based on mathematical modeling, we hypothesize that extrinsic noise from fluctuations in transcription factor activity may be amplified in homozygotes, whereas it is buffered in heterozygotes. While high expression levels are coupled with intrinsic noise reduction, regulatory heterozygosity can contribute to the suppression of extrinsic noise. Conclusions: This mechanism may confer a selective advantage by increasing cell population homogeneity and thereby enhancing the collective action of the cells, especially of those involved in the defense systems in humansope

Characteristic Evolution and Matching

I review the development of numerical evolution codes for general relativity based upon the characteristic initial value problem. Progress is traced from the early stage of 1D feasibility studies to 2D axisymmetric codes that accurately simulate the oscillations and gravitational collapse of relativistic stars and to current 3D codes that provide pieces of a binary black spacetime. A prime application of characteristic evolution is to compute waveforms via Cauchy-characteristic matching, which is also reviewed.Comment: Published version http://www.livingreviews.org/lrr-2005-1

Generation of flavors and fragrances through biotransformation and de novo synthesis

Flavors and fragrances are the result of the presence of volatile and non-volatile compounds, appreciated mostly by the sense of smell once they usually have pleasant odors. They are used in perfumes and perfumed products, as well as for the flavoring of foods and beverages. In fact the ability of the microorganisms to produce flavors and fragrances has been described for a long time, but the relationship between the flavor formation and the microbial growth was only recently established. After that, efforts have been put in the analysis and optimization of food fermentations that led to the investigation of microorganisms and their capacity to produce flavors and fragrances, either by de novo synthesis or biotransformation. In this review, we aim to resume the recent achievements in the production of the most relevant flavors by bioconversion/biotransformation or de novo synthesis, its market value, prominent strains used, and their production rates/maximum concentrations.We would like to thank the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UID/BIO/04469 unit, COMPETE 2020 (POCI-01-0145FEDER-006684), and BiotecNorte operation (NORTE-01-0145FEDER-000004) funded by the European Regional Development Fund under the scope of Norte2020—Programa Operacional Regional do Norte.info:eu-repo/semantics/publishedVersio

KLOTHO heterozygosity attenuates APOE4-related amyloid burden in preclinical AD

OBJECTIVE: To examine whether the KLOTHO gene variant KL-VS attenuates APOE4-associated β-amyloid (Aβ) accumulation in a late-middle-aged cohort enriched with Alzheimer disease (AD) risk factors. METHODS: Three hundred nine late-middle-aged adults from the Wisconsin Registry for Alzheimer's Prevention and the Wisconsin Alzheimer's Disease Research Center were genotyped to determine KL-VS and APOE4 status and underwent CSF sampling (n = 238) and/or 11C-Pittsburgh compound B (PiB)-PET imaging (n = 183). Covariate-adjusted regression analyses were used to investigate whether APOE4 exerted expected effects on Aβ burden. Follow-up regression analyses stratified by KL-VS genotype (i.e., noncarrier vs heterozygous; there were no homozygous individuals) evaluated whether the influence of APOE4 on Aβ was different among KL-VS heterozygotes compared to noncarriers. RESULTS: APOE4 carriers exhibited greater Aβ burden than APOE4-negative participants. This effect was stronger in CSF (t = -5.12, p < 0.001) compared with PiB-PET (t = 3.93, p < 0.001). In the stratified analyses, this APOE4 effect on Aβ load was recapitulated among KL-VS noncarriers (CSF: t = -5.09, p < 0.001; PiB-PET: t = 3.77, p < 0 .001). In contrast, among KL-VS heterozygotes, APOE4-positive individuals did not exhibit higher Aβ burden than APOE4-negative individuals (CSF: t = -1.03, p = 0.308; PiB-PET: t = 0.92, p = 0.363). These differential APOE4 effects remained after KL-VS heterozygotes and noncarriers were matched on age and sex. CONCLUSION: In a cohort of at-risk late-middle-aged adults, KL-VS heterozygosity was associated with an abatement of APOE4-associated Aβ aggregation, suggesting KL-VS heterozygosity confers protections against APOE4-linked pathways to disease onset in AD