Molecular and Chemical Characterization of the Biosynthesis of the 6-MSA-Derived Meroterpenoid Yanuthone D in Aspergillus niger.

SummarySecondary metabolites in filamentous fungi constitute a rich source of bioactive molecules. We have deduced the genetic and biosynthetic pathway of the antibiotic yanuthone D from Aspergillus niger. Our analyses show that yanuthone D is a meroterpenoid derived from the polyketide 6-methylsalicylic acid (6-MSA). Yanuthone D formation depends on a cluster composed of ten genes including yanA and yanI, which encode a 6-MSA polyketide synthase and a previously undescribed O-mevalon transferase, respectively. In addition, several branching points in the pathway were discovered, revealing five yanuthones (F, G, H, I, and J). Furthermore, we have identified another compound (yanuthone X1) that defines a class of yanuthones that depend on several enzymatic activities encoded by genes in the yan cluster but that are not derived from 6-MSA

A Systems Biology Approach Identifies a R2R3 MYB Gene Subfamily with Distinct and Overlapping Functions in Regulation of Aliphatic Glucosinolates

BACKGROUND: Glucosinolates are natural metabolites in the order Brassicales that defend plants against both herbivores and pathogens and can attract specialized insects. Knowledge about the genes controlling glucosinolate regulation is limited. Here, we identify three R2R3 MYB transcription factors regulating aliphatic glucosinolate biosynthesis in Arabidopsis by combining several systems biology tools. METHODOLOGY/PRINCIPAL FINDINGS: MYB28 was identified as a candidate regulator of aliphatic glucosinolates based on its co-localization within a genomic region controlling variation both in aliphatic glucosinolate content (metabolite QTL) and in transcript level for genes involved in the biosynthesis of aliphatic glucosinolates (expression QTL), as well as its co-expression with genes in aliphatic glucosinolate biosynthesis. A phylogenetic analysis with the R2R3 motif of MYB28 showed that it and two homologues, MYB29 and MYB76, were members of an Arabidopsis-specific clade that included three characterized regulators of indole glucosinolates. Over-expression of the individual MYB genes showed that they all had the capacity to increase the production of aliphatic glucosinolates in leaves and seeds and induce gene expression of aliphatic biosynthetic genes within leaves. Analysis of leaves and seeds of single knockout mutants showed that mutants of MYB29 and MYB76 have reductions in only short-chained aliphatic glucosinolates whereas a mutant in MYB28 has reductions in both short- and long-chained aliphatic glucosinolates. Furthermore, analysis of a double knockout in MYB28 and MYB29 identified an emergent property of the system since the absence of aliphatic glucosinolates in these plants could not be predicted by the chemotype of the single knockouts. CONCLUSIONS/SIGNIFICANCE: It seems that these cruciferous-specific MYB regulatory genes have evolved both overlapping and specific regulatory capacities. This provides a unique system within which to study the evolution of MYB regulatory factors and their downstream targets

Genomic Analysis of QTLs and Genes Altering Natural Variation in Stochastic Noise

Quantitative genetic analysis has long been used to study how natural variation of genotype can influence an organism's phenotype. While most studies have focused on genetic determinants of phenotypic average, it is rapidly becoming understood that stochastic noise is genetically determined. However, it is not known how many traits display genetic control of stochastic noise nor how broadly these stochastic loci are distributed within the genome. Understanding these questions is critical to our understanding of quantitative traits and how they relate to the underlying causal loci, especially since stochastic noise may be directly influenced by underlying changes in the wiring of regulatory networks. We identified QTLs controlling natural variation in stochastic noise of glucosinolates, plant defense metabolites, as well as QTLs for stochastic noise of related transcripts. These loci included stochastic noise QTLs unique for either transcript or metabolite variation. Validation of these loci showed that genetic polymorphism within the regulatory network alters stochastic noise independent of effects on corresponding average levels. We examined this phenomenon more globally, using transcriptomic datasets, and found that the Arabidopsis transcriptome exhibits significant, heritable differences in stochastic noise. Further analysis allowed us to identify QTLs that control genomic stochastic noise. Some genomic QTL were in common with those altering average transcript abundance, while others were unique to stochastic noise. Using a single isogenic population, we confirmed that natural variation at ELF3 alters stochastic noise in the circadian clock and metabolism. Since polymorphisms controlling stochastic noise in genomic phenotypes exist within wild germplasm for naturally selected phenotypes, this suggests that analysis of Arabidopsis evolution should account for genetic control of stochastic variance and average phenotypes. It remains to be determined if natural genetic variation controlling stochasticity is equally distributed across the genomes of other multi-cellular eukaryotes

Disaggregation of Sources of Incom Inequality in Sudan

This paper examines income inequality in Sudan, using data of the national labor surveys carried out by Ministry of Labour, in 1996 and 2011. It attempts to explore the contribution of different income sources to over-all income inequality, by disaggregating the Gini measure of household per capita income, and change in the sources relative marginal effects between the two years. A Gini coefficient of 71% is indicated in 1996 with a lower value of 61% shown for 2011. Wages and paid labor income are found to represent the largest share ofhousehold per capita income and ranked first among the different income sources in contribution to overall inequality (63.5% in 1996 and 43% in 2011). Income from agricultural and livestock represented the second largest share (36%) in income composition in 2011 and in relative contribution to inequality (39%) compared to a lower contribution of (around 9%) in 1996, when one fifth of total per capita income was made of remittances and transfers. In 1996 both income and remittances seemed to have benefited the top income recipients. It is argued that this can be attributed to the harsh economic measures implemented in mid-1990, which privatized the provision of vital services to agriculture, including provision of credit. An increase in contribution of non-agricultural income in 2011 seemed to produce favorable impact on inequality as indicated by a marginal effect of -.003. Also in 2011, though contributing less to income than in 1996, remittances and transfers had an equalizing effect on overall inequality (marginal effect of -0.02). It is suggested that improvement in agricultural infrastructure, and provision of inputs like water and credit facilities, especially to small producers, and creation of off-farm activities in rain-fed areas, and support to selfemployed and small producers in services and trade in urban areas, would have a favourable impact on employment and income distribution

Feasibility of diffusion-weighted magnetic resonance imaging in evaluation of early therapeutic response after CT-guided microwave ablation of inoperable lung neoplasms

Objective!#!To determine the early treatment response after microwave ablation (MWA) of inoperable lung neoplasms using the apparent diffusion coefficient (ADC) value calculated 24 h after the ablation.!##!Materials and methods!#!This retrospective study included 47 patients with 68 lung lesions, who underwent percutaneous MWA from January 2008 to December 2017. Evaluation of the lesions was done using MRI including DWI sequence with ADC value calculation pre-ablation and 24 h post-ablation. DWI-MR was performed with b values (50, 400, 800 mm!##!Results!#!Forty-seven patients (mean age: 63.8 ± 14.2 years, 25 women) with 68 lesions having a mean tumor size of 1.5 ± 0.9 cm (range: 0.7-5 cm) were evaluated. Sixty-one lesions (89.7%) showed a complete treatment response, and the remaining 7 lesions (10.3%) showed a local progression (residual activity). There was a statistically significant difference regarding the ADC value measured 24 h after the ablation between the responding (1.7 ± 0.3 × 10!##!Conclusion!#!ADC value assessment following ablation may allow the early prediction of treatment efficacy after MWA of inoperable lung neoplasms.!##!Key points!#!• ADC value calculated 24 h post-treatment may allow the early prediction of MWA efficacy as a treatment of pulmonary tumors and can be used in the early immediate post-ablation imaging follow-up. • The pre-treatment ADC value of lung neoplasms is not different between the responding and non-responding tumors