C. elegans fatty acid two-hydroxylase regulates intestinal homeostasis by affecting heptadecenoic acid production

Background/Aims: The hydroxylation of fatty acids at the C-2 position is the first step of fatty acid α-oxidation and generates sphingolipids containing 2-hydroxy fatty acyl moieties. Fatty acid 2-hydroxylation is catalyzed by Fatty acid 2-hydroxylase (FA2H) enzyme. However, the precise roles of FA2H and fatty acid 2-hydroxylation in whole cell homeostasis still remain unclear. Methods: Here we utilize Caenorhabditis elegans as the model and systemically investigate the physiological functions of FATH-1/C25A1.5, the highly conserved worm homolog for mammalian FA2H enzyme. Immunostaining, dye-staining and translational fusion reporters were used to visualize FATH-1 protein and a variety of subcellular structures. The “click chemistry” method was employed to label 2-OH fatty acid in vivo. Global and tissue-specific RNAi knockdown experiments were performed to inactivate FATH-1 function. Lipid analysis of the fath-1 deficient mutants was achieved by mass spectrometry. Results: C. elegans FATH-1 is expressed at most developmental stages and in most tissues. Loss of fath-1 expression results in severe growth retardation and shortened lifespan. FATH-1 function is crucially required in the intestine but not the epidermis with stereospecificity. The “click chemistry” labeling technique showed that the FATH-1 metabolites are mainly enriched in membrane structures preferable to the apical side of the intestinal cells. At the subcellular level, we found that loss of fath-1 expression inhibits lipid droplets formation, as well as selectively disrupts peroxisomes and apical endosomes. Lipid analysis of the fath-1 deficient animals revealed a significant reduction in the content of heptadecenoic acid, while other major FAs remain unaffected. Feeding of exogenous heptadecenoic acid (C17: 1), but not oleic acid (C18: 1), rescues the global and subcellular defects of fath-1 knockdown worms. Conclusion: Our study revealed that FATH-1 and its catalytic products are highly specific in the context of chirality, C-chain length, spatial distribution, as well as the types of cellular organelles they affect. Such an unexpected degree of specificity for the synthesis and functions of hydroxylated FAs helps to regulate protein transport and fat metabolism, therefore maintaining the cellular homeostasis of the intestinal cells. These findings may help our understanding of FA2H functions across species, and offer potential therapeutical targets for treating FA2H-related diseases

The HD-GYP Domain Protein RpfG of Xanthomonas oryzae pv. oryzicola Regulates Synthesis of Extracellular Polysaccharides that Contribute to Biofilm Formation and Virulence on Rice

Bacterial leaf streak caused by Xanthomonas oryzae pv. oryzicola (Xoc) is one of the most important diseases in rice. However, little is known about the pathogenicity mechanisms of Xoc. Here we have investigated the function of three HD-GYP domain regulatory proteins in biofilm formation, the synthesis of virulence factors and virulence of Xoc. Deletion of rpfG resulted in altered production of extracellular polysaccharides (EPS), abolished virulence on rice and enhanced biofilm formation, but had little effect on the secretion of proteases and motility. In contrast, mutational analysis showed that the other two HD-GYP domain proteins had no effect on virulence factor synthesis and tested phenotypes. Mutation of rpfG led to up-regulation of the type III secretion system and altered expression of three putative glycosyltransferase genes gumD, pgaC and xagB, which are part of operons directing the synthesis of different extracellular polysaccharides. The pgaABCD and xagABCD operons were greatly up-regulated in the Xoc Delta rpfG mutant, whereas the expression of the gum genes was unaltered or slightly enhanced. The elevated biofilm formation of the Xoc Delta rpfG mutant was dramatically reduced upon deletion of gumD, xagA and xagB, but not when pgaA and pgaC were deleted. Interestingly, only the Delta gumD mutant, among these single gene mutants, exhibits multiple phenotype alterations including reduced biofilm and EPS production and attenuated virulence on rice. These data indicate that RpfG is a global regulator that controls biofilm formation, EPS production and bacterial virulence in Xoc and that both gumD- and xagB-dependent EPS contribute to biofilm formation under different conditions

Precision immunization: a new trend in human vaccination

Vaccination has been one of the major revolutions in the history of human health. Vaccination programs have targeted entire populations such as infants or elderly subjects as a matter of being efficient with time and resources. These general populations are heterogeneous in terms of factors such as ethnicity, health status, and socio-economics. Thus, there have been variations in the safety and effectiveness profiles of certain vaccinations according to current population-wide strategies. As the concept of precision medicine has been raised in recent years, many researchers have suggested that vaccines could be administered more precisely in terms of particular target populations, vaccine formulations, regimens, and dosage levels. This review addresses the concept and framework of precision immunization, summarizes recent and representative clinical trials of among specific populations, mentions important factors to be addressed in customizing vaccinations, and provides suggestions on the establishment of precision immunization with the goal of maximizing the effectiveness of vaccines in general

Silencing of a Cotton Actin-Binding Protein GhWLIM1C Decreases Resistance against <i>Verticillium dahliae</i> Infection

LIM proteins are widely spread in various types of plant cells and play diversely crucial cellular roles through actin cytoskeleton assembly and gene expression regulation. Till now, it has not been clear whether LIM proteins function in plant pathogen defense. In this study, we characterized a LIM protein, GhWLIM1C, in upland cotton (Gossypium hirsutum). We found that GhWLIM1C could bind and bundle the actin cytoskeleton, and it contains two LIM domains (LIM1 and LIM2). Both the two domains could bind directly to the actin filaments. Moreover, the LIM2 domain additionally bundles the actin cytoskeleton, indicating that it possesses a different biochemical activity than LIM1. The expression of GhWLIM1C responds to the infection of the cotton fungal pathogen Verticillium dahliae (V. dahliae). Silencing of GhWLIM1C decreased cotton resistance to V. dahliae. These may be associated with the down regulated plant defense response, including the PR genes expression and ROS accumulation in the infected cotton plants. In all, these results provide new evidence that a plant LIM protein functions in plant pathogen resistance and the assembly of the actin cytoskeleton are closely related to the triggering of the plant defense response

A New Business Model Beneficial to Both Retailers and Industrial Customers in Smart Grids

The evolution of smart grids provides opportunities for retailers to get more benefit through improving business models. As the largest energy users in the distribution grid, the industrial customers are the most suitable for retailers to advertise new services. A two-layered optimization model is proposed for a retailer to design consumption scheduling for multiple industrial customers, which aligns the maximization of profits of both parties. It considers detailed production processes of users under the scheme of time-of-use (TOU) prices as well as rewards for their demand response (DR). The scheduling results include the equipment operation time and power settings as well as suggestions for optimal production amount. An augmented realistic case study of a retailer with multiple brickyards is used to illustrate the effectiveness of the proposed framework. The simulation result shows that with the proposed scheduling service all the players have better economic profits while the distribution grid can get more flexible operational resources from demand side

Process Optimization of SiC-Reinforced Aluminum Matrix Composites Prepared Using Laser Powder Bed Fusion and the Effect of Particle Morphology on Performance

Process parameters and powder spreading quality are important factors for aluminum matrix composites (AMCs) prepared using laser powder bed fusion (LPBF). In this study, a Box–Behnken Design (BBD) was used to optimize the process parameters, and near-spherical β-SiC was selected to improve the quality of powder spreading. The rationality of parameter optimization was verified by testing the density of samples prepared using different laser power levels. Al4C3 diffraction peaks were found in XRD patterns, which indicated that interface reactions occurred to form good interface bonding between the Al matrix and the SiC particles. The tensile strength and plasticity of LPBF α-SiC/AlSi10Mg were lower than that of LPBF AlSi10Mg, which was mainly due to the poor fluidity of the powder mixtures and powder spreading quality. For LPBF β-SiC/AlSi10Mg, the tensile strength increased and elongation decreased slightly compared to LPBF α-SiC/AlSi10Mg. The data in this study were compared with the data in other studies. In this study, LPBF AlSi10Mg and LPBF β-SiC/AlSi10Mg not only showed the inherent high strength of their LPBF parts, but also had relatively high plasticity. Matching between strength and plasticity was mainly dependent on the scanning strategy. Most studies use uni-directional or bi-directional scanning strategies with a certain rotation angle between layers. A chessboard scanning strategy was used in this study to form a coarse remelted connected skeleton inside the material and significantly improve plasticity. This study lays a theoretical and experimental foundation for the controllable preparation of SiC-reinforced AMCs using LPBF

1 Tb/s WDM-OFDM-PON over 20km SSMF with Polarization Interleaving and Multi-band

1 Tb/s WDM-OFDM-PON with 50 GHz channel spacing is demonstrated, adopting the polarization interleaving and multi-band schemes. The transmission penalty induced by fiber nonlinearity is investigated by numerical simulations. ? OSA 2013.EI

The Microtubule End Binding Protein Mal3 Is Essential for the Dynamic Assembly of Microtubules during <i>Magnaporthe oryzae</i> Growth and Pathogenesis

Cytoskeletal microtubules (MTs) play crucial roles in many aspects of life processes in eukaryotic organisms. They dynamically assemble physiologically important MT arrays under different cell conditions. Currently, aspects of MT assembly underlying the development and pathogenesis of the model plant pathogenic fungus Magnaporthe oryzae (M. oryzae) are unclear. In this study, we characterized the MT plus end binding protein MoMal3 in M. oryzae. We found that knockout of MoMal3 results in defects in hyphal polar growth, appressorium-mediated host penetration and nucleus division. Using high-resolution live-cell imaging, we further found that the MoMal3 mutant assembled a rigid MT in parallel with the MT during hyphal polar growth, the cage-like network in the appressorium and the stick-like spindle in nuclear division. These aberrant MT organization patterns in the MoMal3 mutant impaired actin-based cell growth and host infection. Taken together, these findings showed that M. oryzae relies on MoMal3 to assemble elaborate MT arrays for growth and infection. The results also revealed the assembly mode of MTs in M. oryzae, indicating that MTs are pivotal for M. oryzae growth and host infection and may be new targets for devastating fungus control