DspA/E-Triggered Non-Host Resistance against E. amylovora Depends on the Arabidopsis GLYCOLATE OXIDASE 2 Gene

DspA/E is a type three effector injected by the pathogenic bacterium Erwinia amylovora inside plant cells. In non-host Arabidopsis thaliana, DspA/E inhibits seed germination, root growth, de novo protein synthesis and triggers localized cell death. To better understand the mechanisms involved, we performed EMS mutagenesis on a transgenic line, 13-1-2, containing an inducible dspA/E gene. We identified three suppressor mutants, two of which belonged to the same complementation group. Both were resistant to the toxic effects of DspA/E. Metabolome analysis showed that the 13-1-2 line was depleted in metabolites of the TCA cycle and accumulated metabolites associated with cell death and defense. TCA cycle and cell-death associated metabolite levels were respectively increased and reduced in both suppressor mutants compared to the 13-1-2 line. Whole genome sequencing indicated that both suppressor mutants displayed missense mutations in conserved residues of Glycolate oxidase 2 (GOX2), a photorespiratory enzyme that we confirmed to be localized in the peroxisome. Leaf GOX activity increased in leaves infected with E. amylovora in a DspA/E-dependent manner. Moreover, the gox2-2 KO mutant was more sensitive to E. amylovora infection and displayed reduced JA-signaling. Our results point to a role for glycolate oxidase in type II non-host resistance and to the importance of central metabolic functions in controlling growth/defense balance.     

Synthesis of Aromatic Polyhedral Oligomeric SilSesquioxane (POSS) Dianilines for Use in High-Temperature Polyimides

A series of novel aromatic Polyhedral Oligomeric SilSesquioxane (POSS) dianiline molecules has been synthesized for use in the preparation of high temperature aromatic polyimides. A general synthetic strategy was devised to improve the structure, yield, and utility of POSS dianilines over those currently available. Peripheral aromatic functionality was specifically incorporated in order to improve thermal properties and to increase compatibility with aromatic polymers. Silyloxy and/or aromatic functional groups were used to link the aniline groups to the POSS cage in order to ensure that this linkage was not a thermal weak point. Additionally, the stereochemistry of the aniline functionality has been varied to produce both meta- and para- isomers. The new dianiline monomers can be used to produce high molecular weight polyimide polymers. These dianilines have been incorporated both as pendants to the polymer backbone, and in a ??bead-on-a-string?? fashion by insertion into the polymer main-chain. In addition to producing POSS polyimides with superior thermal stability, these new monomers will allow full characterization and comparison of POSS-polyimides with differing structures in order to delineate the structure-property relationships of POSS and polymer architectures.     

Influence of hole shape/size on the growth of site-selective quantum dots

The number of quantum dots which nucleate at a certain place has to be controllable for device integration. It was shown that the number of quantum dots per nucleation site depends on the size of the hole in the substrate, but other dimensions of the nucleation site are vague. We report on the influence of hole shape on site-selectively grown InAs quantum dots (QDs) by molecular beam epitaxy. Dry etching of the GaAs wafers was used because of its high anisotropic etching characteristic. Therefore, it was possible to verify the influence of several hole shape parameters on the subsequent QD growth independently. We show that the nucleation of these QDs depends on several properties of the hole, namely its surface area, aspect ratio of the surface area, and depth. Especially, the aspect ratio shows a big influence on the number of nucleating QDs per site. With knowledge of these dependencies, it is possible to influence the number of QDs per site and also its distribution.     

Exact exponential algorithms for 3-machine flowshop scheduling problems

In this paper, we focus on the design of an exact exponential time algorithm with a proved worst-case running time for 3-machine flowshop scheduling problems considering worst-case scenarios. For the minimization of the makespan criterion, a Dynamic Programming algorithm running in \({\mathcal {O}}^*(3^n)\) is proposed, which improves the current best-known time complexity \(2^{{\mathcal {O}}(n)}\times \Vert I\Vert ^{{\mathcal {O}}(1)}\) in the literature. The idea is based on a dominance condition and the consideration of the Pareto Front in the criteria space. The algorithm can be easily generalized to other problems that have similar structures. The generalization on two problems, namely the \(F3\Vert f_\mathrm{max}\) and \(F3\Vert \sum f_i\) problems, is discussed.     

Consequences of Acute or Chronic Methylphenidate Exposure Using Ex Vivo Neurochemistry and In Vivo Electrophysiology in the Prefrontal Cortex and Striatum of Rats

Methylphenidate (MPH) is among the main drugs prescribed to treat patients with attention-deficit and hyperactivity disease (ADHD). MPH blocks both the norepinephrine and dopamine reuptake transporters (NET and DAT, respectively). Our study was aimed at further understanding the mechanisms by which MPH could modulate neurotransmitter efflux, using ex vivo radiolabelled neurotransmitter assays isolated from rats. Here, we observed significant dopamine and norepinephrine efflux from the prefrontal cortex (PFC) after MPH (100 µM) exposure. Efflux was mediated by both dopamine and norepinephrine terminals. In the striatum, MPH (100 µM) triggered dopamine efflux through both sodium- and vesicular-dependent mechanisms. Chronic MPH exposure (4 mg/kg/day/animal, voluntary oral intake) for 15 days, followed by a 28-day washout period, increased the firing rate of PFC pyramidal neurons, assessed by in vivo extracellular single-cell electrophysiological recordings, without altering the responses to locally applied NMDA, via micro-iontophoresis. Furthermore, chronic MPH treatment resulted in decreased efficiency of extracellular dopamine to modulate NMDA-induced firing activities of medium spiny neurons in the striatum, together with lower MPH-induced (100 µM) dopamine outflow, suggesting desensitization to both dopamine and MPH in striatal regions. These results indicate that MPH can modulate neurotransmitter efflux in brain regions enriched with dopamine and/or norepinephrine terminals. Further, long-lasting alterations of striatal and prefrontal neurotransmission were observed, even after extensive washout periods. Further studies will be needed to understand the clinical implications of these findings.     

Teamwork in Multiteam Systems.

The authors examined how networks of teams integrate their efforts to succeed collectively. They proposed that integration processes used to align efforts among multiple teams are important predictors of multiteam performance. The authors used a multiteam system (MTS) simulation to assess how both cross-team and within-team processes relate to MTS performance over multiple performance episodes that differed in terms of required interdependence levels. They found that cross-team processes predicted MTS performance beyond that accounted for by within-team processes. Further, cross-team processes were more important for MTS effectiveness when there were high cross-team interdependence demands as compared with situations in which teams could work more independently. Results are discussed in terms of extending theory and applications from teams to multiteam systems. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Genome-Wide Classification and Phylogenetic Analyses of the GDSL-Type Esterase/Lipase (GELP) Family in Flowering Plants

GDSL-type esterase/lipase (GELP) enzymes have key functions in plants, such as developmental processes, anther and pollen development, and responses to biotic and abiotic stresses. Genes that encode GELP belong to a complex and large gene family, ranging from tens to more than hundreds of members per plant species. To facilitate functional transfer between them, we conducted a genome-wide classification of GELP in 46 plant species. First, we applied an iterative phylogenetic method using a selected set of representative angiosperm genomes (three monocots and five dicots) and identified 10 main clusters, subdivided into 44 orthogroups (OGs). An expert curation for gene structures, orthogroup composition, and functional annotation was made based on a literature review. Then, using the HMM profiles as seeds, we expanded the classification to 46 plant species. Our results revealed the variable evolutionary dynamics between OGs in which some expanded, mostly through tandem duplications, while others were maintained as single copies. Among these, dicot-specific clusters and specific amplifications in monocots and wheat were characterized. This approach, by combining manual curation and automatic identification, was effective in characterizing a large gene family, allowing the establishment of a classification framework for gene function transfer and a better understanding of the evolutionary history of GELP.     

Review of the Existing Translational Pharmacokinetics Modeling Approaches Specific to Monoclonal Antibodies (mAbs) to Support the First-In-Human (FIH) Dose Selection

The interest in therapeutic monoclonal antibodies (mAbs) has continuously growing in several diseases. However, their pharmacokinetics (PK) is complex due to their target-mediated drug disposition (TMDD) profiles which can induce a non-linear PK. This point is particularly challenging during the pre-clinical and translational development of a new mAb. This article reviews and describes the existing PK modeling approaches used to translate the mAbs PK from animal to human for intravenous (IV) and subcutaneous (SC) administration routes. Several approaches are presented, from the most empirical models to full physiologically based pharmacokinetic (PBPK) models, with a focus on the population PK methods (compartmental and minimal PBPK models). They include the translational approaches for the linear part of the PK and the TMDD mechanism of mAbs. The objective of this article is to provide an up-to-date overview and future perspectives of the translational PK approaches for mAbs during a model-informed drug development (MIDD), since the field of PK modeling has gained recently significant interest for guiding mAbs drug development.