The nanos translational control element represses translation in somatic cells by a Bearded box-like motif

Developmental control of translation is frequently mediated by regulatory elements that reside within 3' untranslated regions (3' UTRs). Two stem-loops within the nanos 3' UTR translational control element (TCE) act independently to direct translational repression of maternal nanos mRNA in the ovary or embryo. We have previously shown that the nanos TCE can also function in select somatic sites. Using an ectopic expression screen, we now identify a new site of TCE function, the dorsal pouch epithelium. Analysis of TCE mutants reveals that TCE activity in the dorsal pouch does not depend on either of the stem-loops required for maternal TCE function, but instead requires a third feature-a sequence that closely matches the Bearded box, a regulatory motif found in the 3' UTRs of several Notch pathway genes. In addition, we identify pleiohomeotic mRNA as an endogenous candidate for regulation by Bearded box-like motifs in the dorsal pouch. Together, these results suggest that the TCE has appropriated a conserved regulatory motif to expand its function to somatic tissues.     

Phenoloxidase Activity Acts as a Mosquito Innate Immune Response against Infection with Semliki Forest Virus

Several components of the mosquito immune system including the RNA interference (RNAi), JAK/STAT, Toll and IMD pathways have previously been implicated in controlling arbovirus infections. In contrast, the role of the phenoloxidase (PO) cascade in mosquito antiviral immunity is unknown. Here we show that conditioned medium from the Aedes albopictus-derived U4.4 cell line contains a functional PO cascade, which is activated by the bacterium Escherichia coli and the arbovirus Semliki Forest virus (SFV) (Togaviridae; Alphavirus). Production of recombinant SFV expressing the PO cascade inhibitor Egf1.0 blocked PO activity in U4.4 cell- conditioned medium, which resulted in enhanced spread of SFV. Infection of adult female Aedes aegypti by feeding mosquitoes a bloodmeal containing Egf1.0-expressing SFV increased virus replication and mosquito mortality. Collectively, these results suggest the PO cascade of mosquitoes plays an important role in immune defence against arboviruses.     

不同气候适应类型果蝇体色黑化可塑性的适应性变化(英文)

变温昆虫果蝇Drosophila深受热选择（即遗传效应）或表型诱导效应（即可塑性）的影响。表型可塑性是不同生物进行适应的有效方法, 但是它在不同的果蝇种中较少受到关注。 我们分析了不同发育温度范围和地理分布的果蝇的黑化反应模式。嗜凤梨果蝇D. ananassae 和蒲桃果蝇D. jambulina 对低温敏感, 这些物种可在18~32℃下饲育。相反, D. nepalensis 为耐冷且对热敏感的物种, 可在12~25℃下饲育。世界广为分布的黑腹果蝇D. melanogaster的温度范围宽（13~31℃）, 该物种前3个腹节和后3个腹节的黑化反应模式未见明显差异。D. nepalensis的全部6个腹节（第2~7节）均具有高度的可塑性。不过, 黑腹果蝇D. melanogaster只有后3个腹节具有可塑性。相反, 热带物种嗜凤梨果蝇D. ananassae 的所有腹节均不具有可塑性。世界广为分布的黑腹果蝇, 即使来自冷得多的气候环境, 其体色也不加深, 与D. nepalensis中观察到的体色接近。本研究的目的旨在认识引起体色的形态多样性的过程以及果蝇对不同地理区域的适应性。最后, 将体色黑化与物种系统发育谱系的比较表明, 在不同的演化谱系中不断发生遗传多态性或表型可塑性两种不同模式的适应。     

A genome-wide screen identifies a Bordetella type III secretion effector and candidate effectors in other species

Bordetella bronchiseptica utilizes a type III secretion system (TTSS) for induction of non-apoptotic cytotoxicity in host cells and modulation of host immunity. The identity of Bordetella TTSS effectors, however, has remained elusive. Here we report a genome-wide screen for TTSS effectors based on shared biophysical and functional characteristics of class I chaperones and their frequent colocalization with TTSS effectors. When applied to B. bronchiseptica, the screen identified the first TTSS chaperone-effector locus, btcA-bteA, and we experimentally confirmed its function. Expression of bteA is co-ordinated with expression of TTSS apparatus genes, BteA is secreted through the TTSS of B. bronchiseptica, it is required for cytotoxicity towards mammalian cells, and it is highly conserved in the human-adapted subspecies B. pertussis and B. parapertussis. Transfection of bteA into epithlieal cells results in rapid cell death, indicating that BteA alone is sufficient to induce potent cytotoxicity. Finally, an in vitro interaction between BteA and BtcA was demonstrated. The search for TTSS chaperones and effectors was then expanded to other bacterial genomes, including mammalian and insect pathogens, where we identified a large number of novel candidate chaperones and effectors. Although the majority of putative effectors are proteins of unknown function, several have similarities to eukaryotic protein domains or previously identified effectors from other species.     

Regulation of cell structure and function by actin-binding proteins: villin's perspective

Villin is a tissue-specific actin modifying protein that is associated with actin filaments in the microvilli and terminal web of epithelial cells. It belongs to a large family of actin-binding proteins which includes actin-capping, -nucleating and/or -severing proteins such as gelsolin, severin, fragmin, adseverin/scinderin and actin crosslinking proteins such as dematin and supervillin. Studies done in epithelial cell lines and villin knock-out mice have demonstrated the function of villin in regulating actin dynamics, cell morphology, epithelial-to-mesenchymal transition, cell migration and cell survival. In addition, the ligand-binding properties of villin (F-actin, G-actin, calcium, phospholipids and phospholipase C-gamma1) are mechanistically important for the crosstalk between signaling pathways and actin reorganization in epithelial cells.     

A weed with multiple utility: Lantana camara

L. camara is a terrible weed, exerting huge detrimental effect on biodiversity. Its leaves and flowers contain toxins, lantadene A and B, so unfit for herbivory by ruminants. This weed stunts the growth of neighbouring plants owing to the allelopathic effect of its root leachate. The seeds tide over adverse period and germinate when favourable conditions prevail. Further, pruning makes the thicket denser. Almost all removal strategies of this weed have been unsuccessful so far. So, management of this weed by utilization is required. Recent studies have reported that L. camara improves soil quality by enriching it with nitrogen, exhibits termiticidal effect, acts as lignocellulosic substrate for cultivation of edible mushrooms, acts as potential insecticide and fumigant for grains storage against weevils, antifungal agent, herbicide against water hyacinths. L. camara has bioactive ingredients exhibiting anticancer, antiulcerogenic, hypolipidemic, larvicidal and anti-inflammatory activity. L. camara fibre has been reported to be suitable candidate as reinforcement in biomaterials. Also, this plant extract is effective in bovine dermatophilosis therapy. L. camara has also immense industrial importance, as a source of oleanolic acid and carboxymethylcellulose. L. camara biomass can be implicated as a substrate for bioethanol and biogas production. This invasive weed can also serve as livelihood options, as the woody twigs can be utilized for aesthetic and durable furniture making apart from the use as firewood. The latest published papers on the novel uses of L. camara have been reviewed, with the objective of providing a thrust to weed management by utilization.     

Low reduction potential of Ero1alpha regulatory disulphides ensures tight control of substrate oxidation

Formation of disulphide bonds within the mammalian endoplasmic reticulum (ER) requires the combined activities of Ero1α and protein disulphide isomerase (PDI). As Ero1α produces hydrogen peroxide during oxidation, regulation of its activity is critical in preventing ER-generated oxidative stress. Here, we have expressed and purified recombinant human Ero1α and shown that it has activity towards thioredoxin and PDI. The activity towards PDI required the inclusion of glutathione to ensure sustained oxidation. By carrying out site-directed mutagenesis of cysteine residues, we show that Ero1α is regulated by non-catalytic disulphides. The midpoint reduction potential (E°′) of the regulatory disulphides was calculated to be approximately −275 mV making them stable in the redox conditions prevalent in the ER. The stable regulatory disulphides were only partially reduced by PDI (E°′~−180 mV), suggesting either that this is a mechanism for preventing excessive Ero1α activity and oxidation of PDI or that additional factors are required for Ero1α activation within the mammalian ER.     

Discovery of orally bioavailable imidazo[1,2-a]pyrazine-based Aurora kinase inhibitors

We report a series of potent imidazo[1,2-a]pyrazine-based Aurora kinase inhibitors. Optimization of the solvent accessible 8-position led to improvements in both oral bioavailability and off-target kinase inhibition. Compound 25 demonstrates anti-tumor activity in an A2780 ovarian tumor xenograft model.     

Monitoring and Analyzing Process Streams Towards Understanding Ionic Liquid Pretreatment of Switchgrass (Panicum virgatum L.)

Fundamental understanding of biomass pretreatment and its influence on saccharification kinetics, total sugar yield, and inhibitor formation is essential to develop efficient next-generation biofuel strategies, capable of displacing fossil fuels at a commercial level. In this study, we investigated the effect of residence time and temperature during ionic liquid (IL) pretreatment of switchgrass using 1-ethyl-3-methyl imidazolium acetate. The primary metrics of pretreatment performance are biomass delignification, xylan and glucan depolymerization, porosity, surface area, cellulase kinetics, and sugar yields. Compositional analysis and quantification of process streams of saccharides and lignin demonstrate that delignification increases as a function of pretreatment temperature and is hypothesized to be correlated with the apparent glass transition temperature of lignin. IL pretreatment did not generate monosaccharides from hemicellulose. Compared to untreated switchgrass, Brunauer–Emmett–Teller surface area of pretreated switchgrass increased by a factor of ～30, with a corresponding increase in saccharification kinetics of a factor of ～40. There is an observed dependence of cellulase kinetics with delignification efficiency. Although complete biomass dissolution is observed after 3 h of IL pretreatment, the pattern of sugar release, saccharification kinetics, and total sugar yields are strongly correlated with temperature.