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ABSTRACT Transmission of Yersinia pestis by fleas depends on the formation of condensed bacterial aggregates embedded within a gel-like matrix that localizes to the proventricular valve in the flea foregut and interferes with normal blood feeding. This is essentially a bacterial biofilm phenomenon, which at its end stage requires the production of a Y. pestis exopolysaccharide that bridges the bacteria together in a cohesive, dense biofilm that completely blocks the proventriculus. However, bacterial aggregates are evident within an hour after a flea ingests Y. pestis, and the bacterial exopolysaccharide is not required for this process. In this study, we characterized the biochemical composition of the initial aggregates and demonstrated that the yersinia murine toxin (Ymt), a Y. pestis phospholipase D, greatly enhances rapid aggregation following infected mouse blood meals. The matrix of the bacterial aggregates is complex, containing large amounts of protein and lipid (particularly cholesterol) derived from the flea’s blood meal. A similar incidence of proventricular aggregation occurred after fleas ingested whole blood or serum containing Y. pestis, and intact, viable bacteria were not required. The initial aggregation of Y. pestis in the flea gut is likely due to a spontaneous physical process termed depletion aggregation that occurs commonly in environments with high concentrations of polymers or other macromolecules and particles such as bacteria. The initial aggregation sets up subsequent binding aggregation mediated by the bacterially produced exopolysaccharide and mature biofilm that results in proventricular blockage and efficient flea-borne transmission.IMPORTANCEYersinia pestis, the bacterial agent of plague, is maintained in nature in mammal-flea-mammal transmission cycles. After a flea feeds on a mammal with septicemic plague, the bacteria rapidly coalesce in the flea’s digestive tract to form dense aggregates enveloped in a viscous matrix that often localizes to the foregut. This represents the initial stage of biofilm development that potentiates transmission of Y. pestis when the flea later bites a new host. The rapid aggregation likely occurs via a depletion-aggregation mechanism, a non-canonical first step of bacterial biofilm development. We found that the biofilm matrix is largely composed of host blood proteins and lipids, particularly cholesterol, and that the enzymatic activity of a Y. pestis phospholipase D (Ymt) enhances the initial aggregation. Y. pestis transmitted by flea bite is likely associated with this host-derived matrix, which may initially shield the bacteria from recognition by the host's intradermal innate immune response.

One of the major functions of the semaphorin signaling system is the regulation of cell shape. In the nematode Caenorhabditis elegans, membrane‐bound semaphorins SMP‐1/2 (SMPs) regulate the morphology of epidermal cells via their receptor plexin, PLX‐1. In the larval male tail of the SMP‐PLX‐1 signaling mutants, the border between two epidermal cells, R1.p and R2.p, is displaced anteriorly, resulting in the anterior displacement of the anterior‐most ray, ray 1, in the adult male. To elucidate how the intercellular signaling mediated by SMPs regulates the position of the intercellular border, we performed mosaic gene expression analyses by using infrared laser‐evoked gene operator (IR‐LEGO). We show that PLX‐1 expressed in R1.p and SMP‐1 expressed in R2.p are required for the proper positioning of ray 1. The result suggests that SMP signaling promotes extension, rather than retraction, of R1.p. This is in contrast to a previous finding that SMPs mediate inhibition of cell extension of vulval precursor cells, another group of epidermal cells of C. elegans, indicating the context dependence of cell shape control via the semaphorin signaling system. [ABSTRACT FROM AUTHOR]

This study investigates populist radical right (PRR) influence on aid amid widespread concerns about a potential connection between its rise and the reduction of aid allocation. Previous studies failed to address these concerns owing to the disuse of immigrant inflows as an intervening variable and a bilateral framework capable of investigating properties in donor and recipient countries. By analyzing panel data on Western European parliamentary democracies, the study demonstrates the PRR's reducing effect via a coalitional pathway on bilateral aid to the recipients, failing to stem emigration into the donor countries. Further, analysis shows that such reduction intensifies in conjunction with the donors' weak pluralistic institutions and the recipients' sociocultural characteristics different from the ordinary citizens represented by the PRR. The findings make a novel contribution to the expanding literature on the PRR to integrate insights on the aid–immigration nexus, strategies for policy influence, and ideational profiles. [ABSTRACT FROM AUTHOR]

In order to simultaneously achieve separation and volume reduction of radioactive cesium in the aqueous solution, we proposed a solvent extraction using a fluorinated solvent which is a nonflammable liquid having a low boiling point and is easy to distill for regeneration. Firstly optimum conditions for single extraction were determined in a batch operation. The extraction experiment was carried out by changing the pH of 5 mg/L non-radioactive cesium aqueous solution using bis(2-ethylhexyl)phosphoric acid (D2EHPA) as an extractant. The higher the pH of the aqueous phase and the D2EHPA concentration, the better the removal rate. The highest removal rate was about 60% under the pH=13. From the experimental results, the optimum extraction condition was determined as pH=13 and [D2EHPA]=0.15 mol/L. Next multiple extraction test was carried out under this condition, and 90% cesium removal could be achieved in 3 times extraction. Finally, the flow type device using a static mixer for mixing and extracting parts was proposed and then the cesium removal test was performed. The cesium removal performance of this device was equivalent to the batch system.

Sphingolipids make up a family of molecules associated with an array of biological functions, including cell death and migration. Sphingolipids are often altered in cancer, though how these alterations lead to tumor formation and progression is largely unknown. Here, we analyzed non-small-cell lung cancer (NSCLC) specimens and cell lines and determined that ceramide synthase 6 (CERS6) is markedly overexpressed compared with controls. Elevated CERS6 expression was due in part to reduction of microRNA-101 (miR-101) and was associated with increased invasion and poor prognosis. CERS6 knockdown in NSCLC cells altered the ceramide profile, resulting in decreased cell migration and invasion in vitro, and decreased the frequency of RAC1-positive lamellipodia formation while CERS6 overexpression promoted it. In murine models, CERS6 knockdown in transplanted NSCLC cells attenuated lung metastasis. Furthermore, combined treatment with L-α-dimyristoylphosphatidylcholine liposome and the glucosylceramide synthase inhibitor D-PDMP induced cell death in association with ceramide accumulation and promoted cancer cell apoptosis and tumor regression in murine models. Together, these results indicate that CERS6-dependent ceramide synthesis and maintenance of ceramide in the cellular membrane are essential for lamellipodia formation and metastasis. Moreover, these results suggest that targeting this homeostasis has potential as a therapeutic strategy for CERS6- overexpressing NSCLC., Introduction Recent evidence has shown altered levels of biologically active sphingolipids and enzymes related to sphingolipid metabolism in cancer, indicating roles for these pathways in cancer pathogenesis and progression (1). [...]