Expression,characterization and inhibition of Toxoplasma gondii 1-deoxy-d-xylulose-5-phosphate reductoisomerase

The apicomplexan parasite Toxoplasma gondii, the causative agent of toxoplasmosis, is an important human pathogen. 1-Deoxy-d-xylulose-5-phosphate reductoisomerase (DXR) in the non-mevalonate isoprene biosynthesis pathway is essential to the organism and therefore a target for developing anti-toxoplasmosis drugs. In order to find potent inhibitors, we expressed and purified recombinant T. gondii DXR (TgDXR). Biochemical properties of this enzyme were characterized and an enzyme activity/inhibition assay was developed. A collection of 11 compounds with a broad structural diversity were tested against TgDXR and several potent inhibitors were identified with K_i values as low as 48 nM. Analysis of the results as well as those of Escherichia coli and Plasmodium falciparum DXR enzymes revealed a different structure–activity relationship profile for the inhibition of TgDXR.     

Identifying pathogenicity genes in the rubber tree anthracnose fungus Colletotrichum gloeosporioides through random insertional mutagenesis

To gain more insight into the molecular mechanisms of Colletotrichum gloeosporioides pathogenesis, Agrobacterium tumefaciens-mediated transformation (ATMT) was used to identify mutants of C. gloeosporioides impaired in pathogenicity. An ATMT library of 4128 C. gloeosporioides transformants was generated. Transformants were screened for defects in pathogenicity with a detached copper brown leaf assay. 32 mutants showing reproducible pathogenicity defects were obtained. Southern blot analysis showed 60.4% of the transformants had single-site T-DNA integrations. 16 Genomic sequences flanking T-DNA were recovered from mutants by thermal asymmetric interlaced PCR, and were used to isolate the tagged genes from the genome sequence of wild-type C. gloeosporioides by Basic Local Alignment Search Tool searches against the local genome database of the wild-type C. gloeosporioides. One potential pathogenicity genes encoded calcium-translocating P-type ATPase. Six potential pathogenicity genes had no known homologs in filamentous fungi and were likely to be novel fungal virulence factors. Two putative genes encoded Glycosyltransferase family 28 domain-containing protein and Mov34/MPN/PAD-1 family protein, respectively. Five potential pathogenicity genes had putative function matched with putative protein of other Colletotrichum species. Two known C. gloeosporioides pathogenicity genes were also identified, the encoding Glomerella cingulata hard-surface induced protein and C. gloeosporioides regulatory subunit of protein kinase A gene involved in cAMP-dependent PKA signal transduction pathway.     

EMMPRIN Is an Independent Negative Prognostic Factor for Patients with Astrocytic Glioma

Extracellular matrix metalloproteinase inducer (EMMPRIN), also known as CD147, is a member of the immunoglobulin superfamily that is present on the surface of tumor cells and stimulates adjacent fibroblasts to produce matrix metalloproteinases (MMPs). It has been proved to be associated with tumor invasion and metastasis in various human malignancies. In our study, the protein expression level of EMMPRIN in 306 cases of astrocytic glioma is investigated by immunohistochemistry assay. Statistical analysis was utilized to evaluate the association of EMMPRIN with clinicopathological characteristics and prognosis of patients. It was proved that EMMPRIN protein expression was increased in glioma compared with that in normal brain tissue. Moreover, EMMPRIN immunohistochemical staining was correlated with WHO grade and Karnofsky performance score for strong positive EMMPRIN staining is more frequently detected in glioma of advanced grade or low KPS score. It is also demonstrated that EMMPRIN could be an independent negative prognostic factor in glioma for patients with glioma of strong EMMPRIN staining tend to have high risk of death. These results proved that EMMPRIN is associated with prognosis of glioma, which may also suggest the potential role of EMMPRIN in glioma management.     

Subradiant,Superradiant Plasmon Modes and Fano Resonance in a Multilayer Nanocylinder Array Standing on a Thin Metal Film

The optical properties of a novel nanostructure consisting of a hexagonal array of aligned vertically three-layered metal-dielectric-metal nanodisks on a silver film are theoretically studied through the finite-difference time-domain method. The novel nanostructure exhibits three obvious optical transmission bands due to the excitation of subradiant plasmon modes, superradiant plasmon modes, and Fano resonances. Surface plasmon polaritons of the underlying Ag film also play a significant role on these three optical transmission bands via coupling with localized surface plasmons of nanodisk pairs. Moreover, the nanostructure also exhibits a good tunability of optical response by modifying the sizes of cylinders, the thickness of underlying metal film, and the dielectric constant of middle layer. These results demonstrate the nanostructure with great advantages in optical sensors and filters.

     

Myosins FaMyo2B and Famyo2 Affect Asexual and Sexual Development,Reduces Pathogenicity,and FaMyo2B Acts Jointly with the Myosin Passenger Protein FaSmy1 to Affect Resistance to Phenamacril in Fusarium asiaticum

We previously reported that mutations occurred in the gene myosin5 were responsible for resistance to the fungicide phenamacril in Fusarium graminearum. Here, we determined whether there is a functional link between phenamacril resistance and the myosin proteins FaMyo2B and Famyo2 in Fusarium asiaticum, which is the major causal agent of Fusarium head blight in China. We found that FaMyo2B acts jointly with FaSmy1 to affect resistance to phenamacril in F. asiaticum. We also found that FaMyo2B disruption mutant and Famyo2 deletion mutant were defective in hyphal branching, conidiation, and sexual reproduction. ΔFamyo2 also had an enhanced sensitivity to cell wall damaging agents and an abnormal distribution of septa and nuclei. In addition, the FaMyo2B and Famyo2 mutants had reduced pathogenicity on wheat coleoptiles and flowering wheat heads. Taken together, these results reveal that FaMyo2B and Famyo2 are required for several F. asiaticum developmental processes and activities, which help us better understand the resistance mechanism and find the most effective approach to control FHB.     

Increased Risk of Post-Thrombolysis Intracranial Hemorrhage in Acute Ischemic Stroke Patients with Leukoaraiosis: A Meta-Analysis

BackgroundLeukoaraiosis is common in patients with acute ischemic stroke. The results from many studies investigating the association between leukoaraiosis and intracranial hemorrhage after thrombolysis remain conflicting.MethodsA meta-analysis was performed to compare the risk of post-thrombolytic intracranial hemorrhage in patients with and without leukoaraiosis. Relevant reports were identified by searching PubMed, EmBase, Cochrane Library, and ISI Web of Science through December 2015 using a combination of subjective and random terms. Eligible studies that were original articles with a clear definition of leukoaraiosis and intracranial hemorrhage were selected and analyzed. Funnel plots, Egger’s test, and Begg’s test were conducted to assess the publication bias. Sensitivity analysis was also performed to evaluate the influence of each individual study.ResultsEleven trials that enrolled 6912 participants were included. There was a significantly increased risk for acute ischemic stroke patients with leukoaraiosis (odds ratio: 1.89, 95% confidence interval 1.51–2.37, P<0.001). Low heterogeneity and less publication bias was detected among these studies. The results of both computed tomography and magnetic resonance imaging performed on the subgroups of leukoaraiosis were significant. Furthermore, an association between leukoaraiosis and symptomatic intracranial hemorrhage was also confirmed. The odds ratios remained stable with no obvious variations on the sensitivity analysis. The limitations consisted of types of including trials and not matching some baseline variables.ConclusionsThe results of this meta-analysis show that leukoaraiosis approximately doubles the incidence of intracranial hemorrhage after thrombolytic therapy. However, it does not critically affect decision making regarding thrombolysis for patients with acute ischemic stroke. Additional investigations are required.