Discovery of an ebolavirus-like filovirus in europe

Filoviruses, amongst the most lethal of primate pathogens, have only been reported as natural infections in sub-Saharan Africa and the Philippines. Infections of bats with the ebolaviruses and marburgviruses do not appear to be associated with disease. Here we report identification in dead insectivorous bats of a genetically distinct filovirus, provisionally named Lloviu virus, after the site of detection, Cueva del Lloviu, in Spain.     

The xipotl mutant of Arabidopsis reveals a critical role for phospholipid metabolism in root system development and epidermal cell integrity

Phosphocholine (PCho) is an essential metabolite for plant development because it is the precursor for the biosynthesis of phosphatidylcholine, which is the major lipid component in plant cell membranes. The main step in PCho biosynthesis in Arabidopsis thaliana is the triple, sequential N-methylation of phosphoethanolamine, catalyzed by S-adenosyl-l-methionine:phosphoethanolamine N-methyltransferase (PEAMT). In screenings performed to isolate Arabidopsis mutants with altered root system architecture, a T-DNA mutagenized line showing remarkable alterations in root development was isolated. At the seedling stage, the mutant phenotype is characterized by a short primary root, a high number of lateral roots, and short epidermal cells with aberrant morphology. Genetic and biochemical characterization of this mutant showed that the T-DNA was inserted at the At3g18000 locus (XIPOTL1), which encodes PEAMT (XIPOTL1). Further analyses revealed that inhibition of PCho biosynthesis in xpl1 mutants not only alters several root developmental traits but also induces cell death in root epidermal cells. Epidermal cell death could be reversed by phosphatidic acid treatment. Taken together, our results suggest that molecules produced downstream of the PCho biosynthesis pathway play key roles in root development and act as signals for cell integrity.     

Functional groups and quaternary structure of chicken liver xanthine dehydrogenase

Xanthine dehydrogenase from chicken liver is a dimeric enzyme, each hemimolecule containing one FAD and two Fe/S groups. Determination of sulfhydryl groups with 5,5-dithiobis(2-nitrobenzoic acid) (DTNB) andp-hydroxymercuribenzoic acid (PMB) showed a variable number of sulfhydryl groups depending onpH, ionic strength, and nature of the reaction medium and buffer. The number of disulfide bonds was determined with DTNB and reducing conditions. Amino groups were determined with 2,4,6,-trinitrobencensulfonic acid (TNBS). At constant temperature andpH the reaction of DTNB and TNBS with native xanthine dehydrogenase showed an exponential dependence on time. From the obtained parameters the number of available sulfhydryl and amino groups at infinite concentration of enzyme and the rate constant of the equation were determined. The absorption spectrum of the enzyme changed with time when a chaotropic agent (1 M sodium nitrate) was added to the medium. This difference was detected by measuring the absorbance in the range 450–550 nm. The absorption spectrum (between 350 and 600 nm) also changed when a denaturating agent (sodium dodecyl sulfate) was added. This modification increased with time and depended on the medium.     

Eastward Ho: phylogeographical perspectives on colonization of hosts and parasites across the Beringian nexus

The response of Arctic organisms and their parasites to dramatic fluctuations in climate during the Pleistocene has direct implications for predicting the impact of current climate change in the North. An increasing number of phylogeographical studies in the Arctic have laid a framework for testing hypotheses concerning the impact of shifting environmental conditions on transcontinental movement. We review 35 phylogeographical studies of trans-Beringian terrestrial and freshwater taxa, both hosts and parasites, to identify generalized patterns regarding the number, direction and timing of trans-continental colonizations. We found that colonization across Beringia was primarily from Asia to North America, with many events occurring in the Quaternary period. The 35 molecular studies of trans-Beringian organisms we examined focused primarily on the role of glacial cycles and refugia in promoting diversification. We address the value of establishing testable hypotheses related to high-latitude biogeography. We then discuss future prospects in Beringia related to coalescent theory, palaeoecology, ancient DNA and synthetic studies of arctic host–parasite assemblages highlighting their cryptic diversity, biogeography and response to climate variation.     

Dissection of the insulin-sensitizing effect of liver X receptor ligands

The liver X receptors (LXRalpha and beta) are nuclear receptors that coordinate carbohydrate and lipid metabolism. Treatment of insulin-resistant mice with synthetic LXR ligands enhances glucose tolerance, inducing changes in gene expression expected to decrease hepatic gluconeogenesis (via indirect suppression of gluconeogenic enzymes) and increase peripheral glucose disposal (via direct up-regulation of glut4 in fat). To evaluate the relative contribution of each of these effects on whole-body insulin sensitivity, we performed hyperinsulinemic-euglycemic clamps in high-fat-fed insulin-resistant rats treated with an LXR agonist or a peroxisome proliferator-activated receptor gamma ligand. Both groups showed significant improvement in insulin action. Interestingly, rats treated with LXR ligand had lower body weight and smaller fat cells than controls. Insulin-stimulated suppression of the rate of glucose appearance (Ra) was pronounced in LXR-treated rats, but treatment failed to enhance peripheral glucose uptake (R'g), despite increased expression of glut4 in epididymal fat. To ascertain whether LXR ligands suppress hepatic gluconeogenesis directly, mice lacking LXRalpha (the primary isotype in liver) were treated with LXR ligand, and gluconeogenic gene expression was assessed. LXR activation decreased expression of gluconeogenic genes in wild-type and LXRbeta null mice, but failed to do so in animals lacking LXRalpha. Our observations indicate that despite inducing suggestive gene expression changes in adipose tissue in this model of diet-induced insulin resistance, the antidiabetic effect of LXR ligands is primarily due to effects in the liver that appear to require LXRalpha. These findings have important implications for clinical development of LXR agonists as insulin sensitizers.     

Immunogenicity of recombinant human interleukin-2: Biological features and clinical relevance

The immunogenicity of recombinant interleukin-2 (rIL-2, EuroCetus, Amsterdam, Netherlands) was studied in seventy-six patients receiving different subcutaneous immunotherapy regimens. Patients presented with progressive metastatic renal cell carcinoma, malignant melanoma, colorectal cancer, B-cell lymphoma, and Hodgkin's disease. An enzyme immunoassay (EIA) was employed to screen patients for development of non-neutralizing antibodies against rIL-2, antibody specificity was confirmed by a standard Western blot. Neutralizing serum activity against rIL-2 was detected using a standard CTLL mouse proliferation assay. Additionally, serum levels of soluble interleukin-2 receptors and lymphocyte subsets expressing the CD56 natural killer (NK) associated antigen were measured.In a proportion of approximately 35% to 90% of the patients treated, non-neutralizing antibodies against rIL-2 could be detected after all treatment courses were evaluated. Antibodies were of the IgG, IgM, IgA and IgD subtypes. None of the 76 patients exhibited serum neutralizing activity after one treatment course. Five patients exhibited neutralizing anti-rIL-2 serum activity after two or more treatment courses of systemic rIL-2. In three of these patients, antibodies neutralized both recombinant and natural IL-2. Patients developing neutralizing anti-rIL-2 antibodies, exhibited significantly lower serum sIL-2 receptor levels upon the emergence of serum neutralizing activity than patients without antibody. Additionally, NK cell associated CD56 positivity was significantly lower in patients who exhibited neutralizing anti-rIL-2 serum activity than in patients who did not. A significant decrease in levels of soluble IL-2 receptors and CD56 NK cell positivity was observed, when comparing values prior to and after onset of serum neutralizing activity against rIL-2. However, while emergence of neutralizing antibodies to rIL-2 diminished rIL-2 induced biological activation, it did not coincide with abrogation of treatment response.Abbreviations rIL-2 recombinant interleukin-2 - EIA enzyme immuno assay - rIFN-2 recombinant interferon- 2     

In vitro antimicrobial effect of metallic nanoparticles on phytopathogenic strains of crop plants

In this research, the in vitro antimicrobial effect of zinc oxide (ZnO), copper oxide (CuO) and iron oxide (Fe₂O₃) nanoparticles (NPs)—with average sizes of 20, 46 and 30 nm, respectively—on the root rot disease caused by the fungus Fusarium oxysporum and on blight disease caused by the fungus Alternaria solani were studied. Also, bacterial diseases caused by Clavibacter michiganensis and Pseudomonas syringae that infects a wide range of plant species were assessed. Different concentrations of NPs (0, 100, 250, 500, 700 and 1,000 mg/L) were prepared on PDA agar or King's B medium in a complete randomized design with four replicates. According to the results, ZnO NPs exhibited an outstanding inhibitory effect against fungi and bacteria strains. The above results were associated with the smaller particle size. Fungi strains showed a differential sensitivity depending on the kind of NPs used. A. solani showed the highest sensitivity to ZnO NPs at 1,000 mg/L (99%), followed by CuO NPs at the same dose (95%). Fe₂O₃ NPs at all evaluated doses had no inhibitory effects on the mycelia growth of this strain, although F. oxysporum revealed greater effectiveness of the CuO NPs (96%) compared with ZnO NPs since it only inhibited 91% of the mycelial growth. The antibacterial activity was studied through optical density. C. michiganensis was found to be more sensitive to ZnO NPs because a lesser dose (700 mg/L) was required to reduce the bacterial growth (90%); in comparison, P. syringae required a dose of 1,000 mg/L to inhibit its growth (67%). CuO NPs displayed the smallest growth inhibition against the bacteria strains analysed. The antimicrobial effect of the metallic NPs that were assayed increased with higher doses.     

Genetic diversity and geographic distribution of Bemisia tabaci and Trialeurodes vaporariorum in Costa Rica

The tobacco whitefly Bemisia tabaci (Gennadius) cryptic species complex and of the greenhouse whitefly Trialeurodes vaporariorum (Westwood) are extensively reported as destructive pests in vegetable crops worldwide. A survey was conducted in 2011 and 2012 to determine the occurrence and genetic diversity present in the populations of these whiteflies in the major vegetable production areas of Costa Rica. Insect samples were collected from sweet pepper (Capsicum annuum L.), tomato (Solanum lycopersicum L.), common bean (Phaseolus vulgaris L.) and weeds present in commercial crops either in open field or greenhouse conditions. PCR‐RFLP analysis of mitochondrial cytochrome c oxidase subunit 1 gene (mtCOI) sequences of 621 whitefly individuals confirmed the presence of the Mediterranean (MED) type of the B. tabaci and of T. vaporariorum in most sampled regions. Also, individuals of the Middle East‐Asia Minor 1 (MEAM1) type of the B. tabaci were observed in low numbers. Contingency analyses based on type of crop, geographical region, whitefly species, year of collection and production system confirmed that T. vaporariorum was the most frequent species in vegetable production areas in Costa Rica, both in greenhouses and in open fields. B. tabaci MED is likely spreading to new areas of the country, whereas B. tabaci MEAM1 was mostly absent or rarely found. Comparisons of mtCOI sequences from B. tabaci individuals revealed the presence of four B. tabaci sequence haplotypes (named MED‐i, MED‐ii, MEAM1‐i, MEAM1‐xviii) in Costa Rica, three of them identical to B. tabaci haplotypes previously reported in the Western Hemisphere and other parts of the world. Analysis of sequences of T. vaporariorum individuals revealed a more complex population with the presence of 11 haplotypes, two of which were identical to T. vaporariorum sequences reported from other countries.     

The UBC-40 Urothelial Bladder Cancer cell line index: a genomic resource for functional studies

Background

Urothelial bladder cancer is a highly heterogeneous disease. Cancer cell lines are useful tools for its study. This is a comprehensive genomic characterization of 40 urothelial bladder carcinoma (UBC) cell lines including information on origin, mutation status of genes implicated in bladder cancer (FGFR3, PIK3CA, TP53, and RAS), copy number alterations assessed using high density SNP arrays, uniparental disomy (UPD) events, and gene expression.

Results

Based on gene mutation patterns and genomic changes we identify lines representative of the FGFR3-driven tumor pathway and of the TP53/RB tumor suppressor-driven pathway. High-density array copy number analysis identified significant focal gains (1q32, 5p13.1-12, 7q11, and 7q33) and losses (i.e. 6p22.1) in regions altered in tumors but not previously described as affected in bladder cell lines. We also identify new evidence for frequent regions of UPD, often coinciding with regions reported to be lost in tumors. Previously undescribed chromosome X losses found in UBC lines also point to potential tumor suppressor genes. Cell lines representative of the FGFR3-driven pathway showed a lower number of UPD events.

Conclusions

Overall, there is a predominance of more aggressive tumor subtypes among the cell lines. We provide a cell line classification that establishes their relatedness to the major molecularly-defined bladder tumor subtypes. The compiled information should serve as a useful reference to the bladder cancer research community and should help to select cell lines appropriate for the functional analysis of bladder cancer genes, for example those being identified through massive parallel sequencing.

Electronic supplementary material

The online version of this article (doi:10.1186/s12864-015-1450-3) contains supplementary material, which is available to authorized users.