Circulation of Different Lineages of Dengue Virus Type 2 in Central America, Their Evolutionary Time-Scale and Selection Pressure Analysis

Dengue is caused by any of the four serotypes of dengue virus (DENV-1 to 4). Each serotype is genetically distant from the others, and each has been subdivided into different genotypes based on phylogenetic analysis. The study of dengue evolution in endemic regions is important since the diagnosis is often made by nucleic acid amplification tests, which depends upon recognition of the viral genome target, and natural occurring mutations can affect the performance of these assays. Here we report for the first time a detailed study of the phylogenetic relationships of DENV-2 from Central America, and report the first fully sequenced DENV-2 strain from Guatemala. Our analysis of the envelope (E) protein and of the open reading frame of strains from Central American countries, between 1999 and 2009, revealed that at least two lineages of the American/Asian genotype of DENV-2 have recently circulated in that region. In occasions the co-circulation of these lineages may have occurred and that has been suggested to play a role in the observed increased severity of clinical cases. Our time-scale analysis indicated that the most recent common ancestor for Central American DENV-2 of the American/Asian genotype existed about 19 years ago. Finally, we report positive selection in DENV-2 from Central America in codons of the genes encoding for C, E, NS2A, NS3, and NS5 proteins. Some of these identified codons are novel findings, described for the first time for any of the DENV-2 genotypes

Human Protein Phosphatase PP6 Regulatory Subunits Provide Sit4-Dependent and Rapamycin–Sensitive Sap Function in Saccharomyces cerevisiae

In the budding yeast Saccharomyces cerevisiae the protein phosphatase Sit4 and four associated proteins (Sap4, Sap155, Sap185, and Sap190) mediate G1 to S cell cycle progression and a number of signaling events controlled by the target of rapamycin TOR signaling cascade. Sit4 and the Sap proteins are ubiquitously conserved and their human orthologs, PP6 and three PP6R proteins, share significant sequence identity with their yeast counterparts. However, relatively little is known about the functions of the PP6 and PP6R proteins in mammalian cells. Here we demonstrate that the human PP6R proteins physically interact with Sit4 when expressed in yeast cells. Remarkably, expression of PP6R2 and PP6R3 but not expression of PP6R1 rescues the growth defect and rapamycin hypersensitivity of yeast cells lacking all four Saps, and these effects require Sit4. Moreover, PP6R2 and PP6R3 enhance cyclin G1 gene expression and DNA synthesis, and partially abrogate the G1 cell cycle delay and the budding defect of the yeast quadruple sap mutant strain. In contrast, the human PP6R proteins only modestly support nitrogen catabolite gene expression and are unable to restore normal levels of eIF2α phosphorylation in the quadruple sap mutant strain. These results illustrate that the human PP6-associated proteins are capable of providing distinct rapamycin-sensitive and Sit4-dependent Sap functions in the heterologous context of the yeast cell. We hypothesize that the human Saps may play analogous roles in mTORC1-PP6 signaling events in metazoans

Necessary conditions for classical super-integrability of a certain family of potentials in constant curvature spaces

We formulate the necessary conditions for the maximal super-integrability of a certain family of classical potentials defined in the constant curvature two-dimensional spaces. We give examples of homogeneous potentials of degree -2 on $E^2$ as well as their equivalents on $S^2$ and $H^2$ for which these necessary conditions are also sufficient. We show explicit forms of the additional first integrals which always can be chosen polynomial with respect to the momenta and which can be of an arbitrary high degree with respect to the momenta

The Sinbad retrotransposon from the genome of the human blood fluke, Schistosoma mansoni, and the distribution of related Pao-like elements

BACKGROUND: Of the major families of long terminal repeat (LTR) retrotransposons, the Pao/BEL family is probably the least well studied. It is becoming apparent that numerous LTR retrotransposons and other mobile genetic elements have colonized the genome of the human blood fluke, Schistosoma mansoni. RESULTS: A proviral form of Sinbad, a new LTR retrotransposon, was identified in the genome of S. mansoni. Phylogenetic analysis indicated that Sinbad belongs to one of five discreet subfamilies of Pao/BEL like elements. BLAST searches of whole genomes and EST databases indicated that members of this clade occurred in species of the Insecta, Nematoda, Echinodermata and Chordata, as well as Platyhelminthes, but were absent from all plants, fungi and lower eukaryotes examined. Among the deuterostomes examined, only aquatic species harbored these types of elements. All four species of nematode examined were positive for Sinbad sequences, although among insect and vertebrate genomes, some were positive and some negative. The full length, consensus Sinbad retrotransposon was 6,287 bp long and was flanked at its 5'- and 3'-ends by identical LTRs of 386 bp. Sinbad displayed a triple Cys-His RNA binding motif characteristic of Gag of Pao/BEL-like elements, followed by the enzymatic domains of protease, reverse transcriptase (RT), RNAseH, and integrase, in that order. A phylogenetic tree of deduced RT sequences from 26 elements revealed that Sinbad was most closely related to an unnamed element from the zebrafish Danio rerio and to Saci-1, also from S. mansoni. It was also closely related to Pao from Bombyx mori and to Ninja of Drosophila simulans. Sinbad was only distantly related to the other schistosome LTR retrotransposons Boudicca, Gulliver, Saci-2, Saci-3, and Fugitive, which are gypsy-like. Southern hybridization and bioinformatics analyses indicated that there were about 50 copies of Sinbad in the S. mansoni genome. The presence of ESTs representing transcripts of Sinbad in numerous developmental stages of S. mansoni along with the identical 5'- and 3'-LTR sequences suggests that Sinbad is an active retrotransposon. CONCLUSION: Sinbad is a Pao/BEL type retrotransposon from the genome of S. mansoni. The Pao/BEL group appears to be comprised of at least five discrete subfamilies, which tend to cluster with host species phylogeny. Pao/BEL type elements appear to have colonized only the genomes of the Animalia. The distribution of these elements in the Ecdysozoa, Deuterostomia, and Lophotrochozoa is discontinuous, suggesting horizontal transmission and/or efficient elimination of Pao-like mobile genetic elements from some genomes

Analytical methodologies based on LC–MS/MS for monitoring selected emerging compounds in liquid and solid phases of the sewage sludge

In this work, two analytical methodologies based on liquid chromatography coupled to tandem mass spectrometry (LC–MS/MS) were developed for quantification of emerging pollutants identified in sewage sludge after a previous wide-scope screening. The target list included 13 emerging contaminants (EC): thiabendazole, acesulfame, fenofibric acid, valsartan, irbesartan, salicylic acid, diclofenac, carbamazepine, 4-aminoantipyrine (4- AA), 4-acetyl aminoantipyrine (4-AAA), 4-formyl aminoantipyrine (4-FAA), venlafaxine and benzoylecgonine. The aqueous and solid phases of the sewage sludge were analyzed making use of Solid-Phase Extraction (SPE) and UltraSonic Extraction (USE) for sample treatment, respectively. The methods were validated at three concentration levels: 0.2, 2 and 20mg L 1 for the aqueous phase, and 50, 500 and 2000mg kg 1 for the solid phase of the sludge. In general, the method was satisfactorily validated, showing good recoveries (70–120%) and precision (RSD < 20%). Regarding the limit of quantification (LOQ), it was below 0.1mg L 1 in the aqueous phase and below 50mg kg 1 in the solid phase for the majority of the analytes. The method applicability was tested by analysis of samples from a wider study on degradation of emerging pollutants in sewage sludge under anaerobic digestion. The key benefits of these methodologies are: SPE and USE are appropriate sample procedures to extract selected emerging contaminants from the aqueous phase of the sewage sludge and the solid residue. LC–MS/MS is highly suitable for determining emerging contaminants in both sludge phases. Up to our knowledge, the main metabolites of dipyrone had not been studied before in sewage sludge. ãFinancial support of Generalitat Valenciana (Prometeo II/2014/023,ISIC/2014/016

Behaviour of emerging contaminants in sewage sludge after anaerobic digestion

Nowadays, there is an increasing concern over the presence of contaminants in the aquatic environment, where they can be introduced from wastewater after their incomplete removal in the treatment plants. In this work, degradation of selected emerging pollutants in the aqueous and solid phases of sewage sludge has been investigated after anaerobic digestion using two different digesters: mesophilic and thermophilic. Initially, sludge samples were screened by ultra-high-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UHPLC-QTOF MS) for identification of emerging contaminants in the samples. In a second step, a target quantitative method based on LC coupled to tandem MS was applied for selected pollutants identified in the previous screening. The behaviour of the compounds under anaerobic conditions was studied estimating the degradation efficiency and distribution of compounds between both sludge phases. Irbesartan and benzoylecgonine seemed to be notably degraded in both phases of the sludge. Venlafaxine showed a significant concentration decrease in the aqueous phase in parallel to an increase in the solid phase. The majority of the compounds showed an increase of their concentrations in both phases after the digestion. Concentrations in the solid phase were commonly higher than in the aqueous for most contaminants, indicating that they were preferentially adsorbed onto the solid particles.The authors are very grateful to the Ecophysiology and Biotechnology group (University Jaume I) and to The Institute of Aquaculture “Torre de la Sal” (IATS) (Consejo Superior de Investigaciones Científicas, CSIC) for using their lyophilizer systems. The financial support of Generalitat Valenciana (Prometeo II/2014/023, ISIC/2014/016) is also acknowledged

Efficacy of immune checkpoint inhibitors in alveolar soft-part sarcoma: results from a retrospective worldwide registry

Alveolar soft-part sarcoma; Immune checkpoint; ImmunotherapySarcoma alveolar de partes blandas; Puntos de control inmunológico; InmunoterapiaSarcoma alveolar de parts toves; Punts de control immunològic; ImmunoteràpiaBackground Conventional cytotoxic drugs are not effective in alveolar soft-part sarcoma (ASPS). Immune checkpoint (programmed cell death protein 1/programmed death-ligand 1) inhibitors (ICIs) are promising drugs in ASPS. A worldwide registry explored the efficacy of ICI in ASPS. Materials and methods Data from adult patients diagnosed with ASPS and treated with ICI for advanced disease in expert sarcoma centers from Europe, Australia and North America were retrospectively collected, including demographics and data related to treatments and outcome. Results Seventy-six ASPS patients, with a median age at diagnosis of 25 years (range 3-61 years), were registered. All patients received ICI for metastatic disease. Immunotherapy regimens consisted of monotherapy in 38 patients (50%) and combination in 38 (50%) (23 with a tyrosine kinase inhibitor). Among the 68 assessable patients, there were 3 complete responses and 34 partial responses, translating into an overall response rate of 54.4%. After a median follow-up of 36 months [95% confidence interval (CI) 32-40 months] since the start of immunotherapy, 45 (59%) patients have progressed on ICI, with a median progression-free survival (PFS) of 16.3 months (95% CI 8-25 months). Receiving ICI in first line (P = 0.042) and achieving an objective response (P = 0.043) correlated with a better PFS. Median estimated overall survival (OS) from ICI initiation has not been reached. The 12-month and 24-month OS rates were 94% and 81%, respectively. Conclusions This registry constitutes the largest available series of ASPS treated with ICI. Our results suggest that the ICI treatment provides long-lasting disease control and prolonged OS in patients with advanced ASPS, an ultra-rare entity with limited active therapeutic options.DSM is a recipient of a Sara Borrell postdoctoral fellowship funded by the National Institute of Health Carlos III (ISCIII) (CD20/00155). The authors thank SELNET project. SELNET has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No. 825806

Información espacial, herramientas de análisis en la transformación de las coberturas vegetales

a conceptos que orientan los análisis de dinámicas a escala de paisaje, así también se destacan publicaciones sobre la transformación de las coberturas vegetales ocasionado por actividad humana, ambiental y las implicaciones sobre el medio en el que se producen. La importancia de las herramientas espaciales (pre-procesamientos de imágenes satelitales, georreferenciación, metadatos, matrices de composición y configuración del paisaje y SIG) radica en identificar el balance entre hábitat natural y paisaje urbano-rural, este puede determinar el futuro de la diversidad biológica y la sostenibilidad de los servicios ecosistémicos en cualquier zona del planeta, es decir, establecer la viabilidad ecológica de una zona dada