Differences in the fly-load of Haematobia irritans (Diptera: Muscidae) on cattle is modified by endophyte infection of pastures

Background: The horn fly, Haematobia irritans, is an obligate bloodsucking ectoparasite of pastured cattle and is a major pest of livestock production in North and South America and Europe. In this study, we investigated the potential to use cattle pastures, infected with non-toxic, "friendly" fungal-endophyte-infected (E+) tall fescue, Festuca arundinacea Schreb., as a strategy for reducing horn fly loads in cattle, and to evaluate the possible bioinsecticide effect on horn fly larvae. Results: When cattle grazed in E+ tall fescue, a decrease in fly-load was observed, compared with other pastures (endophyte-free (E-) pastures). The infestation of horn fly load decreased according to an increase in the percentage of endophyte present in the different pastures (0 to 100%). Moreover, two groups of animals with significant differences in the fly-load (high and low fly-load) in the same herd were observed (P < 0.05). Additionally, it was possible to determine a bioinsecticide effect of cattle dung, upon horn fly larvae (80%), from animals fed E+ tall fescue. Conclusions: These results constitute the first report on the potential for exploiting pasture management for controlling 1) horn fly-loads on cattle and 2) the normal development of horn fly larvae. In conclusion, this information provides preliminary understanding of the role of cattle pasture diet management for controlling horn fliesas part of an integrated pest management strategy for this major pest of farmed livestock

Ligand binding and homology modelling of insect odorant-binding proteins

This review describes the main characteristics of odorant-binding proteins (OBPs) for homology modelling and presents a summary of structure prediction studies on insect OBPs, along with the steps involved and some limitations and improvements. The technique involves a computing approach to model protein structures and is based on a comparison between a target (unknown structure) and one or more templates (experimentally determined structures). As targets for structure prediction, OBPs are considered to play a functional role for recognition, desorption, scavenging, protection and transportation of hydrophobic molecules (odourants) across an aqueous environment (lymph) to olfactory receptor neurones (ORNs) located in sensilla, the main olfactory units of insect antennae. Lepidopteran pheromone-binding proteins, a subgroup of OBPs, are characterized by remarkable structural features, in which high sequence identities (approximately 30%) among these OBPs and a large number of available templates can facilitate the prediction of precise homology models. Approximately 30 studies have been performed on insect OBPs using homology modelling as a tool to predict their structures. Although some of the studies have assessed ligand-binding affinity using structural information and biochemical measurements, few have performed docking and molecular dynamic (MD) simulations as a virtual method to predict best ligands. Docking and MD simulations are discussed in the context of discovery of novel semiochemicals (super-ligands) using homology modelling to conceive further strategies in insect management

Overall evaluation of Skylab imagery for mapping of Latin America

The author has identified the following significant results. Skylab imagery is both desired and needed by the Latin American catographic agencies. The imagery is cost beneficial for the production of new mapping and maintenance of existing maps at national topographic series scales. If this information was available on a near time routine coverage basis, it would provide an excellent additional data base to the Latin American cartographic community, specifically Argentina, Bolivia, Chile, Colombia, Dominican Republic, Guatemala, Paraguay, and Venezuela

Antifeedant activity of red clover root isoflavonoids on Hylastinus obscurus.

In the last decade, there has been increasing interest in investigating the impact of flavonoids on insects, specifically for pest control. In this study, we investigated the impact of isoflavonoids upon the feeding behavior of the clover root borer, Hylastinus obscurus Marsham (Coleoptera: Curculionidae), which is one of the most serious global pests associated with red clover, Trifolium pratense L. Four aglycones isoflavonoids: genistein (1), formononetin (2), daidzein (3) and biochanin A (4) were isolated and identified by HPLC, from roots of two Chilean red clover cultivars. The first two compounds, formononetin (2) and genistein (1), showed high feeding deterrent activity when they were evaluated in artificial diets. This antifeedant effect of isoflavones on feeding behavior of H. obscurus suggests that they are responsible for a decreasedin insect weight gain as compared with the control. This information could be useful respectively, to farmers and researcher to produce and create plants resistant to curculioni

Preclinical activity and determinants of response of the GPRC5DxCD3 bispecific antibody talquetamab in multiple myeloma.

Cell surface expression levels of GPRC5D, an orphan G protein-coupled receptor, are significantly higher on multiple myeloma (MM) cells, compared with normal plasma cells or other immune cells, which renders it a promising target for immunotherapeutic strategies. The novel GPRC5D-targeting T-cell redirecting bispecific antibody, talquetamab, effectively kills GPRC5D+ MM cell lines in the presence of T cells from both healthy donors or heavily pretreated MM patients. In addition, talquetamab has potent anti-MM activity in bone marrow (BM) samples from 45 patients, including those with high-risk cytogenetic aberrations. There was no difference in talquetamab-mediated killing of MM cells from newly diagnosed, daratumumab-naïve relapsed/refractory (median of 3 prior therapies), and daratumumab-refractory (median of 6 prior therapies) MM patients. Tumor cell lysis was accompanied by T-cell activation and degranulation, as well as production of pro-inflammatory cytokines. High levels of GPRC5D and high effector:target ratio were associated with improved talquetamab-mediated lysis of MM cells, whereas an increased proportion of T cells expressing PD-1 or HLA-DR, and elevated regulatory T-cell (Treg) counts were associated with suboptimal killing. In cell line experiments, addition of Tregs to effector cells decreased MM cell lysis. Direct contact with bone marrow stromal cells also impaired the efficacy of talquetamab. Combination therapy with daratumumab or pomalidomide enhanced talquetamab-mediated lysis of primary MM cells in an additive fashion. In conclusion, we show that the GPRC5D-targeting T-cell redirecting bispecific antibody talquetamab is a promising novel antimyeloma agent. These results provide the preclinical rationale for ongoing studies with talquetamab in relapsed/refractory MM

Efficacy and safety of daratumumab combined with all-trans retinoic acid in relapsed/refractory multiple myeloma

The efficacy of daratumumab depends partially on CD38 expression on multiple myeloma (MM) cells. We have previously shown that all-trans retinoic acid (ATRA) upregulates CD38 expression and reverts daratumumab-resistance ex vivo. We therefore evaluated the optimal dose, efficacy, and safety of daratumumab combined with ATRA in patients with daratumumab-refractory MM in a phase 1/2 study (NCT02751255). In part A of the study, 63 patients were treated with daratumumab monotherapy. Fifty patients with daratumumabrefractory MM were subsequently enrolled in part B and treated with daratumumab (reintensified schedule) combined with ATRA until disease progression. The recommended phase 2 dose of ATRA in combination with daratumumab was defined as 45 mg/m2. At this dose, the overall response rate (ORR) was 5%, indicating that the primary endpoint (ORR $15%) was not met. However, most patients (66%) achieved at least stable disease. After a median follow-up of 43 months, the median progression-free survival (PFS) for all patients was 2.8 months. Patients who previously achieved at least a partial response or minimal response/stable disease with prior daratumumab monotherapy had a significantly longer PFS compared with patients who immediately progressed during daratumumab as single agent (median PFS 3.4 and 2.8 vs 1.3 months). The median overall survival was 19.1 months. The addition of ATRA did not increase the incidence of adverse events. Flow cytometric analysis revealed that ATRA temporarily increased CD38 expression on immune cell subsets. In conclusion, the addition of ATRA and reintensification of daratumumab had limited activity in patients with daratumumab-refractory MM, which may be explained by the transient upregulation of CD38 expression. This trial was registered at www.clinicaltrials.gov as #NCT02751255

Investigation of Host Candidate Malaria-Associated Risk/Protective SNPs in a Brazilian Amazonian Population

The Brazilian Amazon is a hypo-endemic malaria region with nearly 300,000 cases each year. A variety of genetic polymorphisms, particularly in erythrocyte receptors and immune response related genes, have been described to be associated with susceptibility and resistance to malaria. In order to identify polymorphisms that might be associated with malaria clinical outcomes in a Brazilian Amazonian population, sixty-four human single nucleotide polymorphisms in 37 genes were analyzed using a Sequenom massARRAY iPLEX platform. A total of 648 individuals from two malaria endemic areas were studied, including 535 malaria cases (113 individuals with clinical mild malaria, 122 individuals with asymptomatic infection and 300 individuals with history of previous mild malaria) and 113 health controls with no history of malaria. The data revealed significant associations (p<0.003) between one SNP in the IL10 gene (rs1800896) and one SNP in the TLR4 gene (rs4986790) with reduced risk for clinical malaria, one SNP in the IRF1 gene (rs2706384) with increased risk for clinical malaria, one SNP in the LTA gene (rs909253) with protection from clinical malaria and one SNP in the TNF gene (RS1800750) associated with susceptibility to clinical malaria. Also, a new association was found between a SNP in the CTL4 gene (rs2242665), located at the major histocompatibility complex III region, and reduced risk for clinical malaria. This study represents the first association study from an Amazonian population involving a large number of host genetic polymorphisms with susceptibility or resistance to Plasmodium infection and malaria outcomes. Further studies should include a larger number of individuals, refined parameters and a fine-scale map obtained through DNA sequencing to increase the knowledge of the Amazonian population genetic diversity

In Situ Detection of HY-Specific T Cells in Acute Graft-versus-Host Disease–Affected Male Skin after Sex-Mismatched Stem Cell Transplantation

HY-specific T cells are presumed to play a role in acute graft-versus-host disease (aGVHD) after female-to-male stem cell transplantation (SCT). However, infiltrates of these T cells in aGVHD-affected tissues have not yet been reported. We evaluated the application of HLA-A2/HY dextramers for the in situ detection of HY-specific T cells in cryopreserved skin biopsy specimens. We applied the HLA-A2/HY dextramers on cryopreserved skin biopsy specimens from seven male HLA-A2+ pediatric patients who underwent stem cell transplantation with confirmed aGVHD involving the skin. The dextramers demonstrated the presence of HY-specific T cells. In skin biopsy specimens of three male recipients of female grafts, 68% to 78% of all skin-infiltrating CD8+ T cells were HY-specific, whereas these cells were absent in biopsy specimens collected from sex-matched patient–donor pairs. Although this study involved a small and heterogeneous patient group, our results strongly support the hypothesis that HY-specific T cells are actively involved in the pathophysiology of aGVHD after sex-mismatched stem cell transplantation

Cognition, culture and utility:Plant classification by Paraguayan immigrant farmers in Misiones, Argentina

Background: This study was conducted in three rural communities of small farmers of Paraguayan origin living in the province of Misiones, Argentina. These Criollos (Mestizos) hail chiefly from departments located in the east of Paraguay, where the climate and flora have similar characteristics as those in Misiones. These ecological features contribute to the continuation and maintenance of knowledge and practices related to the use of plants. Methods: Fieldwork was conducted between September 2014 and August 2015. Forty five informants from three rural localities situated along the Parana River participated in an ethno-classification task. For the classification event, photographs of 30 medicinal and edible plants were chosen, specifically those yielding the highest frequency of mention among the members of that community (based on data obtained in the first stage of research in 2014). Variation in local plant classifications was examined and compared using principal component analysis and cluster analysis. Results: We found that people classify plants according to application or use (primarily medicinal, to a lesser extent as edible). Morphology is rarely taken into account, even for very similar and closely-related species such as varieties of palms. In light of our findings, we highlight a dominant functionality model at work in the process of plant cognition and classification among farmers of Paraguayan origin. Salient cultural beliefs and practices associated with rural Paraguayan plant-based medicine are described. Additionally, the manner by which residents’ concepts of plants articulate with local folk epistemology is discussed. Conclusions: Culturally constructed use patterns ultimately override morphological variables in rural Paraguayans’ ethnobotanical classification.Antecedentes: Este trabajo se realizó con pequeños agricultores de origen paraguayo, que habitan en la provincia de Misiones, Argentina. Los criollos (mestizos) en su mayoría provienen de departamentos ubicados al oriente del Paraguay, donde el clima y la flora presentan características similares a la provincia de Misiones. Estas características ecológicas contribuyen a la continuación y el mantenimiento de los conocimientos y las prácticas relacionados al uso de las plantas. Métodos El trabajo de campo se realizó entre septiembre de 2014 y agosto de 2015. En la etnoclasificación participaron 45 informantes, provenientes de tres localidades rurales, situadas a lo largo del río Paraná, frontera entre los dos países. Para la clasificación se utilizaron imágenes fotográficas de 30 especies -comestibles y medicinales- preseleccionadas como las de mayor frecuencia de mención entre los habitantes de la región (a partir de los datos obtenidos en una primera etapa de investigación en el año 2014). Por medio del análisis de componentes principales y el análisis de agrupamiento (cluster) se contrastaron y compararon las variaciones en las etnoclasificaciones locales de plantas. Resultados Se encontró que los pobladores clasifican sus plantas según su aplicación y uso (mayormente asociadas a la categoría medicinal y en menor medida a la comestible). Mientras, la morfología rara vez se tiene en cuenta, incluso en aquellas especies muy similares y estrechamente relacionadas como las palmeras. A la luz de los hallazgos, se destaca un modelo de funcionalidad dominante en el proceso de cognición y de clasificación de las plantas entre los agricultores de origen paraguayo. Se describen las principales creencias y prácticas culturales asociadas a la medicina rural paraguaya. Adicionalmente, se discuten algunos de los conceptos de las plantas que mantienen los paraguayos y su articulación con la epistemología local. Conclusiones En la clasificación etnobotánica de los pobladores de origen paraguayo los patrones de uso construidos culturalmente tienen mayor peso que las variables morfológicas.Fil: Kujawska, Monika. University Of Lodz; ArgentinaFil: Jiménez Escobar, Néstor David. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Antropología de Córdoba. Universidad Nacional de Córdoba. Facultad de Filosofía y Humanidades. Instituto de Antropología de Córdoba; ArgentinaFil: Nolan, Justin M.. University Of Arkansas; Estados UnidosFil: Arias Mutis, Daniel. University of Groningen; Países Bajo