Identifying phenotypes involved in susceptibility to Schistosoma mansoni infection in F1B6CBA mice

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.Schistosomiasis is a disease with a strong genetic component influenced by socioeconomic and ecological factors. Epidemiological studies have identified several genetic regions involved in the schistosomiasis susceptibility. However, it is not well known what physiological traits are predisposing to the disease. The study of experimental infections in inbred mouse strains with variable genetic susceptibility to the disease offers a good opportunity to tackle this question. F1B6CBA hybrid between the most divergent strains was infected in order to characterize the immunophenotypes that correlate with the susceptibility of schistosomiasis disease in mice. Complete blood counts and immunophenotype were determined at 0, 3, 6, and 9 weeks post infection. Nine weeks after cercariae exposure, animals were perfused and worm recovery was assessed. A large number of hepatic lesions, a reduction in the eosinophil and basophil count in the acute phase of infection and the decreased number of monocytes, neutrophils and B-lymphocytes are phenotypes associated with increased susceptibility to S. mansoni infection.The present study was supported by a grant from the Areces Foundation (2010–13) and funding of the Junta de Castilla y Leon (Orden EDU/330/2008).Peer Reviewe

Caracterización radiológica de muestras de suelo: toma de muestra, conservación y preparación, análisis por espectrometría gamma, determinación del índice de actividad beta total y procedimiento de separación radiológica para la determinación del Sr90.

El objetivo principal de este Trabajo Fin de Máster ha sido la caracterización radiológica de muestras de suelo. Las etapas que se han seguido han sido: toma de muestra, conservación y preparación, análisis por espectrometría gamma, determinación del índice de actividad beta total y procedimiento de separación radioquímica para la determinación del isótopo Sr90. Se han utilizado los equipos para la realización del análisis por espectrometría gamma, detector de germanio, y para la determinación del índice de actividad beta total, contador proporcional alfa-beta. Se ha llevado a cabo la revisión y optimización de los procedimientos de toma de muestra y de separaciones radioquímicas. Por último, se ha realizado el análisis de resultados y extraído conclusiones

Combinatorial formulas for Kazhdan-Lusztig polynomials with respect to W-graph ideals

In \cite{y1} Yin generalized the definition of $W$-graph ideal $E_J$ in weighted Coxeter groups and introduced the weighted Kazhdan-Lusztig polynomials $\left \{ P_{x,y} \mid x,y\in E_J\right \}$, where $J$ is a subset of simple generators $S$. In this paper, we study the combinatorial formulas for those polynomials, which extend the results of Deodhar \cite{v3} and Tagawa \cite{h1}.Comment: 16 page

Dysregulated Network of Immune, Endocrine and Metabolic Markers is Associated to More Severe Human Chronic Chagas Cardiomyopathy

Individuals who are infected with Trypanosoma cruzi develop chronic Chagas cardiomyopathy (CCC), which is a complication involving a series of immune pathogenetic mechanisms, although an association between immune and metabolic alterations was more recently proposed. Accordingly, we investigated the immuno-metabolic response in chagasic patients and their possible influence on CCC pathogenesis. To this end, T. cruzi-seropositive (asymptomatic or with CCC) and sero-negative individuals were studied. Serum tumour necrosis factor (TNF)-α, interleukin (IL)-6, adipocytokines and the expression of their receptors in peripheral blood mononuclear cell (PBMC) were evaluated, together with other factors influencing the immune response. CCC patients showed major metabolic and hormonal abnormalities, in parallel with increased IL-6 and leptin serum levels. TNF-α receptor s, leptin and adiponectin receptors (ObR and Adipo-Rs respectively), as well as PPAR-γ expression in PBMCs from CCC patients were compatible with a counteracting response leading to an unfavourable immune-metabolic profile. These results suggest that persistently increased levels of immune-metabolic pro-inflammatory mediators along with the adverse endocrine anti-inflammatory response of CCC individuals, may contribute to the underlying mechanisms dealing with myocardial tissue damage.Fil: González, Florencia Belén. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clínica y Experimental de Rosario, CONICET-UNR; ArgentinaFil: Bottasso, Oscar. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clínica y Experimental de Rosario, CONICET-UNR; Argentin

Explorando el potencial bioestimulante del alga invasora Rugulopterix okamurae en vid

Trabajo presentado en las IV Jornadas del Grupo de Viticultura de la Sociedad Española de Ciencias Hortícolas, celebradas en Pamplona (España), del 26 al 28 de octubre de 202

Propranolol reduces viability and induces apoptosis in hemangioblastoma cells from von Hippel-Lindau patients

[Background] Von Hippel-Lindau (VHL) disease is a rare oncological disease with an incidence of 1:36,000, and is characterized by the growth of different types of tumors: hemangioblastomas in the central nervous system (CNS) and retina, renal carcinoma, pheochromocytomas, pancreatic serous cystadenoma, and endolymphatic sac tumors. These tumors do not express VHL protein (pVHL). pVHL ubiquitinates hypoxia inducible factor (HIF) protein for degradation by the proteasome; in the absence of VHL, HIF translocates to the nucleus to activate the expression of its target genes. Targeting VHL-derived tumors with drugs that have reduced side effects is urgent to avoid repeat CNS surgeries. Recent reports have shown that propranolol, a β-blocker used for the treatment of hypertension and other cardiac and neurological diseases, is the best option for infantile hemangioma (IH). Propranolol could be an efficient treatment to control hemangioblastoma growth in VHL disease because of its antiangiogenic effects demonstrated in IH and the hypothetical impact on HIF levels.[Methods] HeLa 9X (HRE) hypoxia responsive element cell line and primary hemangioblastoma-derived cells were subjected to propranolol treatment and cell viability and apoptosis were evaluated. HIF1-α and Hif-2α expression after propranolol treatment was analyzed by western blotting. Quantitative PCR was performed to study the mRNA expression of HIF target genes. Vascular endothelial growth factor (VEGF) was measured in culture supernatants by immunoassay.[Results] Propranolol downregulated HIF-dependent transcription in HeLa 9XHRE cells. Under hypoxic conditions, propranolol decreased the expression of HIF target genes in hemangioblastoma cells, which stopped proliferating and died following long-term treatment. These results suggests that propranolol treatment promoted reduced HIF protein expression and corresponding downregulation of HIF target genes, and inhibited cell proliferation in parallel with induction of cell death by apoptosis.[Conclusions] Our results suggest that propranolol could reduce the growth of HIF-dependent tumors and may thus be a promising treatment to delay surgery in VHL patients.This work was supported by grants from Ministerio de Economia y Competitividad SAF2011-23475 and from Alianza VHL Spain& Fundación Iberdrola to LMB. Virginia Albiñana was supported by Alianza VHL Spain, Fundación Iberdrola and Fundación Divina Pastora.Peer reviewe

Quinoxaline 1,4-di-N-oxide and the Potential for Treating Tuberculosis

New drugs active against drug-resistant tuberculosis are urgently needed to extend the range of TB treatment options to cover drug resistant infections. Quinoxaline derivatives show very interesting biological properties (antibacterial, antiviral, anticancer, antifungal, antihelmintic, insecticidal) and evaluation of their medicinal chemistry is still in progress. In this review we report the properties and the recent developments of quinoxaline 1,4-di-N-oxide derivatives as potential anti-tuberculosis agents. Specific agents are reviewed that have excellent antitubercular drug properties, are active on drug resistant strains and non-replicating mycobacteria. The properties of select analogs that have in vivo activity in the low dose aerosol infection model in mice will be reviewed

Holistic understanding of the response of grapevines to foliar application of seaweed extracts

Viticulture is highly dependent on phytochemicals to maintain good vineyard health. However, to reduce their accumulation in the environment, green regulations are driving the development of eco-friendly strategies. In this respect, seaweeds have proven to be one of the marine resources with the highest potential as plant protective agents, representing an environmentally-friendly alternative approach for sustainable wine production. The current work follows an interdisciplinary framework to evaluate the capacity of Ulva ohnoi and Rugulopteryx okamurae seaweeds to induce defense mechanisms in grapevine plants. To our knowledge, this is the first study to evaluate Rugulopteryx okamurae as a biostimulator . This macroalgae is relevant since it is an invasive species on the Atlantic and Mediterranean coast causing incalculable economic and environmental burdens. Four extracts (UL1, UL2, RU1 and RU2 developed from Ulva and Rugulopteryx, respectively) were foliar applied to Tempranillo plants cultivated under greenhouse conditions. UL1 and RU2 stood out for their capacity to induce defense genes, such as a PR10, PAL, STS48 and GST1, mainly 24 hours after the first application. The increased expression level of these genes agreed with i) an increase in trans-piceid and trans-resveratrol content, mainly in the RU2 treated leaves, and, ii) an increase in jasmonic acid and decrease in salicylic acid. Moreover, an induction of the activity of the antioxidant enzymes was observed at the end of the experiment, with an increase in superoxide dismutase and catalase in the RU2-treated leaves in particular. Interestingly, while foliar fungal diversity was not influenced by the treatments, alga extract amendment modified fungal composition, RU2 application enriching the content of various groups known for their biocontrol activity. Overall, the results evidenced the capacity of Rugulopteryx okamurae for grapevine biostimulation, inducing the activation of several secondary metabolite pathways and promoting the abundance of beneficial microbiota involved in grapevine protection. While further studies are needed to unravel the bioactive compound(s) involved, including conducting field experiments etc., the current findings are the first steps towards the inclusion of Rugulopteryx okamurae in a circular scheme that would reduce its accumulation on the coast and benefit the viticulture sector at the same time

Integrated flow cytometry and sequencing to reconstruct evolutionary patterns from dysplasia to acute myeloid leukemia

Clonal evolution in acute myeloid leukemia (AML) originates long before diagnosis and is a dynamic process that may affect survival. However, it remains uninvestigated during routine diagnostic workup. We hypothesized that the mutational status of bone marrow dysplastic cells and leukemic blasts, analyzed at the onset of AML using integrated multidimensional flow cytometry (MFC) immunophenotyping and sorting (FACS) with next-generation sequencing (NGS), could reconstruct leukemogenesis. Dysplastic cells were detected by MFC in 285 of 348 (82%) newly-diagnosed AML patients. Presence of dysplasia according to MFC and WHO criteria had no prognostic value in the elderly. NGS of dysplastic cells and blasts isolated at diagnosis identified three evolutionary patterns: stable (n=12/21), branching (n=4/21) and clonal evolution (n=5/21). In patients achieving complete response, integrated MFC and FACS with NGS showed persistent measurable residual disease (MRD) in phenotypically normal cell types, as well as the acquisition of genetic traits associated with treatment resistance. Furthermore, whole-exome sequencing of dysplastic and leukemic cells at diagnosis and of MRD uncovered different clonal involvement in dysplastic myelo-erythropoiesis, leukemic transformation and chemoresistance. Altogether, we showed that it is possible to reconstruct leukemogenesis in approximately 80% of newly diagnosed AML patients, using techniques other than single-cell multiomics.ACKNOWLEDGEMENTS: The authors acknowledge the patients, caregivers, and the biobank of the University of Navarra. This work was supported by grants from the Área de Oncología del Instituto de Salud Carlos III, Centro de Investigacion Biom ´ edica en ´ Red (CIBER-ONC) (CB16/12/00369, CB16/12/00233, CB16/12/ 00489, and CB16/12/00284), Instituto de Salud Carlos III/Subdireccion General de Investigaci ´ on Sanitaria (FIS numbers PI16/ ´ 01661, PI16/00517, and PI19/01518), and the Plan de Investigacion´ de la Universidad de Navarra (PIUNA 2014-18). This work was supported internationally by the Cancer Research UK, FCAECC, and AIRC under the Accelerator Award Program (EDITOR)