Dissecting the Genome for Drug Response Prediction

The prediction of the cancer cell lines sensitivity to a specific treatment is one of the current challenges in precision medicine. With omics and pharmacogenomics data being available for over 1000 cancer cell lines, several machine learning and deep learning algorithms have been proposed for drug sensitivity prediction. However, deciding which omics data to use and which computational methods can efficiently incorporate data from different sources is the challenge which several research groups are working on. In this review, we summarize recent advances in the representative computational methods that have been developed in the last 2 years on three public datasets: COSMIC, CCLE, NCI-60. These methods aim to improve the prediction of the cancer cell lines sensitivity to a given treatment by incorporating drug's chemical information in the input or using a priori feature selection. Finally, we discuss the latest published method which aims to improve the prediction of clinical drug response of real patients starting from cancer cell line molecular profiles

Variation in the co-expression profile highlights a loss of miRNA-mRNA regulation in multiple cancer types

Recent research provides insight into the ability of miRNA to regulate various pathways in several cancer types. Despite their involvement in the regulation of the mRNA via targeting the 3'UTR, there are relatively few studies examining the changes in these regulatory mechanisms specific to single cancer types or shared between different cancer types.We analyzed samples where both miRNA and mRNA expression had been measured and performed a thorough correlation analysis on 7494 experimentally validated human miRNA-mRNA target-gene pairs in both healthy and tumoral samples.We show how more than 90% of these miRNA-mRNA interactions show a loss of regulation in the tumoral samples compared with their healthy counterparts.As expected, we found shared miRNA-mRNA dysregulated pairs among different tumors of the same tissue. However, anatomically different cancers also share multiple dysregulated interactions, suggesting that some cancer-related mechanisms are not tumor-specific. 2865 unique miRNA-mRNA pairs were identified across 13 cancer types, approximate to 40% of these pairs showed a loss of correlation in the tumoral samples in at least 2 out of the 13 analyzed cancers. Specifically, miR-200 family, miR-155 and miR-1 were identified, based on the computational analysis described below, as the miRNAs that potentially lose the highest number of interactions across different samples (only literature-based interactions were used for this analysis).Moreover, the miR-34a/ALDH2 and miR-9/MTHFD2 pairs show a switch in their correlation between healthy and tumor kidney samples suggesting a possible change in the regulation exerted by the miRNAs. Interestingly, the expression of these mRNAs is also associated with the overall survival. The disruption of miRNA regulation on its target, therefore, suggests the possible involvement of these pairs in cell malignant functions.The analysis reported here shows how the regulation of miRNA-mRNA interactions strongly differs between healthy and tumoral cells, based on the strong correlation variation between miRNA and its target that we obtained by analyzing the expression data of healthy and tumor tissue in highly reliable miRNA-target pairs. Finally, a go term enrichment analysis shows that the critical pairs identified are involved in cellular adhesion, proliferation, and migration

BRIO: a web server for RNA sequence and structure motif scan

The interaction between RNA and RNA-binding proteins (RBPs) has a key role in the regulation of gene expression, in RNA stability, and in many other biological processes. RBPs accomplish these functions by binding target RNA molecules through specific sequence and structure motifs. The identification of these binding motifs is therefore fundamental to improve our knowledge of the cellular processes and how they are regulated. Here, we present BRIO (BEAM RNA Interaction mOtifs), a new web server designed for the identification of sequence and structure RNA-binding motifs in one or more RNA molecules of interest. BRIO enables the user to scan over 2508 sequence motifs and 2296 secondary structure motifs identified in Homo sapiens and Mus musculus, in three different types of experiments (PAR-CLIP, eCLIP, HITS). The motifs are associated with the binding of 186 RBPs and 69 protein domains. The web server is freely available at http://brio.bio.uniroma2.it

Captura, acondicionamiento y primer desove de sargo Anisotremus scapularis en la Región Tacna

La presente investigación tuvo como objetivo desarrollar un sistema de captura para acondicionamiento de reproductores de sargo en el Centro de Acuicultura Morro Sama- Tacna. Asimismo, desarrollar una técnica de alta efectividad, medida en sobrevivencia para la captura de ejemplares de sargo, en la Región Tacna. Además de describir los resultados sobre la captura acondicionamiento y reproducción de sargo Anisotremus scapularis. Para esto, se recolectaron 15 peces silvestres, los cuales al final del período de acondicionamiento alcanzaron el estado de maduración gonadal y desovaron en forma espontánea. Los 15 ejemplares de sargos Anisotremus scapularis fueron capturados con anzuelos en las playas de Llostay (Tacna), en el año 2016. Y fueron acondicionados en un tanque de 4 metros de diámetro con un sistema abierto de agua de mar, alimentados con muy muy Emerita analoga y alimento balanceado de formulación propia. Entre los resultados se encuentra una sobrevivencia de 73.33 % (11 sargos) luego de 7 meses de acondicionamiento. El primer desove fue el 29 de octubre del 2016 a una temperatura de 18 °C

Elliptic and hyperelliptic magnetohydrodynamic equilibria

The present study is a continuation of a previous one on "hyperelliptic" axisymmetric equilibria started in [Tasso and Throumoulopoulos, Phys. Plasmas 5, 2378 (1998)]. Specifically, some equilibria with incompressible flow nonaligned with the magnetic field and restricted by appropriate side conditions like "isothermal" magnetic surfaces, "isodynamicity" or P + B^2/2 constant on magnetic surfaces are found to be reducible to elliptic integrals. The third class recovers recent equilibria found in [Schief, Phys. Plasmas 10, 2677 (2003)]. In contrast to field aligned flows, all solutions found here have nonzero toroidal magnetic field on and elliptic surfaces near the magnetic axis.Comment: 9 page

COX-2 expression positively correlates with PD-L1 expression in human melanoma cells.

Abstract BACKGROUND: The resistance to PD-1/PD-L1 inhibitors for the treatment of melanoma have prompted investigators to implement novel clinical trials which combine immunotherapy with different treatment modalities. Moreover is also important to investigate the mechanisms which regulate the dynamic expression of PD-L1 on tumor cells and PD-1 on T cells in order to identify predictive biomarkers of response. COX-2 is currently investigated as a major player of tumor progression in several type of malignancies including melanoma. In the present study we investigated the potential relationship between COX-2 and PD-L1 expression in melanoma. METHODS: Tumor samples obtained from primary melanoma lesions and not matched lymph node metastases were analyzed for both PD-L1 and COX-2 expression by IHC analysis. Status of BRAF and NRAS mutations was analyzed by sequencing and PCR. Co-localization of PD-L1 and COX-2 expression was analyzed by double fluorescence staining. Lastly the BRAFV600E A375 and NRASQ61R SK-MEL-2 melanoma cell lines were used to evaluate the effect of COX-2 inhibition by celecoxib on expression of PD-L1 in vitro. RESULTS: BRAFV600E/V600K and NRASQ61R/Q61L were detected in 57.8 and 8.9% of the metastatic lesions, and in 65.9 and 6.8% of the primary tumors, respectively. PD-L1 and COX-2 expression were heterogeneously expressed in both primary melanoma lesions and not matched lymph node metastases. A significantly lower number of PD-L1 negative lesions was found in primary tumors as compared to not matched metastatic lesions (P = 0.002). COX-2 expression significantly correlated with PD-L1 expression in both primary (P = 0.001) and not matched metastatic (P = 0.048) lesions. Furthermore, in melanoma tumors, cancer cells expressing a higher levels of COX-2 also co-expressed a higher level of PD-L1. Lastly, inhibition of COX-2 activity by celecoxib down-regulated the expression of PD-L1 in both BRAFV600E A375 and NRASQ61R SK-MEL-2 melanoma cell lines. CONCLUSIONS: COX-2 expression correlates with and modulates PD-L1 expression in melanoma cells. These findings have clinical relevance since they provide a rationale to implement novel clinical trials to test COX-2 inhibition as a potential treatment to prevent melanoma progression and immune evasion as well as to enhance the anti-tumor activity of PD-1/PD-L1 based immunotherapy for the treatment of melanoma patients with or without BRAF/NRAS mutations

Características productivas de establecimientos en transición agroecológica y diferencias edáficas con productores convencionales

Se estudiaron sistemas familiares de producción en transición agroecológica (SFTA) y sistemas de producción convencionales (SC), de los partidos de Luján, General Rodríguez y San Andrés de Giles. Se determinó en suelo: materia orgánica, fósforo, pH, CE y respiración; el pH y la conductividad presentaron escasas diferencias entre SFTA y SC, en tanto que la materia orgánica, la respiración y el P fueron superiores en SFTA, indicando que sus sistemas podrían ser sustentables a largo plazo. Se realizaron entrevistas y encuestas a los productores sobre sus formas de organización y comercialización: los SFTA poseen escasas superficies, producen leche de vaca Jersey, cabras y venta de terneros. Los SFTA viven en sus establecimientos, comercializan en ferias locales y vecinos. Presentan formas asociativas, expresan respeto por el ambiente y buscan una mayor calidad de sus productos. Los SC presentan grandes extensiones, no viven en el campo y operan con contratistas.Family production systems in agro-ecological transition (SFTA) and neighbors conventional farm system (SC) matches Lujan, General Rodríguez and San André de Giles were studied. It was determined in soil: organic matter, P, pH, EC and breathing; pH and conductivity showed little difference between SFTA and SC, while organic matter, respiration and P were higher in SFTA, indicating that their systems could be sustainable in the long term. Interviews and surveys were made to farmers on their forms of organization and marketing: the SFTA have poor surfaces, produce milk Jersey cows, goats and selling calves. The SFTA live in their establishments, sold at local fairs and neighbors. They express respect for the environment, shows associative forms and seek a better quality of their products. The SC have large areas, they do not live in the field and operate with contractors.Eje: A1 Sistemas de producción de base agroecológica (Trabajos científicos)Facultad de Ciencias Agrarias y Forestale

Características productivas de establecimientos en transición agroecológica y diferencias edáficas con productores convencionales

Se estudiaron sistemas familiares de producción en transición agroecológica (SFTA) y sistemas de producción convencionales (SC), de los partidos de Luján, General Rodríguez y San Andrés de Giles. Se determinó en suelo: materia orgánica, fósforo, pH, CE y respiración; el pH y la conductividad presentaron escasas diferencias entre SFTA y SC, en tanto que la materia orgánica, la respiración y el P fueron superiores en SFTA, indicando que sus sistemas podrían ser sustentables a largo plazo. Se realizaron entrevistas y encuestas a los productores sobre sus formas de organización y comercialización: los SFTA poseen escasas superficies, producen leche de vaca Jersey, cabras y venta de terneros. Los SFTA viven en sus establecimientos, comercializan en ferias locales y vecinos. Presentan formas asociativas, expresan respeto por el ambiente y buscan una mayor calidad de sus productos. Los SC presentan grandes extensiones, no viven en el campo y operan con contratistas.Family production systems in agro-ecological transition (SFTA) and neighbors conventional farm system (SC) matches Lujan, General Rodríguez and San André de Giles were studied. It was determined in soil: organic matter, P, pH, EC and breathing; pH and conductivity showed little difference between SFTA and SC, while organic matter, respiration and P were higher in SFTA, indicating that their systems could be sustainable in the long term. Interviews and surveys were made to farmers on their forms of organization and marketing: the SFTA have poor surfaces, produce milk Jersey cows, goats and selling calves. The SFTA live in their establishments, sold at local fairs and neighbors. They express respect for the environment, shows associative forms and seek a better quality of their products. The SC have large areas, they do not live in the field and operate with contractors.Eje: A1 Sistemas de producción de base agroecológica (Trabajos científicos)Facultad de Ciencias Agrarias y Forestale

Características productivas de establecimientos en transición agroecológica y diferencias edáficas con productores convencionales

Se estudiaron sistemas familiares de producción en transición agroecológica (SFTA) y sistemas de producción convencionales (SC), de los partidos de Luján, General Rodríguez y San Andrés de Giles. Se determinó en suelo: materia orgánica, fósforo, pH, CE y respiración; el pH y la conductividad presentaron escasas diferencias entre SFTA y SC, en tanto que la materia orgánica, la respiración y el P fueron superiores en SFTA, indicando que sus sistemas podrían ser sustentables a largo plazo. Se realizaron entrevistas y encuestas a los productores sobre sus formas de organización y comercialización: los SFTA poseen escasas superficies, producen leche de vaca Jersey, cabras y venta de terneros. Los SFTA viven en sus establecimientos, comercializan en ferias locales y vecinos. Presentan formas asociativas, expresan respeto por el ambiente y buscan una mayor calidad de sus productos. Los SC presentan grandes extensiones, no viven en el campo y operan con contratistas.Family production systems in agro-ecological transition (SFTA) and neighbors conventional farm system (SC) matches Lujan, General Rodríguez and San André de Giles were studied. It was determined in soil: organic matter, P, pH, EC and breathing; pH and conductivity showed little difference between SFTA and SC, while organic matter, respiration and P were higher in SFTA, indicating that their systems could be sustainable in the long term. Interviews and surveys were made to farmers on their forms of organization and marketing: the SFTA have poor surfaces, produce milk Jersey cows, goats and selling calves. The SFTA live in their establishments, sold at local fairs and neighbors. They express respect for the environment, shows associative forms and seek a better quality of their products. The SC have large areas, they do not live in the field and operate with contractors.Eje: A1 Sistemas de producción de base agroecológica (Trabajos científicos)Facultad de Ciencias Agrarias y Forestale

Inhibition of exosome biogenesis affects cell motility in heterogeneous sub-populations of paediatric-type diffuse high-grade gliomas

Background: Paediatric-type diffuse High-Grade Gliomas (PDHGG) are highly heterogeneous tumours which include distinct cell sub-populations co-existing within the same tumour mass. We have previously shown that primary patient-derived and optical barcoded single-cell-derived clones function as interconnected networks. Here, we investigated the role of exosomes as a route for inter-clonal communication mediating PDHGG migration and invasion. Results: A comprehensive characterisation of seven optical barcoded single-cell-derived clones obtained from two patient-derived cell lines was performed. These analyses highlighted extensive intra-tumour heterogeneity in terms of genetic and transcriptional profiles between clones as well as marked phenotypic differences including distinctive motility patterns. Live single-cell tracking analysis of 3D migration and invasion assays showed that the single-cell-derived clones display a higher speed and longer travelled distance when in co-culture compared to mono-culture conditions. To determine the role of exosomes in PDHGG inter-clonal cross-talks, we isolated exosomes released by different clones and characterised them in terms of marker expression, size and concentration. We demonstrated that exosomes are actively internalized by the cells and that the inhibition of their biogenesis, using the phospholipase inhibitor GW4689, significantly reduced the cell motility in mono-culture and more prominently when the cells from the clones were in co-culture. Analysis of the exosomal miRNAs, performed with a miRNome PCR panel, identified clone-specific miRNAs and a set of miRNA target genes involved in the regulation of cell motility/invasion/migration. These genes were found differentially expressed in co-culture versus mono-culture conditions and their expression levels were significantly modulated upon inhibition of exosome biogenesis. Conclusions: In conclusion, our study highlights for the first time a key role for exosomes in the inter-clonal communication in PDHGG and suggests that interfering with the exosome biogenesis pathway may be a valuable strategy to inhibit cell motility and dissemination for these specific diseases