Problems relevant to town incoming radio TV links

The degradations produced on the wanted TV signal by an interfering signal are examined. The TV protection ratios to be respected are also examined in case of co-channel interference and adjacent channels. Problems related to the possible disturbances produced by the interfering signal on the AGC and the squelch of the interred receiver are also taken into account. Some solutions normally adopted for the above problems are examined, including improvement of the antenna directivity, suitable filtering, and polarization discrimination. Finally, some problems related to the propagation I urban areas for what concerns the possible distortions on a color TV signal are examined

β-Glucan synthase induction in mushrooms grown on olive mill wastewaters

Beta-1-3-Glucan synthase activity and its induction by olive mill wastewaters (OMW) was studied in ten fungal strains (Auricularia auricula-judae, Lentinula edodes, Pleurotus eryngii, Stropharia aeruginosa, Agrocybe aegerita, P. pulmonarius, Armillaria mellea, P. ferulae, P. ostreatus, P. nebrodensis). A microtiter-based enzymatic assay on -1-3-glucan synthase activity was carried out on all mycelia growth both on the control medium and on OMW. Among the fungi assayed, L. edodes -1-3-glucan synthase was highly enhanced in OMW. The main components of OMW, i.e. phenols and lipids, were added separately to the control medium, to highlight the mechanism of L. edodes -1-3-glucan synthase induction. A Southern blot analysis and PCR with degenerated primers were carried out to detect the presence of fks1-like genes in these Basidiomycetes. The sequences obtained from the ten Basidiomycota were remarkably similar to fks1 from Filobasidiella neoformans. Spectrofluorimetric and RT-PCR analyses of -1-3-glucan synthase were performed on the mycelia of L. edodes. In this fungus, a strong stimulation of -1-3-glucan synthase mRNA and protein was recorded in the presence of OMW and phenol

Bienestar Psicológico y Ansiedad Rasgo-Estado en basquetbolistas de Lima Metropolitana

El objetivo del presente estudio es el demostrar que los basquetbolistas profesionales de Lima Metropolitana registran un menor nivel de Bienestar Psicológico, en comparación a las personas que practican dicho deporte de forma recreacional. Además, se espera encontrar un nivel más alto de Ansiedad-Estado y de Ansiedad-Rasgo en los deportistas profesionales. La muestra consiste de 100 jugadores de básquet (57 hombres y 43 mujeres), con una edad media de 23 años. Para ello, se emplean dos escalas y una ficha sociodemográfica. Los estadísticos que se emplean son prueba t de student para muestras independientes, Anova one way, Kruskal-Wallis U de Mann Whitney y correlaciones. Los resultados muestran que hay mayores niveles de Bienestar en los jugadores profesionales. Además, que no hay diferencias en los niveles de Ansiedad de los jugadores profesionales y amateurs

Bioactive Thymosin Alpha-1 Does Not Influence F508del-CFTR Maturation and Activity.

Deletion of phenylalanine 508 (F508del) in the cystic fibrosis transmembrane conductance regulator (CFTR) anion channel is the most frequent mutation causing cystic fibrosis (CF). F508del-CFTR is misfolded and prematurely degraded. Recently thymosin a-1 (Tα-1) was proposed as a single molecule-based therapy for CF, improving both F508del-CFTR maturation and function by restoring defective autophagy. However, three independent laboratories failed to reproduce these results. Lack of reproducibility has been ascribed by the authors of the original paper to the use of DMSO and to improper handling. Here, we address these potential issues by demonstrating that Tα-1 changes induced by DMSO are fully reversible and that Tα-1 peptides prepared from different stock solutions have equivalent biological activity. Considering the negative results here reported, six independent laboratories failed to demonstrate F508del-CFTR correction by Tα-1. This study also calls into question the autophagy modulator cysteamine, since no rescue of mutant CFTR function was detected following treatment with cysteamine, while deleterious effects were observed when bronchial epithelia were exposed to cysteamine plus the antioxidant food supplement EGCG. Although these studies do not exclude the possibility of beneficial immunomodulatory effects of thymosin α-1, they do not support its utility as a corrector of F508del-CFTR

Targeting of Ubiquitin E3 Ligase RNF5 as a Novel Therapeutic Strategy in Neuroectodermal Tumors

RNF5, an endoplasmic reticulum (ER) E3 ubiquitin ligase, participates to the ER-associated protein degradation guaranteeing the protein homeostasis. Depending on tumor model tested, RNF5 exerts pro-or anti-tumor activity. The aim of this study was to elucidate the controversial role of RNF5 in neuroblastoma and melanoma, two neuroectodermal tumors of infancy and adulthood, respectively. RNF5 gene levels are evaluated in publicly available datasets reporting the gene expression profile of melanoma and neuroblastoma primary tumors at diagnosis. The therapeutic effect of Analog-1, an RNF5 pharmacological activator, was investigated on in vitro and in vivo neuroblastoma and melanoma models. In both neuroblastoma and melanoma patients the high expression of RNF5 correlated with a better prognostic outcome. Treatment of neuroblastoma and melanoma cell lines with Analog-1 reduced cell viability by impairing the glutamine availability and energy metabolism through inhibition of F1Fo ATP-synthase activity. This latter event led to a marked increase in oxidative stress, which, in turn, caused cell death. Similarly, neuroblastoma-and melanoma-bearing mice treated with Analog-1 showed a significant delay of tumor growth in comparison to those treated with vehicle only. These findings validate RNF5 as an innovative drug target and support the development of Analog-1 in early phase clinical trials for neuroblastoma and melanoma patients

Journey on VX-809-Based Hybrid Derivatives towards Drug-like F508del-CFTR Correctors: From Molecular Modeling to Chemical Synthesis and Biological Assays

open12Cystic fibrosis (CF) is a genetic disease affecting the lungs and pancreas and causing progressive damage. CF is caused by mutations abolishing the function of CFTR, a protein whose role is chloride's mobilization in the epithelial cells of various organs. Recently a therapy focused on small molecules has been chosen as a main approach to contrast CF, designing and synthesizing compounds acting as misfolding (correctors) or defective channel gating (potentiators). Multi-drug therapies have been tested with different combinations of the two series of compounds. Previously, we designed and characterized two series of correctors, namely, hybrids, which were conceived including the aminoarylthiazole (AAT) core, merged with the benzodioxole carboxamide moiety featured by VX-809. In this paper, we herein proceeded with molecular modeling studies guiding the design of a new third series of hybrids, featuring structural variations at the thiazole moiety and modifications on position 4. These derivatives were tested in different assays including a YFP functional assay on models F508del-CFTR CFBE41o-cells, alone and in combination with VX-445, and by using electrophysiological techniques on human primary bronchial epithelia to demonstrate their F508del-CFTR corrector ability. This study is aimed (i) at identifying three molecules (9b, 9g, and 9j), useful as novel CFTR correctors with a good efficacy in rescuing the defect of F508del-CFTR; and (ii) at providing useful information to complete the structure-activity study within all the three series of hybrids as possible CFTR correctors, supporting the development of pharmacophore modelling studies, taking into account all the three series of hybrids. Finally, in silico evaluation of the hybrids pharmacokinetic (PK) properties contributed to highlight hybrid developability as drug-like correctors.openParodi, Alice; Righetti, Giada; Pesce, Emanuela; Salis, Annalisa; Tomati, Valeria; Pastorino, Cristina; Tasso, Bruno; Benvenuti, Mirko; Damonte, Gianluca; Pedemonte, Nicoletta; Cichero, Elena; Millo, EnricoParodi, Alice; Righetti, Giada; Pesce, Emanuela; Salis, Annalisa; Tomati, Valeria; Pastorino, Cristina; Tasso, Bruno; Benvenuti, Mirko; Damonte, Gianluca; Pedemonte, Nicoletta; Cichero, Elena; Millo, Enric

In vitro recapitulation of the site-specific editing (to wild-type) of mutant IDS mRNA transcripts, and the characterization of IDS protein translated from the edited mRNAs

The transfer of genomic information into the primary RNA sequence can be altered by RNA editing. We have previously shown that genomic variants can be RNA-edited to wild-type. The presence of distinct “edited” iduronate 2-sulfatase (IDS) mRNA transcripts ex vivo evidenced the correction of a nonsense and frameshift variant, respectively, in three unrelated Hunter syndrome patients. This phenomenon was confirmed in various patient samples by a variety of techniques, and was quantified by single-nucleotide primer extension. Western blotting also confirmed the presence of IDS protein similar in size to the wild-type. Since preliminary experimental evidence suggested that the “corrected” IDS proteins produced by the patients were similar in molecular weight and net charge to their wild-type counterparts, an in vitro system employing different cell types was established to recapitulate the site-specific editing of IDS RNA (uridine to cytidine conversion and uridine deletion), and to confirm the findings previously observed ex vivo in the three patients. In addition, confocal microscopy and flow cytometry analyses demonstrated the expression and lysosomal localization in HEK293 cells of GFP-labeled proteins translated from edited IDS mRNAs. Confocal high-content analysis of the two patients’ cells expressing wild-type or mutated IDS confirmed lysosomal localization and showed no accumulation in the Golgi or early endosomes

Systematic genetic analysis of the MHC region reveals mechanistic underpinnings of HLA type associations with disease.

The MHC region is highly associated with autoimmune and infectious diseases. Here we conduct an in-depth interrogation of associations between genetic variation, gene expression and disease. We create a comprehensive map of regulatory variation in the MHC region using WGS from 419 individuals to call eight-digit HLA types and RNA-seq data from matched iPSCs. Building on this regulatory map, we explored GWAS signals for 4083 traits, detecting colocalization for 180 disease loci with eQTLs. We show that eQTL analyses taking HLA type haplotypes into account have substantially greater power compared with only using single variants. We examined the association between the 8.1 ancestral haplotype and delayed colonization in Cystic Fibrosis, postulating that downregulation of RNF5 expression is the likely causal mechanism. Our study provides insights into the genetic architecture of the MHC region and pinpoints disease associations that are due to differential expression of HLA genes and non-HLA genes

Greening Modern Rice Farming Using Vermicompost and Its Impact on Productivity and Efficiency: An Empirical Analysis from Bangladesh

Greening modern rice farming while improving productivity and reducing chemical use is a desirable goal for sustainable agriculture. This paper analyzes the impact of vermicomposting on productivity and efficiency of modern rice farming using a random sample of 340 farmers from the southwestern region of Bangladesh by applying a stochastic production frontier approach. Results reveal that productivity is significantly higher and the use of chemicals is significantly lower for vermicompost users as expected. However, profitability gain is not significantly different mainly due to the high cost of vermicompost. Use of vermicompost significantly increases productivity along with other conventional inputs and its users are relatively more technically efficient. Policy implications include investments to raise farmers’ awareness of the benefits of vermicomposting and support entrepreneurs to expand commercial production of vermicompost, which will synergistically curb the use of chemicals in modern rice farming while improving productivity and efficiency.</jats:p