MECHANISM OF SPLICING REGULATION BY THE MEIOSIS ENHANCER FACTOR Mer1p IN YEAST Saccharomyces cerevisiae

In eukaryotes, genes are presented in a series of coding and non-coding DNA regions (exons/introns) that are transcribed into a premature RNA (pre-mRNA). Introns can be removed from the mature premRNA, before its translation into proteins, in a process called splicing. The splicing reaction occurs in two highly regulated transesterification reactions inside of the cell nucleus, and it is catalyzed by the Spliceosome, involving the binding and release of five small nuclear ribonucleoprotein particles (snRNPs). While some introns are constitutively spliced, others can be alternatively spliced, giving different exon combinations and therefore different proteins, increasing the protein diversity of the species. In humans, misregulation of alternative splicing can result in the production of aberrant proteins, some of which may produce cancer or other severe diseases. In yeast, alternative splicing is regulated by different splicing factors, such as Mer1p. Mer1p is expressed during meiosis in the yeast Saccharomyces cerevisiae and activates the splicing in at least three different genes (AMA1, MER2, and MER3), which contain a conserved intronic splicing enhancer sequence. Previous results have shown that Mer1p is able to interact with the pre-mRNA and with specific proteins of the U1 and U2 snRNPs. However, the specific molecular mechanisms by which Mer1p activates splicing remained unknown. The objective of this work is to determine how Mer1p regulates the splicing of its targets, and how different splicing factors modulate Mer1p activity. Using biochemistry and genetics, the data presented in this work indicate that Mer1p recruits the snRNPs U1, U2 and U6, to pre-mRNA. This recruitment of the snRNPs is dependent of the U1 snRNP protein Nam8p and the U2 snRNP protein Snu17p, but independent on the branchpoint region or ATP. Furthermore, Mer1p accelerates and stabilizes the formation of the early complexes of the spliceosome. Finally, U1 and U2 are recruited to the pre-mRNA at the same time, emerging a new alternative hypothesis of splicing regulation that can be applied to other enhancer regulators and that differs from the classical model of stepwise assembly of the snRNP

Nuevo enfoque de la práctica educativa del Programa UNIGIS Girona. Algunas reflexiones sobre las claves del cambio

En los últimos años, se ha debatido mucho sobre el nuevo modelo pedagógico que promueve el nuevo espacio de educación superior. Este artículo recoge la experiencia del Programa UNIGIS de formación a distancia en SIG, que se imparte desde la Universidad de Girona, como ejemplo innovador de la aplicación de una nueva metodología de aprendizaje. La iniciativa es fruto, en gran medida, de las influencias europeas y de los sistemas de aprendizaje que llevan a cabo distintas universidades de nuestro continente. En un estudio a distancia que sustenta el proceso formativo en plataformas e-learning, resulta fundamental que éstas faciliten la implementación del modelo pedagógico sobre el cual se desarrolla el programa de formación, pero sin olvidar el papel clave que desempeñan las personas implicadas.During the last years a new pedagogical model promoted by the European Higher Education Area it has been discussed. This article gathers the experience of UNIGIS Girona distance learning program in GIS, which is organized by University of Girona, as an innovating example of a new learning methodology application. The initiative is due to the European influences and the learning systems that different European universities are carrying out. In a remote study, where educational processes are based on e-learning platforms, is fundamental that these platforms facilitate the opportunity to apply the pedagogical model, but without forgetting the key paper that the implied people play.En els últims anys, s'ha discutit molt al voltant del nou model pedagògic que promou el nou espai europeu d'educació superior. Aquest article recull l'experiència del Programa UNIGIS de formació a distància en SIG, que s'ofereix des de la Universitat de Girona, com a exemple innovador de l'aplicació d'una nova metodologia d'aprenentatge. La iniciativa és fruit, en gran mesura, de les influències europees i dels sistemes d'aprenentatge que duen a terme diverses universitats del nostre continent. En un estudi a distància que dóna suport al procés formatiu en plataformes e-learning, esdevé fonamental que aquestes facilitin l'aplicació del model pedagògic sobre el qual es desenvolupa el programa de formació, però sense oblidar el paper clau que hi tenen les persones implicades

Human peritoneal mesothelial cell death induced by high-glucose hypertonic solution involves Ca2+ and Na+ ions and oxidative stress with the participation of PKC/NOX2 and PI3K/Akt pathways

Indexación: Web of Science; Scopus.Chronic peritoneal dialysis (PD) therapy is equally efficient as hemodialysis while providing greater patient comfort and mobility. Therefore, PD is the treatment of choice for several types of renal patients. During PD, a high-glucose hyperosmotic (HGH) solution is administered into the peritoneal cavity to generate an osmotic gradient that promotes water and solutes transport from peritoneal blood to the dialysis solution. Unfortunately, PD has been associated with a loss of peritoneal viability and function through the generation of a severe inflammatory state that induces human peritoneal mesothelial cell (HPMC) death. Despite this deleterious effect, the precise molecular mechanism of HPMC death as induced by HGH solutions is far from being understood. Therefore, the aim of this study was to explore the pathways involved in HGH solution-induced HPMC death. HGH-induced HPMC death included influxes of intracellular Ca2+ and Na+. Furthermore, HGH-induced HPMC death was inhibited by antioxidant and reducing agents. In line with this, HPMC death was induced solely by increased oxidative stress. In addition to this, the cPKC/NOX2 and PI3K/Akt intracellular signaling pathways also participated in HGH-induced HPMC death. The participation of PI3K/Akt intracellular is in agreement with previously shown in rat PMC apoptosis. These findings contribute toward fully elucidating the underlying molecular mechanism mediating peritoneal mesothelial cell death induced by high-glucose solutions during peritoneal dialysis.https://www.frontiersin.org/articles/10.3389/fphys.2017.00379/ful

Differential miRNA expression profiling reveals miR-205-3p to be a potential radiosensitizer for low- dose ionizing radiation in DLD-1 cells

Indexación: Scopus.Departamento de Oncología Básico-Clínica, Facultad de Medicina, Universidad de Chile, Santiago, Chile 2Comisión Chilena de Energía Nuclear, Santiago, Chile 3Center for Research and Applications in Plasma Physics and Pulsed Power, P4, Chile 4Departamento de Ciencias Físicas, Universidad Andres Bello, Santiago, Chile 5Centro de Investigación y Tratamiento del Cáncer, Facultad de Medicina, Universidad de Chile, Santiago, Chile 6Current Address: Center of Excellence in Precision Medicine, Pfizer, Chile. on IR responsive modeling. This work was supported by Anillo grant ACT1115 and ACT172101, PIA Program, CONICYT; the Chilean doctoral fellowship 21130246Enhanced radiosensitivity at low doses of ionizing radiation (IR) (0.2 to 0.6 Gy) has been reported in several cell lines. This phenomenon, known as low doses hyperradiosensitivity (LDHRS), appears as an opportunity to decrease toxicity of radiotherapy and to enhance the effects of chemotherapy. However, the effect of low single doses IR on cell death is subtle and the mechanism underlying LDHRS has not been clearly explained, limiting the utility of LDHRS for clinical applications. To understand the mechanisms responsible for cell death induced by low-dose IR, LDHRS was evaluated in DLD-1 human colorectal cancer cells and the expression of 80 microRNAs (miRNAs) was assessed by qPCR array. Our results show that DLD-1 cells display an early DNA damage response and apoptotic cell death when exposed to 0.6 Gy. miRNA expression profiling identified 3 over-expressed (miR-205-3p, miR-1 and miR-133b) and 2 downregulated miRNAs (miR-122-5p, and miR-134-5p) upon exposure to 0.6 Gy. This miRNA profile differed from the one in cells exposed to high-dose IR (12 Gy), supporting a distinct low-dose radiation-induced cell death mechanism. Expression of a mimetic miR- 205-3p, the most overexpressed miRNA in cells exposed to 0.6 Gy, induced apoptotic cell death and, more importantly, increased LDHRS in DLD-1 cells. Thus, we propose miR-205-3p as a potential radiosensitizer to low-dose IR. © Andaur et al.http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path[]=25405&path[]=7956

Formative and Summative Feedback in Solution Generation: The Role of Community and Decision Support System in Open Source Software

Formative feedback is an important aspect of solution generation. This article decomposes formative feedback in four components based on learning literature: likability of feedback, verification feedback, specific elaborated feedback, and general elaborated feedback. However, formative feedback may have different effect in the solver depending in his state of anxiety. In addition, the solver receives formative feedback from the community and summative feedback from DSS. A negative summative feedback from DSS induces anxiety to the solver. Feedback literature not distinguishes between formative or summative feedback, which could explain the contradictory findings. This research theorizes about how summative feedback modifies formative feedback based on ACT. This analysis was performed by using an OSS community, which produced 976,635 lines of code in 36,878 solutions for 5,108 problems. The results suggest that summative feedback modifies how formative feedback affects the solver. Implications for the solution generation, We-intentions, formative and summative feedback are drawn

Clásicos y modernos. Notas barcelonesas sobre Hölderlin, Heidegger y Lukács en la poesía de Jaime Gil de Biedma

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Immune DNA signature of T-cell infiltration in breast tumor exomes.

Tumor infiltrating lymphocytes (TILs) have been associated with favorable prognosis in multiple tumor types. The Cancer Genome Atlas (TCGA) represents the largest collection of cancer molecular data, but lacks detailed information about the immune environment. Here, we show that exome reads mapping to the complementarity-determining-region 3 (CDR3) of mature T-cell receptor beta (TCRB) can be used as an immune DNA (iDNA) signature. Specifically, we propose a method to identify CDR3 reads in a breast tumor exome and validate it using deep TCRB sequencing. In 1,078 TCGA breast cancer exomes, the fraction of CDR3 reads was associated with TILs fraction, tumor purity, adaptive immunity gene expression signatures and improved survival in Her2+ patients. Only 2/839 TCRB clonotypes were shared between patients and none associated with a specific HLA allele or somatic driver mutations. The iDNA biomarker enriches the comprehensive dataset collected through TCGA, revealing associations with other molecular features and clinical outcomes

"Los sueños dialogados". Los límites de la vivencia petrarquista de Antonio Machado

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La syllabe qui ronge le fromage: nature et limites de la dialectique selon Sénèque

Generally speaking, Seneca gives a negative evaluation of dialectics, though he recognizes its power to sway the human mind. Although it is necessary for the elaboration of ethical ideas, it has no real bearing on actual life