Dual Requirement for Yeast hnRNP Nab2p in mRNA poly(A) Tail Length Control and Nuclear Export

Recent studies of mRNA export factors have provided additional evidence for a mechanistic link between mRNA 3′‐end formation and nuclear export. Here, we identify Nab2p as a nuclear poly(A)‐binding protein required for both poly(A) tail length control and nuclear export of mRNA. Loss of NAB2 expression leads to hyperadenylation and nuclear accumulation of poly(A)+ RNA but, in contrast to mRNA export mutants, these defects can be uncoupled in a nab2 mutant strain. Previous studies have implicated the cytoplasmic poly(A) tail‐binding protein Pab1p in poly(A) tail length control during polyadenylation. Although cells are viable in the absence of NAB2 expression when PAB1 is overexpressed, Pab1p fails to resolve the nab2Δ hyperadenylation defect even when Pab1p is tagged with a nuclear localization sequence and targeted to the nucleus. These results indicate that Nab2p is essential for poly(A) tail length control in vivo, and we demonstrate that Nab2p activates polyadenylation, while inhibiting hyperadenylation, in the absence of Pab1p in vitro. We propose that Nab2p provides an important link between the termination of mRNA polyadenylation and nuclear export

Quality Legume-Based Forage Systems for Contrasting Environments: COST Action 852

Agricultural systems that reduce environmental degradation, sustain agricultural productivity and economic viability, maintain stable rural communities, enhance the quality of life and respond to increasing demand for livestock products are promoted in developed countries. Though major challenges exist, forage legumes, adapted to a wide range of soil types, climatic conditions and management systems, will become increasingly important components of sustainable agricultural production systems in Europe. Temporal and spatial variation in legume performance often occurs. Compared to pure grass systems, legume-based systems may lead to increased N losses. To what extent ruminants can use the protein from forage legumes, and whether there are differences among species and cultivars are unknown. To improve reliability and the range of forage legumes, we must understand the constraints of environment, the reasons for divergence between species potential and actual performance and the most efficient way to use the herbage. The COST Action 852 - Quality legume-based forage systems for contrasting environments was set up to help resolve some of these questions

Diminished soil functions occur under simulated climate change in a sup-alpine pasture, but heterotrophic temperature sensitivity indicates microbial resilience

Peer reviewedPublisher PD

e-Tourism: a tourist recommendation and planning application

e-Tourism is a tourist recommendation and planning application to assist users on the organization of a leisure and tourist agenda. First, a recommender system offers the user a list of the city places that are likely of interest to the user. This list takes into account the user demographic classification, the user likes in former trips and the preferences for the current visit. Second, a planning module schedules the list of recommended places according to their temporal characteristics as well as the user restrictions; that is the planning system determines how and when to realize the recommended activities. Having the list of recommended activities organized as an agenda (i.e. an executable plan), is a relevant characteristic that most recommender systems lack.This work has been partially funded by Consolider Ingenio 2010 CSD2007-00022 project, by the Spanish Government MICINN TIN2008-6701-C03-01 project and by the Valencian Government GVPRE/2008/384 project. We thank J. Benton for having provided us with the system Sapa to execute our experiments.Sebastiá Tarín, L.; García García, I.; Onaindia De La Rivaherrera, E.; Gúzman Álvarez, CA. (2009). e-Tourism: a tourist recommendation and planning application. International Journal on Artificial Intelligence Tools. 18(5):717-738. https://doi.org/10.1142/S0218213009000378S71773818

The P-Loop Domain of Yeast Clp1 Mediates Interactions Between CF IA and CPF Factors in Pre-mRNA 3′ End Formation

Cleavage factor IA (CF IA), cleavage and polyadenylation factor (CPF), constitute major protein complexes required for pre-mRNA 3′ end formation in yeast. The Clp1 protein associates with Pcf11, Rna15 and Rna14 in CF IA but its functional role remained unclear. Clp1 carries an evolutionarily conserved P-loop motif that was previously shown to bind ATP. Interestingly, human and archaean Clp1 homologues, but not the yeast protein, carry 5′ RNA kinase activity. We show that depletion of Clp1 in yeast promoted defective 3′ end formation and RNA polymerase II termination; however, cells expressing Clp1 with mutant P-loops displayed only minor defects in gene expression. Similarly, purified and reconstituted mutant CF IA factors that interfered with ATP binding complemented CF IA depleted extracts in coupled in vitro transcription/3′ end processing reactions. We found that Clp1 was required to assemble recombinant CF IA and that certain P-loop mutants failed to interact with the CF IA subunit Pcf11. In contrast, mutations in Clp1 enhanced binding to the 3′ endonuclease Ysh1 that is a component of CPF. Our results support a structural role for the Clp1 P-loop motif. ATP binding by Clp1 likely contributes to CF IA formation and cross-factor interactions during the dynamic process of 3′ end formation

The impact of surgical practice on oncological outcomes in robot-assisted radical hysterectomy for early-stage cervical cancer, Spanish National Registry

Minimal invasive surgery (MIS) has been associated with lower disease-free survival than open surgery among women who underwent radical hysterectomy for early-stage cervical cancer. However, the mechanisms by which MIS increases mortality in cervical cancer remain uncertain. We aimed to determine if surgical practice among centers using robotic surgery has an impact on oncological outcomes. We evaluated 215 women with early-stage cervical cancer (≤IB1 or IIA1, FIGO 2009) who underwent robot-assisted radical hysterectomy in five Spanish tertiary centers between 2009 and 2018. A higher surgical volume, higher participation in clinical trials, higher rate of MRI use for diagnosis, greater use of sentinel lymph node biopsies, and a favorable learning curve with low rates of early recurrences were observed for the centers with better oncological outcomes. These factors might have a significant impact on oncological outcomes in all surgical approaches. Abstract: This study aimed to assess whether surgical practice had a significant impact on oncological outcomes among women who underwent robot-assisted radical hysterectomy for early-stage cervical cancer (≤IB1 or IIA1, FIGO 2009). The secondary objective was to audit the pre-surgical quality indicators (QI) proposed by the European Society of Gynaecological Oncology (ESGO). The top 5 of 10 centers in Spain and Portugal were included in the analysis. The hospitals were divided into group A (n = 118) and group B (n = 97), with recurrence rates of 10%, respectively. After balancing both groups using the propensity score, the ORs for all events were higher and statistically significant for group B (recurrences OR = 1.23, 95% CI = 1.13-1.15, p-value = 0.001; death OR = 1.10, 95% CI = 1.02-1.18, p-value = 0.012; disease-specific mortality ORr = 1.11, 95% CI = 1.04-1.19, p-value = 0.002). A higher surgical volume, higher participation in clinical trials, higher rate of MRI use for diagnosis, greater use of sentinel lymph node biopsies, and a favorable learning curve with low rates of early recurrences were observed among the centers with better oncological outcomes. These factors might have a significant impact on oncological outcomes not only after robot-assisted surgery, but also after laparoscopies and open surgeries in the treatment of cervical cancer