Parallel solvers for virtual element discretizations of elliptic equations in mixed form

The aim of this paper is twofold. On the one hand, we numerically test the performance of mixed virtual elements in three dimensions to solve the mixed formulation of three-dimensional elliptic equations on polyhedral meshes. On the other hand, we focus on the parallel solution of the linear system arising from such discretization, considering both direct and iterative parallel solvers. In the latter case, we develop two block preconditioners, one based on the approximate Schur complement and one on a regularization technique. Both these topics are numerically validated by several parallel tests performed on a Linux cluster. More specifically, we show that the proposed virtual element discretization recovers the expected theoretical convergence rates and we analyze the performance of the direct and iterative parallel solvers taken into account

Coeficiente de metabolizabilidade aparente de diferentes fontes lipídicas com ou sem emulsificante para frangos de corte de 1 a 8 dias.

Óleos e gorduras são utilizados nas rações de aves devido às suas altas concentrações calóricas. Entretanto, a escolha da fonte lipídica a ser utilizada na formulação dependerá de seu custo e da qualidade. O uso de emulsificantes em aves jovens tem o objetivo de auxiliar na digestão e absorção da gordura da dieta devido à imaturidade da circulação entero-hepática nesses animais (5). O objetivo do estudo foi avaliar o coeficiente de metabolizabilidade aparente da matéria seca (CMAMS) e extrato etéreo (CMAEE) e energia metabolizável (EM) em frangos de corte de 1 a 8 dias de idade alimentados com diferentes fontes lipídicas com ou sem a adição de emulsificantes

Digestibilidade de dietas com diferentes formas físicas para frangos de corte.

A peletização é o processamento térmico mais utilizado na indústria avícola, pois favorece o aproveitamento dos ingredientes e modifica a forma física da dieta. A pressão, umidade e temperatura empregadas por determinado tempo no processo, promovem alterações nas estruturas dos carboidratos, bem como das proteínas. O objetivo desse estudo foi avaliar o efeito de diferentes formas físicas (farelada ou peletizada/triturada com diferentes tempos de condicionamento) sobre o coeficiente de digestibilidade ileal aparente da matéria seca (CDIAMS), proteína bruta (CDIAPB) e energia digestível ileal (EDI) em frangos de corte de 1 a 25 dias

Hyper conserved elements in vertebrate mRNA 3’-UTRs reveal a translational network of RNA-binding proteins controlled by HUR

Little is known regarding the post-transcriptional networks that control gene expression in eukaryotes. Additionally, we still need to understand how these networks evolve, and the relative role played in them by their sequence-dependent regulatory factors, non-coding RNAs (ncRNAs) and RNA-binding proteins (RBPs). Here, we used an approach that relied on both phylogenetic sequence sharing and conservation in the whole mapped 30-untranslated regions (30-UTRs) of vertebrate species to gain knowledge on core post-transcriptional networks. The identified human hyper conserved elements (HCEs) were predicted to be preferred binding sites for RBPs and not for ncRNAs, namely microRNAs and long ncRNAs. We found that the HCE map identified a well-known network that post-transcriptionally regulates histone mRNAs. We were then able to discover and experimentally confirm a translational network composed of RNA Recognition Motif (RRM)-type RBP mRNAs that are positively controlled by HuR, another RRM-type RBP. HuR shows a preference for these RBP mRNAs bound in stem\u2013loop motifs, confirming its role as a \u2018regulator of regulators\u2019. Analysis of the transcriptome-wide HCE distribution revealed a profile of prevalently small clusters separated by unconserved intercluster RNA stretches, which predicts the formation of discrete small ribonucleoprotein complexes in the 30-UTRs

po 077 identification of dhx30 as an inhibitor of the translation of pro apoptotic mrnas after p53 activation by nutlin

Introduction The transcription factor p53 can be efficiently activated by the small molecule Nutlin-3 without inducing genotoxic stress. Treatment of different cell lines with this small molecule can result in different phenotypes, ranging from cell cycle arrest to apoptosis. HCT116 (colon cancer-derived cells) and SJSA1 (osteosarcoma-derived cells) were used to model the opposite behaviour respectively, by analysing the transcriptional and translational responses after Nutlin-3 treatment. Material and methods Total and polysomal-bound mRNAs were collected and sequenced after 12 hour of 10 uM Nutlin-3 treatment. A bioinformatics analysis of the polysome-enriched mRNAs using Weeder allowed the identification of a 3'UTR motif ('CG-rich') which is enriched in the translationally upregulated genes of SJSA1. The effect of the motif on translation was evaluated after cloning its consensus sequence in the 3'UTR of the b-globin gene, which was put downstream the luciferase reporter. The activity of the construct was evaluated after 12 or 24 hours of Nutlin-3. The same consensus was used for a pull-down experiment followed by mass spectrometry to identify proteins interacting with it. Results and discussions RNA-seq data indicate that HCT116 and SJSA1, although sharing almost completely the transcriptional program lead by p53, show almost no overlap at a translation level. SJSA1 present different pro-apoptotic translationally-upregulated genes after Nutlin-3, which have one or more instances of a CG-rich motif in the 3'UTR. The impact of the motif is to enhance the activity of the luciferase reported when cloned in two copies flanking the 3'UTR of the b-globin gene, but only in SJSA1. A pull-down experiment using an RNA bait with the consensus motif was used to identify interactors, among which DHX30 was deeply studied. DHX30 silencing in HCT116 causes: 1) enhanced the activity of the reporter construct after Nutlin; 2) polysomal association of selected mRNAs containing the motif; 3) induction of apoptosis as assessed by Annexin-V staining. In addition, silencing of DHX30 in U2OS cells decreased their survival after Nutlin-3 treatment. Conclusion We show how a p53-dependent transcriptional program can be shaped at a translational level thanks to the action of a CG-rich motif which is enriched in the 3'UTR of some pro-apoptotic mRNAs and that can be bound by DHX30. This protein acts as a translational repressor of mRNAs containing the motif. The exact mechanism and the generalisation of the model are currently being investigated

Regulation of HuR structure and function by dihydrotanshinone-I

The Human antigen R protein (HuR) is an RNA-binding protein that recognizes U/AU-rich elements in diverse RNAs through two RNA-recognition motifs, RRM1 and RRM2, and post-transcriptionally regulates the fate of target RNAs. The natural product dihydrotanshinone-I (DHTS) prevents the association of HuR and target RNAs in vitro and in cultured cells by interfering with the binding of HuR to RNA. Here, we report the structural determinants of the interaction between DHTS and HuR and the impact of DHTS on HuR binding to target mRNAs transcriptome-wide. NMR titration and Molecular Dynamics simulation identified the residues within RRM1 and RRM2 responsible for the interaction between DHTS and HuR. RNA Electromobility Shifts and Alpha Screen Assays showed that DHTS interacts with HuR through the same binding regions as target RNAs, stabilizing HuR in a locked conformation that hampers RNA binding competitively. HuR ribonucleoprotein immunoprecipitation followed by microarray (RIP-chip) analysis showed that DHTS treatment of HeLa cells paradoxically enriched HuR binding to mRNAs with longer 3'UTR and with higher density of U/AU-rich elements, suggesting that DHTS inhibits the association of HuR to weaker target mRNAs. In vivo, DHTS potently inhibited xenograft tumor growth in a HuR-dependent model without systemic toxicity

Pain and Frailty in Hospitalized Older Adults

Introduction: Pain and frailty are prevalent conditions in the older population. Many chronic diseases are likely involved in their origin, and both have a negative impact on quality of life. However, few studies have analysed their association. Methods: In light of this knowledge gap, 3577 acutely hospitalized patients 65 years or older enrolled in the REPOSI register, an Italian network of internal medicine and geriatric hospital wards, were assessed to calculate the frailty index (FI). The impact of pain and some of its characteristics on the degree of frailty was evaluated using an ordinal logistic regression model after adjusting for age and gender. Results: The prevalence of pain was 24.7%, and among patients with pain, 42.9% was regarded as chronic pain. Chronic pain was associated with severe frailty (OR = 1.69, 95% CI 1.38–2.07). Somatic pain (OR = 1.59, 95% CI 1.23–2.07) and widespread pain (OR = 1.60, 95% CI 0.93–2.78) were associated with frailty. Osteoarthritis was the most common cause of chronic pain, diagnosed in 157 patients (33.5%). Polymyalgia, rheumatoid arthritis and other musculoskeletal diseases causing chronic pain were associated with a lower degree of frailty than osteoarthritis (OR = 0.49, 95%CI 0.28–0.85). Conclusions: Chronic and somatic pain negatively affect the degree of frailty. The duration and type of pain, as well as the underlying diseases associated with chronic pain, should be evaluated to improve the hospital management of frail older people

The multifaceted spectrum of liver cirrhosis in older hospitalised patients: Analysis of the REPOSI registry

Background: Knowledge on the main clinical and prognostic characteristics of older multimorbid subjects with liver cirrhosis (LC) admitted to acute medical wards is scarce. Objectives: To estimate the prevalence of LC among older patients admitted to acute medical wards and to assess the main clinical characteristics of LC along with its association with major clinical outcomes and to explore the possibility that well-distinguished phenotypic profiles of LC have classificatory and prognostic properties. Methods: A cohort of 6,193 older subjects hospitalised between 2010 and 2018 and included in the REPOSI registry was analysed. Results: LC was diagnosed in 315 patients (5%). LC was associated with rehospitalisation (age-sex adjusted hazard ratio, [aHR] 1.44; 95% CI, 1.10-1.88) and with mortality after discharge, independently of all confounders (multiple aHR, 2.1; 95% CI, 1.37-3.22), but not with in-hospital mortality and incident disability. Three main clinical phenotypes of LC patients were recognised: relatively fit subjects (FIT, N = 150), subjects characterised by poor social support (PSS, N = 89) and, finally, subjects with disability and multimorbidity (D&M, N = 76). PSS subjects had an increased incident disability (35% vs 13%, P < 0.05) compared to FIT. D&M patients had a higher mortality (in-hospital: 12% vs 3%/1%, P < 0.01; post-discharge: 41% vs 12%/15%, P < 0.01) and less rehospitalisation (10% vs 32%/34%, P < 0.01) compared to PSS and FIT. Conclusions: LC has a relatively low prevalence in older hospitalised subjects but, when present, accounts for worse post-discharge outcomes. Phenotypic analysis unravelled the heterogeneity of LC older population and the association of selected phenotypes with different clinical and prognostic features