New Insights into Bile Acids Related Signaling Pathways in the Onset of Colorectal Cancer

Colorectal cancer (CRC) ranks as the second among the causes of tumor death worldwide, with an estimation of 1.9 million new cases in 2020 and more than 900,000 deaths. This rate might increase by 60% over the next 10 years. These data are unacceptable considering that CRC could be successfully treated if diagnosed in the early stages. A high-fat diet promotes the hepatic synthesis of bile acids (BAs) increasing their delivery to the colonic lumen and numerous scientific reports correlate BAs, especially secondary BAs, with CRC incidence. We reviewed the physicochemical and biological characteristics of BAs, focusing on the major pathways involved in CRC risk and progression. We specifically pointed out the role of BAs as signaling molecules and the tangled relationships among their nuclear and membrane receptors with the big bang of molecular and cellular events that trigger CRC occurrence

Abordagem computacional para a identificação de elementos cis-regulatórios no genoma da soja.

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Abordagem computacional para a identificação de elementos cis-regulatóriso no genoma da soja.

bitstream/item/71511/1/ID-31371.pd

Conformational analysis of 2,2-difluoroethylamine hydrochloride: double gauche effect

The gauche effect in fluorinated alkylammonium salts is well known and attributed either to an intramolecular hydrogen bond or to an electrostatic attraction between the positively charged nitrogen and the vicinal electronegative fluorine atom. This work reports the effect of adding a fluorine atom in 2-fluoroethylamine hydrochloride on the conformational isomerism of the resulting 2,2-difluoroethylamine chloride (2). The analysis was carried out using NMR coupling constants in D2O solution, in order to mimic the equilibrium conditions in a physiological medium, in the gas phase and in implicit water through theoretical calculations. Despite the presence of sigma(CH)->sigma(*)(CF) and sigma(CH)->sigma(*)(CN) interactions, which usually rule the hyperconjugative gauche effect in 1,2-disubstituted ethanes, the most important forces leading to the double gauche effect (+NH3 in the gauche relationship with both fluorine atoms) in 2 are the Lewis-type ones. Particularly, electrostatic interactions are operative even in water solution, where they should be significantly attenuated, whereas hyperconjugation and hydrogen bond have secondary importance10877882CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE MINAS GERAIS - FAPEMIGFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPsem informaçãosem informação2012/03933-5; 2011/11098-6; 2011/01170-

Treatment with PCSK9 Inhibitor Evolocumab Improves Vascular Oxidative Stress and Arterial Stiffness in Hypercholesterolemic Patients with High Cardiovascular Risk

Atherosclerosis and atherosclerotic-related cardiovascular diseases (ASCVD) are characterized by high serum levels of low-density lipoprotein cholesterol (LDL-C) that can promote the generation of reactive oxygen species (ROS). To answer the need for better LDL-C control in individuals at high and very high risk for CVD, a new injectable innovative family of lipid-lowering (LL) monoclonal antibodies against the protein convertase subtilisin/kexin type 9 (PCSK9) has been approved. However, the effect of these drugs on vascular function, such as ROS generation and arterial stiffness, has not already been extensively described. In this report, we present data from 18 males with high to very high CV risk undergoing LL treatment (LLT) with either statin and ezetimibe or ezetimibe monotherapy, who experienced, after a 2-month treatment with Evolocumab, a significant improvement in blood pressure (BP)-adjusted carotid-femoral pulse wave velocity (cfPWV) (p-value = 0.0005 in the whole cohort, p-value = 0.0046 in the sub-cohort undergoing background LLT with statin and ezetimibe, p-value = 0.015 in the sub-cohort undergoing background LLT with ezetimibe monotherapy), which was significantly associated with a decrease in freshly isolated leukocytes (PBMCS)-derived H2O2 production (p-value = 0.004, p-value = 0.02 and p-value = 0.05, respectively, in the whole cohort, in the statin + ezetimibe sub-cohort, and the ezetimibe sub-cohort). Our observations support the role of systemic oxidative stress in atherosclerosis and give a further rationale for using Evolocumab also for its effect in vascular disorders linked to oxidative processes

Soybean gene express: plataforma para análise de expressão diferencial e bibliotecas substrativas de cDNA.

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Enabling CUDA acceleration within virtual machines using rCUDA

The hardware and software advances of Graphics Processing Units (GPUs) have favored the development of GPGPU (General-Purpose Computation on GPUs) and its adoption in many scientific, engineering, and industrial areas. Thus, GPUs are increasingly being introduced in high-performance computing systems as well as in datacenters. On the other hand, virtualization technologies are also receiving rising interest in these domains, because of their many benefits on acquisition and maintenance savings. There are currently several works on GPU virtualization. However, there is no standard solution allowing access to GPGPU capabilities from virtual machine environments like, e.g., VMware, Xen, VirtualBox, or KVM. Such lack of a standard solution is delaying the integration of GPGPU into these domains. In this paper, we propose a first step towards a general and open source approach for using GPGPU features within VMs. In particular, we describe the use of rCUDA, a GPGPU (General-Purpose Computation on GPUs) virtualization framework, to permit the execution of GPU-accelerated applications within virtual machines (VMs), thus enabling GPGPU capabilities on any virtualized environment. Our experiments with rCUDA in the context of KVM and VirtualBox on a system equipped with two NVIDIA GeForce 9800 GX2 cards illustrate the overhead introduced by the rCUDA middleware and prove the feasibility and scalability of this general virtualizing solution. Experimental results show that the overhead is proportional to the dataset size, while the scalability is similar to that of the native environment.Peer ReviewedPostprint (author's final draft

Grape pomace for topical application: Green nades sustainable extraction, skin permeation studies, antioxidant and anti-inflammatory activities characterization in 3d human keratinocytes

Food waste is a global problem due to its environmental and economic impact, so there is great demand for the exploitation of new functional applications. The winemaking process leads to an incomplete extraction of high-value compounds, leaving the pomace still rich in polyphenols. This study was aimed at optimising and validating sustainable routes toward the extraction and further valorisation of these polyphenols, particularly for cosmeceutical applications. New formulations based on red grape pomace polyphenols and natural deep eutectic solvents (NaDESs) were here investigated, namely betaine combined with citric acid (BET-CA), urea (BET-U) and ethylene glycol (BET-EG), in which DESs were used both as extracting and carrying agents for polyphenols. The flavonoid profile determined by HPLC-MS/MS analysis showed similar malvidin content (51\u201356 \ub5g mL 121 ) in the DES combinations, while BET-CA gave the best permeation performance in Franz cells, so it was further investigated in 3D human keratinocytes (HaCat spheroids) injured with the pro-oxidant agent menadione. BET-CA treatment showed good intracellular antioxidant activity (IC50 0.15 \ub1 0.02 \ub5g mL 121 in malvidin content) and significantly decreased (p < 0.001) the release of the pro-inflammatory cytokine IL-8, improving cell viability. Thus, BET-CA formulation is worthy of investigation for potential use as a cosmetic ingredient to reduce oxidative stress and inflammation, which are causes of skin aging

Algoritmo computacional para determinar o perfil mínimo de marcadores moleculares que discriminam um conjunto de cultivares.

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Critical accident scenarios for cyclists and how they can be addressed through ITS solutions

It is recognised that ITS applications have been relatively successful in improving road safety primarily through technology applications the vehicle and infrastructure. However, Vulnerable Road Users (VRUs) have not received as much benefit as other road users. The EC-funded VRUITS project places the VRU road user at the centre, assesses the impact of current and upcoming ITS applications on the safety and mobility of VRUs, identifies how the usability and efficiency of ITS applications can be improved and recommends which actions have to be taken at a policy level to improve ITS safety and mobility. A major focus of the VRUITS project involves the safety of cyclists within the EU as a target VRU group. To provide the evidence-base for ITS applications, data were analysed to determine critical scenarios for cyclists and these data included national data in Spain, Austria, Finland, Sweden and the United Kingdom. This analysis was matched to analysis of the European CARE data to determine the consistency between the national and European databases. The main findings from the data analysis are as follows; • The majority of cycling accidents in the accident analysis were found to occur at junctions/intersections. • One of the most common scenarios involved vehicles pulling out into the path of the oncoming cyclist at an intersection • CARE data suggests that the most common scenario involves both cyclist and vehicle heading in the same direction but the vehicle then turns into the cyclist’s path • Overall, males are over-represented in the data. • The majority of the accidents occur in fine dry weather during daylight hours • The majority occur in urban areas at relatively on roads with relatively low speed limits Data from this phase of the VRUITS project will be used to determine the ITS solutions that are relevant to the scenarios determined through accident analysis. Subsequent phases of the project will look at the feasibility of implementation of theses countermeasures which is likely to include some pilot testing of specific applications