Proteomic Analysis Identifies Molecular Players and Biological Processes Specific to SARS-CoV-2 Exposure in Endothelial Cells

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been responsible for the severe pandemic of acute respiratory disease, coronavirus disease 2019 (COVID-19), experienced in the 21st century. The clinical manifestations range from mild symptoms to abnormal blood coagulation and severe respiratory failure. In severe cases, COVID-19 manifests as a thromboinflammatory disease. Damage to the vascular compartment caused by SARS-CoV-2 has been linked to thrombosis, triggered by an enhanced immune response. The molecular mechanisms underlying endothelial activation have not been fully elucidated. We aimed to identify the proteins correlated to the molecular response of human umbilical vein endothelial cells (HUVECs) after exposure to SARS-CoV-2, which might help to unravel the molecular mechanisms of endothelium activation in COVID-19. In this direction, we exposed HUVECs to SARS-CoV-2 and analyzed the expression of specific cellular receptors, and changes in the proteome of HUVECs at different time points. We identified that HUVECs exhibit non-productive infection without cytopathic effects, in addition to the lack of expression of specific cell receptors known to be essential for SARS-CoV-2 entry into cells. We highlighted the enrichment of the protein SUMOylation pathway and the increase in SUMO2, which was confirmed by orthogonal assays. In conclusion, proteomic analysis revealed that the exposure to SARS-CoV-2 induced oxidative stress and changes in protein abundance and pathways enrichment that resembled endothelial dysfunction.     

Targeting PSEN1 by lnc-CYP3A43-2/miR-29b-2-5p to Reduce β Amyloid Plaque Formation and Improve Cognition Function

Presenilin-1 (PSEN1) is a crucial subunit within the γ-secretase complex and regulates β-amyloid (Aβ) production. Accumulated evidence indicates that n-butylidenephthalide (BP) acts effectively to reduce Aβ levels in neuronal cells that are derived from trisomy 21 (Ts21) induced pluripotent stem cells (iPSCs). However, the mechanism underlying this effect remains unclear. This article aims to investigate the possible mechanisms through which BP ameliorates the development of Alzheimer’s disease (AD) and verify the effectiveness of BP through animal experiments. Results from RNA microarray analysis showed that BP treatment in Ts21 iPSC-derived neuronal cells reduced long noncoding RNA (lncRNA) CYP3A43-2 levels and increased microRNA (miR)-29b-2-5p levels. Bioinformatics tool prediction analysis, biotin-labeled miR-29b-2-5p pull-down assay, and dual-luciferase reporter assay confirmed a direct negative regulatory effect for miRNA29b-2-5p on lnc-RNA-CYP3A43-2 and PSEN1. Moreover, BP administration improved short-term memory and significantly reduced Aβ accumulation in the hippocampus and cortex of 3xTg-AD mice but failed in miR-29b-2-5p mutant mice generated by CRISP/Cas9 technology. In addition, analysis of brain samples from patients with AD showed a decrease in microRNA-29b-2-5p expression in the frontal cortex region. Our results provide evidence that the LncCYP3A43-2/miR29-2-5p/PSEN1 network might be involved in the molecular mechanisms underlying BP-induced Aβ reduction.     

The Flavonol Quercitrin Hinders GSK3 Activity and Potentiates the Wnt/β-Catenin Signaling Pathway

The Wnt/β-catenin signaling pathway dictates cell proliferation and differentiation during embryonic development and tissue homeostasis. Its deregulation is associated with many pathological conditions, including neurodegenerative disease, frequently downregulated. The lack of efficient treatment for these diseases, including Alzheimer’s disease (AD), makes Wnt signaling an attractive target for therapies. Interestingly, novel Wnt signaling activating compounds are less frequently described than inhibitors, turning the quest for novel positive modulators even more appealing. In that sense, natural compounds are an outstanding source of potential drug leads. Here, we combine different experimental models, cell-based approaches, neuronal culture assays, and rodent behavior tests with Xenopus laevis phenotypic analysis to characterize quercitrin, a natural compound, as a novel Wnt signaling potentiator. We find that quercitrin potentiates the signaling in a concentration-dependent manner and increases the occurrence of the Xenopus secondary axis phenotype mediated by Xwnt8 injection. Using a GSK3 biosensor, we describe that quercitrin impairs GSK3 activity and increases phosphorylated GSK3β S9 levels. Treatment with XAV939, an inhibitor downstream of GSK3, impairs the quercitrin-mediated effect. Next, we show that quercitrin potentiates the Wnt3a-synaptogenic effect in hippocampal neurons in culture, which is blocked by XAV939. Quercitrin treatment also rescues the hippocampal synapse loss induced by intracerebroventricular injection of amyloid-β oligomers (AβO) in mice. Finally, quercitrin rescues AβO-mediated memory impairment, which is prevented by XAV939. Thus, our study uncovers a novel function for quercitrin as a Wnt/β-catenin signaling potentiator, describes its mechanism of action, and opens new avenues for AD treatments.     

Models and Simulations for Portfolio Rebalancing

In 1950 Markowitz first formalized the portfolio optimization problem in terms of mean return and variance. Since then, the mean-variance model has played a crucial role in single-period portfolio optimization theory and practice. In this paper we study the optimal portfolio selection problem in a multi-period framework, by considering fixed and proportional transaction costs and evaluating how much they affect a re-investment strategy. Specifically, we modify the single-period portfolio optimization model, based on the Conditional Value at Risk (CVaR) as measure of risk, to introduce portfolio rebalancing. The aim is to provide investors and financial institutions with an effective tool to better exploit new information made available by the market. We then suggest a procedure to use the proposed optimization model in a multi-period framework. Extensive computational results based on different historical data sets from German Stock Exchange Market (XETRA) are presented.     

Software reuse: The Brazilian industry scenario

This paper aims at identifying some of the key factors in adopting an organization-wide software reuse program. The factors are derived from practical experience reported by industry professionals, through a survey involving 57 Brazilian small, medium and large software organizations. Some of them produce software with commonality between applications, and have mature processes, while others successfully achieved reuse through isolated, ad hoc efforts. The paper compiles the answers from the survey participants, showing which factors were more associated with reuse success. Based on this relationship, a guide is presented, pointing out which factors should be more strongly considered by small, medium and large organizations attempting to establish a reuse program.     

Isolation and partial characterization of a lectin from Artocarpus incisa L. seeds

A lectin was isolated from the saline extract of Artocarpus incisa seed by affinity chromatography on cross-linked Adenanthera pavonina galactomannan in 0.15 M NaCl. The lectin was also retained in a D-gal-agarose resin and had no requirements for divalent metal cations (Ca2+ and Mn2+) for activity. The lectin contains 2.1% of carbohydrate and is characterized by high contents of acidic and hydroxylated amino acids. The lectin presented two protein bands in SDS-PAGE, with M(r) 15.5 and 12 kDa, respectively, and contains no alpha-helix, 64% antiparallel beta-sheet and 21% parallel beta-sheet/beta-turn. When submitted to gel filtration in Superose 12 R (FPLC) and Superdex 75 HR 5/5 (HPLC) columns, the lectin showed an M(r) of 48-49 kDa, suggesting a tetrameric structure.     

Heterogeneity of V2O5(010) surfaces – the role of alkali metal dopants

Any solid oxide-originated catalyst is extremely heterogeneous due to several factors. First, it may consist of various phases, each exposing different surfaces characterized by different electronic, and thus catalytic, properties. However, even a particular surface of a chosen phase is heterogeneous as it consists of different chemical elements connected in polyhedra bonded with each other via corners and/or edges and/or walls. In addition, dopants and supports change properties of the surface by enriching its heterogeneity. In the following, the role of dopants as potential sources of surface heterogeneity is discussed, using vanadia as an example.     

Detection of GMO in food products in Brazil: the INCQS experience

Regulations for the use and labeling of genetically modified organism products and derived ingredients are being implemented worldwide, what demands reliable and accurate methods to detect genetically modified organisms (GMO) in raw materials and food products. This study aimed at monitoring products derived from GMO in the Brazilian market using detection methods for the presence of Roundup Ready soybean, Bt176 and MON 810 maize. The results demonstrate for the first time the presence of GM-soy in Brazilian food products, reinforcing the need for the development of accurate quantitative methods in routine analyses.     

Inhibition by diazepam of the effect of additional training and of extinction on the retention of shuttle avoidance behavior in rats.

Rats were submitted to a training and a test session in a shuttle avoidance task. In some groups, a second training session was interpolated 2 or 24 hr after the first session. In others, a session of extinction was interpolated 2 or 24 hr after the training session. When the interpolated task was 2 hr after training, training-test interval was 24 hr. When the interpolated task was 24 hr after training, training-test interval was 48 hr. The additional training enhanced, and the extinction depressed, retention test performance. Diazepam, given 30 min prior to the first (or only) training session enhanced the performance of avoidance responses in that session but inhibited it in the subsequent retention test. Diazepam given 90 min after training had no effect on retention. Diazepam given 30 min prior to either the additional training session or the extinction session did not affect performance in that session but canceled their effects on retention test performance. The effects are related to the previously described prevention by diazepam of interfering effects on memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

High exposure to arsenic from drinking water at several localities in eastern Croatia

This study investigated the relationship between arsenic concentrations in drinking water in four towns/villages in eastern Croatia and corresponding hair arsenic concentrations of residents. The mean arsenic concentrations in community drinking water samples were 0.14, 37.88, 171.60, and 611.89 microg/l. The corresponding mean concentrations of the element in hair samples of subjects residing in each of the localities were 0.07 (n=11), 0.26 (n=17), 1.74 (n=11), and 4.31 microg/g (n=23). Chronic exposures to arsenic levels estimated in three investigated locations could present a serious health threat to around 3% of Croatian population.