The Polynomial Eigenvalue Problem is Well Conditioned for Random Inputs

We compute the exact expected value of the squared condition number for the polynomial eigenvalue problem, when the input matrices have entries coming from the standard complex Gaussian distribution, showing that in general this problem is quite well conditioned.The first author's work was partially supported by Agencia Nacional de Investigación e Innovación (ANII), Uruguay, and by CSIC group 618, Universidad de La República, Uruguay. The second author's work was partially supported by MTM2017-83816-P and MTM2017-90682-REDT from Spanish Ministry of Science MICINN and by 21.SI01.64658 from Universidad de Cantabria and Banco de Santander

Effect of injection molding conditions on crystalline structure and electrical resistivity of PP/MWCNT nanocomposites

Polypropylene (PP) / multi-walled carbon nanotube (MWCNT) nanocomposites were prepared by melt-mixing and used to manufacture samples by injection molding. The effect of processing conditions on the crystallinity and electrical resistivity was studied. Accordingly, samples were produced varying the mold temperature and injection rate, and the DC electrical resistivity was measured. The morphology of MWCNT clusters was studied by optical and electron microscopy, while X-ray diffraction was used to study the role of the crystalline structure of PP. As a result, an anisotropic electrical behavior induced by the process was observed, which is further influenced by the injection molding processing condition. It was demonstrated that a reduction of electrical resistivity can be obtained by increasing mold temperature and injection rate, which was associated to the formation of the γ-phase and the related inter-cluster morphology of the MWCNT conductive network

Phytochemical profile of capsicum annuum l. Cv senise, incorporation into liposomes, and evaluation of cellular antioxidant activity

Overproduction of oxidants in the human body is responsible for oxidative stress, which is associated with several diseases. High intake of vegetables and fruits can reduce the risk of chronic diseases, as they are sources of bioactive compounds capable of contrasting the free radical effects involved in cancer, obesity, diabetes, and neurodegenerative and cardiovascular diseases. Capsicum annuum L. cv Senise is a sweet pepper that is grown in the Basilicata region (Italy). It is an important source of polyphenols, carotenoids, and capsinoids and can play a key role in human health. In this study, an ethanol extract was obtained from C. annuum dried peppers and the analysis of the phytochemical composition was performed by LC-ESI/LTQ Orbitrap/MS. The extract was incorporated into liposomes, which showed small size (~80 nm), good homogeneity, negative surface charge, and good stability in storage. The biological activity of the extract was evaluated in the human hepatoma (HepG2) cell line, used as model cells. The extract showed no cytotoxic activity and reduced the intracellular reactive oxygen species (ROS) level in stressed cells. The antioxidant activity was further improved when the extract was loaded into liposomes. Moreover, the extract promoted the expression of endogenous antioxidants, such as catalase, superoxide dismutase, and glutathione peroxidase through the Nrf-2 pathway evaluated by RT-PCR

Morphology and electrical properties of injection-molded PP carbon-based nanocomposites

The aim of this work was to investigate the influence of the process condition on the morphology of PP/MWCNT nanocomposites and its effect on the electrical properties, experimentally developed in this study. Electrical and morphological characterization was performed in order to analyze the multilayered morphology skin-core-skin, validated by a theoretical model

New insights on the functional role of URG7 in the cellular response to ER stress.

BACKGROUND INFORMATION: Up-regulated Gene clone 7 (URG7) is an ER resident protein, whose expression is upregulated in the presence of hepatitis B virus X antigen (HBxAg) during HBV infection. In virus-infected hepatocytes, URG7 shows an anti-apoptotic activity due to the PI3K/AKT signaling activation, does not seem to have tumorigenic properties, but it appears to promote the development and progression of fibrosis. However, the molecular mechanisms underlying URG7 activity remain largely unknown. RESULTS: To shed light on URG7 activity, we first analyzed its interactome in HepG2 transfected cells: this analysis suggests that URG7 could have a role in affecting protein synthesis, folding and promoting proteins degradation. Moreover, keeping into account its subcellular localization in the ER and that several viral infections give rise to ER stress, a panel of experiments was performed to evaluate a putative role of URG7 in ER stress. Our main results demonstrate that in ER stressed cells URG7 is able to modulate the expression of Unfolded Protein Response (UPR) markers toward survival outcomes, upregulating GRP78 protein and downregulating the pro-apoptotic protein CHOP. Furthermore, URG7 reduces the ER stress by decreasing the amount of unfolded proteins, by increasing both the total protein ubiquitination and the AKT activation and reducing caspase 3 activation. CONCLUSIONS: All together these data suggest that URG7 plays a pivotal role as a reliever of ER stress-induced apoptosis. SIGNIFICANCE: This is the first characterization of URG7 activity under ER stress conditions. The results presented here will help to hypothesize new strategies to counteract the antiapoptotic activity of URG7 in the context of the viral infection. This article is protected by copyright. All rights reserved

Two novel precursors of the hiv-1 protease inhibitor darunavir target the UPR/proteasome system in human hepatocellular carcinoma cell line HepG2

Background: Several pre-clinical and clinical reports suggest that HIV-1 protease inhibitors, in addition to the antiretroviral properties, possess pleiotropic pharmacological effects including anti-cancer action. Therefore, we investigated the pro-apoptotic activity in tumor cells of two molecules, RDD-19 and RDD-142, which are hydroxyethylamine derivatives’ precursors of darunavir and several HIV-1 protease inhibitors. Methods: Three hepatoma cell lines and one non-pathological cell line were treated with RDD-19 and RDD-142, and cell viability was assessed. The expression levels of several markers for ER stress, autophagy, cellular ubiquitination, and Akt activation were quantified in HepG2 cells treated with RDD-19 and RDD-142 to evaluate apoptotic and non-apoptotic cell death. Results: RDD-19 and RDD-142 showed a greater dose-dependent cytotoxicity towards the hepatic tumor cell line HepG2 compared to the non-pathological hepatic cell line IHH. Both molecules caused two types of cell death, a caspase-dependent apoptosis, which was ascertained by a series of biochemical and morphological assays, and a caspase-independent death that was characterized by the induction of ER stress and autophagy. The strong increase of ubiquitinated proteins inside the cells suggested that the target of these molecules could be the proteasome and in silico molecular docking analysis that was used to support the plausibility of this hypothesis. Furthermore, cells treated with the two compounds displayed decreased levels of p-AKT, which interferes with cell survival and proliferation. Conclusions: These findings demonstrate that two compounds, RDD-19 and RDD-142, have pleiotropic effects and that they may represent promising anticancer candidates

Quiescent neuronal progenitors are activated in the juvenile guinea pig lateral striatum and give rise to transient neurons

In the adult brain, active stem cells are a subset of astrocytes residing in the subventricular zone (SVZ) and the dentate gyrus (DG) of the hippocampus. Whether quiescent neuronal progenitors occur in other brain regions is unclear. Here, we describe a novel neurogenic system in the external capsule and lateral striatum (EC-LS) of the juvenile guinea pig that is quiescent at birth but becomes active around weaning. Activation of neurogenesis in this region was accompanied by the emergence of a neurogenic-like niche in the ventral EC characterized by chains of neuroblasts, intermediate-like progenitors and glial cells expressing markers of immature astrocytes. Like neurogenic astrocytes of the SVZ and DG, these latter cells showed a slow rate of proliferation and retained BrdU labeling for up to 65 days, suggesting that they are the primary progenitors of the EC-LS neurogenic system. Injections of GFPtagged lentiviral vectors into the SVZ and the EC-LS of newborn animals confirmed that new LS neuroblasts originate from the activation of local progenitors and further supported their astroglial nature. Newborn EC-LS neurons existed transiently and did not contribute to neuronal addition or replacement. Nevertheless, they expressed Sp8 and showed strong tropism for white matter tracts, wherein they acquired complex morphologies. For these reasons, we propose that EC-LS neuroblasts represent a novel striatal cell type, possibly related to those populations of transient interneurons that regulate the development of fiber tracts during embryonic life

Dysbiosis triggers ACF development in genetically predisposed subjects

Background: Colorectal cancer (CRC) is the third most common cancer worldwide, characterized by a multifactorial etiology including genetics, lifestyle, and environmental factors including microbiota composition. To address the role of microbial modulation in CRC, we used our recently established mouse model (theWinnie-APCMin/+) combining inflammation and genetics. Methods: Gut microbiota profiling was performed on 8-week-old Winnie-APCMin/++ mice and their littermates by 16S rDNA gene amplicon sequencing. Moreover, to study the impact of dysbiosis induced by the mother’s genetics in ACF development, the large intestines of APCMin/++ mice born from wild type mice were investigated by histological analysis at 8 weeks. Results: ACF development in 8-week-old Winnie-APCMin/++ mice was triggered by dysbiosis. Specifically, the onset of ACF in genetically predisposed mice may result from dysbiotic signatures in the gastrointestinal tract of the breeders. Additionally, fecal transplant from Winnie donors to APCMin/++ hosts leads to an increased rate of ACF development. Conclusions: The characterization of microbiota profiling supporting CRC development in genetically predisposed mice could help to design therapeutic strategies to prevent dysbiosis. The application of these strategies in mothers during pregnancy and lactation could also reduce the CRC risk in the offspring