Metabolomics applications in children: A right way to go

Metabolomics is a new science based on the study of the metabolome, representing the set of all the metabolites of a biological organism, which are the final products of its gene expression. Metabolomics appears to be a promising tool in perinatal studies, such as hypoxic–ischemic encephalopathy (HIE), intrauterine growth restriction (IUGR), congenital infections, genetic diseases, neonatal nutrition

The difficult alliance between vegan parents and pediatrician: A case report

The number of children on a vegetarian or vegan diet is gradually increasing. If not balanced and adequately supplemented, these dietary regimes can seriously impact the growth of children. Often the pediatrician is not perceived as a figure to rely on in the event of parents’ willingness to follow an alternative diet for their child. The feeling of distrust of parents towards the pediatrician can be dangerous for the health of the child. We present a 22-month-old boy with failure to thrive probably induced by an unbalanced vegetarian diet. The acquisition of the anamnestic data concerning the child’s diet was difficult because initially omitted by the parents. The poor compliance and the difficult follow-up highlights the difficulty in establishing a therapeutic alliance between parents who follow alternative regimens and the pediatrician

Exploring the role of fallopian ciliated cells in the pathogenesis of high-grade serous ovarian cancer

High-grade serous epithelial ovarian cancer (HGSOC) is the fifth leading cause of cancer death in women and the first among gynecological malignancies. Despite an initial response to standard chemotherapy, most HGSOC patients relapse. To improve treatment options, we must continue investigating tumor biology. Tumor characteristics (e.g., risk factors and epidemiology) are valuable clues to accomplish this task. The two most frequent risk factors for HGSOC are the lifetime number of ovulations, which is associated with increased oxidative stress in the pelvic area caused by ovulation fluid, and a positive family history due to genetic factors. In the attempt to identify novel genetic factors (i.e., genes) associated with HGSOC, we observed that several genes in linkage with HGSOC are expressed in the ciliated cells of the fallopian tube. This finding made us hypothesize that ciliated cells, despite not being the cell of origin for HGSOC, may take part in HGSOC tumor initiation. Specifically, malfunction of the ciliary beat impairs the laminar fluid flow above the fallopian tube epithelia, thus likely reducing the clearance of oxidative stress caused by follicular fluid. Herein, we review the up-to-date findings dealing with HGSOC predisposition with the hypothesis that fallopian ciliated cells take part in HGSOC onset. Finally, we review the up-to-date literature concerning genes that are located in genomic loci associated with epithelial ovarian cancer (EOC) predisposition that are expressed by the fallopian ciliated cells

Multiple hazards and risk perceptions over time: the availability heuristic in Italy and Sweden under COVID-19

The severe impact of global crises, such as COVID-19 and climate change, is plausibly reshaping the way in which people perceive risks. In this paper, we examine and compare how global crises and local disasters influence public perceptions of multiple hazards in Italy and Sweden. To this end, we integrate information about the occurrence of hazardous events with the results of two nationwide surveys. These included more than 4000 participants and were conducted in two different phases of the COVID-19 pandemic corresponding to low (August 2020) and high (November 2020) levels of infection rates. We found that, in both countries, people are more worried about risks related to experienced events. This is in line with the cognitive process known as the availability heuristic: individuals assess the risk associated with a given hazard based on how easily it comes to their mind. Epidemics, for example, are perceived as less likely and more impactful in Italy compared to Sweden. This outcome can be explained by cross-country differences in the impact of, as well as governmental responses to, COVID-19. Notwithstanding the ongoing pandemic, people in both Italy and Sweden are highly concerned about climate change, and they rank it as the most likely threat

Evidence of a pressure-induced metallization process in monoclinic VO2_2

Raman and combined trasmission and reflectivity mid infrared measurements have been carried out on monoclinic VO$_2$ at room temperature over the 0-19 GPa and 0-14 GPa pressure ranges, respectively. The pressure dependence obtained for both lattice dynamics and optical gap shows a remarkable stability of the system up to P*$\sim$10 GPa. Evidence of subtle modifications of V ion arrangements within the monoclinic lattice together with the onset of a metallization process via band gap filling are observed for P$>$P*. Differently from ambient pressure, where the VO$_2$ metal phase is found only in conjunction with the rutile structure above 340 K, a new room temperature metallic phase coupled to a monoclinic structure appears accessible in the high pressure regime, thus opening to new important queries on the physics of VO$_2$.Comment: 5 pages, 3 figure

Regulation of NFKB through the nuclear processing of p105 (NFKB1) in Epstein-Barr Virus immortalized B cell lines.

Transcription factors of the NF-κB/Rel family are retained in the cytoplasm as inactive complexes through association with IκB inhibitory proteins. Several NF-κB activators induce the proteolysis of IκB proteins, which results in the nuclear translocation and DNA binding of NF-κB complexes. Here, we report a novel mechanism of NF-κB regulation mediated by p105 (NF-κB1) precursor of p50 directly at the nuclear level. In Epstein- Barr virus-immortalized B cells, p105 was found in the nucleus, where it was complexed with p65. In concomitance with NF-κB activation, mitomycin C induced the processing of p105 to p50 in the nucleus, while it did not affect the steady-state protein levels of IκBα and p105 in the cytoplasm. Differently, phorbol 12-myristate 13-acetate induced a significant proteolysis of both IκBα and p105 in the cytoplasm, while it did not affect the protein level of p105 in the nucleus. These results suggest that in Epstein-Barr virus-positive B cell lines the nuclear processing of p105 can contribute to NF-κB activation in response to specific signaling molecules, such as DNA-damaging agents

Electrodynamics near the Metal-to-Insulator Transition in V3O5

The electrodynamics near the metal-to-insulator transitions (MIT) induced, in V3O5 single crystals, by both temperature (T) and pressure (P) has been studied by infrared spectroscopy. The T- and P-dependence of the optical conductivity may be explained within a polaronic scenario. The insulating phase at ambient T and P corresponds to strongly localized small polarons. Meanwhile the T-induced metallic phase at ambient pressure is related to a liquid of polarons showing incoherent dc transport, in the P-induced metallic phase at room T strongly localized polarons coexist with partially delocalized ones. The electronic spectral weight is almost recovered, in both the T and P induced metallization processes, on an energy scale of 1 eV, thus supporting the key-role of electron-lattice interaction in the V3O5 metal-to-insulator transition.Comment: 7 pages, 5 figure

Ground truth deficiencies in software engineering: when codifying the past can be counterproductive

Many software engineering tools build and evaluate their models based on historical data to support development and process decisions. These models help us answer numerous interesting questions, but have their own caveats. In a real-life setting, the objective function of human decision-makers for a given task might be influenced by a whole host of factors that stem from their cognitive biases, subverting the ideal objective function required for an optimally functioning system. Relying on this data as ground truth may give rise to systems that end up automating software engineering decisions by mimicking past sub-optimal behaviour. We illustrate this phenomenon and suggest mitigation strategies to raise awareness

An NF-kB site in the 5'-untraslated leader region of the Human Immunodeficiency virus type 1 enhances the viral expression in response to NF-kB-activating stimuli.

The 5'-untranslated leader region of human immunodeficiency virus, type 1 (HIV-1), includes a complex array of putative regulatory elements whose role in the viral expression is not completely understood. Here we demonstrate the presence of an NF-κB-responsive element in the trans- activation response (TAR) region of HIV-1 that confers the full induction of HIV-1 long terminal repeat (LTR) in response to NF-κB-activating stimuli, such as DNA alkylating agents, phorbol 12-myristate 13-acetate, and tumor necrosis factor-α. The TAR NF-κB site GGGAGCTCTC spans from positions +31 to +40 and cooperates with the NF-κB enhancer upstream of the TATA box in the NF-κB-mediated induction of HIV-1 LTR. The conclusion stems from the following observations: (i) deletion of the two NF-κB sites upstream of the TATA box reduces, but does not abolish, the HIV-1 LTR activation by NF-κB inducers; (ii) deletion or base pair substitutions of the TAR NF-κB site significantly reduce the HIV-1 LTR activation by NF-κB inducers; (iii) deletions of both the NF-κB sites upstream of the TATA box and the TAR NF- κB site abolish the activation of HIV-1 LTR in response to NF-κB inducers. Moreover, the p50·p65 NF-κB complex binds to the TAR NF-κB sequence and trans-activates the TAR NF-κB-directed expression. The identification of an additional NF-κB site in the HIV-1 LTR points to the relevance of NF-κB factors in the HIV-1 life cycle

Protein-Kinase-C inhibitors and gemfibrozil prevent the enhancing effect of very low density lipoproteins on the biosynthesis of plasminogen activator inhibitor type 1 by HepG2 cells

Triglyceride-rich lipoproteins (VLDL) have been previously shown to enhance the biosynthesis of plasminogen activator inhibitor type 1 (PAl-1) by HepG2 cells. This study was undertaken to assess whether the effect of VLDL on PAI-1 antigen and mRNA induction could be by protein kinase C (PKC) signaling pathway. To this end confluent HepG2 cells were first incubated for 16 h with VLDL isolated from normal donors, at the 100 \ub5g/ml concentration with or without inhibitors of PKC. At the end of incubation PAI-1 antigen released in the conditioned medium was determined by ELISA and PAI-1 mRNA expression was assessed by Northern analysis. Exposure of HepG2 cells to 100 \ub5g/ml VLDL resulted in a twofold increase in PAI-1 antigen release and total PAI-1 mRNA expression. H7 (50 11M) and sphingosine (3-5 \ub5M) almost completely prevented (> 80%) the effect of VLDL on PAI-1 antigen release and total PAI-1 mRNA accumulation. In addition down regulation of PKC, obtained by preincubation of HepG2 cells with PMA (100 nM) for 24h, prevented the effect of VLDL on PAI-1 biosynthesis. Established that the effect of VLDL on PAI-1 biosynthesis was mediated by activation of PKC signaling pathway we evaluated whether fibric acid derivatives influenced PAI-1 biosynthesis in unstimulated HepG2 cells and in cells exposed to VLDL. In unstimulated HepG2 cells, Gemfibrozil (0.1-0.75 mM) significantly reduced PAI-1 antigen release (-85% at the 0.75 mM concentration) and mRNA expression, whereas Bezafibrate at the highest concentration used (1 mM) reduced PAI-1 antigen release by 20%, with no effect on PAI-1 mRNA expression. In VLDL treated cells, only Gemfibrozil, at the 0 .75 mM concentration, attenuated (-50%) the biosynthesis of PAI-1 as induced by VLDL (100 \ub5g/ml) . It is concluded that VLDL enhance PAI-1 biosynthesis through activation of PKC and that Gemfibrozil, but not Bezafibrate, attenuates PAI-1 induction in these cells