95 research outputs found

    Effect of the Soil Organic Content on Slurries Involved in Mudflows

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    AbstractThe effect of the soil organic content on the stability of a soil involved in a rapid mud flow is here experimentally investigated. The soil is collected form a site where a catastrophic landslide took place (Cervinara – AV) and it is chemically treated to selectively remove different aliquots of its original organic carbon. In particular, The Dissolved Organic Carbon (i.e. the carbon soluble in water)results the 6% of the soil organic carbon and it is removed with a mild chemical treatment to obtain the DOC 6 sample, the 77% and 89% of the Total Organic Carbon (i.e.the pool of oxidizable soil organic carbon)is removed with a strong chemical treatment to obtain the TOC 77 and TOC 89 sample, respectively. The stabilizing effect of the organic carbon is investigated by following the evolution of the particle size distribution of soils induced by a mild mixing of diluted slurries and we showed that the particle size distribution of the original soil sample is unaffected by the slurry mixing, while those of DOC 6,TOC 77 and TOC 89 evolve during time, revealing the breakup of soil aggregates. Our findings highlight the stabilizing effect of SOC in the investigated liquid slurries and, furthermore, they suggest that the organic carbon quality, more than its quantity, plays a crucial role in the soil stability. Indeed, it is enough to remove the Dissolved Organic Carbon to register a soil disaggregation process comparable to that observed for TOC 77 and TOC 89 samples. This suggests that Dissolved Organic Carbon is the fundamental organic fraction stabilizing the slurry microstructure

    The microstructural change causing the failure of the Cox-Merz rule in Newtonian suspensions: experiments and simulations

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    Newtonian non-Brownian concentrated suspensions show a mismatch between the steady state and the complex viscosity, whatever the strain amplitude imposed in the oscillatory flow. This result is counterintuitive in the two extreme cases of vanishing strain amplitude and very large one. In the first case, the oscillatory flow should not be able to alter the steady microstructure, as well as in the other opposite limit for which the strain amplitude is so high that the oscillatory flow resembles a steady flow reversal. If the microstructure is not altered with respect to the steady one, similarly the complex viscosity should be equal to the steady one. We here investigate experimentally and numerically the origin of the viscosities mismatch at any imposed strain amplitude. We focus on the first two or three cycles of oscillations and different particle concentrations. Experimental and numerical results agree and allow to prove that for intermediate amplitudes, the oscillatory shear induces the breakage of particle clusters and the microstructure modifies so to minimise particle collisions. For very small strain amplitudes, the oscillatory shear only induces the rotation of few couples of touching particles and the complex viscosity results slightly smaller than the steady one, while for very large strains, the oscillatory flow reshuffles the particles inducing a microstructure as clustered as the steady state one but with a different angular distribution function. We show that the vast majority of the microstructure rearrangement takes place in the first half cycle of oscillation

    An Extract from Ficus carica Cell Cultures Works as an Anti-Stress Ingredient for the Skin

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    Psychological stress activates catecholamine production, determines oxidation processes, and alters the lipid barrier functions in the skin. Scientific evidence associated with the detoxifying effect of fruits and vegetables, the growing awareness of the long-term issues related to the use of chemical-filled cosmetics, the aging of the population, and the increase in living standards are the factors responsible for the growth of food-derived ingredients in the cosmetics market. A Ficus carica cell suspension culture extract (FcHEx) was tested in vitro (on keratinocytes cells) and in vivo to evaluate its ability to manage the stress-hormone-induced damage in skin. The FcHEx reduced the epinephrine (−43% and −24% at the concentrations of 0.002% and 0.006%, respectively), interleukin 6 (−38% and −36% at the concentrations of 0.002% and 0.006%, respectively), lipid peroxide (−25%), and protein carbonylation (−50%) productions; FcHEx also induced ceramide synthesis (+150%) and ameliorated the lipid barrier performance. The in vivo experiments confirmed the in vitro test results. Transepidermal water loss (TEWL; −12.2%), sebum flow (−46.6% after two weeks and −73.8% after four weeks; on the forehead −56.4% after two weeks and −80.1% after four weeks), and skin lightness (+1.9% after two weeks and +2.7% after four weeks) defined the extract’s effects on the skin barrier. The extract of the Ficus carica cell suspension cultures reduced the transepidermal water loss, the sebum production, the desquamation, and facial skin turning to a pale color from acute stress, suggesting its role as an ingredient to fight the signs of psychological stress in the skin

    Characterisation of the immune-related transcriptome in resected biliary tract cancers

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    Although biliary tract cancers (BTCs) are known to have an inflammatory component, a detailed characterisation of immune-related transcripts has never been performed. In these studies, nCounter PanCancer Immune Profiling Panel was used to assess the expression of 770 immune-related transcripts in the tumour tissues (TTs) and matched adjacent tissues (ATs) of resected BTCs. Cox regression analysis and Kaplan-Meier methods were used to correlate findings with relapse-free survival (RFS). The first analysis in the TT and AT of an exploratory set (n = 22) showed deregulation of 39 transcripts associated with T-cell activation. Risk of recurrence was associated with a greater number of genes deregulated in AT in comparison to TT. Analysis in the whole set (n = 53) showed a correlation between AT cytotoxic T-lymphocyte antigen-4 (CTLA4) expression and RFS, which maintained statistical significance at multivariate analysis. CTLA4 expression correlated with forkhead box P3 (FOXP3) expression, suggesting enrichment in T regulatory cells. CTLA4 is known to act by binding to the cluster of differentiation 80 (CD80). No association was seen between AT CD80 expression and RFS. However, CD80 expression differentiated prognosis in patients who received adjuvant chemotherapy. We showed that the immunomodulatory transcriptome is deregulated in resected BTCs. Our study includes a small number of patients and does not enable to draw definitive conclusions; however, it provides useful insights into potential transcripts that may deserve further investigation in larger cohorts of patients. TRANSCRIPT PROFILING: Nanostring data have been submitted to GEO repository: GSE90698 and GSE906

    A novel RAB39B mutation and concurrent de novo NF1 mutation in a boy with neurofibromatosis type 1, intellectual disability, and autism: a case report

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    Background Mutations in RAB39B at Xq28 causes a rare form of X-linked intellectual disability (ID) and Parkinson’s disease. Neurofibromatosis type 1 (NF1) is caused by heterozygous mutations in NF1 occurring de novo in about 50% of cases, usually due to paternal gonadal mutations. This case report describes clinical and genetic findings in a boy with the occurrence of two distinct causative mutations in NF1 and RAB39B explaining the observed phenotype. Case presentation Here we report a 7-year-old boy with multiple café-au-lait macules (CALMs) and freckling, severe macrocephaly, peculiar facial gestalt, severe ID with absent speech, epilepsy, autistic traits, self-harming, and aggressiveness. Proband is an only child born to a father aged 47. Parents did not present signs of NF1, while a maternal uncle showed severe ID, epilepsy, and tremors.By RNA analysis of NF1, we identified a de novo splicing variant (NM_000267.3:c.6579+2T>C) in proband, which explained NF1 clinical features but not the severe ID, behavioral problems, and aggressiveness. Family history suggested an X-linked condition and massively parallel sequencing of X-exome identified a novel RAB39B mutation (NM_171998.2:c.436_447del) in proband, his mother, and affected maternal uncle, subsequently validated by Sanger sequencing in these and other family members. Conclusions The case presented here highlights how concurrent genetic defects should be considered in NF1 patients when NF1 mutations cannot reasonably explain all the observed clinical features

    Analisi fitochimica e attività biologica in vitro di <i>Minthostachys setosa</i> (Biq. Epling.)

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    Il nostro studio si è basato sulla caratterizzazione fitochimica dell’olio essenziale e dei vari estratti ottenibili dalla Minthostachys setosa non trascurando la loro attività antibatterica e antifunginea sia su patogeni umani che vegetali per trovare conferma scientifica dell’uso fatto dalle popolazioni andine sia come antisettico sia come conservante di derrate alimentari

    Mystery(n) Phenotypic Presentation in Europeans: Report of Three Further Novel Missense RNF213 Variants Leading to Severe Syndromic Forms of Moyamoya Angiopathy and Literature Review

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    Moyamoya angiopathy (MMA) is a rare cerebral vasculopathy in some cases occurring in children. Incidence is higher in East Asia, where the heterozygous p.Arg4810Lys variant in RNF213 (Mysterin) represents the major susceptibility factor. Rare variants in RNF213 have also been found in European MMA patients with incomplete penetrance and are today a recognized susceptibility factor for other cardiovascular disorders, from extracerebral artery stenosis to hypertension. By whole exome sequencing, we identified three rare and previously unreported missense variants of RNF213 in three children with early onset of bilateral MMA, and subsequently extended clinical and radiological investigations to their carrier relatives. Substitutions all involved highly conserved residues clustered in the C-terminal region of RNF213, mainly in the E3 ligase domain. Probands showed a de novo occurring variant, p.Phe4120Leu (family A), a maternally inherited heterozygous variant, p.Ser4118Cys (family B), and a novel heterozygous variant, p.Glu4867Lys, inherited from the mother, in whom it occurred de novo (family C). Patients from families A and C experienced transient hypertransaminasemia and stenosis of extracerebral arteries. Bilateral MMA was present in the proband's carrier grandfather from family B. The proband from family C and her carrier mother both exhibited annular figurate erythema. Our data confirm that rare heterozygous variants in RNF213 cause MMA in Europeans as well as in East Asian populations, suggesting that substitutions close to positions 4118-4122 and 4867 of RNF213 could lead to a syndromic form of MMA showing elevated aminotransferases and extracerebral vascular involvement, with the possible association of peculiar skin manifestations

    Identification of a Novel p53 Modulator Endowed with Antitumoural and Antibacterial Activity through a Scaffold Repurposing Approach

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    Intracellular pathogens, such as Chlamydia trachomatis, have been recently shown to induce degradation of p53 during infection, thus impairing the protective response of the host cells. Therefore, p53 reactivation by disruption of the p53-MDM2 complex could reduce infection and restore pro-apoptotic effect of p53. Here, we report the identification of a novel MDM2 inhibitor with potential antitumoural and antibacterial activity able to reactivate p53. A virtual screening was performed on an in-house chemical library, previously synthesised for other targets, and led to the identification of a hit compound with a benzo[a]dihydrocarbazole structure, RM37. This compound induced p53 up-regulation in U343MG glioblastoma cells by blocking MDM2-p53 interaction and reduced tumour cell growth. NMR studies confirmed its ability to dissociate the MDM2-p53 complex. Notably, RM37 reduced Chlamydia infection in HeLa cells in a concentration-dependent manner and ameliorated the inflammatory status associated with infection

    Apoptosis Therapy in Cancer: The First Single-molecule Co-activating p53 and the Translocator Protein in Glioblastoma

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    In the complex scenario of cancer, treatment with compounds targeting multiple cell pathways has been emerging. In Glioblastoma Multiforme (GBM), p53 and Translocator Protein (TSPO), both acting as apoptosis inducers, represent two attractive intracellular targets. On this basis, novel indolylglyoxylyldipeptides, rationally designed to activate TSPO and p53, were synthesized and biologically characterized. The new compounds were able to bind TSPO and to reactivate p53 functionality, through the dissociation from its physiological inhibitor, murine double minute 2 (MDM2). In GBM cells, the new molecules caused Δψm dissipation and inhibition of cell viability. These effects resulted significantly higher with respect to those elicited by the single target reference standards applied alone, and coherent with the synergism resulting from the simultaneous activation of TSPO and p53. Taken together, these results suggest that TSPO/MDM2 dual-target ligands could represent a new attractive multi-modal opportunity for anti-cancer strategy in GBM
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