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To date the coronavirus family is composed of seven different viruses which were commonly known as cold viruses until the appearance of the severe acute respiratory coronavirus (SARS-CoV) in 2002, the middle east respiratory syndrome coronavirus (MERS) in 2012 and the severe acute respiratory coronavirus 2 (SARS-CoV-2) which caused the COVID-19 global pandemic in 2019. Using bioinformatic approaches we tested the potential interactions of human miRNAs, expressed in pulmonary epithelial cells, with the available coronavirus genomes. Putative miRNA binding sites were then compared between pathogenic and non pathogenic virus groups. The pathogenic group shares 6 miRNA binding sites that can be potentially involved in the sequestration of miRNAs already known to be associated with deep vein thrombosis. We then analysed ∼100k SARS-CoV-2 variant genomes for their potential interaction with human miRNAs and this study highlighted a group of 97 miRNA binding sites which is present in all the analysed genomes. Among these, we identified 6 miRNA binding sites specific for SARS-CoV-2 and the other two pathogenic viruses whose down-regulation has been seen associated with deep vein thrombosis and cardiovascular diseases. Interestingly, one of these miRNAs, namely miR-20a-5p, whose expression decreases with advancing age, is involved in cytokine signaling, cell differentiation and/or proliferation. We hypothesize that depletion of poorly expressed miRNA could be related with disease severity.

Background The decision whether to perform endoscopy in children with suspected reflux oesophagitis is not a straightforward one. Few symptoms are specific for oesophagitis and the diagnosis is not always correlated even to visual findings on endoscopy. Aim The aim of this study was to define the role of endoscopy and especially of histology in the diagnosis of reflux oesophagitis and to examine the correlations between symptoms, endoscopic findings and histology in children with suspected gastroesophageal reflux disease. Patients and methods One hundred and thirty-six patients with a clinical diagnosis of reflux oesophagitis, aged 1–18 years (mean 8.43; standard deviation ±4.4), were enrolled from 12 Italian Paediatrics Gastroenterology Centres; symptom score, endoscopic and histologic oesophagitis scores were observed before and after therapy with proton pump inhibitors. Results Before therapy, a high correlation between the prevailing symptom score and endoscopic score was demonstrated, but not with histologic score: there was a significant tendency for histologic grade to exceed visual findings. After therapy, endoscopic score and histologic score were significantly improved. Conclusions Oesophageal biopsies increase the diagnostic accuracy of upper endoscopy. Histologic grading is often much more important than the endoscopic appearance, so that endoscopic oesophageal biopsies are very important aids in the diagnosis of oesophagitis. Appropriate clinical evaluation of symptoms must occur before endoscopic examination.

We investigated the role of strain on the magnetic properties of La0.7Sr0.3MnO3 epitaxial films grown on substrates with different crystallographic orientation. The magnetic characterization confirms the large magnetostriction due to the tensile stress applied by the SrTiO3 substrates. The data demonstrate that the easy direction of magnetization is aligned to the elongated, in-plane axis both in (110)- and (001)-oriented films. The in-plane anisotropy of (110) films is interpreted in the frame of a simple structural model. We provide evidence of a spatial separation between a conducting ferromagnetic and an insulating paramagnetic phase at the Curie temperature. The possible effect of such phase separation on the coercitive field and on the magnetization versus temperature is discussed. (c) 2006 Elsevier B.V. All rights reserved.

The lipoprotein Lp(a) with high plasma concentration is an independent genetic determinant for cardiovascular diseases. It was investigated as a quantitative factor of risk for myocardial infarction. A total of 345 Italian subjects, 127 Cases and 218 Controls, were studied. Lipids and lipoproteins were compared. Cases had atherogenic traits, such as lower HDL cholesterol and higher triglycerides than Controls. In particular, they had Lp(a) concentrations over the risk threshold, (median, 27 mg/dl in Cases vs 17 mg/dl in Controls; P = 0.0075, Mann-Whitney test) which confirmed the association of this parameter with the disease. Two main functional variants of the apo(a) gene, KringleIV and penta-nucleotide repeat, (PNR) were analyzed. Allele and genotype frequency distributions differed between Cases and Controls. Lp(a) concentrations differed according to PNR genotypes in Controls: subjects having alleles >8 showed lower Lp(a). This was not found in Cases. They had a higher prevalence of the smaller KringleIV alleles, the high Lp(a)-expressing ones. In Cases, genotypes consisting of two small KringleIV alleles were prevalently associated to PNR 8/9 and 8/10, thus preventing Lp(a) lowering. The putative apo(a) enhancer within LINE1 in the apo(a)-plasminogen intergenic region was investigated for functional polymorphisms. No variants that could be associated to the Lp(a) variability were found.

A model to describe the linear regime in a Superconducting Tunnel Junction detector has been developed. In the limit of low temperatures, the only effective processes which involve quasi-particles and phonons are the phonon scattering mechanisms and the phonon escape from the area of the detector. The response of the STJ is linear if τ esc −1 >; τ ph −1 for low energy phonons and τ esc −1 τ ph −1 for high energy phonons. The estimate of the mean energy loss ϵ by radiation per excess quasi-particle in the STJ is in agreement with previous determinations. A comparison with some experimental results taken from literature has been produced.

We have studied the expression of the three human acute myeloid leukemia (AML) genes in primary samples of non-Hodgkin's B-cell lymphomas in which translocations involving these loci were not present. We found a widespread expression of the three AML genes in all the lymphoma samples as well as in the purified normal B-lymphocytes. Thus, the presence of the three mRNAs "per se" does not allow the identification of the pathological status. However, AML1 showed a different transcription pattern in the neoplastic tissues with respect to the normal B-cells. The AML1b isoform proved to be peculiar to this lymphoma. Our data support the idea that qualitative and quantitative alterations of AML1 gene expression deriving from deregulating mechanisms other than translocations may be involved in this malignancy. The usage of two differently regulated promoters driving the expression of the transcripts AML1b and AML1c may be one of these mechanisms. Finally, we report the presence of a new alternatively spliced transcript in normal B-cells.

We present novel low-field magnetoresistive devices based on the ferromagnetic manganite La0.7Sr0.3MnO3 operating in the current in plane (CIP) configuration. In these planar spin-valve devices, a focused Ga+ beam is used to create pinning centers for magnetic domain walls. The spin-dependent scattering of polarized electrons at the domain walls (DW) is responsible for the magnetoresistance observed in the patterned tracks. The magneto-transport properties of these devices are interpreted within a model for DW magnetoresistance. Applications such as magnetic data storage can be envisaged for the structures we investigated. (C) 2006 Elsevier B.V. All rights reserved.

We provide a detailed analysis of our new experimental method for the size estimate of the hotspot induced by ionizing particles in a Josephson tunnel junction. This method is based on the effect of ionizing particles on misaligned Abrikosov vortices, which are trapped in the junction by a field-cooling process. The effect of the radiation is the change of the misalignment parameter of a vortex. This, in turn, induces a change of the Josephson critical current, which can be used for an hotspot size estimate.

We studied centenarians to investigate the biological basis of human longevity focusing on the apolipoprotein A-IV and lipoprotein(a), potentially involved in the susceptibility to atherogenic mechanisms. We analyzed two restriction polymorphisms, HinfI347 (alleles +, -) and Fnu4HI360 (alleles 1, 2), and a VNTR (alleles 3, 4) at the 3' region of the apo A-IV gene. The allele frequencies, the lipoprotein concentrations and their association in centenarians and adults have been compared. In centenarians, the HinfI genotype distribution is different (P0.05) and the (+13) haplotype is prevalent (0.54 vs. 0.39), with a greater association of (+3), indicating the selection of a favourable allele. The lipoprotein modulation by the apo A-IV polymorphisms is suggested by significant associations in adults ((+/+) homozygotes have lower LDL-cholesterol and apo B than heterozygotes; (1/1) homozygotes have higher TG and apo B than heterozygotes), that in centenarians still exists as a trend. Centenarians show peculiar lipoprotein features: lower LDL-cholesterol (mean 103 vs. 115 mg/dl; P0.02), and higher lipoprotein(a) (median 17.5 vs. 4.5; P0.002). Large part of them (47%), especially the Hinf(+/+) and the (+13) homozygotes, have a lipoprotein(a)20 mg/dl, value considered as the threshold for atherogenic risk, surprisingly compatible with healthy longevity.

The development of an experimental set-up for radiation detection atT = 0.4 K by Nb-based Superconducting Tunnel junctions is presented. Preliminary results concerning detectors characterization and 6 keV X ray detection are shown and discussed.

A theoretical analysis of the linear regime in a superconducting tunnel junction (STJ) has been carried out on the basis of a kinetic approach to the non-equilibrium superconductivity induced in the detector by an X-ray. A solution of the diffusive equation of the quasi-particles has been obtained assuming very slow recombination processes and an equilibrium 2-DELTA-phonon distribution. Under these conditions, the response of the detector is linear, that is the charge collected by the detector itself is proportional to the energy released. A relation between this released energy and the collected charge has also been obtained, thus achieving an expression of the mean energy-epsilon per excess quasi-particle. A comparison with some experimental results taken from current literature has been also reported.

We studied a case of familial Apolipoprotein CII deficiency. By Southern hybridization, amplification and sequence analysis, the genetic defect was identified. It consists in a point mutation C- greater than G in the third exon of the gene causing a premature stop codon. Truncated at the aa. 36 of the mature form, the protein loses its functional domains, becomes inefficient and cannot be detected in the plasma, because of its high instability. The mutation destroys an RsaI site, present in the normal gene sequence. This point mutation is useful in the diagnosis of this Apolipoprotein CII deficiency.

Aim: Gemcitabine (GEM) and nab-paclitaxel (nab-P) significantly improved overall survival over GEM in metastatic pancreatic adenocarcinoma (PA). Given the synergism of taxanes with platinum compounds and fluoropyrimidines, we determined the recommended phase 2 dose (RP2D) of nab-P in combination with cisplatin, capecitabine, and GEM (PAXG regimen) in a phase Ib trial in patients (pts) with stage III PA (NCT01730222). Methods: GEM, cisplatin and capecitabine were given at fixed dose (800, 30, and 1250 mg/m2, respectively) q 2 weeks. Doses of nab-P were escalated in cohorts of 3 to 6 pts from 100 (level 1), to 125 (level 2) and 150 mg/m2 (level 3) q 2 weeks. The maximum tolerated dose (MTD) was defined as the dose at which > 2 out of 3-6 pts developed dose-limiting toxicity (DLT) during the first month of therapy. DLT was defined as G ≥ 4 neutropenia lasting ≥ 7 days; G ≥ 3 febrile neutropenia, fever ≥38.5°C, thrombocytopenia, diarrhea, nausea or vomiting; G ≥ 2 neurological toxicity or failure to recover to grade ≤ 1 toxicity (except alopecia) or to baseline values after delaying the initiation of next cycle by > 2 weeks. Results: Between Dec 2012 and Mar 2014, 23 pts (16 males; median age 63 years) with unresectable (according to a surgical team performing >100 duodenocephalopancreasectomy/year) stage III PA, were enrolled at a single institution (3 at level 1, 5 at level 2, 15 at level 3). To date, 197 cycles of PAXG were administered. Therapy is ongoing in 5 pts at level 3. No DLT has occurred. Worse per patient toxicity was G3/4 neutropenia 29/29%; G3 fatigue 14%; G3 neuropathy, anemia, nausea, diarrhea 7%. After 123 cycles at 150 mg/m2 the nab-P dose-intensity was 90%. To date, a partial response (PR) was observed in 15 pts (65%) and stable disease (SD) in 8 pts; among 20 pts with positive PET scan a complete response was observed in 8 (40%), PR in 10 (50%), SD in 2; 19 pts had elevated basal CA19-9 which was reduced by >50% in 18 (95%); 15/16 (94%) pts with mature follow-up were progression-free at 6 months from therapy start. Conclusions: The RP2D of nab-P in the PAXG regimen was 150 mg/m2 every 2 weeks. Preliminary results are promising and a phase II randomized trial with this regimen is ongoing. Disclosure: M. Reni: Participation in an Advisory Board : Merck; Celgene; CLOVIS; Genentech; Boehringer L. Gianni: advisory board Celgene. All other authors have declared no conflicts of interest.

Three overlapping genomic clones covering 28 kilobases of the human pro-alpha 2(I) collagen gene have been isolated from a lambda phage library. The analysis of 12 introns and 12 exons in the 3' end region has shown that the human gene has a structure remarkably similar to that reported for the homologous chicken gene. One large intron, in the alpha-chain domain, contains an AluI sequence flanked by short direct repeats; a second AluI sequence is present 4 kilobases downstream from the termination codon. The analysis of the exon coding for the 3'-untranslated region has revealed that the pro-alpha 2(I) collagen gene transcribes at least four different mRNAs in cultured fibroblasts. The colinearity and exact location of the termini of these transcripts was determined by Northern blots, R-looping analysis, S1 protection, and DNA sequencing. The ends of two transcripts are closely preceded by the canonical polyadenylation signal (AAUAAA), whereas two of its variations (AUUAAA and AUUAA) precede the ends of the other two transcripts.

High molecular weight mitochondrial (mt) RNAs were isolated from rat liver mitochondria and hybridized in the presence of excess competitor mt rRNA and/or mt tRNA to restriction fragments of mtDNA. The data reveals that there are a few areas of the mt-genome on which the complementary of these presumptive messenger RNAs is most pronounced. These areas are away from the parts of the genome which are coding for the mt rRNA or containing the D-loop.

Summary To understand the effect of some antibiotics on phagocytic activity, we analysed the influence of different antibiotics on the ingestion phase of human macrophages in vitro . Monolayer cultures were treated with the following drugs: penicillin G, ampicillin, methicillin, cefazolin, cephalothin, tetracycline, doxycycline, streptomycin, gentamicin and tobramycin. The phagocytic activity was assayed by the direct microscopic count of ingested zymosan particles. Penicillin G, gentamicin, tobramycin, doxycycline and tetracycline increased the phagocytic activity of human macrophages in vitro . On the other hand methicillin, ampicillin, cefazolin, and cephalothin appeared to exert an inhibitory effect on phagocytosis.

A new tool for determining and analysing Molecular Electrostatic Potentials (MEP) of very large biomolecules is presented and illustrated. The MEP's are computed in a monopole approximation with inclusion of inductive effects by a chain of computer programs (running even on small computers) based on net charges calculated in a σ-π separation scheme according to the method of Del Re. This method is applicable to virtually any macromolecule and yields fairly reliable net charges. The use of MEP's in the study of reaction mechanisms as well as the solvent problem and use of ad hoc dielectric constants are briefly discussed. Since MEP's are especially well suited to the study of oxido-reaction mechanisms, the scope of the new program is illustrated on the maps of reduced and oxidized states of some monoheme cytochromes at their van der Waals frontiers. The results throw further light on the way in which the protein modulates the properties of the heme group.