Migrazioni e networks urbani

Ripercorrendo l’ampio dibattito sul tema emerge quanto numerose siano le definizioni di integrazione elaborate dagli studiosi che si sono occupati di migrazioni. Soprattutto in anni più recenti, in forza dei rilevanti cambiamenti dei fenomeni migratori in atto, in molti concordano che questi processi sono aperti a molteplici esiti, in gran parte collegati a fattori di contesto politico, sociale, economico e culturale. Questi diversi fattori rappresentano altrettante dimensioni con cui si può guardare all’integrazione, che pertanto si configura come concetto multidimensionale, oltre che dinamico, e che può essere declinato a diversi livelli di analisi. Il livello relazionale (livello meso) rappresenta il punto di convergenza di fattori di integrazione macro e micro: i percorsi di inserimento urbano spesso dipendono dall’efficacia delle reti nelle quali si è inseriti. Questo contributo presenta i risultati di una ricerca condotta nel quartiere Mercato a Napoli, che ha avuto come oggetto di analisi l’integrazione della comunità cabardina, attraverso la metodologia e gli strumenti della Social Network Analysis.There are many definitions of integration developed by scholars of migration. They agree – especially in recent years, due to the significant changes in migration – that these processes are open to multiple outcomes, largely related political, social, economic and cultural factors. These different factors represent the different dimension which you can look to the integration; a term that appears as a multidimensional concept, as well as dynamic, and can be declined at different levels of analysis. The relational level (meso-level) represents the point of convergence between macro and micro factors of integration. In fact, the urban integration processes often depend on the effectiveness of their own social networks. This paper presents the results of a survey in the Mercato neighborhood (Naples). The aim is to analyze the integration of Kabardians community, through Social Network Analysis methods.Peer Reviewe

Exploiting the adenoassociated virus Rep protein to mediate site-specific integration into the human genome and optimisation of Ad/AAV vector design

Gene therapy is an approach to treating diseases in which an exogenous gene is introduced to correct for a defective or missing protein or to affect a biochemical pathway. Few successes have been reported in humans (0), as several technical issues limit its broader application. One question is how to deliver DNA to the appropriate cells. Nature provides one solution in the form of viruses, which are in essence protected gene delivery packages with native ability to introduce their genomes into cells. Once the desired gene is delivered to target cells, another issue that arises is the fate of the DNA. Some strategies rely on long-term expression from extra-chromosomal DNA, but there are cases, such as dividing cells, where it would be highly beneficial to permanently insert the gene into chromosomes. Certain viral genomes can be integrated into host DNA by non-homologous recombination or, in the case of retroviruses, by virally encoded integrases. While integration seems to be not dependent on target sequence, in vivo, retroviruses, such as HIV and murine leukemia virus, integrate preferentially into active genes (1, 2), introducing the possibility of insertional mutagenesis. The theoretical danger inherent in retrovirus-based gene therapy has been concretely demonstrated in a recent clinical trial in which the modified retrovirus integrated into the LMO2 locus, causing leukemia in three of the patients (4). A powerful system to circumvent this critical issue could be to develop a system to site-specific integrate the exogenous gene into a safety zone into the genome. To date, only one animal virus, the adenoassociated virus (AAV), has been identified that integrates its genome into a particular location into human chromosomal DNA. When cells are infected in the absence of helper virus, AAV establishes a latent infection in which the AAV genome integrates into a locus known as AAVS1 on the q arm of chromosome 19 (4). Recombinant AAV (rAAV) vectors too have a series of limitations as gene therapy vectors: they can accommodate only small genes and moreover eliminating most of wild-type AAV (wt AAV) sequences they have lost almost all the site-specific integration capability. On the basis of AAV site-specific integration machinery a series of effort to re-introduce wt AAV’s integration efficiency have been done. Different viruses have been engineered using the AAV’s integration machinery to transform them to target and integrate site-specifically large genes into the chr 19. Development of a maximized integrating, large capacity DNA viral vector is still an unmet goal of gene transfer technology. The initial aim of this project was to characterize the combination of the attributes of both the AAV and adenovirus (Ad) gene therapy vectors to develop an Ad/AAV hybrid virus system able to target site-specifically a large fragment of DNA into the host cell genome. In executing our experimental strategy, we found that, in addition to the known incompatibility of Rep expression and Ad growth, an equally large obstacle was presented by the inefficiency of the integration event when using traditional rAAV integrating elements. The finding that traditional rAAV plasmid vectors lack integration potency compared to wt AAV plasmid constructs led recently to the discovery of an AAV integration enhancer sequence element which functions in cis to an AAV inverted terminal repeat-flanked target gene. This study has addressed both of these problems. Moreover the project aimed also the capability of such vectors to target a large integrating cassette and the differences in the system integration efficiency compairing the dimension of the integrating cassettes. We demonstrated that an Ad can be generated that expresses Rep proteins and that Rep-mediated AAV persistence can occur in the presence of Ad vectors. We exploited the size limit capability introducing a large integrating cassette (12 kb) into the Ad/AAV vector and we obtained a good level of integration into the human genome. Specifically we succeeded in integrating it without any recombination event and in a site-specific fashion at good level. The model we extensively tested in human cell lines was also used successfully into human primary cells where we obtained site-specific integration into human chromosome 19 as expected. Another problem analysed was the flexibility of Ad vector system. Adenoviral vectors maintain the cellular specificity of adenoviruses from which they derive. A good gene therapy vector should have a broad tropism to ensure a good transduction efficiency, and moreover should be able to transduce cells of interest, such as CD34+ cells and other primary cells. We tried to expand Ad tropism engineering the commonly used Ad 5 vector (not able to transduce very well CD34+ and hematopoietic cells), transforming it to an Ad 5/35 modified vector. This approach permitted us to have better CD34+ cell transduction and a very good efficiency with hematopoietic cell lines

Targeted knock-down of miR21 primary transcripts using snoMEN vectors induces apoptosis in human cancer cell lines

We have previously reported an antisense technology, 'snoMEN vectors', for targeted knock-down of protein coding mRNAs using human snoRNAs manipulated to contain short regions of sequence complementarity with the mRNA target. Here we characterise the use of snoMEN vectors to target the knock-down of micro RNA primary transcripts. We document the specific knock-down of miR21 in HeLa cells using plasmid vectors expressing miR21-targeted snoMEN RNAs and show this induces apoptosis. Knock-down is dependent on the presence of complementary sequences in the snoMEN vector and the induction of apoptosis can be suppressed by over-expression of miR21. Furthermore, we have also developed lentiviral vectors for delivery of snoMEN RNAs and show this increases the efficiency of vector transduction in many human cell lines that are difficult to transfect with plasmid vectors. Transduction of lentiviral vectors expressing snoMEN targeted to pri-miR21 induces apoptosis in human lung adenocarcinoma cells, which express high levels of miR21, but not in human primary cells. We show that snoMEN-mediated suppression of miRNA expression is prevented by siRNA knock-down of Ago2, but not by knock-down of Ago1 or Upf1. snoMEN RNAs colocalise with Ago2 in cell nuclei and nucleoli and can be co-immunoprecipitated from nuclear extracts by antibodies specific for Ago2

Reconstruction of primary vertices at the ATLAS experiment in Run 1 proton–proton collisions at the LHC

This paper presents the method and performance of primary vertex reconstruction in proton–proton collision data recorded by the ATLAS experiment during Run 1 of the LHC. The studies presented focus on data taken during 2012 at a centre-of-mass energy of √s=8 TeV. The performance has been measured as a function of the number of interactions per bunch crossing over a wide range, from one to seventy. The measurement of the position and size of the luminous region and its use as a constraint to improve the primary vertex resolution are discussed. A longitudinal vertex position resolution of about 30μm is achieved for events with high multiplicity of reconstructed tracks. The transverse position resolution is better than 20μm and is dominated by the precision on the size of the luminous region. An analytical model is proposed to describe the primary vertex reconstruction efficiency as a function of the number of interactions per bunch crossing and of the longitudinal size of the luminous region. Agreement between the data and the predictions of this model is better than 3% up to seventy interactions per bunch crossing

C57BL/6J substrain differences in response to high-fat diet intervention

C57BL/6J-related mouse strains are widely used animal models for diet-induced obesity (DIO). Multiple vendors breed C57BL/6J-related substrains which may introduce genetic drift and environmental confounders such as microbiome differences. To address potential vendor/substrain specific effects, we compared DIO of C57BL/6J-related substrains from three different vendors: C57BL/6J (Charles Rivers), C57BL/6JBomTac (Taconic Bioscience) and C57BL/6JRj (Janvier). After local acclimatization, DIO was induced by either a high-fat diet (HFD, 60% energy from fat) or western diet (WD, 42% energy from fat supplemented with fructose in the drinking water). All three groups on HFD gained a similar amount of total body weight, yet the relative amount of fat percentage and mass of inguinal- and epididymal white adipose tissue (iWAT and eWAT) was lower in C57BL/6JBomTac compared to the two other C57BL/6J-releated substrains. In contrast to HFD, the three groups on WD responded differently in terms of body weight gain, where C57BL/6J was particularly prone to WD. This was associated with a relative higher amount of eWAT, iWAT, and liver triglycerides. Although the HFD and WD had significant impact on the microbiota, we did not observe any major differences between the three groups of mice. Together, these data demonstrate significant differences in HFD- and WD-induced adiposity in C57BL/6J-related substrains, which should be considered in the design of animal DIO studies.</p

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Stellate cell expression of SPARC-related modular calcium-binding protein 2 is associated with human non-alcoholic fatty liver disease severity

Background &amp; Aims: Histological assessment of liver biopsies is the gold standard for diagnosis of non-alcoholic steatohepatitis (NASH), the progressive form of non-alcoholic fatty liver disease (NAFLD), despite its well-established limitations. Therefore, non-invasive biomarkers that can offer an integrated view of the liver are needed to improve diagnosis and reduce sampling bias. Hepatic stellate cells (HSCs) are central in the development of hepatic fibrosis, a hallmark of NASH. Secreted HSC-specific proteins may, therefore, reflect disease state in the NASH liver and serve as non-invasive diagnostic biomarkers. Methods: We performed RNA-sequencing on liver biopsies from a histologically characterised cohort of obese patients (n = 30, BMI &gt;35 kg/m2) to identify and evaluate HSC-specific genes encoding secreted proteins. Bioinformatics was used to identify potential biomarkers and their expression at single-cell resolution. We validated our findings using single-molecule fluorescence in situ hybridisation (smFISH) and ELISA to detect mRNA in liver tissue and protein levels in plasma, respectively. Results: Hepatic expression of SPARC-related modular calcium-binding protein 2 (SMOC2) was increased in NASH compared to no-NAFLD (p.adj &lt;0.001). Single-cell RNA-sequencing data indicated that SMOC2 was primarily expressed by HSCs, which was validated using smFISH. Finally, plasma SMOC2 was elevated in NASH compared to no-NAFLD (p &lt;0.001), with a predictive accuracy of AUROC 0.88. Conclusions: Increased SMOC2 in plasma appears to reflect HSC activation, a key cellular event associated with NASH progression, and may serve as a non-invasive biomarker of NASH. Impact and implications: Non-alcoholic fatty liver disease (NAFLD) and its progressive form, non-alcoholic steatohepatitis (NASH), are the most common forms of chronic liver diseases. Currently, liver biopsies are the gold standard for diagnosing NAFLD. Blood-based biomarkers to complement liver biopsies for diagnosis of NAFLD are required. We found that activated hepatic stellate cells, a cell type central to NAFLD pathogenesis, upregulate expression of the secreted protein SPARC-related modular calcium-binding protein 2 (SMOC2). SMOC2 was elevated in blood samples from patients with NASH and may hold promise as a blood-based biomarker for the diagnosis of NAFLD.</p

Age-Specific Acute Changes in Carotid-Femoral Pulse Wave Velocity With Head-up Tilt

BACKGROUND: Aortic stiffness as measured by carotid-femoral pulse wave velocity (cfPWV) is known to depend on blood pressure (BP), and this dependency may change with age. Therefore, the hydrostatic BP gradient resulting from a change in body posture may elicit a cfPWV change that is age-dependent. We aimed to analyze the relationship between BP gradient-induced by head-up body tilting-and related changes in cfPWV in individuals of varying age. METHODS: cfPWV and other hemodynamic parameters were measured in 30 healthy individuals at a head-up tilt of 0° (supine), 30°, and 60°. At each angle, the PWV gradient and resulting cfPWV were also estimated (predicted) by assuming a global nonlinear, exponential, pressure-diameter relationship characterized by a constant β0, and taking into account that (diastolic) foot-to-foot cfPWV acutely depends on diastolic BP. RESULTS: cfPWV significantly increased upon body tilting (8.0 ± 2.0 m/s supine, 9.1 ± 2.6 m/s at 30°, 9.5 ± 3.2 m/s at 60°, P for trend <0.01); a positive trend was also observed for heart rate (HR; P < 0.01). When the observed, tilt-induced cfPWV change measured by applanation tonometry was compared with that predicted from the estimated BP hydrostatic gradient, the difference in observed-vs.-predicted PWV change increased nonlinearly as a function of age (R2 for quadratic trend = 0.38, P < 0.01, P vs. linear = 0.04). This result was unaffected by HR tilt-related variations (R2 for quadratic trend = 0.37, P < 0.01, P vs. linear = 0.04). CONCLUSIONS: Under a hydrostatic pressure gradient, the pulse wave traveling along the aorta undergoes an age-related, nonlinear PWV increase exceeding the increase predicted from BP dependency