Analisi genetica e caratterizzazione funzionale del gene <i>CBL</i>-<i>B</i> associato alla predisposizione nella sclerosi multipla

Aim: Multiple Sclerosis (MS) is a multifactorial autoimmune neurodegenerative disease with high frequency in Sardinia compared to the nearest European lands. Recently our research group identified variants in CBL-B gene associated with MS in Sardinians1. We have subsequently refined the initial association results interrogating an ultra-dense sequencing-based map and found that rs9657904, the lead variant reported in along with an indel (rs147983726) in very strong linkage disequilibrium with it, are indeed the most associated variants in the region. CBL-B is a E3 ubiquitin ligase that plays a key role in the regulation of lymphocyte activity down regulating T and B cell-receptor activation. Methods: Hence, to understand the functional consequence of the disease association, we evaluated expression levels of different CBL-B isoforms by RT-qPCR in T and B-cells from volunteers homozygous for protective CC and predisposing TT genotypes of the top associated SNP (rs9657904) which perfectly predict the genotypes also at rs147983726. Cells were stimulated with specific inducers at different concentrations and time-points. We also assessed the effect of this SNP on the activation of T and B-cells in ELISA, monitoring respectively, IL-2 production and NF-kB activation in naïve and stimulated cells. Results: As described in mice where the lack of Cbl-b increases the risk of experimental autoimmune encephalomyelitis2, we observed a small but significant decreased expression of the full length CBL-B isoform in T cells with the TT MS-risk genotype. No conclusive difference in isoform expression was instead detected in B-cells. No conclusive evidence about differences in IL-2 production and NF-kB activation was observed. Conclusion: Although many aspects about the specific role of risk variants at rs9657904 and rs147983726 and their downstream consequences remain unclear, the results suggest that one of these variants act finely at down regulating CBL-B expression. To increase the resolving power of our functional studies we have planned to increase the sample size and to carry out studies in specific subpopulations of T and B cells to evaluate where these variants exert primarily their function.</br

The use of the orthotopic model to validate antivascular therapies for cancer

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Structural Dynamics and Tunability for Colloidal Tin Halide Perovskite Nanostructures

Lead halide perovskite nanocrystals are highly attractive for next-generation optoelectronics because they are easy to synthesize and offer great compositional and morphological tunability. However, the replacement of lead by tin for sustainability reasons is hampered by the unstable nature of Sn2+ oxidation state and by an insufficient understanding of the chemical processes involved in the synthesis. Here we demonstrate an optimized synthetic route to obtain stable, tunable, and monodisperse CsSnI3 nanocrystals, exhibiting well defined excitonic peaks. Similar to lead halide perovskites, we prepare these nanocrystals by combining a precursor mixture of SnI2 , oleylamine and oleic acid, with a Cs-oleate precursor. Among the products, nanocrystals with 10 nm lateral size in the γ-orthorhombic phase prove to be the most stable. To achieve such stability, an excess of precursor SnI2 as well as sub-stoichiometric Sn:ligand ratios are key. Structural, compositional and optical investigations complemented by first-principle DFT calculations confirm that nanocrystal nucleation and growth follow the formation of (R-NH3 + )2 SnI4 nanosheets with R = C18 H35 . Under specific synthetic conditions, stable mixtures of 3D nanocrystals CsSnI3 and 2D nanosheets (Ruddlesden-Popper (R-NH3 + )2 Csn-1 Snn I3n+1 with n>1) are obtained. These results set a path to exploiting the high potential of Sn halide perovskite nanocrystals for opto-electronic applications. This article is protected by copyright. All rights reserved

A Genome-Wide Association Scan on the Levels of Markers of Inflammation in Sardinians Reveals Associations That Underpin Its Complex Regulation

Identifying the genes that influence levels of pro-inflammatory molecules can help to elucidate the mechanisms underlying this process. We first conducted a two-stage genome-wide association scan (GWAS) for the key inflammatory biomarkers Interleukin-6 (IL-6), the general measure of inflammation erythrocyte sedimentation rate (ESR), monocyte chemotactic protein-1 (MCP-1), and high-sensitivity C-reactive protein (hsCRP) in a large cohort of individuals from the founder population of Sardinia. By analysing 731,213 autosomal or X chromosome SNPs and an additional ∼1.9 million imputed variants in 4,694 individuals, we identified several SNPs associated with the selected quantitative trait loci (QTLs) and replicated all the top signals in an independent sample of 1,392 individuals from the same population. Next, to increase power to detect and resolve associations, we further genotyped the whole cohort (6,145 individuals) for 293,875 variants included on the ImmunoChip and MetaboChip custom arrays. Overall, our combined approach led to the identification of 9 genome-wide significant novel independent signals—5 of which were identified only with the custom arrays—and provided confirmatory evidence for an additional 7. Novel signals include: for IL-6, in the ABO gene (rs657152, p = 2.13×10−29); for ESR, at the HBB (rs4910472, p = 2.31×10−11) and UCN119B/SPPL3 (rs11829037, p = 8.91×10−10) loci; for MCP-1, near its receptor CCR2 (rs17141006, p = 7.53×10−13) and in CADM3 (rs3026968, p = 7.63×10−13); for hsCRP, within the CRP gene (rs3093077, p = 5.73×10−21), near DARC (rs3845624, p = 1.43×10−10), UNC119B/SPPL3 (rs11829037, p = 1.50×10−14), and ICOSLG/AIRE (rs113459440, p = 1.54×10−08) loci. Confirmatory evidence was found for IL-6 in the IL-6R gene (rs4129267); for ESR at CR1 (rs12567990) and TMEM57 (rs10903129); for MCP-1 at DARC (rs12075); and for hsCRP at CRP (rs1205), HNF1A (rs225918), and APOC-I (rs4420638). Our results improve the current knowledge of genetic variants underlying inflammation and provide novel clues for the understanding of the molecular mechanisms regulating this complex process

How future surgery will benefit from SARS-COV-2-related measures: a SPIGC survey conveying the perspective of Italian surgeons

COVID-19 negatively affected surgical activity, but the potential benefits resulting from adopted measures remain unclear. The aim of this study was to evaluate the change in surgical activity and potential benefit from COVID-19 measures in perspective of Italian surgeons on behalf of SPIGC. A nationwide online survey on surgical practice before, during, and after COVID-19 pandemic was conducted in March-April 2022 (NCT:05323851). Effects of COVID-19 hospital-related measures on surgical patients' management and personal professional development across surgical specialties were explored. Data on demographics, pre-operative/peri-operative/post-operative management, and professional development were collected. Outcomes were matched with the corresponding volume. Four hundred and seventy-three respondents were included in final analysis across 14 surgical specialties. Since SARS-CoV-2 pandemic, application of telematic consultations (4.1% vs. 21.6%; p &lt; 0.0001) and diagnostic evaluations (16.4% vs. 42.2%; p &lt; 0.0001) increased. Elective surgical activities significantly reduced and surgeons opted more frequently for conservative management with a possible indication for elective (26.3% vs. 35.7%; p &lt; 0.0001) or urgent (20.4% vs. 38.5%; p &lt; 0.0001) surgery. All new COVID-related measures are perceived to be maintained in the future. Surgeons' personal education online increased from 12.6% (pre-COVID) to 86.6% (post-COVID; p &lt; 0.0001). Online educational activities are considered a beneficial effect from COVID pandemic (56.4%). COVID-19 had a great impact on surgical specialties, with significant reduction of operation volume. However, some forced changes turned out to be benefits. Isolation measures pushed the use of telemedicine and telemetric devices for outpatient practice and favored communication for educational purposes and surgeon-patient/family communication. From the Italian surgeons' perspective, COVID-related measures will continue to influence future surgical clinical practice

Multidifferential study of identified charged hadron distributions in ZZ-tagged jets in proton-proton collisions at s=\sqrt{s}=13 TeV

Jet fragmentation functions are measured for the first time in proton-proton collisions for charged pions, kaons, and protons within jets recoiling against a $Z$ boson. The charged-hadron distributions are studied longitudinally and transversely to the jet direction for jets with transverse momentum 20 $< p_{\textrm{T}} < 100$ GeV and in the pseudorapidity range $2.5 < \eta < 4$. The data sample was collected with the LHCb experiment at a center-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 1.64 fb$^{-1}$. Triple differential distributions as a function of the hadron longitudinal momentum fraction, hadron transverse momentum, and jet transverse momentum are also measured for the first time. This helps constrain transverse-momentum-dependent fragmentation functions. Differences in the shapes and magnitudes of the measured distributions for the different hadron species provide insights into the hadronization process for jets predominantly initiated by light quarks.Comment: All figures and tables, along with machine-readable versions and any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-013.html (LHCb public pages

Study of the B−→Λc+Λˉc−K−B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-} decay

The decay $B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-}$ is studied in proton-proton collisions at a center-of-mass energy of $\sqrt{s}=13$ TeV using data corresponding to an integrated luminosity of 5 $\mathrm{fb}^{-1}$ collected by the LHCb experiment. In the $\Lambda_{c}^+ K^{-}$ system, the $\Xi_{c}(2930)^{0}$ state observed at the BaBar and Belle experiments is resolved into two narrower states, $\Xi_{c}(2923)^{0}$ and $\Xi_{c}(2939)^{0}$, whose masses and widths are measured to be $$m(\Xi_{c}(2923)^{0}) = 2924.5 \pm 0.4 \pm 1.1 \,\mathrm{MeV}, \\ m(\Xi_{c}(2939)^{0}) = 2938.5 \pm 0.9 \pm 2.3 \,\mathrm{MeV}, \\ \Gamma(\Xi_{c}(2923)^{0}) = \phantom{000}4.8 \pm 0.9 \pm 1.5 \,\mathrm{MeV},\\ \Gamma(\Xi_{c}(2939)^{0}) = \phantom{00}11.0 \pm 1.9 \pm 7.5 \,\mathrm{MeV},$$ where the first uncertainties are statistical and the second systematic. The results are consistent with a previous LHCb measurement using a prompt $\Lambda_{c}^{+} K^{-}$ sample. Evidence of a new $\Xi_{c}(2880)^{0}$ state is found with a local significance of $3.8\,\sigma$, whose mass and width are measured to be $2881.8 \pm 3.1 \pm 8.5\,\mathrm{MeV}$ and $12.4 \pm 5.3 \pm 5.8 \,\mathrm{MeV}$, respectively. In addition, evidence of a new decay mode $\Xi_{c}(2790)^{0} \to \Lambda_{c}^{+} K^{-}$ is found with a significance of $3.7\,\sigma$. The relative branching fraction of $B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-}$ with respect to the $B^{-} \to D^{+} D^{-} K^{-}$ decay is measured to be $2.36 \pm 0.11 \pm 0.22 \pm 0.25$, where the first uncertainty is statistical, the second systematic and the third originates from the branching fractions of charm hadron decays.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-028.html (LHCb public pages

Measurement of the ratios of branching fractions R(D∗)\mathcal{R}(D^{*}) and R(D0)\mathcal{R}(D^{0})

The ratios of branching fractions $\mathcal{R}(D^{*})\equiv\mathcal{B}(\bar{B}\to D^{*}\tau^{-}\bar{\nu}_{\tau})/\mathcal{B}(\bar{B}\to D^{*}\mu^{-}\bar{\nu}_{\mu})$ and $\mathcal{R}(D^{0})\equiv\mathcal{B}(B^{-}\to D^{0}\tau^{-}\bar{\nu}_{\tau})/\mathcal{B}(B^{-}\to D^{0}\mu^{-}\bar{\nu}_{\mu})$ are measured, assuming isospin symmetry, using a sample of proton-proton collision data corresponding to 3.0 fb${ }^{-1}$ of integrated luminosity recorded by the LHCb experiment during 2011 and 2012. The tau lepton is identified in the decay mode $\tau^{-}\to\mu^{-}\nu_{\tau}\bar{\nu}_{\mu}$. The measured values are $\mathcal{R}(D^{*})=0.281\pm0.018\pm0.024$ and $\mathcal{R}(D^{0})=0.441\pm0.060\pm0.066$, where the first uncertainty is statistical and the second is systematic. The correlation between these measurements is $\rho=-0.43$. Results are consistent with the current average of these quantities and are at a combined 1.9 standard deviations from the predictions based on lepton flavor universality in the Standard Model.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-039.html (LHCb public pages

Differences in Maturity and Anthropometric and Morphological Characteristics among Young Male Basketball and Soccer Players and Non-Players

Background: An aspect that influences sport performance is maturation status, since, within the same chronological age group, boys who have advanced maturation outperform their late maturing peers in tests of muscular strength, power, and endurance. Therefore, the aims of the present study were: (i) to investigate the differences in biological maturation and anthropometric and morphological characteristics among three groups of Italian adolescents, two of which were sportive (practicing basketball and football) and one non-sportive, and (ii) to identify the anthropometric and morphological predictors that best discriminate these three groups. Methods: Sixty-one basketball and 62 soccer players and 68 non-sportive youths were measured (mean age = 13.0 ± 1.1 y). Anthropometric characteristics were taken and body mass index, cormic index, body composition parameters, and somatotype were derived. An estimation of maturity status was carried out considering the years from peak height velocity (PHV). Two-way 3 × 3 ANOVAs was performed on all anthropometric characteristics to test the differences within sport groups and maturity status groups. Discriminant function analysis (stepwise criteria) was then applied to anthropometric and body composition variables to classify subjects into the three different sport categories. Results: Differences in anthropometric characteristics were detected among the three groups. For somatotype, differences among all of the considered groups were higher for endomorphy (p &lt; 0.001; effect size = 0.13). Biological maturity influences the differences in the anthropometric characteristics and body composition among subjects of the same chronological age during adolescence. The variables that best discriminated the three groups were represented by body composition parameters, body proportions, and body build. Conclusions: This study confirms that boys who practice sport present healthier body composition parameters, with lower level of fat parameters. The assessment of maturity status is a fundamental factor in explaining anthropometric and body composition differences among peers in this period. Its comprehension may assist coaches and technical staff in optimizing competitive efficiency and monitoring the success of training regimes

Differences in Maturity and Anthropometric and Morphological Characteristics among Young Male Basketball and Soccer Players and Non-Players

Background: An aspect that influences sport performance is maturation status, since, within the same chronological age group, boys who have advanced maturation outperform their late maturing peers in tests of muscular strength, power, and endurance. Therefore, the aims of the present study were: (i) to investigate the differences in biological maturation and anthropometric and morphological characteristics among three groups of Italian adolescents, two of which were sportive (practicing basketball and football) and one non-sportive, and (ii) to identify the anthropometric and morphological predictors that best discriminate these three groups. Methods: Sixty-one basketball and 62 soccer players and 68 non-sportive youths were measured (mean age = 13.0 +/- 1.1 y). Anthropometric characteristics were taken and body mass index, cormic index, body composition parameters, and somatotype were derived. An estimation of maturity status was carried out considering the years from peak height velocity (PHV). Two-way 3 x 3 ANOVAs was performed on all anthropometric characteristics to test the differences within sport groups and maturity status groups. Discriminant function analysis (stepwise criteria) was then applied to anthropometric and body composition variables to classify subjects into the three different sport categories. Results: Differences in anthropometric characteristics were detected among the three groups. For somatotype, differences among all of the considered groups were higher for endomorphy (p < 0.001; effect size = 0.13). Biological maturity influences the differences in the anthropometric characteristics and body composition among subjects of the same chronological age during adolescence. The variables that best discriminated the three groups were represented by body composition parameters, body proportions, and body build. Conclusions: This study confirms that boys who practice sport present healthier body composition parameters, with lower level of fat parameters. The assessment of maturity status is a fundamental factor in explaining anthropometric and body composition differences among peers in this period. Its comprehension may assist coaches and technical staff in optimizing competitive efficiency and monitoring the success of training regimes