Production of He-4 and (4) in Pb-Pb collisions at root(NN)-N-S=2.76 TeV at the LHC

Results on the production of He-4 and (4) nuclei in Pb-Pb collisions at root(NN)-N-S = 2.76 TeV in the rapidity range vertical bar y vertical bar <1, using the ALICE detector, are presented in this paper. The rapidity densities corresponding to 0-10% central events are found to be dN/dy4(He) = (0.8 +/- 0.4 (stat) +/- 0.3 (syst)) x 10(-6) and dN/dy4 = (1.1 +/- 0.4 (stat) +/- 0.2 (syst)) x 10(-6), respectively. This is in agreement with the statistical thermal model expectation assuming the same chemical freeze-out temperature (T-chem = 156 MeV) as for light hadrons. The measured ratio of (4)/He-4 is 1.4 +/- 0.8 (stat) +/- 0.5 (syst). (C) 2018 Published by Elsevier B.V.Peer reviewe

MicroRNAs Modulate Signaling Pathways in Osteogenic Differentiation of Mesenchymal Stem Cells

Mesenchymal stem cells (MSCs) have been identified in many adult tissues and they have been largely studied in the last years, especially in view of their potential use for treating diseases, damaged tissues and organs. MSCs are capable of self-replication and differentiation into osteo-blasts and are considered an important source of cells in tissue engineering for bone regeneration. Several epigenetic factors are believed to play a role in the osteogenic differentiation of MSCs, in-cluding microRNAs (miRNAs). MiRNAs are small, single-stranded, non-coding RNAs of approxi-mately 22 nucleotides able to regulate cell proliferation, differentiation and apoptosis by binding the 3′ untranslated region (3′-UTR) of target mRNAs, which can be subsequently degraded or trans-lationally silenced. MiRNAs control gene expression in osteogenic differentiation by regulating two crucial signaling cascades in osteogenesis: the transforming growth factor-beta (TGF-β)/bone mor-phogenic protein (BMP) and the Wingless/Int-1(Wnt)/β-catenin signaling pathways. This review provides an overview of the miRNAs involved in osteogenic differentiation and how these miRNAs could regulate the expression of target genes

METHYLATION PROFILE OF IRF6 AND RARB GENE PROMOTERS IN NORMAL VULVAR TISSUES AND VULVAR CARCINOMAS

Interferon regulatory factor 6 (IRF6) and retinoic acid receptor beta (RARB) play an important role in regulating cell proliferation and differentiation of the epithelia. IRF6 and RARB by modulating p63 and c-jun, respectively, arrest cell proliferation thus inducing differentiation. The promoter hypermethylation of tumor suppressor genes may favour the onset of cancers. In this study, IRF6 and RARB promoter methylation profiles were investigated in normal vulvar (NV, n=20) and pathological vulvar tissues from cancer-free lichen sclerosus (cfLS, n=20), cancer-associated lichen sclerosus (caLS, n=20), vulvar intraepithelial neoplasia (VIN, n=6, only IRF6) and vulvar cancer (VC, n=20) specimens. Methylation analyses were performed with the bisulphite-DNA treatment and PCR amplifications/sequencing of IRF6 and RARB promoters. IRF6 and RARB gene expressions, together with p63 and c-jun genes were analysed by qRT-PCR. IRF6 gene promoter was found to be hypermethylated in 10% cfLS, 20% VIN, 45% caLS and 80% VC (p&lt;0.01, caLS and VC versus NV). IRF6 expression decreased 2.2-, 2.9-, 4.5- and 6.6-fold from cfLS, VIN, caLS to VC, respectively, whereas p63 was overexpressed in all specimens compared to NV (p&lt;0.05). RARB gene promoter tested hypermethylated in 50% caLS, 55% cfLS and 90% VC (p&lt;0.01, versus NV). Unlike IRF6, RARB was significantly down-expressed, 4.8-fold, only in VC (p&lt;0.01, versus NV). Consistently, c-jun expression was 2.6-fold up-expressed in VC (p&lt;0.01, versus NV). Interestingly, 2/18 (11.1%) VC, showing full methylation of RARβ gene promoter, were from females with tumor recurrences. IRF6 and RARB expressions are hampered by promoter hypermethylation in vulvar diseases and vulvar cancer. While IRF6 promoter hypermethylation occurs in a stepwise manner from vulvar LS to cancer, RARB promoter hypermethylation was found to be mainly associated to vulvar cancer. IRF6 and RARB dysregulations may play a role in caLS development and progression, respectively

HYPERMETHYLATION-INDUCED INACTIVATION OF IRF6 AND RARβ GENES AS A POTENTIAL PROGNOSTIC BIOMARKER IN VULVAR SQUAMOUS CELL CARCINOMA

Objectives: Vulvar squamous cell carcinoma (VSCC) represents 5% of gynecological malignancies. About 80% of VSCCs arises from inflammatory diseases, such as lichen sclerosus (LS). The molecular alterations involved in onset/progression of LS-associated VSCC are unknown. Interferon regulatory factor 6 (IRF6) and retinoic acid receptor β (RARβ) tumor-suppressor genes have been found to be downregulated by promoter methylation in different carcinomas.1,2 In this study, we aimed to evaluate the involvement of the IRF6 and RARβ promoter methylation in the onset of VSCC from LS. Methods: IRF6 and RARβ mRNA expression and promoter methylation profiles were investigated by quantitative PCR (qPCR) and sequencing of PCR-amplified bisulfite-treated DNA, respectively, in VSCC (n=20) and the adjacent LS (n=20), vulvar intraepithelial neoplasia (VIN; n=5, only for IRF6), cancer-free LS (cfLS, n=20) and normal skin (NS, n=20). IRF6 and RARβ pathway-related genes p63 and c-Jun mRNAs were also investigated by qPCR.3,4 Results: IRF6 expression decreased 2.2-, 2.9-, 4.5- and 6.6-fold from cfLS, VIN, LS to VC, respectively, whereas p63 was overexpressed in all specimens compared to NS (p&lt;0.05). IRF6 promoter was hypermethylated in 9/20 (45%) LS, 1/5 (20%) VIN, 16/20 (80%) VSCC, 2/20 (10%) cfLS, and 0 NS.3 Unlike IRF6, RARB was significantly down-expressed, 4.8-fold, only in VC (p&lt;0.01, versus NS). Consistently, c-jun expression was 2.6-fold up-expressed in VC (p&lt;0.01, versus NV). RARβ gene promoter was hypermethylated in 18/20 (90%) VSCC, 11/20 (55%) cfLS, 10/20 (50%) LS and 5/20 (25%) NS. Interestingly, 2/18 (11.1%) VSCC from females with tumor recurrences showed full methylation of RARβ gene promoter.4 Conclusions: IRF6 and RARB gene expressions are hampered by promoter hypermethylation in vulvar diseases and vulvar cancer. While IRF6 promoter hypermethylation occurs in a stepwise manner from vulvar LS to cancer, RARB promoter hypermethylation was found to be mainly associated to vulvar cancer. IRF6 and RARB dysregulations may play a role in LS development and progression, respectively. Therefore, IRF6 and RARβ promoter hypermethylations may be biomarkers of cancer-risk in LS patients, and prognostic biomarkers of cancer progression in patients affected by LS-associated-VSCC.3,4 References: 1.Ivanova T et al. BMC Cancer.2:4,2002. 2.Botti E et al. PNAS.108:13710-15,2011. 3.Rotondo JC et al. JAMA Dermatol.152:928-33,2016. 4.Rotondo JC et al. JAMA Dermatol.154:1-5,2018

Selective Catalytic Reduction of NOx by CO over Doubly Promoted MeMo/Nb2O5 Catalysts (Me = Pt, Ni, or Co)

Doubly promoted MeMo/Nb2O5 catalysts, in which Me = Pt, Ni, or Co oxides were prepared for the selective catalytic reduction of NOx by CO reaction (CO-SCR). Comparable chemical, textural, and structural analyses revealed similarities between NiMo and CoMo impregnated on Nb2O5, in contrast to PtMo sites, which were not homogeneously dispersed on the support surface. Both the acid function and metal dispersion gave a synergistic effect for CO-SCR at moderate temperatures. The reactivity of PtMo catalysts towards NOx and CO chemisorption was at low reaction temperatures, whereas the NOx conversion over CoMo was greatly improved at relatively high temperatures. Careful XPS, NH3-TPD, and HRTEM analyses confirmed that the large amounts of strong and moderate acid sites from PtOx entrapped on MoO3 sites induced high NOx conversions. NiMo/Nb2O5 showed poor performance in all conditions. Poisoning of the MeMo sites with water vapor or SO2 (or both) provoked the decline of the NOx conversions over NiMo and PtMo sites, whereas the structure of CoMo ones remained very active with a maximum NOx conversion of 70% at 350 &deg;C for 24 h of reaction. This was due to the interaction of the Co3+/Co2+ and Mo6+ actives sites and the weak strength Lewis acid Nb5+ ones, as well

The role of microRNAs in the osteogenic and chondrogenic differentiation of mesenchymal stem cells and bone pathologies

Mesenchymal stem cells (MSCs) have been identified in many adult tissues. MSCs can regenerate through cell division or differentiate into adipocytes, osteoblasts and chondrocytes. As a result, MSCs have become an important source of cells in tissue engineering and regenerative medicine for bone tissue and cartilage. Several epigenetic factors are believed to play a role in MSCs differentiation. Among these, microRNA (miRNA) regulation is involved in the fine modulation of gene expression during osteogenic/chondrogenic differentiation. It has been reported that miRNAs are involved in bone homeostasis by modulating osteoblast gene expression. In addition, countless evidence has demonstrated that miRNAs dysregulation is involved in the development of osteoporosis and bone fractures. The deregulation of miRNAs expression has also been associated with several malignancies including bone cancer. In this context, bone-associated circulating miRNAs may be useful biomarkers for determining the predisposition, onset and development of osteoporosis, as well as in clinical applications to improve the diagnosis, follow-up and treatment of cancer and metastases. Overall, this review will provide an overview of how miRNAs activities participate in osteogenic/chondrogenic differentiation, while addressing the role of miRNA regulatory effects on target genes. Finally, the role of miRNAs in pathologies and therapies will be presented

Serum Antibodies Against the Oncogenic Merkel Cell Polyomavirus Detected by an Innovative Immunological Assay With Mimotopes in Healthy Subjects

International audienceMerkel cell polyomavirus (MCPyV), a small DNA tumor virus, has been detected in Merkel cell carcinoma (MCC) and in normal tissues. Since MCPyV infection occurs in both MCC-affected patients and healthy subjects (HS), innovative immunoassays for detecting antibodies (abs) against MCPyV are required. Herein, sera from HS were analyzed with a novel indirect ELISA using two synthetic peptides mimicking MCPyV capsid protein epitopes of VP1 and VP2. Synthetic peptides were designed to recognize IgGs against MCPyV VP mimotopes using a computer-assisted approach. The assay was set up evaluating its performance in detecting IgGs anti-MCPyV on MCPyV-positive (n=65) and -negative (n=67) control sera. Then, the ELISA was extended to sera (n=548) from HS aged 18-65 yrs old. Age-specific MCPyV-seroprevalence was investigated. Performance evaluation indicated that the assay showed 80% sensitivity, 91% specificity and 83.9% accuracy, with positive and negative predictive values of 94.3% and 71%, respectively. The ratio expected/obtained data agreement was 86%, with a Cohen’s kappa of 0.72. Receiver-operating characteristic (ROC) curves analysis indicated that the areas under the curves (AUCs) for the two peptides were 0.82 and 0.74, respectively. Intra-/inter-run variations were below 9%. The overall prevalence of serum IgGs anti-MCPyV in HS was 62.9% (345/548). Age-specific MCPyV-seroprevalence was 63.1% (82/130), 56.7% (68/120), 64.5% (91/141), and 66.2% (104/157) in HS aged 18-30, 31-40, 41-50 and 51-65 yrs old, respectively (p&gt;0.05). Performance evaluation suggests that our indirect ELISA is reliable in detecting IgGs anti-MCPyV. Our immunological data indicate that MCPyV infection occurs asymptomatically, at a relatively high prevalence, in humans

Structural transformation of vanadate nanotubes into vanadate oxides nanostructures during the dry reforming of methane

The metal-containing vanadate nanotubes namely MeVO-NT (Me=Ni, Co or Pt) were in situ transformed into vanadate oxides nanostructures i.e., MeVxOy, during the methane dry reforming. All the experimental observations through Raman, HRTEM, XRD, XPS, SEM-EDS, TG-FTIR and elemental analysis, strongly suggested that the VOx (MeV2O7, V2O5 and VO2) support contained the metal species that were involved in the dry reforming of methane (DRM) reaction. The pristine VO-NT catalyst exhibited a fairly low activity in DRM due to its degradation. In the case of CoVO-NT, the Co3O4/VO2, Co3O4/Co2V2O7 and Co3O4/V2O5 phases were deactivated by oxidation of the Co particles, instead of being deactivated by sintering and coking, as well. In contrast to CoVO-NT, PtVO-NT having PtOx/V2O5, PtOx/VO2 or even PtOx/V2O7 phases inhibited heavy carbonaceous deposition on surface, but sintering was not avoided. The NiVO-NT was active due to the stability of the Ni°/Ni2V2O7 active phase in hindering heavy whisker and filamentous carbonaceous deposits on such catalyst. Using Halgren-Lipscomb algorithm in the frame of density functional theory (DFT), transition states energy for all three catalysts were obtained. It was found that PtVO-NT energy profile was lower than CoVO-NT and NiVO-NT counterparts. This suggested that the Pt sites dispersed on VOx structure was catalytic active during the methane activation in DRM whereas the CoVO-NT and CoVO-NT solids were prone to perform side reactions