Angiogenic potential of human dental pulp stromal (stem) cells.

Dental pulp is a heterogeneous microenviroment where unipotent progenitor and pluripotent mesenchymal stem cells cohabit. In this study we investigated whether human Dental Pulp Stromal (Stem) Cells (DP-SCs) committed to the angiogenic fate. DP-SCs showed the specific mesenchymal immunophenotypical profile positive for CD29, CD44, CD73, CD105, CD166 and negative for CD14, CD34, CD45, in accordance with that reported for bone marrow-derived SCs. The Oct-4 expression in DP-SCs, evaluated through RT-PCR analysis, increased in relation with the number of the passages in cell culture and decreased after angiogenic induction. In agreement with their multipotency, DP-SCs differentiated toward osteogenic and adipogenic commitments. In angiogenic experiments, differentiation of DP-SCs, through Vascular Endothelial Growth Factor (VEGF) induction, was evaluated by in vitro matrigel assay and by cytometric analysis. Accordingly, endothelial-specific markers like Flt-1 and KDR were basally expressed and they increased after exposure to VEGF together with the occurrence of ICAM-1 and von Willebrand Factor positive cells. In addition, VEGF-induced DP-SCs maintained endothelial cell-like features when cultured in a 3-D fibrin mesh, displaying focal organization into capillary-like structures. The DP-SC angiogenic potential may prove a remarkable tool for novel approaches to developing tissue-engineered vascular grafts which are useful when vascularization of ischemic tissues is required

HIV-1 and recombinant gp120 affect the survival and differentiation of human vessel wall-derived mesenchymal stem cells

BAckground:HIV infection elicits the onset of a progressive immunodeficiency and also damages several other organs and tissues such as the CNS, kidney, heart, blood vessels, adipose tissue and bone. In particular, HIV infection has been related to an increased incidence of cardiovascular diseases and derangement in the structure of blood vessels in the absence of classical risk factors. The recent characterization of multipotent mesenchymal cells in the vascular wall, involved in regulating cellular homeostasis, suggests that these cells may be considered a target of HIV pathogenesis. This paper investigated the interaction between HIV-1 and vascular wall resident human mesenchymal stem cells (MSCs). RESULTS: MSCs were challenged with classical R5 and X4 HIV-1 laboratory strains demonstrating that these strains are able to enter and integrate their retro-transcribed proviral DNA in the host cell genome. Subsequent experiments indicated that HIV-1 strains and recombinant gp120 elicited a reliable increase in apoptosis in sub-confluent MSCs. Since vascular wall MSCs are multipotent cells that may be differentiated towards several cell lineages, we challenged HIV-1 strains and gp120 on MSCs differentiated to adipogenesis and endotheliogenesis. Our experiments showed that the adipogenesis is increased especially by upregulated PPAR\u3b3 activity whereas the endothelial differentiation induced by VEGF treatment was impaired with a downregulation of endothelial markers such as vWF, Flt-1 and KDR expression. These viral effects in MSC survival and adipogenic or endothelial differentiation were tackled by CD4 blockade suggesting an important role of CD4/gp120 interaction in this context. CONCLUSIONS: The HIV-related derangement of MSC survival and differentiation may suggest a direct role of HIV infection and gp120 in impaired vessel homeostasis and in genesis of vessel damage observed in HIV-infected patients

Beni comuni. Quarto rapporto sulla cooperazione sociale in Italia

A dieci anni dalla prima edizione, il quarto rapporto sulla cooperazione sociale aggiorna e amplia il quadro conoscitivo su uno dei più innovativi fenomeni imprenditoriali, che ha contribuito ad arricchire il panorama delle istituzioni sociali del paese.- Indice #5- Premessa di Marco Demarie #13- Presentazione di Corrado Passera #15- Prefazione di Vilma Mazzocco e Johnny Dotti #21- Cap.I La cooperazione sociale in Italia: tendenze evolutive e scenari di sviluppo, Flaviano Zandonai #33- Cap.II Un quadro teorico sull’impresa sociale, Carlo Borzaga #55- Cap.III Le traiettorie di sviluppo della cooperazione sociale, Gianfranco Marocchi #75- Cap.IV Imprenditorialità sociale tra innovazione e controllo dei mercati, Nereo Zamaro #107- Cap.V Cooperazione sociale e Mezzogiorno, Marco Musella #139- Cap.VI Le culture organizzative della cooperazione sociale: identità in movimento, Luca Fazzi e Sandro Stanzani #151- Cap.VII La cooperazione sociale nella rete del welfare locale, Sergio Pasquinelli #187- Cap.VIII I benefici individuali dei lavoratori svantaggiati nelle imprese sociali, Carlo Borzaga, Monica Loss e Domenico Zalla #207- Cap.IX Cooperazione sociale e qualità dei servizi, Giuseppe Scaratti #237- Cap.X La cooperazione sociale in una prospettiva di genere, Barbara Moreschi #265- Cap.XI Cooperativa sociale come impresa sociale? Le condizioni di imprenditorialità nel terzo settore, Michele Andreaus #285- Cap.XII Oltre il contracting out: nuove forme di relazione con le amministrazioni pubbliche, Franco Dalla Mura #319- Cap.XIII Finalità e organizzazione delle cooperative sociali: alcune indicazioni dal nuovo diritto societario, Antonio Fici #349- Cap.XIV L’impresa sociale in Italia: una quantificazione del fenomeno, Stefano Cima #377- Cap.XV Le condizioni di sviluppo delle imprese sociali nelle regioni del Centro-Nord, Carlo Borzaga e Mariangela Mongera #405- Cap.XVI Dal volontariato all’impresa sociale, Gabriella Bartolomeo e Flaviano Zandonai #439- Cap.XVII L’impresa sociale in Europa: alcuni spunti di comparazione, Paola Iamiceli #457- Cap.XVIII La nuova legge sull’impresa sociale, Felice Scalvini #485- Bibliografia #49

Carriers of ADAMTS13 Rare Variants Are at High Risk of Life-Threatening COVID-19

Thrombosis of small and large vessels is reported as a key player in COVID-19 severity. However, host genetic determinants of this susceptibility are still unclear. Congenital Thrombotic Thrombocytopenic Purpura is a severe autosomal recessive disorder characterized by uncleaved ultra-large vWF and thrombotic microangiopathy, frequently triggered by infections. Carriers are reported to be asymptomatic. Exome analysis of about 3000 SARS-CoV-2 infected subjects of different severities, belonging to the GEN-COVID cohort, revealed the specific role of vWF cleaving enzyme ADAMTS13 (A disintegrin-like and metalloprotease with thrombospondin type 1 motif, 13). We report here that ultra-rare variants in a heterozygous state lead to a rare form of COVID-19 characterized by hyper-inflammation signs, which segregates in families as an autosomal dominant disorder conditioned by SARS-CoV-2 infection, sex, and age. This has clinical relevance due to the availability of drugs such as Caplacizumab, which inhibits vWF-platelet interaction, and Crizanlizumab, which, by inhibiting P-selectin binding to its ligands, prevents leukocyte recruitment and platelet aggregation at the site of vascular damage

Gain- and Loss-of-Function CFTR Alleles Are Associated with COVID-19 Clinical Outcomes

Carriers of single pathogenic variants of the CFTR (cystic fibrosis transmembrane conductance regulator) gene have a higher risk of severe COVID-19 and 14-day death. The machine learning post-Mendelian model pinpointed CFTR as a bidirectional modulator of COVID-19 outcomes. Here, we demonstrate that the rare complex allele [G576V;R668C] is associated with a milder disease via a gain-of-function mechanism. Conversely, CFTR ultra-rare alleles with reduced function are associated with disease severity either alone (dominant disorder) or with another hypomorphic allele in the second chromosome (recessive disorder) with a global residual CFTR activity between 50 to 91%. Furthermore, we characterized novel CFTR complex alleles, including [A238V;F508del], [R74W;D1270N;V201M], [I1027T;F508del], [I506V;D1168G], and simple alleles, including R347C, F1052V, Y625N, I328V, K68E, A309D, A252T, G542*, V562I, R1066H, I506V, I807M, which lead to a reduced CFTR function and thus, to more severe COVID-19. In conclusion, CFTR genetic analysis is an important tool in identifying patients at risk of severe COVID-19

MicroRNAome of Spodoptera frugiperda cells (Sf9) and its alteration following baculovirus infection

MicroRNAs (miRNAs) as small non-coding RNAs play important roles in many biological processes such as development, cell signalling and immune response. Studies also suggest that miRNAs are important in host virus interactions where the host limits virus infection by differentially expressing miRNAs that target essential viral genes. Here, we identified conserved and new miRNAs from Spodoptera frugiperda cells (Sf9) using a combination of deep sequencing and bioinformatics as well as experimental approaches. S. frugiperda miRNAs share common features of miRNAs in other organisms, such as uracil (U) at the 5 ' end of miRNA. The 5 ' ends of the miRNAs were more conserved than the 3 ' ends, revealing evolutionary protection of the seed region in miRNAs. The predominant miRNAs were found to be conserved among arthropods. The majority of homologous miRNAs were found in Bombyx mori, with 76 of the 90 identified miRNAs. We found that seed shifting and arm switching have happened in this insect's miRNAs. Expression levels of the majority of miRNAs changed following baculovirus infection. Results revealed that baculovirus infection mainly led to an overall suppression of cellular miRNAs. We found four different genes being regulated by sfr-miR-184 at the post-transcriptional level. The data presented here further support conservation of miRNAs in insects and other organisms. In addition, the results reveal a differential expression of host miRNAs upon baculovirus infection, suggesting their potential roles in host virus interactions. Seed shifting and arm switching happened during evolution of miRNAs in different insects and caused miRNA diversification, which led to changes in the target repository of miRNAs

Immunotherapy of oneiric stupor in Morvan syndrome: Efficacy documented by actigraphy

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Exploiting the Potential of Integrated Public Building Data: Energy Performance Assessment of the Building Stock in a Case Study in Northern Italy

Smart management of urban built environment relies on the availability of data supporting sound policy making and guiding city renovation processes toward more sustainable and performant models. Nevertheless, public managers are unlikely to have comprehensive information on the existing building stock. In addition, tools providing effective insights on potential costs and benefits of retrofit strategies at city/district scale are hardly available. This article describes how data related to existing buildings may be effectively combined together into a so-called Building Information System, and discusses the advantages and shortcomings related to this process. At the same time, the implementation on a real case study in northern Italy demonstrates how the effort due to data harmonization and integration is able to foster applications to support policy makers in the management of the built environment and in the definition of urban sustainability strategies. Building data were harmonized according to the requirements of the international open standard CityGML, therefore facilitating the exchange of building information. The whole project was carried out while considering the characteristics of data sources that are available for each public body in Italy and, as a consequence, it may be replicated to other Italian municipalities