111 research outputs found
Exogenous Activation of BMP-2 Signaling Overcomes TGFβ-Mediated Inhibition of Osteogenesis in Marfan EmbryonicStem Cells and Marfan patient specific induced-pluripotentstem cells
No full textTemporal and spatial expression of RNases from zebrafish (Danio rerio).
No full textIn the present study we have analyzed the temporal and spatial gene expression profiles of three zebrafish (Danio rerio) RNases endowed with diverse bioactivities, including microbicidal and angiogenic activities. Our results indicate that the three ZF-RNase genes have a differential expression pattern, with ZF-RNase-1 having the most unique and dynamic expression profile. This is characterized by expression in embryonic stages and later on, in larvae, juvenile and adult organisms. In contrast, ZF-RNase-2 and -3 are only expressed either in juvenile or adult organisms. Moreover, analysis of spatial expression of ZF-RNase-1, -2 and -3 detected the three different transcripts in liver, heart, gut and swim bladder tissues. Interestingly, ZF-RNase-1 was the only gene expressed in the brain of embryonic and adult organisms. Collectively, the results suggest that the three ZF-RNases may have potential distinct functional role(s) in zebrafish either during embryonic development and/or later on, in juvenile as well as in adult organisms. Indeed, taking advantage of zebrafish as an excellent viable model to study gene function, this study opens the way to an investigation of the in vivo role(s) of ZF-RNase-1 during embryonic development, as well as, during organogenesis
An overview of direct somatic reprogramming: The ins and outs of iPSCs
No full textStem cells are classified into embryonic stem cells and adult stem cells. An evolving alternative to conventional stem cell therapies is induced pluripotent stem cells (iPSCs), which have a multi-lineage potential comparable to conventionally acquired embryonic stem cells with the additional benefits of being less immunoreactive and avoiding many of the ethical concerns raised with the use of embryonic material. The ability to generate iPSCs from somatic cells provides tremendous promise for regenerative medicine. The breakthrough of iPSCs has raised the possibility that patient-specific iPSCs can provide autologous cells for cell therapy without the concern for immune rejection. iPSCs are also relevant tools for modeling human diseases and drugs screening. However, there are still several hurdles to overcome before iPSCs can be used for translational purposes. Here, we review the recent advances in somatic reprogramming and the challenges that must be overcome to move this strategy closer to clinical application
TWIST1 silencing enhances in vitro and in vivo osteogenic differentiation of human Adipose derived Stem Cells (hASCs) by triggering activation of BMP-ERK/FGF signaling and TAZ upregulation.
No full textMesenchymal stem cells (MSCs) show promise for cellular therapy and regenerative medicine. Human adipose tissue-derived stem cells (hASCs) represent an attractive source of seed cells in bone regeneration. How to effectively improve osteogenic differentiation of hASCs in the bone tissue engineering has become a very important question with profound translational implications. Numerous regulatory pathways dominate osteogenic differentiation of hASCs involving transcriptional factors and signaling molecules. However, how these factors combine with each other to regulate hASCs osteogenic differentiation still remains to be illustrated. The highly conserved developmental proteins TWIST play key roles for transcriptional regulation in mesenchymal cell lineages. This study investigates TWIST1 function in hASCs osteogenesis. Our results show that TWIST1 shRNA silencing increased the osteogenic potential of hASCs in vitro and their skeletal regenerative ability when applied in vivo. We demonstrate that the increased osteogenic capacity observed with TWIST1 knockdown in hASCs is mediated through endogenous activation of BMP and ERK/FGF signaling leading, in turn, to upregulation of TAZ, a transcriptional modulator of MSCs differentiation along the osteoblast lineage. Inhibition either of BMP or ERK/FGF signaling suppressed TAZ upregulation and the enhanced osteogenesis in shTWIST1 hASCs. Cosilencing of both TWIST1 and TAZ abrogated the effect elicited by TWIST1 knockdown thus, identifying TAZ as a downstream mediator through which TWIST1 knockdown enhanced osteogenic differentiation in hASCs. Our functional study contributes to a better knowledge of molecular mechanisms governing the osteogenic ability of hASCs, and highlights TWIST1 as a potential target to facilitate in vivo bone healing
Adipose-Derived Stem Cells: A Review of Signaling Networks Governing Cell Fate and Regenerative Potential in the Context of Craniofacial and Long Bone Skeletal Repair
No full textImprovements in medical care, nutrition and social care are resulting in a commendable change in world population demographics with an ever increasing skew towards an aging population. As the proportion of the world’s population that is considered elderly increases, so does the incidence of osteodegenerative disease and the resultant burden on healthcare. The increasing demand coupled with the limitations of contemporary approaches, have provided the impetus to develop novel tissue regeneration therapies. The use of stem cells, with their potential for self-renewal and differentiation, is one potential solution. Adipose-derived stem cells (ASCs), which are relatively easy to harvest and readily available have emerged as an ideal candidate. In this review, we explore the potential for ASCs to provide tangible therapies for craniofacial and long bone skeletal defects, outline key signaling pathways that direct these cells and describe how the developmental signaling program may provide clues on how to guide these cells in vivo. This review also provides an overview of the importance of establishing an osteogenic microniche using appropriately customized scaffolds and delineates some of the key challenges that still need to be overcome for adult stem cell skeletal regenerative therapy to become a clinical reality
A comparative analysis of the osteogenic effects of BMP-2, FGF-2, and VEGFA in a calvarial defect model.
No full textThe utilization of growth factors for bone regeneration is a widely studied field. Since the approval of bone morphogenetic protein-2 (BMP-2) for therapeutic use in humans, the concept of utilizing growth factors for bone regeneration in translational medicine has become even more attractive. Despite many studies published on individual growth factors in various bone models, comparative analysis is largely lacking. The aim of our study was to compare three different proosteogenic factors under identical in vivo conditions. Thus, we tested the bone regeneration capacity of the three different growth factors BMP-2, fibroblast growth factor-2 (FGF-2), and vascular endothelial growth factor A (VEGFA) in a calvarial defect model. We demonstrated that BMP-2 and VEGFA had similar bone healing capacities, resulting in complete calvarial healing as early as week 3. FGF-2 also showed a significantly higher bone regeneration capacity; however, the healing rate was lower than with BMP-2 and VEGFA. Interestingly, these findings were paralleled by an increased angiogenic response upon healing in BMP-2– and VEGFA-treated calvarial defects as compared with FGF-2. Immunohistochemistry for proliferating and osteoprogenitor cells revealed activity at different points after surgery among the groups. In conclusion, we demonstrated an efficient bone regeneration capacity of both BMP-2 and VEGFA, which was superior to FGF-2. Moreover, this study highlights the efficient bone regeneration of VEGFA, which was comparable with BMP-2. These data provide a valuable comparative analysis, which can be used to further optimize growth factor–based strategies in skeletal tissue engineering
A trajetória de (sobre)vivência da personagem Natalina no conto Quantos filhos Natalina Teve? do livro Olhos d'água de Conceição Evaristo
No full textThis paper aims to underscore the path of the character Natalina from the short
story Quantos filhos Natalina teve?, who survived turbulent pregnancies. Through this
narrative, compiled in the book Olhos d’água, written by Conceição Evaristo, the author
highlights elements of resistance of the black poor woman. Using a theoretical perspective that
includes and ponders about the black feminism, from the decolonial feminism. Evaristo is an
admirer of the memory and explores them in hers escrevivências, a word the author uses to
characterize the writing about her perceptions, as well as other women. That’s the approach the writer selected to give voice for those who were historically excluded: black people, poor
people and women.O presente artigo analisa a trajetória de (sobre)vivência da personagem Natalina no conto Quantos filhos Natalina teve?, compilado no livro Olhos d’água da escritora brasileira Conceição Evaristo e busca, por meio das turbulentas gestações, apontar elementos de resistência dessa mulher negra e pobre. Usufruindo, para tanto, de uma perspectiva teórica que reflete a respeito do feminismo negro, do feminismo decolonial. Apreciadora das memórias, Evaristo desfruta delas para produzir as suas “escrevivências” e institui um verossímil lugar de fala às suas personagens: mulheres negras, subalternizadas
Architetture e architetti di Casa Chigi nel primo Rinascimento altolaziale
No full textLa fabbrica del santuario altolaziale di S. Maria della Sughera presso Tolfa venne finanziata dal banchiere senese Agostino Chigi e realizzata fra il 1504 e il 1523 nella forma di una tribuna ottagonale libera avente in asse, nella parte postica, un convento agostiniano. L’argomento è già stato trattato in un volume monografico pubblicato dalla scrivente nel 1998: in esso ha attribuito la paternità del complesso devozionale chigiano a Baldassarre Peruzzi, non senza riserve per alcune peculiarità della grande «cappella» e per la presenza sul cantiere di un architetto minore, Bernardino di Giovanni da Viterbo, più noto come scalpellino-scultore e costruttore. Il presente saggio si è ora proposto d’approfondire la personalità artistica del maestro viterbese per verificare se potesse a lui ascriversi il progetto del santuario tolfetano. È in conclusione apparso probabile che, senza escludere il coinvolgimento del Peruzzi, nel cantiere di Tolfa Bernardino possa aver definito in fase d’esecuzione i dettagli architettonici e costruttivi della Tribuna.
Riassumendo e organizzando gli attuali dati di conoscenza, in mancanza di sue opere architettoniche certe, nel presente contributo si producono riflessioni originali e documenti inediti, utili a proseguire lo studio sull’artista viterbese e sulle sue effettive capacità di architetto. Vagliando la bibliografia già edita sull’architetto viterbese e avvalendosi di nuove ricerche d’archivio, lo studio ha consentito all’autrice di rilevare la presenza dell’architetto e scultore in cantieri dove hanno operato gli architetti Antonio da Sangallo il Giovane e Baldassarre Peruzzi e per il momento solo di ipotizzare, con questi, possibili ripetute collaborazioni. La ricerca ha inoltre permesso di chiarire su basi documentali l’effettivo ruolo di Bernardino da Viterbo nella realizzazione della Chiesa di S. Giovanni degli Almadiani a Viterbo e di proporre la sua identificazione con un omonimo architetto attivo a Ronciglione nel periodo in cui Antonio da Sangallo il Giovane lavorò all’ampliamento farnesiano della città altolaziale. L’identificazione, se comprovata, aggiungerebbe un nuovo tassello di conoscenza della variegata attività di Bernardino.
Allegandolo in 'Appendice' al presente contributo, N. Mannino ha inoltre elaborato il primo regesto biografico ragionato sull’architetto viterbese. Ne emerge una figura di artista, architetto e tecnico dalle molteplici capacità, che entra a buon diritto nel panorama storico-artistico del Rinascimento romano e laziale.Santa Maria della Sughera near Tolfa, financed by the banker from Siena Agostino Chigi, was built in the shape of an octagonal tribuna. In a previous monographic contribution the author attributed the complex to Baldassare Peruzzi, but not without reservations due to several unique characteristics of the large “chapel” and the presence of a less famous architect on the worksite: Bernardino di Giovanni da Viterbo, better known as a chiseller-sculptor and builder. The paper reviews the personality of the maestro from Viterbo to verify whether the design of the sanctuary could be his. Without excluding the fact that Peruzzi did work on the sanctuary, Bernardino probably designed the architectural and building details of the tribuna during its construction. Without the comfort of certified architectural works, and based on current data, the paper discusses and presents original ideas and unpublished documents which can be used in further studies about Bernardino di Giovanni. By screening the bibliography already published on Bernardino and making use of new research in archives, the study allowed the Author to notice the presence of the Architect and Sculptor from Viterbo in building yards where worked the architects Antonio da Sangallo the Younger and Baldassare Peruzzi and for the moment only to suppose possible, repeated collaborations with the same personages. The research also clarified on documentary bases the actual role of Bernardino da Viterbo in the construction of the church of S. Giovanni degli Almadiani in Viterbo and led to propose his identification with a namesake architect active in Ronciglione in the period in which Antonio da Sangallo the Younger worked for the expansion of this city in Northern Lazio on behalf of the Farnese Family. The identification, if ascertained, would add a new element to the knowledge of the varied activities of Bernardino.
The Author has elaborated the first reasoned biographical Regesto on the Architect of Viterbo and has enclosed it in form of Appendix to such essay published. What emerges is the personality of an artist, architect and multi-capable engineer, which enters rightfully in the art-historical landscape of Renaissance of Rome and Lazio
Ribonucleases and angiogenins from fish.
No full textFor the first time fish RNases have been isolated and characterized. Their functional and structural properties indicate that they belong to the RNase A superfamily (or tetrapod RNase superfamily), now more appropriately described as the vertebrate RNase superfamily. Our findings suggest why previously repeated efforts to isolate RNases from fish tissues have met with no success; fish RNases have a very low ribonucleolytic activity, and their genes have a low sequence identity with those of mammalian RNases. The investigated RNases are from the bony fish Danio rerio (or zebrafish). Their cDNAs have been cloned and expressed, and the three recombinant proteins have been purified to homogeneity. Their characterization has revealed that they have indeed a very low RNA-degrading activity, when compared with that of RNase A, the superfamily prototype, but comparable with that of mammalian angiogenins; that two of them have angiogenic activity that is inhibited by the cytosolic RNase inhibitor. These data and a phylogenetic analysis indicate that angiogenic fish RNases are the earliest diverging members of the vertebrate superfamily, suggesting that ribonucleases with angiogenic activity were the ancestors of all ribonucleases in the superfamily. They later evolved into both mammalian angiogenins and, through a successful phylogenesis, RNases endowed with digestive features or with diverse bioactivities
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