1,720,968 research outputs found
A GENE NETWORK FOR HEAD ORGANIZER FORMATION
Get PDFThe Spemann organizer determines the body plan, in its full variety of tissue components, normal proportion and placement. Although individual organizer's inducers responsible for head and trunk inductions have been identified, how these are handed out in perfect quantitative, spatial and temporal coordination remains enigmatic.
Here we focused on the mechanisms establishing the organizer own architecture as key to explain such signaling coordination. We found that a crosstalk between two ligands emanating from the trunk organizer, Nodal and ADMP, defines a miniature anteroposterior axis. At its posterior pole, Nodal protects headinduction by competing ADMP for a shared receptor, ACVR2a; ADMP is allowed to signal more anteriorly to restrain these inductions. These opposing signaling centers reciprocally adjust their strength and range of activity by multiple negative and positive loops. In so doing, the levels of head inducers remains proportional to signals generated in the trunk and buffered against their fluctuations. Several new regulatory elements are essential for this dynamic crosstalk, including a microRNA, miR-15/16, endowing robustness to head formation.
In sum, we propose a model that offers a molecular explanation for key properties of the Spemann's organizer.L'organizzatore di Spemann è un tessuto con proprietà uniche in quanto determina il piano corporeo dei vertebrati: la totalità dei vari componenti tissutali, nelle giuste proporzioni e corretto posizionamento. Nonostante che i singoli “induttori” di testa e tronco siano stati identificati, il come questi si assemblino in modo coordinato (quantitativamente, spazialmente e temporalmente) rimane tuttora un mistero.
Per comprendere questo fenomeno, in questa tesi ci siamo concentrati sui meccanismi che stabiliscono l’architettura interna dello stesso organizzatore. Abbiamo trovato che l’attività di due ligandi, Nodal ed ADMP, realizza una rete genica che definisce un asse antero-posteriore in miniatura, localizzato nell’endoderma dorsale. Al polo posteriore di questo “asse”, Nodal protegge l’induzione della testa competendo con ADMP per un recettore condiviso, ACVR2a; ADMP riesce ad agire solo molto più anteriormente, e nel fare questo, restringe le induzioni di Nodal. Questi segnali opposti riaggiustano la loro forza e dominio di azione in modo reciproco, attraverso feedback negativi e positivi. Così facendo, i livelli di induttori della testa restano proporzionali ai segnali generali dal tronco e tamponati contro eventuali variazioni degli stessi. Nuovi elementi di regolazione sono essenziali in questa dinamica comunicazione; tra questi, un microRNA, miR-15/16, che garantisce robustezza alla formazione della testa.
In conclusione, qui proponiamo un modello che offre una spiegazione molecolare delle proprietà dell’organizzatore di Spemann
Induction of Expandable Tissue-Specific Stem/Progenitor Cells through Transient Expression of YAP/TAZ
Get PDFThe ability to induce autologous tissue-specific stem cells in culture could have a variety of applications in regenerative medicine and disease modeling. Here we show that transient expression of exogenous YAP or its closely related paralogue TAZ in primary differentiated mouse cells can induce conversion to a tissue-specific stem/progenitor cell state. Differentiated mammary gland, neuronal, and pancreatic exocrine cells, identified using a combination of cell sorting and lineage tracing approaches, efficiently convert to proliferating cells with properties of stem/progenitor cells of their respective tissues after YAP induction. YAP-induced mammary stem/progenitor cells show molecular and functional properties similar to endogenous MaSCs, including organoid formation and mammary gland reconstitution after transplantation. Because YAP/TAZ function is also important for self-renewal of endogenous stem cells in culture, our findings have implications for understanding the molecular determinants of the somatic stem cell state
Germ-Layer Specification and Control of Cell Growth by Ectodermin, a Smad4 Ubiquitin Ligase
Get PDFTGF-beta signaling is essential for development and proliferative homeostasis. During embryogenesis, maternal determinants act in concert with TGF-beta signals to form mesoderm and endoderm. In contrast, ectoderm specification requires the TGF-beta response to be attenuated, although the mechanisms by which this is achieved remain unknown. In a functional screen for ectoderm determinants, we have identified Ectodermin (Ecto). In Xenopus embryos, Ecto is essential for the specification of the ectoderm and acts by restricting the mesoderm-inducing activity of TGF-beta signals to the mesoderm and favoring neural induction. Ecto is a RING-type ubiquitin ligase for Smad4, a TGF-beta signal transducer. Depletion of Ecto in human cells enforces TGF-beta-induced cytostasis and, moreover, plays a causal role in limiting the antimitogenic effects of Smad4 in tumor cells. We propose that Ectodermin is a key switch in the control of TGF-beta gene responses during early embryonic development and cell proliferation
Convergence of p53 and TGF-beta signaling networks.
No full textp53 is a protein with many talents. One of the most fundamental is the ability to act as essential growth checkpoint that protects cells against cellular transformation. p53 does so through the induction of genes leading to growth arrest or apoptosis. Most of the studies focusing on the mechanisms of p53 activity have been performed in cultured cells upon treatment with well-established p53-activating inputs, such as high doses of radiations, DNA-damaging drugs and activated oncogenes. However, how the tumor suppressive functions of p53 become concerted with the extracellular cues arriving at the cell surface during tissue homeostasis, remains largely unknown. Intriguingly, two recent papers have shed new light into this unexplored field, indicating that p53 plays a key role in TGF-beta-induced growth arrest and, unexpectedly, in the developmental effects of TGF-beta in early embryos. Here we review and comment on these findings and on their implications for cancer biology
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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