71 research outputs found
Innovation and Design
No full textThe focus of design studies has shifted from a product-centric perspective to a perspective in which value is defined by and co-created with the consumer, rather than embedded in the output. The reasoning hence focuses on the interplay between innovation and design processes. Moving from an earlier conceptualization of design-driven innovation, the attempt is to define the space of interaction between the different components of the innovation process. In this way a 3D innovation space can be sketched where different practices and experiences can be mapped. Through this exercise the key hypothesis of this work is empowered: no innovation is possible without design.Design Conceptualization and Communicatio
Correction to: Correlation between IPSET‐t risk at diagnosis and subsequent hemorrhage in patients with essential thrombocythemia; a single institution experience (Annals of Hematology, (2024), 103, 2, (443-448), 10.1007/s00277-023-05578-8)
No full textThe author regrets that in the original publication, the name of Matteo Liberi who contributed to data collection and analysis, has not been included. The correct authors’ list is presented below. Luca Tosoni1, Matteo Liberi1, Gianluca Morelli1, Maria Elena Zannier1, Davide Lazzarotto1, Carla Filì1, Erica Simeone1, Giulia Battaglia1, Chiara Callegari1, Matteo Fanin1, Daniela Damiani1,2, Renato Fanin1,2, Mario Tiribelli1,2 The author would like to apologize for any inconvenience caused. The original article has been corrected
Functional purification of human and mouse mammary stem cells
No full textNormal and tumor stem cells are present in rare quantities in tissues and this has historically represented a major hurdle to in-depth investigations of their biology. In the case of the mammary gland, the relative promiscuity of the immunophenotypical markers described in several studies for the isolation of human and mouse mammary stem cells limits their usefulness, in particular when highly purified mammary stem cell fractions are required for an in-depth molecular and functional characterization (Stingl et al. Nature 439:993-997, 2006; Shackleton et al. Nature 439:84-88, 2006; Liao et al. Cancer Res 67:8131-8138, 2007; Eirew et al. Nat Med 14:1384-1389, 2008; Raouf et al. Cell Stem Cell 3:109-118, 2008; Lim et al. Nat Med 15:907-913, 2009). In fact, most so-called stem cell markers are not selectively expressed by mammary stem cells, but are instead also expressed by terminally differentiated luminal and/or myoepithelial cells or by bipotent progenitors within the mammary gland (Stingl et al. Nature 439:993-997, 2006; Eirew et al. Nat Med 14:1384-1389, 2008; Raouf et al. Cell Stem Cell 3:109-118, 2008; Stingl et al. Differentiation 63:201-213, 1998; Jones et al. Cancer Res 64:3037-3045, 2004). Here, we describe a new methodology that does not require the use of immunophenotypical markers to obtain highly pure populations of mammary stem cells. This approach exploits two functional properties of mammary stem cells: (1) their quiescent or slowly proliferative phenotype, as compared to their progeny; and (2) their ability to survive and proliferate in anchorage-independent conditions, giving rise to clonal spheroids, commonly known as "mammospheres" (Dontu et al. Genes Dev 17:1253-1270, 2003; Pece et al. Cell 140:62-73, 2010; Cicalese et al. Cell 138:1083-1095, 2009). In the context of mammospheres, stem cells, which perform one or two rounds of division and then reenter quiescence, are identified based on their ability to retain a lipophilic fluorescent dye, PKH26, that is by contrast progressively lost by dilution in the actively proliferating progeny of precursors (Pece et al. Cell 140:62-73, 2010; Cicalese et al. Cell 138:1083-1095, 2009). Following mammosphere dissociation, the differential degree of PKH26 epifluorescence displayed by stem cells compared to precursor cells is exploited for their purification by FACS sorting. As a result, the scarcely represented PKH26-labeled mammary stem cells are purified to near homogeneity and can be used for further molecular and biological studies
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Molecular mechanisms underlying the spatial and temporal regulation of constitutive and ligand-dependent endocytosis
No full textCAP (Cbl associated protein) regulates receptor-mediated endocytosis
No full textAbstractCAP (c-Cbl associated protein)/ponsin belongs to a family of adaptor proteins implicated in cell adhesion and signaling. Here we show that CAP binds to and co-localizes with the essential endocytic factor dynamin. We demonstrate that CAP promotes the formation of dynamin-decorated tubule like structures, which are also coated with actin filaments. Accordingly, we found that the expression of CAP leads to the inhibition of dynamin-mediated endocytosis and increases EGFR stability. Thus, we suggest that CAP may coordinate the function of dynamin with the regulation of the actin cytoskeleton during endocytosis.Structured summary:MINT-6804322: CAP (uniprotkb:Q9BX66) physically interacts (MI:0218) with Cbl (uniprotkb:Q8K4S7) and dynamin 2 (uniprotkb:P39052) by pull down (MI:0096)MINT-6804285: CAP (uniprotkb:Q9BX66) physically interacts (MI:0218) with FAK (uniprotkb:O35346), vinculin (uniprotkb:P85972) and dynamin 2 (uniprotkb:P39052) by pull down (MI:0096)MINT-6804245, MINT-6804259, MINT-6804272: CAP (uniprotkb:Q9BX66) physically interacts (MI:0218) with dynamin 2 (uniprotkb:P39052) by pull down (MI:0096)MINT-6804344: CAP (uniprotkb:Q9BX66) physically interacts (MI:0218) with dynamin 2 (uniprotkb:P50570) by anti tag coimmunoprecipitation (MI:0007)MINT-6804371: dynamin 1 (uniprotkb:P21575) physically interacts (MI:0218) with CAP (uniprotkb:O35413) by anti bait coimmunoprecipitation (MI:0006)MINT-6804446, MINT-6804464: F-actin (uniprotkb:P60709), CAP (uniprotkb:Q9BX66) and dynamin 2 (uniprotkb:P50570) colocalize (MI:0403) by fluorescence microscopy (MI:0416
Clathrin-Mediated Internalization Is Essential for Sustained EGFR Signaling but Dispensable for Degradation
No full textSummaryClathrin-mediated endocytosis (CME) is the major pathway of epidermal growth factor receptor (EGFR) internalization. It is commonly believed that CME mediates long-term attenuation of EGFR signaling by targeting the receptor for degradation. However, the EGFR can also be internalized through (a) clathrin-independent pathway(s), and it remains unclear why distinct mechanisms of internalization have evolved. Here, we report that EGFRs internalized via CME are not targeted for degradation, but instead are recycled to the cell surface. By contrast, clathrin-independent internalization preferentially commits the receptor to degradation. This finding has profound implications for signaling, as by skewing EGFR fate toward recycling rather than degradation, CME prolongs the duration of signaling. Our data show that CME determines the longevity of some EGFR-activated signaling pathways and that EGF-dependent biological responses, such as DNA synthesis, absolutely require CME. Thus, CME of the EGFR unexpectedly has a greater impact on receptor signaling than on receptor degradation
NUMB controls p53 tumour suppressor activity
No full textNUMB is a cell fate determinant, which, by asymmetrically partitioning at mitosis, controls cell fate choices by antagonising the activity of the plasma membrane receptor of the NOTCH family. NUMB is also an endocytic protein, and the NOTCH-NUMB counteraction has been linked to this function. There might be, however, additional functions of NUMB, as witnessed by its proposed role as a tumour suppressor in breast cancer. Here we describe a previously unknown function for human NUMB as a regulator of tumour protein p53 (also known as TP53). NUMB enters in a tricomplex with p53 and the E3 ubiquitin ligase HDM2 (also known as MDM2), thereby preventing ubiquitination and degradation of p53. This results in increased p53 protein levels and activity, and in regulation of p53-dependent phenotypes. In breast cancers there is frequent loss of NUMB expression. We show that, in primary breast tumour cells, this event causes decreased p53 levels and increased chemoresistance. In breast cancers, loss of NUMB expression causes increased activity of the receptor NOTCH. Thus, in these cancers, a single event - loss of NUMB expression - determines activation of an oncogene (NOTCH) and attenuation of the p53 tumour suppressor pathway. Biologically, this results in an aggressive tumour phenotype, as witnessed by findings that NUMB-defective breast tumours display poor prognosis. Our results uncover a previously unknown tumour suppressor circuitry
Binding of sFRP-3 to EGF in the extra-cellular space affects proliferation, differentiation and morphogenetic events regulated by the two molecules.
No full textsFRP-3 is a soluble antagonist of Wnts, widely expressed in developing embryos. The Wnt gene family comprises cysteine-rich secreted ligands that regulate cell proliferation, differentiation, organogenesis and oncogenesis of different organisms ranging from worms to mammals. In the canonical signal transduction pathway Wnt proteins bind to the extracellular domain of Frizzled receptors and consequently recruit Dishevelled (Dsh) to the cell membrane. In addition to Wnt membrane receptors belonging to the Frizzled family, several other molecules have been described which share homology in the CRD domain and lack the putative trans-membrane domain, such as sFRP molecules (soluble Frizzled Related Protein). Among them, sFRP-3 was originally isolated from bovine articular cartilage and also as a component of the Spemann organizer. sFRP-3 blocks Wnt-8 induced axis duplication in Xenopus embryos and binds to the surface of cells expressing a membrane-anchored form of Wnt-1. Injection of sFRP-3 mRNA blocks expression of XMyoD mRNA and leads to embryos with enlarged heads and shortened trunks
Social Construction of Technology
No full textThe chapter focuses on the Social Construction of Technology approach (SCOT) by Trevor Pinch and Wiebe Bijker, introducing the reader to its initial formulation (1984), and to the subsequent extensions – and sometimes reformulations – elaborated in more than 30 year of empirical research. It first clarifies how the Empirical Programme of Relativism, elaborated by the Bath School to address the social construction of scientific facts, was adapted to technological artifacts. In particular the concepts of relevant social groups, interpretative flexibility, closure or stabilization are in-depth discussed. Regarding relevant social groups, the chapter dedicates a peculiar attention to users, sellers and testers, all understudied in the original formulation of SCOT. The chapter then clarifies SCOT’s take on materiality, and discusses its main differences with the idea of nonhuman agency proposed by Actor-Network Theory (ANT). Finally, it goes back to the Golem Trilogy to discuss with the author the specific take on politics implied by SCOT.</p
p63 sustains self-renewal of mammary cancer stem cells through regulation of Sonic Hedgehog signaling
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