The Sustainable Development Goals and the New Urban Agenda recognise the role of cities in achieving sustainable development. However, these agendas were agreed and signed by national governments and thus implementing them at the local level requires a process of adaptation or localisation. In this paper, we analyse five aspects that practitioners and researchers need to consider when localising them: (1) delimitation of the urban boundary; (2) integrated governance; (3) actors; (4) synergies and trade-offs and (5) indicators. These considerations are interrelated, and while not exhaustive, provide an important initial step for reflection on the challenges and opportunities of working with these global agendas at the local level. The paper draws on the inception phase of an international comparative transdisciplinary research project in seven cities on four continents: Buenos Aires
Src homology 2 domain-containing phosphatase 2 (Shp2), encoded by Ptpn11, is a member of the nonreceptor proteintyrosine phosphatase family, and functions in cell survival, proliferation, migration, and differentiation in many tissues. Here we report that loss of IntroductionHematopoiesis is maintained by a small number of multipotent long-term hematopoietic stem cells (LT-HSCs) with extensive self-renewal capability. These cells give rise to lineage-committed progenitors, which produce various types of mature blood cells. Cytokine and growth factor signaling is critical for the sustained production of HSCs and progenitors and directs cellular survival, migration, and differentiation. 1,2 Src homology 2 (SH2) domain-containing phosphatase 2 (Shp2) is a ubiquitously expressed nonreceptor protein-tyrosine phosphatase (PTP), encoded by the Ptpn11 gene, which regulates signaling networks and cell fates in many organisms. Shp2 is composed of 2 SH2 domains (N-SH2 and C-SH2), a PTP domain, a C-terminal tail with tyrosyl phosphorylation sites that modulate some RTK signaling pathways, and a proline-rich motif of unknown function. In multiple tissues, Shp2 positively regulates Ras/Erk signaling downstream of receptor tyrosine kinases (RTKs) and cytokine receptors. 3 Shp2 also appears to have cell-type-and/or agonistdependent effects on the activation of Akt, Jnk, NF-B, Rho, and Nfat. 3 Germline PTPN11 mutations underlie approximately 50% of Noonan syndrome, which is characterized by short stature, skeletal abnormalities, cardiac defects, learning disabilities, and a predisposition to hematologic abnormalities, particularly juvenile myelomonocytic leukemia. Somatic gain-of-function mutations in PTPN11 also are the most common cause of sporadic juvenile myelomonocytic leukemia. 4 Although Shp2 is required for normal Ras/Erk activation in many contexts, 3 the underlying mechanism shows great diversity and depends on the precise cell type and stimulus involved. Epistasis studies in Caenorhabditis elegans and Drosophila show that activated Ras/let-60/ras1 suppresses the effects of Shp2/ptp-2/ csw loss, 5,6 arguing that Shp2 acts upstream of Ras in these signaling pathways. However, in C elegans vulva development and Drosophila R7 photoreceptors and muscle precursors, Shp2/ptp-2/ csw appears to act downstream of Ras/let-60/ras1 in some contexts. 5,7-9 Furthermore, in the EGL-15/Egfr signaling pathway, ptp-2 may act parallel to let-60. 10 In mice, expression of activated Kras (Kras G12D ) does not completely restore defective lens proliferation and lacrimal gland development caused by the loss of Ptpn11. 11 Collectively, these results indicate that Shp2 can act upstream, downstream, or parallel to Ras in different systems, and imply that the consequences and the mediators of Shp2 action must be specifically delineated in particular biologic contexts.Homozygous inactivation of murine Shp2 results in early embryonic lethality 12-14 because of a critical role of Shp2 in trophoblast stem cell survival. 14 Loss of Shp2 also reduces...
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