How to Build Collective Capabilities: The 3C-Model for Grassroots-led Development

Capabilities need to be built from the bottom-up. Social innovations at the grassroots seek to present new solutions to existing social problems. However, since the poor suffer from limitations on their individual capabilities and agency, they engage in acts of collective agency to generate new collective capabilities that each individual alone would not be able to achieve. The question is: how can these acts of collective agency be initiated, supported and sustained in practice? What roles can development actors (such as the state, donors and NGOs) play in supporting these acts of collective agency? Drawing on the literature on social innovation, the capability approach, participation and empowerment, the paper argues that three crucial C-processes are integral conditions for promoting successful, scalable and sustainable social innovations at the grassroots, namely: (1) Conscientization; (2) Conciliation and (3) Collaboration. By linking the individual, collective and institutional levels of analysis, the paper demonstrates the importance of individual behavioural changes, collective agency and local institutional reforms for the success, sustainability and scalability of social innovations at the grassroots. The paper acknowledges conflict, capture and cooptation as potential limitations and recognizes the role of contextual factors in initiating, implementing and sustaining social innovations at the grassroots

Maternal Embryonic Leucine Zipper Kinase is Associated with Metastasis in Triple-negative Breast Cancer

UNLABELLED: Triple-negative breast cancer (TNBC) has high relapse and metastasis rates and a high proportion of cancer stem-like cells (CSC), which possess self-renewal and tumor initiation capacity. MELK (maternal embryonic leucine zipper kinase), a protein kinase of the Snf1/AMPK kinase family, is known to promote CSC maintenance and malignant transformation. However, the role of MELK in TNBC metastasis is unknown; we sought to address this in the current study. We found that SIGNIFICANCE: These findings indicate that MELK is a driver of aggressiveness and metastasis in TNBC

Para que servem os inventários de fauna?

Inventários de fauna acessam diretamente a diversidade de uma localidade, em um determinado espaço e tempo. Os dados primários gerados pelos inventários compõem uma das ferramentas mais importantes na tomada de decisões a respeito do manejo de áreas naturais. Entretanto, vários problemas têm sido observados em diversos níveis relacionados aos inventários de fauna no Brasil e vão desde a formação de recursos humanos até a ausência de padronização, de desenho experimental e de seleção de métodos inadequados. São apresentados estudos de caso com mamíferos, répteis, anfíbios e peixes, nos quais são discutidos problemas como variabilidade temporal e métodos para detecção de fauna terrestre, sugerindo que tanto os inventários quanto os programas de monitoramento devam se estender por prazos maiores e que os inventários devem incluir diferentes metodologias para que os seus objetivos sejam plenamente alcançados.Inventories of fauna directly access the diversity of a locality in a certain period of time. The primary data generated by these inventories comprise one of the most important steps in decisions making regarding the management of natural areas. However, several problems have been observed at different levels related to inventories of fauna in Brazil, and range from the training of humans to the lack of standardization of experimental design and selection of inappropriate methods. We present case studies of mammals, reptiles, amphibians and fishes, where they discussed issues such temporal variability and methods for detection of terrestrial fauna, suggesting that both inventories and monitoring programs should be extended for longer terms and that inventories should include different methodologies to ensure that their goals are fully achieved

Asymptotic behavior of solutions to the σk\sigma_k-Yamabe equation near isolated singularities

$\sigma_k$-Yamabe equations are conformally invariant equations generalizing the classical Yamabe equation. In an earlier work YanYan Li proved that an admissible solution with an isolated singularity at $0\in \mathbb R^n$ to the $\sigma_k$-Yamabe equation is asymptotically radially symmetric. In this work we prove that an admissible solution with an isolated singularity at $0\in \mathbb R^n$ to the $\sigma_k$-Yamabe equation is asymptotic to a radial solution to the same equation on $\mathbb R^n \setminus \{0\}$. These results generalize earlier pioneering work in this direction on the classical Yamabe equation by Caffarelli, Gidas, and Spruck. In extending the work of Caffarelli et al, we formulate and prove a general asymptotic approximation result for solutions to certain ODEs which include the case for scalar curvature and $\sigma_k$ curvature cases. An alternative proof is also provided using analysis of the linearized operators at the radial solutions, along the lines of approach in a work by Korevaar, Mazzeo, Pacard, and Schoen.Comment: 55 page

Plant ARGONAUTEs: Features, Functions and Unknowns

ARGONAUTEs (AGOs) are the effector proteins in eukaryotic small RNA(sRNA)– based gene silencing pathways controlling gene expression and transposon activity. In plants, AGOs regulate key biological processes such as development, response to stress, genome structure and integrity, and pathogen defense. Canonical functions of plant AGO–sRNA complexes include the endonucleolytic cleavage or translational inhibition of target RNAs, and the methylation of target DNAs. Here, I provide a brief update on the major features, molecular functions and biological roles of plant AGOs. A special focus is given to the more recent discoveries related to emerging molecular or biological functions of plant AGOs, as well as to the major unknowns in the plant AGO field.This work was supported by an Individual Fellowship from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement No. 655841 to A.C.Carbonell Olivares, A. (2017). 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Design and development of a peptide-based adiponectin receptor agonist for cancer treatment

<p>Abstract</p> <p>Background</p> <p>Adiponectin, a fat tissue-derived adipokine, exhibits beneficial effects against insulin resistance, cardiovascular disease, inflammatory conditions, and cancer. Circulating adiponectin levels are decreased in obese individuals, and this feature correlates with increased risk of developing several metabolic, immunological and neoplastic diseases. Thus, pharmacological replacement of adiponectin might prove clinically beneficial, especially for the obese patient population. At present, adiponectin-based therapeutics are not available, partly due to yet unclear structure/function relationships of the cytokine and difficulties in converting the full size adiponectin protein into a viable drug.</p> <p>Results</p> <p>We aimed to generate adiponectin-based short peptide that can mimic adiponectin action and be suitable for preclinical and clinical development as a cancer therapeutic. Using a panel of 66 overlapping 10 amino acid-long peptides covering the entire adiponectin globular domain (residues 105-254), we identified the 149-166 region as the adiponectin active site. Three-dimensional modeling of the active site and functional screening of additional 330 peptide analogs covering this region resulted in the development of a lead peptidomimetic, ADP 355 (H-DAsn-Ile-Pro-Nva-Leu-Tyr-DSer-Phe-Ala-DSer-NH₂). In several adiponectin receptor-positive cancer cell lines, ADP 355 restricted proliferation in a dose-dependent manner at 100 nM-10 μM concentrations (exceeding the effects of 50 ng/mL globular adiponectin). Furthermore, ADP 355 modulated several key signaling pathways (AMPK, Akt, STAT3, ERK1/2) in an adiponectin-like manner. siRNA knockdown experiments suggested that ADP 355 effects can be transmitted through both adiponectin receptors, with a greater contribution of AdipoR1. <it>In vivo</it>, intraperitoneal administration of 1 mg/kg/day ADP 355 for 28 days suppressed the growth of orthotopic human breast cancer xenografts by ~31%. The peptide displayed excellent stability (at least 30 min) in mouse blood or serum and did not induce gross toxic effects at 5-50 mg/kg bolus doses in normal CBA/J mice.</p> <p>Conclusions</p> <p>ADP 355 is a first-in-class adiponectin receptor agonist. Its biological activity, superior stability in biological fluids as well as acceptable toxicity profile indicate that the peptidomimetic represents a true lead compound for pharmaceutical development to replace low adiponectin levels in cancer and other malignancies.</p

The Legacy of a ‘Living Library’: On the Reception of John Smith

John Smith was among the first of the Cambridge Platonists. He was therefore in a position to influence not only his contemporaries but all those who followed after him well into the twentieth century and beyond. Well established lines of influence both to and from Whichcote, Cudworth, and More are explored first before moving on to less well-known connections to Bishop Simon Patrick and mathematician Isaac Barrow. Smith’s continued significance for eighteenth century theology is demonstrated through discussion of his inspiration of the doctrines of spiritual sensation developed by Jonathan Edwards and John Wesley. Special notice is also given to Smith’s authority as an interpreter of Biblical prophecy through the eighteenth and nineteenth centuries. The chapter concludes with looks at Smith’s influence on Samuel Taylor Coleridge, Ralph Waldo Emerson, William Ralph Inge, Rufus Jones, Pierre Hadot, and others. This chapter, offers a broad, but highly selective, overview of the reception and influence of Smith’s life and work. It is intended, however, as a call for future research more than as an authoritative presentation of Smith’s legacy. For, if the Cambridge Platonists have been underappreciated until recently, none of them have been unjustly ignored as consistently as Smith