NOX-driven ROS formation in cell transformation of FLT3-ITD positive AML

In different types of myeloid leukemia, increased formation of reactive oxygen species (ROS) has been noted and associated with aspects of cell transformation including the promotion of leukemic cell proliferation and migration, as well as DNA-damage and accumulation of mutations. Work reviewed in this article has shown the involvement of NADPH oxidase (NOX)-derived ROS downstream of oncogenic protein-tyrosine kinases in both processes, and the related pathways have been partially identified. FLT3-ITD, an important oncoprotein in a subset of AML, causes activation of AKT and subsequently stabilization of p22phox, a regulatory subunit for NOX1-4. This process is linked to ROS formation and DNA damage. Moreover, FLT3-ITD signaling through STAT5 enhances expression of NOX4, ROS formation and inactivation of the protein-tyrosine phosphatase DEP-1/PTPRJ, a negative regulator of FLT3 signaling, by reversible oxidation of its catalytic cysteine residue. Genetic inactivation of NOX4 restored DEP-1 activity and attenuated cell transformation by FLT3-ITD in vitro and in vivo. Future work is required to further explore these mechanisms and their causal involvement in leukemic cell transformation, which may result in the identification of novel candidate targets for therapy.

Sources, Fate and Transformation of Organic Matter in Wetlands and Estuaries

Dissolved organic matter (DOM) is a complex mixture of organic compounds and represents the largest reservoirs of carbon (C) on earth. Particulate organic matter (POM) is another important carbon component in C cycling and controls a variety of biogeochemical processes. Estuaries, as important interfaces between land and ocean, play important roles in retaining and transforming such organic matter (OM) and serve as both sources and sinks of DOM and POM. There is a diverse array of both autochthonous and allochthonous OM sources in wetland/estuarine ecosystems. A comprehensive study on the sources, transformation and fate of OM in such ecosystems is essential in advancing our understanding of C cycling and better constraining the global C budget. In this work, DOM characteristics were investigated in different estuaries. Dissolved organic matter source strengths and dynamics were assessed in a seagrass-dominated subtropical estuarine lagoon. DOM dynamics controlled by hydrology and seagrass primary productivity were confirmed, and the primary source of DOM was quantified using the combination of excitation emission matrix fluorescence with parallel factor analysis (EEM-PARAFAC) and stable C isotope analysis. Seagrass can contribute up to 72% of the DOM in the study area. The spatial and temporal variation of DOM dynamics was also studied in a freshwated dominated estuary fringed with extensive salt marshes. The data showed that DOM was primarily derived from freshwater marshes and controlled by hydrology while salt marsh plants play a significant role in structuring the distribution patterns of DOM quality and quantity. The OM dynamics was also investigated in a mangrove-dominate estuary and a comparative study was conducted between the DOM and POM pools. The results revealed both similarity and dissimilarity in DOM and POM composition. The dynamics of both OM pools are largely uncoupled as a result of source differences. Fringe mangrove swamps are suggested to export similar amounts of DOM and POM and should be considered as an important source in coastal C budgets. Lastly, chemical characterizations were conducted on the featured fluorescence component in OM in an attempt to better understand the composition and origins of the specific PARAFAC component. The traditionally defined ‘protein-like’ fluorescence was found to contain both proteinaceous and phenolic compounds, suggesting that the application of this parameter as a proxy for amino acid content and bioavailability may be limited.

Reconceptualising International Intervention: Statebuilding, ‘Organic Processes’ and the Limits of Causal Knowledge

This article examines the transformation in the conceptual understanding of international intervention over the last two decades. It suggests that this conceptual shift can be usefully interrogated through its imbrication within broader epistemological shifts highlighting the limits of causal knowledge claims: heuristically framed in this article in terms of the shift from policy interventions within the problematic of causation to those concerned with the management of effects. In this shift, the means and mechanisms of international intervention have been transformed, no longer focused on the universal application of Western causal knowledge through policy interventions but rather on the effects of specific and unique local and organic processes at work in societies themselves. The focus on effects takes the conceptualisation of intervention out of the traditional terminological lexicon of International Relations theory and instead recasts problems in increasingly organicised ways, suggesting that artificial or hubristic attempts at socio-political intervention should be excluded or minimised.

Health reforms in Latin America: processes and results

Two types of health reforms in Latin America are analysed: one based on insurance and service commodification and the one referred to the unified public systems of progressive governments. Health insurance with explicit service packages has not fulfilled their purposes of universal coverage, equal access to necessary health services and improvement of health conditions but has opened health as a field of profit making for insurance companies and private health providers. The national health services as a state obligation have developed territorialized health services and widened substantially timely access to the majority of the population. The adoption of an integrated and wide social policy has an impact on population well fare. It faces some problems derived from the old health systems and the power of the insurance and medical complex.

Three horizons: a pathways practice for transformation

Global environmental change requires responses that involve marked or qualitative changes in individuals, institutions, societies, and cultures. Yet, while there has been considerable effort to develop theory about such processes, there has been limited research on practices for facilitating transformative change. We present a novel pathways approach called Three Horizons that helps participants work with complex and intractable problems and uncertain futures. The approach is important for helping groups work with uncertainty while also generating agency in ways not always addressed by existing futures approaches. We explain how the approach uses a simple framework for structured and guided dialogue around different patterns of change by using examples. We then discuss some of the key characteristics of the practice that facilitators and participants have found to be useful. This includes (1) providing a simple structure for working with complexity, (2) helping develop future consciousness (an awareness of the future potential in the present moment), (3) helping distinguish between incremental and transformative change, (4) making explicit the processes of power and patterns of renewal, (5) enabling the exploration of how to manage transitions, and (6) providing a framework for dialogue among actors with different mindsets. The complementarity of Three Horizons to other approaches (e.g., scenario planning, dilemma thinking) is then discussed. Overall, we highlight that there is a need for much greater attention to researching practices of transformation in ways that bridge different kinds of knowledge, including episteme and phronesis. Achieving this will itself require changes to contemporary systems of knowledge production. The practice of Three Horizons could be a useful way to explore how such transformations in knowledge production and use could be achieved.

Resilience and development: mobilizing for transformation

In 2014, the Third International Conference on the resilience of social-ecological systems chose the theme “resilience and development: mobilizing for transformation.” The conference aimed specifically at fostering an encounter between the experiences and thinking focused on the issue of resilience through a social and ecological system perspective, and the experiences focused on the issue of resilience through a development perspective. In this perspectives piece, we reflect on the outcomes of the meeting and document the differences and similarities between the two perspectives as discussed during the conference, and identify bridging questions designed to guide future interactions. After the conference, we read the documents (abstracts, PowerPoints) that were prepared and left in the conference database by the participants (about 600 contributions), and searched the web for associated items, such as videos, blogs, and tweets from the conference participants. All of these documents were assessed through one lens: what do they say about resilience and development? Once the perspectives were established, we examined different themes that were significantly addressed during the conference. Our analysis paves the way for new collective developments on a set of issues: (1) Who declares/assign/cares for the resilience of what, of whom? (2) What are the models of transformations and how do they combine the respective role of agency and structure? (3) What are the combinations of measurement and assessment processes? (4) At what scale should resilience be studied? Social transformations and scientific approaches are coconstructed. For the last decades, development has been conceived as a modernization process supported by scientific rationality and technical expertise. The definition of a new perspective on development goes with a negotiation on a new scientific approach. Resilience is presently at the center of this negotiation on a new science for development.

Adaptability, Transformation and Complex Changes in Namibia and Tanzania: Resilience and Innovation System Development in Local Communities

This thesis is a research about the recent complex spatial changes in Namibia and Tanzania and local communities’ capacity to cope with, adapt to and transform the unpredictability engaged to these processes. I scrutinise the concept of resilience and its potential application to explaining the development of local communities in Southern Africa when facing various social, economic and environmental changes. My research is based on three distinct but overlapping research questions: what are the main spatial changes and their impact on the study areas in Namibia and Tanzania? What are the adaptation, transformation and resilience processes of the studied local communities in Namibia and Tanzania? How are innovation systems developed, and what is their impact on the resilience of the studied local communities in Namibia and Tanzania? I use four ethnographic case studies concerning environmental change, global tourism and innovation system development in Namibia and Tanzania, as well as mixed-methodological approaches, to study these issues. The results of my empirical investigation demonstrate that the spatial changes in the localities within Namibia and Tanzania are unique, loose assemblages, a result of the complex, multisided, relational and evolutional development of human and non-human elements that do not necessarily have linear causalities. Several changes co-exist and are interconnected though uncertain and unstructured and, together with the multiple stressors related to poverty, have made communities more vulnerable to different changes. The communities’ adaptation and transformation measures have been mostly reactive, based on contingency and post hoc learning. Despite various anticipation techniques, coping measures, adaptive learning and self-organisation processes occurring in the localities, the local communities are constrained by their uneven power relationships within the larger assemblages. Thus, communities’ own opportunities to increase their resilience are limited without changing the relations in these multiform entities. Therefore, larger cooperation models are needed, like an innovation system, based on the interactions of different actors to foster cooperation, which require collaboration among and input from a diverse set of stakeholders to combine different sources of knowledge, innovation and learning. Accordingly, both Namibia and Tanzania are developing an innovation system as their key policy to foster transformation towards knowledge-based societies. Finally, the development of an innovation system needs novel bottom-up approaches to increase the resilience of local communities and embed it into local communities. Therefore, innovation policies in Namibia have emphasised the role of indigenous knowledge, and Tanzania has established the Living Lab network.

Physical modeling of processes of sediment transport in inlets

During the transformation of the low tide to the high tide, an exactly inverse phenomenon is occurred and the high tidal delta is formed at the mouth upstream. Increasing the tidal range does not affect the nature of this phenomenon and just change its intensity. In this situation, the inlet will be balance over time. A new relationship between equilibrium cross section and tidal prism for different tidal levels as well as sediment grading has been provided which its results are corresponded with results of numerical modeling. In the combination state, the wave height significantly affects the current and sedimentary pattern such that the wave height dimensionless index (Hw/Ht) determines the dominant parameter (the short period wave or tide) in the inlet. It is notable that in this state, the inlet will be balanced over the time. In order to calculate sedimentary phenomena, each of which are individually determined under solely wave and only tide conditions and then they are added. Estimated values are similar to numerical modeling results of the combination state considering nonlinear terms. Also, it is clear that the wave and tide performance is of meaning in the direct relationship with the water level. The water level change causes variations of the position of the breaking line and sedimentary active area. It changes the current and sedimentary pattern coastward while does not change anything seaward. Based on modeling results of sediment transport due to the wave, tide and their combination, it could be said that the erosion at the mouth due to the wave is less than that due to the wave and tide combination. In these situations, tide and wave-tide combination increase the low tidal and high tidal delta volume, respectively. Hence, tide plays an effective role in changing sedimentary phenomena at the channel and mouth downstream. Whereas, short period and combined waves have a crucial role in varying the morphology and sediment transport coast ward.

Shifting Processes with Cyclically Exchangeable Increments at Random

International audience

The Effect of Iron Oxide Nanoparticles on the Fate and Transformation of Arsenic in Aquatic Environments

Iron oxides and arsenic are prevalent in the environment. With the increase interest in the use of iron oxide nanoparticles (IONPs) for contaminant remediation and the high toxicity of arsenic, it is crucial that we evaluate the interactions between IONPs and arsenic. The goal was to understand the environmental behavior of IONPs in regards to their particle size, aggregation and stability, and to determine how this behavior influences IONPs-arsenic interactions. A variety of dispersion techniques were investigated to disperse bare commercial IONPs. Vortex was able to disperse commercial hematite nanoparticles into unstable dispersions with particles in the micrometer size range while probe ultrasonication dispersed the particles into stable dispersions of nanometer size ranges for a prolonged period of time. Using probe ultrasonication and vortex to prepare IONPs suspensions of different particle sizes, the adsorption of arsenite and arsenate to bare hematite nanoparticles and hematite aggregates were investigated. To understand the difference in the adsorptive behavior, adsorption kinetics and isotherm parameters were determined. Both arsenite and arsenate were capable of adsorbing to hematite nanoparticles and hematite aggregates but the rate and capacity of adsorption is dependent upon the hematite particle size, the stability of the dispersion and the type of sorbed arsenic species. Once arsenic was adsorbed onto the hematite surface, both iron and arsenic can undergo redox transformation both microbially and photochemically and these processes can be intertwined. Arsenic speciation studies in the presence of hematite particles were performed and the effect of light on the redox process was preliminary quantified. The redox behavior of arsenite and arsenate were different depending on the hematite particle size, the stability of the suspension and the presence of environmental factors such as microbes and light. The results from this study are important and have significant environmental implications as arsenic mobility and bioavailability can be affected by its adsorption to hematite particles and by its surface mediated redox transformation. Moreover, this study furthers our understanding on how the particle size influences the interactions between IONPs and arsenic thereby clarifying the role of IONPs in the biogeochemical cycling of arsenic.