Search

Ongoing debates in conservation studies stress the dire consequences of 'fortress' and 'militarized' conservation at violent frontiers. Presenting evidence from Kahuzi‐Biega National Park in war‐torn eastern Democratic Republic of Congo (DRC), this article shows how the park has become a focal point for armed insurgent groups in the region. Although fortress conservation has contributed to one major incident of violent resistance in recent years, it plays only a marginal role in defining the structures shaping the actions of armed groups. These structures — some of which are reproduced and (occasionally) reshaped by armed groups — include the legacies of poverty and insecurity, the geographical features of the park and the presence of illicit trading networks. This perspective emerges only when we zoom out from the park to place it within the context of the history and broader political economy of the DRC. On the one hand, these dynamics severely constrain the agency of conservation organizations, leaving militarized conservation as the only feasible form of enforcement. This approach at times generates violent outcomes for certain groups of people and produces a resource‐rich, isolated terrain which provides a staging ground for broader conflicts to play out. On the other hand, militarized conservation could provide basic law and order at the forest's edge. Ultimately, therefore, militarized conservation plays an ambivalent role vis‐à‐vis security and stability. [ABSTRACT FROM AUTHOR]

Continual learning is the problem of learning from a nonstationary stream of data, a fundamental issue for sustainable and efficient training of deep neural networks over time. Unfortunately, deep learning libraries only provide primitives for offline training, assuming that model's architecture and data are fixed. Avalanche is an open source library maintained by the ContinualAI non-profit organization that extends PyTorch by providing first-class support for dynamic architectures, streams of datasets, and incremental training and evaluation methods. Avalanche provides a large set of predefined benchmarks and training algorithms and it is easy to extend and modular while supporting a wide range of continual learning scenarios. Documentation is available at https://avalanche.continualai.org. [ABSTRACT FROM AUTHOR]

As the urgency of responding to climate change and the insufficiency of current demand-side policies to mitigate greenhouse gas emissions become clearer, supply-side initiatives are beginning to gain prominence and acceptance globally. Policies such as moratoria and compensation for leaving fossil fuels unextracted in exchange for financial compensation of rights owners are likely to be effective and complementary to existing policies. A number of unknowns remain regarding the operationalization of supply-side policies, such as how to establish a binding international agreement and how to raise and allocate financial compensation for nonextraction. Nevertheless, the need for supply-side policies only emphasizes the importance of imaginative and bold initiatives within the current conjuncture of global environmental politics. [ABSTRACT FROM AUTHOR]

To limit the increase in global mean temperature to 1.5°C, CO2 emissions should be capped at 440 gigatons. To achieve this, about 89 percent, 59 percent, and 58 percent of existing coal and conventional gas and oil reserves, respectively, need to remain unburned. This implies an economic cost for fossil fuel rights owners, and any successful climate policy will rely on resolving the distributional challenge of how to allocate the right to use the remaining burnable reserves. We discuss the possibility of compensating rights holders of unburnable oil and gas reserves, producing the first estimates of the financial resources needed to secure full compensation. We estimate that approximately US$ 5,400 billion (10 9) would be needed. Despite the vast amounts required, compensation is nevertheless economically feasible. We suggest a Keynesian "whatever it takes" approach for climate action, combining partial compensation for unburnable fuels and investment in low-carbon technologies to drastically reduce emissions in the rapidly closing window of opportunity before 2030. [ABSTRACT FROM AUTHOR]

Since the early 2000s, there has been an 'extractive imperative' in Latin America that made intensified extraction the policy solution to all socioeconomic challenges. More recently, a similar consensus has emerged in a diversity of political, economic and geographical contexts – such as Turkey, India and the United States – that makes it possible to speak of a 'global extractive imperative'. The imperative is especially evident in settings also characterised by authoritarian neoliberalism and the burden of resistance against extractivism is suffered overwhelmingly by marginalised communities at extractive frontiers. Emerging efforts to declare a share of existing reserves of fossil fuels 'unburnable' would not only help make progress towards tackling the climate crisis, it would also broaden the societal bases of societal struggles against capitalism's extractive excesses. [ABSTRACT FROM AUTHOR]

We chronicle a four-decades-long struggle that has been taking place in the Peruvian Amazon between indigenous groups, oil companies, and the state. We provide a broad overview of the strategies of the communities in the area, juxtaposing the outcomes of different negotiating strategies. In addition to documenting what is an especially important case of socio-environmental conflict in the Peruvian Amazon, we go beyond the dominant approach in the literature, which sees dialogue as inherently desirable and conflict as necessarily unwelcome, and describe the Achuar decision to engage in open conflict with the oil company as one that testifies to the existence of a conflict imperative. In other words, the overcoming of environmental injustice in certain circumstances requires various forms of direct action that take grievance and complaint to the level of open conflict. The corollary of this hypothesis is that dialogue is sometimes neither peaceful nor useful for affected communities. This calls for a rethinking of the boundaries between conflict and negotiation. In our chronicle, conflict itself was often the antecedent to a new round of dialogue and negotiation made possible by the presence of government officials purposively and urgently dispatched to the area. Echoing Clausewitz's famous dictum concerning the continuity between war and policy, indigenous decisions to occupy, blockade, and disrupt the working of oil operations might tentatively be understood as an attempt to continue negotiating with the state and corporations by using other tools they have at their disposal. [ABSTRACT FROM AUTHOR]

Waste sorting at the household level is a virtuous process that can greatly increase material recycling and boost the circular economy. To this purpose, waste must be differentiated by material (e.g., PVC, Polyethylene, Paper, Glass, Aluminum, etc.), a task that can be simplified by printing a recycling code on the product case. Unfortunately, the large number of recycling codes printed on products makes this process unfriendly for many users. In this work, we propose a vision-based mobile application to support users in recognizing recycling codes for proper waste sorting. The proposed system combines a dual-head CNN with an image processing pipeline (based on domain knowledge) in order to improve: (i) the reliability of symbol detection/classification and (ii) the weakly-supervised labeling of new samples during iterative training. Our experimental results prove the feasibility of developing effective applications with minimum effort in terms of data collection and labeling, which is one of the main obstacles to successfully applying deep-learning techniques to real-world problems. • We propose a mobile application to recognize recycling codes for waste sorting. • Combining deep learning with domain knowledge improves accuracy and efficiency. • We propose to train the system iteratively by using a weakly supervised scheme. • The proposed training scheme reduces data collection and labeling efforts. • A novel dataset of recycling codes is released. [ABSTRACT FROM AUTHOR]

Sub-Saharan countries are facing multiple simultaneous challenges that include the need to both increase access to electricity and combat morbidity and mortality caused by malaria. This study is the first to explore the nexus between electrification and malaria incidence using country-wide representative household-level data. The focus is on rural Uganda. Despite the fact that data used in this analysis come from a multi-topic survey and therefore do not include the ideal indicators for a malaria-related study, we do find evidence that household members having access to electricity are more likely to experience malaria. Our interpretation is that electric light attracts malaria vectors and that lifestyle changes associated with outdoor lighting increase human exposure to the vectors. Our findings suggest that the electrification process in Uganda should be complemented by anti-malaria strategies. [ABSTRACT FROM AUTHOR]

Learning continually is a key aspect of intelligence and a necessary ability to solve many real-life problems. One of the most effective strategies to control catastrophic forgetting, the Achilles' heel of continual learning, is storing part of the old data and replaying them interleaved with new experiences (also known as the replay approach). Generative replay, which is using generative models to provide replay patterns on demand, is particularly intriguing, however, it was shown to be effective mainly under simplified assumptions, such as simple scenarios and low-dimensional data. In this paper, we show that, while the generated data are usually not able to improve the classification accuracy for the old classes, they can be effective as negative examples (or antagonists) to better learn the new classes, especially when the learning experiences are small and contain examples of just one or few classes. The proposed approach is validated on complex class-incremental and data-incremental continual learning scenarios (CORe50 and ImageNet-1000) composed of high-dimensional data and a large number of training experiences: a setup where existing generative replay approaches usually fail. [ABSTRACT FROM AUTHOR]

Summary Dependence on biomass to meet domestic energy needs raises several socio-environmental concerns. In contrast, cattle manure, which may be used to generate biogas, is considered a cleaner and cheaper energy source. Despite several initiatives toyears of education promote biogas, systematic analyses of its effects are limited. This paper uses data from Rwanda to examine the effects of participating in a biogas program on energy-related expenditures and consumption of traditional fuels. We find evidence of substantial reductions in firewood use and large savings. However, the attractiveness of the program is hampered by a long payback period and low rates of return. [ABSTRACT FROM AUTHOR]

In the last few years, we have witnessed a renewed and fast-growing interest in continual learning with deep neural networks with the shared objective of making current AI systems more adaptive, efficient and autonomous. However, despite the significant and undoubted progress of the field in addressing the issue of catastrophic forgetting, benchmarking different continual learning approaches is a difficult task by itself. In fact, given the proliferation of different settings, training and evaluation protocols, metrics and nomenclature, it is often tricky to properly characterize a continual learning algorithm, relate it to other solutions and gauge its real-world applicability. The first Continual Learning in Computer Vision challenge held at CVPR in 2020 has been one of the first opportunities to evaluate different continual learning algorithms on a common hardware with a large set of shared evaluation metrics and 3 different settings based on the realistic CORe50 video benchmark. In this paper, we report the main results of the competition, which counted more than 79 teams registered and 11 finalists. We also summarize the winning approaches, current challenges and future research directions. [ABSTRACT FROM AUTHOR]

Conservation efforts must develop strategies to perform at violent frontiers where environmental values, mineral extraction and conflict intersect. Using war-torn eastern Democratic Republic of Congo's Itombwe Nature Reserve as an illustrative example, this article explores how community conservation is implemented and received at a violent frontier. Taking inspiration from an emerging body of literature which portrays conservation as a form of 'social contract' in regions where the nation state is weak or absent, it explores some of the expectations and obligations that surround community conservation initiatives. It draws the conclusion that conservation social contracts are likely to produce unintended consequences when left unfulfilled or broken. Conservation actors perceived to be breaking the terms of (implicit) social contracts can inadvertently encourage local communities to embrace alternative contracts with other actors seeking to extract value from the resources located in frontiers, such as industrial mining companies. [ABSTRACT FROM AUTHOR]

Despite its widely recognized importance, electricity is not yet available everywhere, and there are many areas of the globe which still depend on alternative sources of energy such as wood, charcoal and kerosene. In contrast, the USA was the first country to be fully electrified. This article explores the current challenges faced by developing countries, presents the historical evidence from the USA and compares these experiences discussing the policy relevance of the comparison. Far from being a smooth process, the electrification process in the USA was a long and complex transition. The article analyses the challenges and policy responses that characterized the US electrification process. One of the outstanding features of these policies is that they are quite comprehensive and include subsidies and credit schemes, house ownership policies, mass media campaigns, the provision of adequate repair service and the direct involvement of women. [ABSTRACT FROM AUTHOR]

Bolivia is part of the left-turn that Latin America has seen since the end of the 1990s. The country was traditionally ruled by a conservative establishment and political instability characterized a decade of conflicts that culminated in the ascendency of the Movement towards Socialism (Movimiento al Socialismo, MAS) and, in 2006, of the first indigenous president -Evo Morales. The election of Morales and the subsequent changes to the Bolivian state have been praised by some scholars as revolutionary, while others have argued that these changes essentially consist of a continuation and re-constitution of neo-liberal regimes. This paper highlights the changes in compensation and redistribution policies that have accompanied the nationalization of hydrocarbons and the institutionalization of consultation processes for indigenous peoples affected by hydrocarbons activities. In this context, we analyse an oil exploration project that took place in the north of the La Paz Department. In particular, focus is on how the compensation and consultation frameworks debilitated opposition to the project. We conclude that the government's priorities are intertwined with the continuation of the extractive economic model. In these circumstances questioning extractive projects is not an option. [ABSTRACT FROM AUTHOR]

The article analyzes how the main planning documents "Poverty Reduction Strategy Paper (PRSP)" and the "National Development Plan (PND)" have been able to capture popular participation in development discourse in Bolivia in the first decade of the 200s, with focus on natural resources as a component of the plan and its role in the Bolivian economy. Comparison showed that the PRSP is oriented toward country ownership and aims to improve governance through accountability, while the PND is organized under the strategic lines of social policies, democratization and decentralization, the economy, and international relations. Analysis confirmed the importance of natural resources to Bolivian socioeconomic processes and to the claims and struggles of social movements.

The article presents an interview with economist Joan Martinez-Alier. Topics addressed include his interest in ecological economics and activism related to socio-environmental issues, his founding of the International Society for Ecological Economics (ISEE) and its role in the field of ecological economics, and the importance of history in the study of economics.

This study is a policy assessment contrasting forestry reforms and their intended objectives against the state of the forestry sector in Bolivia, Honduras and Nicaragua. The study finds that there is a gap between policy objectives and the state of forestry in the three countries, and that the policy frameworks are characterized by lack of policy implementation and intrinsically flawed design. In other words, reform failure matched by failure to reform is present in each country. The Poverty Reduction Strategy Papers followed, and possibly reinforced, existing policy trends but they were unable to solve the implementation problems and lack of coherence that mark the policies of the sector.Cette étude est une évaluation de politiques mettant en contraste les réformes forestières et leurs objectifs d′une part et l′état de l′industrie forestière en Bolivie, au Honduras et au Nicaragua, d′autre part. L′étude constate un écart entre les objectifs de la politique forestière et l′état des forêts dans ces trois pays et montre que les cadres politiques sont caractérisés par une absence de mise en œuvre des réformes, et par une conception intrinsèquement imparfaite. En d′autres termes, dans chacun de ces pays, à l′échec des politiques s′ajoute un manque de réformes. Les Documents de Stratégie de Réduction de la Pauvreté ont suivi, et peut être renforcé, les tendances politiques déjà existantes mais n′ont pas pu résoudre les problèmes liés à la mise en œuvre et au manque de cohérence caractérisant les politiques concernant le secteur forestier. [ABSTRACT FROM AUTHOR]

In this paper, we analyse the impact of tenancy reform in the Indian state of West Bengal on consumption expenditure of tenants. We use a difference-in-difference methodology with data from a household survey (the National Sample Survey) to compare the growth of consumption expenditure of tenants with that of non-tenants. Contrary to the conclusions of other authors, we do not find indications of substantial improvements in the living standards of the reform's beneficiaries. Finally, we analyse possible reasons for the discrepancy between our results and the rest of the literature.Cet article analyse l'impact de la réforme des conditions de bail dans l'Etat Indien du Bengale occidental sur la consommation des locataires. Nous employons une méthode des écarts dans les différences avec les données d'une enquête de ménage officielle - la «National Sample Survey» - afin de comparer l'augmentation des dépenses des locataires à celle des non-locataires. Contrairement aux conclusions d'autres chercheurs, nous ne trouvons aucune indication d'améliorations substantielles du niveau de vie des bénéficiaires de la réforme. Nous concluons par une discussion des raisons possibles expliquant cette divergence entre nos résultats et ceux du reste de la littérature.European Journal of Development Research (2009) 21, 231-249. doi:10.1057/ejdr.2008.18 [ABSTRACT FROM AUTHOR]

Basilicata is a region of Southern Italy where the expansion of oil operations in the 1990s was promoted as an opportunity to foster economic development. Flash-forward to 2020, Basilicata is one of the poorest regions in Italy despite the exploitation of some of the largest onshore hydrocarbon reserves within the European Union. The coincidence of high poverty rates with abundant natural resources suggests that the region is experiencing a 'resource curse'; however, socio-economic problems predate the oil boom, complicating any causality claim. To disentangle and estimate the effects of oil exploitation, we employ the synthetic control method that compares the actual trends of development indicators of Basilicata with a counterfactual that is created by taking a weighted average of trends of other Italian regions –a 'synthetic' Basilicata. The analysis finds that the development of oil operations has generated no detectable improvement to employment, nor to a range of social indicators, nor to educational attainment. The absence of quantifiable beneficial effects is coupled with negative impacts on other dimensions of development that are more difficult to estimate with our method –especially on the environment and human health. Taken together the evidence offers a sobering prospect over the potential of resource-based development for disadvantaged regions in developed countries. [ABSTRACT FROM AUTHOR]

The article focuses on issues related to major environmental challenges faced by people worldwide and how societies address such problem. It discusses various reports presented by international research institutes, including Worldwatch Institute, and humanitarian agencies such as the International Federation of Red Cross (IFRC) and Red Crescent Societies. Their reports highlight the future environmental challenges that communities face, provide reliable reference data on environmental issues and offer solutions for the problem which can be combined with social justice.

Theoretical and empirical studies have shown that democracy and corruption influence environmental policies. In this article, the authors empirically analyze the relative importance of these determinants of environmental policy. When these variables are jointly included as explanatory variables in a multiple regression analysis, the authors found that corruption stands out as a substantial and significant determinant of environmental policies, while proxies for democracy have an insignificant impact. Nevertheless, democracy could affect environmental policy stringency given that countries with a history of democratic rule tend to be less corrupted. The authors argue that improving environmental quality following increasing income is less probable in developing countries with institutional disarray. Finally, and more optimistically, when considering the results in the context of institutions and growth, the authors conclude that there is scope for reaping a double dividend, when institutional improvements and reductions in corruption induce higher economic growth rates and stricter environmental policies. [ABSTRACT FROM AUTHOR]

A common finding of recent theoretical and empirical literature is that corruption has a negative effect on economic growth. In the paper, through growth regression analysis, we estimate the direct and indirect effects of corruption on economic growth. The indirect transmission channels, specifically investments, trade policy, schooling, and political stability, analysed in our study prove to be significant in explaining the deleterious effect of corruption on growth rates. We find that one standard deviation increase in the corruption index is associated with a decrease in investments of 2.46 per centage points, which in turn decreases economic growth by 0.34 per cent per year. The second, by importance, transmission channel is openness: a standard deviation increase in the corruption index is associated with a decrease of the openness index by 0.19, resulting in a decrease in economic growth by 0.30 percent per year. Jointly, the transmission channels explain 81 per cent of the effect of corruption on growth. While combating corruption is a long-term task, an understanding of the transmission channels, through which corruption affects the economy, may suggest ways to limit corruption's negative, but indirect, effects on growth. [ABSTRACT FROM AUTHOR]

Membrane phosphoinositides control a variety of cellular processes through the recruitment and/or regulation of cytosolic proteins. One mechanism ensuring spatial specificity in phosphoinositide signalling is the targeting of enzymes that mediate their metabolism to specific subcellular sites. Phosphatidylinositol phosphate kinase type 1γ (PtdInsPKIγ) is a phosphatidylinositol-4-phosphate 5-kinase that is expressed at high levels in brain, and is concentrated at synapses. Here we show that the predominant brain splice variant of PtdInsPKIγ (PtdInsPKIγ90) binds, by means of a short carboxy-terminal peptide, to the FERM domain of talin, and is strongly activated by this interaction. Talin, a principal component of focal adhesion plaques, is also present at synapses. PtdInsPKIγ-90 is expressed in nonneuronal cells, albeit at much lower levels than in neurons, and is concentrated at focal adhesion plaques, where phosphatidylinositol-4,5-bisphosphate has an important regulatory role. Overexpression of PtdInsPKIγ-90, or expression of its C-terminal domain, disrupts focal adhesion plaques, probably by local disruption of normal phosphoinositide balance. These findings define an interaction that has a regulatory role in cell adhesion and suggest new similarities between molecular interactions underlying synaptic junctions and general mechanisms of cell adhesion. [ABSTRACT FROM AUTHOR]

This paper reports on an ongoing initiative that seeks to enhance the detection, monitoring, and reporting capabilities of local communities in the Northern Ecuadorian Amazon through the introduction of hardware and digital tools, as a strategy to strengthen their ability to produce socio-environmental evidence. A Community Based Monitoring (CBM) system has been created to link social organizations, fighting for environmental justice, and academics working on the region in topics related to oil extraction and environmental change. This paper first, conceptualize the need for rural participatory systems of data collection, analysis, and distribution of environmental liabilities in extractive frontiers. Second, the paper provides a description of this community monitoring system in the Ecuadorian Amazon, in a way that can be used by communities and researchers in different contexts. Finally, the paper reflects on lessons learned to understand the main challenges and opportunities of similar systems. [ABSTRACT FROM AUTHOR]

Better, swifter and more responsive international coordination is needed within our global financial system for the containment of the pandemic and its effects. This requires better international tax coordination with a higher global minimum corporate tax, comprehensive coverage of sectors and firms, inclusion of all current tax havens and more generous redistribution of excess profits to developing nations based on user location. There also needs to be a more substantial and easier-to-access mechanism for debt relief and restructuring, one that generously suspends debt payments in periods of crises and provides financial support without strict and painful conditionalities. [ABSTRACT FROM AUTHOR]

Background The Glanville fritillary (Melitaea cinxia) butterfly is a model system for metapopulation dynamics research in fragmented landscapes. Here, we provide a chromosome-level assembly of the butterfly's genome produced from Pacific Biosciences sequencing of a pool of males, combined with a linkage map from population crosses. Results The final assembly size of 484 Mb is an increase of 94 Mb on the previously published genome. Estimation of the completeness of the genome with BUSCO indicates that the genome contains 92–94% of the BUSCO genes in complete and single copies. We predicted 14,810 genes using the MAKER pipeline and manually curated 1,232 of these gene models. Conclusions The genome and its annotated gene models are a valuable resource for future comparative genomics, molecular biology, transcriptome, and genetics studies on this species. [ABSTRACT FROM AUTHOR]

Tuba is a novel scaffold protein that functions to bring together dynamin with actin regulatory proteins. It is concentrated at synapses in brain and binds dynamin selectively through four N-terminal Src homology-3 (SH3) domains. Tuba binds a variety of actin regulatory proteins, including N-WASP, CR16, WAVE1, WIRE, PIR121, NAP1, and Ena/VASP proteins, via a C-terminal SH3 domain. Direct binding partners include N-WASP and Ena/VASP proteins. Forced targeting of the C-terminal SH3 domain to the mitochondrial surface can promote accumulation of F-actin around mitochondria. A Dbl homology domain present in the middle of Tuba upstream of a Birdamphiphysin/Rvs (BAR) domain activates Cdc42, but not Rac and Rho, and may thus cooperate with the C terminus of the protein in regulating actin assembly. The BAR domain, a lipid-binding module, may functionally replace the pleckstrin homology domain that typically follows a Dbl homology domain. The properties of Tuba provide new evidence for a close functional link between dynamin, Rho GTPase signaling, and the actin cytoskeleton. [ABSTRACT FROM AUTHOR]

Reports on a study which indicates that phosphatidylinositol 4-kinase type IIalpha is responsible for the phosphatidylinositol 4-kinase activity associated with synaptic vesicles. Generation of phosphatidylinositol 4-phosphate [Pl(4)P] from phosphatidylinositol; Evidence for the occurrence of a cycle phosphoinositide synthesis.

Examines the role of synaphin at the squid giant synapse. Cytosolic protein that preferentially binds to syntaxin within the SNAP receptor complex; Identification and characterization of a squid synaphin ortholog; Syntaxin binding region of synaphin; Mechanism of action of synaphin.

Autosomal dominant polycystic kidney disease (ADPKD), caused by mutations of PKD1 or PKD2 genes, is characterized by development and growth of cysts causing progressive kidney enlargement. Reduced resting cytosolic calcium and increased cAMP levels associated with the tonic action of vasopressin are two central biochemical defects in ADPKD. Here we show that co-targeting two GPCRs, the vasopressin V2 receptor (V2R) and the calcium sensing receptor, using the novel V2R antagonist lixivaptan in combination with the calcimimetic R-568, reduced cyst progression in two animal models of human PKD. Lixivaptan is expected to have a safer liver profile compared to tolvaptan, the only drug approved to delay PKD progression, based on computational model results and initial clinical evidence. PCK rat and Pkd1RC/RC mouse littermates were fed without or with lixivaptan (0.5%) and R-568 (0.025% for rats and 0.04% for mice), alone or in combination, for 7 (rats) or 13 (mice) weeks. In PCK rats, the combined treatment strongly decreased kidney weight, cyst and fibrosis volumes by 20%, 49%, and 73%, respectively, compared to untreated animals. In Pkd1RC/RC mice, the same parameters were reduced by 20%, 56%, and 69%, respectively. In both cases the combined treatment appeared nominally more effective than the individual drugs used alone. These data point to an intriguing new application for two existing drugs in PKD treatment. The potential for synergy between these two compounds suggested in these animal studies, if confirmed in appropriate clinical investigations, would represent a welcome advancement in the treatment of ADPKD. [ABSTRACT FROM AUTHOR]

Vasopressin V2 receptor (V2R) antagonists (vaptans) are a new generation of diuretics. Compared with classical diuretics, vaptans promote the excretion of retained body water in disorders in which plasma vasopressin concentrations are inappropriately high for any given plasma osmolality. Under these conditions, an aquaretic drug would be preferable over a conventional diuretic. The clinical efficacy of vaptans is in principle due to impaired vasopressin-regulated water reabsorption via the water channel aquaporin-2 (AQP2). Here, the effect of lixivaptan—a novel selective V2R antagonist—on the vasopressin-cAMP/PKA signaling cascade was investigated in mouse renal collecting duct cells expressing AQP2 (MCD4) and the human V2R. Compared to tolvaptan—a selective V2R antagonist indicated for the treatment of clinically significant hypervolemic and euvolemic hyponatremia—lixivaptan has been predicted to be less likely to cause liver injury. In MCD4 cells, clinically relevant concentrations of lixivaptan (100 nM for 1 h) prevented dDAVP-induced increase of cytosolic cAMP levels and AQP2 phosphorylation at ser-256. Consistent with this finding, real-time fluorescence kinetic measurements demonstrated that lixivaptan prevented dDAVP-induced increase in osmotic water permeability. These data represent the first detailed demonstration of the central role of AQP2 blockade in the aquaretic effect of lixivaptan and suggest that lixivaptan has the potential to become a safe and effective therapy for the treatment of disorders characterized by high plasma vasopressin concentrations and water retention. [ABSTRACT FROM AUTHOR]