Background: Malaria remains as a major global problem, being one of the infectious diseases that engender highest mortality across the world. Due to the appearance of resistance and the lack of an effective vaccine, the search of novel anti-malarials is required. Deoxyuridine 5'-triphosphate nucleotido-hydrolase (dUTPase) is responsible for the hydrolysis of dUTP to dUMP within the parasite and has been proposed as an essential step in pyrimidine metabolism by providing dUMP for thymidylate biosynthesis. In this work, efforts to validate dUTPase as a drug target in Plasmodium falciparum are reported.

As an increasing variety and complexity of environmental issues confront scientists and natural resource managers, assembling the most relevant and informative data into accessible data systems becomes critical to timely problem solving. Data interoperability is the key criterion for succeeding in that assembly, and much informatics research is focused on data federation, or synthesis to produce interoperable data. However, when candidate data come from numerous, diverse, and high-value legacy data sources, the issue of data variety or heterogeneity can be a significant impediment to interoperability. Research in informatics, computer science and philosophy has frequently focused on resolving data heterogeneity with automation, but subject matter expertise still plays a large role. In particular, human expertise is a large component in the development of tools such as data dictionaries, crosswalks, and ontologies. Such representations may not always match from one data system to another, presenting potentially inconsistent results even with the same data. Here, we use a long-term data set on management actions designed to improve stream habitat for endangered salmon in the Pacific Northwest, to illustrate how different representations can change the underlying information content in the data system. We pass the same data set comprised of 49,619 records through three ontologies, each developed to address a rational management need, and show that the inferences drawn from the data can change with choice of data representation or ontology. One striking example shows that the use of one ontology would suggest water quality improvement projects are the rarest and most expensive restoration actions undertaken, while another will suggest these actions to be the most common and least expensive type of management actions. The discrepancy relates to the origins of the data dictionaries themselves, with one designed to catalog management actions and the other focused on ecological processes. Thus, we argue that in data federation efforts humans are "in the loop" rationally, in the form of the ontologies they have chosen, and diminishing the human component in favor of automation carries risks. Consequently, data federation exercises should be accompanied by validations in order to evaluate and manage those risks.

Kinetic analysis of dopamine receptor activation and inactivation and the study of dopamine-dependent signaling requires precise simulation of the presynaptic release of the neurotransmitter dopamine and tight temporal control over the release of dopamine receptor antagonists. The 8-cyano-7-hydroxyquinolinyl (CyHQ) photoremovable protecting group was conjugated to dopamine and the dopamine receptor antagonist sulpiride to generate "caged" versions of these neuromodulators (CyHQ-O-DA and CyHQ sulpiride, respectively) that could release their payloads with 365 or 405 nm light or through 2-photon excitation (2PE) at 740 nm. These compounds are stable under physiological conditions in the dark, yet photolyze rapidly and cleanly to yield dopamine or sulpiride and the caging remnant CyHQ-OH. CyHQ-O-DA mediated the light activation of dopamine-1 (DI) receptors on the breast cancer cell line MDA-MB-231 in culture. In mouse brain slice from the substantia nigra pars compacta, localized flash photolysis of CyHQ-O-DA accurately mimicked the natural presynaptic release of dopamine and activation of dopamine-2 (D2) receptors, causing a robust, concentration-dependent, and repeatable G protein-coupled inwardly rectifying potassium channel-mediated outward current in whole-cell voltage clamp recordings that was amplified by cocaine and blocked by sulpiride. Photolysis of CyHQ-sulpiride rapidly blocked synaptic activity, enabling measurement of the unbinding rates of dopamine and quinpirole, a D2 receptor agonist. These tools will enable more detailed study of dopamine receptors, their interactions with other GPCRs, and the physiology of dopamine signaling in the brain.

Long-term research provides a unique perspective on environmental processes, dynamics of populations and communities of organisms, and emergent properties of ecosystems. Many key ecological relationships can be obscured in short term studies by common features such as time lags, natural variability, nonlinear relationships, interactive drivers, or relatively slow processes. Aquatic ecosystems have yielded major scientific discoveries through long-term research, through both observational and experimental studies. These research results have ranged from the detection of multi-decadal climate oscillation effects on ecosystems to finer-scale understanding of the trophic and biogeochemical pathways through which nutrient pollution affects water quality. In this special issue of Limnology and Oceanography, the contributing authors demonstrate that-whether designed for the monitoring of managed natural resources, to answer fundamental scientific questions, or both-long-term research enables researchers to move far beyond their initial questions as unexpected dynamics are revealed over time. With the widespread maturation of long-term data sets and rapid emergence of new technologies that enhance research capabilities, opportunities for synthesizing knowledge are now creating unprecedented opportunity for scientific discovery that builds on this legacy of long-term aquatic research.

There is an increasing appreciation that food energy water (FEW) nexus problems are approaching criticality in both the developing and developed world. As researchers and managers attempt to address these complex resource management issues, the concept of the FEW nexus has generated a rapidly growing footprint in global sustainability discourse. However, this momentum in the FEW nexus space could be better guided if researchers could more clearly identify what is and is not a FEW problem. Without this conceptual clarity, it can be difficult to defend the position that FEW innovations will produce desired outcomes and avoid unintended consequences. Here we examine the growing FEW nexus scholarship to critically evaluate what features are necessary to define a FEW nexus. This analysis suggests that the FEW nexus differs from sector-focused natural resource or sustainability problems in both complexity and stakes. It also motivates two new foci for research: the identification of low-dimension indexes of FEW system status and approaches for identifying boundaries of specific FEW nexuses.

Freshwater ecosystems are heavily impacted by multiple stressors, and a freshwater biodiversity crisis is underway. This realization has prompted calls to integrate global freshwater ecosystem data, including traditional taxonomic and newer types of data (e.g., eDNA, remote sensing), to more comprehensively assess change among systems, regions, and organism groups. We argue that data integration should be done, not only with the important purpose of filling gaps in spatial, temporal, and organismal representation, but also with a more ambitious goal: to study fundamental cross-scale biological phenomena. Such knowledge is critical for discerning and projecting ecosystem functional dynamics, a realm of study where generalizations may be more tractable than those relying on taxonomic specificity. Integration could take us beyond cataloging biodiversity losses, and toward predicting ecosystem change more broadly. Fundamental biology questions should be central to integrative, interdisciplinary research on causal ecological mechanisms, combining traditional measures and more novel methods at the leading edge of the biological sciences. We propose a conceptual framework supporting this vision, identifying key questions and uncertainties associated with realizing this research potential. Our framework includes five interdisciplinary "complementarities." First, research approaches may provide comparative complementarity when they offer separate realizations of the same focal phenomenon. Second, for translational complementarity, data from one research approach is used to translate that from another, facilitating new inferences. Thirdly, causal complementarity arises when combining approaches allows us to "fill in" cause-effect relationships. Fourth, contextual complementarity is realized when together research methodologies establish the wider ecological and spatiotemporal context within which focal biological responses occur. Finally, integration may allow us to cross inferential scales through scaling complementarity. Explicitly identifying the modes and purposes of integrating research approaches, and reaching across disciplines to establish appropriate collaboration will allow researchers to address major biological questions that are more than the sum of the parts.

Synthesis centers are a form of scientific organization that catalyzes and supports research that integrates diverse theories, methods and data across spatial or temporal scales to increase the generality, parsimony, applicability, or empirical soundness of scientific explanations. Synthesis working groups are a distinctive form of scientific collaboration that produce consequential, high-impact publications. But no one has asked if synthesis working groups synthesize: are their publications substantially more diverse than others, and if so, in what ways and with what effect? We investigate these questions by using Latent Dirichlet Analysis to compare the topical diversity of papers published by synthesis center collaborations with that of papers in a reference corpus. Topical diversity was operationalized and measured in several ways, both to reflect aggregate diversity and to emphasize particular aspects of diversity (such as variety, evenness, and balance). Synthesis center publications have greater topical variety and evenness, but less disparity, than do papers in the reference corpus. The influence of synthesis center origins on aspects of diversity is only partly mediated by the size and heterogeneity of collaborations: when taking into account the numbers of authors, distinct institutions, and references, synthesis center origins retain a significant direct effect on diversity measures. Controlling for the size and heterogeneity of collaborative groups, synthesis center origins and diversity measures significantly influence the visibility of publications, as indicated by citation measures. We conclude by suggesting social processes within collaborations that might account for the observed effects, by inviting further exploration of what this novel textual analysis approach might reveal about interdisciplinary research, and by offering some practical implications of our results.

The lower Columbia River (Washington and Oregon, USA) has been heavily invaded by a large number of planktonic organisms including the invasive copepod Pseudodiaptomus forbesi and the planktonic juveniles of the invasive clam, Corbicula fluminea. In order to assess the ecological impacts of these highly abundant invaders, we developed a multivariate auto-regressive (MAR) model of food web dynamics based upon a 12-year time-series of plankton community and environmental data from the Columbia River. Our model results indicate that plankton communities in the lower Columbia River are strongly impacted by the copepod P. forbesi at multiple trophic levels. We observed different ecological effects across different life stages of P. forbesi, with nauplii negatively impacting ciliates and autotrophs, and copepodite stages negatively impacting Daphnia and cyclopoid copepods. Although juvenile C. fluminea were highly abundant in the summer and autumn of each year, our best fit MAR model did not show significant C. fluminea impacts. Our results illustrate the strong ecological impact that some zooplankton invaders may cause within rivers and estuarine systems, and highlight the need for further research on the feeding ecology of the planktonic life-stage of C. fluminea. Overall, our study demonstrates the manner in which long-term, high resolution data sets can be used to better understand the ecological impacts of invasive species among complex and highly dynamic communities.

The study of environmental communication originated as a diverse multidisciplinary field encompassing a wide array of communicator perspectives. However, as the field evolved, mass media and journalism became its perceived scholarly focus. As a result, environmental communication processes may be less well-understood across other settings, such as scientific and research institutions, non-governmental organizations, and federal agencies. To understand how communicators describe their goals, ethics, and strategies within these contexts, we conducted a three-part study of researchers and practitioners working on environmental issues in the Washington, DC, region between October 2019 and January 2020. Employing Q methodology, we identified four distinct perspectives: capacity-builders, translators, policy and decision-supporters, and cultural changemakers. Each of these perspectives is associated with a different range of goals, ethics, and strategic approaches. We describe graduate educational competencies for each of the perspectives and discuss implications for the design of communication research to meet practitioners' needs.

Climate warming impacts ecosystems through multiple interacting pathways, including via direct thermal responses of individual taxa and the combined responses of closely interacting species. In this study, we examined how warming and infection by an oomycete parasite (Saprolegnia) affect the dominant zooplankter of Russia's Lake Baikal, the endemic copepodEpischurella baikalensis. We used a combination of laboratory experiments, long-term monitoring data, and population modeling. Experiments showed a large difference in the thermal optima of host and parasite, with strong negative effects of warm temperatures onE. baikalensissurvival and reproduction and a negative effect ofSaprolegniainfection on survival.Saprolegniainfection had an unexpected positive effect onE. baikalensisreproductive output, which may be consistent with fecundity compensation by females exposed to the parasite. Long-term monitoring data suggested thatSaprolegniainfections were most common during the warmest periods of the year. Population models, parameterized with experimental and literature data, correctly predicted the timing ofSaprolegniaepizootics, but overestimated the negative effect of warming onE. baikalensispopulations. Models suggest that diel vertical migration may allowE. baikalensisto escape the negative effects of increasing temperatures and parasitism and enableE. baikalensisto persist in the face of moderate warming of Lake Baikal. Our results contribute to understanding of how warming and parasitism interact to affect the pelagic ecosystems of cold lakes and oceans and how the consequences of these interacting stressors can vary seasonally, spatially, and interannually.