The ice-covered period on lakes in the northern hemisphere has often been neglected or assumed to have less importance relative to the open water season. However, recent studies challenge this convention, suggesting that the winter period is more dynamic than previously thought. In this review, we synthesize the current understanding of under-ice carbon dioxide (CO2) and methane (CH4) dynamics, highlighting the annual importance of CO2 and CH4 emissions from lakes at ice-melt. We compiled data from 25 studies that showed that the ice-melt period represents 17% and 27% of the annual CO2 and CH4 emissions, respectively. We also found evidence that the magnitude and type of emission (i.e., CO2 and CH4) varies with characteristics of lakes including geographic location, lake morphometry, and physicochemical conditions. The scarcity of winter and spring carbon data from northern lakes represents a major gap in our understanding of annual budgets in these lakes and calls for future research during this key period.

Food production hinges largely upon access to phosphorus (P) fertilizer. Most fertilizer P used in the global agricultural system comes from mining of nonrenewable phosphate rock deposits located within few countries. However, P contained in livestock manure or urban wastes represents a recyclable source of P. To inform development of P recycling technologies and policies, we examined subnational, national, and global spatial patterns for two intersections of land use affording high P recycling potential: (a) manure-rich cultivated areas and (b) populous cultivated areas. In turn, we examined overlap between P recycling potential and nation-level P fertilizer import dependency. Populous cultivated areas were less abundant globally than manure-rich cultivated areas, reflecting greater segregation between crops and people compared to crops and livestock, especially in the Americas. Based on a global hexagonal grid (290-km(2) grid cell area), disproportionately large shares of subnational "hot spots" for P recycling potential occurred in India, China, Southeast Asia, Europe, and parts of Africa. Outside of China, most of the remaining manure-rich or pulous cultivated areas occurred within nations that had relatively high imports of P fertilizer (net P import:consumption ratios >= 0.4) or substantial increases in fertilizer demand between the 2000s (2002-2006) and 2010s (2010-2014). Manure-rich cultivated grid cells (those above the 75th percentiles for both manure and cropland extent) represented 12% of the global grid after excluding cropless cells. Annually, the global sum of animal manure P was at least 5 times that contained in human excreta, and among cultivated cells the ratio was frequently higher (median = 8.9). The abundance of potential P recycling hot spots within nations that have depended on fertilizer imports or experienced rising fertilizer demand could prove useful for developing local P sources and maintaining agricultural independence.

Identifying significant changes across lake ecosystems is important for understanding impacts of global environmental change. Synthesizing data on lake warming trends is challenging because individual lake datasets differ in the: (1) length of the time series available for analysis and (2) frequency of data collection (e.g., daily vs. monthly observations). This study aimed to address how dataset length, frequency of data collection, and strength of temperature trends could impact both the accuracy of summer surface-water temperature trends and their statistical significance. Using Monte Carlo simulations, we found that accuracy in trend estimates and the ability to recover statistically significant trends were both directly related to trend strength, dataset length, and sampling frequency. To consistently retrieve statistically significant trend estimates that deviated < 25% from the true values, 30-yr datasets with high warming rates (>= 0.75 degrees C decade(-1)) were required. These findings have important implications for efforts to analyze lake temperature trends, as the characteristics of many existing datasets fall within a range where our simulations predict low accuracy in trend estimates as well as a low probability of achieving statistical significance. Longer datasets are needed to accurately estimate warming trends and evaluate drivers of lake surface-temperature changes, highlighting the need to support existing long-term monitoring projects occurring across the globe, and to encourage updates to remotely sensed lake temperature datasets.

Lake Baikal, one of the world's largest and most biologically diverse lakes, has recently begun to experience uncharacteristic nuisance blooms of filamentous benthic algae. To contribute to understanding the causes of these blooms, we deployed nutrient-diffusing substrata (NDS) at 10 sites varying in shoreline land use in the southwestern portion of the lake. Our objectives were to assess the nature of nutrient limitation of benthic algae in Lake Baikal, the relationship between land use and limitation status, and the effect of enrichment on algal community composition. Algal biomass measured as chlorophyll a (Chl a) responded strongly to nutrient enrichment and showed serial limitation by N and P at all sites. Chl a levels were similar to 2 and 4x higher on N- and N+P-amended NDS, respectively, than on unenriched controls. Periphyton biomass varied significantly among sites, but differences in periphyton biomass and nutrient limitation status were not related to shoreline land use. The taxonomic composition of periphyton varied significantly among landuse categories, nutrient treatments, and sites. The filamentous green alga Stigeoclonium tenue, which has been associated with recently observed nuisance blooms in Lake Baikal, tended to be most abundant on N- and N+ P-amended NDS. The results of our study demonstrate strong nutrient limitation of the periphyton in Lake Baikal and highlight the potential value of improved nutrient controls for addressing benthic algal blooms in the lake.

Pharmaceuticals and personal care products (PPCPs) garner increasing attention globally for both their usefulness as indicators of human waste and their potency as emerging organic toxicants. Three decades of rapid increase in PPCP study combined with an increasing number of PPCPs on the global market have created an opportunity (1) to review trends in diversity of compounds, sewage treatment techniques (STTs), and ecosystems investigated as well as (2) to identify knowledge gaps in the literature. We conducted a quantitative evidence synthesis of 6517 abstracts from primary articles in the environmental PPCP literature by examining relative abundance of specific PPCP classes, STTs, and ecosystem types. Our results demonstrate that nonprescription drugs and antibiotics dominated PPCP abstracts, appearing in 51% and 39% of reviewed abstracts, respectively, in comparison to hormones (18%), prescription drugs (18%), fragrances (0.3%), and antioxidants (0.0%), which can all elicit physiological and ecological responses even at low concentrations. References to centralized STTs (e.g., activated sludge, 37%) were more frequent than decentralized STTs (e.g., septic, 2%), despite decentralized STTs being common and frequently high impact sources of sewage pollution worldwide. Freshwater lotic systems (63%) were more prevalent than freshwater lentic (24%) and terrestrial (20%) systems. This discrepancy is notable because the longer residence times of lentic and terrestrial systems may enable PPCPs to concentrate and thus increase risk of biological consequences. These results highlight distinct opportunities to address knowledge gaps in the environmental PPCP literature, including underrepresented compounds (e.g., fragrances), sewage treatment techniques (e.g., septic systems), and ecosystem types (e.g., lakes).

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.