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Present and future climatic trends are expected to markedly alter water fluxes and stores in the hydrologic cycle. In addition, water demand continues to grow due to increased human use and a growing population. Sustainably managing water resources requires a thorough understanding of water storage and flow in natural, agricultural, and urban ecosystems. Measurements of stable isotopes of water (hydrogen and oxygen) in the water cycle (atmosphere, soils, plants, surface water, and groundwater) can provide information on the transport pathways, sourcing, dynamics, ages, and storage pools of water that is difficult to obtain with other techniques. However, the potential of these techniques for practical questions has not been fully exploited yet. Here, we outline the benefits and limitations of potential applications of stable isotope methods useful to water managers, farmers, and other stakeholders. We also describe several case studies demonstrating how stable isotopes of water can support water management decision-making. Finally, we propose a workflow that guides users through a sequence of decisions required to apply stable isotope methods to examples of water management issues. We call for ongoing dialogue and a stronger connection between water management stakeholders and water stable isotope practitioners to identify the most pressing issues and develop best-practice guidelines to apply these techniques.

Terrestrial production and export of dissolved organic and inorganic carbon (DOC and DIC) to streams depends on water flow and biogeochemical processes in and beneath soils. Yet, understanding of these processes in a rapidly changing climate is limited. Using the watershed-scale reactive-transport model BioRT-HBV and stream data from a snow-dominated catchment in the Rockies, we show deeper groundwater flow averaged about 20% of annual discharge, rising to ∼35% in drier years. DOC and DIC production and export peaked during snowmelt and wet years, driven more by hydrology than temperature. DOC was primarily produced in shallow soils (1.94 ± 1.45 gC/m2/year), stored via sorption, and flushed out during snowmelt. Some DOC was recharged to and further consumed in the deeper subsurface via respiration (−0.27 ± 0.02 gC/m2/year), therefore reducing concentrations in deeper groundwater and stream DOC concentrations at low discharge. Consequently, DOC was primarily exported from the shallow zone (1.62 ± 0.96 gC/m2/year, compared to 0.12 ± 0.02 gC/m2/year from the deeper zone). DIC was produced in both zones but at higher rates in shallow soils (1.34 ± 1.00 gC/m2/year) than in the deep subsurface (0.36 ± 0.02 gC/m2/year). Deep respiration elevated DIC concentrations in the deep zone and stream DIC concentrations at low discharge. In other words, deep respiration is responsible for the commonly-observed increasing DOC concentrations (flushing) and decreasing DIC concentrations (dilution) with increasing discharge. DIC export from the shallow zone was ~66% of annual export but can drop to ∼53% in drier years. Numerical experiments suggest lower carbon production and export in a warmer, drier future, and a higher proportion from deeper flow and respiration processes. These results underscore the often-overlooked but growing importance of deeper processes in a warming climate.

Geologic features (e.g., fractures and alluvial fans) can play an important role in the locations and volumes of groundwater discharge and degree of groundwater-surface water (GW-SW) interactions. However, the role of these features in controlling GW-SW dynamics and streamflow generation processes are not well constrained. GW-SW interactions and streamflow generation processes are further complicated by variability in precipitation inputs from summer and fall monsoon rains, as well as declines in snowpack and changing melt dynamics driven by warming temperatures. Using high spatial and temporal resolution radon and water stable isotope sampling and a 1D groundwater flux model, we evaluated how groundwater contributions and GW-SW interactions varied along a stream reach impacted by fractures (fractured-zone) and downstream of the fractured hillslope (non-fractured zone) in Coal Creek, a Colorado River headwater stream affected by summer monsoons. During early summer, groundwater contributions from the fractured zone were high, but declined throughout the summer. Groundwater contributions from the non-fractured zone were constant throughout the summer and became proportionally more important later in the summer. We hypothesize that groundwater in the non-fractured zone is dominantly sourced from a high-storage alluvial fan at the base of a tributary that is connected to Coal Creek throughout the summer and provides consistent groundwater influx. Water isotope data revealed that Coal Creek responds quickly to incoming precipitation early in the summer, and summer precipitation becomes more important for streamflow generation later in the summer. We quantified the change in catchment dynamic storage and found it negatively related to stream water isotope values, and positively related to modeled groundwater discharge and the ratio of fractured zone to non-fractured zone groundwater. We interpret these relationships as declining hydrologic connectivity throughout the summer leading to late summer streamflow supported predominantly by shallow flow paths, with variable response to drying from geologic features based on their storage. As groundwater becomes more important for sustaining summer flows, quantifying local geologic controls on groundwater inputs and their response to variable moisture conditions may become critical for accurate predictions of streamflow.

Understanding connectivity between the soil and deeper bedrock groundwater is needed to accurately predict a watershed's response to perturbation, such as drought. Yet, the bedrock groundwater dynamics in mountainous environments are typically under-constrained and excluded from watershed hydrologic models. Here, we investigate the role of groundwater characterized with decadal and longer water ages on the hydrologic and mass-transport processes within a steep snow-dominated mountain hillslope in the Central Rocky Mountains (USA). We quantify subsurface and surface water mass-balance, groundwater flowpaths, and age distributions using the ParFlow-CLM integrated hydrologic and EcoSLIM particle tracking models, which are compared to hydrometric and environmental tracer observations. An ensemble of models with varied soil and hydrogeologic parameters reproduces observed groundwater levels and century-scale mean ages inferred from environmental tracers. The numerical models suggest soil water near the toe of the hillslope contains considerable (>60 % of the mass-flux) contributions from bedrock flowpaths characterized with water ages >10 years. Flowpath connectivity between the deeper bedrock and soil systems is present throughout the year, highlighting the potentially critical role of groundwater with old ages on processes such as evapotranspiration and streamflow generation. The coupled numerical model and groundwater age observations show the bedrock groundwater system influences the hillslope hydrodynamics and should be considered in mountain watershed conceptual and numerical models.

The positions and magnitudes of deuterium offsets between bulk xylem and corresponding source waters are under debate and quantifying them is essential for isotope-based ecohydrological investigations. In this study, stable isotopes (δ2H, δ18O, and δ13C), iteration method, and rehydration experiments were combined to quantitatively determine the magnitude of cryogenic vacuum extraction (CVE)- and radial water transport (RWT)-induced deuterium offsets using one riparian tree species Salix babylonica L. A modified potential water source line (MPWL) was proposed to identify the total δ2H offsets between bulk xylem and source waters. The relationships between δ2H offsets induced by CVE or RWT and plant water content, leaf δ13C values, soil water content (SWC), and the depth to the water table (WTD) were investigated. Results showed that the bulk xylem waters in different tissue positions of S. babylonica showed −7.0 ‰ to −4.0 ‰ deuterium depletion relative to MPWL at four different sites (p < 0.01). The isotopic compositions of sap water coincided well with MPWL on the dual-isotope plot at the four sites. The CVE- and RWT-induced δ2H offsets accounted for 75.1 % and 24.9 % of the total δ2H offsets, respectively. The CVE-induced δ2H offsets were significantly negatively correlated with plant water content. In comparison, the RWT-induced δ2H offsets were negatively related to plant leaf δ13C values, trunk water content, and SWC, but positively correlated with WTD. This study provides a quantitative contribution of two major sources of deuterium offsets. The results provide critical insights into isotope-based plant water source identification and evapotranspiration partitioning.

Understanding the mechanisms that control seasonal groundwater recharge at local and intermediate scales is critical for understanding contaminant transport. The recharge mechanism of seasonal precipitation and irrigation, companied with legacy wastewater in porewater in alluvial aquifer were complicated due to the seasonal variation of multiple recharge sources. In this study, a long-term wastewater leakage and irrigation region along the Tanghe Wastewater Reservoir (TWR) in the alluvial plain area of North China Plain to investigate the recharge mechanism from unsaturated zone to the upper shallow groundwater affected by multiple water sources. Water chemical ions and stable isotopes of water (2H and 18O) of 30 m deep sediment profiles and groundwater boreholes were used to trace the recharge processes. The porewater stable isotopes of the sediment profiles revealed vertical recharge rates ranging from 0.63 to 1.09 m/year for the layered unsaturated zone with silt and silty clay. Due to the matrix flow through unsaturated zone, the legacy wastewater in the unsaturated zone affected the variation of groundwater quality in long term. However, fast flow (i.e., preferential or lateral flow) occurred in sand layers of alluvial aquifers lead to significant precipitation contributions (44 to 61 %) to the upper shallow groundwater (USGW) recharge, resulting in the seasonal variation of stable isotopes and water chemical ions. Affected by the fast flow with seasonal variations and matrix flow with legacy wastewater in the unsaturated zone, the δ2H and δ18O relationship of the USGW showed two types of hysteresis loops in the dual isotope space: 1) groundwater in regions affected by the TWR wastewater leakage shows narrow loops and a nearly straight line with end-members of precipitation that recharged to groundwater by fast flow, and evaporated porewater plotting along the TWR evaporation line; and 2) groundwater in irrigated farmlands with low and high irrigation amounts and intense evaporation shows stronger hysteresis with loops overlapping with shallow porewater, suggesting the impact of legacy wastewater of the unsaturated zone on groundwater. The residual pollutants in soil and the type of fast flow determine the different seasonal variation of groundwater quality. Preferential flow in alluvial aquifer regions can increase the proportion of seasonal recharge from precipitation, resulting in the rapid introduction of contaminants from surface or shallow soils into the alluvial aquifer.

About 80 % of the precipitation at the Colorado River s headwaters is snow, and the resulting snowmeltdriven hydrograph is a crucial water source for about 40 million people. Snowmelt from alpine and subalpine snowpack contributes substantially to groundwater recharge and river flow. However, the dynamics of snowmelt progression are not well understood because observations of the highelevation snowpack are difficult due to challenging access in complex mountainous terrain as well as the cost and labor intensity of currently available methods. We present a novel approach to infer the processes and dynamics of highelevation snowmelt contributions predicated upon stable hydrogen and oxygen isotope ratios observed in streamflow. We show that deuterium-excess (d-excess) values of stream water could serve as a comparatively cost-effective proxy for a catchment-integrated signal of high-elevation snowmelt contributions to catchment runoff. We sampled stable hydrogen and oxygen isotope ratios of the precipitation, snowpack, and stream water in the East River, a headwater catchment of the Colorado River, and the stream water of larger catchments at sites on the Gunnison River and Colorado River. The d-excess of snowpack increased with elevation; the upper subalpine and alpine snowpack (> 3200 m) had substantially higher d-excess compared to lower elevations (< 3200 m) in the study area. The d-excess values of stream water reflected this because d-excess values increased as the higher-elevation snowpack contributed more to stream water generation later in the snowmelt/runoff season. End-member mixing analyses based on the d-excess data showed that the share of high-elevation snowmelt contributions within the snowmelt hydrograph was on average 44 % and generally increased during melt period progression, up to 70 %. The observed pattern was consistent during 6 years for the East River, and a similar relation was found for the larger catchments on the Gunnison and Colorado rivers. High-elevation snowpack contributions were found to be higher for years with lower snowpack and warmer spring temperatures. Thus, we conclude that the d-excess of stream water is a viable proxy to observe changes in high-elevation snowmelt contributions in catchments at various scales. Inter-catchment comparisons and temporal trends of the d-excess of stream water could therefore serve as a catchment-integrated measure to monitor if mountain systems rely on high-elevation water inputs more during snow drought compared to years of average snowpack depths.

Agricultural water management is increasingly prioritized throughout the world as producers are tasked with meeting growing crop demand while also managing environmental resources more sustainably. Likewise, agriculture is increasingly modifying the terrestrial water cycle. In response to these dynamics, the informal research discipline of agrohydrology continues to grow, fueled by a new era of rapidly evolving research tools and big data availability. While many researchers are actively invested in agrohydrology as a research topic, there remains a gap in formalizing this valuable discipline. This article aims to: (a) identify key research themes in agrohydrology, (b) conceptualize future research topics within each theme, and (c) estimate a timeframe before topics become pressing (i.e., before a topic becomes a limiting factor in advancing water management in an agricultural context). This commentary is meant to guide the trajectory of an evolving discipline of agrohydrology, the practice of agricultural water management at multiple nested scales, and the conversation of the invested public.

The hydrological cycle of sub-arctic areas is dominated by the snowmelt event. An understanding of the mechanisms that control water fluxes during high-volume infiltration events in sub-arctic till soils is needed to assess how future changes in the timing and magnitude of snowmelt can affect soil water storage dynamics. We conducted a tracer experiment in which deuterated water was used to irrigate a plot on a forested hilltop in Lapland, tracked water fluxes of different mobility and monitored how the later snowmelt modifies the labelled soil water storage. We used lysimeters and destructive soil coring for soil water sampling and monitored and sampled the groundwater. Large spatiotemporal variability between the waters of different mobility was observed in the subsurface, while surface water flow during the tracer experiment was largely controlled by a fill-and-spill mechanism. Extensive soil saturation induced the flow of labelled water into the roots of nearby trees. We found that labelled water remained in deeper soil layers over the winter, but the snowmelt event gradually displaced all deuterated water and fully homogenized all water fluxes at the soil–vegetation interface. The conditions required for the full displacement of the old soil water occur only during a snowmelt with a persistently high groundwater table. We propose a conceptual model where infiltration into the soil and eventual soil water replenishment occur in three stages. First, unsaturated macropore flow is initiated via the surface microtopography and is directed towards the groundwater storage. The second stage is characterized by groundwater rise through the macropore network, subsequent pore water saturation and increased horizontal connectivity of macropores. Shallow subsurface lateral fluxes develop in more permeable shallow soil layers. In the third stage, which materializes during a long period with a high groundwater table and high hydrological connectivity within the soil, the soil water is replenished via enhanced matrix flow and pore water exchange with the macropore network.

Introduction: Immune checkpoint inhibitors (ICIs) have substantially advanced the treatment of patients with malignant melanoma. However, improving therapeutic efficacy requires identifying drug combinations that elicit durable responses without inducing intolerable toxicity. Within that context, selinexor emerges as a possible combination option that has been shown in preclinical studies to enhance the efficacy of ICI therapy. Methods: In this phase 1b study, we investigated selinexor in combination with pembrolizumab in 25 patients with advanced non-uveal melanoma. Patients received selinexor at a dosage of 60 mg taken orally twice weekly, and pembrolizumab intravenously at a dosage of 200 mg every 3 weeks. Results: Despite the high incidence of adverse events (96%), most treatment-related toxicities were manageable with supportive care and dose reductions. The most common adverse events of any grade were nausea (n = 20; 80%), decreased white blood cell count (n = 15; 60%), vomiting (n = 14; 56%), anemia (n = 12; 48%), fatigue (n = 12; 48%), and decreased platelet count (n = 12; 48%). The 10 patients with treatment-naïve evaluable disease had an objective response rate (ORR) of 70% (n = 7, including three patients with complete response), which was significantly higher than that of the 14 patients with prior anti–programmed cell death protein 1 (anti-PD-1) therapy, whose ORR was 7% (n = 1; p = 0.002). Stable disease was observed in two patients (20%) with treatment-naïve disease and seven patients (50%) with prior anti-PD-1 therapy. Conclusion: Selinexor combined with pembrolizumab showed promising antitumor activity in patients with treatment-naïve metastatic melanoma. The toxicity profile of the combination was consistent with that reported for individual agents, with no additional safety concerns.

Weather forecasts at subseasonal-to-seasonal (S2S) timescales have little forecast skill in the troposphere: individual ensemble members are mostly uncorrelated and span a range of atmospheric evolutions that are possible for the given set of external forcings. The uncertainty of such a probabilistic forecast is then determined by this range of possible evolutions – often quantified in terms of ensemble spread. Various dynamical processes can affect the ensemble spread within a given region, including extreme events simulated in individual members. For forecasts of geopotential height at 1000 hPa (Z1000) over Europe, such extremes are mainly comprised of synoptic storms propagating along the North Atlantic storm track. We use ECMWF reforecasts from the S2S database to investigate the connection between different storm characteristics and ensemble spread in more detail. We find that the presence of storms in individual ensemble members at S2S timescales contributes about 20 % to the total Z1000 forecast uncertainty over northern Europe. Furthermore, certain atmospheric conditions associated with substantial anomalies in the North Atlantic storm track show reduced Z1000 ensemble spread over northern Europe. For example, during periods with a weak stratospheric polar vortex, the genesis frequency of Euro-Atlantic storms is reduced and their tracks are shifted equatorwards. As a result, we find weaker storm magnitudes and lower storm counts, and hence anomalously low subseasonal ensemble spread, over northern Europe.

Background: Elongation factor protein (EF-P) in bacteria helps ribosomes to incorporate contiguous proline residues (xPro) into proteins. In this way, EF-P rescues ribosomes from stalling at these xPro motifs. Whereas EF-P deficiency is lethal for some species, others show reduced virulence or generally lower growth rates, such as Escherichia coli (E. coli). EF-P needs to be post-translationally modified to gain full functionality. Methods: We constructed E. coli K-12 mutant strains with deletion of the serA gene leading to an auxotrophy for L-serine. Then, we engineered a 6xPro motif in the recombinant serA gene, which was then chromosomally inserted under its native promoter. Furthermore, mutant strains which were deleted for efp and/or epmA (encoding the EF-P modification protein EpmA) were engineered. Results: Δefp, ΔepmA, and Δefp/ΔepmA double mutants showed already significantly reduced growth rates in minimal media. ΔserA derivatives of these strains were complemented by the wt serA gene but not by 6xPro-serA. ΔserA mutants with intact efp were complemented by all serA-constructs. Chromosomal expression of the recombinant efp gene from E. coli or from the pathogen, Staphylococcus aureus (S. aureus), restored growth, even without epmA expression. Conclusions: We provide a novel synthetic reporter system for in vivo evaluation of EF-P deficiency. In addition, we demonstrated that both EF-P-E. coli and EF-P-S. aureus restored the growth of a 6xPro-serA: Δefp, ΔepmA strain, which is evidence that modification of EF-P might be dispensable for rescuing of ribosomes stalled during translation of proline repeats.

Soft tissue elasticity is directly related to different stages of diseases and can be used for tissue identification during minimally invasive procedures. By palpating a tissue with a robot in a minimally invasive fashion force-displacement curves can be acquired. However, force-displacement curves strongly depend on the tool geometry which is often complex in the case of medical tools. Hence, a tool calibration procedure is desired to directly map force-displacement curves to the corresponding tissue elasticity.We present an experimental setup for calibrating medical tools with a robot. First, we propose to estimate the elasticity of gelatin phantoms by spherical indentation with a state-of-the-art contact model. We estimate force-displacement curves for different gelatin elasticities and temperatures. Our experiments demonstrate that gelatin elasticity is highly dependent on temperature, which can lead to an elasticity offset if not considered. Second, we propose to use a more complex material model, e.g., a neural network, that can be trained with the determined elasticities. Considering the temperature of the gelatin sample we can represent different elasticities per phantom and thereby increase our training data.We report elasticity values ranging from 10 to 40 kPa for a 10% gelatin phantom, depending on temperature.

With the "pictorial turn", the picture has gained a new significance as a medium. It is impossible to imagine a digitalized world affected by mass media without pictures. While there are several studies on the impact of pictures in the discourse on climate change in the media, there has been no analysis of the visual representation of climate change in textbooks, which remain an important teaching medium. The aim of this study is to identify the visual representations in textbooks in terms of form, image theme and motif related to the topic of climate change. The procedure is based on the method of qualitative content analysis. The results show that mainly photos, graphics and diagrams are used, whose contents differ from those of the media coverage. Besides diagrams and models, the impacts of climate change and the topic of nature are most frequently depicted. Representations of mitigation measures that would promote perceived self-efficacy are underrepresented in the textbooks studied.

Learner-centered instruction fosters 21st-century skills and must be implemented in geography classrooms. In this South African case study, most teachers predominantly implemented teacher-centered instruction. The analysis of the results established a moderate but highly significant relationship between geography teachers' years of teaching and their implementation of teacher-centered instruction and a weak significant relation in the implementation of individual instructional strategies. Teachers with more years of teaching implemented more teacher-centered and individual learner-centered instructional strategies than early-career teachers. Teachers stated that learners and parents expected them to teach and that large classes hindered the implementation of learner-centered instruction.

Abstract: In November 2021, the Artificial Intelligence for Earth System Predictability (AI4ESP) workshop was held, which involved hundreds of researchers from dozens of institutions. There were 17 sessions held at the workshop, including one on ecohydrology. The ecohydrology session included various breakout rooms that addressed specific topics, including 1) soils and belowground areas; 2) watersheds; 3) hydrology; 4) ecophysiology and plant hydraulics; 5) ecology; 6) extremes, disturbance and fire, and land-use and land-cover change; and 7) uncertainty quantification methods and techniques. In this paper, we investigate and report on the potential application of artificial intelligence and machine learning in ecohydrology, highlight outcomes of the ecohydrology session at the AI4ESP workshop, and provide visionary perspectives for future research in this area.

HIV-1 can rapidly infect the brain upon initial infection, establishing latent reservoirs that induce neuronal damage and/or death, resulting in HIV-Associated Neurocognitive Disorder. Though anti-HIV-1 antiretrovirals (ARVs) suppress viral load, the blood-brain barrier limits drug access to the brain, largely because of highly expressed efflux proteins like P-glycoprotein (P-gp). While no FDA-approved P-gp inhibitor currently exists, HIV-1 protease inhibitors show promise as partial P-gp inhibitors, potentially enhancing drug delivery to the brain. Herein, we employed docking and molecular dynamics simulations to elucidate key differences in P-gp’s interactions with several antiretrovirals, including protease inhibitors, with known inhibitory or substrate-like behaviors towards P-gp. Our results led us to hypothesize new mechanistic details of small-molecule efflux by and inhibition of P-gp, where the “Lower Pocket” in P-gp’s transmembrane domain serves as the primary initial site for small-molecule binding. Subsequently, this pocket merges with the more traditionally studied drug binding site—the “Upper Pocket”—thus funneling small-molecule drugs, such as ARVs, towards the Upper Pocket for efflux. Furthermore, our results reinforce the understanding that both binding energetics and changes in protein dynamics are crucial in discerning small molecules as non-substrates, substrates, or inhibitors of P-gp. Our findings indicate that interactions between P-gp and inhibitory ARVs induce bridging of transmembrane domain helices, impeding P-gp conformational changes and contributing to the inhibitory behavior of these ARVs. Overall, insights gained in this study could serve to guide the design of future P-gp-targeting therapeutics for a wide range of pathological conditions and diseases, including HIV-1.