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Increasingly frequent severe drought events are pushing Mediterranean forests to unprecedented responses. Lack of management leads to dense forests that are highly susceptible to drought stress, potentially resulting in extensive dieback and increased vulnerability to other disturbances. Forest treatments like thinning and slash burning reduce competition for resources and have the potential to enhance tree growth and vigor and minimize tree vulnerability to drought. Here, we used tree rings to study the growth and physiological response of black pine (Pinus nigra) to drought in northeastern Spain under different treatments, including two thinning intensities (light and heavy, with 10% and 40% basal area reduction, respectively) followed by two understory treatments (clearing alone and in combination with slash burning), resulting in a research design of four treatments plus an untreated control with three replicates. Specifically, we studied basal area increment (BAI), resilience indices, and intrinsic water use efficiency (iWUE) using carbon and oxygen isotope composition (δ13C and δ18O in tree‐ring cellulose) before and after treatments. Our results showed that BAI and resistance to drought increased in the heavy‐thin (burned and unburned) and light‐thin burned units. Resilience increased in the burned units regardless of the thinning intensity, while recovery was not affected by treatment. Slash burning additionally increased BAI in the light‐thin and resistance and resilience in the heavy‐thin units compared with clearing alone. The stable isotope analysis revealed a minor effect of treatments on δ13C and δ18O. No change in iWUE among treatments was presumably linked to a proportional increase in both net CO2 assimilation and stomatal conductance, which particularly increased in the heavy‐thin (burned and unburned) and light‐thin burned units, indicating that these trees were the least affected by drought. This study shows that management approaches aimed at reducing wildfire hazard can also increase the vigor of dominant trees under drought stress. By reducing competition both from the overstory and the understory, thinning followed by clearing alone or in combination with slash burning promotes tree growth and vigor and increases its resistance and resilience to drought. [ABSTRACT FROM AUTHOR]

Exploring the contributions of new and old water to runoff during precipitation events in agricultural catchments is essential for understanding runoff generation, solute transport, and soil erosion. The aim of this study was to investigate the variability in the isotopic composition of precipitation and runoff in the 66 ha agricultural catchment in Austria, in the Hydrological Open Air Laboratory (HOAL), in order to compare two isotope hydrograph separation methods. The classical two‐component (IHS) and the ensemble hydrograph separation (EHS) were applied to multiple large events in May–October of 2013–2018 using δ18O and δ2H. The peak flow new water contributions obtained by IHS were compared with the average new water fraction from EHS. The average new water fraction calculated with EHS based on regular weekly sampling was close to zero, which can be explained by the large diffuse groundwater discharge into the stream between the events. When only investigating events with high temporal resolution sampling, the results suggest that EHS provided average new water fractions during peak flows (0.46 ± 0.04 for δ18O, 0.47 ± 0.03 for δ2H) that were close to the averages obtained by IHS (0.47 for δ18O, 0.50 for δ2H). New water fractions tended to be higher for larger rainfall intensities. High peak flow new water fractions could be explained by the agricultural land use and soils with low permeability promoting overland flow generation and by some of the tile drainage systems contributing to the delivery of water. In conclusion, a weekly sampling frequency was not sufficient in the HOAL but instead high‐resolution sampling during events was necessary to estimate the average new water contributions during events. While EHS may be a more robust approach compared to IHS, as it relaxes some of the assumptions of IHS, IHS can provide information on the variability of new water contributions of individual events. [ABSTRACT FROM AUTHOR]

Problem: Vaginal bleeding during early pregnancy is estimated to occur in 20% of all pregnancies and it is often difficult to predict who will ultimately miscarry. The role of immune cells in early pregnancy loss is poorly understood. Method of Study: In this prospective cohort study, 28 pregnant women presenting with first‐trimester vaginal bleeding donated vaginal blood, peripheral venous blood, and saliva during their initial emergency room visit, and at a follow‐up. The composition, frequency, and phenotype of immune cells in the vaginal blood were determined using flow cytometry. The proteome of serum and saliva was analyzed with OLINK proximity extension assay and correlated to vaginal immune cell phenotype and outcome of pregnancy. The course and outcome of pregnancies were followed and recorded. Results: Vaginal blood contained all main immune cell lineages including B cells, NK cells, T cells, and monocytes/macrophages. Notably, vaginal blood immune cells expressed tissue residency markers including CD49a. Women who subsequently miscarried had a higher frequency of vaginal blood CD49a+ NK cells compared to those who did not miscarry, and this correlated with serum levels of granzyme A and H, as well as CSF1, CAIX, and TWEAK. Women in the miscarriage group also had a higher frequency of peripheral blood T cells expressing CD49a. Conclusions: Our study provides novel insight into human reproductive immunology in relation to miscarriage. Tissue‐resident NK cells in vaginal blood alone or in combination with serological biomarkers hold potential as prognostic factors in the prediction of pregnancy outcome in women with early pregnancy bleedings. [ABSTRACT FROM AUTHOR]

Rationale: A silver phosphate reference material (Ag3PO4) for the measurement of stable oxygen isotope compositions is much needed; however, it is not available from the authorities distributing reference materials. This study aims to fill this gap by calibrating a new Ag3PO4 stable isotope comparison material produced by the University of Natural Resources and Life Sciences (BOKU). Methods: Aliquots of Ag3PO4 were distributed to four laboratories who frequently measure the δ18O value in Ag3PO4; the University of Natural Resources and Life Sciences (BOKU), the University of Western Australia (UWA), the University of Helsinki (UH), and the Helmholtz Centre for Environmental Research (UFZ). The instruments used to perform the measurements were high‐temperature conversion elemental analysers coupled with continuous flow isotope ratio mass spectrometers. The working gas δ18O value was set to 0‰ and the normalization was done by a three‐point linear regression using the reference materials IAEA‐601, IAEA‐602, and NBS127. Results: The mean δ18O value of the new BOKU Ag3PO4 comparison material on the VSMOW‐SLAP scale is 13.71‰ and the combined uncertainty is estimated as ±0.34‰. This estimated uncertainty is within the range typical for comparison materials of phosphates and sulphates. Consistent results from the different laboratories probably derived from similar instrumentation, and use of the same reference materials and normalization procedure. The matrix effect of the different reference materials used in this study was deemed negligible. Conclusions: The BOKU Ag3PO4 can be used as an alternative comparison material for stable oxygen isotope analysis and is available for stable isotope research laboratories to facilitate calibration. [ABSTRACT FROM AUTHOR]

The Austrian network of isotopes in rivers comprises about 15 sampling locations and has been operated since 1976. The Danube isotope time series goes back to 1963. The isotopic composition of river water in Central Europe is mainly governed by the isotopic composition of precipitation in the catchment area; evaporation effects play only a minor role. Short-term and long-term isotope signals in precipitation are thus transmitted through the whole catchment. The influence of climatic changes has become observable in the long-term stable isotope time series of precipitation and surface waters. Environmental 3H values were around 8 TU in 2015, short-term 3H pulses up to about 80 TU in the rivers Danube and March were a consequence of releases from nuclear power plants. The complete isotope data series of this network will be included in the Global Network of Isotopes in Rivers database of the International Atomic Energy Agency (IAEA) in 2017. This article comprises a review of 50 years isotope monitoring on rivers and is also intended to provide base information on the (isotope-)hydrological conditions in Central Europe specifically for the end-users of these data, e.g. for modelling hydrological processes. Furthermore, this paper includes the 2006-2015 supplement adding to the Danube isotope set published earlier. [ABSTRACT FROM AUTHOR]

Research on global multivendor information systems development (ISD) outsourcing projects has uncovered several management challenges, resulting mainly from the complexity of coordinating multiple vendors across geographical locations. However, a gap persists regarding effective management practices in this context. This study employs an exploratory, single-case study design with grounded theory techniques to generate new, empirically grounded theory regarding mindful management practices. In particular, (1) relational knowledge should be viewed as an enabler but not as a standard recipe for interfirm cooperation, (2) cross-organizational trial-and-error learning processes should be leveraged early in the project, (3) intervendor power relations should be determined on the basis of expertise, and (4) multichannel communication should be structured around the context. These four practices are supported by theoretical insights drawn from organizational mindfulness theory: commitment to resilience, preoccupation with failure, under-specification of structures, and sensitivity to operations. Therefore, the papers main theoretical contribution is the introduction and extension of organizational mindfulness to the domain of global multivendor sourcing, marking an important first step for extending prior theory to the context of interorganizational exchange relationships and networks, with key implications for research and practice. [ABSTRACT FROM AUTHOR]

The hydrological application of isotope-ratio measurements is based upon variations of ²H, ³H and 18O in the natural water cycle. Main targets of isotope-hydrological projects are the investigation of hydrological relationships, the hydrogeological situation, the residence times of groundwater, and the possible transport of pollutants. Isotope-hydrological data also play an important role in climate research. A good knowledge of the "isotopic environment" is necessary for the interpretation of isotope data. For this purpose, basic isotope data of all parts of the hydrological cycle have been gathered at the Vienna Arsenal for nearly fifty years. The emphasis was on the isotope ratios in precipitation as they represent the input values for isotopic investigations in the terrestrial part of the water cycle. The influence of climatic changes has become observable in the long-term isotope time series of precipitation and surface waters. This influence must also be taken into account when using isotope data from a longer time period in hydrology. Environmental 3H values were around 10 TU in 2010, while slightly higher values can be observed in hydrological systems which still contain significant water portions from the sixties and seventies. Aside from a survey of the development of the "isotopic environment" in the last decades and a few key results, which helped to understand (isotope)hydrological processes, this paper includes some data sets meant for application purposes. [ABSTRACT FROM AUTHOR]

The sodium (Na + ) leak channel (NALCN) is a member of the four-domain voltage-gated cation channel family that includes the prototypical voltage-gated sodium and calcium channels (Na V s and Ca V s, respectively). Unlike Na V s and Ca V s, which have four lateral fenestrations that serve as routes for lipophilic compounds to enter the central cavity to modulate channel function, NALCN has bulky residues (W311, L588, M1145 and Y1436) that block these openings. Structural data suggest that oc-cluded lateral fenestrations underlie the pharmacological resistance of NALCN to lipophilic compounds, but functional evidence is lacking. To test this hypothesis, we unplugged the fenestrations of NALCN by substituting the four aforementioned resi-dues with alanine (AAAA) and compared the effects of Na V , Ca V and NALCN block-ers on both wild-type (WT) and AAAA channels. Most compounds behaved in a simi-lar manner on both channels, but phenytoin and 2-aminoethoxydiphenyl borate (2-APB) elicited additional, distinct responses on AAAA channels. Further experiments using single alanine mutants revealed that phenytoin and 2-APB enter the inner cav-ity through distinct fenestrations, implying structural specificity to their modes of ac-cess. Using a combination of computational and functional approaches, we identified amino acid residues critical for 2-APB activity, supporting the existence of drug bind-ing site(s) within the pore region. Intrigued by the activity of 2-APB and its ana-logues, we tested additional compounds containing the diphenylmethane/amine moiety on WT channels. We identified compounds from existing clinically used drugs that exhibited diverse activity, thus expanding the pharmacological toolbox for NALCN. While the low potencies of active compounds reiterate the resistance of NALCN to pharmacological targeting, our findings lay the foundation for rational drug design to develop NALCN modulators with refined properties., Significance Statement: The sodium leak channel (NALCN) is essential for survival: mutations cause life-threatening developmental disorders in humans. However, no treatment is currently available due to the resistance of NALCN to pharmacological targeting. One likely reason is that the lateral fenestrations, a common route for clinically used drugs to enter and block related ion channels, are occluded in NALCN. Using a combination of computational and functional approaches, we unplugged the fenestrations of NALCN which led us to the first molecularly defined drug binding site within the pore region. Besides that, we also identified additional NALCN modulators from existing clinically used therapeutics, thus expanding the pharmacological toolbox for this leak channel.