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The Grand Portage Band of Lake Superior Chippewa manages for sustainable subsistence harvests of moose (mooz; Alces alces) and white‐tailed deer (waawaashkeshi; Odocoileus virginianus). Moose populations in northern Minnesota, USA, are declining, which may necessitate alterations to Indigenous subsistence practices. Moose and deer exhibit seasonal behaviors such as altered space use and movement strategies, to which gray wolves (ma'iingan; Canis lupus) and humans may adapt, resulting in seasonal mortality patterns. Identifying periods of increased moose and deer vulnerability is important for achieving tribal conservation objectives. We assessed seasonal cause‐specific mortality of adult moose (2010–2021) and deer (2016–2022) fitted with global positioning system collars on and near the Grand Portage Indian Reservation (Gichi Onigaming; GPIR) in Minnesota and hypothesized mortality risk would be influenced by species‐specific space use patterns and weather. We estimated survival rates and mortality risk using time‐to‐event models. We recorded 42 moose mortalities (17 health issues, 8 predations, 4 subsistence harvests, 13 unknown causes) and 49 deer mortalities (26 predations, 13 harvests, 4 other causes, 6 unknown causes). Mean annual moose survival was 83.2%, and mortality risk peaked during late winter (~25 April) and fall (~8 October). Mean annual deer survival was 48.0%, and mortality risk peaked during late winter (~25 March) and during their fall migration period (~11 November). Mortality timing coincided with transitions between space use states (i.e., periods of spatial stability), suggesting ungulates are at greater risk during these transitional periods, though movement strategy (i.e., resident vs. migratory) did not influence mortality risk. Further, increased winter severity corresponded with increased deer mortality. We observed similar temporal peaks in mortality risk when harvest mortalities were censored, suggesting our observed seasonal mortality peaks occur naturally despite harvest comprising most fall deer mortality. Our results can inform population models and harvest regulations by identifying periods of mortality risk on GPIR under Anishinaabe principles of seventh‐generation conservation planning. [ABSTRACT FROM AUTHOR]

This project evaluated the applicability of existing alternative data, such as chemical, biological and metabolite similarity, to improve the selection of relevant source compound (SC). This information was modularly integrated into read‐across (RAX) case studies addressing systemic toxicity after repeated exposure or developmental toxicity. For this purpose, data‐rich reference classes of pesticides were defined, with propiconazole and iodosulfuron methyl sodium as target compounds (TCs). The combination of chemical and biological similarity for TC propiconazole detected mostly relevant SC from reference class compounds. Biological similarity was calculated using binary hit call from ToxCast dataset, which is highly dependent on the data density. Low data density was used as a measure of uncertainty. In the case of the TC iodosulfuron methyl sodium, ToxCast data confirmed overall low activity. Second case study started with biological similarity calculated from ToxCast dataset. This approach resulted in an overwhelming number of candidate SCs. This indicates that the biological hit call data are relatively unspecific, as they are activated by many compounds. The integration of shared metabolites can efficiently restrict the selection of SCs to the most relevant compounds, coupled with integration of chemical and/or biological similarity. In absence of observed in vivo data, metabolites can be predicted using available tools, which generated comparable results. Based on apical findings from in vivo legacy studies, compound classes were not able to be discerned, primarily due to induced hepatotoxicity observed in about 60% of all repeated dose oral exposure studies. Overall, a RAX assessment framework integrating existing information on metabolites and biological properties to identify SC in a modular approach is recommended. The case studies presented suggest an increased confidence of SC identification using metabolite similarity. This suggestion complements the workflow proposed by EU‐ToxRisk, which focuses on targeted testing and assessment of SC upon their identification. [ABSTRACT FROM AUTHOR]

As global tree‐growing efforts have escalated in the past decade, copious failures and unintended consequences have prompted many reforestation best practices guidelines. The extent to which organizations have integrated these ecological and socioeconomic recommendations, however, remains uncertain. We reviewed websites of 99 intermediary organizations that promote and fund tree‐growing projects to determine how well they report following best practices. Nearly half the organizations stated tree or area planting targets, but only 25% had measurable, time‐bound objectives. Most organizations discussed the benefits local communities would receive from trees, but only 38% reported measures of these outcomes. Nonprofit organizations with greater prior experience converged more closely on best practices, and their level of scientific expertise was positively associated with clearer project selection standards. Although many tree‐growing organizations acknowledge the importance of clear goals, local community involvement, and monitoring, our results raise questions regarding whether long‐term benefits are being achieved and emphasize the need for stronger public accountability standards. [ABSTRACT FROM AUTHOR]

Summary: Acute myeloid leukaemia (AML) relapse after allogeneic haematopoietic cell transplantation (allo‐HCT) is often driven by immune‐related mechanisms and associated with poor prognosis. Immune checkpoint inhibitors combined with hypomethylating agents (HMA) may restore or enhance the graft‐versus‐leukaemia effect. Still, data about using this combination regimen after allo‐HCT are limited. We conducted a prospective, phase II, open‐label, single‐arm study in which we treated patients with haematological AML relapse after allo‐HCT with HMA plus the anti‐PD‐1 antibody nivolumab. The response was correlated with DNA‐, RNA‐ and protein‐based single‐cell technology assessments to identify biomarkers associated with therapeutic efficacy. Sixteen patients received a median number of 2 (range 1–7) nivolumab applications. The overall response rate (CR/PR) at day 42 was 25%, and another 25% of the patients achieved stable disease. The median overall survival was 15.6 months. High‐parametric cytometry documented a higher frequency of activated (ICOS+, HLA‐DR+), low senescence (KLRG1−, CD57−) CD8+ effector T cells in responders. We confirmed these findings in a preclinical model. Single‐cell transcriptomics revealed a pro‐inflammatory rewiring of the expression profile of T and myeloid cells in responders. In summary, the study indicates that the post‐allo‐HCT HMA/nivolumab combination induces anti‐AML immune responses in selected patients and could be considered as a bridging approach to a second allo‐HCT. Trial‐registration: EudraCT‐No. 2017‐002194‐18. [ABSTRACT FROM AUTHOR]

Usage of alkaline and saline groundwater with elevated concentrations of fluoride (F−) for irrigation of pastures requires an assessment of the mobility of F− within the plant‐water‐soil continuum. Factors influencing F− sorption and desorption in 95 Australian soils were examined. Pronounced differences in F− sorption were observed across the soils, but these differences could not be explained by differences in soil pH, electrical conductivity or organic carbon. Rather, sorption was correlated with the content of Fe/Al hydrous oxides and kaolinite in soil. Sorption of F− onto soils increased the solution pH and the ratio of (F− adsorbed) to (OH− desorbed) was consistently below 1, thereby indicating that adsorption of F− results in the release of water and hydroxyl groups from, or co‐adsorption of protons to, the sorbent surface. Maximum sorption occurred at pH values of approximately 5–6, whilst sulphate slightly increased (<5%) F− sorption. Desorption was slightly decreased (~3%–7%) in presence of sulphate anions. Hence, it is unlikely that irrigation of soil with alkaline and saline groundwater, in combination with soil applications of gypsum and sulphur to limit pH fluctuations, would increase mobility of F− in soil. Finally, the irrigation of soil columns with 1200–1500 mm of alkaline and saline groundwater containing 0.18 mM F−, as would commonly occur in irrigation systems using coal seam gas associated water in Australia, resulted in a F− concentration of 0.05 mM at 10 cm depth and the measured values were in excellent agreement with modelled F− movement based on sorption parameters. Thus, sorption parameters can be used to identify soils which minimize movement of F− because of their strong F− sorption. Based on these results, safe limits for irrigation of soil can be established which avoid F− toxicity risks to plants, animals and contamination of water resources. [ABSTRACT FROM AUTHOR]

Rationale: The simultaneous analysis of the three stable isotopes of oxygen—triple oxygen isotope analysis—has become an important analytical technique in natural sciences. Determination of the abundance of the rare 17O isotope in CO2 gas using magnetic sector isotope ratio mass spectrometry is complicated by the isobaric interference of 17O by 13C (13C16O16O and 12C16O17O, both have mass 45 amu). A number of analytical techniques have been used to measure the 17O/16O ratio of CO2 gas. They either are time consuming and technically challenging or have limited precision. A rapid and precise alternative to the available analytical methods is desirable. Methods: We present the results of triple oxygen isotope analyses using an Aerodyne tunable infrared laser direct absorption spectroscopy (TILDAS) CO2 analyzer configured for 16O, 17O, and 18O combined with a custom gas inlet system. We evaluate the sensitivity of our results to a number of parameters. CO2 samples with a wide range of δ18O values (from −9.28‰ to 39.56‰) were measured and compared to results using the well‐established fluorination‐gas source mass spectrometry method. Results: The TILDAS system has a precision (standard error, 2σ) of better than ±0.03‰ for δ18O and ±10 per meg for Δ′17O values, equivalent to the precision of previous analytical methods. Samples as small as 3 μmol CO2 (equivalent to 300 μg CaCO3) can be analyzed with a total analysis time of ~30 min. Conclusions: We have successfully developed an analytical technique for the simultaneous determination of the δ17O and δ18O values of CO2 gas. The precision is equal to or better than that of existing techniques, with no additional chemical treatments required. Analysis time is rapid, and the system is easily automated so that large numbers of samples can be analyzed with minimal effort. [ABSTRACT FROM AUTHOR]

Understanding the types and magnitude of human‐caused mortality is essential for maintaining viable large carnivore populations. We used a database of cause‐specific mortality to examine how hunting regulations and landscape configurations influenced human‐caused mortality of North American gray wolves (Canis lupus). Our dataset included 21 studies that monitored the fates of 3564 wolves and reported 1442 mortalities. Human‐caused mortality accounted for 61% of mortality overall, with 23% due to illegal harvest, 16% due to legal harvest, and 12% the result of management removal. The overall proportion of anthropogenic wolf mortality was lowest in areas with an open hunting season compared to areas with a closed hunting season or mixed hunting regulations, suggesting that harvest mortality was neither fully additive nor compensatory. Proportion of mortality from management removal was reduced in areas with an open hunting season, suggesting that legal harvest may reduce human‐wolf conflicts or alternatively that areas with legal harvest have less potential for management removals (e.g., less livestock depredation). Proportion of natural habitat was negatively correlated with the proportion of anthropogenic and illegal harvest mortality. Additionally, the proportion of mortality due to illegal harvest increased with greater natural habitat fragmentation. The observed association between large patches of natural habitat and reductions in several sources of anthropogenic wolf mortality reiterate the importance of habitat preservation to maintain wolf populations. Furthermore, effective management of wolf populations via implementation of harvest may reduce conflict with humans. Effective wolf conservation will depend on holistic strategies that integrate ecological and socioeconomic factors to facilitate their long‐term coexistence with humans. [ABSTRACT FROM AUTHOR]

Aims: Heart failure (HF) is a systemic inflammatory disorder with infections being an important cause of morbidity and mortality. We asked if HF patients have a higher susceptibility to infections compared with the general population and if a subtle secondary immunodeficiency facilitates infectious complications. Methods and results: In a cohort of 92 patients with HF with reduced ejection fraction, we analysed recirculating lymphocyte subpopulations, serum immunoglobulin levels, and specific antibody titres against pneumococcal antigens. We quantified susceptibility to infections of the respiratory tract with a validated questionnaire and compared it to the general population. Susceptibility to infections of the respiratory tract was comparable in HF patients and the general population. Hypogammaglobulinaemia was present in 16% of HF patients, but anti‐pneumococcal titres showed no evidence of specific secondary antibody deficiency. Relative lymphopaenia in our HF cohort was due to B lymphocytopenia with a relative reduction in naive B‐cells and expansion of memory B‐cells while CD4+ and CD8+ T‐lymphocytes as well as NK‐cell counts were comparable between HF and healthy donors. The intake of the angiotensin receptor neprilysin (CD10) inhibitor (ARNI) sacubitril/valsartan was associated with increased B‐lymphocyte counts, possibly by an increased output of CD10+ transitional B lymphocytes from the bone marrow. Conclusion: Despite a reduction of B lymphocytes in HF and mild hypogammaglobulinaemia, patients showed no evidence of secondary immunodeficiency or increased susceptibility to infections. The relevance of B‐cell lymphopenia in HF patients and modulation of B‐cell counts under ARNI treatment remains to be investigated. [ABSTRACT FROM AUTHOR]

The article presents evidence about the Middle Palaeolithic and Middle to Upper Palaeolithic transition interval in the karst area of the Danube Gorges in the Lower Danube Basin. We review the extant data and present new evidence from two recently investigated sites found on the Serbian side of the Danube River – Tabula Traiana and Dubočka‐Kozja caves. The two sites have yielded layers dating to both the Middle and Upper Palaeolithic and have been investigated by the application of modern standards of excavation and recovery along with a suite of state‐of‐the‐art analytical procedures. The presentation focuses on micromorphological analyses of the caves' sediments, characterisation of cryptotephra, a suite of new radiometric dates (accelerator mass spectrometry and optically stimulated luminescence) as well as proteomics (zooarchaeology by mass spectrometry) and stable isotope data in discerning patterns of human occupation of these locales over the long term. [ABSTRACT FROM AUTHOR]

The InSight mission to Mars is currently monitoring the seismic activity of the planet. Interpretation of seismological observations in terms of composition and mineralogy requires the knowledge of density and thermo‐elastic properties of constituent materials at pertinent conditions. We thus performed phase equilibria experiments and carried out sound velocity and density measurements on aggregates representative of the Martian mantle over pressures and temperatures directly relevant for Mars' upper and mid mantle. Our results indicate the stability of magnetite, although in a small amount, in phase assemblages at upper mantle conditions, especially in an oxidized environment. The measured pressure and temperature derivatives of compressional and shear velocities show that the temperature‐induced reduction of seismic wave speeds dominates over pressure‐induced effects at Mars' shallow mantle conditions for the predicted areotherms and, independently from mineralogy, support the presence of a low‐shear‐wave‐velocity layer between 150 and 350 km depth, in agreement with seismic observations. Plain Language Summary: The InSight mission operating on Mars is currently monitoring the planet's seismic activity. The recorded marsquakes can be used to obtain information on Mars' internal composition. However, the interpretation of these observations requires knowledge of the physical properties of the minerals expected to compose the Martian mantle at the relevant conditions. In this study we report: (1) experiments investigating the nature and abundance of the mineral phases stable at Martian mantle conditions; (2) sound velocity and density measurements on these rocks over a pressure and temperature range directly relevant for Mars' mantle, providing information that can be directly compared to the seismological findings from the InSight mission. Our results reveal the stability of small amounts of magnetite, an Fe3+‐rich mineral not reported in previous studies but a likely candidate in Mars' oxidized mantle environment. Moreover, measured wave velocities indicate the existence of a region between 150 and 350 km depth where, due to large temperature‐induced reduction, shear wave velocities decrease with depth as opposed to an expected increase. This finding is consistent with recent observations from the InSight mission on Mars. Key Points: Sound wave velocities and density were measured for pressures, temperatures, and mineralogical assemblages representative of Mars' mantleExperimental results support the existence of a low shear velocity layer in the shallow Martian mantlePhase equilibria experiments suggest the existence of ferrian minerals in the oxidized regions of the uppermost Martian mantle [ABSTRACT FROM AUTHOR]

Recent longitudinal observations show that human menstrual cycles, sleep‐wake cycles and manic‐depressive cycles can become synchronized with lunar cycles, but do so in uniquely complex and heterogeneous ways that are unlikely to have been detected by past studies. Past studies' negative results have given rise to a scientific consensus that human biology and behavior are unaffected by lunar cycles. The recent observations show that synchrony can be temporary, and can occur with more than one type of lunar cycle, more than one phase of a lunar cycle and more than one resonant frequency of a lunar cycle. Given the variability of human responses to lunar cycles, aggregate analyses used in almost all previous studies would likely have cancelled out individuals' responses and led to false negative results. In light of these observations, the question of lunar influence should be investigated further, with longitudinal observations and case‐by‐case analyses of individuals' data. [ABSTRACT FROM AUTHOR]

We carried out a series of silicate fractional crystallization experiments at lower mantle pressures using the laser‐heated diamond anvil cell. Phase relations and the compositional evolution of the cotectic melt and equilibrium solids along the liquid line of descent were determined and used to assemble the melting phase diagram. In a pyrolitic magma ocean, the first mineral to crystallize in the deep mantle is iron‐depleted calcium‐bearing bridgmanite. From the phase diagram, we estimate that the initial 33%–36% of the magma ocean will crystallize to form such a buoyant bridgmanite. Substantial calcium solubility in bridgmanite is observed up to 129 GPa, and significantly delays the crystallization of the calcium silicate perovskite phase during magma ocean solidification. Residual melts are strongly iron‐enriched as crystallization proceeds, making them denser than any of the coexisting solids at deep mantle conditions, thus supporting the terrestrial basal magma ocean hypothesis (Labrosse et al., 2007). Plain Language Summary: The first 100 million years of Earth's history saw the mantle extensively molten by energetic impacts during its formation. How this melt solidified (i.e. from the bottom up or from the top down?) and the composition and signature of the "primitive" solid mantle it produced depend on the crystallization sequence of molten mantle silicates at large depths. In order to constrain this experimentally, we compressed and melted silicates whose composition is relevant to the bulk mantle, and then let them crystallize, using the laser‐heated diamond anvil cell. We established the melting phase diagram of mantle silicates at 52 GPa (1300 km depth, a minimum for Earth's magma ocean), and show that about 1/3rd of the molten mantle solidifies to a buoyant mineral, calcium‐bearing iron‐poor bridgmanite, pushing the denser liquid downwards. Additional experiments up to 129 GPa show that this behaviour is observed up to core‐mantle boundary conditions. This experimentally supports the terrestrial basal magma ocean hypothesis where the Earth's molten mantle crystallized from the top down, with the last remnants of melt located deep in the mantle, and challenges earlier bottom‐up scenarios. Our experiments also support the formation of primitive bridgmanite mantle structures with a peculiar geochemical signature. Key Points: Experimental determination of lower mantle melting reltaions and phase diagram by laser‐heated diamond anvil cellOne third of a pyrolitic magma ocean would first crystallize iron‐depleted bridgmanite, than contains a substantial amounts of calciumCalcium concentration in liquidus bridgmanite is constant from 52 to 129 GPa, and delays the crystallization of calcium‐silicate perovskite [ABSTRACT FROM AUTHOR]

Soil constraints limit crop water and nutrient extraction and lead to yield loss globally. In rainfed agriculture, the selection of crop species more likely to yield well under constrained conditions is an important management tool. However, information on the most appropriate crops is often difficult to access due to its publication in a wide range of disparate sources and the various measures of crop tolerance used. This study aimed to improve our ability to identify crops for constrained areas in rainfed subtropical cropping systems by compiling published information that had assessed the grain yield response to acidic, saline, or sodic conditions of 17 cereal, pulse, and oilseed crops. This information was used to develop a 'traffic light' system for salinity and acidity to provide guidance on when soil pH or the electrical conductivity of a saturated soil extract (ECe) is likely to be 'good', 'potentially limiting', or 'poor' for grain yield. Crops were also ranked according to their likely ability to yield well under saline, acidic, or sodic conditions. For all crops, the point at which grain yield was affected by soil constraints was variable and there was often only a small amount of published information available to help guide the identification of tolerance limits and rankings, particularly for sodicity. Many studies were also conducted under experimental conditions that differed from rainfed farming, which can affect the transferability of results. Confidence in the tolerance limits and rankings is thus only moderate and further work is required to confirm their applicability. [ABSTRACT FROM AUTHOR]

The applications of sugars as inexpensive, renewable, and nontoxic sources of hydrogen gas are systematically demonstrated by means of dehydrogenation and catalytic transfer hydrogenation reactions. The chiral bifunctional Noyori‐type catalyst, Cp*Ir(TsDPEN), is found to effectively, regioselectively, and stereoselectively dehydrogenate various sugars possessing different steric hindrance and stereochemistry. Furthermore, kinetics experiments for these dehydrogenation reactions reveal that many sugars are superior sources of hydrogen gas when compared with a traditional hydrogen donor, isopropanol. Applications of sugars in transfer hydrogenation with various hydrogen acceptors are also investigated. [ABSTRACT FROM AUTHOR]

This evidence‐based clinical guideline provides consensus‐recommendations for the treatment and care of patients with primary antibody deficiencies (PADs). The guideline group comprised 20 clinical and scientific expert associations of the German, Swiss, and Austrian healthcare system and representatives of patients. Recommendations were based on results of a systematic literature search, data extraction, and evaluation of methodology and study quality in combination with the clinical expertise of the respective representatives. Consensus‐based recommendations were determined via nominal group technique. PADs are the largest clinically relevant group of primary immunodeficiencies. Most patients with PADs present with increased susceptibility to infections, however immune dysregulation, autoimmunity, and cancer affect a significant number of patients and may precede infections. This guideline therefore covers interdisciplinary clinical and therapeutic aspects of infectious (e.g., antibiotic prophylaxis, management of bronchiectasis) and non‐infectious manifestations (e.g., management of granulomatous disease, immune cytopenia). PADs are grouped into disease entities with definitive, probable, possible, or unlikely benefit of IgG‐replacement therapy. Summary and consensus‐recommendations are provided for treatment indication, dosing, routes of administration, and adverse events of IgG‐replacement therapy. Special aspects of concomitant impaired T‐cell function are highlighted as well as clinical data on selected monogenetic inborn errors of immunity formerly classified into PADs (APDS, CTLA‐4‐, and LRBA‐deficiency). [ABSTRACT FROM AUTHOR]

Spatiotemporal variability in ozone dry deposition is often overlooked despite its implications for interpreting and modeling tropospheric ozone concentrations accurately. Understanding the influences of stomatal versus nonstomatal deposition processes on ozone deposition velocity is important for attributing observed changes in the ozone depositional sink and associated damage to ecosystems. Here, we aim to identify the stomatal versus nonstomatal deposition processes driving observed variability in ozone deposition velocity over the northeastern United States during June–September. We use ozone eddy covariance measurements from Harvard Forest in Massachusetts, which span a decade, and from Kane Experimental Forest in Pennsylvania and Sand Flats State Forest in New York, which span one growing season each, along with observation‐driven modeling. Using a cumulative precipitation indicator of soil wetness, we infer that high soil uptake during dry years and low soil uptake during wet years may contribute to the twofold interannual variability in ozone deposition velocity at Harvard Forest. We link stomatal deposition and humidity to variability in ozone deposition velocity on daily timescales. The humidity dependence may reflect higher uptake by leaf cuticles under humid conditions, noted in previous work. Previous work also suggests that uptake by leaf cuticles may be enhanced after rain, but we find that increases in ozone deposition velocity on rainy days are instead mostly associated with increases in stomatal conductance. Our analysis highlights a need for constraints on subseasonal variability in ozone dry deposition to soil and fast in‐canopy chemistry during ecosystem stress. Key Points: Stomatal and cuticular deposition are inferred as drivers of day‐to‐day variability in deposition velocityHigher stomatal uptake increases deposition velocity on rainy daysObserved interannual variability at Harvard Forest may reflect enhanced ozone deposition to dry soil [ABSTRACT FROM AUTHOR]

Fatty acids are essential to macroinvertebrate growth and reproduction and can indicate food web structure and nutritional quality of basal resources. However, broad‐scale examinations of how catchment land cover and associated stressors affect the proportions of fatty acids (FAs) in stream food webs are few.Here, we: (1) examine relationships among proportions of FAs among benthic periphyton and macroinvertebrate collector/gatherers, shredders, and predators; and (2) test if relationships between periphytic and macroinvertebrate FAs were altered due to the intensity of urban development in catchments.Proportions of the ≥20‐C eicosapentaenoic acid (EPA 20:5ω3), arachidonic acid (ARA 20:4ω6), and docosahexaenoic acid (22:6ω3) indicated collector/gatherers had a diet richer in periphyton than in shredders, which had significantly lower proportions of these FAs. Collector/gatherers were in turn likely to be high‐quality sources of ω3 and ≥ 20‐C FAs for predators, which also had significantly greater EPA and ARA proportions than those in shredders. Linoleic (18:2ω6) and α‐linolenic acid (18:3ω3) comprised the greatest proportions of FAs in shredders, which suggested a diet dominated by leaf litter and associated hyphomycetes.As catchment urbanisation increased, proportions of total ω3 FAs and EPA in periphyton were significantly greater. This pattern also was seen through macroinvertebrate consumers and predators, given that proportions of these FAs in macroinvertebrates also were significantly correlated with factors associated with catchment urbanisation. The significant increase in total ω3 FAs and EPA proportions within shredders indicated that periphyton growth, and their FAs, increased on leaf litter, probably due to greater nutrient concentrations associated with catchment urbanisation. Proportions of total ω6 FAs in biota were not significantly correlated with factors associated with urban development, which could indicate that they were of sufficient abundance for consumers regardless of urban intensity or possible changes in their sources.Our study provides an informative first step that identified notable differences in proportions of FAs among macroinvertebrates in urban streams and an increase in proportions of total ω3 FAs and EPA in periphyton, consumers, and predators as catchment urbanisation increases. Identifying how FA relationships within food webs change in response to catchment alterations and stressors could inform land use and management decisions by linking environmental changes to measures important to ecosystem outcomes. [ABSTRACT FROM AUTHOR]

We describe a rapid-cycling bipolar patient whose mood cycle oscillated in synchrony with 14.8-day recurrences of every lunar spring-neap cycle, and whose times of sleep- onset and wake-onset shifted their timing in synchrony with 24.84-hour transits of each of the moon's two daily tidal cycles. [ABSTRACT FROM AUTHOR]

Abstract: Forecasting changes in the distributions of macrophytes is essential to understanding how aquatic ecosystems will respond to climate and environmental changes. Previous work in aquatic ecosystems has used climate data at large scales and chemistry data at small scales; the consequence of using these different data types has not been evaluated. This study combines a survey of macrophyte diversity and water chemistry measurements at a large regional scale to demonstrate the feasibility and necessity of including ecological measurements, in addition to climate data, in species distribution models of aquatic macrophytes. A survey of 740 water bodies stratified across 327,000 square kilometers was conducted to document Characeae (green macroalgae) species occurrence and water chemistry data. Chemistry variables and climate data were used separately and in concert to develop species distribution models for ten species across the study area. The impacts of future environmental changes on species distributions were modeled using a range of global climate models (GCMs), representative concentration pathways (RCPs), and pollution scenarios. Models developed with chemistry variables generally gave the most accurate predictions of species distributions when compared with those using climate variables. Calcium and conductivity had the highest total relative contribution to models across all species. Habitat changes were most pronounced in scenarios with increased road salt and deicer influences, with two species predicted to increase in range by >50% and four species predicted to decrease in range by >50%. Species of Characeae have distinct habitat ranges that closely follow spatial patterns of water chemistry. Species distribution models built with climate data alone were insufficient to predict changes in distributions in the study area. The development and implementation of standardized, large‐scale water chemistry databases will aid predictions of habitat changes for aquatic ecosystems. [ABSTRACT FROM AUTHOR]

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Ichthyoses are a group of rare genetic skin disorders that pose numerous clinical challenges, in particular with respect to the correct diagnosis and appropriate management. The present update of the German ichthyosis guidelines addresses recent diagnostic advances that have resulted in the Sorèze consensus classification. In this context, we provide an updated diagnostic algorithm, taking into account clinical features as well as the molecular genetic basis of these disorders. Moreover, we highlight current therapeutic approaches such as psychosocial support, balneotherapy, mechanical scale removal, topical therapy, and systemic retinoid therapy. General aspects such as the indication for physical therapy, ergotherapy, or genetic counseling are also discussed. The present update was consented by an interdisciplinary consensus conference that included dermatologists, pediatricians, human geneticists, and natural scientists as well as representatives of the German patient support organization Selbsthilfe Ichthyose e. V. [ABSTRACT FROM AUTHOR]

Enhanced NRG1- ERBB4 signaling is a risk pathway in schizophrenia, and corresponding mouse models display several endophenotypes of the disease. Nonetheless, pathway-directed treatment strategies with clinically applicable compounds have not been identified. Here, we applied a cell-based assay using the split TEV technology to screen a library of clinically applicable compounds to identify modulators of NRG1- ERBB4 signaling for repurposing. We recovered spironolactone, known as antagonist of corticosteroids, as an inhibitor of the ERBB4 receptor and tested it in pharmacological and biochemical assays to assess secondary compound actions. Transgenic mice overexpressing Nrg1 type III display cortical Erbb4 hyperphosphorylation, a condition observed in postmortem brains from schizophrenia patients. Spironolactone treatment reverted hyperphosphorylation of activated Erbb4 in these mice. In behavioral tests, spironolactone treatment of Nrg1 type III transgenic mice ameliorated schizophrenia-relevant behavioral endophenotypes, such as reduced sensorimotor gating, hyperactivity, and impaired working memory. Moreover, spironolactone increases spontaneous inhibitory postsynaptic currents in cortical slices supporting an ERBB4-mediated mode-of-action. Our findings suggest that spironolactone, a clinically safe drug, provides an opportunity for new treatment options for schizophrenia. [ABSTRACT FROM AUTHOR]

The seasonal pattern of the carbon isotope content (δ13C) of atmospheric CO2 depends on local and nonlocal land-atmosphere exchange and atmospheric transport. Previous studies suggested that the δ13C of the net land-atmosphere CO2 flux ( δsource) varies seasonally as stomatal conductance of plants responds to vapor pressure deficit of air (VPD). We studied the variation of δsource at seven sites across the United States representing forests, grasslands, and an urban center. Using a two-part mixing model, we calculated the seasonal δsource for each site after removing background influence and, when possible, removing δ13C variation of nonlocal sources. Compared to previous analyses, we found a reduced seasonal (March-September) variation in δsource at the forest sites (0.5‰ variation). We did not find a consistent seasonal relationship between VPD and δsource across forest (or other) sites, providing evidence that stomatal response to VPD was not the cause of the global, coherent seasonal pattern in δsource. In contrast to the forest sites, grassland and urban sites had a larger seasonal variation in δsource (5‰) dominated by seasonal transitions in C3/C4 grass productivity and in fossil fuel emissions, respectively. Our findings were sensitive to the location used to account for atmospheric background variation within the mixing model method that determined δsource . Special consideration should be given to background location depending on whether the intent is to understand site level dynamics or regional scale impacts of land-atmosphere exchange. The seasonal amplitude in δ13C of land-atmosphere CO2 exchange ( δsource ) varied across land cover types and was not driven by seasonal changes in vapor pressure deficit. The largest seasonal amplitudes of δsource were at grassland and urban sites, driven by changes in C3/C4 grass productivity and fossil fuel emissions, respectively. Mixing model approaches may incorrectly calculate δsource when background atmospheric observations are remote and/or prone to anthropogenic influence. [ABSTRACT FROM AUTHOR]

Many freshwater systems receive substantial inputs of terrestrial organic matter. Terrestrially derived dissolved organic carbon (t-DOC) inputs can modify light availability, the spatial distribution of primary production, heat, and oxygen in aquatic systems, as well as inorganic nutrient bioavailability. It is also well-established that some terrestrial inputs (such as invertebrates and fruits) provide high-quality food resources for consumers in some systems., In small to moderate-sized streams, leaf litter inputs average approximately three times greater than the autochthonous production. Conversely, in oligo/mesotrophic lakes algal production is typically five times greater than the available flux of allochthonous basal resources., Terrestrial particulate organic carbon (t-POC) inputs to lakes and rivers are comprised of 80%-90% biochemically recalcitrant lignocellulose, which is highly resistant to enzymatic breakdown by animal consumers. Further, t-POC and heterotrophic bacteria lack essential biochemical compounds that are critical for rapid growth and reproduction in aquatic invertebrates and fishes. Several studies have directly shown that these resources have very low food quality for herbivorous zooplankton and benthic invertebrates., Much of the nitrogen assimilated by stream consumers is probably of algal origin, even in systems where there appears to be a significant terrestrial carbon contribution. Amino acid stable isotope analyses for large river food webs indicate that most upper trophic level essential amino acids are derived from algae. Similarly, profiles of essential fatty acids in consumers show a strong dependence on the algal food resources., Primary production to respiration ratios are not a meaningful index to assess consumer allochthony because respiration represents an oxidised carbon flux that cannot be utilised by animal consumers. Rather, the relative importance of allochthonous subsidies for upper trophic level production should be addressed by considering the rates at which terrestrial and autochthonous resources are consumed and the growth efficiency supported by this food., Ultimately, the biochemical composition of a particular basal resource, and not just its quantity or origin, determines how readily this material is incorporated into upper trophic level consumers. Because of its highly favourable biochemical composition and greater availability, we conclude that microalgal production supports most animal production in freshwater ecosystems. [ABSTRACT FROM AUTHOR]

Gross ecosystem productivity ( GEP) in tropical forests varies both with the environment and with biotic changes in photosynthetic infrastructure, but our understanding of the relative effects of these factors across timescales is limited. Here, we used a statistical model to partition the variability of seven years of eddy covariance-derived GEP in a central Amazon evergreen forest into two main causes: variation in environmental drivers (solar radiation, diffuse light fraction, and vapor pressure deficit) that interact with model parameters that govern photosynthesis and biotic variation in canopy photosynthetic light-use efficiency associated with changes in the parameters themselves. Our fitted model was able to explain most of the variability in GEP at hourly ( R2 = 0.77) to interannual ( R2 = 0.80) timescales. At hourly timescales, we found that 75% of observed GEP variability could be attributed to environmental variability. When aggregating GEP to the longer timescales (daily, monthly, and yearly), however, environmental variation explained progressively less GEP variability: At monthly timescales, it explained only 3%, much less than biotic variation in canopy photosynthetic light-use efficiency, which accounted for 63%. These results challenge modeling approaches that assume GEP is primarily controlled by the environment at both short and long timescales. Our approach distinguishing biotic from environmental variability can help to resolve debates about environmental limitations to tropical forest photosynthesis. For example, we found that biotically regulated canopy photosynthetic light-use efficiency (associated with leaf phenology) increased with sunlight during dry seasons (consistent with light but not water limitation of canopy development) but that realized GEP was nonetheless lower relative to its potential efficiency during dry than wet seasons (consistent with water limitation of photosynthesis in given assemblages of leaves). This work highlights the importance of accounting for differential regulation of GEP at different timescales and of identifying the underlying feedbacks and adaptive mechanisms. [ABSTRACT FROM AUTHOR]

Aluminium (Al) toxicity adversely impacts plant productivity in acid soils by restricting root growth and although several mechanisms are involved the physiological basis of decreased root elongation remains unclear. Understanding the primary mechanisms of Al rhizotoxicity is hindered due to the rapid effects of soluble Al on root growth and the close proximity of many cellular components within the cell wall, plasma membrane, cytosol and nucleus with which Al may react. To overcome some of these difficulties, we report on a novel method for investigating Al interactions with Komagataeibacter xylinus bacterial cellulose (BC)-pectin composites as cell wall analogues. The growth of K. xylinus in the presence of various plant cell wall polysaccharides, such as pectin, has provided a unique in vitro model system with which to investigate the interactions of Al with plant cell wall polysaccharides. The BC-pectin composites reacted in a similar way with Al as do plant cell walls, providing insights into the effects of Al on the mechanical properties of the BC-pectin composites as cell wall analogues. Our findings indicated that there were no significant effects of Al (4-160 μM) on the tensile stress, tensile strain or Young's modulus of the composites. This finding was consistent with cellulose, not pectin, being the major load bearing component in BC-pectin composites, as is also the case in plant cell walls. [ABSTRACT FROM AUTHOR]

Persistent polyclonal B lymphocytosis (PPBL) is a benign hematological disorder characterized by a selective expansion of circulating polyclonal marginal zone (MZ)‐like B cells. Previous reports demonstrated that cases of PPBL showed poor activation, proliferation and survival of B cells in vitro, yet the underlying defect remains unknown. Here we report for the first time an attenuated activation of the canonical NF‐κB (nuclear factor of kappa light polypeptide gene enhancer in B cells) and mitogen‐activated protein kinase/extracellular signal‐regulated kinase pathway after CD40 stimulation. This defect was selective, as alternative NF‐κB signaling after CD40 stimulation and both B‐cell receptor‐ and Toll‐like receptor 9‐mediated activation remained unaffected. Reduced canonical NF‐κB activation resulted in decreased IκBα and CD40 expression in resting cells. In PPBL patients, expression of Bcl‐xL in MZ‐like B cells did not increase upon activation, consistent with the high apoptosis rates of PPBL‐derived B cells that were observed in vitro. The B‐cell phenotype of mice with selective knockouts of early components of the CD40 signaling pathway resembles PPBL, but sequencing corresponding genes in sorted MZ‐like B cells of PPBL patients did not reveal relevant genetic alterations. Nevertheless, the frequently observed mutations in early signaling components of the NF‐κB pathway in MZ lymphomas underline the relevance of our findings for the pathogenesis of PPBL. [ABSTRACT FROM AUTHOR]

B-cell maturation antigen ( BCMA, also termed TNFRSF17) is an attractive therapeutic target due to its restricted expression on normal and malignant plasma cells ( PC). GSK2857916 (or J6M0- MMAF) is a BCMA-specific antibody conjugated to the microtubule-disrupting agent monomethyl auristatin F ( MMAF) via a protease-resistant linker. To evaluate the clinical potential of this agent, tumour cells from seventy multiple myeloma ( MM) patients were assessed for BCMA expression by immunohistochemistry and flow cytometry. All patients tested expressed BCMA, at varying levels, and both surface and intracellular expression were observed. BCMA expression is maintained through relapse, extramedullary spread and in residual disease post therapy. BCMA levels may also be prognostically useful as higher levels of BCMA were associated with poorer outcomes, even taking into account genetic risk. We observed rapid internalization of surface BCMA and newly expressed protein by 1 h, suggesting a mechanism for J6M0- MMAF activity even with low surface antigen. J6M0- MMAF mediated cytotoxicity of MM cells varied with dose and antigen levels, with clonogenic progenitors killed at lower doses than mature cells. In comparison, J6M0- MMAF killing of primary CD138+ myeloma cells occurred with slower kinetics. Our observations support BCMA to be a promising therapeutic target in MM for novel therapies such as J6M0- MMAF. [ABSTRACT FROM AUTHOR]

Objectives Introducing medical students to wilderness medicine provides skills in leadership, teamwork, improvisation, and managing medical emergencies; however, wilderness medicine ( WM) education is typically reserved for senior medical students and often requires expensive travel. Here, we describe the Winter Wilderness Medicine Race ( WWMR). The race was held at a large allopathic medical school and targeted towards preclinical medical students. Race planning was performed by senior medical students with the supervision of doctors from the Department of Emergency Medicine. We hypothesized that this intervention in medical education would enhance students' WM knowledge, and build teamwork and improvisational skills. Methods The research involved a one day WM race that required teams of first- and second-year medical students to navigate a 5-km course and complete medical scenarios. Races that were held annually between 2011 and 2014 are included in the study. The educational effectiveness of the race was evaluated by pre- and post-race knowledge assessments of the medical students participating in a WWMR. Qualitative data regarding student perceptions of the skills learned were obtained by focus group interviews. Results Between 2011 and 2014, 122 preclinical medical students from a Midwestern US allopathic medical school participated in the study. Overall, the mean scores for pre- and post-race knowledge assessments were 48 and 85 per cent, respectively, a 37 per cent increase in scores (p < 0.0001). Participants cited improvisational and communication skills as the most important educational feature of the race. Conclusions The Winter Wilderness Medicine Race ( WWMR) enhanced preclinical medical students' wilderness medicine knowledge, teamwork skills and improvisational abilities. [ABSTRACT FROM AUTHOR]

Copyright of Materialwissenschaft und Werkstoffechnik is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Guatemala's rural indigenous population suffers from one of the highest rates of chronic child malnutrition (stunting) in the world. Successfully addressing stunting requires defining the barriers to and opportunities for new behaviour‐change initiatives. We undertook a mixed‐methods assessment of feeding practices and food purchasing behaviours around infants and young children aged 6–36 months in two rural indigenous Guatemalan communities. We found that most caregivers were aware only of acute forms of child malnutrition and that they greatly underestimated the local prevalence of malnutrition. Despite moderate adherence to exclusive breastfeeding and timing of complementary food introduction, diets had poor diversity and inadequate meal frequency. Furthermore, perceptions of food insecurity were high even in the presence of land ownership and agricultural production. Although fortified foods were highly valued, they were considered expensive. At the same time, proportionally equivalent amounts of money were spent on junk foods or other processed foods by most participants. Biological mothers often lacked autonomy for food purchasing and nutritional decisions because of the power exerted by husbands and paternal grandmothers. Our findings suggest several creative and community‐based programming initiatives including education about the acute vs. chronic malnutrition distinction, engaging landowners in discussions about domestic food consumption, engaging with caregivers to redirect funds towards fortified foods rather than junk food purchases and directing behaviour‐change initiatives towards all household stakeholders. [ABSTRACT FROM AUTHOR]

Forty-eight, cross-bred ( GL × LW × P) piglets were used in a 42-day tolerance trial to assess the effects of feeding diets supplemented with vitamin D or increasing levels of 25-hydroxyvitamin D3 (25- OH-D3). Six-week-old piglets (24 castrate males, 24 females) were used. Two replicate groups of 6 piglets were randomized by weight and allocated to four dietary treatments. The control group (T1) was supplemented with 50 μg vitamin D3/kg feed. The experimental groups received 25- OH-D3 at the recommended dose (T2: 50 μg/kg = 1x), at 250 μg/kg (T3: 5x) or at 500 μg/kg (T4: 10x) respectively. Feed intake and daily weight gain were measured weekly, and the animals were examined by a veterinarian daily. After 42 days, body mass, blood, urine, bone and tissue samples were analysed and a pathology examination conducted. Dietary treatments had no significant effect on final body mass or daily weight gain. The 25- OH-D3 plasma concentration in T1 was 17 ± 3 ng/ml (mean ± SD) while the respective values of the experimental groups were significantly increased in T2, T3 and T4. Tissue concentrations of 25- OH-D3 were higher in liver and muscle for T3 and T4 and in skin for T4 than in T1. However, neither gross pathology nor histology, nor blood and urine characteristics, nor bone parameters were affected by dietary treatments. Weight of organs as well as dry matter, ash and calcium content of kidneys remained unaffected by dietary 25- OH-D3 intake. Furthermore, no changes were observed for general indicators of health. The results of this study demonstrated that feeding piglets with 25- OH-D3 at 5 or 10 times the recommended level had no adverse effects on any of the biological parameters measured. It was concluded that 25- OH-D3 can be regarded as a supplement with a very high safety margin when used at the recommended level. [ABSTRACT FROM AUTHOR]

Included in the Earth, Clouds, Aerosols, and Radiation Explorer ( EarthCARE) satellite's array of instruments is a multi-view broad-band radiometer (BBR). BBR data will facilitate a radiative closure assessment of cloud and aerosol properties inferred from data gathered by EarthCARE's other passive and active sensors. The closure assessment will consist, in part, of comparisons between BBR radiances and radiances computed by three-dimensional (3D) radiative transfer models (RTM) that act on narrow 3D domains that derive from, and include, the retrieved cross-section of cloud and aerosol properties. Assessment domains D will be ∼100 km2. Following a brief outline of the closure experiment, a method is proposed for estimating the likelihood of BBR radiances providing a meaningful closure assessment of cloud and aerosol properties in D. The method capitalizes on the ability of Monte Carlo RTMs to compute contributions to radiances from any constituent in any given D. While this methodology introduces some circularity into the closure test, it might, nevertheless, be tolerable, given that the method's purpose is simply to identify, and thus avoid, assessments that are likely to be fruitless or misleading. A 3000 km long stretch of A-Train satellite data was used in this initial demonstration of the proposed methodology. Only results for solar radiation are shown. All radiative quantities used here were computed by a 3D Monte Carlo RTM. A control simulation provided proxy BBR measurements. Random 'errors' were introduced into the A-Train field to produce experimental fields that roughly mimic retrievals. Experimental and control radiances were compared in mock-closure assessments. Arbitrarily assuming that a fruitful assessment requires ∼75% of a BBR radiance to result from cloud and aerosol scattering events inside D, ∼70% of the (11 km)2 domains were flagged as reliably testable for this example. [ABSTRACT FROM AUTHOR]

Particle detectors are constantly being built and refitted with new technology to improve the spatial resolution, radiation hardness, and speed at which the detector can capture particle events. One of the most crucial components of a modern collider experiment is the hadron calorimeter. One of the proposed improvements on future hadron calorimeters is to utilize resistive plate chambers (RPCs). They provide the spatial and energy resolution as well as could provide speed and radiation hardness. RPCs depend on manufacturing electrically conductive glasses that are mechanically strong, durable, radiation resistant, and not ionically conductive. To achieve such requirements, vanadate glasses were developed as alternatives to current prototypes which use soda lime silicate glasses. The conductivity, oxidation states of vanadium, radiation hardness, as well as the prototype performance, were tested on vanadate glasses. The prototype tests show that using 0.40ZnO-0.40TeO2 -0.20V2O5 can improve the RPC detector rate up to 100 times. [ABSTRACT FROM AUTHOR]

Introduction The impact of induction immunosuppression on long-term survival in heart transplant recipients is unclear. Over the past three decades, practices have varied as induction agents have changed and experiences grew. We sought to evaluate the effect of contemporary induction immunosuppression agents in heart transplant recipients with the primary endpoint of survival, utilizing national registry data. Methods We queried the United Network for Organ Sharing ( UNOS) data registry for all heart transplants from 1987 to 2012. We restricted our analysis to adult (≥18 yr) recipients performed from 2001-2011 (to allow for the potential for a minimum of 12 months post-transplant follow-up) who received either: no antibody based induction ( NONE) or the contemporary agents ( INDUCED) of either: basiliximab/daclizumab ( IL-2Rab), alemtuzumab, or ATG/ ALG/thymoglobulin. Kaplan-Meier estimates of the survival function as well as Cox proportional hazards models were utilized. Results Of the 17 857 heart transplants that met the inclusion criteria, there were 4635 (26%) reported deaths during the follow-up period. There were 8216 (46%) patients who were INDUCED. Of the INDUCED agents, 55% were IL-2Rab, 4% alemtuzumab, and 40% ALG/ ATG/thymoglobulin. Donor and recipient characteristics were evaluated. Overall, being INDUCED did not significantly affect survival in univariable (p = 0.522) and multivariable (p = 0.130) Cox models as well as a propensity score adjusted model (p = 0.733). Among those induced, ATG/ ALG/thymoglobulin appeared to have superior survival as compared with IL-2Rab (log-rank p = 0.007, univariable hazard ratio [ HR] = 0.886; 95% CI: 0.811-0.968; p = 0.522). However, in a multivariable Cox model that adjusted for recipient age, VAD, BMI, steroid use, CMV match, and ischemic time, the hazard ratio for ALG/ ATG/thymoglobulin vs. IL-2Rab was no longer statistically significant ( HR = 0.948; 95% CI: 0.850-1.058; p = 0.341). Conclusion In a contemporary analysis of heart transplant recipients, an overall analysis of induction agents does not appear to impact survival, as compared to no induction immunosuppression. While ALG/ ATG/thymoglobulin appeared to have a beneficial effect on survival compared to IL-2Rab in the univariable model, this difference was no longer statistically significant once we adjusted for clinically relevant covariates. [ABSTRACT FROM AUTHOR]

Introduction The impact of induction immunosuppression on long-term survival in lung transplant recipients remains unclear. We sought to evaluate the effect of contemporary induction immunosuppression agents in lung transplant recipients' survival, utilizing national registry data. Methods We queried the United Network for Organ Sharing registry from 2001 to 2012 for adult, deceased donor lung transplants who received no antibody-based induction ( NONE) or the contemporary agents of basiliximab, alemtuzumab, thymoglobulin, antilymphocyte globulin, or antithymocyte globulin ( INDUCED). Kaplan- Meier estimates of the survival and Cox proportional hazards models assessed differences in overall survival between the INDUCED and NONE groups; logistic regression models assessed differences in survival and rejection ( TR1 Y). Results There were 23 951 lung transplants performed with 12 858 meeting the inclusion criteria; 5713 (44%) were INDUCED. Of INDUCED agents, 62% were basiliximab and 14% alemtuzumab. Being INDUCED significantly increased overall survival (p < 0.0001). Median INDUCED survival was 71.3 months (confidence interval [ CI]: 65.7-75.5) as compared with 63.2 months ( CI: 60.1-65.9). Of INDUCED, both basiliximab and alemtuzumab had higher median survival times at 75.1 months ( CI: 68.6-81.3) and 75.5 months ( CI: 63.5-∞), respectively. There was less TR1Y in INDUCED patients (37%), as compared to NONE (42%; p < 0.0001). Conclusion In a contemporary analysis of lung transplant recipients, induction immunosuppression has a significantly positive effect on survival. [ABSTRACT FROM AUTHOR]

Mechanisms whereby metal cations are toxic to plant roots remain largely unknown. Aluminum, for example, has been recognized as rhizotoxic for approximately 100 yr, but there is no consensus on its mode of action. The authors contend that the primary mechanism of rhizotoxicity of many metal cations is nonspecific and that the magnitude of toxic effects is positively related to the strength with which they bind to hard ligands, especially carboxylate ligands of the cell-wall pectic matrix. Specifically, the authors propose that metal cations have a common toxic mechanism through inhibiting the controlled relaxation of the cell wall as required for elongation. Metal cations such as Al3+ and Hg2+, which bind strongly to hard ligands, are toxic at relatively low concentrations because they bind strongly to the walls of cells in the rhizodermis and outer cortex of the root elongation zone with little movement into the inner tissues. In contrast, metal cations such as Ca2+, Na+, Mn2+, and Zn2+, which bind weakly to hard ligands, bind only weakly to the cell wall and move farther into the root cylinder. Only at high concentrations is their weak binding sufficient to inhibit the relaxation of the cell wall. Finally, different mechanisms would explain why certain metal cations (for example, Tl+, Ag+, Cs+, and Cu2+) are sometimes more toxic than expected through binding to hard ligands. The data presented in the present study demonstrate the importance of strength of binding to hard ligands in influencing a range of important physiological processes within roots through nonspecific mechanisms. Environ Toxicol Chem 2014;33:268-277. © 2013 SETAC [ABSTRACT FROM AUTHOR]

Background: Cognitive aging is associated with impaired episodic memory formation (Small et al., 1999), which requires the neurocomputational process of pattern separation to disambiguate similar stimulus input. Pattern separation relies on the dentate gyrus (DG) (Yassa & Stark, 2011), a hippocampal subfield that is susceptible to age‐related change (Small et al., 2011). Cognitive aging is also associated with impaired performance on putative measures of behavioral pattern separation (Yassa et al., 2010), called mnemonic discrimination tasks in humans. Prior work using high‐resolution fMRI suggests that age‐related impairments in mnemonic discrimination are linked to aberrant activation patterns in the DG/CA3 (Yassa et al., 2010). Whereas aging is associated with impaired DG integrity and mnemonic discrimination ability, cardiorespiratory fitness is associated with enhanced DG integrity and improved mnemonic discrimination ability. Given that cardiorespiratory fitness has been positively linked to DG/CA3 integrity in young adults (Nauer et al., 2019), it is conceivable that in older adults, cardiorespiratory fitness will modulate age‐related changes in DG/CA3 activation, which in turn, will dampen age‐related impairments in mnemonic discrimination. Methods: 18 older adults (55‐85 years) and 18 young adults (18‐35 years) underwent a submaximal treadmill test to estimate cardiorespiratory fitness and high‐resolution fMRI to examine hippocampal subfield BOLD signal during encoding and retrieval of a mnemonic discrimination task (MDT). Results: In older adults, we found increased right DG/CA3 BOLD signal in incorrect mnemonic discrimination trials contrasted with correct mnemonic discrimination trials, specifically during stimulus retrieval. Additionally, in both young and older adults, we found that right DG/CA3 BOLD signal in the mnemonic discrimination fMRI contrast during stimulus encoding marginally significantly predicted MDT corrected accuracy. Finally, in both young and older adults, fitness significantly negatively predicted left DG/CA3 BOLD signal in the mnemonic discrimination fMRI contrast during stimulus retrieval. Conclusions: These results suggest that DG/CA3 BOLD signal relates to performance on a MDT designed to tax pattern separation, and that cardiorespiratory fitness modulates BOLD signal in these subregions. Altogether, these results suggest a link between fitness, DG/CA3 functional integrity, and mnemonic discrimination that may be critical to understanding how to dampen age‐related impairments in episodic memory. [ABSTRACT FROM AUTHOR]

The biochemical composition of primary food resources may affect secondary production, growth, reproduction and other physiological responses in consumers and may be an important driver of food-web dynamics. Changes in land use, riparian clearing and non-point nutrient inputs to streams have the potential to alter the biochemical composition of periphyton, and characterising this relationship may be critical to understand the processes by which environmental change can affect food webs and ecosystem function., We conducted a manipulative, in situ experiment to examine the effect of light and nutrient availability on stream periphyton biomass, nutrient content, stoichiometry and fatty acid composition. Greater light increased periphyton biomass [chl- a, ash-free dry mass ( AFDM)], periphyton carbon concentrations and monounsaturated fatty acids ( MUFAs), but decreased saturated fatty acids ( SAFAs). Greater light availability also increased levels of <20C polyunsaturated fatty acids ( PUFAs), but decreased quantities of several long-chain (20-22 C), highly unsaturated fatty acids ( HUFAs)., Nutrient (+N, +P) addition had no significant effect on periphyton biomass in the study streams, but did increase periphyton carbon content. For fatty acids, despite non-significant effects on periphyton biomass, nutrient additions resulted in an increased ratio of SAFA to PUFA, greater concentrations of stearidonic acid (18:4ω3) and near-significant increases in α-linolenic acid (18:3ω3). Nutrient additions also resulted in decreased quantities of the physiologically important docosahexaenoic acid ( DHA; 22:6ω3) and increased the ratio of omega-3 to omega-6 fatty acids. An interaction between nutrient addition and greater light also resulted in decreased percentages of another physiologically important fatty acid, eicosapentaenoic acid ( EPA; 20:5ω3)., Results from this study suggest that increased light and nutrients, a condition common in urban and agricultural catchments, would increase 18C PUFA intermediates that would be available in periphyton food sources, but decrease the availability of essential 20-22C HUFAs. If stream consumers are unable to elongate PUFAs into essential HUFAs, there may be important effects on food webs, including shifts by invertebrate consumers from herbivory to omnivory or carnivory, or changes in the species composition of aquatic consumers., Our results demonstrate that fatty acid measures were more sensitive to changes in light and nutrient conditions than more traditional measures of biomass, nutrient content and stoichiometry. We recommend routine measurement of fatty acid content in monitoring the effect of changing environmental conditions in rivers and streams, particularly studies on food quality and ecosystem health. [ABSTRACT FROM AUTHOR]

Two different lanthanum salts, lanthanum carbonate (LaCO3) and Lancer®, a lanthanide citrate mixture, were tested for their effects on bone metabolism in a small animal model for post-menopausal osteoporosis. Forty female outbred Wistar Han rats, sham-operated (SHAM, positive control, n = 10) or ovariectomized (OVX, n = 30) at 4 months of age, were allotted into following groups ( n = 10/group): (i) SHAM, (ii) OVX control (negative control), (iii) OVX + LaCO3 (1.74 g/kg feed) and (iv) OVX + Lancer® (8 g/kg feed). Effects on bone were investigated by bone markers [osteocalcin (Oc) in serum and excretion of pyridinoline (PYD) in urine] and by physical parameters of bone structure and bone composition (bone mass, calcium, phosphorus and magnesium content in bone crude ash). Bone micro-architecture and bone mineral density were evaluated by peripheral quantitative computed tomography and micro-computed tomography (μCT). The animal model could be validated by differences between OVX control and SHAM. Body mass and feed intake were the same among the four groups. Oc was clearly increased in the two experimental groups (p < 0.001) vs. SHAM and OVX control. Bone mass and calcium content in bone ash were significantly higher than in OVX control. The Ca/P ratio in bone ash of the two lanthanide groups did not differ from SHAM. Bone-protecting effects of lanthanides were clearly demonstrated by an increased trabecular density which is the region of interest for osteoporotic bone loss. A 3D imaging of bone micro-architecture by μCT visualized descriptively the positive effects of lanthanides on bone formation. The results of this study demonstrate an improvement of bone formation and bone-protecting effects of lanthanides in the OVX rat. Thus, lanthanum salts suggest a prevention of post-menopausal bone loss and may be of benefit in experimental osteopenia following ovariectomy. [ABSTRACT FROM AUTHOR]

Receptor-targeted therapies have become standard in the treatment of various lymphomas. In view of its unparalleled specificity for the malignant B-cell clone, the B-cell receptor (BCR) on B cell lymphoma cells is a potential therapeutic target. We have used two BCR epitope mimicking peptides binding to the Burkitt's lymphoma cell lines CA46 and SUP-B8. We proved their functionality by demonstrating calcium flux and BCR-mediated endocytosis upon peptide receptor binding. Toxicity experiments in vitro via cross-linking of the BCR with tetramerized epitope mimics lead to apoptosis in both cell lines but was far more effective in SUP-B8 cells. We established a SUP-B8-based disseminated Burkitt's lymphoma model in NOD/SCID mice. Treatment of tumor-bearing mice with tetramerized epitope mimics had significant anti-tumor effects in vivo. We conclude that peptide-mediated, BCR-targeted therapy is a promising approach which may be explored and further developed for application in highly aggressive lymphoma. [ABSTRACT FROM AUTHOR]

Baustellenerfahrungen und systematische Modellversuche zeigen, dass eine Säulenherstellung von Rüttelstopfsäulen (RSV) mit dem Tiefenrüttler auch in sehr weichen Böden ab einem Grenzwert der undränierten Kohäsion von cu = 4 kN/m2 möglich ist. Der alte Grenzwert cu = 15 kN/m2 von 1979 verliert damit seine Gültigkeit. In der aktuellen allgemeinen bauaufsichtlichen Zulassung Z-34.2-3 für 'Vermörtelte Stopfsäulen (VSS), Fertigmörtel-Stopfsäulen (FSS) und Betonstopfsäulen (BSS)' der Keller Grundbau GmbH wurde diesen neuen Erkenntnissen mit der Anpassung der Anwendbarkeitsgrenzen und der Herstellung einer Kiesvergütung nun Rechnung getragen. Installation of columns with depth vibrators in soils with undrained cohesion cu < 15 kN/m2. Site experiences and systematic model tests show that the installation of vibro stone columns and vibro mortar columns is possible with a depth vibrator even in a very soft soil with an undrained cohesion of cu = 4 kN/m2. The old limit value of cu = 15 kN/m2 is no longer valid. The DIBt ('Deutsches Institut für Bautechnik', German federal institute for construction technique, Berlin) accommodates this fact in the actual version of the general technical approval Nr. Z-34.2-3 for vibro concrete columns (VCC) and ready-mixed vibro mortar columns (VMC). [ABSTRACT FROM AUTHOR]

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Summary. Combined pegylated interferon (PegIFN) and ribavirin represents the standard therapy for patients with chronic hepatitis C (CHC), which allows for sustained viral response (SVR) in up to 90% of patients depending on certain viral and host factors. Clinical studies have demonstrated the importance of adherence to therapy, that is, the ability of patients to tolerate and sustain a fully dosed therapy regimen. Adherence is markedly impaired by treatment-related adverse effects. In particular, haemolytic anaemia often requires dose reduction or termination of ribavirin treatment, which compromises treatment efficacy. Recent evidence points to a beneficial role of recombinant erythropoietin (EPO) in alleviating ribavirin-induced anaemia thereby improving quality of life, enabling higher ribavirin dosage and consequently improving SVR. However, no general consensus exists regarding the use of EPO for specific indications: its optimal dosing, treatment benefits and potential risks or cost efficiency. The Swiss Association for the Study of the Liver (SASL) has therefore organized an expert meeting to critically review and discuss the current evidence and to phrase recommendations for clinical practice. A consensus was reached recommending the use of EPO for patients infected with viral genotype 1 developing significant anaemia below 100 g/L haemoglobin and a haematocrit of <30% during standard therapy to improve quality of life and sustain optimal ribavirin dose. However, the evidence supporting its use in patients with pre-existing anaemia, non-1 viral genotypes, a former relapse or nonresponse, liver transplant recipients and cardiovascular or pulmonary disease is considered insufficient. [ABSTRACT FROM AUTHOR]

Lipid accumulation product (LAP) is an emerging cardiovascular risk factor, which is calculated from waist circumference (WC) and triglyceride (TG) levels. The aim of this study was to elucidate the relationship between LAP and cardiovascular mortality as well as the presence of type 2 diabetes with respect to gender-specific differences. We determined WC and fasting TG levels and the cardiovascular and metabolic phenotypes coronary artery disease (CAD), hypertension, metabolic syndrome, and diabetes mellitus in 2,279 men and 875 postmenopausal women who were routinely referred to coronary angiography. The LAP was calculated as (WC (cm) - 65) × (TG (mmol/l)) for men and as (WC (cm) - 58) × (TG (mmol/l)) for women. LAP levels were independently associated with congestive heart failure mortality in all postmenopausal women and with all-cause mortality in diabetic postmenopausal women but not in men. Multivariable-adjusted hazard ratios (with 95% confidence intervals) for all-cause, cardiovascular, and congestive heart failure mortality in the third compared to the first LAP tertile were 4.28 (1.94-9.44; P < 0.001), 3.47 (1.28-9.40; P = 0.015), and 10.77 (1.21-95.88; P = 0.033), respectively, in normal weight postmenopausal women, whereas no significant associations were found in men. LAP levels were highly associated with type 2 diabetes in all subjects, postmenopausal women, and men. High LAP values are predictive of mortality independently of other cardiovascular risk factors in normal weight and diabetic postmenopausal women but not in men. Type 2 diabetes (T2DM) was highly associated with LAP in women and men. Our study validates an inexpensive and simple risk profiling that may allow identifying postmenopausal women at high cardiovascular risk. [ABSTRACT FROM AUTHOR]

Aims Accumulating evidence suggests that androgen deficiency is associated with cardiovascular disease. We aimed at evaluating whether total testosterone (TT) and free testosterone (FT) are associated with specific cardiovascular events. Methods and results We measured TT and sex-hormone-binding globulin levels in 2078 men who were routinely referred for coronary angiography between 1997 and 2000. Free testosterone was calculated according to Vermeulen. Main outcome measures were Cox proportional hazard ratios (HRs) for sudden cardiac death, fatal myocardial infarction, death from congestive heart failure (CHF), as well as other cardiac deaths according to quartiles of TT and FT. The median follow-up time was 7.7 years. Multivariable adjusted HRs (with 95% confidence intervals) in the fourth compared with the first FT quartile and per 1 SD increase in FT for CHF mortality were 0.38 (0.17–0.87) and 0.37 (0.15–0.89), respectively. We observed no independent significant association of FT with sudden cardiac death, fatal myocardial infarction, or other cardiac death. There was no independent association of TT levels with cardiovascular events or cardiac disease. Conclusion Low levels of FT are independently associated with increased CHF mortality. [ABSTRACT FROM PUBLISHER]