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Structures at serine‐proline sites in proteins were analyzed using a combination of peptide synthesis with structural methods and bioinformatics analysis of the PDB. Dipeptides were synthesized with the proline derivative (2S,4S)‐(4‐iodophenyl)hydroxyproline [hyp(4‐I‐Ph)]. The crystal structure of Boc‐Ser‐hyp(4‐I‐Ph)‐OMe had two molecules in the unit cell. One molecule exhibited cis‐proline and a type VIa2 β‐turn (BcisD). The cis‐proline conformation was stabilized by a C–H/O interaction between Pro C–Hα and the Ser side‐chain oxygen. NMR data were consistent with stabilization of cis‐proline by a C–H/O interaction in solution. The other crystallographically observed molecule had trans‐Pro and both residues in the PPII conformation. Two conformations were observed in the crystal structure of Ac‐Ser‐hyp(4‐I‐Ph)‐OMe, with Ser adopting PPII in one and the β conformation in the other, each with Pro in the δ conformation and trans‐Pro. Structures at Ser‐Pro sequences were further examined via bioinformatics analysis of the PDB and via DFT calculations. Ser‐Pro versus Ala–Pro sequences were compared to identify bases for Ser stabilization of local structures. C–H/O interactions between the Ser side‐chain Oγ and Pro C–Hα were observed in 45% of structures with Ser‐cis‐Pro in the PDB, with nearly all Ser‐cis‐Pro structures adopting a type VI β‐turn. 53% of Ser‐trans‐Pro sequences exhibited main‐chain COi•••HNi+3 or COi•••HNi+4 hydrogen bonds, with Ser as the i residue and Pro as the i + 1 residue. These structures were overwhelmingly either type I β‐turns or N‐terminal capping motifs on α‐helices or 310‐helices. These results indicate that Ser‐Pro sequences are particularly potent in favoring these structures. In each, Ser is in either the PPII or β conformation, with the Ser Oγ capable of engaging in a hydrogen bond with the amide N–H of the i + 2 (type I β‐turn or 310‐helix; Ser χ1t) or i + 3 (α‐helix; Ser χ1g+) residue. Non‐proline cis amide bonds can also be stabilized by C–H/O interactions. [ABSTRACT FROM AUTHOR]

The type II polyproline helix (PPII) is a fundamental secondary structure of proteins, important in globular proteins, in intrinsically disordered proteins, and at protein‐protein interfaces. PPII is stabilized in part by n→π* interactions between consecutive carbonyls, via electron delocalization between an electron‐donor carbonyl lone pair (n) and an electron‐acceptor carbonyl (π*) on the subsequent residue. We previously demonstrated that changes to the electronic properties of the acyl donor can predictably modulate the strength of n→π* interactions, with data from model compounds, in solution in chloroform, in the solid state, and computationally. Herein, we examined whether the electronic properties of acyl capping groups could modulate the stability of PPII in peptides in water. In X−PPGY‐NH2 peptides (X=10 acyl capping groups), the effect of acyl group identity on PPII was quantified by circular dichroism and NMR spectroscopy. Electron‐rich acyl groups promoted PPII relative to the standard acetyl (Ac−) group, with the pivaloyl and iso‐butyryl groups most significantly increasing PPII. In contrast, acyl derivatives with electron‐withdrawing substituents and the formyl group relatively disfavored PPII. Similar results, though lesser in magnitude, were also observed in X−APPGY‐NH2 peptides, indicating that the capping group can impact PPII conformation at both proline and non‐proline residues. The pivaloyl group was particularly favorable in promoting PPII. The effects of acyl capping groups were further analyzed in X–DfpPGY‐NH2 and X−ADfpPGY‐NH2 peptides, Dfp=4,4‐difluoroproline. Data on these peptides indicated that acyl groups induced order Piv‐ > Ac‐ > For‐. These results suggest that greater consideration should be given to the identity of acyl capping groups in inducing structure in peptides. [ABSTRACT FROM AUTHOR]

Climate change, with warming and drying weather conditions, is reducing the growth, seed production, and survival of fire‐adapted plants in fire‐prone regions such as Mediterranean‐type ecosystems. These effects of climate change on local plant demographics have recently been shown to reduce the persistence time of local populations of the fire‐killed shrub Banksia hookeriana dramatically. In principle, extinctions of local populations may be partly compensated by recolonization events through long‐distance dispersal mechanisms of seeds, such as post‐fire wind and bird‐mediated dispersal, facilitating persistence in spatially structured metapopulations. However, to what degree and under which assumptions metapopulation dynamics might compensate for the drastically increased local extinction risk remains to be explored. Given the long timespans involved and the complexity of interwoven local and regional processes, mechanistic, process‐based models are one of the most suitable approaches to systematically explore the potential role of metapopulation dynamics and its underlying ecological assumptions for fire‐prone ecosystems. Here we extend a recent mechanistic, process‐based, spatially implicit population model for the well‐studied fire‐killed and serotinous shrub species B. hookeriana to a spatially explicit metapopulation model. We systematically tested the effects of different ecological processes and assumptions on metapopulation dynamics under past (1988–2002) and current (2003–2017) climatic conditions, including (i) effects of different spatio‐temporal fires, (ii) effects of (likely) reduced intraspecific plant competition under current conditions and (iii) effects of variation in plant performance among and within patches. In general, metapopulation dynamics had the potential to increase the overall regional persistence of B. hookeriana. However, increased population persistence only occurred under specific optimistic assumptions. In both climate scenarios, the highest persistence occurred with larger fires and intermediate to long inter‐fire intervals. The assumption of lower intraspecific plant competition caused by lower densities under current conditions alone was not sufficient to increase persistence significantly. To achieve long‐term persistence (defined as >400 years) it was necessary to additionally consider empirically observed variation in plant performance among and within patches, that is, improved habitat quality in some large habitat patches (≥7) that could function as source patches and a higher survival rate and seed production for a subset of plants, specifically the top 25% of flower producers based on current climate conditions monitoring data. Our model results demonstrate that the impacts of ongoing climate change on plant demographics are so severe that even under optimistic assumptions, the existing metapopulation dynamics shift to an unstable source‐sink dynamic state. Based on our findings, we recommend increased research efforts to understand the consequences of intraspecific trait variation on plant demographics, emphasizing the variation of individual traits both among and within populations. From a conservation perspective, we encourage fire and land managers to revise their prescribed fire plans, which are typically short interval, small fires, as they conflict with the ecologically appropriate spatio‐temporal fire regime for B. hookeriana, and likely as well for many other fire‐killed species. [ABSTRACT FROM AUTHOR]

Importance: Critically ill children with pre‐existing mental health conditions may have an increased risk of poor health outcomes. Objective: We aimed to evaluate if pre‐existing mental health conditions in critically ill pediatric patients would be associated with worse clinical outcomes, compared to children with no documented mental health conditions. Methods: This retrospective observational cohort study utilized the TriNetX electronic health record database of critically ill subjects aged 12–18 years. Data were analyzed for demographics, pre‐existing conditions, diagnostic, medication, procedural codes, and mortality. Results: From a dataset of 102 027 critically ill children, we analyzed 1999 subjects (284 [14.2%] with a pre‐existing mental health condition and 1715 [85.8%] with no pre‐existing mental health condition). Multivariable analysis demonstrated that death within one year was associated with the presence of pre‐existing mental health conditions (odds ratio 8.97 [3.48–23.15], P < 0.001), even after controlling for the presence of a complex chronic condition. Interpretation: The present study demonstrates that the presence of pre‐existing mental health conditions was associated with higher odds of death within 1 year after receiving critical care. However, the confidence interval was wide and hence, the findings are inconclusive. Future studies with a larger sample size may be necessary to evaluate the true long‐term impact of children with pre‐existing mental health conditions who require critical care services. [ABSTRACT FROM AUTHOR]

Objective: Spearfishing is a common activity used to harvest coastal marine species worldwide and can be a significant contributor to landings of ecologically and economically relevant species. As such, it is important to monitor spearfishing catch and effort. Spearfishing is commonly practiced throughout the Caribbean, yet characteristics of this gear's fishery remain understudied in the region. Thus, the objectives of this study were to provide a description of the Puerto Rico spearfishing fishery utilizing a long-term MRIP APAIS data set, examine the data set quality of this survey, and provide suggestions to improve MRIP implementation in the U.S. Caribbean. Methods: We described the Puerto Rico recreational spearfishing fishery using a multidecadal (2000-2015) Marine Recreational Information Program (MRIP) Access Point Angler Intercept Survey conducted along the coast of Puerto Rico and surrounding territories. Data issues were identified in the survey results, including possible errors in measurement and identification; therefore, we limited analyses to species composition, enumeration, and mean catch rates. Result: There were 89 species identified, with snappers (family Lutjanidae) being the most encountered family. Other economically relevant finfish frequently reported were Hogfish Lachnolaimus maximus (n = 121), Queen Triggerfish Balistes vetula (n = 115), and Red Hind Epinephelus guttatus (n = 90). Multiple reef fishes were landed during their spawning season, while prohibited by seasonal closures. Further, spearfishing accounted for 25.8% of the total harvest throughout the study period. Conclusion: Our results suggest that spearfishing could be a considerable contributor to finfish landings in Puerto Rico, warranting its continued and improved monitoring in the region. Further, modifications in the design of fisheries surveys are warranted. We suggest increasing the allocation of resources, training, data quality assurance and quality control, and funding for the MRIP to maximize the accuracy of data obtained and meet MRIP U.S. Caribbean priorities. Implementation of a recreational fishing license would assist by creating a registry to monitor total recreational fishing effort and by generating funds to supplement the MRIP. The use of electronic reporting can help mitigate discrepancies with species identification and size measurements and enhance overall recreational fisheries data collection. [ABSTRACT FROM AUTHOR]

Rainfall intensity in the United Kingdom is projected to increase under climate change with significant implications for rainfall‐driven (combined pluvial and fluvial) flooding. In the UK, the current recommended best practice for estimating changes in pluvial flood hazard under climate change involves applying a simple percentage uplift to spatially uniform catchment rainfall, despite the known importance of the spatial and temporal characteristics of rainfall in the generation of pluvial floods. The UKCP Local Convective Permitting Model (CPM) has for the first time provided the capacity to assess changes in flood hazard using hourly, 2.2 km CPM precipitation data that varies in space and time. Here, we use an event set of ∼13,500 precipitation events across the three UKCP Local epochs (1981–2000, 2021–2040, and 2061–2080) to simulate rainfall‐driven flooding using the LISFLOOD‐FP hydrodynamic model at 20 m resolution over a 750 km2 area of Bristol and Bath, UK. We find that both the event set and uplift approaches indicate an increase in flood hazard under near‐term (2021–2040) and future (2061–2080) climate change. However, the event set produces markedly higher estimates of flood hazard when compared to the uplift approach, ranging from 19% to 49% higher depending on the return period. This suggests including the full spatiotemporal rainfall variability and its future change in rainfall‐driven flood modeling is critical for future flood risk assessment. Plain Language Summary: Climate change is making rainfall more extreme. However, the detailed change in the space and time characteristics of rainfall are not well known and not represented in flood risk assessment. Instead, standard practice uses spatially uniform rainfall derived from historical records and increases them by a fixed percentage uplift to account for the impact of climate change. These uplifts are generated from climate model simulations that are analyzed to determine average rainfall changes. Failure to account for the changing space‐time characteristics of rainfall means that this standard approach likely mis‐estimates future changes in flooding. To test this hypothesis, we use high space and time resolution predictions of future rainfall patterns considering climate change to drive a detailed flood inundation model over the Bristol and Bath urban region in south‐west UK. Flood hazard is projected to increase in future, with increases greater when using full space‐time rainfall data rather than the standard uplift approach. This has important implications for how we estimate changes in flooding from changing rainfall with global warming. Key Points: We produce flood hazard estimates using spatiotemporal rainfall data from new convection permitting climate projections (UKCP Local)We find the UKCP Local rainfall data gives higher estimates of flood hazard compared to standard climate change uplift approachesRepresenting full spatiotemporal rainfall and its future change is crucial for future flood risk assessment [ABSTRACT FROM AUTHOR]

Atlantic tarpon Megalops atlanticus are highly migratory sportfish that support recreational fisheries throughout their range. In US waters, juveniles can be found in coastal and estuarine habitats along the Gulf of Mexico and Atlantic seaboard, with temperature limiting their northern latitudinal distribution. Juveniles may overwinter in these areas during the first several years of life. Low temperatures are known to cause mortality in adults, but the challenges of temperature are less understood for juveniles. Furthermore, salinity, which can change dramatically in these habitats, may have a synergistic effect with temperature. To examine the physiological effects of temperature and salinity on juvenile tarpon, wild fish were acclimated to a range of conditions that potentially occur in the northern range of their estuarine habitats. The haematology of juvenile tarpon was examined in two salinity (≤2 and ≥30 ppt) and temperature (15 and 25°C) treatments, followed by a low‐temperature tolerance test. After 2 weeks in treatment conditions, blood samples were analysed for haematocrit, pH, red blood cell concentration, haemoglobin content and plasma osmolality. Increased plasma osmolality was observed in fish at low temperature (15°C compared to 25°C) and at high salinity (≥30 ppt compared to ≤2 ppt). Blood pH was increased at 15°C compared to 25°C, with the highest pH at 15°C and low salinity. Haemoglobin, haematocrit and red blood cell concentration were higher at 25°C than 15°C, with haemoglobin lowest at 15°C and low salinity. For the low‐temperature tolerance test, all fish were acclimated to 15°C for 2 weeks, then transferred to separate tanks where temperature was gradually decreased at 0.9 ± 0.1°C/h until fish lost equilibrium. Fish at low salinity lost equilibrium more rapidly (1 ppt, 12.65 ± 0.46°C) than fish at high salinity (30 ppt, 11.26 ± 0.14°C). The results indicate juvenile tarpon are susceptible to low temperature, which is exacerbated by low salinity, findings useful in the assessment of juvenile tarpon overwintering habitat. [ABSTRACT FROM AUTHOR]

Mitochondrial dysfunction is considered a highly conserved hallmark of ageing. However, most of the studies in both model and non‐model organisms are cross‐sectional in design; therefore, little is known, at the individual level, on how mitochondrial function changes with age, its link to early developmental conditions or its relationship with survival. Here we manipulated the postnatal growth in zebra finches (Taeniopygia guttata) via dietary modification that induced accelerated growth without changing adult body size. In the same individuals, we examined blood cells mitochondrial functioning (mainly erythrocytes) when they were young (ca. 36 weeks) and again in mid‐aged (ca. 91 weeks) adulthood. Mitochondrial function was strongly influenced by age but not by postnatal growth conditions. Across all groups, within individual ROUTINE respiration, OXPHOS and OXPHOS coupling efficiency significantly declined with age, while LEAK respiration increased. However, we found no link between mitochondrial function and the probability of survival into relatively old age (ca. 4 years). Our results suggest that the association between accelerated growth and reduced longevity, evident in this as in other species, is not attributable to age‐related changes in any of the measured mitochondrial function traits. [ABSTRACT FROM AUTHOR]

Background: Intracardiac catheter ablation for atrial fibrillation with pulmonary vein isolation may result in Takotsubo syndrome (TS), but the frequency, predisposing factors (age, sex, mental health disorders), and outcomes are currently unknown. This study sought to assess the frequency, predisposing factors, and outcomes of subjects who underwent intracardiac catheter ablation for atrial fibrillation with pulmonary vein isolation and were diagnosed with TS. Methods: This was a retrospective observational cohort study utilizing TriNetX® electronic health record (EHR) data. We included subjects aged older than 18 years who underwent intracardiac catheter ablation for atrial fibrillation with pulmonary vein isolation. The study population was divided into two groups (no TS diagnostic code presence and TS diagnostic code presence). We analyzed the distributions of age, sex, race, diagnostic codes, common terminology procedures (CPT), and vasoactive medication codes and examined mortality rate within 30 days. Results: We included 69,116 subjects. Of these, 27 (0.04%) had a TS diagnostic code, the cohort was comprised mostly of females [17 (63.0%)], and 1 (3.7%) death within 30 days was reported. There were no significant differences in age and frequency of mental health disorders between those patients in TS and non‐TS cohorts. Adjusting for age, sex, race, ethnicity, patient regionality, and mental health disorder diagnostic code, those patients who developed TS had a significantly higher odds of dying in 30 days after catheter ablation compared to those without TS (OR = 15.97, 95% CI: 2.10–121.55, p =.007). Conclusions: Approximately 0.04% of subjects who underwent intracardiac catheter ablation of atrial fibrillation by pulmonary vein isolation had a subsequent diagnostic code of TS. Further study is needed to determine whether there are predisposing factors associated with the development of TS in subjects who undergo catheter ablation of atrial fibrillation by pulmonary vein isolation. [ABSTRACT FROM AUTHOR]

Researchers from diverse disciplines, including organismal and cellular physiology, sports science, human nutrition, evolution and ecology, have sought to understand the causes and consequences of the surprising variation in metabolic rate found among and within individual animals of the same species. Research in this area has been hampered by differences in approach, terminology and methodology, and the context in which measurements are made. Recent advances provide important opportunities to identify and address the key questions in the field. By bringing together researchers from different areas of biology and biomedicine, we describe and evaluate these developments and the insights they could yield, highlighting the need for more standardisation across disciplines. We conclude with a list of important questions that can now be addressed by developing a common conceptual and methodological toolkit for studies on metabolic variation in animals. [ABSTRACT FROM AUTHOR]

Tarpon Megalops atlanticus is a popular and economically important inshore sport fish in Puerto Rico, and the pursuit of this species by local anglers and tourists contributes to the economy. This species is managed as a no-take fishery, which aims to preserve populations by catching and releasing fish that would otherwise be subjected to harvest and removal from the population. The approach assumes minimal mortality and/or reduced fitness of released fish, yet the process of angling can produce many sublethal side effects or direct mortality. In this study, charter angling for Tarpon in the San Juan lagoon system in Puerto Rico was examined to determine postrelease mortality. Angled fish were externally tagged with acoustic transmitters and relocated periodically to determine the fate after release. Postrelease mortality was at least 4.5% (two fish observed dead) and at most 18.2% (observed dead plus classified dead based on lack of movement; confidence interval [CI] = 7.5-28.9%). Some tag loss was observed, which could have artificially elevated classified mortality estimates. Potential factors that contribute to mortality are discussed and compared to the literature. Hook type, gear action, landing procedures, and air exposure were key areas of possible improvement. Recommendations to minimize fish harm during angling include the use of heavier action gear to reduce fight time, a circle hook requirement for live bait to reduce deep hooking, maintaining fish in the water during landing and photography, and limiting air exposure to 2 min or less if fish are removed from the water. [ABSTRACT FROM AUTHOR]

The speckled peacock bass Cichla temensis is a popular sport and food fish that generates substantial angling tourism and utilitarian harvest within its range. Its popularity and value make this species important for management and a potential aquaculture candidate for both fisheries enhancement and food fish production. However, little is known of optimal physiochemical conditions in natural habitats, which also are important for the development of hatchery protocols for handling, spawning and grow‐out. Speckled peacock bass have been documented to have high sensitivity to extreme temperatures, but the metabolic underpinnings have not been evaluated. In this study, the effects of temperature (25, 30 and 35°C) on the standard metabolic rate (SMR) and lower dissolved oxygen tolerance (LDOT) of juvenile speckled peacock bass (mean ± standard error total length 153 ± 2 mm and wet weight 39.09 ± 1.37 g) were evaluated using intermittent respirometers after an acclimation period of 2 weeks. Speckled peacock bass had the highest SMR at 35°C (345.56 ± 19.89 mgO2 kg−1 h−1), followed by 30°C (208.16 ± 12.45 mgO2 kg−1 h−1) and 25°C (144.09 ± 10.43 mgO2 kg−1 h−1). Correspondingly, the Q10, or rate of increase in aerobic metabolic rate (MO2) relative to 10°C, for 30–35°C was also greater (2.76) than from 25 to 30°C (2.08). Similarly, speckled peacock bass were the most sensitive to hypoxia at the warmest temperature, with an LDOT at pO2 of 90 mmHg (4.13 mg l−1) at 35°C compared to pO2 values of 45 mmHg (2.22 mg l−1) and 30 mmHg (1.61 mg l−1) at 30 and 25°C, respectively. These results indicate that speckled peacock bass are sensitive to temperatures near 35°C, therefore we recommend managing and rearing this species at 25–30°C. [ABSTRACT FROM AUTHOR]

Aims: Responses of ecological restoration projects to disturbances are rarely explored, yet their capacity to withstand and recover from disturbance (resilience) is a critical measure of restoration success. In many plant communities, the soil seed bank (SSB) provides an important source of propagules for species persistence and community resilience to disturbance. Understanding how SSBs develop with time can inform restoration of resilient ecosystems. Here, in fire‐prone Banksia woodland restoration following sand mining, we ask: (a) how does the smoke‐responsive (dormancy broken by smoke) SSB develop over time; (b) what plant‐trait and climate factors influence its development; and (c) what do the data suggest for the resilience of these restored woodlands to fire? Location: Ellenbrook, Swan Coastal Plain, Western Australia (latitude −31.76, longitude 115.95). Methods: We used smoke, a key germination cue associated with fire disturbance, to trigger germination of the SSB in Banksia woodland restoration. Using a chronosequence of nine ages between 3 and 26 years since initiation of restoration, we tested how the SSB develops using counts and richness of germinating native and invasive annuals, and native perennial obligate seeding and resprouting species. To understand the contribution of above‐ground restored vegetation to SSB development, we compared Sørensen's similarity of the smoke germinable SSB (smoked SSB) and untreated germinable SSB (control SSB) with above‐ground vegetation. Results: Smoked SSB germinant density decreased with restoration age for both native and invasive annuals, but was stable for native perennials. Similarity between smoked SSB and above‐ground vegetation was higher for perennial obligate seeders than for resprouters and peaked for perennials at 23 years. Conclusions: Post‐fire regeneration potential of the SSB was evident across the chronosequence, with restoration age influencing the density of native annuals and overall composition of the SSB. The findings for perennial species suggest an increase in resilience to fire with restoration age.Seeds are necessary for successful restoration, but few studies track the development of the soil seed bank. Using smoke, we assessed germination of smoke‐responsive plant species across a restoration chronosequence. There was germination across the chronosequence, with composition changing with age. Our data for native perennial plant species suggest resilience of restored Banksia woodlands to fire increases with restoration age. [ABSTRACT FROM AUTHOR]

Eliglustat is a glucosylceramide synthase inhibitor indicated as a long‐term substrate reduction therapy for adults with type 1 Gaucher disease, a lysosomal rare disease. It is primarily metabolized by cytochrome P450 2D6 (CYP2D6), and variants in the gene encoding this enzyme are important determinants of eliglustat pharmacokinetics (PK) and drug–drug interactions (DDIs). The existing drug label addresses the DDIs to some extent but has omitted scenarios where both metabolizing CYPs (2D6 and 3A4) are mildly or moderately inhibited. The objectives of this study were (i) to develop and validate an eliglustat physiologically‐based pharmacokinetic (PBPK) model with and without drug interactions, (ii) to simulate untested DDI scenarios, and (iii) to explore potential dosing flexibility using lower dose strength of eliglustat (commercially not available). PK data from healthy adults receiving eliglustat with or without interacting drugs were obtained from literature and used for the PBPK model development and validation. The model‐predicted single‐dose and steady‐state maximum concentration (Cmax) and area under the concentration‐time curve (AUC) of eliglustat were within 50–150% of the observed values when eliglustat was administered alone or coadministered with ketoconazole or paroxetine. Then as model‐based simulations, we illustrated eliglustat exposure as a victim of interaction when coadministered with fluvoxamine following the US Food and Drug Administration (FDA) dosing recommendations. Second, we showed that with lower eliglustat doses (21 mg, 42 mg once daily) the exposure in participants of intermediate and poor metabolizer phenotypes was within the outlined safety margin (Cmax <250 ng/mL) when eliglustat was administered with ketoconazole, where the current recommendation is a contraindication of coadministration (84 mg). The present study demonstrated that patients with CYP2D6 deficiency may benefit from lower doses of eliglustat. [ABSTRACT FROM AUTHOR]

Aerobic energy demands have led to the evolution of complex mitochondrial reticula in highly oxidative muscles, but the extent to which metabolic challenges can be met with adaptive changes in physiology of specific mitochondrial fractions remains unresolved. We examined mitochondrial mechanisms supporting adaptive increases in aerobic performance in deer mice (Peromyscus maniculatus) adapted to the hypoxic environment at high altitude. High‐altitude and low‐altitude mice were born and raised in captivity, and exposed as adults to normoxia or hypobaric hypoxia (12 kPa O2 for 6–8 weeks). Subsarcolemmal and intermyofibrillar mitochondria were isolated from the gastrocnemius, and a comprehensive substrate titration protocol was used to examine mitochondrial physiology and O2 kinetics by high‐resolution respirometry and fluorometry. High‐altitude mice had greater yield, respiratory capacity for oxidative phosphorylation, and O2 affinity (lower P50) of subsarcolemmal mitochondria compared to low‐altitude mice across environments, but there were no species difference in these traits in intermyofibrillar mitochondria. High‐altitude mice also had greater capacities of complex II relative to complexes I + II and higher succinate dehydrogenase activities in both mitochondrial fractions. Exposure to chronic hypoxia reduced reactive oxygen species (ROS) emission in high‐altitude mice but not in low‐altitude mice. Our findings suggest that functional changes in subsarcolemmal mitochondria contribute to improving aerobic performance in hypoxia in high‐altitude deer mice. Therefore, physiological variation in specific mitochondrial fractions can help overcome the metabolic challenges of life at high altitude. [ABSTRACT FROM AUTHOR]

Climate change is thawing and potentially mobilizing vast quantities of organic carbon (OC) previously stored for millennia in permafrost soils of northern circumpolar landscapes. Climate‐driven increases in fire and thermokarst may play a key role in OC mobilization by thawing permafrost and promoting transport of OC. Yet, the extent of OC mobilization and mechanisms controlling terrestrial‐aquatic transfer are unclear. We demonstrate that hydrologic transport of soil dissolved OC (DOC) from the active layer and thawing permafrost to headwater streams is extremely heterogeneous and regulated by the interactions of soils, seasonal thaw, fire, and thermokarst. Repeated sampling of streams in eight headwater catchments of interior Alaska showed that the mean age of DOC for each stream ranges widely from modern to ∼2,000 years B.P. Together, an endmember mixing model and nonlinear, generalized additive models demonstrated that Δ14C‐DOC signature (and mean age) increased from spring to fall, and was proportional to hydrologic contributions from a solute‐rich water source, related to presumed deeper flow paths found predominantly in silty catchments. This relationship was correlated with and mediated by catchment properties. Mean DOC ages were older in catchments with >50% burned area, indicating that fire is also an important explanatory variable. These observations underscore the high heterogeneity in aged C export and difficulty of extrapolating estimates of permafrost‐derived DOC export from watersheds to larger scales. Our results provide the foundation for developing a conceptual model of permafrost DOC export necessary for advancing understanding and prediction of land‐water C exchange in changing boreal landscapes. Plain Language Summary: In high latitude environments, soils that have been frozen for millennia are thawing, releasing organic carbon (OC). Thawing and export of OC to downstream aquatic ecosystems is a potential biogeochemical feedback that may accelerate climate warming if large amounts of ancient OC are transformed and released to the atmosphere as greenhouse gases. The magnitude and timing of ancient OC thaw and mobilization are not well defined, so predicting these patterns at local to global scales is challenging. Using a suite of diverse headwater catchments in the discontinuous permafrost zone of Alaska, USA, we identify the main controls on the mobilization of ancient OC from thawing landscapes into adjacent streams. Our surveys show that ancient OC export depends on the complex interaction between fire history, soil type and thawing characteristics, and seasonal warming. We find that all of these factors play a role, resulting in highly heterogeneous release of ancient OC to headwater streams. Key Points: Aged dissolved organic carbon (DOC) in headwater streams in interior Alaska is heterogeneous across permafrost landscapes indicating the interplay of multiple driversAged DOC concentrations increase from spring to fall and are highest in catchments with >50% burned extent and dominated by silty uplandsAged DOC is proportional to stream solute loads, indicating that deeper flow paths deliver permafrost C to streams [ABSTRACT FROM AUTHOR]

An electrochemical method for the green and practical synthesis of a broad range of substituted isoxazoline cores is presented. Both aryl and more challenging alkyl aldoximes are converted to the desired isoxazoline in an electrochemically enabled regio‐ and diastereoselective reaction with electron‐deficient alkenes. Additionally, in‐situ reaction monitoring methods compatible with electrochemistry equipment have been developed in order to probe the reaction pathway. Supporting analyses from kinetic (time‐course) modelling and density functional theory support a stepwise, radical‐mediated mechanism, and discounts hypothesised involvement of closed shell [3+2] cycloaddition pathways. [ABSTRACT FROM AUTHOR]

Background/Objectives: When a severe asthma exacerbation occurs in an obese pediatric patient, it is unknown if this body type persists in future encounters. Persistent obesity can lead to future asthma exacerbations. The main study objective is to evaluate the persistence of a BMI percentile ≥85th in children 5 years after the first reported diagnosis of status asthmaticus. We hypothesized that a hospital admission for status asthmaticus was associated with persistence of a BMI percentile ≥85th. Methods: This was a long‐term retrospective observational cohort study utilizing TriNetX ® electronic health record (EHR) data. We included subjects aged 2 to 18 years of age with a diagnosis of status asthmaticus. Study population was divided into two groups based on their admission body mass index percentile: (underweight/healthy weight [<85th percentile] and overweight/obese [≥85th percentile]) and evaluated for the following outcomes: age, race, ethnicity, diagnostic codes, and BMI percentiles (initially and 5 years after diagnosis of status asthmaticus). Results: A total of 129 subjects (n%) (76 [58.9%] underweight/healthy weight and 53 [41.1%] overweight/obese) were included. Children that were initially overweight/obese with status asthmaticus had significantly increased odds of continuing to be overweight/obese 5 years after diagnosis compared to children who were underweight/healthy weight at baseline (OR = 7.50 [95% confidence interval, 3.20–17.60; p < 0.001]). Conclusions: Overweight/obese asthmatic children are at risk of continuing to be obese several years after being diagnosed with status asthmaticus. This study reinforces the notion that when an asthmatic obese child presents with status asthmaticus, a thorough evaluation of nutrition, physical activity, and asthma control should be considered to reduce the risk of persistent obesity and possibly future asthma exacerbations. [ABSTRACT FROM AUTHOR]

Understanding the key mechanisms that control northern treelines is important to accurately predict biome shifts and terrestrial feedbacks to climate. At a global scale, it has long been observed that elevational and latitudinal treelines occur at similar mean growing season air temperature (GSAT) isotherms, inspiring the growth limitation hypothesis (GLH) that cold GSAT limits aboveground growth of treeline trees, with mean treeline GSAT ~6–7°C. Treelines with mean GSAT warmer than 6–7°C may indicate other limiting factors. Many treelines globally are not advancing despite warming, and other climate variables are rarely considered at broad scales. Our goals were to test whether current boreal treelines in northern Alaska correspond with the GLH isotherm, determine which environmental factors are most predictive of treeline presence, and identify areas beyond the current treeline where advance is most likely. We digitized ~12 400 km of treelines (>26 K points) and computed seasonal climate variables across northern Alaska. We then built a generalized additive model predicting treeline presence to identify key factors determining treeline. Two metrics of mean GSAT at Alaska's northern treelines were consistently warmer than the 6–7°C isotherm (means of 8.5°C and 9.3°C), indicating that direct physiological limitation from low GSAT is unlikely to explain the position of treelines in northern Alaska. Our final model included cumulative growing degree‐days, near‐surface (≤1 m) permafrost probability and growing season total precipitation, which together may represent the importance of soil temperature. Our results indicate that mean GSAT may not be the primary driver of treeline in northern Alaska or that its effect is mediated by other more proximate, and possibly non‐climatic, controls. Our model predicts treeline potential in several areas beyond current treelines, pointing to possible routes of treeline advance if unconstrained by non‐climatic factors. [ABSTRACT FROM AUTHOR]

Unseasonal fire occurrence is increasing globally, driven by climate change and other human activity. Changed timing of fire can inhibit postfire seedling recruitment through interactions with plant phenology (the timing of key processes, e.g., flower initiation, seed production, dispersal, germination), and therefore threaten the persistence of many plant species. Although empirical evidence from winter‐rainfall ecosystems shows that optimal seedling recruitment is expected following summer and autumn (dry season) fires, we sought experimental evidence isolating the mechanisms of poor recruitment following unseasonal (wet season) fire. We implemented a seed‐sowing experiment using nine species native to fire‐prone, Mediterranean‐climate woodlands in southwestern Australia to emulate the timing of postfire recruitment and test key mechanisms of fire seasonality effects. For seeds sown during months when fire is unseasonal (i.e., August–September: end of the wet winter season), seedling recruitment was reduced by up to 99% relative to seeds sown during seasonal fire months (i.e., May–June: end of the dry summer season) because of varying seed persistence, seedling emergence, and seedling survival. We found that up to 70 times more seedlings emerged when seeds were sown during seasonal fire months compared to when seeds were sown during unseasonal fire months. The few seedlings that emerged from unseasonal sowings all died with the onset of the dry season. Of the seeds that failed to germinate from unseasonal sowings, only 2% survived exposure on the soil surface over the ensuing hot and dry summer. Our experimental results demonstrate the potential for unseasonal fire to inhibit seedling recruitment via impacts on pregermination seed persistence and seedling establishment. As ongoing climate change lengthens fire seasons (i.e., unseasonal wildfires become more common) and managed fires are implemented further outside historically typical fire seasons, postfire seedling recruitment may become more vulnerable to failure, causing shifts in plant community composition towards those with fewer species solely dependent on seeds for regeneration. [ABSTRACT FROM AUTHOR]

Supplemental stocking of crappie is a primary management strategy in many small southern reservoirs, but survival and contribution to the year‐class in these systems is not known. We assessed the contribution of hatchery fish to the age‐1 year‐class within established crappie populations in four reservoirs ranging 29–74 ha in surface area. Chemically marked White Crappie Pomoxis annularis and magnolia crappie (Black Crappie Pomoxis nigromaculatus × ♀White Crappie) were stocked at 125 fish/ha in 2015 and 2016, respectively. We also stocked a renovated reservoir (40 ha) with White Crappie in 2015 to serve as a reference without intraspecific competition and to provide an estimate of marking efficacy and mark retention. The total length of wild age‐0 fish at the time of stocking averaged 52–60 mm larger than that of their hatchery conspecifics. We only recaptured 11 marked crappie, 10 of which were from the reference reservoir. The recovery of only one hatchery fish from the supplemental stockings yielded a combined stocking contribution of 0.59%, or 0.71% when adjusted for marking efficacy (at least 83%). We concluded that supplemental stocking of crappie in smaller reservoirs is not effective under current the stocking protocols, as contributions <1% cannot justify hatchery and personnel costs. It may be possible to modify the stocking procedures, and potential modifications are discussed. [ABSTRACT FROM AUTHOR]

Climate change has been documented for over 120 years with increasing scientific rigor, and its impacts are already observable in marine and freshwater fisheries. But after decades of communication to underscore the validity of these changes, and the urgency for action, a large component of the public and many elected officials deny the scientific consensus and reject the need for action. Therefore, we outline a more effective strategy to convey the climate message to stakeholders and inspire them to act. [ABSTRACT FROM AUTHOR]

Omega‐3 long‐chain polyunsaturated fatty acids (n − 3 LC‐PUFA) are essential micronutrients for optimal functioning of cellular metabolism and for somatic growth of all vertebrates including fishes. In addition, n − 3 LC‐PUFA could also play a key role in response of fishes and other ectothermic vertebrates to changing temperatures.An important, but largely overlooked, consequence of climate change is the reduced availability of dietary n − 3 LC‐PUFA in aquatic food webs. Changes in availability of dietary n − 3 LC‐PUFA have recently been proposed as a major driver of novel adaptations and diversification of consumers. Yet, there is only limited knowledge about how n − 3 LC‐PUFA depletion in aquatic food webs will affect the performance of wild fishes.Here we combine biochemistry and physiology at the cellular level with physiological and cognitive processes at the whole‐animal level to test how ecologically relevant deprivation of n − 3 LC‐PUFA affects performance of wild juvenile Atlantic salmon Salmo salar.We found that juvenile salmon had a limited capacity to maintain the fatty acid profile of both muscle and brain under an n − 3 LC‐PUFA‐deficient diet. Despite these findings, brain tissues showed remarkable functional stability in mitochondrial metabolism, and we found no effect of diet on learning ability. However, we found that mitochondrial efficiency in muscles and the somatic growth were reduced under an n − 3 LC‐PUFA‐deficient diet. Importantly, we discovered that the somatic growth of juvenile salmon within both treatments decreased with increasing rate of DHA synthesis and retention.Since DHA is essential for functioning of cellular metabolism, which together with body size are traits closely related to fitness of wild fishes, we suggest that the trade‐off between growth rate and accumulation of DHA could play a critical role in resilience of juvenile salmon to the ongoing rapid environmental change. A free Plain Language Summary can be found within the Supporting Information of this article. [ABSTRACT FROM AUTHOR]

BACKGROUND: Anti human epidermal growth factor receptor 2 (anti‐HER2) therapy with trastuzumab improves overall survival in patients with advanced, HER2‐positive gastroesophageal adenocarcinoma (GEA) and is now incorporated into national guidelines. However, little is known about adherence to and determinants of timely HER2 testing and trastuzumab initiation in routine practice. METHODS: The authors performed a cross‐sectional study of patients who had advanced GEA diagnosed between January 2011 and June 2019 in a nationwide electronic health record‐derived database. The annual prevalences of both timely HER2 testing (defined within 21 days after advanced diagnosis) and timely trastuzumab initiation (defined within 14 days after a positive HER2 result) were calculated. Log‐binomial regressions estimated adjusted prevalence ratios comparing timely HER2 testing and trastuzumab initiation by patient and tumor characteristics. RESULTS: In total, the cohort included 6032 patients with advanced GEA of whom 1007 were HER2‐positive. Between 2011 and 2019, timely HER2 testing increased from 22.4% to 44.5%, whereas timely trastuzumab initiation remained stable at 16.3%. No appreciable differences in timely testing or trastuzumab initiation were noted by age, sex, race, or insurance status. Compared with patients who had metastatic disease at diagnosis, patients who had early stage GEA who did not undergo surgery were less likely to receive timely HER2 testing and trastuzumab initiation (testing prevalence ratio, 0.69; 95% CI, 0.64‐0.75; treatment prevalence ratio, 0.32; 95% CI, 0.18‐0.56), as were patients with early stage disease who subsequently developed a distant recurrence (testing prevalence ratio, 0.56; 95% CI, 0.47‐0.65; treatment prevalence ratio, 0.61; 95% CI, 0.24‐1.55). CONCLUSIONS: In patients with advanced GEA, guideline‐recommended HER2 testing and anti‐HER2 therapy remain underused. Uptake may improve with universal HER2 testing regardless of stage. Timely HER2 biomarker testing and targeted therapy administration remain in use for patients with advanced gastroesophageal adenocarcinoma. Compared with patients initially diagnosed with de novo metastatic disease, those diagnosed with early stage disease who develop a recurrence or who do not undergo curative surgery are less likely to receive timely precision oncology care. [ABSTRACT FROM AUTHOR]

Purpose: Patients enrolled in Phase 1 clinical trials have typically exhausted standard therapies and often are choosing between a clinical trial and hospice care. Significant symptom burden can result in early trial discontinuation and confound trial outcomes. This study aimed to examine differences in study duration, symptom burden, adverse events (AE), and quality of life (QOL) between those receiving structured palliative care versus usual supportive care. Patients and methods: Sixty‐eight patients enrolled in phase 1 clinical trials and 39 of their CGs were randomly assigned to receive structured palliative care or usual supportive care. Patient QOL was measured monthly using the Functional Assessment of Cancer Therapy and Memorial Symptom Assessment Scale. The Quality of Life in Life‐Threatening Illness–Family Care Version and Caregiver Reaction Assessment were used for CGs. AEs and use of palliative care resources were compared between arms. Results: Mean duration of the phase 1 study was 142 days in the palliative care arm versus 116 days in the usual care arm (p = 0.55). Although not statistically significant, patients in the palliative care arm experienced fewer AEs and better QOL, as did their CGs, compared to those receiving usual care. Conclusions: Phase 1 patients and their CGs have physical and psychosocial needs warranting palliative care services. Results suggest that structured palliative care is associated with the increased duration of the study and improved patient and CG QOL. Phase 1 patients and their caregivers have physical and psychosocial needs warranting palliative care services. Providing structured palliative care servies to this population was associated with increased duration on phase 1 study and improved patient and caregiver QOL. [ABSTRACT FROM AUTHOR]

Ecological resilience is widely acknowledged as a vital attribute of successful ecosystem restoration, with potential for restoration practice to contribute to this goal. Hence, defining common metrics of resilience to naturally occurring disturbances is essential for restoration planning, efforts, and monitoring. Here, we reviewed how plant community ecologists have measured resilience of restoration projects to disturbances and propose a framework to guide measurement of restoration projects to disturbance. We found 22 studies that investigated the impact of disturbances on restoration projects, from three continents and for three disturbance types. Over half of the studies were from Australia, with the dataset biased toward fire responses of restored, or partially restored, forest ecosystems. Native plant species richness, cover, and density were common response variables. Studies varied in restoration context, design, response variables, and statistical approaches, limiting generalizations. Nonetheless we have identified several response variables that offer potential as lagging indicators (e.g. species richness) and leading indicators (e.g. recruitment) of resilience in diverse vegetation types exposed to a variety of disturbance regimes. We suggest a third set of variables, proxy measures of resilience (e.g. functional redundancy), to complement lagging and leading indicators. We conclude with a framework to guide decisions about when to use each of the three types of measures to assess resilience of restoration projects to disturbance, providing some clarity to decision‐making despite the uncertainty of changing disturbance regimes. Lastly, we invite researchers to understand the impact of disturbance on the resilience of restoration projects, rather than assume resilience. [ABSTRACT FROM AUTHOR]

River‐wide changes in morphologic character following channelization and impoundment alter the occurrence and distribution of surface water and available habitats for aquatic organisms. Quantifying patterns of creation, redistribution or disappearance of habitats at river‐wide and decadal spatiotemporal scales can promote understanding regarding trajectories of different habitat types following alteration and prospects of direct habitat enhancement projects within altered alluvial rivers. Newly available remote‐sensing tools and databases may improve detection of river‐wide changes in habitat through time. We used a combination of remote‐sensing data and generalized linear models to assess changes in surface water coverage from 1984 to 2015 among aquatic habitats of 496 km of the Arkansas River within Arkansas, USA. Changes through time in surface area of permanent and episodically inundated areas — and thus the availability of aquatic habitat — were variable along the river. Overall, the river lost a total 2.1% of permanent and 12.1% of episodic water surface area. The general trend of loss of off‐main‐channel habitat and increased coverage of permanent water along main‐channel habitats may indicate a long‐term transition (i.e. ramp‐type disturbance) within areas of the Arkansas River where backwaters are transitioning to terrestrial environments, and habitat heterogeneity in the main channel is decreasing. As such, a decadal‐scale change of channel form and backwater habitats may be the dominant pattern with limited regeneration of diverse habitat types. Understanding changes to permanent and episodic water availability may aid predictions regarding ecological effects of channelization and impoundments, including both increases and decreases in riverine productivity, biotic diversity and population abundances through space and time. Water resource managers and biologists can use information regarding river‐wide changes in habitat availability obtained through remote sensing data to direct river management practices, including dredging and side‐channel construction, and to assess ecological responses to such changes. [ABSTRACT FROM AUTHOR]

Ongoing changes in fire regimes have the potential to drive widespread shifts in Earth's vegetation. Plant traits and vital rates provide insight into vulnerability to fire‐driven vegetation shifts because they can be indicators of the ability of individuals to survive fire (resistance) and populations to persist (resilience) following fire.In 15 study sites spanning climatic gradients in the southern Rocky Mountains, USA, we quantified variation in key traits and vital rates of two co‐occurring, widely distributed conifers (Pinus ponderosa Douglas ex. P. Lawson & C. Lawson and Pseudotsuga menziesii (Mirb.) Franco). We used mixed‐effects models to explain inter‐ and intraspecific variation in tree growth, survival, bark thickness and seed cone production, as a function of species, tree life stage (i.e. diameter, height and age), average climate, local competition and site conditions.Pinus ponderosa was predicted to survive low‐severity fire at a 23% earlier age than P. menziesii. Pinus ponderosa had thicker bark and more rapid juvenile height growth, traits conferring greater fire resistance. In contrast, P. menziesii was predicted to produce seed cones at a 28% earlier age than P. ponderosa. For both species, larger individuals were more likely to survive fire and to produce cones. For P. ponderosa, cone production increased where average actual evapotranspiration (AET) was higher and local competition was lower. More frequent cone production on productive sites with higher AET is an important and underappreciated mechanism that may help to explain greater resilience to fire in these areas.Synthesis. Our analyses indicated that many plant traits and vital rates related to fire differed between Pinus ponderosa and Pseudotsuga menziesii, with trade‐offs between investment in traits that promote individual defence to fire and those that promote recolonization of disturbed sites. Future changes in fire regimes will act as a filter throughout North American forests, with our findings helping to infer which individuals and populations of two iconic species are most vulnerable to future change and offering a framework for future inquiry in other forests facing an uncertain future. [ABSTRACT FROM AUTHOR]

Questions: Globally, ecological restoration is required to restore degraded landscapes and to contribute to biodiversity conservation. Ecological theory suggests that manipulating dispersal, abiotic and biotic filters limiting plant re‐establishment will improve restoration outcomes. Here, we manipulated spread depth of soil containing a salvaged soil seedbank (dispersal filter), soil compaction (abiotic filter) and herbivore grazing (biotic filter) in a topsoil transfer experiment to test their effects on restoration success. Location: Banksia woodland of the Swan Coastal Plain, Western Australia. Methods: Topsoil (upper ~7 cm) with its seedbank was removed from a donor site (20 ha) of recently cleared native vegetation and transferred to six recipient restoration sites (16 ha). Deep (10 cm thick) and shallow (5 cm thick) layers of topsoil were applied in a fully factorial experiment, with and without soil ripping and fencing, respectively. We analysed emergence, survival and functional types (alien/native, life form, fire response) of all vascular plant species for two consecutive years after topsoil transfer. Results: The most successful restoration treatment was deep topsoil with a mean density of 14.3 m−2 native perennial germinants in year one and 7.3 m−2 in year two. Application of deep topsoil increased native seedling emergence by 34% and decreased weed density by 21% compared with shallow topsoil. Overall seedling survival across the two‐year period was unaffected by filter treatments (range 0.6%–5%). After two years, the resulting plant community was 6%–38% weed species and of native perennial species, 12%–48% were capable of resprouting. Conclusions: Manipulation of the dispersal filter alone, that is deep topsoil application, can lead to near‐equivalent native species number emerging on restoration sites as compared to pre‐cleared woodland. However, more research is required to test additional restoration tools to improve survival of biodiverse plant communities. For example, targeted herbicide application coupled with soil ripping to improve weed management and native seedling establishment. [ABSTRACT FROM AUTHOR]

Standard anatomical atlases are common in neuroimaging because they facilitate data analyses and comparisons across subjects and studies. The purpose of this study was to develop a standardized human brain atlas based on the physical mechanical properties (i.e., tissue viscoelasticity) of brain tissue using magnetic resonance elastography (MRE). MRE is a phase contrast‐based MRI method that quantifies tissue viscoelasticity noninvasively and in vivo thus providing a macroscopic representation of the microstructural constituents of soft biological tissue. The development of standardized brain MRE atlases are therefore beneficial for comparing neural tissue integrity across populations. Data from a large number of healthy, young adults from multiple studies collected using common MRE acquisition and analysis protocols were assembled (N = 134; 78F/ 56 M; 18–35 years). Nonlinear image registration methods were applied to normalize viscoelastic property maps (shear stiffness, μ, and damping ratio, ξ) to the MNI152 standard structural template within the spatial coordinates of the ICBM‐152. We find that average MRE brain templates contain emerging and symmetrized anatomical detail. Leveraging the substantial amount of data assembled, we illustrate that subcortical gray matter structures, white matter tracts, and regions of the cerebral cortex exhibit differing mechanical characteristics. Moreover, we report sex differences in viscoelasticity for specific neuroanatomical structures, which has implications for understanding patterns of individual differences in health and disease. These atlases provide reference values for clinical investigations as well as novel biophysical signatures of neuroanatomy. The templates are made openly available (github.com/mechneurolab/mre134) to foster collaboration across research institutions and to support robust cross‐center comparisons. [ABSTRACT FROM AUTHOR]

Records of Earth's primitive crust are scarce. Eoarchean (older than 3.6 Ga) banded mafic to felsic gneisses have been discovered in the São Francisco Craton, Brazil, pushing back by over 100 million years the oldest gneisses known to date in South America (3.5 Ga). Zircon U‐Pb data yield rock ages from 3,598 to 3,642 Ma with a few ca. 3.65–3.69 Ga grains suggesting even older rocks in the area. Zircon grains show significantly negative to nearly chondritic initial εHf values and two‐stage model ages from 3.82 to 4.33 Ga, which may indicate the existence of a recycled Hadean to early Eoarchean crust in the region. The felsic gneisses are chemically similar to the low‐pressure Tonalite‐Trondhjemite‐Granodiorite association whereas the mafic gneisses have geochemical signatures that resemble within‐plate basaltic andesite to andesite of Iceland (icelandites). The results are relevant to constrain the composition of Earth's first continental crust. [ABSTRACT FROM AUTHOR]

Type 1 Gaucher disease (GD1), a glycosphingolipid storage disorder caused by deficient activity of lysosomal glucocerebrosidase, is classically considered non‐neuronopathic. However, current evidence challenges this view. Multiple studies show that mutations in GBA1 gene and decreased glucocerebrosidase activity are associated with increased risk for Parkinson disease. We tested the hypothesis that subjects with GD1 will show neurochemical abnormalities consistent with cerebral involvement. We performed Magnetic Resonance Spectroscopy at 7 T to quantify neurochemical profiles in participants with GD1 (n = 12) who are on stable therapy. Age and gender matched healthy participants served as controls (n = 13). Neurochemical profiles were obtained from parietal white matter (PWM), posterior cingulate cortex (PCC), and putamen. Further, in the GD1 group, the neurochemical profiles were compared between individuals with and without a single L444P allele. We observed significantly lower levels of key neuronal markers, N‐acetylaspartate, γ‐aminobutyric acid, glutamate and glutamate‐to‐glutamine ratio in PCC of participants with GD1 compared to healthy controls (P <.015). Glutamate concentration was also lower in the putamen in GD1 (P =.01). Glucose + taurine concentration was significantly higher in PWM (P =.04). Interestingly, individuals without L444P had significantly lower aspartate and N‐acetylaspartylglutamate in PCC (both P <.001), although this group was 7 years younger than those with an L444P allele. This study demonstrates neurochemical abnormalities in individuals with GD1, for which clinical and prognostic significance remains to be determined. Further studies in a larger cohort are required to confirm an association of neurochemical levels with mutation status and glucocerebrosidase structure and function. Synopsis: Ultrahigh field magnetic resonance spectroscopy reveals abnormalities in neurochemical profiles in patients with GD1 compared to matched healthy controls. [ABSTRACT FROM AUTHOR]

Cysteine sulfinic acid is a protein posttranslational modification that is formed under oxidative conditions and is regulated both enzymatically and nonenzymatically. Cysteine oxidation to the sulfinic acid has been observed broadly throughout the proteome and can induce activation or inhibition of function in proteins. Recently, wide‐scale, reversible regulation of the sulfinic acid state of cysteine within proteins was identified, posing new questions in cysteine sulfinic acid biology. Existing methods to synthesize peptides with cysteine sulfinic acid can suffer from low yield, due to the formation of side products in the disulfide, sulfenic acid, and/or sulfonic acid oxidation states. Herein, a method for the synthesis of peptides with cysteine sulfinic acids was developed, via protection of cysteine sulfinic acid as the methoxybenzyl (Mob) sulfone. Cysteine Mob sulfone was synthesized as an Fmoc amino acid in one step from the commercially available Mob‐protected Fmoc‐cysteine (Fmoc‐Cys(Mob)‐OH). This amino acid was directly incorporated into peptides via solid‐phase peptide synthesis. Alternatively, peptides were synthesized using Fmoc‐Cys(Mob)‐OH, followed by subsequent oxidation within peptides of the thioether to the Mob sulfone via H2O2 and catalytic niobium carbide. Deprotection of peptides under strongly acidic conditions (50% triflic acid, 45% trifluoroacetic acid, 5% water) generated peptides with cysteine sulfinic acid. This approach was applied to the synthesis of peptides containing cysteine sulfinic acid within diverse peptide sequence contexts. [ABSTRACT FROM AUTHOR]

Large animals provide crucial seed dispersal services, yet face continued threats and are susceptible to changes in landscape composition and configuration. Thus, there is a growing imperative to improve understanding of animal‐generated seed dispersal using models that incorporate spatial complexity in a realistic, yet tractable, way.We developed a spatially explicit agent‐based seed dispersal model, with disperser movements informed by biotelemetry data, to evaluate how landscape composition and configuration affect seed dispersal patterns. We illustrated this approach for the world's second largest ratite, the emu (Dromaius novaehollandiae), a highly mobile generalist frugivore considered an important long‐distance disperser for many plant species across Australia.When animal movement is unrestricted, model parameters related to seed gut passage largely determine seed dispersal kernels. However, as habitat loss and fragmentation increase, the extent of long‐distance dispersal events is reduced and seed shadows became progressively more aggregated. This effect is due to the emu not being able to move between disconnected parts of the landscape, with small changes in habitat structure causing decreased long‐distance dispersal.We simulated seed dispersal patterns generated by three commonly used generic models of animal movement – unbiased and biased correlated random walks and Lévy walks – to evaluate how different representations of movement affect estimations of animal movements and emergent seed dispersal patterns. Simulated movements informed by the emu biotelemetry data resulted in longer median seed dispersal distances than do the three generic models.Synthesis. Changes in landscape composition and configuration can dramatically alter patterns of zoochorous seed dispersal as they influence animal movement. However, when models are used to simulate the patterns of seed dispersal, decisions about how animal movement is represented also affect estimates of seed dispersal. [ABSTRACT FROM AUTHOR]

Researchers have taken a number of different approaches in their exploration of hippocampal function. One approach seeks to describe hippocampal function by probing the memory representations that the hippocampus supports. Another approach focuses on the role of the hippocampus in pattern separation and completion. Each of these approaches to understanding hippocampal function utilizes a distinct set of specialized tasks, and both of these task sets are known to be sensitive to changes in hippocampal function with age and disease status. But the question remains whether the tasks utilized in these two approaches tap into the same aspects of hippocampal function. We explored this question in the context of hippocampal development. Preadolescent children (N = 73) and young adults (N = 41) completed an identical battery of cognitive tasks consisting of a spatial reconstruction relational memory task, the mnemonic similarity task (MST)—an object‐based pattern separation task, and a novel hybrid task—the Object Discrimination and Distribution (ODD) Task—designed to integrate and simultaneously tax pattern separation and spatial relational memory. Children did not demonstrate impairments in lure discrimination relative to young adults on either the object‐based pattern separation task or for aspects of the ODD task that required pattern separation in the absence of relational memory demands but performed more poorly across aspects of tasks that required relational binding. [ABSTRACT FROM AUTHOR]

"Peacock Bass: Diversity, Ecology and Conservation" is a comprehensive reference guide on the peacock bass genus Cichla spp. The book combines scientific knowledge with personal experiences to provide a vivid and engaging narrative about the species and their habitats. It includes colorful photos, gyotaku prints, and illustrations to enhance the reader's understanding and appreciation of the subject. Each chapter focuses on a specific Cichla species, providing detailed information on their taxonomy, distribution, natural history, and ecology. The book also discusses the evolutionary relationships, zoogeography, and conservation of the genus. It is a valuable resource for researchers, managers, anglers, and anyone interested in peacock bass and their conservation. [Extracted from the article]

Innovations in clinical pharmacy education have advanced patient‐centered care knowledge in skills of pharmacy graduates through the use of simulation, virtual reality, and gaming. Pharmacy schools and colleges, as well as health care institutions, have adopted simulation education in various clinical education formats for all levels of learners and practitioners. Over the past 15 years, the University of Pittsburgh School of Pharmacy has embraced innovative approaches to learning and documented advancement of clinical pharmacy education. This brief report will discuss advances in national and international pharmacy education, as well as the PittPharmacy experience with simulation education. A particular emphasis is on human patient simulation, computer‐based simulation, virtual patient, and gaming in the settings of direct patient care‐related education and assessment. The available literature and the experience at PittPharmacy shows improvement in learner satisfaction, knowledge enhancement, critical thinking skills, and problem solving in patient care topics. The evidence included provides support for the use of simulation to advance clinical pharmacy education and can serve to encourage further scholarship in this area. [ABSTRACT FROM AUTHOR]

4‐Substitution on proline directly impacts protein main chain conformational preferences. The structural effects of N‐acyl substitution and of 4‐substitution were examined by NMR spectroscopy and X‐ray crystallography on minimal molecules with a proline 4S‐nitrobenzoate. The effects of N‐acyl substitution on conformation were attenuated in the 4S‐nitrobenzoate context, due to the minimal role of the n→π* interaction in stabilizing extended conformations. By X‐ray crystallography, an extended conformation was observed for most molecules. The formyl derivative adopted a δ conformation that is observed at the i+2 position of β‐turns. Computational analysis indicated that the structures observed crystallographically represent the inherent conformational preferences of 4S‐substituted prolines with electron‐withdrawing 4‐position substituents. The divergent conformational preferences of 4R‐ and 4S‐substituted prolines suggest their wider structure‐specific application in molecular design. In particular, the proline endo ring pucker favored by 4S‐substituted prolines uniquely promotes the δ conformation [(ϕ, ψ) ≈(−80°, 0°)] found in β‐turns. In contrast to other acyl capping groups, the pivaloyl group strongly promoted trans amide bond and polyproline II helix conformation, with a close n→π* interaction in the crystalline state, despite the endo ring pucker, suggesting its special capabilities in promoting compact conformations in ϕ due to its strongly electron‐donating character. [ABSTRACT FROM AUTHOR]

Disruption of seed dispersal processes may affect plant population spatial structure. We used a spatial simulation model and an empirical case study to assess the conditions under which the loss of seed dispersers has a detectable effect on a species' spatial pattern. Our simulation experiments suggested that detecting spatial change following disperser loss will be difficult, except when rates of fruit removal are initially high and then completely disappear. To contextualize the simulation modeling, we used spatial point pattern analyses to characterize the spatial pattern of two large‐seeded species (Leucopogon nutans, a fire‐killed seeder shrub and Macrozamia riedlei, a long‐lived, resprouting cycad) in the jarrah (Eucalyptus marginata) forests of southwestern Australia. The plant species' primary disperser, the emu (Dromaius novaehollandiae), was absent from one of the sites we considered, but present at the other two. There was no detectable difference for either plant species in the strength of aggregation between sites with and without emu. However, even if disperser loss may not greatly affect local spatial structure for most plant species, it is likely to be important for long distance dispersal and genetic structuring of populations, so accurate characterization of the dispersal kernel is critical, especially in terms of plant emigration. [ABSTRACT FROM AUTHOR]

Trait divergence between populations is considered an adaptive response to different environments, but to what extent this response is accompanied by genetic differentiation is less clear since it may be phenotypic plasticity. In this study, we analyzed phenotypic variation between two Banksia attenuata growth forms, lignotuberous (shrub) and epicormic resprouting (tree), in fire‐prone environments to identify the environmental factors that have driven this phenotypic divergence. We linked genotype with phenotype and traced candidate genes using differential gene expression analysis. Fire intervals determined the phenotypic divergence between growth forms in B. attenuata. A genome‐wide association study identified 69 single nucleotide polymorphisms, putatively associated with growth form, whereas no growth form‐ or phenotype‐specific genotypes were identified. Genomic differentiation between the two growth forms was low (Fst = 0.024). Differential gene expression analysis identified 37 genes/transcripts that were differentially expressed in the two growth forms. A small heat‐shock protein gene, associated with lignotuber presence, was differentially expressed in the two forms. We conclude that different fire regimes induce phenotypic polymorphism in B. attenuata, whereas phenotypic trait divergence involves the differential expression of a small fraction of genes that interact strongly with the disturbance regime. Thus, phenotypic plasticity among resprouters is the general strategy for surviving varying fire regimes. Banksia attenuata has tree and shrub growth forms in ecosystems with frequent fire as an ecological disturbance in southwestern Australia. The divergence in growth form is determined by fire frequency in their habitats and by the differential expression of a small number of genes that interact with the disturbance regime. [ABSTRACT FROM AUTHOR]

Contemporary climate change in Alaska has resulted in amplified rates of press and pulse disturbances that drive ecosystem change with significant consequences for socio‐environmental systems. Despite the vulnerability of Arctic and boreal landscapes to change, little has been done to characterize landscape change and associated drivers across northern high‐latitude ecosystems. Here we characterize the historical sensitivity of Alaska's ecosystems to environmental change and anthropogenic disturbances using expert knowledge, remote sensing data, and spatiotemporal analyses and modeling. Time‐series analysis of moderate—and high‐resolution imagery was used to characterize land‐ and water‐surface dynamics across Alaska. Some 430,000 interpretations of ecological and geomorphological change were made using historical air photos and satellite imagery, and corroborate land‐surface greening, browning, and wetness/moisture trend parameters derived from peak‐growing season Landsat imagery acquired from 1984 to 2015. The time series of change metrics, together with climatic data and maps of landscape characteristics, were incorporated into a modeling framework for mapping and understanding of drivers of change throughout Alaska. According to our analysis, approximately 13% (~174,000 ± 8700 km2) of Alaska has experienced directional change in the last 32 years (±95% confidence intervals). At the ecoregions level, substantial increases in remotely sensed vegetation productivity were most pronounced in western and northern foothills of Alaska, which is explained by vegetation growth associated with increasing air temperatures. Significant browning trends were largely the result of recent wildfires in interior Alaska, but browning trends are also driven by increases in evaporative demand and surface‐water gains that have predominately occurred over warming permafrost landscapes. Increased rates of photosynthetic activity are associated with stabilization and recovery processes following wildfire, timber harvesting, insect damage, thermokarst, glacial retreat, and lake infilling and drainage events. Our results fill a critical gap in the understanding of historical and potential future trajectories of change in northern high‐latitude regions. Arctic and boreal landscapes have experienced unprecedented changes in recent decades that have significant consequences for socio‐environmental systems. Despite a legacy of studies that have documented the heightened sensitivity of northern landscapes to change, characterization and prognosis of ecosystem change has remained elusive. Here, we combine remote sensing and climate reanalysis data into an integrated modeling framework to fingerprint the historical (1984–2015) sensitivity of Alaska's ecosystems to changing environmental conditions and disturbances. Our results fill a critical gap in the understanding of the historical and potential future trajectories of change in Alaska, with direct relevance to other northern high‐latitude regions. [ABSTRACT FROM AUTHOR]

Abstract: Wetlands are critical terrestrial ecosystems in Alaska, covering ~177,000 km2, an area greater than all the wetlands in the remainder of the United States. To assess the relative influence of changing climate, atmospheric carbon dioxide (CO2) concentration, and fire regime on carbon balance in wetland ecosystems of Alaska, a modeling framework that incorporates a fire disturbance model and two biogeochemical models was used. Spatially explicit simulations were conducted at 1‐km resolution for the historical period (1950–2009) and future projection period (2010–2099). Simulations estimated that wetland ecosystems of Alaska lost 175 Tg carbon (C) in the historical period. Ecosystem C storage in 2009 was 5,556 Tg, with 89% of the C stored in soils. The estimated loss of C as CO2 and biogenic methane (CH4) emissions resulted in wetlands of Alaska increasing the greenhouse gas forcing of climate warming. Simulations for the projection period were conducted for six climate change scenarios constructed from two climate models forced under three CO2 emission scenarios. Ecosystem C storage averaged among climate scenarios increased 3.94 Tg C/yr by 2099, with variability among the simulations ranging from 2.02 to 4.42 Tg C/yr. These increases were driven primarily by increases in net primary production (NPP) that were greater than losses from increased decomposition and fire. The NPP increase was driven by CO2 fertilization (~5% per 100 parts per million by volume increase) and by increases in air temperature (~1% per °C increase). Increases in air temperature were estimated to be the primary cause for a projected 47.7% mean increase in biogenic CH4 emissions among the simulations (~15% per °C increase). Ecosystem CO2 sequestration offset the increase in CH4 emissions during the 21st century to decrease the greenhouse gas forcing of climate warming. However, beyond 2100, we expect that this forcing will ultimately increase as wetland ecosystems transition from being a sink to a source of atmospheric CO2 because of (1) decreasing sensitivity of NPP to increasing atmospheric CO2, (2) increasing availability of soil C for decomposition as permafrost thaws, and (3) continued positive sensitivity of biogenic CH4 emissions to increases in soil temperature. [ABSTRACT FROM AUTHOR]

Gaucher disease (GD) is associated with an increased risk for malignancies. Next to hematological malignancies, the development of solid tumors in several organs has been described. The liver is one of the major storage sites involved in GD pathogenesis, and is also affected by liver-specific complications. In this case series, we describe 16 GD type 1 (GD1) patients from eight different referral centers around the world who developed hepatocellular carcinoma (HCC). Potential factors contributing to the increased HCC risk in GD patients are studied. Eleven patients had undergone a splenectomy in the past. Liver cirrhosis, one of the main risk factors for the development of HCC, was present in nine out of 14 patients for whom data was available. Three out of seven examined patients showed a transferrin saturation > 45%. In these three patients the presence of iron overload after histopathological examination of the liver was shown. Chronic hepatitis C infection was present in three of 14 examined cases. We summarized all findings and made a comparison to the literature. We recommend that GD patients, especially those with prior splenectomy or iron overload, be evaluated for signs of liver fibrosis and if found to be monitored for HCC development. [ABSTRACT FROM AUTHOR]

Background: The authors hypothesized that patients with metastatic colorectal cancer (mCRC) who had tumors with low thymidylate synthase (TS-L) expression would have a higher response rate to combined 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) plus bevacizumab (FOLFOX/Bev) than those with high TS (TS-H) expression and that combined irinotecan and oxaliplatin (IROX) plus bevacizumab (IROX/Bev) would be more effective than FOLFOX/Bev in those with TS-H tumors.Methods: TS protein expression was determined in mCRC tissue. Patients who had TS-L tumors received FOLFOX/Bev, and those who had TS-H tumors were randomly assigned to receive either FOLFOX/Bev or IROX/Bev. The primary endpoint was the response rate (complete plus partial responses).Results: In total, 211 of 247 patients (70% TS-H) were registered to the treatment phase. Efficacy analyses included eligible patients who had started treatment (N = 186). The response rates for patients who received IROX/Bev (TS-H), FOLFOX/Bev (TS-H), and FOLFOX/Bev (TS-L) were 33%, 38%, and 49%, respectively (P = nonsignificant). The median progression-free survival (PFS) was 10 months (95% confidence interval [CI], 9-12 months; 10 months in the IROX/Bev TS-H group, 9 months in the FOLFOX/Bev TS-H group, and 13 months in the FOLFOX/Bev TS-L group). The TS-L group had improved PFS compared with the TS-H group that received FOLFOX/Bev (hazard ratio, 1.6; 95% CI, 1.0%-2.4%; P = .04; Cox regression). The median overall survival (OS) was 22 months (95% CI, 20 29 months; 18 months in the IROX/Bev TS-H group, 21 months in the FOLFOX/Bev TS-H group, and 32 months in the TS-L group). OS comparisons for the 2 TS-H arms and for the FOLFOX/Bev TS-H versus TS-L arms were not significantly different.Conclusions: TS expression was prognostic: Patients with TS-L tumors who received FOLFOX/Bev had a longer PFS than those with TS-H tumors, along with a trend toward longer OS. Patients with TS-H tumors did not benefit more from IROX/Bev than from FOLFOX/Bev. Cancer 2018;124:688-97. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]