Search

Leaf litter in coastal wetlands lays the foundation for carbon storage, and the creation of coastal wetland soils. As climate change alters the biogeochemical conditions and macrophyte composition of coastal wetlands, a better understanding of the interactions between microbial communities, changing chemistry, and leaf litter is required to understand the dynamics of coastal litter breakdown in changing wetlands. Coastal wetlands are dynamic systems with shifting biogeochemical conditions, with both tidal and seasonal redox fluctuations, and marine subsidies to inland habitats. Here, we investigated gene expression associated with various microbial redox pathways to understand how changing conditions are affecting the benthic microbial communities responsible for litter breakdown in coastal wetlands. We performed a reciprocal transplant of leaf litter from four distinct plant species along freshwater-to-marine gradients in the Florida Coastal Everglades, tracking changes in environmental and litter biogeochemistry, as well as benthic microbial gene expression associated with varying redox conditions, carbon degradation, and phosphorus acquisition. Early litter breakdown varied primarily by species, with highest breakdown in coastal species, regardless of the site they were at during breakdown, while microbial gene expression showed a strong seasonal relationship between sulfate cycling and salinity, and was not correlated with breakdown rates. The effect of salinity is likely a combination of direct effects, and indirect effects from associated marine subsidies. We found a positive correlation between sulfate uptake and salinity during January with higher freshwater inputs to coastal areas. However, we found a peak of dissimilatory sulfate reduction at intermediate salinity during April when freshwater inputs to coastal sites are lower. The combination of these two results suggests that sulfate acquisition is limiting to microbes when freshwater inputs are high, but that when marine influence increases and sulfate becomes more available, dissimilatory sulfate reduction becomes a key microbial process. As marine influence in coastal wetlands increases with climate change, our study suggests that sulfate dynamics will become increasingly important to microbial communities colonizing decomposing leaf litter., (© 2024 The Author(s). Ecology published by Wiley Periodicals LLC on behalf of The Ecological Society of America.)

We report the bottom-up synthesis of colloidal two-dimensional (2D) layered silicon carbide (SiC) quantum dots with a cubic structure, lateral size of 5-10 nm, ⟨110⟩ exfoliation to few atomic layers, and surface passivation with 1-dodecene. Samples shielded from oxygen and plasma-annealed for purity exhibit narrow blue photoluminescence (PL) with quantum yields (QYs) over 60% in exceptional cases, while unshielded nanocrystals (NCs) exhibit broad blue/green/white PL with 10-15% QY. The latter scenario is attributed to excess surface carbon and oxygen accrued during synthesis and processing, with size separation through ultracentrifugation revealing size-dependent impurity emission. In contrast, the shape of the bright narrow blue PL shows little variation with NC size, while in both scenarios, the maximum QY occurs near four atomic layers. When dried under heat, the disk-like NC suspensions are observed to aggregate into microscale domains, with further self-assembly into planar superlattice domains with common crystalline orientation. The results are compared with photophysical simulations and bring clarity to the broad emission commonly reported for top-down approaches, while inspiring bottom-up schemes directed at improved material quality.

Multiple acyl-CoA dehydrogenase deficiency (MADD) is a primary mitochondrial dysfunction affecting mitochondrial fatty acid and protein metabolism, caused by biallelic pathogenic variants in ETFA, ETFB, or ETFDH genes. The heterogeneous phenotypes associated with MADD have been classified into three groups: neonatal onset with congenital anomalies (type 1), neonatal onset without congenital anomalies (type 2), and attenuated and/or later onset (type 3). Here, we present two cases with biochemical profiles mimicking late-onset MADD but negative genetic testing, associated with the use of sertraline, a commonly used antidepressant. Case 1 is a 22 yo woman diagnosed with depression and profound fatigue who was referred to the metabolic clinic because of carnitine deficiency and a plasma acylcarnitine profile with a MADD-like pattern. Case 2 is a 61 yo woman with a history of chronic fatigue who was admitted to the emergency department with difficulty swallowing, metabolic acidosis, and mild rhabdomyolysis. Plasma acylcarnitine profile showed a MADD-like pattern. The muscle biopsy revealed lipid droplet accumulation and proliferation of mitochondria with abnormal osmiophilic inclusions, and a biochemical assay of the respiratory chain showed a deficit in complex II activity. In both cases, urine organic acid profile was normal, and genetic tests did not detect variants in the genes involved in MADD. Sertraline was on their list of medications and considering its association with inhibition of mitochondrial function and rhabdomyolysis, the team recommended the discontinuation under medical supervision. In Case 1 after discontinuation, the plasma acylcarnitine test normalized, only to return abnormal when the patient resumed sertraline. In Case 2, after sertraline was discontinued rhabdomyolysis resolved, and the muscle biopsy and biochemical assay of the respiratory chain normalized. Although sertraline is considered a safe drug, these two cases suggest that the use of sertraline may be associated with a potentially reversible form of mitochondrial dysfunction mimicking MADD. Further studies are needed to confirm and estimate the risk of MADD-like presentations with the use of sertraline, as well as identifying additional contributing factors, including genetic factors. Metabolic physicians should consider sertraline use in the differential diagnosis of MADD, particularly when genetic testing is negative., Competing Interests: None., (© 2024 The Authors. Published by Elsevier Inc.)

The mild hypothermia response (MHR) maintains organismal homeostasis during cold exposure and is thought to be critical for the neuroprotection documented with therapeutic hypothermia. To date, little is known about the transcriptional regulation of the MHR. We utilize a forward CRISPR-Cas9 mutagenesis screen to identify the histone lysine methyltransferase SMYD5 as a regulator of the MHR. SMYD5 represses the key MHR gene SP1 at euthermia. This repression correlates with temperature-dependent levels of histone H3 lysine 26 trimethylation (H3K36me3) at the SP1 locus and globally, indicating that the mammalian MHR is regulated at the level of histone modifications. We have identified 37 additional SMYD5-regulated temperature-dependent genes, suggesting a broader MHR-related role for SMYD5. Our study provides an example of how histone modifications integrate environmental cues into the genetic circuitry of mammalian cells and provides insights that may yield therapeutic avenues for neuroprotection after catastrophic events., Competing Interests: Declaration of interests H.T.B. is a consultant for Mahzi Therapeutics and founder of Kaldur Therapeutics. S.R. and H.T.B. have a European patent application (23167505.9) on a therapeutic strategy to activate the MHR., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: To investigate subconjunctival administration of a single-stranded, adeno-associated virus, serotype 2, engineered to express stanniocalcin-1 with a FLAG tag (ssAAV2-STC-1-FLAG) as a novel sustained (IOP) lowering agent with a reduced ocular surface side effect profile., Design: In vivo preclinical investigation in mice., Subjects: C57BL/6J, DBA/2J, prostaglandin F (FP) receptor knockout mice., Methods: Normotensive C57BL/6J mice were treated with a subconjunctival injection of ssAAV2-STC-1-FLAG (2 μL; 6 × 10 9 viral genomes [VGs]) in 1 eye and the same volume and concentration of ssAAV2-green fluorescent protein (GFP) or the same volume of phosphate-buffered saline in the fellow eye. Ocular hypertensive DBA/2J mice were subconjunctivally injected with 6 × 10 9 VGs of ssAAV2-STC-1-FLAG or ssAAV2-GFP. Steroid-mediated ocular hypertension was induced in C57BL/6J mice with weekly injections of dexamethasone into the conjunctival fornix, and mice were then injected subconjunctivally with 6 × 10 9 VGs of ssAAV2-STC-1-FLAG or ssAAV2-GFP. Prostaglandin F receptor knockout mice were injected subconjunctivally with 6 × 10 9 VGs of ssAAV2-STC-1-FLAG or phosphate-buffered saline. An identical vector was constructed without the FLAG tag (ssAAV2-STC-1) and evaluated in normotensive C57BL/6J mice. Intraocular pressure was assessed using the Tonolab tonometer for all experiments. Tumor necrosis factor alpha (TNFα), a marker of ocular surface inflammation, was compared between subconjunctivally delivered ssAAV2-STC-1-FLAG and other treatments including daily topical latanoprost., Main Outcome Measures: Intraocular pressure assessment., Results: Subconjunctival delivery of ssAAV2-STC-1-FLAG significantly reduced IOP for 10 weeks post injection in normotensive mice. Maximal IOP reduction was seen at week 3 postinjection (17.4%; 17.1 ± 0.8 vs. 14.1 ± 0.8 mmHg, P  < 0.001). After the IOP-lowering effect had waned, a second injection restored the ocular hypotensive effect. Subconjunctivally delivered ssAAV2-STC-1-FLAG lowered IOP in DBA/2J mice (16.9%; 17.8 ± 2.0 vs. 14.8 ± 0.9 mmHg, P  < 0.001) and steroid-mediated ocular hypertensive mice (20.0%; 19.0 ± 0.6 vs. 15.2 ± 0.7 mmHg, P < 0.001) over the experimental period. This construct also reduced IOP to a similar extent in wild-type (15.9%) and FP receptor knockout (15.7%) mice compared with the fellow eye. A related construct also lowered IOP without the FLAG tag in a similar manner. Reduction in conjunctival TNFα was seen when comparing subconjunctivally delivered ssAAV2-STC-1-FLAG to daily topical latanoprost., Conclusions: Subconjunctival delivery of the STC-1 transgene with a vector system may represent a novel treatment strategy for sustained IOP reduction and improved ocular tolerability that also avoids the daily dosing requirements of currently available medications., Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (© 2024 by the American Academy of Ophthalmology.)

Understanding the distribution of hundreds of thousands of plant metabolites across the plant kingdom presents a challenge. To address this, we curated publicly available LC-MS/MS data from 19,075 plant extracts and developed the plantMASST reference database encompassing 246 botanical families, 1,469 genera, and 2,793 species. This taxonomically focused database facilitates the exploration of plant-derived molecules using tandem mass spectrometry (MS/MS) spectra. This tool will aid in drug discovery, biosynthesis, (chemo)taxonomy, and the evolutionary ecology of herbivore interactions.

Objective: To examine the influence of dynamic and trending descriptive norms on increasing physical activity and decreasing the sedentary behaviors of university students while on campus., Participants: One-hundred fifty-six university students from a Canadian university completed this study., Methods: Participants were randomly assigned to receive one of four online messages containing normative information about the on-campus behavior of university students. On-campus physical activity and sedentary behavior were measured pre- and post-message., Results: The results revealed that students exposed to the trending norm reported a greater decrease in sedentary behavior than students in the control condition, p  = .007., Conclusion: Results provide preliminary experimental evidence that trending norm messages may serve to decrease the sedentary behavior of students while on campus.

Numerous studies have shown reduced performance in plants that are surrounded by neighbours of the same species 1,2 , a phenomenon known as conspecific negative density dependence (CNDD) 3 . A long-held ecological hypothesis posits that CNDD is more pronounced in tropical than in temperate forests 4,5 , which increases community stabilization, species coexistence and the diversity of local tree species 6,7 . Previous analyses supporting such a latitudinal gradient in CNDD 8,9 have suffered from methodological limitations related to the use of static data 10-12 . Here we present a comprehensive assessment of latitudinal CNDD patterns using dynamic mortality data to estimate species-site-specific CNDD across 23 sites. Averaged across species, we found that stabilizing CNDD was present at all except one site, but that average stabilizing CNDD was not stronger toward the tropics. However, in tropical tree communities, rare and intermediate abundant species experienced stronger stabilizing CNDD than did common species. This pattern was absent in temperate forests, which suggests that CNDD influences species abundances more strongly in tropical forests than it does in temperate ones 13 . We also found that interspecific variation in CNDD, which might attenuate its stabilizing effect on species diversity 14,15 , was high but not significantly different across latitudes. Although the consequences of these patterns for latitudinal diversity gradients are difficult to evaluate, we speculate that a more effective regulation of population abundances could translate into greater stabilization of tropical tree communities and thus contribute to the high local diversity of tropical forests., (© 2024. The Author(s).)

Objectives: Ring chromosome 14 is a rarely observed chromosomal abnormality characterized by a circular, ring-like appearance in one or both copies of chromosome 14. Ring chromosome 14 syndrome (OMIM #616606) is marked by global developmental delays, drug-resistant epilepsy, microcephaly, and ocular abnormalities. To date, fewer than 100 cases of ring chromosome 14 syndrome have been described in the medical literature. We describe a case of ring chromosome 14 and its clinical presentation in a 10-year-old female, adding to the literature about this rare condition., (Copyright© by the Association of Genetic Technologists.)

Background: Hip and knee arthritis are two of the most common conditions that result in referral to orthopaedic outpatient clinics. Many patients now use the internet to research their condition and to inform their decision about treatment options. This has implications for the process of informed consent., Aim: To assess the quality of patient information on the internet regarding hip and knee arthritis., Methods: 'Hip arthritis' and 'Knee arthritis' were entered as search terms into a popular search engine. To adjust for temporal variation, the process was repeated one month and one year later. Of the 200 results analysed, 83 websites met the inclusion criteria. The quality of patient information presented on these websites was assessed using a validated scoring instrument by two independent observers., Results: Most websites assessed were of poor quality; nearly half of all websites did not mention any risks or complications associated with surgical intervention for these conditions., Conclusions: As part of their professional obligation to provide a robust process of informed consent, clinicians should be aware of the variable quality of patient information available on the internet. As such, they should be prepared to advise their patients about quality websites where reliable information can be sought.

Background: RAB11B was described previously once with a severe form of intellectual disability. We aim at validation and delineation of the role of RAB11B in neurodevelopmental disorders., Methods: We present seven novel individuals with disease-associated variants in RAB11B when compared with the six cases described in the literature. We performed a cross-sectional analysis to identify the clinical spectrum and the core phenotype. Additionally, structural effects of the variants were assessed by molecular modeling., Results: Seven distinct de novo missense variants were identified, three of them recurrent (p.(Gly21Arg), p.(Val22Met), and p.(Ala68Thr)). Molecular modeling suggests that those variants either affect the nucleotide binding (at amino acid positions 21, 22, 33, 68) or the interaction with effector molecules (at positions 72 and 75). Our data confirmed the main manifestations as neurodevelopmental disorder with intellectual disability (85%), muscular hypotonia (83%), structural brain anomalies (77%), and visual impairment (70%). Combined analysis indicates a genotype-phenotype correlation; variants impacting the nucleotide binding cause a severe phenotype with intellectual disability, and variants outside the binding pocket lead to a milder phenotype with epilepsy., Conclusions: We confirm that disease-associated missense variants in RAB11B cause a neurodevelopmental disorder and suggest a genotype-phenotype correlation based on the impact on nucleotide binding functionality of RAB11B., Competing Interests: Declaration of competing interest T.B.P., R.E.S., and I.M.W. are employees of GeneDx, LLC. S.C.J. is supported by NIH/National Heart Lung and Blood Institute (NHLBI) Pathway to Independence award R00HL143036-02, the Clinical & Translational Research Funding Program award (CTSA1405), the Hydrocephalus Association Innovator Award, and the Cerebral Palsy Alliance Research Foundation Project Grant. The authors declare no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

One mechanism proposed to explain high species diversity in tropical systems is strong negative conspecific density dependence (CDD), which reduces recruitment of juveniles in proximity to conspecific adult plants. Although evidence shows that plant-specific soil pathogens can drive negative CDD, trees also form key mutualisms with mycorrhizal fungi, which may counteract these effects. Across 43 large-scale forest plots worldwide, we tested whether ectomycorrhizal tree species exhibit weaker negative CDD than arbuscular mycorrhizal tree species. We further tested for conmycorrhizal density dependence (CMDD) to test for benefit from shared mutualists. We found that the strength of CDD varies systematically with mycorrhizal type, with ectomycorrhizal tree species exhibiting higher sapling densities with increasing adult densities than arbuscular mycorrhizal tree species. Moreover, we found evidence of positive CMDD for tree species of both mycorrhizal types. Collectively, these findings indicate that mycorrhizal interactions likely play a foundational role in global forest diversity patterns and structure., (© 2023. Springer Nature Limited.)

Trees continuously regulate leaf physiology to acquire CO 2 while simultaneously avoiding excessive water loss. The balance between these two processes, or water use efficiency (WUE), is fundamentally important to understanding changes in carbon uptake and transpiration from the leaf to the globe under environmental change. While increasing atmospheric CO 2 (iCO 2 ) is known to increase tree intrinsic water use efficiency (iWUE), less clear are the additional impacts of climate and acidic air pollution and how they vary by tree species. Here, we couple annually resolved long-term records of tree-ring carbon isotope signatures with leaf physiological measurements of Quercus rubra (Quru) and Liriodendron tulipifera (Litu) at four study locations spanning nearly 100 km in the eastern United States to reconstruct historical iWUE, net photosynthesis (A net ), and stomatal conductance to water (g s ) since 1940. We first show 16%-25% increases in tree iWUE since the mid-20th century, primarily driven by iCO 2 , but also document the individual and interactive effects of nitrogen (NO x ) and sulfur (SO 2 ) air pollution overwhelming climate. We find evidence for Quru leaf gas exchange being less tightly regulated than Litu through an analysis of isotope-derived leaf internal CO 2 (C i ), particularly in wetter, recent years. Modeled estimates of seasonally integrated A net and g s revealed a 43%-50% stimulation of A net was responsible for increasing iWUE in both tree species throughout 79%-86% of the chronologies with reductions in g s attributable to the remaining 14%-21%, building upon a growing body of literature documenting stimulated A net overwhelming reductions in g s as a primary mechanism of increasing iWUE of trees. Finally, our results underscore the importance of considering air pollution, which remains a major environmental issue in many areas of the world, alongside climate in the interpretation of leaf physiology derived from tree rings., (© 2023 The Authors. Global Change Biology published by John Wiley & Sons Ltd.)

Within vascular plants, the partitioning of hydraulic resistance along the soil-to-leaf continuum affects transpiration and its response to environmental conditions. In trees, the fractional contribution of leaf hydraulic resistance (R leaf ) to total soil-to-leaf hydraulic resistance (R total ), or fR leaf (=R leaf /R total ), is thought to be large, but this has not been tested comprehensively. We compiled a multibiome data set of fR leaf using new and previously published measurements of pressure differences within trees in situ. Across 80 samples, fR leaf averaged 0.51 (95% confidence interval [CI] = 0.46-0.57) and it declined with tree height. We also used the allometric relationship between field-based measurements of soil-to-leaf hydraulic conductance and laboratory-based measurements of leaf hydraulic conductance to compute the average fR leaf for 19 tree samples, which was 0.40 (95% CI = 0.29-0.56). The in situ technique produces a more accurate descriptor of fR leaf because it accounts for dynamic leaf hydraulic conductance. Both approaches demonstrate the outsized role of leaves in controlling tree hydrodynamics. A larger fR leaf may help stems from loss of hydraulic conductance. Thus, the decline in fR leaf with tree height would contribute to greater drought vulnerability in taller trees and potentially to their observed disproportionate drought mortality., (© 2022 John Wiley & Sons Ltd.)

Plant recruitment interactions (i.e., what recruits under what) shape the composition, diversity, and structure of plant communities. Despite the huge body of knowledge on the mechanisms underlying recruitment interactions among species, we still know little about the structure of the recruitment networks emerging in ecological communities. Modeling and analyzing the community-level structure of plant recruitment interactions as a complex network can provide relevant information on ecological and evolutionary processes acting both at the species and ecosystem levels. We report a data set containing 143 plant recruitment networks in 23 countries across five continents, including temperate and tropical ecosystems. Each network identifies the species under which another species recruits. All networks report the number of recruits (i.e., individuals) per species. The data set includes >850,000 recruiting individuals involved in 118,411 paired interactions among 3318 vascular plant species across the globe. The cover of canopy species and open ground is also provided. Three sampling protocols were used: (1) The Recruitment Network (RN) protocol (106 networks) focuses on interactions among established plants ("canopy species") and plants in their early stages of recruitment ("recruit species"). A series of plots was delimited within a locality, and all the individuals recruiting and their canopy species were identified; (2) The paired Canopy-Open (pCO) protocol (26 networks) consists in locating a potential canopy plant and identifying recruiting individuals under the canopy and in a nearby open space of the same area; (3) The Georeferenced plot (GP) protocol (11 networks) consists in using information from georeferenced individual plants in large plots to infer canopy-recruit interactions. Some networks incorporate data for both herbs and woody species, whereas others focus exclusively on woody species. The location of each study site, geographical coordinates, country, locality, responsible author, sampling dates, sampling method, and life habits of both canopy and recruit species are provided. This database will allow researchers to test ecological, biogeographical, and evolutionary hypotheses related to plant recruitment interactions. There are no copyright restrictions on the data set; please cite this data paper when using these data in publications., (© 2022 The Authors. Ecology published by Wiley Periodicals LLC on behalf of The Ecological Society of America.)

Rising temperatures are influencing forests on many scales, with potentially strong variation vertically across forest strata. Using published research and new analyses, we evaluate how microclimate and leaf temperatures, traits, and gas exchange vary vertically in forests, shaping tree, and ecosystem ecology. In closed-canopy forests, upper canopy leaves are exposed to the highest solar radiation and evaporative demand, which can elevate leaf temperature (T leaf ), particularly when transpirational cooling is curtailed by limited stomatal conductance. However, foliar traits also vary across height or light gradients, partially mitigating and protecting against the elevation of upper canopy T leaf . Leaf metabolism generally increases with height across the vertical gradient, yet differences in thermal sensitivity across the gradient appear modest. Scaling from leaves to trees, canopy trees have higher absolute metabolic capacity and growth, yet are more vulnerable to drought and damaging T leaf than their smaller counterparts, particularly under climate change. By contrast, understory trees experience fewer extreme high T leaf 's but have fewer cooling mechanisms and thus may be strongly impacted by warming under some conditions, particularly when exposed to a harsher microenvironment through canopy disturbance. As the climate changes, integrating the patterns and mechanisms reviewed here into models will be critical to forecasting forest-climate feedback., (© 2022 Smithsonian Institution and The Authors. New Phytologist © 2022 New Phytologist Foundation.)

Exposure to stress triggers biological changes throughout the body. Accumulating evidence indicates that alterations in immune system function are associated with the development of stress-associated illnesses such as major depressive disorder and post-traumatic stress disorder, increasing interest in identifying immune markers that provide insight into mental health. Recombination events during T-cell receptor rearrangement and T-cell maturation in the thymus produce circular DNA fragments called T-cell receptor excision circles (TRECs) that can be utilized as indicators of thymic function and numbers of newly emigrating T-cells. Given data suggesting that stress affects thymus function, we examined whether blood levels of TRECs might serve as a quantitative peripheral index of cumulative stress exposure and its physiological correlates. We hypothesized that chronic stress exposure would compromise thymus function and produce corresponding decreases in levels of TRECs. In male mice, exposure to chronic social defeat stress (CSDS) produced thymic involution, adrenal hypertrophy, and decreased levels of TRECs in blood. Extending these studies to humans revealed robust inverse correlations between levels of circulating TRECs and childhood emotional and physical abuse. Cell-type specific analyses also revealed associations between TREC levels and blood cell composition, as well as cell-type specific methylation changes in CD4T + and CD8T + cells. Additionally, TREC levels correlated with epigenetic age acceleration, a common biomarker of stress exposure. Our findings demonstrate alignment between findings in mice and humans and suggest that blood-borne TRECs are a translationally-relevant biomarker that correlates with, and provides insight into, the cumulative physiological and immune-related impacts of stress exposure in mammals., (© 2022. The Author(s).)

We performed x-ray photoelectron spectroscopy measurements on a thin film of Si nanocrystals (SiNCs) while applying DC or AC external biases to extract the resistance and the capacitance of the thin film. The measurement consists of the application of 10 V DC or square wave pulses of 10 V amplitude to the sample at various frequencies ranging from 0.01 to 1 MHz while recording x-ray photoemission data. To analyze the data, we propose three different models with varying degrees of accuracy. The calculated capacitance of SiNCs agrees with the experimental value in the literature.

As the climate changes, warmer spring temperatures are causing earlier leaf-out 1-3 and commencement of CO 2 uptake 1,3 in temperate deciduous forests, resulting in a tendency towards increased growing season length 3 and annual CO 2 uptake 1,3-7 . However, less is known about how spring temperatures affect tree stem growth 8,9 , which sequesters carbon in wood that has a long residence time in the ecosystem 10,11 . Here we show that warmer spring temperatures shifted stem diameter growth of deciduous trees earlier but had no consistent effect on peak growing season length, maximum growth rates, or annual growth, using dendrometer band measurements from 440 trees across two forests. The latter finding was confirmed on the centennial scale by 207 tree-ring chronologies from 108 forests across eastern North America, where annual ring width was far more sensitive to temperatures during the peak growing season than in the spring. These findings imply that any extra CO 2 uptake in years with warmer spring temperatures 4,5 does not significantly contribute to increased sequestration in long-lived woody stem biomass. Rather, contradicting projections from global carbon cycle models 1,12 , our empirical results imply that warming spring temperatures are unlikely to increase woody productivity enough to strengthen the long-term CO 2 sink of temperate deciduous forests., (© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Ornithine transcarbamylase deficiency (OTCD) is an X-linked inborn error caused by loss of function variants in the OTC gene typically associated with severe neonatal hyperammonemia. Rare examples of late-onset OTCD have also been described. Here, we describe an OTC promoter variant, c.-106C>A, in a conserved HNF4a binding site, identified in two male siblings in Family 1 whose first and only recognized episodes of severe hyperammonemia occurred at ages 14 and 39 years, respectively. We identified the same OTC variant segregating in a large family with late-onset OTCD with variable expressivity (Family 2). We show that this OTC promoter variant reduces expression >5-fold in a dual-luciferase assay that tests promoter function. Addition of an upstream OTC enhancer increases expression of both the wild type and the c.-106C>A variant promoter constructs >5-fold with the mutant promoter still about fourfold lower than the wild type. Thus, in both contexts, the promoter variant results in substantially lower OTC expression. Under normal demand on urea cycle function, OTC expression in hemizygous males, although reduced, is sufficient to meet the demand for waste nitrogen excretion. However, in response to severe metabolic stress with attendant increased requirements on urea cycle function, the impaired promoter function results in inadequate OTC expression with resultant hyperammonemia. In the absence of precipitating events, hemizygotes with this allele are asymptomatic, explaining the late age of onset of hyperammonemia in affected individuals and the incomplete penetrance observed in some individuals in Family 2., (© 2022 SSIEM.)

Wiedemann-Steiner syndrome (WDSTS) is a neurodevelopmental disorder caused by de novo variants in KMT2A, which encodes a multi-domain histone methyltransferase. To gain insight into the currently unknown pathogenesis of WDSTS, we examined the spatial distribution of likely WDSTS-causing variants across the 15 different domains of KMT2A. Compared to variants in healthy controls, WDSTS variants exhibit a 61.9-fold overrepresentation within the CXXC domain-which mediates binding to unmethylated CpGs-suggesting a major role for this domain in mediating the phenotype. In contrast, we find no significant overrepresentation within the catalytic SET domain. Corroborating these results, we find that hippocampal neurons from Kmt2a-deficient mice demonstrate disrupted histone methylation (H3K4me1 and H3K4me3) preferentially at CpG-rich regions, but this has no systematic impact on gene expression. Motivated by these results, we combine accurate prediction of the CXXC domain structure by AlphaFold2 with prior biological knowledge to develop a classification scheme for missense variants in the CXXC domain. Our classifier achieved 92.6% positive and 92.9% negative predictive value on a hold-out test set. This classification performance enabled us to subsequently perform an in silico saturation mutagenesis and classify a total of 445 variants according to their functional effects. Our results yield a novel insight into the mechanistic basis of WDSTS and provide an example of how AlphaFold2 can contribute to the in silico characterization of variant effects with very high accuracy, suggesting a paradigm potentially applicable to many other Mendelian disorders., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: HTB is a consultant for Mahzi therapeutics. No other authors have any potential conflict of interest.

The factors driving therapy resistance in diffuse glioma remain poorly understood. To identify treatment-associated cellular and genetic changes, we analyzed RNA and/or DNA sequencing data from the temporally separated tumor pairs of 304 adult patients with isocitrate dehydrogenase (IDH)-wild-type and IDH-mutant glioma. Tumors recurred in distinct manners that were dependent on IDH mutation status and attributable to changes in histological feature composition, somatic alterations, and microenvironment interactions. Hypermutation and acquired CDKN2A deletions were associated with an increase in proliferating neoplastic cells at recurrence in both glioma subtypes, reflecting active tumor growth. IDH-wild-type tumors were more invasive at recurrence, and their neoplastic cells exhibited increased expression of neuronal signaling programs that reflected a possible role for neuronal interactions in promoting glioma progression. Mesenchymal transition was associated with the presence of a myeloid cell state defined by specific ligand-receptor interactions with neoplastic cells. Collectively, these recurrence-associated phenotypes represent potential targets to alter disease progression., Competing Interests: Declaration of interests R.G.W.V. is a co-founder of Boundless Bio and a consultant for Stellanova Therapeutics. M.K. has received research funding from AbbVie and Bristol Myers Squibb, and he is on the advisory board for Janssen; he has received honoraria from the Jackson Laboratory. D.R.O. has received funding from Integra and Agios. F.P.B. has performed consulting for Bristol Myers Squibb. M.W. has received research grants from AbbVie, Adastra, Apogenix, Merck, Sharp & Dohme, Novocure, and Quercis and honoraria for lectures or advisory board participation or consulting from AbbVie, Adastra, Basilea, Bristol Meyer Squibb, Celgene, Medac, Merck, Sharp & Dohme, Merck, Nerviano Medical Sciences, Novartis, Orbus, Philogen, Roche, Tocagen, and yMabs. A.M.E.W. reported receiving institutional financial support for an advisory role from Polyphor, IPSEN, Karyopharm, and Novartis; unrestricted research grants from IPSEN and Novartis; and study budgets from AbbVie, BMS, Genzyme, Karyopharm Therapeutics, and Roche, all outside the submitted work. H.K.G. has performed consulting for AbbVie, and he is a member of the speaker bureau for AbbVie and Igynta. K.P. is a scientific advisory board member and owns stock in Cue BioPharma., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Tree size shapes forest carbon dynamics and determines how trees interact with their environment, including a changing climate. Here, we conduct the first global analysis of among-site differences in how aboveground biomass stocks and fluxes are distributed with tree size. We analyzed repeat tree censuses from 25 large-scale (4-52 ha) forest plots spanning a broad climatic range over five continents to characterize how aboveground biomass, woody productivity, and woody mortality vary with tree diameter. We examined how the median, dispersion, and skewness of these size-related distributions vary with mean annual temperature and precipitation. In warmer forests, aboveground biomass, woody productivity, and woody mortality were more broadly distributed with respect to tree size. In warmer and wetter forests, aboveground biomass and woody productivity were more right skewed, with a long tail towards large trees. Small trees (1-10 cm diameter) contributed more to productivity and mortality than to biomass, highlighting the importance of including these trees in analyses of forest dynamics. Our findings provide an improved characterization of climate-driven forest differences in the size structure of aboveground biomass and dynamics of that biomass, as well as refined benchmarks for capturing climate influences in vegetation demographic models., (© 2022 The Authors. New Phytologist © 2022 New Phytologist Foundation.)

Glaucoma is the leading cause of irreversible blindness worldwide. Therapies for glaucoma are directed toward reducing intraocular pressure (IOP), the leading risk factor and only reliable therapeutic target via topical medications or with procedural intervention including laser or surgery. Though topical therapeutics are typically first line, less than 50% of patients take drops as prescribed. Sustained release technologies that decrease IOP for extended periods of time are being examined for clinical use. We recently identified Stanniocalcin-1, a naturally occurring hormone, as an IOP-lowering agent. Here, we show that a single injection into the anterior chamber of mice with an adeno-associated viral vector containing the transgene of stanniocalcin-1 results in diffuse and sustained expression of the protein and produces IOP reduction for up to 6 months. As the treatment effect begins to wane, IOP-lowering can be rescued with a repeat injection. Aqueous humor dynamic studies revealed an increase in outflow facility as the mechanism of action. This first-in-class therapeutic approach has the potential to improve care and reduce the rates of vision loss in the 80 million people worldwide currently affected by glaucoma., Competing Interests: The authors declare no competing interests.

The growth and survival of individual trees determine the physical structure of a forest with important consequences for forest function. However, given the diversity of tree species and forest biomes, quantifying the multitude of demographic strategies within and across forests and the way that they translate into forest structure and function remains a significant challenge. Here, we quantify the demographic rates of 1961 tree species from temperate and tropical forests and evaluate how demographic diversity (DD) and demographic composition (DC) differ across forests, and how these differences in demography relate to species richness, aboveground biomass (AGB), and carbon residence time. We find wide variation in DD and DC across forest plots, patterns that are not explained by species richness or climate variables alone. There is no evidence that DD has an effect on either AGB or carbon residence time. Rather, the DC of forests, specifically the relative abundance of large statured species, predicted both biomass and carbon residence time. Our results demonstrate the distinct DCs of globally distributed forests, reflecting biogeography, recent history, and current plot conditions. Linking the DC of forests to resilience or vulnerability to climate change, will improve the precision and accuracy of predictions of future forest composition, structure, and function., (© 2022 John Wiley & Sons Ltd.)

Purpose: To evaluate the effect of ATP-sensitive potassium channel openers cromakalim prodrug 1 (CKLP1) and diazoxide on IOP in three independent mouse models of ocular hypertension., Methods: Baseline IOP was measured in TGFβ2 overexpression, steroid-induced, and iris dispersion (DBA/2J) ocular hypertension mouse models, followed by once daily eyedrop administration with CKLP1 (5 mM) or diazoxide (5 mM). The IOP was measured in conscious animals with a handheld rebound tonometer. Aqueous humor dynamics were assessed by a constant perfusion method. Effect of treatment on ocular tissues was evaluated by transmission electron microscopy., Results: CKLP1 decreased the IOP by 20% in TGFβ2 overexpressing mice (n = 6; P < 0.0001), 24% in steroid-induced ocular hypertensive mice (n = 8; P < 0.0001), and 43% in DBA/2J mice (n = 15; P < 0.0001). Diazoxide decreased the IOP by 32% in mice with steroid-induced ocular hypertension (n = 13; P < 0.0001) and by 41% in DBA/2J mice (n = 4; P = 0.005). An analysis of the aqueous humor dynamics revealed that CKLP1 decreased the episcleral venous pressure by 29% in TGFβ2 overexpressing mice (n = 13; P < 0.0001) and by 72% in DBA/2J mice (n = 4 control, 3 treated; P = 0.0002). Diazoxide lowered episcleral venous pressure by 35% in steroid-induced ocular hypertensive mice (n = 3; P = 0.03). Tissue histology and cell morphology appeared normal when compared with controls. Accumulation of extracellular matrix was reduced in CKLP1- and diazoxide-treated eyes in the steroid-induced ocular hypertension model., Conclusions: ATP-sensitive potassium channel openers CKLP1 and diazoxide effectively decreased the IOP in ocular hypertensive animal models by decreasing the episcleral venous pressure, supporting a potential therapeutic application of these agents in ocular hypertension and glaucoma.

California's Cap-and-Trade Program sets a limit on the major sources of greenhouse gas emissions and allows a portion of excess emissions to be offset through purchase of credits for climate benefits accrued elsewhere. Badgley et al. (2021, Global Change Biology, https://doi.org/10.1111/gcb.15943) describe how the use of mean forest carbon stocks from ecological supersections can create perverse incentives for project developers, potentially leading to over-crediting and nonadditional offsets. Carbon markets remain a valuable tool in combating climate change, but ensuring projects' additionality is of critical importance to effective carbon mitigation. Badgley's article should serve as a call to action to redouble efforts at integrating the latest carbon science into effective and timely policy solutions., (© 2021 John Wiley & Sons Ltd.)

Tree rings provide an invaluable long-term record for understanding how climate and other drivers shape tree growth and forest productivity. However, conventional tree-ring analysis methods were not designed to simultaneously test effects of climate, tree size, and other drivers on individual growth. This has limited the potential to test ecologically relevant hypotheses on tree growth sensitivity to environmental drivers and their interactions with tree size. Here, we develop and apply a new method to simultaneously model nonlinear effects of primary climate drivers, reconstructed tree diameter at breast height (DBH), and calendar year in generalized least squares models that account for the temporal autocorrelation inherent to each individual tree's growth. We analyze data from 3811 trees representing 40 species at 10 globally distributed sites, showing that precipitation, temperature, DBH, and calendar year have additively, and often interactively, influenced annual growth over the past 120 years. Growth responses were predominantly positive to precipitation (usually over ≥3-month seasonal windows) and negative to temperature (usually maximum temperature, over ≤3-month seasonal windows), with concave-down responses in 63% of relationships. Climate sensitivity commonly varied with DBH (45% of cases tested), with larger trees usually more sensitive. Trends in ring width at small DBH were linked to the light environment under which trees established, but basal area or biomass increments consistently reached maxima at intermediate DBH. Accounting for climate and DBH, growth rate declined over time for 92% of species in secondary or disturbed stands, whereas growth trends were mixed in older forests. These trends were largely attributable to stand dynamics as cohorts and stands age, which remain challenging to disentangle from global change drivers. By providing a parsimonious approach for characterizing multiple interacting drivers of tree growth, our method reveals a more complete picture of the factors influencing growth than has previously been possible., (© 2021 The Authors. Global Change Biology published by John Wiley & Sons Ltd. This article has been contributed to by US Government employees and their work is in the public domain in the USA.)

Background: Intratumoral heterogeneity is a hallmark of diffuse gliomas. DNA methylation profiling is an emerging approach in the clinical classification of brain tumors. The goal of this study is to investigate the effects of intratumoral heterogeneity on classification confidence., Methods: We used neuronavigation to acquire 133 image-guided and spatially separated stereotactic biopsy samples from 16 adult patients with a diffuse glioma (7 IDH-wildtype and 2 IDH-mutant glioblastoma, 6 diffuse astrocytoma, IDH-mutant and 1 oligodendroglioma, IDH-mutant and 1p19q codeleted), which we characterized using DNA methylation arrays. Samples were obtained from regions with and without abnormalities on contrast-enhanced T1-weighted and fluid-attenuated inversion recovery MRI. Methylation profiles were analyzed to devise a 3-dimensional reconstruction of (epi)genetic heterogeneity. Tumor purity was assessed from clonal methylation sites., Results: Molecular aberrations indicated that tumor was found outside imaging abnormalities, underlining the infiltrative nature of this tumor and the limitations of current routine imaging modalities. We demonstrate that tumor purity is highly variable between samples and explains a substantial part of apparent epigenetic spatial heterogeneity. We observed that DNA methylation subtypes are often, but not always, conserved in space taking tumor purity and prediction accuracy into account., Conclusion: Our results underscore the infiltrative nature of diffuse gliomas and suggest that DNA methylation subtypes are relatively concordant in this tumor type, although some heterogeneity exists., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.)

Glioma intratumoral heterogeneity enables adaptation to challenging microenvironments and contributes to therapeutic resistance. We integrated 914 single-cell DNA methylomes, 55,284 single-cell transcriptomes and bulk multi-omic profiles across 11 adult IDH mutant or IDH wild-type gliomas to delineate sources of intratumoral heterogeneity. We showed that local DNA methylation disorder is associated with cell-cell DNA methylation differences, is elevated in more aggressive tumors, links with transcriptional disruption and is altered during the environmental stress response. Glioma cells under in vitro hypoxic and irradiation stress increased local DNA methylation disorder and shifted cell states. We identified a positive association between genetic and epigenetic instability that was supported in bulk longitudinally collected DNA methylation data. Increased DNA methylation disorder associated with accelerated disease progression and recurrently selected DNA methylation changes were enriched for environmental stress response pathways. Our work identified an epigenetically facilitated adaptive stress response process and highlights the importance of epigenetic heterogeneity in shaping therapeutic outcomes., (© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Deep-water access is arguably the most effective, but under-studied, mechanism that plants employ to survive during drought. Vulnerability to embolism and hydraulic safety margins can predict mortality risk at given levels of dehydration, but deep-water access may delay plant dehydration. Here, we tested the role of deep-water access in enabling survival within a diverse tropical forest community in Panama using a novel data-model approach. We inversely estimated the effective rooting depth (ERD, as the average depth of water extraction), for 29 canopy species by linking diameter growth dynamics (1990-2015) to vapor pressure deficit, water potentials in the whole-soil column, and leaf hydraulic vulnerability curves. We validated ERD estimates against existing isotopic data of potential water-access depths. Across species, deeper ERD was associated with higher maximum stem hydraulic conductivity, greater vulnerability to xylem embolism, narrower safety margins, and lower mortality rates during extreme droughts over 35 years (1981-2015) among evergreen species. Species exposure to water stress declined with deeper ERD indicating that trees compensate for water stress-related mortality risk through deep-water access. The role of deep-water access in mitigating mortality of hydraulically-vulnerable trees has important implications for our predictive understanding of forest dynamics under current and future climates., (No claim to original US Government works New Phytologist © 2021 New Phytologist Foundation.)

As climate change drives increased drought in many forested regions, mechanistic understanding of the factors conferring drought tolerance in trees is increasingly important. The dendrochronological record provides a window through which we can understand how tree size and traits shape growth responses to droughts. We analyzed tree-ring records for 12 species in a broadleaf deciduous forest in Virginia (USA) to test hypotheses for how tree height, microenvironment characteristics, and species' traits shaped drought responses across the three strongest regional droughts over a 60-yr period. Drought tolerance (resistance, recovery, and resilience) decreased with tree height, which was strongly correlated with exposure to higher solar radiation and evaporative demand. The potentially greater rooting volume of larger trees did not confer a resistance advantage, but marginally increased recovery and resilience, in sites with low topographic wetness index. Drought tolerance was greater among species whose leaves lost turgor (wilted) at more negative water potentials and experienced less shrinkage upon desiccation. The tree-ring record reveals that tree height and leaf drought tolerance traits influenced growth responses during and after significant droughts in the meteorological record. As climate change-induced droughts intensify, tall trees with drought-sensitive leaves will be most vulnerable to immediate and longer-term growth reductions., (© 2020 No claim to US Government works New Phytologist ©2020 New Phytologist Foundation.)

Ecology cannot yet fully explain why so many tree species coexist in natural communities such as tropical forests. A major difficulty is linking individual-level processes to community dynamics. We propose a combination of tree spatial data, spatial statistics and dynamical theory to reveal the relationship between spatial patterns and population-level interaction coefficients and their consequences for multispecies dynamics and coexistence. Here we show that the emerging population-level interaction coefficients have, for a broad range of circumstances, a simpler structure than their individual-level counterparts, which allows for an analytical treatment of equilibrium and stability conditions. Mechanisms such as animal seed dispersal, which result in clustering of recruits that is decoupled from parent locations, lead to a rare-species advantage and coexistence of otherwise neutral competitors. Linking spatial statistics with theories of community dynamics offers new avenues for explaining species coexistence and calls for rethinking community ecology through a spatial lens.

Ionizing radiation causes DNA damage and is a mainstay for cancer treatment, but understanding of its genomic impact is limited. We analyzed mutational spectra following radiotherapy in 190 paired primary and recurrent gliomas from the Glioma Longitudinal Analysis Consortium and 3,693 post-treatment metastatic tumors from the Hartwig Medical Foundation. We identified radiotherapy-associated significant increases in the burden of small deletions (5-15 bp) and large deletions (20+ bp to chromosome-arm length). Small deletions were characterized by a larger span size, lacking breakpoint microhomology and were genomically more dispersed when compared to pre-existing deletions and deletions in non-irradiated tumors. Mutational signature analysis implicated classical non-homologous end-joining-mediated DNA damage repair and APOBEC mutagenesis following radiotherapy. A high radiation-associated deletion burden was associated with worse clinical outcomes, suggesting that effective repair of radiation-induced DNA damage is detrimental to patient survival. These results may be leveraged to predict sensitivity to radiation therapy in recurrent cancer., (© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: Stress is implicated in the pathophysiology of major depression and posttraumatic stress disorder. These conditions share core features, including motivational deficits, heighted anxiety, and sleep dysregulation. Chronic stress produces these same features in rodents, with some individuals being susceptible or resilient, as seen in humans. While stress-induced neuroadaptations within the nucleus accumbens are implicated in susceptibility-related dysregulation of motivational and emotional behaviors, their effects on sleep are unclear., Methods: We used chemogenetics (DREADDs [designer receptors exclusively activated by designer drugs]) to examine the effects of selective alterations in activity of nucleus accumbens medium spiny neurons expressing dopamine D 1 receptors (D1-MSNs) or dopamine D 2 receptors (D2-MSNs) on sleep-related end points. Mice were implanted with wireless transmitters enabling continuous collection of data to quantify vigilance states over a 20-day test period. Parallel cohorts were examined in behavioral tests assessing stress susceptibility., Results: D1- and D2-MSNs play dissociable roles in sleep regulation. Stimulation of inhibitory or excitatory DREADDs expressed in D1-MSNs exclusively affects rapid eye movement sleep, whereas targeting D2-MSNs affects slow wave sleep. The combined effects of D1-MSN inhibition and D2-MSN activation on sleep resemble those of chronic social defeat stress. Alterations in D1-MSN function also affect stress susceptibility in social behavior tests. Elevation of CREB (cAMP response element-binding protein) within D1-MSNs is sufficient to produce stress-like effects on rapid eye movement sleep., Conclusions: In addition to regulation of motivational and emotional behaviors, the nucleus accumbens also influences sleep, an end point with high translational relevance. These findings provide a neural basis for comorbidity in key features of stress-related illness., (Copyright © 2021 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Carbon (C) fixation, allocation, and metabolism by trees set the basis for energy and material flows in forest ecosystems and define their interactions with Earth's changing climate. However, while many studies have considered variation in productivity with latitude and climate, we lack a cohesive synthesis on how forest carbon fluxes vary globally with respect to climate and one another. Here, we draw upon 1,319 records from the Global Forest Carbon Database, representing all major forest types and the nine most significant autotrophic carbon fluxes, to comprehensively review how annual C cycling in mature, undisturbed forests varies with latitude and climate on a global scale. Across all flux variables analyzed, rates of C cycling decreased continuously with absolute latitude-a finding that confirms multiple previous studies and contradicts the idea that net primary productivity of temperate forests rivals that of tropical forests. C flux variables generally displayed similar trends across latitude and multiple climate variables, with no differences in allocation detected at this global scale. Temperature variables in general, and mean annual temperature or temperature seasonality in particular, were the best single predictors of C flux, explaining 19%-71% of variation in the C fluxes analyzed. The effects of temperature were modified by moisture availability, with C flux reduced under hot and dry conditions and sometimes under very high precipitation. Annual C fluxes increased with growing season length and were also influenced by growing season climate. These findings clarify how forest C flux varies with latitude and climate on a global scale. In an era when forests will play a critical yet uncertain role in shaping Earth's rapidly changing climate, our synthesis provides a foundation for understanding global patterns in forest C cycling., (© 2021 John Wiley & Sons Ltd. This article has been contributed to by US Government employees and their work is in the public domain in the USA.)

The effects of climate change on tropical forests will depend on how diverse tropical tree species respond to drought. Current distributions of evergreen and deciduous tree species across local and regional moisture gradients reflect their ability to tolerate drought stress, and might be explained by functional traits. We measured leaf water potential at turgor loss (i.e. 'wilting point'; π tlp ), wood density (WD) and leaf mass per area (LMA) on 50 of the most abundant tree species in central Panama. We then tested their ability to explain distributions of evergreen and deciduous species within a 50 ha plot on Barro Colorado Island and across a 70 km rainfall gradient spanning the Isthmus of Panama. Among evergreen trees, species with lower π tlp were associated with drier habitats, with π tlp explaining 28% and 32% of habitat association on local and regional scales, respectively, greatly exceeding the predictive power of WD and LMA. In contrast, π tlp did not predict habitat associations among deciduous species. Across spatial scales, π tlp is a useful indicator of habitat preference for tropical tree species that retain their leaves during periods of water stress, and holds the potential to predict vegetation responses to climate change., (© 2021 The Authors. New Phytologist © 2021 New Phytologist Foundation.)

Annual influenza vaccination greatly reduces morbidity and mortality, but effectiveness remains sub-optimal. Weaknesses of current vaccines include low effectiveness against mismatched strains, lack of mucosal and other effective tissue-resident immune responses, weak cellular immune responses, and insufficiently durable immune responses. The safety and immunogenicity of NasoVAX, a monovalent intranasal influenza vaccine based on a replication-deficient adenovirus type 5 platform, were evaluated in a placebo-controlled single ascending-dose study. Sixty healthy adults (18-49 years) received a single intranasal dose of 1×10 9 viral particles (vp), 1 × 10 10 vp, or 1 × 10 11 vp of NasoVAX or placebo. NasoVAX was well-tolerated and elicited robust influenza-specific systemic and mucosal immune responses. The highest NasoVAX dose and the approved Fluzone ® influenza vaccine elicited comparable hemagglutination inhibition (HAI) geometric mean titers (152.8 vs. 293.4) and microneutralization (MN) geometric mean titers (142.5 vs. 162.8), with NasoVAX HAI titers maintained more than 1-year on average following a single dose. Hemagglutinin-specific T cells responses were also documented in peripheral mononuclear cell (PBMC) preparations. Consistent with the intranasal route of administration, NasoVAX elicited antigen-specific mucosal IgA responses in the nasopharyngeal cavity with an increase of approximately 2-fold over baseline GMT at the mid- and high-doses. In summary, NasoVAX appeared safe and elicited a broad immune response, including humoral, cellular, and mucosal immunity, with no impact of baseline anti-adenovirus antibody at the most immunogenic dose.

Atmospheric carbon dioxide concentration ([CO 2 ]) is increasing, which increases leaf-scale photosynthesis and intrinsic water-use efficiency. These direct responses have the potential to increase plant growth, vegetation biomass, and soil organic matter; transferring carbon from the atmosphere into terrestrial ecosystems (a carbon sink). A substantial global terrestrial carbon sink would slow the rate of [CO 2 ] increase and thus climate change. However, ecosystem CO 2 responses are complex or confounded by concurrent changes in multiple agents of global change and evidence for a [CO 2 ]-driven terrestrial carbon sink can appear contradictory. Here we synthesize theory and broad, multidisciplinary evidence for the effects of increasing [CO 2 ] (iCO 2 ) on the global terrestrial carbon sink. Evidence suggests a substantial increase in global photosynthesis since pre-industrial times. Established theory, supported by experiments, indicates that iCO 2 is likely responsible for about half of the increase. Global carbon budgeting, atmospheric data, and forest inventories indicate a historical carbon sink, and these apparent iCO 2 responses are high in comparison to experiments and predictions from theory. Plant mortality and soil carbon iCO 2 responses are highly uncertain. In conclusion, a range of evidence supports a positive terrestrial carbon sink in response to iCO 2 , albeit with uncertain magnitude and strong suggestion of a role for additional agents of global change., (© 2020 The Authors New Phytologist Foundation © 2020 New Phytologist.)

Tropical forests vary widely in biomass carbon (C) stocks and fluxes even after controlling for forest age. A mechanistic understanding of this variation is critical to accurately predicting responses to global change. We review empirical studies of spatial variation in tropical forest biomass, productivity and woody residence time, focusing on mature forests. Woody productivity and biomass decrease from wet to dry forests and with elevation. Within lowland forests, productivity and biomass increase with temperature in wet forests, but decrease with temperature where water becomes limiting. Woody productivity increases with soil fertility, whereas residence time decreases, and biomass responses are variable, consistent with an overall unimodal relationship. Areas with higher disturbance rates and intensities have lower woody residence time and biomass. These environmental gradients all involve both direct effects of changing environments on forest C fluxes and shifts in functional composition - including changing abundances of lianas - that substantially mitigate or exacerbate direct effects. Biogeographic realms differ significantly and importantly in productivity and biomass, even after controlling for climate and biogeochemistry, further demonstrating the importance of plant species composition. Capturing these patterns in global vegetation models requires better mechanistic representation of water and nutrient limitation, plant compositional shifts and tree mortality., (© 2020 The Authors New Phytologist © 2020 New Phytologist Foundation.)

In addition to being the most common sexually transmitted infection, the human papillomavirus (HPV) is associated with six types of cancer in men and women. The HPV vaccine provides long-lasting, effective protection from high-risk HPV infection, thus serving as a means of cancer prevention. An effective healthcare provider recommendation is well-established as the most significant influence on HPV vaccine uptake, and, as emerging providers, it is critical that medical students receive comprehensive training in this area. However, the type and extent of such training for current medical students in the USA is unclear. An online survey assessing HPV and HPV vaccine knowledge, attitudes, and vaccine status was distributed to all medical students at an Alabama university. Scales were developed to assess composite HPV and HPV knowledge scores and HPV vaccination intentions. Of those age-eligible, 32.1% reported completion of the HPV vaccine series while 15.2% reported partial completion. Knowledge of both HPV and HPV vaccination significantly increased with program year (p < 0.0001 and p = 0.0069, respectively); however, there were knowledge gaps across all years regarding HPV-associated cancers. Attitudes and intentions showed a similar association, with more advanced students demonstrating more positive attitudes toward HPV vaccination (p = 0.0003). There is a need within the current curriculum to include more education and training on HPV, HPV vaccination, and counseling-particularly for students in the first 2 years of their program. Implementation of a classroom module or interactive workshop would likely improve knowledge and attitudes, better preparing students for their future role as potential immunizers.

In some turtle species, temperature selection may be influenced by environmental conditions, including acclimation temperature and substrate quality. These factors may be particularly important for softshell turtles that are highly aquatic and often thermoregulate by burying in the substrate in shallow water microhabitats. We tested for effects of acclimation temperature (22 °C or 27 °C) and substrate type (sand or gravel) on the selected temperature and movement patterns of 20 juvenile spiny softhshell turtles (Apalone spinifera; Reptilia: Trionychidae) in an aquatic thermal gradient of 14-34 °C. Among 7-11 month old juvenile softshell turtles, acclimation temperature and substrate type did not influence temperature selection, nor alter activity and movement patterns. During thermal gradient tests, both 22- and 27 °C-acclimated turtles selected the warmest temperature (34 °C) available most frequently, regardless of substrate type (sand or gravel). Similarly, acclimation temperature and substrate type did not influence movement patterns of turtles, nor the number of chambers used in the gradient tests. These results suggest that juvenile Apalone spinifera are capable of detecting small temperature increments and prefer warm temperatures that may positively influence growth and metabolism, and that thermal factors more significantly influence aquatic thermoregulation in this species than does substrate type., (Copyright © 2020 Elsevier Ltd. All rights reserved.)