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Background: More than 20 million children in the United States lack access to primary health care. Practice Learning: Research shows that students with regular access to physical and mental health services have fewer absences, are more social, less likely to participate in risky behaviors, have improved focus and higher test scores. Implication For School Health Policy, Practice, And Equity: School‐based health centers (SBHCs) can be an important, valuable and viable health care delivery option to meet the full‐range of primary health care needs of students where they spend the majority of their wake hours, ie, in school. Children in rural and other underserved communities, as well as those underinsured, non‐insured, economically challenged, underserved, and the most vulnerable among us are especially at risk. Conclusions: This paper discusses the history, value, and importance of SBHCs from myriad perspectives, including physical and emotional wellbeing, academic and social success, and the promotion of a positive transition to adulthood. In addition, the authors' experiences that resulted in building the first SBHC in the Mid‐Hudson Valley Region of New York State are shared. These experiences form the foundation for creating an important roadmap for individuals and school leaders that are interested in bringing a SBHC to their school and district. [ABSTRACT FROM AUTHOR]

The mountains of Southwest China comprise a significant large mountain range and biodiversity hotspot imperiled by global climate change. The high species diversity in this mountain system has long been attributed to a complex set of factors, and recent large‐scale macroevolutionary investigations have placed a broad timeline on plant diversification that stretches from 10 million years ago (Mya) to the present. Despite our increasing understanding of the temporal mode of speciation, finer‐scale population‐level investigations are lacking to better refine these temporal trends and illuminate the abiotic and biotic influences of cryptic speciation. This is largely due to the dearth of organismal sampling among closely related species and populations, spanning the incredible size and topological heterogeneity of this region. Our study dives into these evolutionary dynamics of speciation using genomic and eco‐morphological data of Stellera chamaejasme L. We identified four previously unrecognized cryptic species having indistinct morphological traits and large metapopulation of evolving lineages, suggesting a more recent diversification (~2.67–0.90 Mya), largely influenced by Pleistocene glaciation and biotic factors. These factors likely influenced allopatric speciation and advocated cyclical warming–cooling episodes along elevational gradients during the Pleistocene. The study refines the evolutionary timeline to be much younger than previously implicated and raises the concern that projected future warming may influence the alpine species diversity, necessitating increased conservation efforts. [ABSTRACT FROM AUTHOR]

Summary: Anthropogenetic climate change has caused range shifts among many species. Species distribution models (SDMs) are used to predict how species ranges may change in the future. However, most SDMs rarely consider how climate‐sensitive traits, such as phenology, which affect individuals' demography and fitness, may influence species' ranges.Using > 120 000 herbarium specimens representing 360 plant species distributed across the eastern United States, we developed a novel 'phenology‐informed' SDM that integrates phenological responses to changing climates. We compared the ranges of each species forecast by the phenology‐informed SDM with those from conventional SDMs. We further validated the modeling approach using hindcasting.When examining the range changes of all species, our phenology‐informed SDMs forecast less species loss and turnover under climate change than conventional SDMs. These results suggest that dynamic phenological responses of species may help them adjust their ecological niches and persist in their habitats as the climate changes.Plant phenology can modulate species' responses to climate change, mitigating its negative effects on species persistence. Further application of our framework will contribute to a generalized understanding of how traits affect species distributions along environmental gradients and facilitate the use of trait‐based SDMs across spatial and taxonomic scales. [ABSTRACT FROM AUTHOR]

Sex differences in drug pharmacokinetics include variations in the expression of the cytochrome P450 enzymes, which are involved in the metabolism of benzodiazepines. It is unclear whether sex influences outcomes associated with intranasally administered drugs. A post hoc analysis of sex differences was conducted to evaluate the effectiveness and safety of diazepam nasal spray, which included examining changes in the number of days between seizure clusters over time (SEIzure interVAL [SEIVAL]). Diazepam nasal spray is approved for acute treatment of seizure clusters in patients with epilepsy aged ≥6 years. Data from a phase 3 safety study were used to determine the proportion of second doses used within 24 h (ie, a proxy for effectiveness) and SEIVAL. Adverse events were recorded. Of 163 treated patients, 89 were female, and 74 were male. Approximately 16% of both sexes self‐administered the study drug. A slightly higher proportion of seizure clusters was treated with a second dose in female (14.7%) than male (9.4%) patients. SEIVAL increased significantly and substantially over a year for all patients. The safety profile was generally similar between the sexes. These results suggest that potential sex differences in benzodiazepine pharmacokinetics do not meaningfully influence outcomes associated with diazepam nasal spray. Plain Language Summary: Some drugs may have differences in absorption and metabolism between genders that could translate into differences in safety and effectiveness. This safety study looked at diazepam nasal spray for treating seizure clusters in patients at least 6 years old. It found that safety was about the same for females and males. For both groups, most clusters stopped after only 1 dose of the drug, and the time between treated clusters got longer over a year. [ABSTRACT FROM AUTHOR]

In this article, the authors focus on the intersection of the study of activism and the urban community college. Leveraging the Actors, Contexts, Tactics, and Strategies (ACTS) Framework, the authors (re)examine activism scholarship that illuminates similarities and differences between 2‐ and 4‐year institutions. Ultimately, the article concludes with implications for practice and future research that can deepen and sustain the position of community colleges as contributors to the rich legacy of urban activism. [ABSTRACT FROM AUTHOR]

Background: Highly pathogenic avian influenza A(H5) human infections are a global concern, with many A(H5) human cases detected in Vietnam, including a case in October 2022. Using avian influenza virus surveillance from March 2017–September 2022, we described the percent of pooled samples that were positive for avian influenza A, A(H5), A(H5N1), A(H5N6), and A(H5N8) viruses in live bird markets (LBMs) in Vietnam. Methods: Monthly at each LBM, 30 poultry oropharyngeal swab specimens and five environmental samples were collected. Samples were pooled in groups of five and tested for influenza A, A(H5), A(H5N1), A(H5N6), and A(H5N8) viruses by real‐time reverse‐transcription polymerase chain reaction. Trends in the percent of pooled samples that were positive for avian influenza were summarized by LBM characteristics and time and compared with the number of passively detected avian influenza outbreaks using Spearman's rank correlation. Results: A total of 25,774 pooled samples were collected through active surveillance at 167 LBMs in 24 provinces; 36.9% of pooled samples were positive for influenza A, 3.6% A(H5), 1.9% A(H5N1), 1.1% A(H5N6), and 0.2% A(H5N8). Influenza A(H5) viruses were identified January–December and at least once in 91.7% of sampled provinces. In 246 A(H5) outbreaks in poultry; 20.3% were influenza A(H5N1), 60.2% A(H5N6), and 19.5% A(H5N8); outbreaks did not correlate with active surveillance. Conclusions: In Vietnam, influenza A(H5) viruses were detected by active surveillance in LBMs year‐round and in most provinces sampled. In addition to outbreak reporting, active surveillance for A(H5) viruses in settings with high potential for animal‐to‐human spillover can provide situational awareness. [ABSTRACT FROM AUTHOR]

Summary: Urbanization can affect the timing of plant reproduction (i.e. flowering and fruiting) and associated ecosystem processes. However, our knowledge of how plant phenology responds to urbanization and its associated environmental changes is limited.Herbaria represent an important, but underutilized source of data for investigating this question. We harnessed phenological data from herbarium specimens representing 200 plant species collected across 120 yr from the eastern US to investigate the spatiotemporal effects of urbanization on flowering and fruiting phenology and frost risk (i.e. time between the last frost date and flowering).Effects of urbanization on plant reproductive phenology varied significantly in direction and magnitude across species ranges. Increased urbanization led to earlier flowering in colder and wetter regions and delayed fruiting in regions with wetter spring conditions. Frost risk was elevated with increased urbanization in regions with colder and wetter spring conditions.Our study demonstrates that predictions of phenological change and its associated impacts must account for both climatic and human effects, which are context dependent and do not necessarily coincide. We must move beyond phenological models that only incorporate temperature variables and consider multiple environmental factors and their interactions when estimating plant phenology, especially at larger spatial and taxonomic scales. See also the Commentary on this article by Zhu & Song, 239: 2057–2059. [ABSTRACT FROM AUTHOR]

Broadly neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) variants are sought to curb coronavirus disease 2019 (COVID‐19) infections. Here we produced and characterized a set of mouse monoclonal antibodies (mAbs) specific for the ancestral SARS‐CoV‐2 receptor binding domain (RBD). Two of them, 17A7 and 17B10, were highly potent in microneutralization assay with 50% inhibitory concentration (IC50) ≤135 ng/mL against infectious SARS‐CoV‐2 variants, including G614, Alpha, Beta, Gamma, Delta, Epsilon, Zeta, Kappa, Lambda, B.1.1.298, B.1.222, B.1.5, and R.1. Both mAbs (especially 17A7) also exhibited strong in vivo efficacy in protecting K18‐hACE2 transgenic mice from the lethal infection with G614, Alpha, Beta, Gamma, and Delta viruses. Structural analysis indicated that 17A7 and 17B10 target the tip of the receptor binding motif in the RBD‐up conformation. A third RBD‐reactive mAb (3A6) although escaped by Beta and Gamma, was highly effective in cross‐neutralizing Delta and Omicron BA.1 variants in vitro and in vivo. In competition experiments, antibodies targeting epitopes similar to these 3 mAbs were rarely enriched in human COVID‐19 convalescent sera or postvaccination sera. These results are helpful to inform new antibody/vaccine design and these mAbs can be useful tools for characterizing SARS‐CoV‐2 variants and elicited antibody responses. [ABSTRACT FROM AUTHOR]

Premise: Quantifying how closely related plant species differ in susceptibility to insect herbivory is important for understanding the variation in evolutionary pressures on plant functional traits. However, empirically measuring in situ variation in herbivory spanning the geographic range of a plant–insect complex is logistically difficult. Recently, new methods have been developed using herbarium specimens to investigate patterns in plant–insect symbioses across large geographic scales. Such investigations provide insights into how accelerated anthropogenic changes may impact plant–insect interactions that are of ecological or agricultural importance. Methods: Here, we analyze 274 pressed herbarium samples to investigate variation in herbivory damage in 13 different species of the economically important plant genus Cucurbita (Cucurbitaceae). This collection is composed of specimens of wild, undomesticated Cucurbita that were collected from across their native range, and Cucurbita cultivars collected from both within their native range and from locations where they have been introduced for agriculture in temperate North America. Results: Herbivory is common on individuals of all Cucurbita species collected throughout their geographic ranges. However, estimates of herbivory varied considerably among individuals, with mesophytic species accruing more insect damage than xerophytic species, and wild specimens having more herbivory than specimens collected from human‐managed habitats. Conclusions: Our study suggests that long‐term evolutionary changes in habitat from xeric to mesic climates and wild to human‐managed habitats may mediate the levels of herbivory pressure from coevolved herbivores. Future investigations into the potential factors that contribute to herbivory may inform the management of domesticated crop plants and their insect herbivores. [ABSTRACT FROM AUTHOR]

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

Conceptual knowledge is dynamic, fluid, and flexible, changing as a function of contextual factors at multiple scales. The Covid‐19 pandemic can be considered a large‐scale, global context that has fundamentally altered most people's experiences with the world. It has also introduced a new concept, COVID (or COVID‐19), into our collective knowledgebase. What are the implications of this introduction for how existing conceptual knowledge is structured? Our collective emotional and social experiences with the world have been profoundly impacted by the Covid‐19 pandemic, and experience‐based perspectives on concept representation suggest that emotional and social experiences are critical components of conceptual knowledge. Such changes in collective experience should, then, have downstream consequences on knowledge of emotion‐ and social‐related concepts. Using a naturally occurring dataset derived from the social media platform Twitter, we show that semantic spaces for concepts related to our emotional experiences with Covid‐19 (i.e., emotional concepts like FEAR)—but not for unrelated concepts (i.e., animals like CAT)—show quantifiable shifts as a function of the emergence of COVID‐19 as a concept and its associated emotional and social experiences, shifts which persist 6 months after the onset of the pandemic. The findings support a dynamic view of conceptual knowledge wherein shared experiences affect conceptual structure. [ABSTRACT FROM AUTHOR]

Objective: Intermittent rescue therapy may be used for seizure clusters, which are clinical emergencies that may persist ≥24 h and increase risk of status epilepticus, emergency room visits, and reduced quality of life for patients with epilepsy. Beyond effectiveness for aborting seizure clusters, no data exist on how intermittent rescue therapy may impact the long‐term natural course of seizure clusters. This novel analysis explores SEIzure interVAL (SEIVAL; time between seizure clusters) in patients from a long‐term safety study of diazepam nasal spray (Valtoco) to assess SEIVAL changes with intermittent rescue therapy across time. Methods: Patients were aged 6–65 years. Age‐ and weight‐based doses of diazepam nasal spray were administered during a 12‐month treatment period with an optional follow‐up period. SEIVAL was evaluated in patients receiving two or more doses of diazepam nasal spray using 90‐day periods. Results: Of 163 treated patients, 151 had one or more SEIVALs. One hundred twenty had SEIVALs in Period 1 and one or more other periods. An increase in SEIVAL was noted from Period 1 compared with all subsequent periods (p ≤.001). A consistent cohort (n = 76) had one or more SEIVALs in each of Periods 1–4 (360 days); mean SEIVALs increased significantly (p <.01) from 12.2 days (Period 1) to 25.7 days (Period 4). Similar SEIVAL patterns occurred when repeat doses within a seizure cluster were eliminated and irrespective of age group, treatment duration, and change to concomitant medications. In adults, Quality of Life in Epilepsy scores were maintained with increased SEIVALs. Significance: Across 12 months, increases in SEIVAL were demonstrated in patients using diazepam nasal spray for seizure cluster treatment in a phase 3 safety study. Increased time between seizure clusters may reflect a previously unrecognized beneficial effect of intermittent rescue therapy. These results generate a range of biological and behavioral hypotheses and warrant exploration of the impact of intermittent rescue therapy. [ABSTRACT FROM AUTHOR]

Aim: Mangrove forests are important coastal wetlands for the blue carbon budget and play a significant role in mitigating global climate change. However, spatial patterns of carbon stocks in mangrove forests on an island scale have not been quantified owing to methodological limitations and lack of understanding of controlling factors. We took the entire Hainan Island as a case study and aimed to carry out a comprehensive investigation of the spatial patterns and driving factors of carbon stocks in mangrove forests. Location: Southern China. Time period: 2017–2020. Major taxa studied: Mangrove forest. Methods: The upscaling method combined with field surveys and Sentinel‐2 imagery analysis were used to compare different models for optimization of mangrove ecosystem carbon stock estimations. We also used structural equation modelling (SEM) to evaluate the factors driving the distributional patterns of mangrove carbon stocks on an island scale. Results: The current total mangrove carbon stock of the entire Hainan Island was estimated to be 703,181 Mg C (with a mean density of 192 Mg C/ha), with the above‐ and below‐ground carbon stocks averaging at 44.7 and 147.3 Mg C/ha, respectively. The mangrove carbon storage in the north‐eastern region of the island was the highest and in the west region the lowest. Sediment nitrogen content and plant species diversity had the most positive driving effects on the distribution of total carbon stock for Hainan Island mangroves. Main conclusions: The combination of field surveys and Sentinel‐2 imagery analysis can be applied to regional‐scale estimations of carbon stocks for mangrove forests. Spatial pattens of mangrove carbon stocks vary among locations on Hainan Island, and soil nutrient (especially nitrogen) availability is the dominant factor regulating carbon stock variations along the land‐to‐sea gradient. Our findings have significant implications for better understanding the distribution of mangrove carbon stocks and quantification of the global blue carbon budget. [ABSTRACT FROM AUTHOR]

Cryptic species diversity is a major challenge regarding the species‐rich community of parasitoids attacking oak gall wasps due to a high degree of sexual dimorphism, morphological plasticity, small size and poorly known biology. As such, we know very little about the number of species present, nor the evolutionary forces responsible for generating this diversity. One hypothesis is that trait diversity in the gall wasps, including the morphology of the galls they induce, has evolved in response to selection imposed by the parasitoid community, with reciprocal selection driving diversification of the parasitoids. Using a rare, continental‐scale data set of Sycophila parasitoid wasps reared from 44 species of cynipid galls from 18 species of oak across the USA, we combined mitochondrial DNA barcodes, ultraconserved elements (UCEs), morphological and natural history data to delimit putative species. Using these results, we generate the first large‐scale assessment of ecological specialization and host association in this species‐rich group, with implications for evolutionary ecology and biocontrol. We find most Sycophila target specific subsets of available cynipid host galls with similar morphologies, and generally attack larger galls. Our results suggest that parasitoid wasps such as Sycophila have adaptations allowing them to exploit particular host trait combinations, while hosts with contrasting traits are resistant to attack. These findings support the tritrophic niche concept for the structuring of plant–herbivore–parasitoid communities. [ABSTRACT FROM AUTHOR]

The development of next‐generation sequencing technologies allows researchers to address complex problems in species delimitation, especially for non‐model organisms. The taxonomic status of North American Nyssa species has long been debated and remains controversial. To elucidate the genetic structure and phylogenetic relationships of the five currently recognized North American Nyssa species, we conducted whole‐genome sequencing of representative individuals and identified genome‐wide single‐nucleotide polymorphisms (SNPs) by utilizing the recently released chromosome‐level assembly of Nyssa sinensis genome. Population genetic and phylogenetic analyses consistently inferred four well‐supported genetic clusters from our sampled individuals, that is, N. aquatica, N. ogeche, N. sylvatica, and N. biflora–N. ursina. Although the identification of N. biflora and N. ursina is primarily based on the morphological characteristics of leaves and drupes, the present evidence, including our principal components analysis of leaf morphological traits, strongly supports the taxonomic designation of N. biflora and N. ursina as a single species. In addition, these four genetic clusters were grouped into two major clades, that is, clade 1 (N. aquatica and N. ogeche) and clade 2 (N. sylvatica and N. biflora–N. ursina). Despite the fact that no evidence of widespread gene flow was found between these two major clades, our analyses revealed the possibility of introgression from N. sylvatica into N. biflora, albeit at a relatively low frequency. This study demonstrates the use of whole‐genome sequences as a promising avenue for delimiting species boundaries and further advocates for an integrative approach in the assessment of species delimitation. [ABSTRACT FROM AUTHOR]

Understanding the role of divergent host‐use in promoting population differentiation among herbivorous insects provides valuable insight into the origin of diversity in this species‐rich group. A strong signature of divergent selection in promoting population differentiation is provided by parallel phenotypic divergence across multiple insect species adapting to the same set of divergent host plants.In this study, we explored whether a key phenotype of gall‐forming insects—gall size—exhibits parallel patterns of divergence across a community of gall‐forming insect species because of adaptation to different host plant species. A previous study found parallel divergence in gall morphology across two gall‐forming insect species adapted to two sister species of oaks (Fagaceae). Here, we expand this question to four additional members of the gall‐forming insect community that specialise on the same two host plant species: Quercus geminata (Qg) and Quercus virginiana (Qv).Consistent with the previous result, all four additional gall‐forming species tended to induce larger galls on Qg than on Qv, with two of the four species exhibited statistically significant differences and one species showed marginally significant differences. Moreover, we found gall size was similar for two gall‐forming species when cross‐reared on natural versus planted hosts, ruling out environmental causes of parallel host‐associated gall size difference across multiple species.Our study documents parallel divergence in a key phenotype of gall‐forming insects associated with different host environments, shedding light on the important role of divergent host use in driving the evolution of gall morphology. [ABSTRACT FROM AUTHOR]

Wetlands are highly productive ecosystems that host unique biota and provide vital ecosystem services. Despite their critical importance, we still lack a fundamental understanding of factors controlling species suitability and climate change impacts in wetlands essential to conserving these imperiled ecosystems in the face of anthropogenic threats. Here, we applied ecological niche models (ENMs) inferred from a massive nationwide data set including field surveys and herbarium specimens representing 101 dominant plant species of China's inland wetlands, to explore the potential climate‐driven shifts in these ecosystems. Our optimal models applying machine learning and integrating key aspects of climate, soil, topographic hydrology, and anthropogenic disturbance, identified that (a) species of different types (e.g., woody/nonwoody) showed significant differences in their sensitivity to extracted key environmental factors (e.g., isothermality, water table depth) in wetlands; (b) native wetland species likely face habitat shrinkage under climate change, especially in Northeast China, as well as potential encroachment of xeric and nonnative species; (c) only less than 20% of projected conservation hotspots are currently protected. We propose four protection gaps that need to be addressed urgently in China's current wetland protection framework. This study clarifies the conservation priorities of China's inland wetlands and provides practical guidelines for the improvement of wetland conservation efforts. Plain Language Summary: Wetlands are among the most productive ecosystems on Earth and provide multiple key ecosystem services for wildlife and human societies. However, global wetlands have been experiencing extensive degradation and loss under anthropogenic threats, and anthropogenic climate change poses new challenges and uncertainties to wetland conservation efforts. Thus, there is a pressing need to assess climatic risks in wetlands, to identify potential climate‐change hotspots and develop climate‐smart conservation strategies. This study compiled a massive wetland data set and applied machine learning tools to perform the first nationwide climatic risk assessment in China's inland wetlands. The results revealed that native wetland species would face habitat shrinkage, especially woody species, whereas nonwetland and nonnative species would benefit from climate change and expand their distributions. Northeast China is a hotspot with its native wetland species under high climatic risk, while in the Tibetan Plateau, the habitats for native wetland species and nonwetland species are both likely to expand in the future. This study highlights the conservation priorities in China's inland wetlands and offers guidelines for filling the current wetland protection gaps. Key Points: Different species types vary in their sensitivity to the key environmental factors in inland wetlandsNative wetland species will overall face habitat loss, especially in Northeast China, as well as invasion of xeric and alien speciesLess than 20% of projected conservation hotspots are currently protected [ABSTRACT FROM AUTHOR]

Background: Regulatory T cells (Tregs) play a neuroprotective role by suppressing inflammation. We previously documented that Treg immunomodulatory mechanisms are compromised in people with Alzheimer's disease (AD) and are associated with activation of peripheral monocytes and upregulation of inflammatory mediators. In this original study, we investigated the feasibility and potential impact of low‐dose IL‐2 immunotherapy on restoring Tregs and modifying inflammation in an AD clinical setting. Method: Eight patients with mild‐to‐moderate AD dementia (MMSE:12‐25) were enrolled in a phase 1, open‐label, feasibility study of IL‐2 treatment. The presence of elevated brain amyloid, as demonstrated by either CSF or amyloid positron emission tomography (PET) scan, was confirmed in all participants. Enrolled individuals received monthly five‐day‐courses of subcutaneous IL‐2 (1 million units/day) for four months and were followed for an additional two months post‐treatment. Treg immunophenotype and functional analysis were obtained serially at screening, day 1 (before IL‐2 treatment) and day 8 (three days after the fifth dose) of each treatment cycle during therapy, and then at weeks 17 and 24. Two‐sided paired t‐tests were used to assess the statistical significance of changes in each analyte or clinical outcome at each timepoint. Result: Overall, low‐dose IL‐2 immunotherapy was well‐tolerated and all patients received the treatment as planned. The number of CD4+CD25highFoxP3+ Tregs increased two to three‐fold after each IL‐2 treatment cycle (p<0.01) and returned to baseline before the next cycle. Treg suppressive function on responder T cell (Tresp) proliferation also progressively increased through the four‐month IL‐2 treatment phase (p<0.01). IL‐2 treatment down‐regulated IL‐1β, IL‐6 and TNFa transcripts in circulating monocytes and modulated plasma pro‐inflammatory chemokines and cytokines (IL‐15, CCL2, CCL4, CCL11 and FLT3LG; p<0.01). Clinical benefits (mean change ± SE) were observed on the Mini‐Mental State Exam (+2.25 ± 0.59, p = 0.007) and the Clinical Dementia Rating Sum of Boxes (‐0.56 ± 0.24; p = 0.051). Conclusion: IL‐2 immunotherapy restored peripheral Treg function and ameliorated systemic pro‐inflammatory mediators in AD patients. The results of this study warrant conducting a well‐controlled clinical study to further evaluate the safety and efficacy of low‐dose IL‐2 as a potential treatment for AD. [ABSTRACT FROM AUTHOR]

Premise: The application of high‐throughput sequencing, especially to herbarium specimens, is rapidly accelerating biodiversity research. Low‐coverage sequencing of total genomic DNA (genome skimming) is particularly promising and can simultaneously recover the plastid, mitochondrial, and nuclear ribosomal regions across hundreds of species. Here, we introduce PhyloHerb, a bioinformatic pipeline to efficiently assemble phylogenomic data sets derived from genome skimming. Methods and Results: PhyloHerb uses either a built‐in database or user‐specified references to extract orthologous sequences from all three genomes using a BLAST search. It outputs FASTA files and offers a suite of utility functions to assist with alignment, partitioning, concatenation, and phylogeny inference. The program is freely available at https://github.com/lmcai/PhyloHerb/. Conclusions: We demonstrate that PhyloHerb can accurately identify genes using a published data set from Clusiaceae. We also show via simulations that our approach is effective for highly fragmented assemblies from herbarium specimens and is scalable to thousands of species. [ABSTRACT FROM AUTHOR]

In March 2021, Lao People's Democratic Republic (Laos) reported an avian influenza A(H5N6) virus infection in a 5‐year‐old child identified through sentinel surveillance. This was the first human A(H5N6) infection reported outside of China. A multidisciplinary investigation undertook contact tracing and enhanced human and animal surveillance in surrounding villages and live bird markets. Seven Muscovy ducks tested positive for highly pathogenic avian influenza A(H5N6) viruses. Sequenced viruses belonged to clade 2.3.4.4h and were closely related to viruses detected in poultry in Vietnam and to previous viruses detected in Laos. Surveillance and coordinated outbreak response remain essential to global health security. [ABSTRACT FROM AUTHOR]

Herbaria may represent remarkable sources of viable diaspores for recovering lost genetic variation and extinct plant species, but the application of rewilding extinct species using these collections has not been explored in detail. De‐extinction in plants may be achieved by germinating viable diaspores or culturing tissues preserved in herbarium specimens. Germination of old diaspores (fruits, seeds, spores) preserved in sub‐optimal uncontrolled storage conditions demonstrates that the recovery of extinct plants from herbarium specimens may be possible. Plant de‐extinction via herbarium specimens relies on the availability of samples containing viable diaspores, and on the inclination of curators and the conservation community to use such material for this purpose. We developed an internet‐based survey to assess (i) whether the scientific community would consent to the use of herbarium specimens of extinct species to attempt de‐extinction, and (ii) the limitations of removing diaspores from specimens. Despite the risk of potential damages to valuable specimens from historical collections when harvesting diaspores, a consensus for using specimens of extinct plant species emerged. Most respondents would permit the collection of a low number of diaspores, preferably from duplicate specimens and only if the integrity of the specimen is preserved. These considerations would be more restrictive for type specimens and those of historical value. These results help to formalise a decision framework for the grant and use of material from natural history collections and a pragmatic approach to attempt to resurrect extinct species from herbarium specimens. [ABSTRACT FROM AUTHOR]

Summary: Interactions between species can influence successful reproduction, resulting in reproductive character displacement, where the similarity of reproductive traits – such as flowering time – among close relatives growing together differ from when growing apart. Evidence for the overall prevalence and direction of this phenomenon, and its stability under environmental change, remains untested across large scales.Using the power of crowdsourcing, we gathered phenological information from over 40 000 herbarium specimens, and investigated displacement in flowering time across 110 animal‐pollinated species in the eastern USA.Overall, flowering time displacement is not common across large scales. However, displacement is generally greater among species pairs that flower close in time, regardless of direction. Furthermore, with climate change, the flowering times of closely related species are predicted, on average, to shift further apart by the mid‐21st century.We demonstrate that the degree and direction of phenological displacement among co‐occurring closely related species pairs varies tremendously. However, future climate change may alter the differences in reproductive timing among many of these species pairs, which may have significant consequences for species interactions and gene flow. Our study provides one promising path towards understanding how the phenological landscape is structured and may respond to future environmental change. [ABSTRACT FROM AUTHOR]

Summary: Endoparasitic plants are the most reduced flowering plants, spending most of their lives as a network of filaments within the tissues of their hosts. Despite their extraordinary life form, we know little about their biology. Research into a few species has revealed unexpected insights, such as the total loss of plastome, the reduction of the vegetative phase to a proembryonic stage, and elevated information exchange between host and parasite. To consolidate our understanding, we review life history, anatomy, and molecular genetics across the four independent lineages of endoparasitic plants. We highlight convergence across these clades and a striking trans‐kingdom convergence in life history among endoparasitic plants and disparate lineages of fungi at the molecular and physiological levels. We hypothesize that parasitism of woody plants preselected for the endoparasitic life history, providing parasites a stable host environment and the necessary hydraulics to enable floral gigantism and/or high reproductive output. Finally, we propose a broader view of endoparasitic plants that connects research across disciplines, for example, pollen–pistil and graft incompatibility interactions and plant associations with various fungi. We shine a light on endoparasitic plants and their hosts as under‐explored ecological microcosms ripe for identifying unexpected biological processes, interactions and evolutionary convergence. [ABSTRACT FROM AUTHOR]

Humans seamlessly make sense of a rapidly changing environment, using a seemingly limitless knowledgebase to recognize and adapt to most situations we encounter. This knowledgebase is called semantic memory. Embodied cognition theories suggest that we represent this knowledge through simulation: understanding the meaning of coffee entails reinstantiating the neural states involved in touching, smelling, seeing, and drinking coffee. Distributional semantic theories suggest that we are sensitive to statistical regularities in natural language, and that a cognitive mechanism picks up on these regularities and transforms them into usable semantic representations reflecting the contextual usage of language. These appear to present contrasting views on semantic memory, but do they? Recent years have seen a push toward combining these approaches under a common framework. These hybrid approaches augment our understanding of semantic memory in important ways, but current versions remain unsatisfactory in part because they treat sensory‐perceptual and distributional‐linguistic data as interacting but distinct types of data that must be combined. We synthesize several approaches which, taken together, suggest that linguistic and embodied experience should instead be considered as inseparably entangled: just as sensory and perceptual systems are reactivated to understand meaning, so are experience‐based representations endemic to linguistic processing; further, sensory‐perceptual experience is susceptible to the same distributional principles as language experience. This conclusion produces a characterization of semantic memory that accounts for the interdependencies between linguistic and embodied data that arise across multiple timescales, giving rise to concept representations that reflect our shared and unique experiences. This article is categorized under:Psychology > LanguageNeuroscience > CognitionLinguistics > Language in Mind and Brain [ABSTRACT FROM AUTHOR]

Introduction: Amyloid beta (Aβ) oligomers are one of the most toxic structural forms of the Aβ protein and are hypothesized to cause synaptotoxicity and memory failure as they build up in Alzheimer's disease (AD) patients' brain tissue. We previously demonstrated that antagonists of the sigma‐2 receptor complex effectively block Aβ oligomer toxicity. CT1812 is an orally bioavailable, brain penetrant small molecule antagonist of the sigma‐2 receptor complex that appears safe and well tolerated in healthy elderly volunteers. We tested CT1812's effect on Aβ oligomer pathobiology in preclinical AD models and evaluated CT1812's impact on cerebrospinal fluid (CSF) protein biomarkers in mild to moderate AD patients in a clinical trial (ClinicalTrials.gov NCT02907567). Methods: Experiments were performed to measure the impact of CT1812 versus vehicle on Aβ oligomer binding to synapses in vitro, to human AD patient post mortem brain tissue ex vivo, and in living APPSwe/PS1dE9 transgenic mice in vivo. Additional experiments were performed to measure the impact of CT1812 versus vehicle on Aβ oligomer‐induced deficits in membrane trafficking rate, synapse number, and protein expression in mature hippocampal/cortical neurons in vitro. The impact of CT1812 on cognitive function was measured in transgenic Thy1 huAPPSwe/Lnd+ and wild‐type littermates. A multicenter, double‐blind, placebo‐controlled parallel group trial was performed to evaluate the safety, tolerability, and impact on protein biomarker expression of CT1812 or placebo given once daily for 28 days to AD patients (Mini‐Mental State Examination 18–26). CSF protein expression was measured by liquid chromatography with tandem mass spectrometry or enzyme‐linked immunosorbent assay in samples drawn prior to dosing (Day 0) and at end of dosing (Day 28) and compared within each patient and between pooled treated versus placebo‐treated dosing groups. Results: CT1812 significantly and dose‐dependently displaced Aβ oligomers bound to synaptic receptors in three independent preclinical models of AD, facilitated oligomer clearance into the CSF, increased synaptic number and protein expression in neurons, and improved cognitive performance in transgenic mice. CT1812 significantly increased CSF concentrations of Aβ oligomers in AD patient CSF, reduced concentrations of synaptic proteins and phosphorylated tau fragments, and reversed expression of many AD‐related proteins dysregulated in CSF. Discussion: These preclinical studies demonstrate the novel disease‐modifying mechanism of action of CT1812 against AD and Aβ oligomers. The clinical results are consistent with preclinical data and provide evidence of target engagement and impact on fundamental disease‐related signaling pathways in AD patients, supporting further development of CT1812. [ABSTRACT FROM AUTHOR]

Species interactions drive ecosystem processes and are a major focus of global change research. Among the most consequential interactions expected to shift with climate change are those between insect herbivores and plants, both of which are highly sensitive to temperature. Insect herbivores and their host plants display varying levels of synchrony that could be disrupted or enhanced by climate change, yet empirical data on changes in synchrony are lacking. Using evidence of herbivory on herbarium specimens collected from the northeastern United States and France from 1900 to 2015, we provide evidence that plant species with temperature‐sensitive phenologies experience higher levels of insect damage in warmer years, while less temperature‐sensitive, co‐occurring species do not. While herbivory might be mediated by interactions between warming and phenology through multiple pathways, we suggest that warming might lengthen growing seasons for phenologically sensitive plant species, exposing their leaves to herbivores for longer periods of time in warm years. We propose that elevated herbivory in warm years may represent a previously underappreciated cost to phenological tracking of climate change over longer timescales. [ABSTRACT FROM AUTHOR]

The digitization of herbarium collections is greatly transforming plant biodiversity science, yet most herbarium data remain inaccessible. Here, we present a novel, single‐user photostation and associated workflow for efficiently mobilizing herbarium specimens. Our apparatus represents a significant improvement to existing technology and is scalable to a variety of digitization tasks from small to massive collections. [ABSTRACT FROM AUTHOR]

Premise: A subset of parasitic plants bear extremely reduced features and grow nearly entirely within their hosts. Until recently, most of these endoparasites were thought to represent a single clade united by their reduced morphology. Current phylogenetic understanding contradicts this assumption and indicates these plants represent distantly related clades, thus offering an opportunity to examine convergence among plants with this life history. Methods: We sampled species from Apodanthaceae, Cytinaceae, Mitrastemonaceae, and Rafflesiaceae spanning a range of developmental stages. To provide a broader comparative framework, Santalaceae mistletoes with a similar lifestyle were also analyzed. Microtomography and microscopy were used to analyze growth patterns and the ontogeny of host–parasite vascular connections. Results: Apodanthaceae, Cytinaceae, Mitrastemonaceae, and Rafflesiaceae species demonstrated a common development characterized by late cell differentiation. These species were also observed to form direct connections to host vessels and to cause severe alterations of host xylem development. Apodanthaceae and Rafflesiaceae species were additionally observed to form sieve elements, which connect with the host phloem. Endophytic Santalaceae species demonstrated a dramatically different developmental pattern, featuring early cell differentiation and tissue organization, and little effect on host anatomy and cambial activity. Conclusions: Our results illuminate two distinct developmental trajectories in endoparasites. One involves the retention of embryonic characteristics and late connection with host vessels, as demonstrated in species of Apodanthaceae, Cytinaceae, Mitrastemonaceae, and Rafflesiaceae. The second involves tissue specialization and early connection with host xylem, as exemplified by Santalaceae species. These differences are hypothesized to be related to the absence/presence of photosynthesis in these plants. [ABSTRACT FROM AUTHOR]

Many targeted therapies are administered at or near the maximum tolerated dose (MTD). With the advent of precision medicine, a larger therapeutic window is expected. Therefore, dose optimization will require a new approach to early clinical trial design. We analyzed publicly available data for 21 therapies targeting six kinases, and four poly (ADP‐ribose) polymerase inhibitors, focusing on potency and exposure to gain insight into dose selection. The free average steady‐state concentration (Css) at the approved dose was compared to the in vitro cell potency (half‐maximal inhibitory concentration (IC50)). Average steady‐state area under the plasma concentration‐time curve, the fraction unbound drug in plasma, and the cell potency were taken from the US drug labels, US and European regulatory reviews, and peer‐reviewed journal articles. The Css was remarkably similar to the IC50. The median Css/IC50 value was 1.2, and 76% of the values were within 3‐fold of unity. However, three drugs (encorafenib, erlotinib, and ribociclib) had a Css/IC50 value > 25. Seven other therapies targeting the same 3 kinases had much lower Css/IC50 values ranging from 0.5 to 4. These data suggest that these kinase inhibitors have a large therapeutic window that is not fully exploited; lower doses may be similarly efficacious with improved tolerability. We propose a revised first‐in‐human trial design in which dose cohort expansion is initiated at doses less than the MTD when there is evidence of clinical activity and Css exceeds a potency threshold. This potency‐guided approach is expected to maximize the therapeutic window thereby improving patient outcomes. [ABSTRACT FROM AUTHOR]

Summary: The expansion of angiosperm‐dominated forests in the Cretaceous and early Cenozoic had a profound effect on terrestrial biota by creating novel ecological niches. The majority of modern fern lineages are hypothesized to have arisen in response to this expansion, particularly fern epiphytes that radiated into the canopy. Recent evidence, however, suggests that epiphytism does not correlate with increased diversification rates in ferns, calling into question the role of the canopy habitat in fern evolution.To understand the role of the canopy in structuring fern community diversity, we investigated functional traits of fern sporophytes and gametophytes across a broad phylogenetic sampling on the island of Moorea, French Polynesia, including > 120 species and representatives of multiple epiphytic radiations.While epiphytes showed convergence in small size and a higher frequency of noncordate gametophytes, they showed greater functional diversity at the community level relative to terrestrial ferns.These results suggest previously overlooked functional diversity among fern epiphytes, and raise the hypothesis that while the angiosperm canopy acted as a complex filter that restricted plant size, it also facilitated diversification into finely partitioned niches. Characterizing these niche axes and adaptations of epiphytic ferns occupying them should be a priority for future pteridological research. [ABSTRACT FROM AUTHOR]

Summary: Though substantial effort has gone into predicting how global climate change will impact biodiversity patterns, the scarcity of taxon‐specific information has hampered the efficacy of these endeavors. Further, most studies analyzing spatiotemporal patterns of biodiversity focus narrowly on species richness.We apply machine learning approaches to a comprehensive vascular plant database for the United States and generate predictive models of regional plant taxonomic and phylogenetic diversity in response to a wide range of environmental variables.We demonstrate differences in predicted patterns and potential drivers of native vs nonnative biodiversity. In particular, native phylogenetic diversity is likely to decrease over the next half century despite increases in species richness. We also identify that patterns of taxonomic diversity can be incongruent with those of phylogenetic diversity.The combination of macro‐environmental factors that determine diversity likely varies at continental scales; thus, as climate change alters the combinations of these factors across the landscape, the collective effect on regional diversity will also vary. Our study represents one of the most comprehensive examinations of plant diversity patterns to date and demonstrates that our ability to predict future diversity may benefit tremendously from the application of machine learning. [ABSTRACT FROM AUTHOR]

Summary: The panzootic caused by A/goose/Guangdong/1/96‐lineage highly pathogenic avian influenza (HPAI) A(H5) viruses has occurred in multiple waves since 1996. From 2013 onwards, clade 2.3.4.4 viruses of subtypes A(H5N2), A(H5N6), and A(H5N8) emerged to cause panzootic waves of unprecedented magnitude among avian species accompanied by severe losses to the poultry industry around the world. Clade 2.3.4.4 A(H5) viruses have expanded in distinct geographical and evolutionary pathways likely via long distance migratory bird dispersal onto several continents and by poultry trade among neighboring countries. Coupled with regional circulation, the viruses have evolved further by reassorting with local viruses. As of February 2019, there have been 23 cases of humans infected with clade 2.3.4.4 H5N6 viruses, 16 (70%) of which had fatal outcomes. To date, no HPAI A(H5) virus has caused sustainable human‐to‐human transmission. However, due to the lack of population immunity in humans and ongoing evolution of the virus, there is a continuing risk that clade 2.3.4.4 A(H5) viruses could cause an influenza pandemic if the ability to transmit efficiently among humans was gained. Therefore, multisectoral collaborations among the animal, environmental, and public health sectors are essential to conduct risk assessments and develop countermeasures to prevent disease and to control spread. In this article, we describe an assessment of the likelihood of clade 2.3.4.4 A(H5) viruses gaining human‐to‐human transmissibility and impact on human health should such human‐to‐human transmission occur. This structured analysis assessed properties of the virus, attributes of the human population, and ecology and epidemiology of these viruses in animal hosts. [ABSTRACT FROM AUTHOR]

Mutations in the influenza virus neuraminidase (NA) that cause reduced susceptibility to the NA inhibitor (NAI) oseltamivir may occur naturally or following antiviral treatment. Currently, detection uses either a traditional NA inhibition assay or gene sequencing to identify known markers associated with reduced inhibition by oseltamivir. Both methods are laborious and require trained personnel. The influenza antiviral resistance test (iART), a prototype system developed by Becton, Dickinson and Company for research use only, offers a rapid and simple method to identify such viruses. This study investigated application of iART to influenza A viruses isolated from non‐human hosts with a variety of NA subtypes (N1‐N9). [ABSTRACT FROM AUTHOR]

Background: Dextromethorphan (DM) / quinidine (Q) was approved for pseudobulbar affect (PBA) treatment based on efficacy and safety trials in patients with PBA caused by amyotrophic lateral sclerosis or multiple sclerosis. The PRISM II trial evaluated DM/Q as PBA treatment in patients with stroke, dementia, or traumatic brain injury.Objective: To report results from the stroke cohort of PRISM II, including the Stroke Impact Scale (SIS).Design: Open-label trial evaluating twice-daily DM/Q over 90 days.Study Participants: Adults (n = 113) with a clinical diagnosis of PBA secondary to stroke; stable psychiatric medications were allowed.Methods: PRISM II was an open-label, 12-week trial enrolling adults with PBA caused by dementia, stroke (reported here), or TBI. All study participants received DM/Q 20/10 mg twice daily. Study visits occurred at baseline and at days 30 and 90.Setting: 150 U.S. centers.Main Outcome Measurements: Primary efficacy measure was changed from baseline to day 90 in Center for Neurologic Study-Lability Scale (CNS-LS) scores. Secondary outcomes included PBA episodes (estimated over 7 days), Clinical and Patient/Caregiver Global Impression of Change (CGI-C and PGI-C), Quality of Life-Visual Analog Scale (QOL-VAS), SIS, Patient Health Questionnaire (PHQ-9), and Mini-Mental State Examination (MMSE).Results: Compared with baseline, CNS-LS scores (SD) improved by -6.2 (6.1, P < .001) at day 30 and -7.6 (6.7, P < .001) at day 90. PBA episodes were reduced by 65% and 75% at day 30 and 90, respectively. Seventy-five percent of clinicians and 67% of patients/caregivers rated PBA as "much" or "very much improved." All SIS items significantly improved from baseline (P < .05, all). Adverse events included diarrhea (4.4%), headache (3.5%), constipation (2.7%), and dizziness (2.7%); 5.3% had adverse events leading to study discontinuation.Conclusions: DM/Q effectively treated PBA and was associated with global and functional improvement; adverse events were consistent with the known safety profile of DM/Q. [ABSTRACT FROM AUTHOR]

Summary: Whole‐genome duplications (WGDs) are widespread and prevalent in vascular plants and frequently coincide with major episodes of global and climatic upheaval, including the mass extinction at the Cretaceous–Tertiary boundary (c. 65 Ma) and during more recent periods of global aridification in the Miocene (c. 10–5 Ma). Here, we explore WGDs in the diverse flowering plant clade Malpighiales.Using transcriptomes and complete genomes from 42 species, we applied a multipronged phylogenomic pipeline to identify, locate, and determine the age of WGDs in Malpighiales using three means of inference: distributions of synonymous substitutions per synonymous site (Ks) among paralogs, phylogenomic (gene tree) reconciliation, and a likelihood‐based gene‐count method.We conservatively identify 22 ancient WGDs, widely distributed across Malpighiales subclades. Importantly, these events are clustered around the Eocene–Paleocene transition (c. 54 Ma), during which time the planet was warmer and wetter than any period in the Cenozoic.These results establish that the Eocene Climatic Optimum likely represents a previously unrecognized period of prolific WGDs in plants, and lends further support to the hypothesis that polyploidization promotes adaptation and enhances plant survival during episodes of global change, especially for tropical organisms like Malpighiales, which have tight thermal tolerances. See also the Commentary on this article by Sessa, 221: 5–6. [ABSTRACT FROM AUTHOR]

Gracilariaceae has a worldwide distribution including numerous economically important species. We applied high‐throughput sequencing to obtain organellar genomes (mitochondria and chloroplast) from 10 species of Gracilariaceae and, combined with published genomes, to infer phylogenies and compare genome architecture among species representing main lineages. We obtained similar topologies between chloroplast and mitochondrial genomes phylogenies. However, the chloroplast phylogeny was better resolved with full support. In this phylogeny, Melanthalia intermedia is sister to a monophyletic clade including Gracilaria and Gracilariopsis, which were both resolved as monophyletic genera. Mitochondrial and chloroplast genomes were highly conserved in gene synteny, and variation mainly occurred in regions where insertions of plasmid‐derived sequences (PDS) were found. In mitochondrial genomes, PDS insertions were observed in two regions where the transcription direction changes: between the genes cob and trnL, and trnA and trnN. In chloroplast genomes, PDS insertions were in different positions, but generally found between psdD and rrs genes. Gracilariaceae is a good model system to study the impact of PDS in genome evolution due to the frequent presence of these insertions in organellar genomes. Furthermore, the bacterial leuC/leuD operon was found in chloroplast genomes of Gracilaria tenuistipitata, G. chilensis, and M. intermedia, and in extrachromosomal plasmid of G. vermiculophylla. Phylogenetic trees show two different origins of leuC/leuD: genes found in chloroplast and plasmid were placed with proteobacteria, and genes encoded in the nucleus were close to Viridiplantae and cyanobacteria. [ABSTRACT FROM AUTHOR]

Plant and fungal specimens in herbaria are becoming primary resources for investigating how plant phenology and geographic distributions shift with climate change, greatly expanding inferences across spatial, temporal, and phylogenetic dimensions. However, these specimens contain a wealth of additional data, including nutrients, defensive compounds, herbivore damage, disease lesions, and signatures of physiological processes, that capture ecological and evolutionary responses to the Anthropocene but which are less frequently utilized. Here, we outline the diversity of herbarium data, global change topics to which they have been applied, and new hypotheses they could inform. We find that herbarium data have been used extensively to study impacts of climate change and invasive species, but that such data are less commonly used to address other drivers of biodiversity loss, including habitat conversion, pollution, and overexploitation. In addition, we note that fungal specimens are under‐explored relative to vascular plants. To facilitate broader application of plant and fungal specimens in global change research, we consider the limitations of these data and modern sampling and statistical tools that may be applied to surmount challenges they present. Using a case study of insect herbivory, we illustrate how novel herbarium data may be employed to test hypotheses for which few data exist. With the goal of positioning herbaria as hubs for global change research, we suggest future research directions and curation priorities. [ABSTRACT FROM AUTHOR]

Background: Dextromethorphan 20 mg / quinidine 10 mg (DM/Q) was approved to treat pseudobulbar affect (PBA) based on phase 3 trials conducted in participants with amyotrophic lateral sclerosis or multiple sclerosis. PRISM II evaluated DM/Q effectiveness, safety, and tolerability for PBA following stroke, dementia, or traumatic brain injury (TBI).Objective: To report results from the TBI cohort of PRISM II, including a TBI-specific functional scale.Design: Open-label trial evaluating twice-daily DM/Q over 90 days.Study Participants: Adults (n = 120) with a clinical diagnosis of PBA secondary to nonpenetrating TBI; stable psychiatric medications were allowed.Methods: PRISM II was an open-label, 12-week trial enrolling adults with PBA secondary to dementia, stroke, or TBI (NCT01799941). All study participants received DM/Q 20/10 mg twice daily. Study visits occurred at baseline and at day 30 and day 90.Setting: 150 U.S. centers.Main Outcome Measurements: Primary endpoint was change in Center for Neurologic Study-Lability Scale (CNS-LS) score from baseline to day 90. Secondary outcomes included PBA episode count, Clinical and Patient Global Impression of Change (CGI-C; PGI-C), Quality of Life-Visual Analog Scale (QOL-VAS), treatment satisfaction, Neurobehavioral Functioning Inventory (NFI), Patient Health Questionnaire (PHQ-9), and Mini Mental State Examination (MMSE).Results: DM/Q-treated participants showed significant mean (SD) reductions in CNS-LS from baseline (day 30, -5.6 [5.2]; day 90, -8.5 [5.2]; both, P<.001). Compared with baseline, PBA episodes were reduced by 61.3% and 78.5% at days 30 and 90 (both, P<.001). At day 90, 78% and 73% of study participants had "much improved" or "very much improved" on the CGI-C and PGI-C. QOL-VAS scores were significantly reduced from baseline (-3.7 [3.3], P<.001). Mean (SD) PHQ-9 scores improved compared to baseline at day 30 (-3.2 [5.3], P<.001) and 90 (-5.2 [6.4], P<.001). NFI T scores were significantly improved (P<.001), whereas MMSE scores were unchanged. Adverse events (AEs) were consistent with the known DM/Q safety profile; the most common AE was diarrhea (8.3%).Conclusions: DM/Q was well tolerated, and it significantly reduced PBA episodes in study participants with TBI. Changes in CNS-LS and PBA episode count were similar to changes with DM/Q in phase 3 trials.Level Of Evidence: II. [ABSTRACT FROM AUTHOR]

Aim: Self-pollinating plants ('selfers') have larger geographical ranges and inhabit higher latitudes than their outcrossing relatives. This finding has led to the hypothesis that selfers also have broader climatic niches ('niches') because the increased likelihood of successful colonization into new areas and the initial purging of deleterious mutations could offset the inability of selfers to adapt to new environments owing to low heterozygosity. Here, we examine the niches of hundreds of closely related selfing and outcrossing species to determine whether selfers do indeed have larger niche breadths. Location: Global. Time period: Current. Major taxa studied: Twenty clades of flowering plants comprising 424 species. Methods: We estimated and compared the climatic niches of 194 pairs of sister species across 15 families, which differed in mating system. We incorporated these results into models predicting niche breadth and its change over time to estimate the effects of mating system on niche breadth. Furthermore, we compared the degree of niche divergence between sister-species pairs of various mating system combinations. Results: Selfers did not have wider niche breadths than their outcrossing sister taxa. Sister pairs of selfers also exhibited greater niche overlap than outcrossing sisters, implying that niche expansion becomes limited after the transition to selfing. Furthermore, the niche breadth of selfers was predicted to decrease significantly faster than that of closely related outcrossers. Main conclusions: Our results demonstrate a decoupling in the range size and niche breadth of selfers. The larger geographical range and comparable niche breadths of many selfers is most likely to be a temporary phenomenon caused by a transiently expanded realized niche, and both will become constricted over time in comparison to outcrossers. [ABSTRACT FROM AUTHOR]

Abstract: Aim: During its entire history, the Earth has gone through periods of climate change similar in scale and pace to the warming trend observed today in the Anthropocene. The impact of these ancient climatic events on the evolutionary trajectories of organisms provides clues on the organismal response to climate change, including extinction, migration and persistence. Here, we examine the evolutionary response to climate cooling/warming events of the clusioid families Calophyllaceae, Podostemaceae and Hypericaceae (CPH clade) and the genus Hypericum as test cases. Location: Holarctic. Time period: Late Cretaceous–Cenozoic. Major taxa studied: Angiosperms. Methods: We use palaeoclimate simulations, species distribution models and phylogenetic comparative approaches calibrated with fossils. Results: Ancestral CPH lineages could have been distributed in the Holarctic 100 Ma, occupying tropical subhumid assemblages, a finding supported by the fossil record. Expansion to closed‐canopy tropical rain forest habitats occurred after 60 Ma, in the Cenozoic, in agreement with earlier ideas of a post‐Cretaceous origin of current tropical rain forest. Posterior Cooling during the Eocene triggered diversification declines in CPH tropical lineages, and was associated with a climatic shift towards temperate affinities in Hypericum. Hypericum subsequently migrated to tropical mountains, where it encountered different temperate conditions than in the Holarctic. Main conclusions: We hypothesize that most clusioid CPH lineages failed to adapt to temperate regimes during periods of Cenozoic climate change, and went extinct in the Holarctic. In contrast, boreotropical descendants including Hypericum that underwent niche evolution demonstrated selective advantages as climates became colder. Our results point toward macroevolutionary trajectories involving the altering fates of closely related clades that adapt to periods of global climate change versus those that do not. Moreover, they suggest the hypothesis that potentially many clades, particularly inhabitants of boreotropical floras, were likely extirpated from the Holarctic and persist today (if at all) in more southern tropical locations. [ABSTRACT FROM AUTHOR]

The billions of specimens housed in natural science collections provide a tremendous source of under-utilized data that are useful for scientific research, conservation, commerce, and education. Digitization and mobilization of specimen data and images promises to greatly accelerate their utilization. While digitization of natural science collection specimens has been occurring for decades, the vast majority of specimens remain un-digitized. If the digitization task is to be completed in the near future, innovative, high-throughput approaches are needed. To create a dataset for the study of global change in New England, we designed and implemented an industrial-scale, conveyor-based digitization workflow for herbarium specimen sheets. The workflow is a variation of an object-to-image-to-data workflow that prioritizes imaging and the capture of storage container-level data. The workflow utilizes a novel conveyor system developed specifically for the task of imaging flattened herbarium specimens. Using our workflow, we imaged and transcribed specimen-level data for almost 350,000 specimens over a 131-week period; an additional 56 weeks was required for storage container-level data capture. Our project has demonstrated that it is possible to capture both an image of a specimen and a core database record in 35 seconds per herbarium sheet (for intervals between images of 30 minutes or less) plus some additional overhead for container-level data capture. This rate was in line with the pre-project expectations for our approach. Our throughput rates are comparable with some other similar, heighthroughput approaches focused on digitizing herbarium sheets and is as much as three times faster than rates achieved with more conventional non-automated approaches used during the project. We report on challenges encountered during development and use of our system and discuss ways in which our workflow could be improved. The conveyor apparatus software, database schema, configuration files, hardware list, and conveyor schematics are available for download on GitHub. [ABSTRACT FROM AUTHOR]

* Nonrandom collecting practices may bias conclusions drawn from analyses of herbarium records. Recent efforts to fully digitize and mobilize regional floras online offer a timely opportunity to assess commonalities and differences in herbarium sampling biases. * We determined spatial, temporal, trait, phylogenetic, and collector biases in c. 5 million herbarium records, representing three of the most complete digitized floras of the world: Australia (AU), South Africa (SA), and New England, USA (NE). * We identified numerous shared and unique biases among these regions. Shared biases included specimens collected close to roads and herbaria; specimens collected more frequently during biological spring and summer; specimens of threatened species collected less frequently; and specimens of close relatives collected in similar numbers. Regional differences included overrepresentation of graminoids in SA and AU and of annuals in AU; and peak collection during the 1910s in NE, 1980s in SA, and 1990s in AU. Finally, in all regions, a disproportionately large percentage of specimens were collected by very few individuals. We hypothesize that these mega-collectors, with their associated preferences and idiosyncrasies, shaped patterns of collection bias via 'founder effects'. * Studies using herbarium collections should account for sampling biases, and future collecting efforts should avoid compounding these biases to the extent possible. [ABSTRACT FROM AUTHOR]

Rafflesiaceae, crowned 'the greatest prodigy of the vegetable world', produce the largest flowers in angiosperms. They are also holoparasites residing inside their vine hosts, and emerge only during flowering. The floral gigantism and obligate parasitism of Rafflesiaceae have rendered their structure unrecognizable to most plant biologists. The vegetative body is composed of highly reduced strands of cells embedded in the host tissue, and does not differentiate into leaves, stems, or roots. The flowers look and smell like decaying animal flesh and exhibit numerous features unknown in the vast majority of flowering plants. This unusual combination of characters, alongside their generally elevated rates of molecular evolution among commonly used phylogenetic markers and propensity for host-to-parasite horizontal gene transfer, has obscured the phylogenetic affinities of Rafflesiaceae since their discovery two centuries ago. Here, we review the phylogenetic placement of Rafflesiaceae and how it has informed a deeper understanding of the pattern and magnitude of horizontal gene transfer in parasitic plants. We also examine the vegetative and reproductive morphology of Rafflesiaceae to provide insight into how these unusual plants are constructed, and offer clues on their evolution from tiny flowered ancestors to floral giants. [ABSTRACT FROM AUTHOR]

Aim When precise coordinate data for training species distribution models ( SDMs) are lacking, climatic variables are often assigned to centroids of geopolitically defined regions, frequently counties. This is problematic because approximations using centroids may not be representative of the regional climate or the locality from where species actually occur, thus leading to spurious conclusions. We evaluated county centroid climate versus simple alternatives for assigning climate to species observations in the absence of precise occurrence data. Location United States of America. Methods We assessed the disparity between the actual climate of all points within a county and metrics estimating county climate using the climate of geographical centroid, mean county climate and median county climate. To further evaluate the performance of these metrics, we generated SDMs of four common species using these estimates and compared the results with observed species distributions (red trillium, Pacific trillium, tall thistle and annual fleabane). Finally, we projected future ranges for annual fleabane to examine the difference in predicted range change between models. Results Mean and median climate metrics were significantly better fits for approximating the climate of specimen records than climate of the geographical centroid. Moreover, county mean climate SDMs were the most similar to SDMs using actual coordinate data. In contrast, models applying climate to county centroid significantly overpredicted species range. This had implications for future projections of annual fleabane SDMs: the county centroid model predicted a decrease in suitable habitats for this species while other models predicted an increase. Main conclusions County centroid climate, although commonly applied, is not suitable for SDMs as a means to approximate species climate when locality data are less precise. When only county level data are available, and more computationally intensive methods of accounting for spatial uncertainty cannot be readily implemented, we suggest considering mean county climate as an alternative. [ABSTRACT FROM AUTHOR]

PREMISE OF THE STUDY: Partitioning of population genetic variation in plants may be affected by numerous factors including life history and dispersal characteristics. In parasitic plants, interactions with host populations may be an additional factor infl uencing partitioning. To test for hierarchical population genetic patterns related to obligate endoparasitism, we studied three species of Rafflesiaceae, which grow as extremely reduced endophytes infecting Tetrastigma vines in Southeast Asia. METHODS: Microsatellite markers were developed and multilocus genotypes were determined for Rafflesia cantleyi, Rafflesia tuan-mudae , and Sapria himalayana and each of their Tetrastigma hosts. Relatedness among parasite individuals was estimated, and AMOVAs were used to determine levels of population genetic subdivision. KEY RESULTS: Microsatellite genotypes for 340 paired parasite and host samples revealed that host vines were infected by numerous Rafflesiaceae individuals that may spread for up to 14 m within stem tissues. Surprisingly, Rafflesiaceae parasites within a given host are significantly more closely related to each other than individuals of the same species in other host individuals. The pattern of hierarchical population genetic subdivision we detected across species is likely due to limited seed dispersal with reinfection of natal host vines. CONCLUSIONS: These findings demonstrate common population genetic patterns between animal and plant parasites, potentially indicating advantages of close relatives infecting hosts. This study also has important conservation implications for Rafflesiaceae since our data suggest that destruction of a single infected host vine could result in large genetic losses. [ABSTRACT FROM AUTHOR]

Phenology is a key aspect of plant success. Recent research has demonstrated that herbarium specimens can provide important information on plant phenology. Massive digitization efforts have the potential to greatly expand herbarium-based phenological research, but also pose a serious challenge regarding efficient data collection., Here, we introduce CrowdCurio, a crowdsourcing tool for the collection of phenological data from herbarium specimens. We test its utility by having workers collect phenological data (number of flower buds, open flowers and fruits) from specimens of two common New England ( USA) species: Chelidonium majus and Vaccinium angustifolium. We assess the reliability of using nonexpert workers (i.e. Amazon Mechanical Turk) against expert workers. We also use these data to estimate the phenological sensitivity to temperature for both species across multiple phenophases., We found no difference in the data quality of nonexperts and experts. Nonexperts, however, were a more efficient way of collecting more data at lower cost. We also found that phenological sensitivity varied across both species and phenophases., Our study demonstrates the utility of CrowdCurio as a crowdsourcing tool for the collection of phenological data from herbarium specimens. Furthermore, our results highlight the insight gained from collecting large amounts of phenological data to estimate multiple phenophases. [ABSTRACT FROM AUTHOR]

Ferns are the only major lineage of vascular plants that have nutritionally independent sporophyte (diploid) and gametophyte (haploid) life stages. However, the implications of this unique life cycle for fern community ecology have rarely been considered. To compare patterns of community structure between fern sporophytes and gametophytes, we conducted a survey of the ferns of the islands of Moorea and Tahiti (French Polynesia). We first constructed a DNA barcode library (plastid rbcL and trnH- psbA) for the two island floras including 145 fern species. We then used these DNA barcodes to identify more than 1300 field-collected gametophytes from 25 plots spanning an elevational gradient from 200 to 2000 m. We found that species richness of fern sporophytes conforms to the well-known unimodal (i.e., mid-elevation peak) pattern, reaching a maximum at ~1000-1200 m. Moreover, we found that fern sporophyte communities become increasingly phylogenetically clustered at high elevations. In contrast, species richness of fern gametophytes was consistent across sites, and gametophytes showed no correlation of phylogenetic community structure with elevation. Turnover of sporophyte and gametophyte communities was closely linked with elevation at shallow phylogenetic levels, but not at deeper nodes in the tree. Finally, we found several species for which gametophytes had broader ranges than sporophytes, including a vittarioid fern with abundant gametophytes but extremely rare sporophytes. Our study highlights the importance of including diverse life history stages in surveys of community structure, and has implications for the possible impacts of climate change on the distribution of fern diversity. [ABSTRACT FROM AUTHOR]

Media attention to earthquake risks linked to the underground injection of produced waters from oil and gas fracking operations has increased over the past few years. However, little scholarly attention has been devoted to newspaper coverage of events and state policy actions that are associated with 'induced seismicity.' A key concern addressed in this article is whether newspaper coverage is largely unrestrained or is restricted by other factors. Is coverage by differing newspapers influenced by frames emphasizing the economic importance of oil and gas production within the state? We conclude that the answer is 'yes' based on information gleaned from content analyses of newspapers in Ohio, Oklahoma, and Texas from 2009 through 2014. Related Articles [ABSTRACT FROM AUTHOR]

Species in the genus Gracilaria that display conspicuously flattened vegetative morphologies are a taxonomically challenging group of marine benthic red algae. This is a result of their species richness, morphological similarity, and broad phenotypic plasticity. Within this group, the Gracilaria domingensis complex is one of the most common, conspicuous, and morphologically variable species along the tropical western Atlantic Ocean. Previous research has identified that members of this complex belong to two distantly related clades. However, despite this increased phylogentic resolution, species delimitations within each of these clades remain unclear. Our study assessed the species diversity within this difficult complex using morphological and molecular data from three genetic markers ( cox1, UPA, and rbcL). We additionally applied six single-marker species delimitation methods ( SDM: ABGD, GMYCs, GMYCm, SPN, bPTP, and PTP) to rbcL, which were largely in agreement regarding species delimitation. These results, combined with our analysis of morphology, indicate that the G. domingensis complex includes seven distinct species, each of which are not all most closely related: G. cervicornis; a ressurected G. ferox; G. apiculata subsp. apiculata; a new species, Gracilaria baiana sp. nov.; G. intermedia subsp. intermedia; G. venezuelensis; and G. domingensis sensu stricto, which includes the later heterotypic synonym, G. yoneshigueana. Our study demonstrates the value of multipronged strategies, including the use of both molecular and morphological approaches, to decipher cryptic species of red algae. [ABSTRACT FROM AUTHOR]