Evolution of phenotypic disparity in the plant kingdom.

The plant kingdom exhibits diverse bodyplans, from single-celled algae to complex multicellular land plants, but it is unclear how this phenotypic disparity was achieved. Here we show that the living divisions comprise discrete clusters within morphospace, separated largely by reproductive innovations, the extinction of evolutionary intermediates and lineage-specific evolution. Phenotypic complexity correlates not with disparity but with ploidy history, reflecting the role of genome duplication in plant macroevolution. Overall, the plant kingdom exhibits a pattern of episodically increasing disparity throughout its evolutionary history that mirrors the evolutionary floras and reflects ecological expansion facilitated by reproductive innovations. This pattern also parallels that seen in the animal and fungal kingdoms, suggesting a general pattern for the evolution of multicellular bodyplans.

Low tropical diversity during the adaptive radiation of early land plants.

The latitudinal biodiversity gradient, with tropical regions acting as 'evolutionary cradles', is a cornerstone of current biogeographical and ecological theory1. In the modern world floral biodiversity and biomass are overwhelmingly concentrated in the tropics, and it is often assumed that the tropics were evolutionary cradles throughout land plant evolutionary history. For example, the origination and diversification of angiosperms is believed to have taken place in the Cretaceous tropics2 and modern gymnosperms in the Permian tropics3. Here, we show that during the first major diversification of land plants, in the Late Silurian-Early Devonian, land plant biodiversity was much lower at the equator compared to medium-high southern latitudes. Throughout this crucial interval of plant evolution, tropical vegetation remained depauperate and of very low taxonomic biodiversity, although with similar morphological disparity to the more diverse higher latitude floras. Possible explanations for this low tropical floral biodiversity include palaeocontinental configuration or adverse palaeotropical environmental conditions. We discount the possibility that it was simply a fortuitous feature of the biogeographical spread of the earliest vascular land plants.

A possible billion-year-old holozoan with differentiated multicellularity.

Sediments of the Torridonian sequence of the Northwest Scottish Highlands contain a wide array of microfossils, documenting life in a non-marine setting a billion years ago (1 Ga).1-4 Phosphate nodules from the Diabaig Formation at Loch Torridon preserve microorganisms with cellular-level fidelity,5,6 allowing for partial reconstruction of the developmental stages of a new organism, Bicellum brasieri gen. et sp. nov. The mature form of Bicellum consists of a solid, spherical ball of tightly packed cells (a stereoblast) of isodiametric cells enclosed in a monolayer of elongated, sausage-shaped cells. However, two populations of naked stereoblasts show mixed cell shapes, which we infer to indicate incipient development of elongated cells that were migrating to the periphery of the cell mass. These simple morphogenetic movements could be explained by differential cell-cell adhesion.7,8 In fact, the basic morphology of Bicellum is topologically similar to that of experimentally produced cell masses that were shown to spontaneously segregate into two distinct domains based on differential cadherin-based cell adhesion.9 The lack of rigid cell walls in the stereoblast renders an algal affinity for Bicellum unlikely: its overall morphology is more consistent with a holozoan origin. Unicellular holozoans are known today to form multicellular stages within complex life cycles,10-13 so the occurrence of such simple levels of transient multicellularity seen here is consistent with a holozoan affinity. Regardless of precise phylogenetic placement, these fossils demonstrate simple cell differentiation and morphogenic processes that are similar to those seen in some metazoans today.

A novel reproductive strategy in an Early Devonian plant.

Bonacorsi et al. describe a new fossil from the Early Devonian that provides the earliest clear evidence for more advanced reproductive biology in land plants. The plant produced multiple spore size classes, which is an essential innovation necessary for all advanced plant reproductive strategies, including seeds and flowers.

Positron Emission Tomography Imaging With [18F]flortaucipir and Postmortem Assessment of Alzheimer Disease Neuropathologic Changes.

Importance: Positron emission tomography (PET) may increase the diagnostic accuracy and confirm the underlying neuropathologic changes of Alzheimer disease (AD). Objective: To determine the accuracy of antemortem [18F]flortaucipir PET images for predicting the presence of AD-type tau pathology at autopsy. Design, Setting, and Participants: This diagnostic study (A16 primary cohort) was conducted from October 2015 to June 2018 at 28 study sites (27 in US sites and 1 in Australia). Individuals with a terminal illness who were older than 50 years and had a projected life expectancy of less than 6 months were enrolled. All participants underwent [18F]flortaucipir PET imaging, and scans were interpreted by 5 independent nuclear medicine physicians or radiologists. Supplemental autopsy [18F]flortaucipir images and pathological samples were also collected from 16 historically collected cases. A second study (FR01 validation study) was conducted from March 26 to April 26, 2019, in which 5 new readers assessed the original PET images for comparison to autopsy. Main Outcomes and Measures: [18F]flortaucipir PET images were visually assessed and compared with immunohistochemical tau pathology. An AD tau pattern of flortaucipir retention was assessed for correspondence with a postmortem B3-level (Braak stage V or VI) pathological pattern of tau accumulation and to the presence of amyloid-ß plaques sufficient to meet the criteria for high levels of AD neuropathological change. Success was defined as having at least 3 of the 5 readers above the lower bounds of the 95% CI for both sensitivity and specificity of 50% or greater. Results: A total of 156 patients were enrolled in the A16 study and underwent [18F]flortaucipir PET imaging. Of these, 73 died during the study, and valid autopsies were performed for 67 of these patients. Three autopsies were evaluated as test cases and removed from the primary cohort (n = 64). Of the 64 primary cohort patients, 34 (53%) were women and 62 (97%) were white; mean (SD) age was 82.5 (9.6) years; and 49 (77%) had dementia, 1 (2%) had mild cognitive impairment, and 14 (22%) had normal cognition. Prespecified success criteria were met for the A16 primary cohort. The flortaucipir PET scans predicted a B3 level of tau pathology, with sensitivity ranging from 92.3% (95% CI, 79.7%-97.3%) to 100.0% (95% CI, 91.0%-100.0%) and specificity ranging from 52.0% (95% CI, 33.5%-70.0%) to 92.0% (95% CI, 75.0%-97.8%). A high level of AD neuropathological change was predicted with sensitivity of 94.7% (95% CI, 82.7%-98.5%) to 100.0% (95% CI, 90.8%-100.0%) and specificity of 50.0% (95% CI, 32.1%-67.9%) to 92.3% (95% CI, 75.9%-97.9%). The FR01 validation study also met prespecified success criteria. Addition of the supplemental autopsy data set and 3 test cases, which comprised a total of 82 patients and autopsies for both the A16 and FR01 studies, resulted in improved specificity and comparable overall accuracy. Among the 156 enrolled participants, 14 (9%) experienced at least 1 treatment-emergent adverse event. Conclusions and Relevance: This study's findings suggest that PET imaging with [18F]flortaucipir could be used to identify the density and distribution of AD-type tau pathology and the presence of high levels of AD neuropathological change, supporting a neuropathological diagnosis of AD.

Mid-Devonian Archaeopteris Roots Signal Revolutionary Change in Earliest Fossil Forests.

The origin of trees and forests in the Mid Devonian (393-383 Ma) was a turning point in Earth history, marking permanent changes to terrestrial ecology, geochemical cycles, atmospheric CO2 levels, and climate. However, how all these factors interrelate remains largely unknown. From a fossil soil (palaeosol) in the Catskill region near Cairo NY, USA, we report evidence of the oldest forest (mid Givetian) yet identified worldwide. Similar to the famous site at Gilboa, NY, we find treefern-like Eospermatopteris (Cladoxylopsida). However, the environment at Cairo appears to have been periodically drier. Along with a single enigmatic root system potentially belonging to a very early rhizomorphic lycopsid, we see spectacularly extensive root systems here assigned to the lignophyte group containing the genus Archaeopteris. This group appears pivotal to the subsequent evolutionary history of forests due to possession of multiple advanced features and likely relationship to subsequently dominant seed plants. Here we show that Archaeopteris had a highly advanced root system essentially comparable to modern seed plants. This suggests a unique ecological role for the group involving greatly expanded energy and resource utilization, with consequent influence on global processes much greater than expected from tree size or rooting depth alone.

Palaeontology: The Rhynie Chert Is the Gift that Keeps on Giving.

The earliest record of a terrestrial testate amoeba is reported. This provides further evidence that early terrestrial ecosystems were more complex and modern in aspect than previously considered, in terms of biota, ecological interactions and biogeochemical cycling.

Randomized clinical trial of a community navigation intervention to improve well-being in persons living with HIV and other co-morbidities.

Long-term survival of people living with HIV (PLWH) is associated with the development of co-morbid conditions and need for symptom management and other efforts to enhance quality of life. We conducted a longitudinal, randomized trial over 36 months to evaluate the effect of a community-based navigator intervention to provide early palliative care to 179 PLWH and other chronic conditions. Outcomes included quality of life, symptom management, coping ability, social support, self-management, and completion of advance directives. Data were analyzed using SAS mixed effects model repeat measurement. Our navigator program showed variable improvement over time of three outcome variables, self-blame, symptom distress, and HIV self-management. However, the program did not improve overall quality of life, social support, or completion of advance directives.

Safe and Appropriate Use of Methadone in Hospice and Palliative Care: Expert Consensus White Paper.

Methadone has several unique characteristics that make it an attractive option for pain relief in serious illness, but the safety of methadone has been called into question after reports of a disproportionate increase in opioid-induced deaths in recent years. The American Pain Society, College on Problems of Drug Dependence, and the Heart Rhythm Society collaborated to issue guidelines on best practices to maximize methadone safety and efficacy, but guidelines for the end-of-life scenario have not yet been developed. A panel of 15 interprofessional hospice and palliative care experts from the U.S. and Canada convened in February 2015 to evaluate the American Pain Society methadone recommendations for applicability in the hospice and palliative care setting. The goal was to develop guidelines for safe and effective management of methadone therapy in hospice and palliative care. This article represents the consensus opinion of the hospice and palliative care experts for methadone use at end of life, including guidance on appropriate candidates for methadone, detail in dosing, titration, and monitoring of patients' response to methadone therapy.

The Interrelationships of Land Plants and the Nature of the Ancestral Embryophyte.

The evolutionary emergence of land plant body plans transformed the planet. However, our understanding of this formative episode is mired in the uncertainty associated with the phylogenetic relationships among bryophytes (hornworts, liverworts, and mosses) and tracheophytes (vascular plants). Here we attempt to clarify this problem by analyzing a large transcriptomic dataset with models that allow for compositional heterogeneity between sites. Zygnematophyceae is resolved as sister to land plants, but we obtain several distinct relationships between bryophytes and tracheophytes. Concatenated sequence analyses that can explicitly accommodate site-specific compositional heterogeneity give more support for a mosses-liverworts clade, "Setaphyta," as the sister to all other land plants, and weak support for hornworts as the sister to all other land plants. Bryophyte monophyly is supported by gene concatenation analyses using models explicitly accommodating lineage-specific compositional heterogeneity and analyses of gene trees. Both maximum-likelihood analyses that compare the fit of each gene tree to proposed species trees and Bayesian supertree estimation based on gene trees support bryophyte monophyly. Of the 15 distinct rooted relationships for embryophytes, we reject all but three hypotheses, which differ only in the position of hornworts. Our results imply that the ancestral embryophyte was more complex than has been envisaged based on topologies recognizing liverworts as the sister lineage to all other embryophytes. This requires many phenotypic character losses and transformations in the liverwort lineage, diminishes inconsistency between phylogeny and the fossil record, and prompts re-evaluation of the phylogenetic affinity of early land plant fossils, the majority of which are considered stem tracheophytes.

The timescale of early land plant evolution.

Establishing the timescale of early land plant evolution is essential for testing hypotheses on the coevolution of land plants and Earth's System. The sparseness of early land plant megafossils and stratigraphic controls on their distribution make the fossil record an unreliable guide, leaving only the molecular clock. However, the application of molecular clock methodology is challenged by the current impasse in attempts to resolve the evolutionary relationships among the living bryophytes and tracheophytes. Here, we establish a timescale for early land plant evolution that integrates over topological uncertainty by exploring the impact of competing hypotheses on bryophyte-tracheophyte relationships, among other variables, on divergence time estimation. We codify 37 fossil calibrations for Viridiplantae following best practice. We apply these calibrations in a Bayesian relaxed molecular clock analysis of a phylogenomic dataset encompassing the diversity of Embryophyta and their relatives within Viridiplantae. Topology and dataset sizes have little impact on age estimates, with greater differences among alternative clock models and calibration strategies. For all analyses, a Cambrian origin of Embryophyta is recovered with highest probability. The estimated ages for crown tracheophytes range from Late Ordovician to late Silurian. This timescale implies an early establishment of terrestrial ecosystems by land plants that is in close accord with recent estimates for the origin of terrestrial animal lineages. Biogeochemical models that are constrained by the fossil record of early land plants, or attempt to explain their impact, must consider the implications of a much earlier, middle Cambrian-Early Ordovician, origin.

Palaeoecology and palaeophytogeography of the Rhynie chert plants: further evidence from integrated analysis of in situ and dispersed spores.

The remarkably preserved Rhynie chert plants remain pivotal to our understanding of early land plants. The extraordinary anatomical detail they preserve is a consequence of exceptional preservation, by silicification, in the hot-springs environment they inhabited. However, this has prompted questions as to just how typical of early land plants the Rhynie chert plants really are. Some have suggested that they were highly adapted to the unusual hot-springs environment and are unrepresentative of 'normal' plants of the regional flora. New quantitative analysis of dispersed spore assemblages from the stratigraphical sequence of the Rhynie outlier, coupled with characterization of the in situ spores of the Rhynie chert plants, permits investigation of their palaeoecology and palaeophytogeography. It is shown that the Rhynie inland intermontane basin harboured a relatively diverse flora with only a small proportion of these plants actually inhabiting the hot-springs environment. However, the flora of the Rhynie basin differed from coeval lowland floodplain deposits on the same continent, as it was less diverse, lacked some important spore groups and contained some unique elements. At least some of the Rhynie plants (e.g. Horneophyton lignieri) existed outside the hot-springs environment, inhabiting the wider basin, and were indeed palaeogeographically widespread. They probably existed in the hot-springs environment because they were preadapted to this unstable and harsh setting.This article is part of a discussion meeting issue 'The Rhynie cherts: our earliest terrestrial ecosystem revisited'.

The predictive value of fall assessment tools for patients admitted to hospice care.

OBJECTIVES: Fall assessment tools are commonly used to evaluate the likelihood of fall. For patients found to be at high risk, patient-specific fall prevention interventions are implemented. The purposes of this study were to describe the population, evaluate and compare the efficacy of fall assessment tools, and suggest the best use for these tools in hospice. METHODS: Data were downloaded from the electronic medical record for all patients who were admitted to and died in hospice care in 2013. Variables included demographic, clinical and initial fall assessment scores that had been computed on admission to hospice care, using our standard fall assessment tool. To facilitate comparison among three tools, additional fall assessment calculations were made for each patient using the Morse Fall Scale and MACH-10, two tools commonly used in a variety of healthcare settings. RESULTS: Data were available for 3446 hospice patients. Female patients were less likely to fall than males; Fallers lived longer than Nonfallers; and patients with a primary dementia diagnosis fell 10 days sooner than those with a primary non-dementia diagnosis. A comparison of three fall assessment tools revealed that no tool had a good positive predictive value, but each demonstrated a good negative predictive value. CONCLUSIONS: Fall assessment scores should not be used as the sole predictor of likelihood of fall, and are best used as a supplement to clinical judgement. Patients with a primary dementia diagnosis are likely to fall earlier in their hospice care than those with other primary diagnoses.

Palaeoecology of a billion-year-old non-marine cyanobacterium from the Torridon Group and Nonesuch Formation.

A new chroococcalean cyanobacterium is described from approximately 1-billion-year-old non-marine deposits of the Torridonian Group of Scotland and the Nonesuch Formation of Michigan, USA. Individual cells of the new microfossil, Eohalothece lacustrina gen. et sp. nov., are associated with benthic microbial biofilms, but the majority of samples are recovered in palynological preparations in the form of large, apparently planktonic colonies, similar to extant species of Microcystis. In the Torridonian, Eohalothece is associated with phosphatic nodules, and we have developed a novel hypothesis linking Eohalothece to phosphate deposition in ancient freshwater settings. Extant cyanobacteria can be prolific producers of extracellular microcystins, which are non-ribosomal polypeptide phosphatase inhibitors. Microcystins may have promoted the retention and concentration of sedimentary organic phosphate prior to mineralization of francolite and nodule formation. This has a further implication that the Torridonian lakes were nitrogen limited as the release of microcystins is enhanced under such conditions today. The abundance and wide distribution of Eohalothece lacustrina attests to the importance of cyanobacteria as oxygen-producing photoautotrophs in lacustrine ecosystems at the time of the Mesoproterozoic-Neoproterozoic transition.

Fixed-Dose Subcutaneous Methylnaltrexone in Patients with Advanced Illness and Opioid-Induced Constipation: Results of a Randomized, Placebo-Controlled Study and Open-Label Extension.

BACKGROUND: Subcutaneous methylnaltrexone (MNTX), dosed based on body weight, is efficacious and well tolerated in inducing bowel movements in patients with advanced illness and opioid-induced constipation (OIC); however, fixed-dose administration of MNTX may improve ease of administration. OBJECTIVE: The study objective was to assess safety and efficacy of fixed-dose MNTX in two phase 4 trials. METHODS: In a double-blind, randomized, placebo-controlled trial (RCT), patients with advanced illness and OIC received MNTX (8 mg or 12 mg by body weight [38 kg to <62 kg or ≥62 kg, respectively]) or placebo every other day (QOD) for two weeks. Patients completing the RCT could enroll in an open-label extension (OLE) study with MNTX administered as needed (PRN). The primary endpoint was percentage of patients with a rescue-free bowel movement (RFBM) within four hours after ≥2 of the first 4 doses in the first week. RESULTS: In the RCT, 116 and 114 patients received MNTX and placebo, respectively, and 149 patients continued to the OLE study. The percentage of patients achieving primary endpoint was 62.9% and 9.6% for MNTX and placebo groups, respectively (p<0.0001). Median time to RFBM after the first dose was 0.8 hour and 23.6 hours in MNTX and placebo groups, respectively (p<0.0001). Efficacy results during the OLE study were consistent with the RCT. MNTX demonstrated a favorable safety profile in the RCT and OLE study. CONCLUSION: Fixed-dose MNTX administered QOD in the RCT and PRN in the OLE study demonstrated robust efficacy and was well tolerated in treating OIC in patients with advanced illness.

Conservation of Male Sterility 2 function during spore and pollen wall development supports an evolutionarily early recruitment of a core component in the sporopollenin biosynthetic pathway.

The early evolution of plants required the acquisition of a number of key adaptations to overcome physiological difficulties associated with survival on land. One of these was a tough sporopollenin wall that enclosed reproductive propagules and provided protection from desiccation and UV-B radiation. All land plants possess such walled spores (or their derived homologue, pollen). We took a reverse genetics approach, consisting of knock-out and complementation experiments to test the functional conservation of the sporopollenin-associated gene MALE STERILTY 2 (which is essential for pollen wall development in Arabidopsis thaliana) in the bryophyte Physcomitrella patens. Knock-outs of a putative moss homologue of the A. thaliana MS2 gene, which is highly expressed in the moss sporophyte, led to spores with highly defective walls comparable to that observed in the A. thaliana ms2 mutant, and extremely compromised germination. Conversely, the moss MS2 gene could not rescue the A. thaliana ms2 phenotype. The results presented here suggest that a core component of the biochemical and developmental pathway required for angiosperm pollen wall development was recruited early in land plant evolution but the continued increase in pollen wall complexity observed in angiosperms has been accompanied by divergence in MS2 gene function.

Lacustrine Nostoc (Nostocales) and associated microbiome generate a new type of modern clotted microbialite.

Microbialites are mineral formations formed by microbial communities that are often dominated by cyanobacteria. Carbonate microbialites, known from Proterozoic times through the present, are recognized for sequestering globally significant amounts of inorganic carbon. Recent ecological work has focused on microbial communities dominated by cyanobacteria that produce microbial mats and laminate microbialites (stromatolites). However, the taxonomic composition and functions of microbial communities that generate distinctive clotted microbialites (thrombolites) are less well understood. Here, microscopy and deep shotgun sequencing were used to characterize the microbiome (microbial taxa and their genomes) associated with a single cyanobacterial host linked by 16S sequences to Nostoc commune Vaucher ex Bornet & Flahault, which dominates abundant littoral clotted microbialites in shallow, subpolar, freshwater Laguna Larga in southern Chile. Microscopy and energy-dispersive X-ray spectroscopy suggested the hypothesis that adherent hollow carbonate spheres typical of the clotted microbialite begin development on the rigid curved outer surfaces of the Nostoc balls. A surface biofilm included >50 nonoxygenic bacterial genera (taxa other than Nostoc) that indicate diverse ecological functions. The Laguna Larga Nostoc microbiome included the sulfate reducers Desulfomicrobium and Sulfospirillum and genes encoding all known proteins specific to sulfate reduction, a process known to facilitate carbonate deposition by increasing pH. Sequences indicating presence of nostocalean and other types of nifH, nostocalean sulfide:ferredoxin oxidoreductase (indicating anoxygenic photosynthesis), and biosynthetic pathways for the secondary products scytonemin, mycosporine, and microviridin toxin were identified. These results allow comparisons with microbiota and microbiomes of other algae and illuminate biogeochemical roles of ancient microbialites.