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In mammalian embryos, proper zygotic genome activation (ZGA) underlies totipotent development. Double homeobox (DUX)-family factors participate in ZGA, and mouse Dux is required for forming cultured two-cell (2C)-like cells. Remarkably, in mouse embryonic stem cells, Dux is activated by the tumor suppressor p53, and Dux expression promotes differentiation into expanded-fate cell types. Long-read sequencing and assembly of the mouse Dux locus reveals its complex chromatin regulation including putative positive and negative feedback loops. We show that the p53–DUX/DUX4 regulatory axis is conserved in humans. Furthermore, we demonstrate that cells derived from patients with facioscapulohumeral muscular dystrophy (FSHD) activate human DUX4 during p53 signaling via a p53-binding site in a primate-specific subtelomeric long terminal repeat (LTR)10C element. In summary, our work shows that p53 activation convergently evolved to couple p53 to Dux/DUX4 activation in embryonic stem cells, embryos and cells from patients with FSHD, potentially uniting the developmental and disease regulation of DUX-family factors and identifying evidence-based therapeutic opportunities for FSHD. p53 activates Dux in mouse embryos and embryonic stem cells, as well as DUX4 in human facioscapulohumeral muscular dystrophy cell models.

Background Myotonic dystrophy type 1 (DM1) is caused by CTG repeat expansions in the DMPK gene and is the most common form of muscular dystrophy. Patients can have long delays from onset to diagnosis, since clinical signs and symptoms are often nonspecific and overlapping with other disorders. Clinical genetic testing by Southern blot or triplet‐primed PCR (TP‐PCR) is technically challenging and cost prohibitive for population surveys. Methods Here, we present a high throughput, low‐cost screening tool for CTG repeat expansions using TP‐PCR followed by high resolution melt curve analysis with saturating concentrations of SYBR GreenER dye. Results We determined that multimodal melt profiles from the TP‐PCR assay are a proxy for amplicon length stoichiometry. In a screen of 10,097 newborn blood spots, melt profile analysis accurately reflected the tri‐modal distribution of common alleles from 5 to 35 CTG repeats, and identified the premutation and full expansion alleles. Conclusion We demonstrate that robust detection of expanded CTG repeats in a single tube can be achieved from samples derived from specimens with minimal template DNA such as dried blood spots (DBS). This technique is readily adaptable to large‐scale testing programs such as population studies and newborn screening programs., Myotonic dystrophy type 1 is one of the most common forms of muscular dystrophy, caused by a CTG repeat expansion in the DMPK gene. Here, we present a high throughput, low‐cost screening tool to detect an expansion of the CTG repeat using TP‐PCR followed by melt curve analysis with saturating concentrations of SYBR GreenER dye. We demonstrate that accurate and robust detection of expanded CTG repeats in a single tube can be achieved from samples derived from specimens with minimal template DNA such as dried blood spots.

Increasing temperatures and drought in desert ecosystems are predicted to cause decreased vegetation density combined with barren ground expansion. It remains unclear how nutrient availability, microbial diversity, and the associated functional capacity vary between the vegetated canopy and gap soils. The specific aim of this study was to characterize canopy versus gap microsite effect on soil microbial diversity, the capacity of gap soils to serve as a canopy soil microbial reservoir, nitrogen (N)-mineralization genetic potential (ureC gene abundance) and urease enzyme activity, and microbial-nutrient pool associations in four arid-hyperarid geolocations of the western Sonoran Desert, Arizona, United States. Microsite combined with geolocation explained 57% and 45.8% of the observed variation in bacterial/archaeal and fungal community composition, respectively. A core microbiome of amplicon sequence variants was shared between the canopy and gap soil communities; however, canopy soils included abundant taxa that were not present in associated gap communities, thereby suggesting that these taxa cannot be sourced from the associated gap soils. Linear mixed-effects models showed that canopy soils have significantly higher microbial richness, nutrient content, and organic N-mineralization genetic and functional capacity. Furthermore, ureC gene abundance was detected in all samples, suggesting that ureC is a relevant indicator of N mineralization in deserts. Additionally, novel phylogenetic associations were observed for ureC, with the majority belonging to Actinobacteria and uncharacterized bacteria. Thus, key N-mineralization functional capacity is associated with a dominant desert phylum. Overall, these results suggest that lower microbial diversity and functional capacity in gap soils may impact ecosystem sustainability as aridity drives open-space expansion in deserts. IMPORTANCE Increasing aridity will drive a shift in desert vegetation and interspace gap (microsite) structure toward gap expansion. To evaluate the impact of gap expansion, we assess microsite effects on soil nutrients, microbiome community composition and functional capacity, and the potential of gap soils to serve as microbial reservoirs for plant root-associated microbiomes in an arid ecosystem. Results indicate that gap soils have significantly lower bioavailable nutrients, microbial richness, and N-mineralization functional capacity. Further, abundance of the bacterial urease gene (ureC) correlates strongly with N availability, and its major phylogenetic association is with Actinobacteria, the dominant phylum found in deserts. This finding is relevant because it identifies an important N-mineralization capacity indicator in the arid soil microbiome. Such indicators are needed to understand the relationships between interplant gap expansion and microbial diversity and functional potential associated with plant sustainability. This will be a critical step in recovery of land degraded by aridity stress.

[Motivation]: Trait data are fundamental to the quantitative description of plant form and function. Although root traits capture key dimensions related to plant responses to changing environmental conditions and effects on ecosystem processes, they have rarely been included in large-scale comparative studies and global models. For instance, root traits remain absent from nearly all studies that define the global spectrum of plant form and function. Thus, to overcome conceptual and methodological roadblocks preventing a widespread integration of root trait data into large-scale analyses we created the Global Root Trait (GRooT) Database. GRooT provides ready to use data by combining the expertise of root ecologists with data mobilization and curation. Specifically, we (a) determined a set of core root traits relevant to the description of plant form and function based on an assessment by experts, (b) maximized species coverage through data standardization within and among traits, and (c) implemented data quality checks., [Main types of variables contained]: GRooT contains 114,222 trait records on 38 continuous root traits.Spatial location and grain: Global coverage with data from arid, continental, polar, temperate and tropical biomes. Data on root traits were derived from experimental studies and field studies., [Time period and grain]: Data were recorded between 1911 and 2019., [Major taxa and level of measurement]: GRooT includes root trait data for which taxonomic information is available. Trait records vary in their taxonomic resolution, with subspecies or varieties being the highest and genera the lowest taxonomic resolution available. It contains information for 184 subspecies or varieties, 6,214 species, 1,967 genera and 254 families. Owing to variation in data sources, trait records in the database include both individual observations and mean values., [Software format]: GRooT includes two csv files. A GitHub repository contains the csv files and a script in R to query the database., The study has been supported by the TRY initiative on plant traits (http://www.try-db.org). The TRY initiative and database are hosted, developed and maintained at the Max Planck Institute for Biogeochemistry, Jena, Germany. TRY is currently supported by DIVERSITAS/Future Earth and the German Centre for Integrative Biodiversity Research (iDiv) Halle-Jena-Leipzig. Open access funding enabled and organized by Projekt DEAL.

Background Very few studies have been conducted on the seroprevalence of syphilis in Gabon. According to the World Health Organization, the average seroprevalence of syphilis has declined from 5.5 to 1.1% in Central Africa. The aim of this study was to test the hypothesis that syphilis decreased in Gabon between 2004 and 2016 and to identify factors involved in this pattern by testing a large sample of first-time blood donors in the capital Libreville. Methods The detection of Treponema pallidum was done using a Rapid Plasma Reagin test (RPR) and confirmed by an ELISA test using the Biorad Syphilis Total Antibody EIA II kit or BioMerieux Trepanostika TP recombinant. Assays were performed by dedicated technicians according to manufacturers’ recommendations and following the laboratory standard operating procedures. Test results were manually transferred into the laboratory Excel files and hand-written in the laboratory logbook for syphilis testing. Logistic regression was used to assess the impact of sociodemographic characteristics on syphilis marker seroprevalence in both univariate and multivariable analysis. Odds ratios (OR) and 95% confidence intervals were calculated. Results The seroprevalence of syphilis markers was 8.4% (95% CI = 7.9–8.9) in 2004 and 2.4% (95% CI = 2.1–2.7) in 2016. The difference was significant [OR = 3.78; 95% CI (3.26–4.38); P

The challenges of restoration in dryland ecosystems are growing due to a rise in anthropogenic disturbance and increasing aridity. Plant functional traits are often used to predict plant performance and can offer a window into potential outcomes of restoration efforts across environmental gradients. We analyzed a database including 15 yr of seeding outcomes across 150 sites on the Colorado Plateau, a cold desert ecoregion in the western United States, and analyzed the independent and interactive effects of functional traits (seed mass, height, and specific leaf area) and local biologically relevant climate variables on seeding success. We predicted that the best models would include an interaction between plant traits and climate, indicating a need to match the right trait value to the right climate conditions to maximize seeding success. Indeed, we found that both plant height and seed size significantly interacted with temperature seasonality, with larger seeds and taller plants performing better in more seasonal environments. We also determined that these trait-environment patterns are not influenced by whether a species is native or nonnative. Our results inform the selection of seed mixes for restoring areas with specific climatic conditions, while also demonstrating the strong influence of temperature seasonality on seeding success in the Colorado Plateau region.

Cardiomyopathy develops in >90% of Duchenne muscular dystrophy (DMD) patients by the second decade of life. We assessed the associations between DMD gene mutations, as well as Latent transforming growth factor-beta-binding protein 4 (LTBP4) haplotypes, and age at onset of myocardial dysfunction in DMD. DMD patients with baseline normal left ventricular systolic function and genotyping between 2004 and 2013 were included. Patients were grouped in multiple ways: specific DMD mutation domains, true loss-of-function mutations (group A) versus possible residual gene expression (group B), and LTBP4 haplotype. Age at onset of myocardial dysfunction was the first echocardiogram with an ejection fraction DMD genotype mutation domains (13.7±4.8 versus 14.3±1.0 versus 14.3±2.9 versus 13.8±2.5, p=0.97), groups A and B (14.4±2.8 versus 12.1±4.4, p=0.09), or LTBP4 haplotypes (14.5±3.2 versus 13.1±3.2 versus 11.0±2.8, p=0.18). DMD gene mutations involving the hinge 3 region, actin-binding domain, and exons 45–49, as well as the LTBP4 IAAM haplotype, were not associated with age of left ventricular dysfunction onset in DMD.

We describe a new assemblage of small carbonaceous fossils (SCFs) from diagenetically 9 minimally altered clays and siltstones of Terreneuvian age from the Lontova and Voosi formations of 10 Estonia, Lithuania and Russia. This is the first detailed account of an SCF assemblage from the 11 Terreneuvian, and includes a number of previously undocumented Cambrian organisms. Recognisably 12 bilaterian-derived SCFs include abundant protoconodonts (total-group Chaetognatha), and distinctive 13 cuticular spines of scalidophoran worms. Alongside these metazoan remains are a range of protistan-14 grade fossils, including Retiranus balticus gen. et sp. nov., a distinctive funnel-shaped or sheet-like 15 problematicum characterized by terminal or marginal vesicles, and Lontohystrichosphaera grandis 16 gen. et sp. nov., a large (100–550 μm) ornamented vesicular microfossil. Together these data offer a 17 fundamentally enriched view of Terreneuvian life in the epicratonic seas of Baltica, from an episode 18 where records of non-biomineralized life are currently sparse. Even so, the recovered assemblages 19 contain a lower diversity of metazoans than SCF biotas from younger (Stage 4) Baltic successions that 20 represent broadly equivalent environments, echoing the diversification signal recorded in the coeval 21 shelly and trace-fossil records. Close comparison to the biostratigraphic signal from Fortunian small 22 shelly fossils (SSFs) supports a late Fortunian age for most of the Lontova/Voosi succession, rather 23 than a younger (wholly Stage 2) range.

Variation in climate has been demonstrated to be a powerful driver of selection and local adaptation among plant populations. Variation in functional traits among populations can also be indicative of the drivers of local adaptation. However, it is not clear to what extent species exhibit consistent patterns of local adaptation as revealed by common, heritable trait–environment relationships among populations. To address this, we conducted a meta-analysis of common garden studies of grass populations to quantify the degree of heritability of several commonly measured functional traits, and whether demonstrated heritability was driven by climate. We found that leaf size, specific leaf area (SLA) and total biomass all displayed strong broad-sense of heritability. Both leaf area and SLA decreased significantly with increasing temperature seasonality among populations within species, while total biomass increased with increasing annual and dry season precipitation, and decreased with increasing precipitation seasonality. These results indicate similar, consistent drivers of local adaptation among species of grasses. Further information on trait–environment relationships within species could greatly improve our ability to predict broad scale patterns in functional diversity across multiple levels of ecological organization. Expanding the range of traits and regions incorporated in common garden research, in the present case by incorporating root traits and Southern Hemisphere taxa, will provide even greater benefits to the fields of restoration, conservation, and global change ecology.

Bedding-plane assemblages of Ediacaran fossils from Mistaken Point, Newfoundland, are among the oldest known records of complex multicellular life on Earth (dated to ~565 Ma). The in situ preservation of these sessile but otherwise deeply enigmatic organisms means that statistical analyses of specimen positions can be used to illuminate their underlying ecological dynamics, including the interactions between taxa.Fossil assemblages on Mistaken Point D and E surfaces were mapped to millimeter accuracy using differentiated GPS. Spatial correlations between 10 well-defined taxa (Bradgatia, Charniid,Charniodiscus,Fractofusus, Ivesheadiomorphs, Lobate Discs,Pectinifrons,Plumeropriscum,Hiemalora, andThectardis) were identified using Bayesian network inference (BNI), and then described and analyzed using spatial point-process analysis. BNI found that the E-surface community had a complex web of interactions and associations between taxa, with all but one taxon (Thectardis) interacting with at least one other. The unique spatial distribution ofThectardissupports previous, morphology-based arguments for its fundamentally distinct nature. BNI revealed that the D-surface community showed no interspecific interactions or associations, a pattern consistent with a homogeneous environment.On the E surface, all six of the abundant taxonomic groups (Fractofusus,Bradgatia, Charniid,Charniodiscus,Thectardis, andPlumeropriscum) were found to have a unique set of interactions with other taxa, reflecting a broad range of underlying ecological responses. Four instances of habitat associations were detected between taxa, of which two (Charniodiscus–PlumeropriscumandPlumeropriscum–Fractofusus) led to weak competition for resources. One case of preemptive competition between Charniid and Lobate Discs was detected. There were no instances of interspecific facilitation. Ivesheadiomorph interactions mirror those ofFractofususandCharniodiscus, identifying them as a form-taxonomic grouping of degradationally homogenized taphomorphs. The absence of increased fossil abundance in proximity to these taphomorphs argues against scavenging or saprophytic behaviors dominating the E-surface community.

IntroductionComputational analysis of genome or exome sequences may improve inherited disease diagnosis, but is costly and time-consuming.MethodsWe describe the use of iobio, a web-based tool suite for intuitive, real-time genome diagnostic analyses.ResultsWe used iobio to identify the disease-causing variant in a patient with early infantile epileptic encephalopathy with prior nondiagnostic genetic testing.ConclusionsIobio tools can be used by clinicians to rapidly identify disease-causing variants from genomic patient sequencing data.

While the relationship between plant and microbial diversity has been well studied in grasslands, less is known about similar relationships in forests, especially for obligately symbiotic arbuscular mycorrhizal (AM) fungi. To assess the effect of varying tree diversity on microbial alpha- and beta-diversity, we sampled soil from plots in a high-density tree diversity experiment in Minnesota, USA, 3 years after establishment. About 3 of 12 tree species are AM hosts; the other 9 primarily associate with ectomycorrhizal fungi. We used phospho- and neutral lipid fatty acid analysis to characterize the biomass and functional identity of the whole soil bacterial and fungal community and high throughput sequencing to identify the species-level richness and composition of the AM fungal community. We found that plots of differing tree composition had different bacterial and fungal communities; plots with conifers, and especially Juniperus virginiana, had lower densities of several bacterial groups. In contrast, plots with a higher density or diversity of AM hosts showed no sign of greater AM fungal abundance or diversity. Our results indicate that early responses to plant diversity vary considerably across microbial groups, with AM fungal communities potentially requiring longer timescales to respond to changes in host tree diversity.

Variation in life-history strategies can affect metapopulation dynamics and consequently the composition and diversity of communities. However, data sets that allow for the full range of species turnover from colonization to extinction over relevant time periods are limited. The late Quaternary record provides unique opportunities to explore the traits that may have influenced interspecific variation in responses to past climate warming, in particular the rate at which species colonized newly suitable habitat or went locally extinct from degrading habitat. We controlled for differences in species climate niches in order to predict expected colonization and extinction sequences recorded in packrat middens from 15 localities in the Mohave, Sonoran, and Chihuahuan deserts of North America. After accounting for temperature niche differences, we tested the hypotheses that dispersal syndrome (none, wind, vertebrate), growth form (herb, shrub, tree) and seed mass mediated variation in postglacial colonization lags among species, whereas clonality (clonal, non-clonal), growth form, and seed mass affected extinction lags. Growth form and dispersal syndrome interactively affected colonization lags, where herbaceous species lacking long-distance dispersal mechanisms exhibited lags that exceeded those of woody, wind or vertebrate-dispersed species by an average of 2,000-5,000 yr. Growth form and seed mass interactively affected extinction lags, with very small-seeded shrubs persisting for 4,000-8,000 yr longer than other functional groups. Taller, vertebrate-dispersed plants have been shown in other studies to disperse farther than shorter plants without specialized dispersal mechanisms. We found that variation along this axis of dispersal syndromes resulted in dramatic differences in colonization rates in response to past climate change. Very small seeded shrubs may have a unique combination of long vegetative and seed bank lifetimes that may allow them to persist for long periods despite declines in habitat condition. This study indicates that readily measurable traits may help predict which species will be more or less sensitive to future climate change, and inform interventions that can stabilize and promote at-risk populations.

International audience; The clinical application of advanced next-generation sequencing technologies is increasingly uncovering novel classes of mutations that may serve as potential targets for precision medicine therapeutics. Here, we show that a deep intronic splice defect in the COL6A1 gene, originally discovered by applying muscle RNA sequencing in patients with clinical findings of collagen VI-related dystrophy (COL6-RD), inserts an in-frame pseudoexon into COL6A1 mRNA, encodes a mutant collagen a1(VI) protein that exerts a dominant-negative effect on collagen VI matrix assembly, and provides a unique opportunity for splice-correction approaches aimed at restoring normal gene expression. Using splicemodulating antisense oligomers, we efficiently skipped the pseudoexon in patient-derived fibroblast cultures and restored a wild-type matrix. Similarly, we used CRISPR/Cas9 to precisely delete an intronic sequence containing the pseudoexon and efficiently abolish its inclusion while preserving wild-type splicing. Considering that this splice defect is emerging as one of the single most frequent mutations in COL6-RD, the design of specific and effective splice-correction therapies offers a promising path for clinical translation.

Background Previous studies have demonstrated improvements in efficiency when specific procedures are performed in a designated preoperative area prior to proceeding to the operating room. In this study the authors sought to evaluate if spinal anesthesia could be safely and efficiently administered prior to proceeding to the operating room when compared to general anesthesia and spinal anesthesia administered in the operating room. Methods The authors reviewed the electronic health record at a single institution between the years 2012 to 2018. Total joint arthroplasties by a single surgeon were identified and the specific time frames of interest were measured and compared between patients who received a spinal anesthetic in the preoperative area, patients who received a general anesthetic, and patients who received a spinal anesthetic in the operating room. These time frames of interest included: anesthesia induction time, operating room recovery time, post anesthesia recovery unit time, and operating room turnover time. The electronic medical record was also reviewed for spinal-related adverse events. Categorical variables were compared using the Fisher exact test and continuous variables were compared using equal-variance t-test and one-way ANOVA. Results The study cohort consisted of 246 patients (142 total hip arthroplasty and 104 total knee arthroplasty); 40.2% (99) of patients received a general anesthetic (GA), 52% (128) of patients received a preoperative spinal anesthetic (PSA), and 7.7% (19) of patients received an intraoperative spinal anesthetic (ISA). Preoperative spinal anesthetics demonstrated a shorter anesthesia induction time, shorter operating room recovery times, shorter PACU recovery times, and longer operating room turnover times when compared to general anesthesia and intraoperative spinals. There were no spinal-related adverse events. Conclusion The results of this retrospective cohort study demonstrate that administration of spinal anesthesia in the preoperative area is safe as compared with intra-operative spinal administration. Pre-operative spinal for total joint arthroplasty reduces time spent in the operating room and PACU when compared with general anesthesia and intraoperative spinal but it does not substantially affect overall perioperative efficiency.

Aridity is an important environmental filter in the assembly of plant communities worldwide. The extent to which root traits mediate responses to aridity, and how they are coordinated with leaf traits, remains unclear. Here, we measured variation in root tissue density (RTD), specific root length (SRL), specific leaf area (SLA), and seed size within and among thirty perennial grass communities distributed along an aridity gradient spanning 190–540 mm of climatic water deficit (potential minus actual evapotranspiration). We tested the hypotheses that traits exhibited coordinated variation (1) among species, as well as (2) among communities varying in aridity, and (3) functional diversity within communities declines with increasing aridity, consistent with the “stress-dominance” hypothesis. Across communities, SLA and RTD exhibited a coordinated response to aridity, shifting toward more conservative (lower SLA, higher RTD) functional strategies with increasing aridity. The response of SRL to aridity was more idiosyncratic and was independent of variation in SLA and RTD. Contrary to the stress-dominance hypothesis, the diversity of SRL values within communities increased with aridity, while none of the other traits exhibited significant diversity responses. These results are consistent with other studies that have found SRL to be independent of an SLA–RTD axis of functional variation and suggest that the dynamic nature of soil moisture in arid environments may facilitate a wider array of resource capture strategies associated with variation in SRL.

One of ecology's grand challenges is developing general rules to explain and predict highly complex systems. Understanding and predicting ecological processes from species' traits has been considered a 'Holy Grail' in ecology. Plant functional traits are increasingly being used to develop mechanistic models that can predict how ecological communities will respond to abiotic and biotic perturbations and how species will affect ecosystem function and services in a rapidly changing world; however, significant challenges remain. In this review, we highlight recent work and outstanding questions in three areas: (i) selecting relevant traits; (ii) describing intraspecific trait variation and incorporating this variation into models; and (iii) scaling trait data to community- and ecosystem-level processes. Over the past decade, there have been significant advances in the characterization of plant strategies based on traits and trait relationships, and the integration of traits into multivariate indices and models of community and ecosystem function. However, the utility of trait-based approaches in ecology will benefit from efforts that demonstrate how these traits and indices influence organismal, community, and ecosystem processes across vegetation types, which may be achieved through meta-analysis and enhancement of trait databases. Additionally, intraspecific trait variation and species interactions need to be incorporated into predictive models using tools such as Bayesian hierarchical modelling. Finally, existing models linking traits to community and ecosystem processes need to be empirically tested for their applicability to be realized.

Panarthropods are typified by disparate grades of neurological organization reflecting a complex evolutionary history. The fossil record offers a unique opportunity to reconstruct early character evolution of the nervous system via exceptional preservation in extinct representatives. Here we describe the neurological architecture of the ventral nerve cord (VNC) in the upper-stem group euarthropod Chengjiangocaris kunmingensis from the early Cambrian Xiaoshiba Lagerstätte (South China). The VNC of C. kunmingensis comprises a homonymous series of condensed ganglia that extend throughout the body, each associated with a pair of biramous limbs. Submillimetric preservation reveals numerous segmental and intersegmental nerve roots emerging from both sides of the VNC, which correspond topologically to the peripheral nerves of extant Priapulida and Onychophora. The fuxianhuiid VNC indicates that ancestral neurological features of Ecdysozoa persisted into derived members of stem-group Euarthropoda but were later lost in crown-group representatives. These findings illuminate the VNC ground pattern in Panarthropoda and suggest the independent secondary loss of cycloneuralian-like neurological characters in Tardigrada and Euarthropoda.

Background Radiodonta, large Palaeozoic nektonic predators, occupy a pivotal evolutionary position as stem-euarthropods and filled important ecological niches in early animal ecosystems. Analyses of the anatomy and phylogenetic affinity of these large nektonic animals have revealed the origins of the euarthropod compound eye and biramous limb, and interpretations of their diverse feeding styles have placed various radiodont taxa as primary consumers and apex predators. Critical to our understanding of both radiodont evolution and ecology are the paired frontal appendages; however, the vast differences in frontal appendage morphology between and within different radiodont families have made it difficult to identify the relative timings of character acquisitions for this body part. Results Here we describe a new genus of hurdiid, Ursulinacaris, from the middle Cambrian (Miaolingian, Wuliuan) Mount Cap Formation (Northwest Territories, Canada) and Jangle Limestone (Nevada, USA). Ursulinacaris has the same organisation as other hurdiid frontal appendages, with elongate endites on the first five podomeres in the distal articulated region and auxiliary spines on the distal margin of endites only. Unlike all other hurdiid genera, which possess a single row of elongated and blade-like ventral endites, this taxon uniquely bears paired slender endites. Conclusion The blade-like endite morphology is shown to be a hurdiid autapomorphy. Two other frontal appendage characters known only in hurdiids, namely auxiliary spines on the distal margin of endites only, and elongate endites on the first five podomeres in the distal articulated region only, predate this innovation.

Intraspecific trait variation can be substantial and is driven by many factors. To develop predictive models of intraspecific trait variation, an understanding of the drivers of that variation is essential. At fairly broad scales, differences in the environment are expected to drive genetic variation in functional traits among populations. To isolate this genetic variability, we conducted a greenhouse common garden experiment using nine grass species native to the western United States. We assessed relationships between several root, leaf, and whole plant traits and a number of environmental conditions from the source population locations, including aspects of temperature, precipitation, vapor pressure deficit and soil moisture. We tested the hypotheses that (1) above- and belowground functional traits vary significantly within and among species, and (2) trait-environment relationships among populations of a species are consistent among species. First, we found that trait variation between species ranged from 13 to 77%, while trait variation within species ranged from 11 to nearly 39%. Traits related to overall plant size and growth rate exhibited the greatest intraspecific variation, and root traits the least variation. Second, while we found significant trait-environment relationships, they were highly variable among species. The magnitude of intraspecific trait variability found in this study indicates significant local adaptation with respect to specific trait-environment combinations, but that characterizing trait-environment relationships requires species-specific measurements and models.

Early infantile epileptic encephalopathy (EIEE) is a devastating epilepsy syndrome with onset in the first months of life. Although mutations in more than 50 different genes are known to cause EIEE, current diagnostic yields with gene panel tests or whole-exome sequencing are below 60%. We applied whole-genome analysis (WGA) consisting of whole-genome sequencing and comprehensive variant discovery approaches to a cohort of 14 EIEE subjects for whom prior genetic tests had not yielded a diagnosis. We identified both de novo point and INDEL mutations and de novo structural rearrangements in known EIEE genes, as well as mutations in genes not previously associated with EIEE. The detection of a pathogenic or likely pathogenic mutation in all 14 subjects demonstrates the utility of WGA to reduce the time and costs of clinical diagnosis of EIEE. While exome sequencing may have detected 12 of the 14 causal mutations, 3 of the 12 patients received non-diagnostic exome panel tests prior to genome sequencing. Thus, given the continued decline of sequencing costs, our results support the use of WGA with comprehensive variant discovery as an efficient strategy for the clinical diagnosis of EIEE and other genetic conditions., Pediatric neurology: whole-genome analysis finds mutations causing severe newborn seizures Whole-genome sequencing combined with specialized bioinformatics can diagnose disease mutations in newborns with devastating seizures. Josh Bonkowsky, Gabor Marth, Aaron Quinlan, and colleagues from the University of Utah in Salt Lake City, USA, thoroughly detailed the genomic variation of 14 babies with early infantile epileptic encephalopathy (EIEE). EIEE is a severe pediatric neurodevelopmental disorder causing seizures and early death. In the 14 infants, who had previous testing that did not identify the cause, the research team found the genetic cause for all of the infants. Prior to this work, approaches for EIEE diagnosed only up to 60% of infants. With the cost of DNA sequencing continuing to fall, the authors suggest that whole-genome testing could be a cost-effective approach to diagnosing EIEE and other genetic conditions.

INTRODUCTION Locations of gliomas may influence clinical presentations, molecular profiles, treatment options, and prognoses. Using the Mayo Clinic Arizona Cancer Center registry, we analyzed the frequency at which gliomas were identified in different regions of the brain. We evaluated molecular profiles, clinical courses and survival by anatomic location. METHODS Registry was queried to include patients with glioma over a 10-year period. Statistical analyses were used to compare demographic, genetic, and clinical characteristics among patients with gliomas in different locations. RESULTS 182 gliomas were identified. Of the tumors confined to a single lobe, there were 51 frontal (28.0%), 50 temporal (27.5%), 22 parietal (12.1%), and 7 occipital tumors (3.8%) identified. Multifocal disease was noted in 38 patients (20.9%). Tumors affecting temporal lobe were associated with reduced overall survival when compared to all other tumors (11.0 months vs. 13.0 months, log-rank p=0.0068). However, this disparity became insignificant when adjusted for tumor grade, age, and surgical approach [HR(95% CI) 1.26(0.87, 1.82), p=0.212]. Out of 82 cases tested for IDH-1, 10 were mutated (5.5%). IDH-1 mutation was present in 6 frontal, 2 temporal, 1 thalamic, and 1 multifocal tumor. Out of 21 cases tested for 1p19q deletions, 12 were co-deleted, 9 of which were frontal lobe tumors. MGMT methylation was assessed in 45 cases; 7 of 14 frontal tumors and 6 of 13 temporal tumors were methylated. ATRX loss was detected in 2/42 assessed cases. CONCLUSION Our results support the hypothesis that the anatomical locations of gliomas influence patients’ clinical courses. Tumors involving the temporal lobe were associated with poorer survival, though this association appeared to be driven by these patients’ more aggressive tumor profiles and higher risk baseline demographics. Molecular analysis was limited by low prevalence of genetic testing in the study sample, highlighting the importance of capturing this information for all gliomas.

Summary The nature of the relationship between water limitation and facilitation has been one of the most contentious debates surrounding the stress-gradient hypothesis (SGH), which states that plant-plant interactions shift from competition to facilitation with increasing environmental stress. We take a closer look at the potential role of soil moisture in mediating plant-plant interaction outcomes by assessing effects of climate and soil texture on plant modulation of soil moisture. Using an empirically-parameterized soil moisture model, we simulated soil moisture dynamics beneath shrubs and in un-vegetated coarse and fine soils for 1000 sites in the Western United States with

Efforts to improve the diversity of seed resources for important restoration species has become a high priority for land managers in many parts of the world. Relationships between functional trait values and the environment from which seed sources are collected can provide important insights into patterns of local adaptation and guidelines for seed transfer. However, little is known about which functional traits exhibit genetic differentiation across populations of restoration species and thus may contribute to local adaptation. Here, we report the results of a common garden experiment aimed at assessing genetic (including ploidy level) and environmental regulation of several functional traits among populations of Bouteloua gracilis, a dominant C4 grass and the most highly utilized restoration species across much of the Colorado Plateau. We found that leaf size and specific leaf area (SLA) varied significantly among populations, and were strongly correlated with the source population environment from which seeds were collected. However, variation in ploidy level had no significant effect on functional traits. Leaves of plants grown from commercial seed releases were significantly larger and had lower SLA than those from natural populations, a result that is concordant with the overall relation between climate and these two functional traits. We suggest that the patterns of functional trait variation shown here may extend to other grass species in the western USA, and may serve as useful proxies for more extensive genecology research. Furthermore, we argue that care should be taken to develop commercial seed lines with functional trait values that match those of natural populations occupying climates similar to target restoration sites.

We describe Collinsium ciliosum from the early Cambrian Xiaoshiba Lagerstätte in South China, an armored lobopodian with a remarkable degree of limb differentiation including a pair of antenna-like appendages, six pairs of elongate setiferous limbs for suspension feeding, and nine pairs of clawed annulated legs with an anchoring function. Collinsium belongs to a highly derived clade of lobopodians within stem group Onychophora, distinguished by a substantial dorsal armature of supernumerary and biomineralized spines (Family Luolishaniidae). As demonstrated here, luolishaniids display the highest degree of limb specialization among Paleozoic lobopodians, constitute more than one-third of the overall morphological disparity of stem group Onychophora, and are substantially more disparate than crown group representatives. Despite having higher disparity and appendage complexity than other lobopodians and extant velvet worms, the specialized mode of life embodied by luolishaniids became extinct during the Early Paleozoic. Collinsium and other superarmored lobopodians exploited a unique paleoecological niche during the Cambrian explosion.

The modern biosphere owes its idiosyncratic expression to the activities of oxygen metabolizing organisms, especially animals and eukaryotes (Butterfield, 2011). And with a permanently oxygenated atmosphere established during the ~2.4 Ga Great Oxidation Event (GOE), the stage was set for their early evolutionary debut. Curiously, however, eukaryotic organisms do not appear in the fossil record for another ~800 million years, and animals for another billion years beyond that (Butterfield, 2015a). Since oxygen availability determines the activity of aerobic organisms, there is a longstanding view that, although free oxygen was certainly present through these extended intervals, it remained persistently below levels necessary to support multicellular animals (Nursall, 1959) – or if not animals per se, at least organ-grade bilaterians (Planavsky et al., 2014) – or if not bilaterians per se, at least the large carnivorous bilaterians capable of driving a major evolutionary radiation like the Cambrian explosion (Sperling et al., 2013). Such ‘permissive environment’ causality provides an intuitively satisfying explanation for the delayed arrival of Phanerozoic-style ecosystems, and is supported empirically by geochemical evidence for the expanding oxygenation of mid-late Neoproterozoic oceans (Och & Shields-Zhou, 2012; Cole et al. 2016; Hardisty et al. 2017).

Pinyon-juniper (PJ) plant communities cover a large area across North America and provide critical habitat for wildlife, biodiversity and ecosystem functions, and rich cultural resources. These communities occur across a variety of environmental gradients, disturbance regimes, structural conditions and species compositions, including three species of juniper and two species of pinyon. PJ communities have experienced substantial changes in recent decades and identifying appropriate management strategies for these diverse communities is a growing challenge. Here, we surveyed the literature and compiled 441 studies to characterize patterns in research on PJ communities through time, across geographic space and climatic conditions, and among focal species. We evaluate the state of knowledge for three focal topics: 1) historical stand dynamics and responses to disturbance, 2) land management actions and their effects, and 3) potential future responses to changing climate. We identified large and potentially important gaps in our understanding of pinyon-juniper communities both geographically and topically. The effect of drought on Pinus edulis, the pinyon pine species in eastern PJ communities was frequently addressed, while few studies focused on drought effects on Pinus monophylla, which occurs in western PJ communities. The largest proportion of studies that examined land management actions only measured their effects for one year. Grazing was a common land-use across the geographic range of PJ communities yet was rarely studied. We found only 39 studies that had information on the impacts of anthropogenic climate change and most were concentrated on Pinus edulis. These results provide a synthetic perspective on PJ communities that can help natural resource managers identify relevant knowledge needed for decision-making and researchers design new studies to fill important knowledge gaps.

Contains fulltext : 153425.pdf (Publisher’s version ) (Closed access) Collagen 6-related dystrophies and myopathies (COL6-RD) are a group of disorders that form a wide phenotypic spectrum, ranging from severe Ullrich congenital muscular dystrophy, intermediate phenotypes, to the milder Bethlem myopathy. Both inter- and intrafamilial variable expressivity are commonly observed. We present clinical, immunohistochemical, and genetic data on four COL6-RD families with marked intergenerational phenotypic heterogeneity. This variable expression seemingly masquerades as anticipation is due to parental mosaicism for a dominant mutation, with subsequent full inheritance and penetrance of the mutation in the heterozygous offspring. We also present an additional fifth simplex patient identified as a mosaic carrier. Parental mosaicism was confirmed in the four families through quantitative analysis of the ratio of mutant versus wild-type allele (COL6A1, COL6A2, and COL6A3) in genomic DNA from various tissues, including blood, dermal fibroblasts, and saliva. Consistent with somatic mosaicism, parental samples had lower ratios of mutant versus wild-type allele compared with the fully heterozygote offspring. However, there was notable variability of the mutant allele levels between tissues tested, ranging from 16% (saliva) to 43% (fibroblasts) in one mosaic father. This is the first report demonstrating mosaicism as a cause of intrafamilial/intergenerational variability of COL6-RD, and suggests that sporadic and parental mosaicism may be more common than previously suspected.

The evolution of eukaryotes represents one of the most fundamental transitions in the history of life on Earth; however, there is little consensus as to when or over what timescale it occurred. Review of recent hypotheses and data in a phylogenetic context yields a broadly coherent account. Critical re-assessment of the palaeontological record provides convincing evidence for the presence of crown-group eukaryotes in the late Palaeoproterozic, and stem-group eukaryotes extending back to the early Archaean. Despite their relatively early establishment, crown-eukaryotes appear not to have become ecologically significant until the middle Neoproterozoic. I argue that this billion-year delay was due to the singular, contingent evolution of crown-group animals and their unique capacity to drive co-evolutionary change.

Experimental burial of polychaete (Nereis) and crustacean (Crangon) carcasses in kaolinite, calcite, quartz, and montmorillonite demonstrates a marked effect of sediment mineralogy on the stabilization of nonbiomineralized integuments, the first step in producing carbonaceous compression fossils and Burgess Shale–type (BST) preservation. The greatest positive effect was with Nereis buried in kaolinite, and the greatest negative effect was with Nereis buried in montmorillonite, a morphological trend paralleled by levels of preserved protein. Similar but more attenuated effects were observed with Crangon. The complex interplay of original histology and sediment mineralogy controls system pH, oxygen content, and major ion concentrations, all of which are likely to feed back on the preservation potential of particular substrates in particular environments. The particular susceptibility of Nereis to both diagenetically enhanced preservation and diagenetically enhanced decomposition most likely derives from the relative lability of its collagenous cuticle vs. the inherently more recalcitrant cuticle of Crangon. We propose a mechanism of secondary, sediment-induced taphonomic tanning to account for instances of enhanced preservation. In light of the marked effects of sediment mineralogy on fossilization, the Cambrian to Early Ordovician taphonomic window for BST preservation is potentially related to a coincident interval of glauconite-prone seas.

Background Bees and flies are the two most dominant pollinator taxa in mountain environments of the Southwest USA. Communities of both taxa change dramatically along elevation gradients. We examined whether bee and fly traits would also change along elevation gradients and if so, do they change in a predictable way related to a decrease in temperature as elevation increases. Methods We used insect body size and darkness traits as proxies for energetic requirements and indicators of cold tolerance in order to assess patterns of bee and fly community trait differences along an elevation gradient. We examined 1,922 individuals of bees and flies sampled along an elevation gradient ranging from 2,400 meters to 3,200 meters and from 9.6 °C to 5.2 °C mean annual temperature. We examined bees and flies separately using community weighted means (site-level trait values weighted by species abundance) and estimates of environmental filtering (quantified as the inverse of the standardized range of trait values). Results Bees and flies exhibited two somewhat distinct patterns; (1) Community weighted mean body volume and darkness of bees increased sharply at the highest elevation, and the intensity of environmental filtering also increased with elevation. This was due to both a change among bee populations within a species as well as species replacement at the highest elevation. (2) Community weighted mean body volume and darkness of flies also increased moderately with increasing elevation, but did not exhibit patterns of significant environmental filtering. In fact, the intensity of environmental filtering as indicated by the range of fly body volume weakened with elevation. Conclusion The increase in filter intensity at high elevations exhibited by bees suggests a significant limitation on the breadth of viable functional strategies for coping with extreme cold, at least within this regional species pool. Flies, on the other hand, do not appear to be limited by high elevations, indicating that the shift from bee to fly dominance at high elevations may be due, at least in part, to greater environmental constraints on bee adaptation to colder environments.

The thalloid carbonaceous fossil Nematothallus Lang, 1937, has been widely interpreted as an early Palaeozoic land-plant, despite the absence of a convincing modern analogue. Exceptionally well-preserved nematophyte cuticle from the Late Silurian Burgsvik Sandstone Formation, Gotland provides additional insight into the organism’s anatomy, phylogenetic affiliations and ecology. Because this material exhibits additional characters not present in the type material we assign it to Nematothallopsis gotlandii gen. et sp. nov. The organism was constituted of a close-packed layer of palisade-like filaments covered by a cuticle that bears a characteristic pseudocellular pattern on its inner surface. Apertures in this cuticle are often encircled by a ring of multicellular filaments, which are sometimes associated with spheroidal, spore-like entities. In the light of the conspicuous similarity of the palisade layers to the pseudoparenchymatous tissue of coralline red algae, and of the filament-fringed apertures to their reproductive conceptacles, we reconstruct the Nematothallopsis organism as an extinct rhodophyte and re-evaluate the putative terrestrial habit of cuticular nematophytes in general.

Microscopic animals that live among and between sediment grains (meiobenthic metazoans) are key constituents of modern aquatic ecosystems, but are effectively absent from the fossil record. We describe an assemblage of microscopic fossil loriciferans (Ecdysozoa, Loricifera) from the late Cambrian Deadwood Formation of western Canada. The fossils share a characteristic head structure and minute adult body size (~300 μm) with modern loriciferans, indicating the early evolution and subsequent conservation of an obligate, permanently meiobenthic lifestyle. The unsuspected fossilization potential of such small animals in marine mudstones offers a new search image for the earliest ecdysozoans and other animals, although the anatomical complexity of loriciferans points to their evolutionary miniaturization from a larger-bodied ancestor. The invasion of animals into ecospace that was previously monopolized by protists will have contributed considerably to the revolutionary geobiological feedbacks of the Proterozoic/Phanerozoic transition.

Palaeontology published by John Wiley & Sons Ltd on behalf of The Palaeontological Association.Exceptionally preserved ‘Burgess Shale-type’ fossil assemblages from the Cambrian of Laurentia, South China and Australia record a diverse array of non-biomineralizing organisms. During this time, the palaeocontinent Baltica was geographically isolated from these regions, and is conspicuously lacking in terms of comparable accessible early Cambrian Lagerstätten. Here we report a diverse assemblage of small carbonaceous fossils (SCFs) from the early Cambrian (Stage 4) File Haidar Formation of southeast Sweden and surrounding areas of the Baltoscandian Basin, including exceptionally preserved remains of Burgess Shale-type metazoans and other organisms. Recovered SCFs include taxonomically resolvable ecdysozoan elements (priapulid and palaeoscolecid worms), lophotrochozoan elements (annelid chaetae and wiwaxiid sclerites), as well as ‘protoconodonts’, denticulate feeding structures, and a background of filamentous and spheroidal microbes. The annelids, wiwaxiids and priapulids are the first recorded from the Cambrian of Baltica. The File Haidar SCF assemblage is broadly comparable to those recovered from Cambrian basins in Laurentia and South China, though differences at lower taxonomic levels point to possible environmental or palaeogeographical controls on taxon ranges. These data reveal a fundamentally expanded picture of early Cambrian diversity on Baltica, and provide key insights into high-latitude Cambrian faunas and patterns of SCF preservation. We establish three new taxa based on large populations of distinctive SCFs: $\textit{Baltiscalida njorda}$ gen. et sp. nov. (a priapulid), $\textit{Baltichaeta jormunganda}$ gen. et sp. nov. (an annelid) and $\textit{Baltinema rana}$ gen. et sp. nov. (a filamentous problematicum).

Objectives The collagen VI related muscular dystrophies (COL6-RD), Ullrich congenital muscular dystrophy (UCMD) and Bethlem myopathy (BM) are among the most common congenital muscular dystrophies and are characterized by distal joint laxity and a combination of distal and proximal joint contractures. Inheritance can be dominant negative (DN) or recessive depending on the type and location of the mutation. DN mutations allow incorporation of abnormal chains into secreted tetramers and are the most commonly identified mutation type in COL6-RD. Null alleles (nonsense, frameshift, and large deletions) do not allow incorporation of abnormal chains and act recessively. To better define the pathways disrupted by mutations in collagen VI, we have used a transcriptional profiling approach with RNA-Seq to identify differentially expressed genes in COL6-RD individuals from controls. Methods RNA-Seq allows precise detection of all expressed transcripts in a sample and provides a tool for quantification of expression data on a genomic scale. We have used RNA-Seq to identify differentially expressed genes in cultured dermal fibroblasts from 13 COL6-RD individuals (8 dominant negative and 5 null) and 6 controls. To better assess the transcriptional changes induced by abnormal collagen VI in the extracellular matrix (ECM); we compared transcriptional profiles from subjects with DN mutations and subjects with null mutations to transcriptional profiles from controls. Results Differentially expressed transcripts between COL6-RD and control fibroblasts include upregulation of ECM components and downregulation of factors controlling matrix remodeling and repair. DN and null samples are differentiated by downregulation of genes involved with DNA replication and repair in null samples. Conclusions Differentially expressed genes identified here may help identify new targets for development of therapies and biomarkers to assess the efficacy of treatments.

Summary Functional traits can be used to describe the composition of communities through indices that seek to explain the factors that drive community assembly, biotic effects on ecosystem processes or both. Appropriately representing functional composition is therefore essential for predicting the consequences of environmental context and management actions for the provisioning of multiple ecosystem services (ESs) in heterogeneous landscapes. Functional indices can be constructed from single or multiple traits; however, it is not clear how they differ in information content or ability to predict biodiversity – ecosystem function relationships in complex landscapes. Here, we compare the utility of analogous single- and multi-trait indices in linking environmental variation and functional composition to ESs in a heterogeneous landscape, relating functional indices based on three plant traits [height, relative growth rate and root density (RD)] to variation in the physical environment and to two ESs (forage production and soil carbon) and their net ES level. Two orthogonal gradients, elevation and soil bulk density (BD), explained significant variation in several dimensions of functional composition comprised of single traits. These traits in turn significantly predicted variation in ESs and their net values. Only one index measured with multiple traits (functional richness) varied with the physical environment, while none predicted variation in ES or net ES levels. One ES, soil carbon, increased with the community-average value of RD, while the other, forage production, was related to the range and community-average value of height. In turn, average RD increased with soil BD while the average and range of height declined with elevation. Due to these environmental patterns, soil carbon and forage production did not covary strongly, leading to moderate net ES levels across the landscape. Synthesis: Single-trait indices of functional composition best linked variation in environmental gradients with productivity and soil carbon. Because the environment–trait functioning relationships were independent of one another, the ESs were independently distributed across the landscape, providing little evidence of synergies or trade-offs. Single- and multi-trait indices contained unique information about functional composition of these communities, and both are likely to have a place in predicting variation in ESs under different scenarios.

Diverse carbonaceous microfossils, including exceptionally preserved remains of non-biomineralizing metazoans, are reported from a basal middle Cambrian interval of the Kaili Formation (Guizhou Province, China). The application of a gentle acid maceration technique complements previous palynological studies by revealing a larger size-class of acritarchs, a richer assemblage of filamentous microfossils, and a variety of previously unrecovered forms. Metazoan fossils include Wiwaxia sclerites and elements derived from biomineralizing taxa, including chancelloriids, brachiopods and hyolithids, in common with previously studied assemblages from the early and middle Cambrian of Canada. In addition, the Kaili Formation has yielded pterobranch remains and an assemblage of cuticle fragments representing “soft-bodied” worms, including a priapulid-like scalidophoran. Our results demonstrate the wide distribution and palaeobiological importance of microscopic “Burgess Shale-type” fossils, and provide insights into t...

Use of a low-manipulation hydrofluoric acid-extraction procedure on Cambrian mudstones reveals an unexpectedly abundant and diverse range of small carbonaceous fossils (SCFs), primarily the disarticulated sclerites and cuticular fragments of animals. Relatively recalcitrant forms such as Wiwaxia sclerites and priapulid-like scalids are sufficiently common to yield a reasonably reliable biostratigraphic signal, unlike their rare macroscopic counterparts. Molluscan radulae, crustacean appendages, and the carbonaceous components of originally mineralized metazoan sclerites provide further insights into the histology, diversity, and distribution of early metazoans. The widespread occurrence of SCFs is due in part to their enhanced biostratinomic potential for transport, burial, and preservation, particularly in well-aerated epicratonic settings not represented by Burgess Shale–type macrofossils. More generally, the SCF record represents a largely untapped measure of ecological and evolutionary dynamics through the early Paleozoic.

Objective: The major histocompatibility complex (MHC) is the primary genetic contributor to multiple sclerosis (MS) and experimental allergic encephalomyelitis (EAE), but multiple additional interacting loci are required for genetic susceptibility. The identity of most of these non-MHC genes is unknown. In this report, we identify genes within evolutionarily conserved genetic pathways leading to MS and EAE. Methods: To identify non-MHC binary and quantitative trait loci (BTL/QTL) important in the pathogenesis of EAE, we generated phenotype-selected congenic mice using EAE-resistant B10.S and EAE-susceptible SJL mice. We hypothesized that genes linked to EAE BTL/QTL and MS-GWAS can be identified if they belong to common evolutionarily conserved pathways, which can be identified with a bioinformatic approach using Ingenuity software. Results: Many known BTL/QTL were retained and linked to susceptibility during phenotype selection, the most significant being a region on chromosome 17 distal to H2 (Eae5). We show in pathway analysis that T helper (TH)-cell differentiation genes are critical for both diseases. Bioinformatic analyses predicted that Eae5 is important in CD4 T-effector and/or Foxp3+ T-regulatory cells (Tregs), and we found that B10.S-Eae5SJL congenic mice have significantly greater numbers of lymph node CD4 and Tregs than B10.S mice. Interpretation: These results support the polygenic model of MS/EAE, whereby MHC and multiple minor loci are required for full susceptibility, and confirm a critical genetic dependence on CD4 TH-cell differentiation and function in the pathogenesis of both diseases. ANN NEUROL 2011;70:887–896

The origin and expansion of biomineralization in eukaryotes played a critical role in Earth history, linking biological and geochemical processes. However, the onset of this phenomenon is poorly constrained due to a limited early fossil record of biomineralization. Although macroscopic evidence for biomineralization is not known until the late Ediacaran, we here report biologically controlled phosphatic biomineralization of scale microfossils from mid-Neoproterozoic (pre-Sturtian) strata of northwest Canada. Primary biological control on mineralization is supported by the identification of apatite in both chert-hosted and limestone-hosted specimens, the conspicuously rigid original morphology of the scale microfossils relative to co-occurring organic-walled cyanobacteria and acritarchs, and the microstructure of the constituent phosphate. Cell-enveloping mineralized scales occur in a wide range of extant protists, but the apparent restriction of phosphate scales to one modern taxon of green algae suggests a possible affiliation for these fossils. Documentation of primary phosphate biomineralization in Fifteenmile Group (Yukon Territory, Canada) microfossils greatly extends the known record of biologically controlled mineralization and provides a unique window into the diversity of early eukaryotes.

Animals do not just occupy the modern biosphere, they permeate its structure and define how it works. Their unique combination of organ-grade multicellularity, motility and heterotrophic habit makes them powerful geobiological agents, imposing myriad feedbacks on nutrient cycling, productivity and environment. Most significantly, animals have 'engineered' the biosphere over evolutionary time, forcing the diversification of, for example, phytoplankton, land plants, trophic structure, large body size, bioturbation, biomineralization and indeed the evolutionary process itself. This review surveys how animals contribute to the modern world and provides a basis for reconstructing ancient ecosystems. Earlier, less animal-influenced biospheres worked quite differently from the one currently occupied, with the Ediacaran-Cambrian radiation of organ-grade animals marking a fundamental shift in macroecological and macroevolutionary expression.

Summary 1. New insights into the mechanisms and outcomes of facilitation have led to important advances in our understanding of ecological patterns and processes. However, the effects of facilitation on non-successional community dynamics have yet to be developed into a general theory. 2. By synthesizing spatial and temporal relationships between biotic interactions and environmental severity, a new model of facilitation-driven community dynamics is presented that applies to any facilitative mechanism related to abiotic stress or resource limitation. 3. In general, facilitation tends to stabilize community dynamics in moderately severe environments, due to a buffering effect of increased facilitation during more severe periods and enhanced competitive effects in milder conditions. In contrast, a strong negative relationship between environmental severity and facilitative strength in highly severe environments leads to a destabilizing effect of facilitation on community dynamics. 4. If only mature plants have significant facilitative effects, developmental lags may be introduced that decouple environmental fluctuations and community dynamics, decreasing the effects of facilitation on community stability. Additionally, dual regulation of facilitation by environmental and demographic factors decouples abundance from climate and produces periodic local extinctions. In general, the interplay of facilitation and competition produce highly variable dynamics in moderate-severity environments, whereas qualitatively similar results were found in high-severity environments regardless of facilitative mechanism or model parameters. 5. Additional variation in community dynamics can be explained by the combination of effect and response functional traits of species within a community. The relative abundance and proportion of species within a community falling into one of four different effect and response categories provide an effective framework for predicting responses to climatic variation and biotic interactions. 6.Synthesis. Facilitation either increases or decreases community stability in predictable ways as a function of empirically identifiable environmental gradients. Effects of developmental lags, complex controls of facilitative mechanisms and species’ functional traits explain additional variation in community dynamics that can be applied to a broad array of ecosystems in which facilitation occurs.

A multicellular grade of organization is widely distributed among extant organisms and widely represented in the pre-Ediacaran fossil record. A review of the pre-Ediacaran record identifies nine general categories of multicellular organization: (1) simple clonal colonies; (2) integrated coenobial colonies; (3) simple uniseriate filaments; (4) simple multiseriate filaments; (5) simple coenocytic filaments; (6) branched coenocytic filaments; (7) complex multicellular filaments; (8) complex multicellular vesicles; and (9) problematic macrofossils. A small subset of these fossils can be assigned to extant lineages based on taxonomically diagnostic patterns of cell division, including compelling evidence for chroococcacean, oscillatoriacean and pleurocapsalean cyanobacteria, bangiophycaceaen red algae and hydrodictaceaen green algae. The identification of pre-Ediacaran vaucheriaceaen xanthophyte algae and siphonocladalean green algae is almost as secure, whereas the case for early multicellular nostocalean/stigonematalean cyanobacteria and fungi requires further corroboration; a distinctively patterned acritarch is tentatively identified as an early Neoproterozoic poriferan. Despite this breadth of early multicellular experimentation, there is no evidence for organ-grade differentiation prior to the Ediacaran. Indeed, it is the absence of eumetazoans and embryophytes that distinguishes the pre-Ediacaran world from the fundamentally richer and more dynamic biosphere of the Phanerozoic.

We describe a novel form of juvenile recessive ALS (JRALS) affecting four of six offspring from a consanguineous first cousin marriage. The syndrome is characterized by early and prominent upper motor neuron signs, along with striking amyotrophy of the upper and lower limbs and bulbar involvement. After excluding linkage to loci with known association to ALS and other motor neuron diseases, we used a homozygosity mapping approach to identify loci on chromosomes 6p25 and 21q22, each with an equal probability of linkage to the trait (with a LOD score = 3.1, the maximum possible given the family structure). Mutation analysis of seven candidate genes that are expressed in the CNS or have roles in neuronal function did not reveal any pathogenic mutations. Identification of additional families will help to distinguish between which of the two autosomal loci contains the disease-causing gene, or whether this is a digenic trait.