ranacapa: An R package and Shiny web app to explore environmental DNA data with exploratory statistics and interactive visualizations.

Environmental DNA (eDNA) metabarcoding is becoming a core tool in ecology and conservation biology, and is being used in a growing number of education, biodiversity monitoring, and public outreach programs in which professional research scientists engage community partners in primary research. Results from eDNA analyses can engage and educate natural resource managers, students, community scientists, and naturalists, but without significant training in bioinformatics, it can be difficult for this diverse audience to interact with eDNA results. Here we present the R package ranacapa, at the core of which is a Shiny web app that helps perform exploratory biodiversity analyses and visualizations of eDNA results. The app requires a taxonomy-by-sample matrix and a simple metadata file with descriptive information about each sample. The app enables users to explore the data with interactive figures and presents results from simple community ecology analyses. We demonstrate the value of ranacapa to two groups of community partners engaging with eDNA metabarcoding results

Genomic and transcriptomic signals of thermal tolerance in heat-tolerant corals (Platygyra daedalea) of the Arabian/Persian Gulf

© 2018 John Wiley & Sons Ltd Scleractinian corals occur in tropical regions near their upper thermal limits and are severely threatened by rising ocean temperatures. However, several recent studies have shown coral populations can harbour genetic variation in thermal tolerance. Here, we have extended these approaches to study heat tolerance of corals in the Persian/Arabian Gulf, where heat-tolerant local populations experience extreme summer temperatures (up to 36°C). To evaluate whether selection has depleted genetic variation in thermal tolerance, estimate potential future adaptive responses and understand the functional basis for these corals’ unusual heat tolerance, we conducted controlled crosses in the Gulf coral Platygyra daedalea. Heat tolerance is highly heritable in this population (h 2 = 0.487–0.748), suggesting substantial potential for adaptive responses to selection for elevated temperatures. To identify genetic markers associated with this variation, we conducted genomewide SNP genotyping in parental corals and tested for relationships between paternal genotype and offspring thermal tolerance. Resulting multilocus SNP genotypes explained a large fraction of variation in thermal tolerance in these crosses (69%). To investigate the functional basis of these differences in thermal tolerance, we profiled transcriptional responses in tolerant and susceptible families, revealing substantial sire effects on transcriptional responses to thermal stress. We also studied sequence variation in these expressed sequences, identifying alleles and functional groups of differentially expressed genes associated with thermal tolerance. Our findings demonstrate that corals in this population harbour extensive genetic variation in thermal tolerance, and heat-tolerant phenotypes differ in both gene sequences and transcriptional stress responses from their susceptible counterparts

Enhancing the heat tolerance of reef-building corals to future warming

Reef-building corals thriving in extreme thermal environments may provide genetic variation that can assist the evolution of populations to rapid climate warming. However, the feasibility and scale of genetic improvements remain untested despite ongoing population declines from recurrent thermal stress events. Here, we show that corals from the hottest reefs in the world transfer sufficient heat tolerance to a naïve population sufficient to withstand end-of-century warming projections. Heat survival increased up to 84% when naïve mothers were selectively bred with fathers from the hottest reefs because of strong heritable genetic effects. We identified genomic loci associated with tolerance variation that were enriched for heat shock proteins, oxidative stress, and immune functions. Unexpectedly, several coral families exhibited survival rates and genomic associations deviating from origin predictions, including a few naïve purebreds with exceptionally high heat tolerance. Our findings highlight previously uncharacterized enhanced and intrinsic potential of coral populations to adapt to climate warming

miR-196b target screen reveals mechanisms maintaining leukemia stemness with therapeutic potential.

We have shown that antagomiR inhibition of miRNA miR-21 and miR-196b activity is sufficient to ablate MLL-AF9 leukemia stem cells (LSC) in vivo. Here, we used an shRNA screening approach to mimic miRNA activity on experimentally verified miR-196b targets to identify functionally important and therapeutically relevant pathways downstream of oncogenic miRNA in MLL-r AML. We found Cdkn1b (p27Kip1) is a direct miR-196b target whose repression enhanced an embryonic stem cell–like signature associated with decreased leukemia latency and increased numbers of leukemia stem cells in vivo. Conversely, elevation of p27Kip1 significantly reduced MLL-r leukemia self-renewal, promoted monocytic differentiation of leukemic blasts, and induced cell death. Antagonism of miR-196b activity or pharmacologic inhibition of the Cks1-Skp2–containing SCF E3-ubiquitin ligase complex increased p27Kip1 and inhibited human AML growth. This work illustrates that understanding oncogenic miRNA target pathways can identify actionable targets in leukemia

On the origins of the mitotic shift in proliferating cell layers

Background: During plant and animal development, monolayer cell sheets display a stereotyped distribution of polygonal cell shapes. In interphase cells these shapes range from quadrilaterals to decagons, with a robust average of six sides per cell. In contrast, the subset of cells in mitosis exhibits a distinct distribution with an average of seven sides. It remains unclear whether this ‘mitotic shift’ reflects a causal relationship between increased polygonal sidedness and increased division likelihood, or alternatively, a passive effect of local proliferation on cell shape. Methods: We use a combination of probabilistic analysis and mathematical modeling to predict the geometry of mitotic polygonal cells in a proliferating cell layer. To test these predictions experimentally, we use Flp-Out stochastic labeling in the Drosophila wing disc to induce single cell clones, and confocal imaging to quantify the polygonal topologies of these clones as a function of cellular age. For a more generic test in an idealized cell layer, we model epithelial sheet proliferation in a finite element framework, which yields a computationally robust, emergent prediction of the mitotic cell shape distribution. Results: Using both mathematical and experimental approaches, we show that the mitotic shift derives primarily from passive, non-autonomous effects of mitoses in neighboring cells on each cell’s geometry over the course of the cell cycle. Computationally, we predict that interphase cells should passively gain sides over time, such that cells at more advanced stages of the cell cycle will tend to have a larger number of neighbors than those at earlier stages. Validating this prediction, experimental analysis of randomly labeled epithelial cells in the Drosophila wing disc demonstrates that labeled cells exhibit an age-dependent increase in polygonal sidedness. Reinforcing these data, finite element simulations of epithelial sheet proliferation demonstrate in a generic framework that passive side-gaining is sufficient to generate a mitotic shift. Conclusions: Taken together, our results strongly suggest that the mitotic shift reflects a time-dependent accumulation of shared cellular interfaces over the course of the cell cycle. These results uncover fundamental constraints on the relationship between cell shape and cell division that should be general in adherent, polarized cell layers

Publisher Correction: An engineered human Fc domain that behaves like a pH-toggle switch for ultra-long circulation persistence.

An amendment to this paper has been published and can be accessed via a link at the top of the paper

Evoked potentials differentiate Developmental Coordination Disorder from Attention-Deficit/Hyperactivity Disorder in a stop-signal task: A pilot study

Developmental Coordination Disorder and Attention-Deficit/Hyperactivity Disorder are unique neurodevelopmental disorders with overlaps in executive functions and motor control. The conditions co-occur in up to 50% of cases, raising questions of the pathological mechanisms of DCD versus ADHD. Few studies have examined these overlaps in adults with DCD and/or ADHD. Therefore, to provide insights about executive functions and motor control between adults with DCD, ADHD, both conditions (DCD+ADHD), or typically developed controls, this study used a stop-signal task and parallel EEG measurement. We assessed executive performance via go accuracy and go reaction time, as well as motor response inhibition via stop signal reaction time. This was complemented with analysis of event-related potentials (ERPs). Based on existing investigations of adults with DCD or ADHD, we expected groups would (1) not differ in behavioral performance on stop and go trials, but (2) differences in ERPs, particularly in components N200 (index of cognitive control) and P300 (index of attention and inhibition) would be evident. The sample included N=50 adults with DCD (n=12), ADHD (n=9), DCD+ADHD (n=7), and control participants (n=22). We replicated that there were no between-group differences for behavioral-level executive performance and motor response inhibition. However, on a physiological level, ERP components N200 and P300 differed between groups, particularly during successful response inhibition. These ERPs reflect potential endophenotypic differences not evident in overt behavior of participants with ADHD and/or DCD. This suggests a disorder specific employment of inhibition or general executive functions in groups of adults with DCD, DCD+ADHD, ADHD, or control participants