Vive la différence: biogenesis and evolution of microRNAs in plants and animals

MicroRNAs are pervasive in both plants and animals, but many aspects of their biogenesis, function and evolution differ. We reveal how these differences contribute to characteristic features of microRNA evolution in the two kingdoms

A Two-Hit Trigger for siRNA Biogenesis in Plants

SummaryIn Arabidopsis, microRNA-directed cleavage can define one end of RNAs that then generate phased siRNAs. However, most miRNA-targeted RNAs do not spawn siRNAs, suggesting the existence of additional determinants within those that do. We find that in moss, phased siRNAs arise from regions flanked by dual miR390 cleavage sites. AtTAS3, an siRNA locus important for development and conserved among higher plants, also has dual miR390 complementary sites. Both sites bind miR390 in vitro and are functionally required in Arabidopsis, but cleavage is undetectable at the 5′ site—demonstrating that noncleavable sites can be functional in plants. Phased siRNAs also emanate from the bounded regions of every Arabidopsis gene with two known microRNA/siRNA complementary sites, but only rarely from genes with single sites. Therefore, two “hits,”—often, but not always, two cleavage events—constitute a conserved trigger for siRNA biogenesis, a finding with implications for recognition and silencing of aberrant RNA

The Pathway Forward: Uncovering the Barriers Faced by Women Police Chiefs

Women have encountered many obstacles in their quest to gain leadership in law enforcement. While research has studied how well women officers strive to achieve higher-level positions within police departments, the challenges women face when they gain top leadership roles remain largely unexplored. This research paper will discuss the unique challenges faced by women police chiefs, drawing from first-hand experiences of women police chiefs and existing literature. The study finds that women police chiefs encounter challenges in communication, transferring to a new department, overtasking, introvertedness, and general police chief stress. The study also finds that women police chiefs implement ways to improve communication, quiet time to think, emotional intelligence, delegate, and remain consistent with overcoming their challenges. This study informs law enforcement leaders on better supporting women police chiefs and future generations

A computational approach to managing coupled human–environmental systems: the POSEIDON model of ocean fisheries

Sustainable management of complex human–environment systems, and the essential services they provide, remains a major challenge, felt from local to global scales. These systems are typically highly dynamic and hard to predict, particularly in the context of rapid environmental change, where novel sets of conditions drive coupled socio-economic-environmental responses. Faced with these challenges, our tools for policy development, while informed by the past experience, must not be unduly constrained; they must allow equally for both the fine-tuning of successful existing approaches and the generation of novel ones in unbiased ways. We study ocean fisheries as an example class of complex human–environmental systems, and present a new model (POSEIDON) and computational approach to policy design. The model includes an adaptive agent-based representation of a fishing fleet, coupled to a simplified ocean ecology model. The agents (fishing boats) do not have programmed responses based on empirical data, but respond adaptively, as a group, to their environment (including policy constraints). This conceptual model captures qualitatively a wide range of empirically observed fleet behaviour, in response to a broad set of policies. Within this framework, we define policy objectives (of arbitrary complexity) and use Bayesian optimization over multiple model runs to find policy parameters that best meet the goals. The trade-offs inherent in this approach are explored explicitly. Taking this further, optimization is used to generate novel hybrid policies. We illustrate this approach using simulated examples, in which policy prescriptions generated by our computational methods are counterintuitive and thus unlikely to be identified by conventional frameworks

Quantifying intra-seasonal variations in physical performance measures using player tracking data from an elite football (soccer) academy

Quantifying intra-seasonal variations in physical performance measures using player tracking data from an elite football (soccer) academ

Player tracking data analytics as a tool for physical performance management in football: A case study from Chelsea Football Club Academy

Background: Global positioning system (GPS) based player movement tracking data are widely used by professional football (soccer) clubs and academies to provide insights into activity demands during training and competitive matches. However, the use of movement tracking data to inform the design of training programmes is still an open research question. Objectives: The objective of this study is to analyze player tracking data to understand the activity level differences between training and match sessions, with respect to different playing positions. Methods: This study analyses per-session summary of historical movement data collected through GPS tracking to profile high speed running activity as well as distance covered during training sessions as a whole and competitive matches. We utilize 20913 data points collected from 53 football players aged between 18-23 at an elite football academy, across four full seasons (2014-2018). Through ANOVA analysis and probability distribution analysis, we compare the activity demands, measured by the number of high speed runs, amount of high speed distance and distance covered by players in key playing positions, such as Central Midfielders, Full Backs and Centre Forwards. Results and Implications: While there are significant positional differences of physical activity demands during competitive matches, the physical activity levels during training sessions does not show positional variations. In matches, the Centre Forwards face the highest demand for HSRs, compared to Central Midfielders and Full Backs. However on average the Central Midfielders tend to cover more distance than Centre Forwards and Full Backs. An increase in high speed work demand in matches and training over the past 4 seasons, also shown by a gradual change in the extreme values of high speed running activity was also found. This large-scale, longitudinal study makes an important contribution to the literature, providing novel insights from an elite performance environment about the relationship between player activity levels during training and match play, and how these vary by playing position

Functional Specialization of the Plant miR396 Regulatory Network through Distinct MicroRNA–Target Interactions

MicroRNAs (miRNAs) are ∼21 nt small RNAs that regulate gene expression in animals and plants. They can be grouped into families comprising different genes encoding similar or identical mature miRNAs. Several miRNA families are deeply conserved in plant lineages and regulate key aspects of plant development, hormone signaling, and stress response. The ancient miRNA miR396 regulates conserved targets belonging to the GROWTH-REGULATING FACTOR (GRF) family of transcription factors, which are known to control cell proliferation in Arabidopsis leaves. In this work, we characterized the regulation of an additional target for miR396, the transcription factor bHLH74, that is necessary for Arabidopsis normal development. bHLH74 homologs with a miR396 target site could only be detected in the sister families Brassicaceae and Cleomaceae. Still, bHLH74 repression by miR396 is required for margin and vein pattern formation of Arabidopsis leaves. MiR396 contributes to the spatio-temporal regulation of GRF and bHLH74 expression during leaf development. Furthermore, a survey of miR396 sequences in different species showed variations in the 5′ portion of the miRNA, a region known to be important for miRNA activity. Analysis of different miR396 variants in Arabidopsis thaliana revealed that they have an enhanced activity toward GRF transcription factors. The interaction between the GRF target site and miR396 has a bulge between positions 7 and 8 of the miRNA. Our data indicate that such bulge modulates the strength of the miR396-mediated repression and that this modulation is essential to shape the precise spatio-temporal pattern of GRF2 expression. The results show that ancient miRNAs can regulate conserved targets with varied efficiency in different species, and we further propose that they could acquire new targets whose control might also be biologically relevant

Deciphering the genome structure and paleohistory of _Theobroma cacao_

We sequenced and assembled the genome of _Theobroma cacao_, an economically important tropical fruit tree crop that is the source of chocolate. The assembly corresponds to 76% of the estimated genome size and contains almost all previously described genes, with 82% of them anchored on the 10 _T. cacao_ chromosomes. Analysis of this sequence information highlighted specific expansion of some gene families during evolution, for example flavonoid-related genes. It also provides a major source of candidate genes for _T. cacao_ disease resistance and quality improvement. Based on the inferred paleohistory of the T. cacao genome, we propose an evolutionary scenario whereby the ten _T. cacao_ chromosomes were shaped from an ancestor through eleven chromosome fusions. The _T. cacao_ genome can be considered as a simple living relic of higher plant evolution

Physcomitrella patens DCL3 Is Required for 22–24 nt siRNA Accumulation, Suppression of Retrotransposon-Derived Transcripts, and Normal Development

Endogenous 24 nt short interfering RNAs (siRNAs), derived mostly from intergenic and repetitive genomic regions, constitute a major class of endogenous small RNAs in flowering plants. Accumulation of Arabidopsis thaliana 24 nt siRNAs requires the Dicer family member DCL3, and clear homologs of DCL3 exist in both flowering and non-flowering plants. However, the absence of a conspicuous 24 nt peak in the total RNA populations of several non-flowering plants has raised the question of whether this class of siRNAs might, in contrast to the ancient 21 nt microRNAs (miRNAs) and 21–22 nt trans-acting siRNAs (tasiRNAs), be an angiosperm-specific innovation. Analysis of non-miRNA, non-tasiRNA hotspots of small RNA production within the genome of the moss Physcomitrella patens revealed multiple loci that consistently produced a mixture of 21–24 nt siRNAs with a peak at 23 nt. These Pp23SR loci were significantly enriched in transposon content, depleted in overlap with annotated genes, and typified by dense concentrations of the 5-methyl cytosine (5 mC) DNA modification. Deep sequencing of small RNAs from two independent Ppdcl3 mutants showed that the P. patens DCL3 homolog is required for the accumulation of 22–24 nt siRNAs, but not 21 nt siRNAs, at Pp23SR loci. The 21 nt component of Pp23SR-derived siRNAs was also unaffected by a mutation in the RNA-dependent RNA polymerase mutant Pprdr6. Transcriptome-wide, Ppdcl3 mutants failed to accumulate 22–24 nt small RNAs from repetitive regions while transcripts from two abundant families of long terminal repeat (LTR) retrotransposon-associated reverse transcriptases were up-regulated. Ppdcl3 mutants also displayed an acceleration of leafy gametophore production, suggesting that repetitive siRNAs may play a role in the development of P. patens. We conclude that intergenic/repeat-derived siRNAs are indeed a broadly conserved, distinct class of small regulatory RNAs within land plants

Defective sphingosine-1-phosphate receptor 1 (S1P1) phosphorylation exacerbates TH17-mediated autoimmune neuroinflammation

Sphingosine-1-phosphate (S1P) signaling regulates lymphocyte egress from lymphoid organs into systemic circulation. Sphingosine phosphate receptor 1 (S1P1) agonist, FTY-720 (Gilenya™) arrests immune trafficking and prevents multiple sclerosis (MS) relapses. However, alternative mechanisms of S1P-S1P1 signaling have been reported. Phosphoproteomic analysis of MS brain lesions revealed S1P1 phosphorylation on S351, a residue crucial for receptor internalization. Mutant mice harboring a S1pr1 gene encoding phosphorylation-deficient receptors [S1P1(S5A)] developed severe experimental autoimmune encephalomyelitis (EAE) due to T helper (TH) 17-mediated autoimmunity in the peripheral immune and nervous system. S1P1 directly activated Janus-like kinase–signal transducer and activator of transcription 3 (JAK-STAT3) pathway via interleukin 6 (IL-6). Impaired S1P1 phosphorylation enhances TH17 polarization and exacerbates autoimmune neuroinflammation. These mechanisms may be pathogenic in MS