The 3' poly(A) tail of messenger RNA is fundamental to regulating eukaryotic gene expression. Shortening of the poly(A) tail, termed deadenylation, reduces transcript stability and inhibits ...translation. Nonetheless, the mechanism for poly(A) recognition by the conserved deadenylase complexes Pan2-Pan3 and Ccr4-Not is poorly understood. Here we provide a model for poly(A) RNA recognition by two DEDD-family deadenylase enzymes, Pan2 and the Ccr4-Not nuclease Caf1. Crystal structures of Saccharomyces cerevisiae Pan2 in complex with RNA show that, surprisingly, Pan2 does not form canonical base-specific contacts. Instead, it recognizes the intrinsic stacked, helical conformation of poly(A) RNA. Using a fully reconstituted biochemical system, we show that disruption of this structure-for example, by incorporation of guanosine into poly(A)-inhibits deadenylation by both Pan2 and Caf1. Together, these data establish a paradigm for specific recognition of the conformation of poly(A) RNA by proteins that regulate gene expression.
The evolution and maintenance of secondary sexual characteristics and behavior are heavily influenced by the variance in mating success among individuals in a population. The operational sex ratio ...(OSR) is often used as a predictor of the intensity of competition for mates, as it describes the relative number of males and females who are ready to mate. We investigate changes in aggression, courtship, mate guarding, and sperm release as a function of changes in the OSR using meta-analytic techniques. As the OSR becomes increasingly biased, aggression increases as competitors attempt to defend mates, but this aggression begins to decrease at an OSR of 1.99, presumably due to the increased costs of competition as rivals become more numerous. Sperm release follows a similar but not significant trend. By contrast, courtship rate decreases as the OSR becomes increasingly biased, whereas mate guarding and copulation duration increase. Overall, predictable behavioral changes occur in response to OSR, although the nature of the change is dependent on the type of mating behavior. These results suggest considerable flexibility of mating system structure within species, which can be predicted by OSR and likely results in variation in the strength of sexual selection.
Large-scale presence-absence monitoring programs have great promise for many conservation applications. Their value can be limited by potential incorrect inferences owing to observational errors, ...especially when data are collected by the public. To combat this, previous analytical methods have focused on addressing non-detection from public survey data. Misclassification errors have received less attention but are also likely to be a common component of public surveys, as well as many other data types. We derive estimators for dynamic occupancy parameters (extinction and colonization), focusing on the case where certainty can be assumed for a subset of detections. We demonstrate how to simultaneously account for non-detection (false negatives) and misclassification (false positives) when estimating occurrence parameters for gray wolves in northern Montana from 2007-2010. Our primary data source for the analysis was observations by deer and elk hunters, reported as part of the state's annual hunter survey. This data was supplemented with data from known locations of radio-collared wolves. We found that occupancy was relatively stable during the years of the study and wolves were largely restricted to the highest quality habitats in the study area. Transitions in the occupancy status of sites were rare, as occupied sites almost always remained occupied and unoccupied sites remained unoccupied. Failing to account for false positives led to over estimation of both the area inhabited by wolves and the frequency of turnover. The ability to properly account for both false negatives and false positives is an important step to improve inferences for conservation from large-scale public surveys. The approach we propose will improve our understanding of the status of wolf populations and is relevant to many other data types where false positives are a component of observations.
The ability to transmit information between individuals through social learning is a foundational component of cultural evolution. However, how this transmission occurs is still debated. On the one ...hand, the copying account draws parallels with biological mechanisms for genetic inheritance, arguing that learners copy what they observe and novel variations occur through random copying errors. On the other hand, the reconstruction account claims that, rather than directly copying behaviour, learners reconstruct the information that they believe to be most relevant on the basis of pragmatic inference, environmental and contextual cues. Distinguishing these two accounts empirically is difficult based on data from typical transmission chain studies because the predictions they generate frequently overlap. In this study we present a methodological approach that generates different predictions of these accounts by manipulating the task context between model and learner in a transmission episode. We then report an empirical proof-of-concept that applies this approach. The results show that, when a model introduces context-dependent embedded signals to their actions that are not intended to be transmitted, it is possible to empirically distinguish between competing predictions made by these two accounts. Our approach can therefore serve to understand the underlying cognitive mechanisms at play in cultural transmission and can make important contributions to the debate between preservative and reconstructive schools of thought.
When observing two individuals, people are faster and better able to identify them as other people if they are facing each other than if they are facing away from each other. This advantage ...disappears when the images are inverted, suggesting that the visual system is particularly sensitive to dyads in this upright configuration, and perceptually groups socially engaged dyads into a single holistic unit. This dyadic inversion effect was obtained with images of full bodies. Body information was sufficient to elicit this effect even when information about head orientation was absent. However, it has not been tested whether the dyadic inversion effect occurs with face images and whether the emotions displayed by the faces modulate the effect. In three experiments we obtained robust dyadic inversion with face images. Holistic processing of upright face pairs occurred for neutral, happy, and sad faces but not for angry and fearful face pairs. Thus, perceptual grouping of individuals into pairs appears to depend on the emotional expressions of individual faces and the interpersonal relations they imply.
In an attempt to restore the connectivity of fragmented river habitats, a variety of passage facilities have been installed at river barriers. Despite the cost of building these structures, there has ...been no quantitative evaluation of their overall success at restoring fish passage. We reviewed articles from 1960 to 2011, extracted data from 65 papers on fish passage efficiency, size and species of fish, and fishway characteristics to determine the best predictors of fishway efficiency. Because data were scarce for fishes other than salmonids (order Salmoniformes), we combined data for all non‐salmonids for our analysis. On average, downstream passage efficiency was 68.5%, slightly higher than upstream passage efficiency of 41.7%, and neither differed across the geographical regions of study. Salmonids were more successful than non‐salmonids in passing upstream (61.7 vs. 21.1%) and downstream (74.6 vs. 39.6%) through fish passage facilities. Passage efficiency differed significantly between types of fishways; pool and weir, pool and slot and natural fishways had the highest efficiencies, whereas Denil and fish locks/elevators had the lowest. Upstream passage efficiency decreased significantly with fishway slope, but increased with fishway length, and water velocity. An information‐theoretic analysis indicated that the best predictors of fish passage efficiency were order of fish (i.e. salmonids > non‐salmonids), type of fishway and length of fishway. Overall, the low efficiency of passage facilities indicated that most need to be improved to sufficiently mitigate habitat fragmentation for the complete fish community across a range of environmental conditions.
Translation and decay of eukaryotic mRNAs is controlled by shortening of the poly(A) tail and release of the poly(A)-binding protein Pab1/PABP. The Ccr4-Not complex contains two exonucleases—Ccr4 and ...Caf1/Pop2—that mediate mRNA deadenylation. Here, using a fully reconstituted biochemical system with proteins from the fission yeast Schizosaccharomyces pombe, we show that Pab1 interacts with Ccr4-Not, stimulates deadenylation, and differentiates the roles of the nuclease enzymes. Surprisingly, Pab1 release relies on Ccr4 activity. In agreement with this, in vivo experiments in budding yeast show that Ccr4 is a general deadenylase that acts on all mRNAs. In contrast, Caf1 only trims poly(A) not bound by Pab1. As a consequence, Caf1 is a specialized deadenylase required for the selective deadenylation of transcripts with lower rates of translation elongation and reduced Pab1 occupancy. These findings reveal a coupling between the rates of translation and deadenylation that is dependent on Pab1 and Ccr4-Not.
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•Poly(A)-binding protein is efficiently released by Ccr4-Not nuclease activity•Ccr4, but not Caf1, removes poly(A) tails bound to Pab1•Ccr4 acts on all transcripts and Caf1 acts on transcripts with low codon optimality•Deadenylation by Ccr4-Not connects translation with mRNA stability
Ccr4-Not is a conserved deadenylation complex that contains two exonucleases, Ccr4 and Caf1. Webster et al. show that Ccr4 is a general deadenylase that removes Pab1-bound poly(A) tails. In contrast, Caf1 is a specialized exonuclease that acts on transcripts with low codon optimality, coupling translation elongation and mRNA stability.
Most cancer-related deaths are a result of metastasis, and thus the importance of this process as a target of therapy cannot be understated. By asking 'how can we effectively treat cancer?', we do ...not capture the complexity of a disease encompassing >200 different cancer types - many consisting of multiple subtypes - with considerable intratumoural heterogeneity, which can result in variable responses to a specific therapy. Moreover, we have much less information on the pathophysiological characteristics of metastases than is available for the primary tumour. Most disseminated tumour cells that arrive in distant tissues, surrounded by unfamiliar cells and a foreign microenvironment, are likely to die; however, those that survive can generate metastatic tumours with a markedly different biology from that of the primary tumour. To treat metastasis effectively, we must inhibit fundamental metastatic processes and develop specific preclinical and clinical strategies that do not rely on primary tumour responses. To address this crucial issue, Cancer Research UK and Cancer Therapeutics CRC Australia formed a Metastasis Working Group with representatives from not-for-profit, academic, government, industry and regulatory bodies in order to develop recommendations on how to tackle the challenges associated with treating (micro)metastatic disease. Herein, we describe the challenges identified as well as the proposed approaches for discovering and developing anticancer agents designed specifically to prevent or delay the metastatic outgrowth of cancer.
The occurrence of false positive detections in presence-absence data, even when they occur infrequently, can lead to severe bias when estimating species occupancy patterns. Building upon previous ...efforts to account for this source of observational error, we established a general framework to model false positives in occupancy studies and extend existing modeling approaches to encompass a broader range of sampling designs. Specifically, we identified three common sampling designs that are likely to cover most scenarios encountered by researchers. The different designs all included ambiguous detections, as well as some known-truth data, but their modeling differed in the level of the model hierarchy at which the known-truth information was incorporated (site level or observation level). For each model, we provide the likelihood, as well as R and BUGS code needed for implementation. We also establish a clear terminology and provide guidance to help choosing the most appropriate design and modeling approach.
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