Molecular Clocks without Rocks: New Solutions for Old Problems.

Molecular data have been used to date species divergences ever since they were described as documents of evolutionary history in the 1960s. Yet, an inadequate fossil record and discordance between gene trees and species trees are persistently problematic. We examine how, by accommodating gene tree discordance and by scaling branch lengths to absolute time using mutation rate and generation time, multispecies coalescent (MSC) methods can potentially overcome these challenges. We find that time estimates can differ - in some cases, substantially - depending on whether MSC methods or traditional phylogenetic methods that apply concatenation are used, and whether the tree is calibrated with pedigree-based mutation rates or with fossils. We discuss the advantages and shortcomings of both approaches and provide practical guidance for data analysis when using these methods

The role and assembly mechanism of nucleoprotein in influenza A virus ribonucleoprotein complexes.

The nucleoprotein of negative-strand RNA viruses forms a major component of the ribonucleoprotein complex that is responsible for viral transcription and replication. However, the precise role of nucleoprotein in viral RNA transcription and replication is not clear. Here we show that nucleoprotein of influenza A virus is entirely dispensable for replication and transcription of short viral RNA-like templates in vivo, suggesting that nucleoprotein represents an elongation factor for the viral RNA polymerase. We also find that the recruitment of nucleoprotein to nascent ribonucleoprotein complexes during replication of full-length viral genes is mediated through nucleoprotein-nucleoprotein homo-oligomerization in a 'tail loop-first' orientation and is independent of RNA binding. This work demonstrates that nucleoprotein does not regulate the initiation and termination of transcription and replication by the viral polymerase in vivo, and provides new mechanistic insights into the assembly and regulation of viral ribonucleoprotein complexes

Pedigree-based and phylogenetic methods support surprising patterns of mutation rate and spectrum in the gray mouse lemur

Mutations are the raw material on which evolution acts, and knowledge of their frequency and genomic distribution is crucial for understanding how evolution operates at both long and short timescales. At present, the rate and spectrum of de novo mutations have been directly characterized in relatively few lineages. Our study provides the first direct mutation-rate estimate for a strepsirrhine (i.e., the lemurs and lorises), which comprises nearly half of the primate clade. Using high-coverage linked-read sequencing for a focal quartet of gray mouse lemurs (Microcebus murinus), we estimated the mutation rate to be among the highest calculated for a mammal at 1.52 × 10(–8) (95% credible interval: 1.28 × 10(−8)–1.78 × 10(−8)) mutations/site/generation. Further, we found an unexpectedly low count of paternal mutations, and only a modest overrepresentation of mutations at CpG sites. Despite the surprising nature of these results, we found both the rate and spectrum to be robust to the manipulation of a wide range of computational filtering criteria. We also sequenced a technical replicate to estimate a false-negative and false-positive rate for our data and show that any point estimate of a de novo mutation rate should be considered with a large degree of uncertainty. For validation, we conducted an independent analysis of context-dependent substitution types for gray mouse lemur and five additional primate species for which de novo mutation rates have also been estimated. These comparisons revealed general consistency of the mutation spectrum between the pedigree-based and the substitution-rate analyses for all species compared

The Dynamics and Distribution of Angular Momentum in HiZELS Star – Forming Galaxies at z = 0.8 – 3.3

We present adaptive optics assisted integral field spectroscopy of 34 star–forming galaxies at z = 0.8–3.3 selected from the HiZELS narrow-band survey. We measure the kinematics of the ionised interstellar medium on ∼1 kpc scales, and show that the galaxies are turbulent, with a median ratio of rotational to dispersion support of V / σ = 0.82 ± 0.13. We combine the dynamics with high-resolution rest-frame optical imaging and extract emission line rotation curves. We show that high-redshift star forming galaxies follow a similar power-law trend in specific angular momentum with stellar mass as that of local late type galaxies. We exploit the high resolution of our data and examine the radial distribution of angular momentum within each galaxy by constructing total angular momentum profiles. Although the stellar mass of a typical star-forming galaxy is expected to grow by a factor ∼ 8 in the ∼5 Gyrs between z ∼ 3.3 and z ∼ 0.8, we show that the internal distribution of angular momentum becomes less centrally concentrated in this period i.e the angular momentum grows outwards. To interpret our observations, we exploit the EAGLE simulation and trace the angular momentum evolution of star forming galaxies from z ∼ 3 to z ∼ 0, identifying a similar trend of decreasing angular momentum concentration. This change is attributed to a combination of gas accretion in the outer disk, and feedback that preferentially arises from the central regions of the galaxy. We discuss how the combination of the growing bulge and angular momentum stabilises the disk and gives rise to the Hubble sequence

Development of an improved polykaryon-based influenza virus rescue system

<p>Abstract</p> <p>Background</p> <p>Virus rescue from transfected cells is an extremely useful technique that allows defined viral clones to be engineered for the purpose of rational vaccine design or fundamental reverse genetics studies. However, it is often hindered by low primary rescue success rates or yields, especially with field-derived viral strains.</p> <p>Approach</p> <p>We investigated the possibility of enhancing influenza virus rescue by eliciting cell fusion to increase the chances of having all necessary plasmids expressed within the same polykaryon. To this end we used the Maedi-Visna Virus envelope protein which has potent fusion activity in cells from a wide range of different species.</p> <p>Results</p> <p>Co-transfecting cells with the eight plasmids necessary to rescue influenza virus plus a plasmid expressing the Maedi-Visna Virus envelope protein resulted in increased rescue efficiency. In addition, partial complements of the 8-plasmid rescue system could be transfected into two separate populations of cells, which upon fusion led to live virus rescue.</p> <p>Conclusion</p> <p>The simple modification described here has the potential to improve the efficiency of the virus rescue process and expand the potential applications for reverse genetic studies.</p

Recruitment of a protein complex containing Tat and cyclin T1 to TAR governs the species specificity of HIV-1 Tat.

Human cyclin T1 (hCycT1), a major subunit of the essential elongation factor P-TEFb, has been proposed to act as a cofactor for human immunodeficiency virus type 1 (HIV-1) Tat. Here, we show that murine cyclin T1 (mCycT1) binds the activation domain of HIV-1 Tat but, unlike hCycT1, cannot mediate Tat function because it cannot be recruited efficiently to TAR. In fact, overexpression of mCycT1, but not hCycT1, specifically inhibits Tat-TAR function in human cells. This discordant phenotype results from a single amino acid difference between hCycT1 and mCycT1, a tyrosine in place of a cysteine at residue 261. These data indicate that the ability of Tat to recruit CycT1/P-TEFb to TAR determines the species restriction of HIV-1 Tat function in murine cells and therefore demonstrate that this recruitment is a critical function of the Tat protein

The influence of training and experience on memory strategy

© 2015, Psychonomic Society, Inc. This paper investigates whether, and if so how much, prior training and experience overwrite the influence of the constraints of the task environment on strategy deployment. This evidence is relevant to the theory of soft constraints that focuses on the role of constraints in the task environment (Gray, Simms, Fu, & Schoelles, Psychological Review, 113: 461–482, 2006). The theory explains how an increase in the cost of accessing information induces a more memory-based strategy involving more encoding and planning. Experiments 1 and 3 adopt a traditional training and transfer design using the Blocks World Task in which participants were exposed to training trials involving a 2.5-s delay in accessing goal-state information before encountering transfer trials in which there was no access delay. The effect of prior training was assessed by the degree of memory-based strategy adopted in the transfer trials. Training with an access delay had a substantial carry-over effect and increased the subsequent degree of memory-based strategy adopted in the transfer environment. However, such effects do not necessarily occur if goal-state access cost in training is less costly than in transfer trials (Experiment 2). Experiment 4 used a fine-grained intra-trial design to examine the effect of experiencing access cost on one, two, or three occasions within the same trial and found that such experience on two consecutive occasions was sufficient to induce a more memory-based strategy. This paper establishes some effects of training that are relevant to the soft constraints theory and also discusses practical implications