Messenger RNAs (mRNAs) encode information in both their primary sequence and their higher order structure. The independent contributions of factors like codon usage and secondary structure to ...regulating protein expression are difficult to establish as they are often highly correlated in endogenous sequences. Here, we used 2 approaches, global inclusion of modified nucleotides and rational sequence design of exogenously delivered constructs, to understand the role of mRNA secondary structure independent from codon usage. Unexpectedly, highly expressed mRNAs contained a highly structured coding sequence (CDS). Modified nucleotides that stabilize mRNA secondary structure enabled high expression across a wide variety of primary sequences. Using a set of eGFP mRNAs with independently altered codon usage and CDS structure, we find that the structure of the CDS regulates protein expression through changes in functional mRNA half-life (i.e., mRNA being actively translated). This work highlights an underappreciated role of mRNA secondary structure in the regulation of mRNA stability.
emcee: The MCMC Hammer Foreman-Mackey, Daniel; Hogg, David W.; Lang, Dustin ...
Publications of the Astronomical Society of the Pacific,
03/2013, Letnik:
125, Številka:
925
Journal Article
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ABSTRACT We introduce a stable, well tested Python implementation of the affine-invariant ensemble sampler for Markov chain Monte Carlo (MCMC) proposed by Goodman & Weare (2010). The code is open ...source and has already been used in several published projects in the astrophysics literature. The algorithm behind emcee has several advantages over traditional MCMC sampling methods and it has excellent performance as measured by the autocorrelation time (or function calls per independent sample). One major advantage of the algorithm is that it requires hand-tuning of only 1 or 2 parameters compared to ∼N2 for a traditional algorithm in an N-dimensional parameter space. In this document, we describe the algorithm and the details of our implementation. Exploiting the parallelism of the ensemble method, emcee permits any user to take advantage of multiple CPU cores without extra effort. The code is available online at http://dan.iel.fm/emcee under the GNU General Public License v2.
Adaptive accounts of modern low human fertility argue that small family size maximizes the inheritance of socioeconomic resources across generations and may consequently increase long-term fitness. ...This study explores the long-term impacts of fertility and socioeconomic position (SEP) on multiple dimensions of descendant success in a unique Swedish cohort of 14 000 individuals born during 1915–1929. We show that low fertility and high SEP predict increased descendant socioeconomic success across four generations. Furthermore, these effects are multiplicative, with the greatest benefits of low fertility observed when SEP is high. Low fertility and high SEP do not, however, predict increased descendant reproductive success. Our results are therefore consistent with the idea that modern fertility limitation represents a strategic response to the local costs of rearing socioeconomically competitive offspring, but contradict adaptive models suggesting that it maximizes long-term fitness. This indicates a conflict in modern societies between behaviours promoting socioeconomic versus biological success. This study also makes a methodological contribution, demonstrating that the number of offspring strongly predicts long-term fitness and thereby validating use of fertility data to estimate current selective pressures in modern populations. Finally, our findings highlight that differences in fertility and SEP can have important long-term effects on the persistence of social inequalities across generations.
Source Code Repositories * Github (http://github.com): A web-based hosting service for software development projects that use the Git revision control system, including many open-source projects. * ...Git (http://git-scm.com): A free and open-source distributed version control system designed to handle everything from small to very large projects with speed and efficiency. * Mercurial (http://mercurial.selenic.com): A free, distributed source control management tool. Systems to Package, Access, and Execute Data and Code * IPython Notebook (http://ipython.org/notebook.html): A web-based interactive computational environment where you can combine code execution, text, mathematics, plots, and rich media into a single document. * ROpenSci (http://ropensci.org): A suite of packages that allow access to data repositories through the R statistical programming environment. * Authorea (https://authorea.com): A collaborative online word processor for scholarly papers that allows the writing of web-native, living, dynamic, "executable" articles that include text, mathematical notation, images, and data.
Speciation begins when populations become genetically separated through a substantial reduction in gene flow, and it is at this point that a genetically cohesive set of populations attain the sole ...property of species: the independent evolution of a population-level lineage. The comprehensive delimitation of species within biodiversity hotspots, regardless of their level of divergence, is important for understanding the factors that drive the diversification of biota and for identifying them as targets for conservation. However, delimiting recently diverged species is challenging due to insufficient time for the differential evolution of characters--including morphological differences, reproductive isolation, and gene tree monophyly--that are typically used as evidence for separately evolving lineages.
In this study, we assembled multiple lines of evidence from the analysis of mtDNA and nDNA sequence data for the delimitation of a high diversity of cryptically diverged population-level mouse lemur lineages across the island of Madagascar. Our study uses a multi-faceted approach that applies phylogenetic, population genetic, and genealogical analysis for recognizing lineage diversity and presents the most thoroughly sampled species delimitation of mouse lemur ever performed.
The resolution of a large number of geographically defined clades in the mtDNA gene tree provides strong initial evidence for recognizing a high diversity of population-level lineages in mouse lemurs. We find additional support for lineage recognition in the striking concordance between mtDNA clades and patterns of nuclear population structure. Lineages identified using these two sources of evidence also exhibit patterns of population divergence according to genealogical exclusivity estimates. Mouse lemur lineage diversity is reflected in both a geographically fine-scaled pattern of population divergence within established and geographically widespread taxa, as well as newly resolved patterns of micro-endemism revealed through expanded field sampling into previously poorly and well-sampled regions.
With ongoing colony losses driven in part by the Varroa mite and the associated exacerbation of the virus load, there is an urgent need to protect honey bees (
) from fatal levels of virus infection ...and from the non-target effects of insecticides used in agricultural settings. A continuously replicating cell line derived from the honey bee would provide a valuable tool for the study of molecular mechanisms of virus-host interaction, for the screening of antiviral agents for potential use within the hive, and for the assessment of the risk of current and candidate insecticides to the honey bee. However, the establishment of a continuously replicating honey bee cell line has proved challenging. Here, we provide an overview of attempts to establish primary and continuously replicating hymenopteran cell lines, methods (including recent results) of establishing honey bee cell lines, challenges associated with the presence of latent viruses (especially
) in established cell lines and methods to establish virus-free cell lines. We also describe the potential use of honey bee cell lines in conjunction with infectious clones of honey bee viruses for examination of fundamental virology.
Analyses of phylogenetic topology and estimates of divergence timing have facilitated a reconstruction of Madagascar's colonization events by vertebrate animals, but that information alone does not ...reveal the major factors shaping the island's biogeographic history. Here, we examine profiles of Malagasy vertebrate clades through time within the context of the island's paleogeographical evolution to determine how particular events influenced the arrival of the island's extant groups. First we compare vertebrate profiles on Madagascar before and after selected events; then we compare tetrapod profiles on Madagascar to contemporary tetrapod compositions globally. We show that changes from the Mesozoic to the Cenozoic in the proportions of Madagascar's tetrapod clades (particularly its increase in the representation of birds and mammals) are tied to changes in their relative proportions elsewhere on the globe. Differences in the representation of vertebrate classes from the Mesozoic to the Cenozoic reflect the effects of extinction (i.e., the non-random susceptibility of the different vertebrate clades to purported catastrophic global events 65 million years ago), and new evolutionary opportunities for a subset of vertebrates with the relatively high potential for transoceanic dispersal potential. In comparison, changes in vertebrate class representation during the Cenozoic are minor. Despite the fact that the island's isolation has resulted in high vertebrate endemism and a unique and taxonomically imbalanced extant vertebrate assemblage (both hailed as testimony to its long isolation), that isolation was never complete. Indeed, Madagascar's extant tetrapod fauna owes more to colonization during the Cenozoic than to earlier arrivals. Madagascar's unusual vertebrate assemblage needs to be understood with reference to the basal character of clades originating prior to the K-T extinction, as well as to the differential transoceanic dispersal advantage of other, more recently arriving clades. Thus, the composition of Madagascar's endemic vertebrate assemblage itself provides evidence of the island's paleogeographic history.
Prosthetic joint infection PJI after total knee arthroplasty (TKA) remains a common and challenging problem for joint replacement surgeons and patients. Once the diagnosis of PJI has been made, ...patient goals and characteristics as well as the infection timeline dictate treatment. Most commonly, this involves a two‐stage procedure with the removal of all implants, debridement, and placement of a static or dynamic antibiotic spacer. Static spacers are commonly indicated for older, less healthy patients that would benefit from soft tissue rest after initial debridement. Mobile spacers are typically used in younger, healthier patients to improve quality of life and reduce soft‐tissue contractures during antibiotic spacer treatment. Spacers are highly customizable with regard to antibiotic choice, cement variety, and spacer design, each with reported advantages, drawbacks, and indications that will be covered in this article. While no spacer is superior to any other, the modern arthroplasty surgeon must be familiar with the available modalities to optimize treatment for each patient. Here we propose a treatment algorithm to assist surgeons in deciding on treatment for PJI after TKA.
How, when, and from where Madagascar's vertebrates arrived on the island is poorly known, and a comprehensive explanation for the distribution of its organisms has yet to emerge. We begin to break ...that impasse by analyzing vertebrate arrival patterns implied by currently existing taxa. For each of 81 clades, we compiled arrival date, source, and ancestor type (obligate freshwater, terrestrial, facultative swimmer, or volant). We analyzed changes in arrival rates, with and without adjusting for clade extinction. Probability of successful transoceanic dispersal is negatively correlated with distance traveled and influenced by ocean currents and ancestor type. Obligate rafters show a decrease in probability of successful transoceanic dispersal from the Paleocene onward, reaching the lowest levels after the mid-Miocene. This finding is consistent with a paleoceanographic model Ali JR, Huber M (2010) Nature 463:653–656 that predicts Early Cenozoic surface currents periodically conducive to rafting or swimming from Africa, followed by a reconfiguration to present-day flow 15–20 million years ago that significantly diminished the ability for transoceanic dispersal to Madagascar from the adjacent mainland.
Regulation of Corepressor Function by Nuclear NADH Zhang, Qinghong; Piston, David W.; Goodman, Richard H.
Science (American Association for the Advancement of Science),
03/2002, Letnik:
295, Številka:
5561
Journal Article
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The corepressor CtBP (carboxyl-terminal binding protein) is involved in transcriptional pathways important for development, cell cycle regulation, and transformation. We demonstrate that CtBP binding ...to cellular and viral transcriptional repressors is regulated by the nicotinamide adenine dinucleotides NAD+and NADH, with NADH being two to three orders of magnitude more effective. Levels of free nuclear nicotinamide adenine dinucleotides, determined using two-photon microscopy, correspond to the levels required for half-maximal CtBP binding and are considerably lower than those previously reported. Agents capable of increasing NADH levels stimulate CtBP binding to its partners in vivo and potentiate CtBP-mediated repression. We propose that this ability to detect changes in nuclear NAD+/NADH ratio allows CtBP to serve as a redox sensor for transcription.
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