Phylogenetic MCMC algorithms are misleading on mixtures of trees

Markov chain Monte Carlo (MCMC) algorithms play a critical role in the Bayesian approach to phylogenetic inference. We present a theoretical analysis of the rate of convergence of many of the widely used Markov chains. For N characters generated from a uniform mixture of two trees, we prove that the Markov chains take an exponentially long (in N) number of iterations to converge to the posterior distribution. Nevertheless, the likelihood plots for sample runs of the Markov chains deceivingly suggest that the chains converge rapidly to a unique tree. Our results rely on novel mathematical understanding of the log-likelihood function on the space of phylogenetic trees. The practical implications of our work are that Bayesian MCMC methods can be misleading when the data are generated from a mixture of trees. Thus, in cases of data containing potentially conflicting phylogenetic signals, phylogenetic reconstruction should be performed separately on each signal.     

Observation of polymer conformation hysteresis in extensional flow

Highly extensible Escherichia coli DNA molecules in planar extensional flow were visualized in dilute solution by fluorescence microscopy. For a narrow range of flow strengths, the molecules were found in either a coiled or highly extended conformation, depending on the deformation history of the polymer. This conformation hysteresis persists for many polymer relaxation times and is due to conformation-dependent hydrodynamic forces. Polymer conformational free-energy landscapes were calculated from computer simulations and show two free-energy minima for flow strengths near the coil-stretch transition. Hysteresis cycles may directly influence bulk-solution stresses and the development of stress-strain relations for dilute polymer flows.     

Two G protein oncogenes in human endocrine tumors

Somatic mutations in a subset of growth hormone (GH)-secreting pituitary tumors convert the gene for the alpha polypeptide chain (alpha s) of Gs into a putative oncogene, termed gsp. These mutations, which activate alpha s by inhibiting its guanosine triphosphatase (GTPase) activity, are found in codons for either of two amino acids, each of which is completely conserved in all known G protein alpha chains. The likelihood that similar mutations would activate other G proteins prompted a survey of human tumors for mutations that replace either of these two amino acids in other G protein alpha chain genes. The first gene so far tested, which encodes the alpha chain of Gi2, showed mutations that replaced arginine-179 with either cysteine or histidine in 3 of 11 tumors of the adrenal cortex and 3 of 10 endocrine tumors of the ovary. The mutant alpha i2 gene is a putative oncogene, referred to as gip2. In addition, gsp mutations were found in 18 of 42 GH-secreting pituitary tumors and in an autonomously functioning thyroid adenoma. These findings suggest that human tumors may harbor oncogenic mutations in various G protein alpha chain genes.     

A single IGF1 allele is a major determinant of small size in dogs

The domestic dog exhibits greater diversity in body size than any other terrestrial vertebrate. We used a strategy that exploits the breed structure of dogs to investigate the genetic basis of size. First, through a genome-wide scan, we identified a major quantitative trait locus (QTL) on chromosome 15 influencing size variation within a single breed. Second, we examined genetic variation in the 15-megabase interval surrounding the QTL in small and giant breeds and found marked evidence for a selective sweep spanning a single gene (IGF1), encoding insulin-like growth factor 1. A single IGF1 single-nucleotide polymorphism haplotype is common to all small breeds and nearly absent from giant breeds, suggesting that the same causal sequence variant is a major contributor to body size in all small dogs.     

CoRoT measures solar-like oscillations and granulation in stars hotter than the Sun

Oscillations of the Sun have been used to understand its interior structure. The extension of similar studies to more distant stars has raised many difficulties despite the strong efforts of the international community over the past decades. The CoRoT (Convection Rotation and Planetary Transits) satellite, launched in December 2006, has now measured oscillations and the stellar granulation signature in three main sequence stars that are noticeably hotter than the sun. The oscillation amplitudes are about 1.5 times as large as those in the Sun; the stellar granulation is up to three times as high. The stellar amplitudes are about 25% below the theoretic values, providing a measurement of the nonadiabaticity of the process ruling the oscillations in the outer layers of the stars.     

Drosophila RNAi screen reveals CD36 family member required for mycobacterial infection

Certain pathogens, such as Mycobacterium tuberculosis, survive within the hostile intracellular environment of a macrophage. To identify host factors required for mycobacterial entry and survival within macrophages, we performed a genomewide RNA interference screen in Drosophila macrophage-like cells, using Mycobacterium fortuitum. We identified factors required for general phagocytosis, as well as those needed specifically for mycobacterial infection. One specific factor, Peste (Pes), is a CD36 family member required for uptake of mycobacteria, but not Escherichia coli or Staphylococcus aureus. Moreover, mammalian class B scavenger receptors (SRs) conferred uptake of bacteria into nonphagocytic cells, with SR-BI and SR-BII uniquely mediating uptake of M. fortuitum, which suggests a conserved role for class B SRs in pattern recognition and innate immunity.     

A persistent oxygen anomaly reveals the fate of spilled methane in the deep Gulf of Mexico

Methane was the most abundant hydrocarbon released during the 2010 Deepwater Horizon oil spill in the Gulf of Mexico. Beyond relevancy to this anthropogenic event, this methane release simulates a rapid and relatively short-term natural release from hydrates into deep water. Based on methane and oxygen distributions measured at 207 stations throughout the affected region, we find that within ~120 days from the onset of release ~3.0 × 10(10) to 3.9 × 10(10) moles of oxygen were respired, primarily by methanotrophs, and left behind a residual microbial community containing methanotrophic bacteria. We suggest that a vigorous deepwater bacterial bloom respired nearly all the released methane within this time, and that by analogy, large-scale releases of methane from hydrate in the deep ocean are likely to be met by a similarly rapid methanotrophic response.     

DUBA: a deubiquitinase that regulates type I interferon production

Production of type I interferon (IFN-I) is a critical host defense triggered by pattern-recognition receptors (PRRs) of the innate immune system. Deubiquitinating enzyme A (DUBA), an ovarian tumor domain-containing deubiquitinating enzyme, was discovered in a small interfering RNA-based screen as a regulator of IFN-I production. Reduction of DUBA augmented the PRR-induced IFN-I response, whereas ectopic expression of DUBA had the converse effect. DUBA bound tumor necrosis factor receptor-associated factor 3 (TRAF3), an adaptor protein essential for the IFN-I response. TRAF3 is an E3 ubiquitin ligase that preferentially assembled lysine-63-linked polyubiquitin chains. DUBA selectively cleaved the lysine-63-linked polyubiquitin chains on TRAF3, resulting in its dissociation from the downstream signaling complex containing TANK-binding kinase 1. A discrete ubiquitin interaction motif within DUBA was required for efficient deubiquitination of TRAF3 and optimal suppression of IFN-I. Our data identify DUBA as a negative regulator of innate immune responses.