Accelerated FoxP2 Evolution in Echolocating Bats

FOXP2 is a transcription factor implicated in the development and neural control of orofacial coordination, particularly with respect to vocalisation. Observations that orthologues show almost no variation across vertebrates yet differ by two amino acids between humans and chimpanzees have led to speculation that recent evolutionary changes might relate to the emergence of language. Echolocating bats face especially challenging sensorimotor demands, using vocal signals for orientation and often for prey capture. To determine whether mutations in the FoxP2 gene could be associated with echolocation, we sequenced FoxP2 from echolocating and non-echolocating bats as well as a range of other mammal species. We found that contrary to previous reports, FoxP2 is not highly conserved across all nonhuman mammals but is extremely diverse in echolocating bats. We detected divergent selection (a change in selective pressure) at FoxP2 between bats with contrasting sonar systems, suggesting the intriguing possibility of a role for FoxP2 in the evolution and development of echolocation. We speculate that observed accelerated evolution of FoxP2 in bats supports a previously proposed function in sensorimotor coordination

Spin Relaxation in Ge/Si Core-Shell Nanowire Qubits

Controlling decoherence is the most challenging task in realizing quantum information hardware. Single electron spins in gallium arsenide are a leading candidate among solid- state implementations, however strong coupling to nuclear spins in the substrate hinders this approach. To realize spin qubits in a nuclear-spin-free system, intensive studies based on group-IV semiconductor are being pursued. In this case, the challenge is primarily control of materials and interfaces, and device nanofabrication. We report important steps toward implementing spin qubits in a predominantly nuclear-spin-free system by demonstrating state preparation, pulsed gate control, and charge-sensing spin readout of confined hole spins in a one-dimensional Ge/Si nanowire. With fast gating, we measure T1 spin relaxation times in coupled quantum dots approaching 1 ms, increasing with lower magnetic field, consistent with a spin-orbit mechanism that is usually masked by hyperfine contributions

fMRI scanner noise interaction with affective neural processes

The purpose of the present study was the investigation of interaction effects between functional MRI scanner noise and affective neural processes. Stimuli comprised of psychoacoustically balanced musical pieces, expressing three different emotions (fear, neutral, joy). Participants (N=34, 19 female) were split into two groups, one subjected to continuous scanning and another subjected to sparse temporal scanning that features decreased scanner noise. Tests for interaction effects between scanning group (sparse/quieter vs continuous/noisier) and emotion (fear, neutral, joy) were performed. Results revealed interactions between the affective expression of stimuli and scanning group localized in bilateral auditory cortex, insula and visual cortex (calcarine sulcus). Post-hoc comparisons revealed that during sparse scanning, but not during continuous scanning, BOLD signals were significantly stronger for joy than for fear, as well as stronger for fear than for neutral in bilateral auditory cortex. During continuous scanning, but not during sparse scanning, BOLD signals were significantly stronger for joy than for neutral in the left auditory cortex and for joy than for fear in the calcarine sulcus. To the authors' knowledge, this is the first study to show a statistical interaction effect between scanner noise and affective processes and extends evidence suggesting scanner noise to be an important factor in functional MRI research that can affect and distort affective brain processes

HIV Evolution in Early Infection: Selection Pressures, Patterns of Insertion and Deletion, and the Impact of APOBEC

The pattern of viral diversification in newly infected individuals provides information about the host environment and immune responses typically experienced by the newly transmitted virus. For example, sites that tend to evolve rapidly across multiple early-infection patients could be involved in enabling escape from common early immune responses, could represent adaptation for rapid growth in a newly infected host, or could represent reversion from less fit forms of the virus that were selected for immune escape in previous hosts. Here we investigated the diversification of HIV-1 env coding sequences in 81 very early B subtype infections previously shown to have resulted from transmission or expansion of single viruses (n = 78) or two closely related viruses (n = 3). In these cases, the sequence of the infecting virus can be estimated accurately, enabling inference of both the direction of substitutions as well as distinction between insertion and deletion events. By integrating information across multiple acutely infected hosts, we find evidence of adaptive evolution of HIV-1 env and identify a subset of codon sites that diversified more rapidly than can be explained by a model of neutral evolution. Of 24 such rapidly diversifying sites, 14 were either i) clustered and embedded in CTL epitopes that were verified experimentally or predicted based on the individual's HLA or ii) in a nucleotide context indicative of APOBEC-mediated G-to-A substitutions, despite having excluded heavily hypermutated sequences prior to the analysis. In several cases, a rapidly evolving site was embedded both in an APOBEC motif and in a CTL epitope, suggesting that APOBEC may facilitate early immune escape. Ten rapidly diversifying sites could not be explained by CTL escape or APOBEC hypermutation, including the most frequently mutated site, in the fusion peptide of gp41. We also examined the distribution, extent, and sequence context of insertions and deletions, and we provide evidence that the length variation seen in hypervariable loop regions of the envelope glycoprotein is a consequence of selection and not of mutational hotspots. Our results provide a detailed view of the process of diversification of HIV-1 following transmission, highlighting the role of CTL escape and hypermutation in shaping viral evolution during the establishment of new infections

Powerful Bivariate Genome-Wide Association Analyses Suggest the SOX6 Gene Influencing Both Obesity and Osteoporosis Phenotypes in Males

Current genome-wide association studies (GWAS) are normally implemented in a univariate framework and analyze different phenotypes in isolation. This univariate approach ignores the potential genetic correlation between important disease traits. Hence this approach is difficult to detect pleiotropic genes, which may exist for obesity and osteoporosis, two common diseases of major public health importance that are closely correlated genetically. was previously found to be essential to both cartilage formation/chondrogenesis and obesity-related insulin resistance, suggesting the gene's dual role in both bone and fat. gene's importance in co-regulation of obesity and osteoporosis

Consensus-Phenotype Integration of Transcriptomic and Metabolomic Data Implies a Role for Metabolism in the Chemosensitivity of Tumour Cells

Using transcriptomic and metabolomic measurements from the NCI60 cell line panel, together with a novel approach to integration of molecular profile data, we show that the biochemical pathways associated with tumour cell chemosensitivity to platinum-based drugs are highly coincident, i.e. they describe a consensus phenotype. Direct integration of metabolome and transcriptome data at the point of pathway analysis improved the detection of consensus pathways by 76%, and revealed associations between platinum sensitivity and several metabolic pathways that were not visible from transcriptome analysis alone. These pathways included the TCA cycle and pyruvate metabolism, lipoprotein uptake and nucleotide synthesis by both salvage and de novo pathways. Extending the approach across a wide panel of chemotherapeutics, we confirmed the specificity of the metabolic pathway associations to platinum sensitivity. We conclude that metabolic phenotyping could play a role in predicting response to platinum chemotherapy and that consensus-phenotype integration of molecular profiling data is a powerful and versatile tool for both biomarker discovery and for exploring the complex relationships between biological pathways and drug response

Comprehensive annotation of the Parastagonospora nodorum reference genome using next-generation genomics, transcriptomics and proteogenomics

Parastagonospora nodorum, the causal agent of Septoria nodorum blotch (SNB), is an economically important pathogen of wheat (Triticum spp.), and a model for the study of necrotrophic pathology and genome evolution. The reference P. nodorum strain SN15 was the first Dothideomycete with a published genome sequence, and has been used as the basis for comparison within and between species. Here we present an updated reference genome assembly with corrections of SNP and indel errors in the underlying genome assembly from deep resequencing data as well as extensive manual annotation of gene models using transcriptomic and proteomic sources of evidence (https://github.com/robsyme/Parastagonospora_nodorum_SN15). The updated assembly and annotation includes 8,366 genes with modified protein sequence and 866 new genes. This study shows the benefits of using a wide variety of experimental methods allied to expert curation to generate a reliable set of gene models

HIV and Syphilis Co-Infection Increasing among Men Who Have Sex with Men in China: A Systematic Review and Meta-Analysis

BACKGROUND: This study aims to estimate the magnitude and changing trends of HIV, syphilis and HIV-syphilis co-infections among men who have sex with men (MSM) in China during 2003-2008 through a systematic review of published literature. METHODOLOGY/PRINCIPAL FINDINGS: Chinese and English literatures were searched for studies reporting HIV and syphilis prevalence among MSM from 2003 to 2008. The prevalence estimates were summarized and analysed by meta-analyses. Meta-regression was used to identify the potential factors that are associated with high heterogeneities in meta-analysis. Seventy-one eligible articles were selected in this review (17 in English and 54 in Chinese). Nationally, HIV prevalence among MSM increased from 1.3% during 2003-2004 to 2.4% during 2005-2006 and to 4.7% during 2007-2008. Syphilis prevalence increased from 6.8% during 2003-2004 to 10.4% during 2005-2006 and to 13.5% during 2007-2008. HIV-syphilis co-infection increased from 1.4% during 2005-2006 to 2.7% during 2007-2008. Study locations and study period are the two major contributors of heterogeneities of both HIV and syphilis prevalence among Chinese MSM. CONCLUSIONS/SIGNIFICANCE: There have been significant increases in HIV and syphilis prevalence among MSM in China. Scale-up of HIV and syphilis screening and implementation of effective public health intervention programs should target MSM to prevent further spread of HIV and syphilis infection

Evaluation in artificial intelligence: From task-oriented to ability-oriented measurement

The final publication is available at Springer via http://dx.doi.org/ 10.1007/s10462-016-9505-7.The evaluation of artificial intelligence systems and components is crucial for the progress of the discipline. In this paper we describe and critically assess the different ways AI systems are evaluated, and the role of components and techniques in these systems. We first focus on the traditional task-oriented evaluation approach. We identify three kinds of evaluation: human discrimination, problem benchmarks and peer confrontation. We describe some of the limitations of the many evaluation schemes and competitions in these three categories, and follow the progression of some of these tests. We then focus on a less customary (and challenging) ability-oriented evaluation approach, where a system is characterised by its (cognitive) abilities, rather than by the tasks it is designed to solve. We discuss several possibilities: the adaptation of cognitive tests used for humans and animals, the development of tests derived from algorithmic information theory or more integrated approaches under the perspective of universal psychometrics. We analyse some evaluation tests from AI that are better positioned for an ability-oriented evaluation and discuss how their problems and limitations can possibly be addressed with some of the tools and ideas that appear within the paper. Finally, we enumerate a series of lessons learnt and generic guidelines to be used when an AI evaluation scheme is under consideration.I thank the organisers of the AEPIA Summer School On Artificial Intelligence, held in September 2014, for giving me the opportunity to give a lecture on 'AI Evaluation'. This paper was born out of and evolved through that lecture. The information about many benchmarks and competitions discussed in this paper have been contrasted with information from and discussions with many people: M. Bedia, A. Cangelosi, C. Dimitrakakis, I. GarcIa-Varea, Katja Hofmann, W. Langdon, E. Messina, S. Mueller, M. Siebers and C. Soares. Figure 4 is courtesy of F. Martinez-Plumed. Finally, I thank the anonymous reviewers, whose comments have helped to significantly improve the balance and coverage of the paper. This work has been partially supported by the EU (FEDER) and the Spanish MINECO under Grants TIN 2013-45732-C4-1-P, TIN 2015-69175-C4-1-R and by Generalitat Valenciana PROMETEOII2015/013.José Hernández-Orallo (2016). Evaluation in artificial intelligence: From task-oriented to ability-oriented measurement. 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