Search for Gravitational Waves from Primordial Black Hole Binary Coalescences in the Galactic Halo

We use data from the second science run of the LIGO gravitational-wave detectors to search for the gravitational waves from primordial black hole (PBH) binary coalescence with component masses in the range 0.2--$1.0 M_\odot$. The analysis requires a signal to be found in the data from both LIGO observatories, according to a set of coincidence criteria. No inspiral signals were found. Assuming a spherical halo with core radius 5 kpc extending to 50 kpc containing non-spinning black holes with masses in the range 0.2--$1.0 M_\odot$, we place an observational upper limit on the rate of PBH coalescence of 63 per year per Milky Way halo (MWH) with 90% confidence.Comment: 7 pages, 4 figures, to be submitted to Phys. Rev.

Model-based clustering of DNA methylation array data: a recursive-partitioning algorithm for high-dimensional data arising as a mixture of beta distributions

<p>Abstract</p> <p>Background</p> <p>Epigenetics is the study of heritable changes in gene function that cannot be explained by changes in DNA sequence. One of the most commonly studied epigenetic alterations is cytosine methylation, which is a well recognized mechanism of epigenetic gene silencing and often occurs at tumor suppressor gene loci in human cancer. Arrays are now being used to study DNA methylation at a large number of loci; for example, the Illumina GoldenGate platform assesses DNA methylation at 1505 loci associated with over 800 cancer-related genes. Model-based cluster analysis is often used to identify DNA methylation subgroups in data, but it is unclear how to cluster DNA methylation data from arrays in a scalable and reliable manner.</p> <p>Results</p> <p>We propose a novel model-based recursive-partitioning algorithm to navigate clusters in a beta mixture model. We present simulations that show that the method is more reliable than competing nonparametric clustering approaches, and is at least as reliable as conventional mixture model methods. We also show that our proposed method is more computationally efficient than conventional mixture model approaches. We demonstrate our method on the normal tissue samples and show that the clusters are associated with tissue type as well as age.</p> <p>Conclusion</p> <p>Our proposed recursively-partitioned mixture model is an effective and computationally efficient method for clustering DNA methylation data.</p

Childhood adversity, mental ill-health and aggressive behavior in an African orphanage: Changes in response to trauma-focused therapy and the implementation of a new instructional system

<p>Abstract</p> <p>Background</p> <p>The number of orphans in Sub-Saharan Africa is constantly rising. While it is known that family or community care is preferable over institutional care of African orphans, little is known about the quality of care in orphanages and possibilities of improvement.</p> <p>Study 1</p> <p>Methods</p> <p>Exposure to traumatic stress, experiences of violence in the home, school and orphanage, as well as mental ill-health and aggression of 38 children (mean age of <it>M </it>= 8.64 years) living in an orphanage in rural Tanzania were assessed at two time points. The severity of post-traumatic stress disorder symptoms (PTSD), depressive symptoms, and internalizing and externalizing problems were used as indicators of mental ill-health.</p> <p>Results</p> <p>Violence experienced in the orphanage correlated more strongly with all indicators of mental ill-health than violence in the former home, school or neighborhood at time point 1. Additionally, violence experienced in the orphanage had a positive relationship with the aggressive behavior of the children at time point 2.</p> <p>Study 2</p> <p>Methods</p> <p>With the help of the pre-post assessment of Study 1, the implementation of a new instructional system and psychotherapeutic treatment (KIDNET) for trauma-related illness were evaluated.</p> <p>Results</p> <p>In response to both, a change in the instructional system and psychotherapeutic treatment of PTSD, a massive decline in experienced violence and in the severity of PTSD-symptoms was found, whereas depressive symptoms and internalizing and externalizing problems exhibited little change.</p> <p>Conclusions</p> <p>These studies show that violence, especially in the orphanage, can severely contribute to mental ill-health in orphans and that mental health can be improved by implementing a new instructional system and psychotherapeutic treatment in an orphanage. Moreover, the results indicate that the experience of violence in an orphanage also plays a crucial role in aggressive behavior of the orphans.</p

Fast Homozygosity Mapping and Identification of a Zebrafish ENU-Induced Mutation by Whole-Genome Sequencing

Forward genetics using zebrafish is a powerful tool for studying vertebrate development through large-scale mutagenesis. Nonetheless, the identification of the molecular lesion is still laborious and involves time-consuming genetic mapping. Here, we show that high-throughput sequencing of the whole zebrafish genome can directly locate the interval carrying the causative mutation and at the same time pinpoint the molecular lesion. The feasibility of this approach was validated by sequencing the m1045 mutant line that displays a severe hypoplasia of the exocrine pancreas. We generated 13 Gb of sequence, equivalent to an eightfold genomic coverage, from a pool of 50 mutant embryos obtained from a map-cross between the AB mutant carrier and the WIK polymorphic strain. The chromosomal region carrying the causal mutation was localized based on its unique property to display high levels of homozygosity among sequence reads as it derives exclusively from the initial AB mutated allele. We developed an algorithm identifying such a region by calculating a homozygosity score along all chromosomes. This highlighted an 8-Mb window on chromosome 5 with a score close to 1 in the m1045 mutants. The sequence analysis of all genes within this interval revealed a nonsense mutation in the snapc4 gene. Knockdown experiments confirmed the assertion that snapc4 is the gene whose mutation leads to exocrine pancreas hypoplasia. In conclusion, this study constitutes a proof-of-concept that whole-genome sequencing is a fast and effective alternative to the classical positional cloning strategies in zebrafish

Sicily statement on classification and development of evidence-based practice learning assessment tools

<p>Abstract</p> <p>Background</p> <p>Teaching the steps of evidence-based practice (EBP) has become standard curriculum for health professions at both student and professional levels. Determining the best methods for evaluating EBP learning is hampered by a dearth of valid and practical assessment tools and by the absence of guidelines for classifying the purpose of those that exist. Conceived and developed by delegates of the Fifth International Conference of Evidence-Based Health Care Teachers and Developers, the aim of this statement is to provide guidance for purposeful classification and development of tools to assess EBP learning.</p> <p>Discussion</p> <p>This paper identifies key principles for designing EBP learning assessment tools, recommends a common taxonomy for new and existing tools, and presents the Classification Rubric for EBP Assessment Tools in Education (CREATE) framework for classifying such tools. Recommendations are provided for developers of EBP learning assessments and priorities are suggested for the types of assessments that are needed. Examples place existing EBP assessments into the CREATE framework to demonstrate how a common taxonomy might facilitate purposeful development and use of EBP learning assessment tools.</p> <p>Summary</p> <p><it>The widespread adoption of EBP into professional education requires valid and reliable measures of learning. Limited tools exist with established psychometrics. This international consensus statement strives to provide direction for developers of new EBP learning assessment tools and a framework for classifying the purposes of such tools</it>.</p

Reconstruction of metabolic pathways for the cattle genome

<p>Abstract</p> <p>Background</p> <p>Metabolic reconstruction of microbial, plant and animal genomes is a necessary step toward understanding the evolutionary origins of metabolism and species-specific adaptive traits. The aims of this study were to reconstruct conserved metabolic pathways in the cattle genome and to identify metabolic pathways with missing genes and proteins. The MetaCyc database and PathwayTools software suite were chosen for this work because they are widely used and easy to implement.</p> <p>Results</p> <p>An amalgamated cattle genome database was created using the NCBI and Ensembl cattle genome databases (based on build 3.1) as data sources. PathwayTools was used to create a cattle-specific pathway genome database, which was followed by comprehensive manual curation for the reconstruction of metabolic pathways. The curated database, CattleCyc 1.0, consists of 217 metabolic pathways. A total of 64 mammalian-specific metabolic pathways were modified from the reference pathways in MetaCyc, and two pathways previously identified but missing from MetaCyc were added. Comparative analysis of metabolic pathways revealed the absence of mammalian genes for 22 metabolic enzymes whose activity was reported in the literature. We also identified six human metabolic protein-coding genes for which the cattle ortholog is missing from the sequence assembly.</p> <p>Conclusion</p> <p>CattleCyc is a powerful tool for understanding the biology of ruminants and other cetartiodactyl species. In addition, the approach used to develop CattleCyc provides a framework for the metabolic reconstruction of other newly sequenced mammalian genomes. It is clear that metabolic pathway analysis strongly reflects the quality of the underlying genome annotations. Thus, having well-annotated genomes from many mammalian species hosted in BioCyc will facilitate the comparative analysis of metabolic pathways among different species and a systems approach to comparative physiology.</p

Pliocene-Quaternary crustal melting in central and northern Tibet and insights into crustal flow

There is considerable controversy over the nature of geophysically recognized low-velocity-high-conductivity zones (LV-HCZs) within the Tibetan crust, and their role in models for the development of the Tibetan Plateau. Here we report petrological and geochemical data on magmas erupted 4.7-0.3 Myr ago in central and northern Tibet, demonstrating that they were generated by partial melting of crustal rocks at temperatures of 700-1,050°C and pressures of 0.5-1.5 GPa. Thus Pliocene-Quaternary melting of crustal rocks occurred at depths of 15-50 km in areas where the LV-HCZs have been recognized. This provides new petrological evidence that the LV-HCZs are sources of partial melt. It is inferred that crustal melting played a key role in triggering crustal weakening and outward crustal flow in the expansion of the Tibetan Plateau

The Marine Microbial Eukaryote Transcriptome Sequencing Project (MMETSP): illuminating the functional diversity of eukaryotic life in the oceans through transcriptome sequencing.

Microbial ecology is plagued by problems of an abstract nature. Cell sizes are so small and population sizes so large that both are virtually incomprehensible. Niches are so far from our everyday experience as to make their very definition elusive. Organisms that may be abundant and critical to our survival are little understood, seldom described and/or cultured, and sometimes yet to be even seen. One way to confront these problems is to use data of an even more abstract nature: molecular sequence data. Massive environmental nucleic acid sequencing, such as metagenomics or metatranscriptomics, promises functional analysis of microbial communities as a whole, without prior knowledge of which organisms are in the environment or exactly how they are interacting. But sequence-based ecological studies nearly always use a comparative approach, and that requires relevant reference sequences, which are an extremely limited resource when it comes to microbial eukaryotes. In practice, this means sequence databases need to be populated with enormous quantities of data for which we have some certainties about the source. Most important is the taxonomic identity of the organism from which a sequence is derived and as much functional identification of the encoded proteins as possible. In an ideal world, such information would be available as a large set of complete, well curated, and annotated genomes for all the major organisms from the environment in question. Reality substantially diverges from this ideal, but at least for bacterial molecular ecology, there is a database consisting of thousands of complete genomes from a wide range of taxa, supplemented by a phylogeny-driven approach to diversifying genomics [2]. For eukaryotes, the number of available genomes is far, far fewer, and we have relied much more heavily on random growth of sequence databases, raising the question as to whether this is fit for purpose

Quantitative Organization of GABAergic Synapses in the Molecular Layer of the Mouse Cerebellar Cortex

In the cerebellar cortex, interneurons of the molecular layer (stellate and basket cells) provide GABAergic input to Purkinje cells, as well as to each other and possibly to other interneurons. GABAergic inhibition in the molecular layer has mainly been investigated at the interneuron to Purkinje cell synapse. In this study, we used complementary subtractive strategies to quantitatively assess the ratio of GABAergic synapses on Purkinje cell dendrites versus those on interneurons. We generated a mouse model in which the GABAA receptor α1 subunit (GABAARα1) was selectively removed from Purkinje cells using the Cre/loxP system. Deletion of the α1 subunit resulted in a complete loss of GABAAR aggregates from Purkinje cells, allowing us to determine the density of GABAAR clusters in interneurons. In a complementary approach, we determined the density of GABA synapses impinging on Purkinje cells using α-dystroglycan as a specific marker of inhibitory postsynaptic sites. Combining these inverse approaches, we found that synapses received by interneurons represent approximately 40% of all GABAergic synapses in the molecular layer. Notably, this proportion was stable during postnatal development, indicating synchronized synaptogenesis. Based on the pure quantity of GABAergic synapses onto interneurons, we propose that mutual inhibition must play an important, yet largely neglected, computational role in the cerebellar cortex