Common and low Frequency variants in MERTK are independently associated with multiple sclerosis susceptibility with discordant association dependent upon HLA-DRB1*15:01 status

Multiple Sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system. The risk of developing MS is strongly influenced by genetic predisposition, and over 100 loci have been established as associated with susceptibility. However, the biologically relevant variants underlying disease risk have not been defined for the vast majority of these loci, limiting the power of these genetic studies to define new avenues of research for the development of MS therapeutics. It is therefore crucial that candidate MS susceptibility loci are carefully investigated to identify the biological mechanism linking genetic polymorphism at a given gene to the increased chance of developing MS. MERTK has been established as an MS susceptibility gene and is part of a family of receptor tyrosine kinases known to be involved in the pathogenesis of demyelinating disease. In this study we have refined the association of MERTK with MS risk to independent signals from both common and low frequency variants. One of the associated variants was also found to be linked with increased expression of MERTK in monocytes and higher expression of MERTK was associated with either increased or decreased risk of developing MS, dependent upon HLA-DRB1*15:01 status. This discordant association potentially extended beyond MS susceptibility to alterations in disease course in established MS. This study provides clear evidence that distinct polymorphisms within MERTK are associated with MS susceptibility, one of which has the potential to alter MERTK transcription, which in turn can alter both susceptibility and disease course in MS patients

Ten Simple Rules for Organizing an Unconference

This is an open access article distributed under the terms of the Creative Commons Attribution License.Peer Reviewe

A Potential Neural Substrate for Processing Functional Classes of Complex Acoustic Signals

Categorization is essential to all cognitive processes, but identifying the neural substrates underlying categorization processes is a real challenge. Among animals that have been shown to be able of categorization, songbirds are particularly interesting because they provide researchers with clear examples of categories of acoustic signals allowing different levels of recognition, and they possess a system of specialized brain structures found only in birds that learn to sing: the song system. Moreover, an avian brain nucleus that is analogous to the mammalian secondary auditory cortex (the caudo-medial nidopallium, or NCM) has recently emerged as a plausible site for sensory representation of birdsong, and appears as a well positioned brain region for categorization of songs. Hence, we tested responses in this non-primary, associative area to clear and distinct classes of songs with different functions and social values, and for a possible correspondence between these responses and the functional aspects of songs, in a highly social songbird species: the European starling. Our results clearly show differential neuronal responses to the ethologically defined classes of songs, both in the number of neurons responding, and in the response magnitude of these neurons. Most importantly, these differential responses corresponded to the functional classes of songs, with increasing activation from non-specific to species-specific and from species-specific to individual-specific sounds. These data therefore suggest a potential neural substrate for sorting natural communication signals into categories, and for individual vocal recognition of same-species members. Given the many parallels that exist between birdsong and speech, these results may contribute to a better understanding of the neural bases of speech

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Transferring biodiversity-ecosystem function research to the management of ‘real-world’ ecosystems

Biodiversity-ecosystem functioning (BEF) research grew rapidly following concerns that biodiversity loss would negatively affect ecosystem functions and the ecosystem services they underpin. However, despite evidence that biodiversity strongly affects ecosystem functioning, the influence of BEF research upon policy and the management of ‘real-world’ ecosystems, i.e., semi-natural habitats and agroecosystems, has been limited. Here, we address this issue by classifying BEF research into three clusters based on the degree of human control over species composition and the spatial scale, in terms of grain, of the study, and discussing how the research of each cluster is best suited to inform particular fields of ecosystem management. Research in the first cluster, small-grain highly controlled studies, is best able to provide general insights into mechanisms and to inform the management of species-poor and highly managed systems such as croplands, plantations, and the restoration of heavily degraded ecosystems. Research from the second cluster, small-grain observational studies, and species removal and addition studies, may allow for direct predictions of the impacts of species loss in specific semi-natural ecosystems. Research in the third cluster, large-grain uncontrolled studies, may best inform landscape-scale management and national-scale policy. We discuss barriers to transfer within each cluster and suggest how new research and knowledge exchange mechanisms may overcome these challenges. To meet the potential for BEF research to address global challenges, we recommend transdisciplinary research that goes beyond these current clusters and considers the social-ecological context of the ecosystems in which BEF knowledge is generated. This requires recognizing the social and economic value of biodiversity for ecosystem services at scales, and in units, that matter to land managers and policy makers.</p

'Vernacular Voices: Black British Poetry'

ABSTRACT Black British poetry is the province of experimenting with voice and recording rhythms beyond the iambic pentameter. Not only in performance poetry and through the spoken word, but also on the page, black British poetry constitutes and preserves a sound archive of distinct linguistic varieties. In Slave Song (1984) and Coolie Odyssey (1988), David Dabydeen employs a form of Guyanese Creole in order to linguistically render and thus commemorate the experience of slaves and indentured labourers, respectively, with the earlier collection providing annotated translations into Standard English. James Berry, Louise Bennett, and Valerie Bloom adapt Jamaican Patois to celebrate Jamaican folk culture and at times to represent and record experiences and linguistic interactions in the postcolonial metropolis. Grace Nichols and John Agard use modified forms of Guyanese Creole, with Nichols frequently constructing gendered voices whilst Agard often celebrates linguistic playfulness. The borders between linguistic varieties are by no means absolute or static, as the emergence and marked growth of ‘London Jamaican’ (Mark Sebba) indicates. Asian British writer Daljit Nagra takes liberties with English for different reasons. Rather than having recourse to established Creole languages, and blending them with Standard English, his heteroglot poems frequently emulate ‘Punglish’, the English of migrants whose first language is Punjabi. Whilst it is the language prestige of London Jamaican that has been significantly enhanced since the 1990s, a fact not only confirmed by linguistic research but also by its transethnic uses both in the streets and on the page, Nagra’s substantial success and the mainstream attention he receives also indicate the clout of vernacular voices in poetry. They have the potential to connect with oral traditions and cultural memories, to record linguistic varieties, and to endow ‘street cred’ to authors and texts. In this chapter, these double-voiced poetic languages are also read as signs of resistance against residual monologic ideologies of Englishness. © Book proposal (02/2016): The Cambridge History of Black and Asian British Writing p. 27 of 4

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Quantum Leap from Gold and Silver to Aluminum Nanoplasmonics for Enhanced Biomedical Applications

Nanotechnology has been used in many biosensing and medical applications, in the form of noble metal (gold and silver) nanoparticles and nanostructured substrates. However, the translational clinical and industrial applications still need improvements of the efficiency, selectivity, cost, toxicity, reproducibility, and morphological control at the nanoscale level. In this review, we highlight the recent progress that has been made in the replacement of expensive gold and silver metals with the less expensive aluminum. In addition to low cost, other advantages of the aluminum plasmonic nanostructures include a broad spectral range from deep UV to near IR, providing additional signal enhancement and treatment mechanisms. New synergistic treatments of bacterial infections, cancer, and coronaviruses are envisioned. Coupling with gain media and quantum optical effects improve the performance of the aluminum nanostructures beyond gold and silver