Genome sequencing of the extinct Eurasian wild aurochs, Bos primigenius, illuminates the phylogeography and evolution of cattle

Background Domestication of the now-extinct wild aurochs, Bos primigenius, gave rise to the two major domestic extant cattle taxa, B. taurus and B. indicus. While previous genetic studies have shed some light on the evolutionary relationships between European aurochs and modern cattle, important questions remain unanswered, including the phylogenetic status of aurochs, whether gene flow from aurochs into early domestic populations occurred, and which genomic regions were subject to selection processes during and after domestication. Here, we address these questions using whole-genome sequencing data generated from an approximately 6,750-year-old British aurochs bone and genome sequence data from 81 additional cattle plus genome-wide single nucleotide polymorphism data from a diverse panel of 1,225 modern animals. Results Phylogenomic analyses place the aurochs as a distinct outgroup to the domestic B. taurus lineage, supporting the predominant Near Eastern origin of European cattle. Conversely, traditional British and Irish breeds share more genetic variants with this aurochs specimen than other European populations, supporting localized gene flow from aurochs into the ancestors of modern British and Irish cattle, perhaps through purposeful restocking by early herders in Britain. Finally, the functions of genes showing evidence for positive selection in B. taurus are enriched for neurobiology, growth, metabolism and immunobiology, suggesting that these biological processes have been important in the domestication of cattle. Conclusions This work provides important new information regarding the origins and functional evolution of modern cattle, revealing that the interface between early European domestic populations and wild aurochs was significantly more complex than previously thought

High-Resolution Analysis of Parent-of-Origin Allelic Expression in the Arabidopsis Endosperm

Genomic imprinting is an epigenetic phenomenon leading to parent-of-origin specific differential expression of maternally and paternally inherited alleles. In plants, genomic imprinting has mainly been observed in the endosperm, an ephemeral triploid tissue derived after fertilization of the diploid central cell with a haploid sperm cell. In an effort to identify novel imprinted genes in Arabidopsis thaliana, we generated deep sequencing RNA profiles of F1 hybrid seeds derived after reciprocal crosses of Arabidopsis Col-0 and Bur-0 accessions. Using polymorphic sites to quantify allele-specific expression levels, we could identify more than 60 genes with potential parent-of-origin specific expression. By analyzing the distribution of DNA methylation and epigenetic marks established by Polycomb group (PcG) proteins using publicly available datasets, we suggest that for maternally expressed genes (MEGs) repression of the paternally inherited alleles largely depends on DNA methylation or PcG-mediated repression, whereas repression of the maternal alleles of paternally expressed genes (PEGs) predominantly depends on PcG proteins. While maternal alleles of MEGs are also targeted by PcG proteins, such targeting does not cause complete repression. Candidate MEGs and PEGs are enriched for cis-proximal transposons, suggesting that transposons might be a driving force for the evolution of imprinted genes in Arabidopsis. In addition, we find that MEGs and PEGs are significantly faster evolving when compared to other genes in the genome. In contrast to the predominant location of mammalian imprinted genes in clusters, cluster formation was only detected for few MEGs and PEGs, suggesting that clustering is not a major requirement for imprinted gene regulation in Arabidopsis

Effect of within-session breaks in play on responsible gambling behaviour during sustained monetary losses

Rapid, continuous gambling formats are associated with higher risks for gambling-related harm in terms of excessive monetary and time expenditure. The current study investigated the effect on gambling response latency and persistence, of a new form of within-game intervention that required players to actively engage in response inhibition via monitoring for stop signals. Seventy-four experienced electronic gaming machine gamblers, with a mean age of 35.28 years, were recruited to participate in a rapid, continuous gambling task where real money could be won and lost. Participants were randomly allocated to either the control condition where no intervention was presented, or either a condition with a passive three minute break in play or a condition with a three minute intervention that required participants to engage in response inhibition. Although there was no main effect for experimental condition on gambling persistence, both interventions were effective in elevating response latency during a period of sustained losses. It was concluded that within-game interventions that create an enforced break in play are effective in increasing response latency between bets during periods of sustained losses. Furthermore, within-game interventions that require active involvement appear to be more effective in increasing response latency than standard, passive breaks in play

Do community medicine residency trainees learn through journal club? An experience from a developing country

BACKGROUND: Journal clubs are an internationally recognized teaching tool in many postgraduate medical education fields. In developing countries lack of funds for current print materials may have limited journal club use. But with advancing information technology trainees in developing countries increasingly have more access to high quality journals online. However, we are aware of no studies describing journal club existence and effectiveness in postgraduate medical training in Pakistan. Also we have found no published effectiveness studies of this teaching modality in Community Medicine (Public Health) in any country. This study evaluated the effectiveness of Community Medicine (Public Health) Resident Journal Club (CMR-JC) in Aga Khan University, Pakistan using international criteria for successful journal clubs (2 years continuous existence and more than 50% attendance) and examining resident and alumni satisfaction. METHODS: Journal club effectiveness criteria were searched using electronic search databases. Departmental records were reviewed from September1999–September 2005. Ninety percent of residents and alumni of Community Medicine Residency Programme participated voluntarily in a confidential survey. RESULTS: The CMR-JC was regularly conducted. More than 95% of residents attended. (Total residents in the CMR-Programme: 32). Twenty-seven out of 29 current residents/alumni responded to the anonymous questionnaire. Acquisition of critical appraisal skills (23 respondents) and keeping up with current literature (18 respondents) were the two most important objectives achieved. Respondents recommended improved faculty participation and incorporating a structured checklist for article review. CONCLUSION: CMR-JC fulfils criteria for effective journal clubs. Residents and alumni agree CMR-JC meets its objectives. Incorporating suggested recommendations will further improve standards. The journal club learning modality should be included in residency training programs in developing countries. Effective use of online resources to support journal clubs is demonstrated as a successful alternative to excessive expenditure for obtaining print journals. Those trying to start or improve journal clubs can benefit from our experience

Evolutionary origins of Brassicaceae specific genes in Arabidopsis thaliana

<p>Abstract</p> <p>Background</p> <p>All sequenced genomes contain a proportion of lineage-specific genes, which exhibit no sequence similarity to any genes outside the lineage. Despite their prevalence, the origins and functions of most lineage-specific genes remain largely unknown. As more genomes are sequenced opportunities for understanding evolutionary origins and functions of lineage-specific genes are increasing.</p> <p>Results</p> <p>This study provides a comprehensive analysis of the origins of lineage-specific genes (LSGs) in <it>Arabidopsis thaliana </it>that are restricted to the Brassicaceae family. In this study, lineage-specific genes within the nuclear (1761 genes) and mitochondrial (28 genes) genomes are identified. The evolutionary origins of two thirds of the lineage-specific genes within the <it>Arabidopsis thaliana </it>genome are also identified. Almost a quarter of lineage-specific genes originate from non-lineage-specific paralogs, while the origins of ~10% of lineage-specific genes are partly derived from DNA exapted from transposable elements (twice the proportion observed for non-lineage-specific genes). Lineage-specific genes are also enriched in genes that have overlapping CDS, which is consistent with such novel genes arising from overprinting. Over half of the subset of the 958 lineage-specific genes found only in <it>Arabidopsis thaliana </it>have alignments to intergenic regions in <it>Arabidopsis lyrata</it>, consistent with either <it>de novo </it>origination or differential gene loss and retention, with both evolutionary scenarios explaining the lineage-specific status of these genes. A smaller number of lineage-specific genes with an incomplete open reading frame across different <it>Arabidopsis thaliana </it>accessions are further identified as accession-specific genes, most likely of recent origin in <it>Arabidopsis thaliana</it>. Putative <it>de novo </it>origination for two of the <it>Arabidopsis thaliana</it>-only genes is identified via additional sequencing across accessions of <it>Arabidopsis thaliana </it>and closely related sister species lineages. We demonstrate that lineage-specific genes have high tissue specificity and low expression levels across multiple tissues and developmental stages. Finally, stress responsiveness is identified as a distinct feature of Brassicaceae-specific genes; where these LSGs are enriched for genes responsive to a wide range of abiotic stresses.</p> <p>Conclusion</p> <p>Improving our understanding of the origins of lineage-specific genes is key to gaining insights regarding how novel genes can arise and acquire functionality in different lineages. This study comprehensively identifies all of the Brassicaceae-specific genes in <it>Arabidopsis thaliana </it>and identifies how the majority of such lineage-specific genes have arisen. The analysis allows the relative importance (and prevalence) of different evolutionary routes to the genesis of novel ORFs within lineages to be assessed. Insights regarding the functional roles of lineage-specific genes are further advanced through identification of enrichment for stress responsiveness in lineage-specific genes, highlighting their likely importance for environmental adaptation strategies.</p

Outlook for inverse design in nanophotonics

Recent advancements in computational inverse design have begun to reshape the landscape of structures and techniques available to nanophotonics. Here, we outline a cross section of key developments at the intersection of these two fields: moving from a recap of foundational results to motivation of emerging applications in nonlinear, topological, near-field and on-chip optics.Comment: 13 pages, 6 figure

Cytoskeletal control of B cell responses to antigens.

The actin cytoskeleton is essential for cell mechanics and has increasingly been implicated in the regulation of cell signalling. In B cells, the actin cytoskeleton is extensively coupled to B cell receptor (BCR) signalling pathways, and defects of the actin cytoskeleton can either promote or suppress B cell activation. Recent insights from studies using single-cell imaging and biophysical techniques suggest that actin orchestrates BCR signalling at the plasma membrane through effects on protein diffusion and that it regulates antigen discrimination through the biomechanics of immune synapses. These mechanical functions also have a role in the adaptation of B cell subsets to specialized tasks during antibody responses

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe