80 research outputs found

    Rapid Evolutionary Rates and Unique Genomic Signatures Discovered in the First Reference Genome for the Southern Ocean Salp, Salpa thompsoni (Urochordata, Thaliacea)

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    A preliminary genome sequence has been assembled for the Southern Ocean salp, Salpa thompsoni (Urochordata, Thaliacea). Despite the ecological importance of this species in Antarctic pelagic food webs and its potential role as an indicator of changing Southern Ocean ecosystems in response to climate change, no genomic resources are available for S. thompsoni or any closely related urochordate species. Using a multiple-platform, multiple-individual approach, we have produced a 318,767,936-bp genome sequence, covering \u3e50% of the estimated 602 Mb (±173 Mb) genome size for S. thompsoni. Using a nonredundant set of predicted proteins, \u3e50% (16,823) of sequences showed significant homology to known proteins and ∼38% (12,151) of the total protein predictions were associated with Gene Ontology functional information. We have generated 109,958 SNP variant and 9,782 indel predictions for this species, serving as a resource for future phylogenomic and population genetic studies. Comparing the salp genome to available assemblies for four other urochordates, Botryllus schlosseri, Ciona intestinalis, Ciona savignyi and Oikopleura dioica, we found that S. thompsoni shares the previously estimated rapid rates of evolution for these species. High mutation rates are thus independent of genome size, suggesting that rates of evolution \u3e1.5 times that observed for vertebrates are a broad taxonomic characteristic of urochordates. Tests for positive selection implemented in PAML revealed a small number of genes with sites undergoing rapid evolution, including genes involved in ribosome biogenesis and metabolic and immune process that may be reflective of both adaptation to polar, planktonic environments as well as the complex life history of the salps. Finally, we performed an initial survey of small RNAs, revealing the presence of known, conserved miRNAs, as well as novel miRNA genes; unique piRNAs; and mature miRNA signatures for varying developmental stages. Collectively, these resources provide a genomic foundation supporting S. thompsoni as a model species for further examination of the exceptional rates and patterns of genomic evolution shown by urochordates. Additionally, genomic data will allow for the development of molecular indicators of key life history events and processes and afford new understandings and predictions of impacts of climate change on this key species of Antarctic pelagic ecosystems

    Determination of Dosage Compensation of the Mammalian X Chromosome by RNA-seq is Dependent on Analytical Approach

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    Background An enduring question surrounding sex chromosome evolution is whether effective hemizygosity in the heterogametic sex leads inevitably to dosage compensation of sex-linked genes, and whether this compensation has been observed in a variety of organisms. Incongruence in the conclusions reached in some recent reports has been attributed to different high-throughput approaches to transcriptome analysis. However, recent reports each utilizing RNA-seq to gauge X-linked gene expression relative to autosomal gene expression also arrived at diametrically opposed conclusions regarding X chromosome dosage compensation in mammals. Results Here we analyze RNA-seq data from X-monosomic female human and mouse tissues, which are uncomplicated by genes that escape X-inactivation, as well as published RNA-seq data to describe relative X expression (RXE). We find that the determination of RXE is highly dependent upon a variety of computational, statistical and biological assumptions underlying RNA-seq analysis. Parameters implemented in short-read mapping programs, choice of reference genome annotation, expression data distribution, tissue source for RNA and RNA-seq library construction method have profound effects on comparing expression levels across chromosomes. Conclusions Our analysis shows that the high number of paralogous gene families on the mammalian X chromosome relative to autosomes contributes to the ambiguity in RXE calculations, RNA-seq analysis that takes into account that single- and multi-copy genes are compensated differently supports the conclusion that, in many somatic tissues, the mammalian X is up-regulated compared to the autosomes

    Establishment of Centromeric Chromatin by the CENP-A Assembly Factor CAL1 Requires FACT-Mediated Transcription

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    SummaryCentromeres are essential chromosomal structures that mediate accurate chromosome segregation during cell division. Centromeres are specified epigenetically by the heritable incorporation of the centromeric histone H3 variant CENP-A. While many of the primary factors that mediate centromeric deposition of CENP-A are known, the chromatin and DNA requirements of this process have remained elusive. Here, we uncover a role for transcription in Drosophila CENP-A deposition. Using an inducible ectopic centromere system that uncouples CENP-A deposition from endogenous centromere function and cell-cycle progression, we demonstrate that CENP-A assembly by its loading factor, CAL1, requires RNAPII-mediated transcription of the underlying DNA. This transcription depends on the CAL1 binding partner FACT, but not on CENP-A incorporation. Our work establishes RNAPII passage as a key step in chaperone-mediated CENP-A chromatin establishment and propagation

    Whither Critical Masculinity Studies? Notes on Inclusive Masculinity Theory, Postfeminism, and Sexual Politics

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    Inclusive masculinity theory has recently been proposed as a new approach to theo- rizing contemporary masculinities. Focusing particularly on the work of the theory’s key exponent, Eric Anderson, this article offers a critical reading of inclusive masculinity theory in relation to the context of contemporary postfeminism. Building on feminist scholarship that analyzes the emergence of a distinctive postfeminist sensibility within the academy, I consider how inclusive masculinity theory both reflects and reproduces certain logics of postfeminism. My central concern is the manner in which this scho- larship deemphasizes key issues of sexual politics and promotes a discourse of optimism about men, masculinities, and social change. Against this view, I argue that critical masculinity studies must foreground the analysis of gendered power relations and posit that the interrogation of contemporary postfeminism is critical to this endeavor

    Mapping the disease-specific LupusQoL to the SF-6D

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    Purpose To derive a mapping algorithm to predict SF-6D utility scores from the non-preference-based LupusQoL and test the performance of the developed algorithm on a separate independent validation data set. Method LupusQoL and SF-6D data were collected from 320 patients with systemic lupus erythematosus (SLE) attending routine rheumatology outpatient appointments at seven centres in the UK. Ordinary least squares (OLS) regression was used to estimate models of increasing complexity in order to predict individuals’ SF-6D utility scores from their responses to the LupusQoL questionnaire. Model performance was judged on predictive ability through the size and pattern of prediction errors generated. The performance of the selected model was externally validated on an independent data set containing 113 female SLE patients who had again completed both the LupusQoL and SF-36 questionnaires. Results Four of the eight LupusQoL domains (physical health, pain, emotional health, and fatigue) were selected as dependent variables in the final model. Overall model fit was good, with R2 0.7219, MAE 0.0557, and RMSE 0.0706 when applied to the estimation data set, and R2 0.7431, MAE 0.0528, and RMSE 0.0663 when applied to the validation sample. Conclusion This study provides a method by which health state utility values can be estimated from patient responses to the non-preference-based LupusQoL, generalisable beyond the data set upon which it was estimated. Despite concerns over the use of OLS to develop mapping algorithms, we find this method to be suitable in this case due to the normality of the SF-6D data

    The many possible climates from the Paris Agreement’s aim of 1.5 °C warming

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    The United Nations’ Paris Agreement includes the aim of pursuing efforts to limit global warming to only 1.5 °C above pre-industrial levels. However, it is not clear what the resulting climate would look like across the globe and over time. Here we show that trajectories towards a ‘1.5 °C warmer world’ may result in vastly different outcomes at regional scales, owing to variations in the pace and location of climate change and their interactions with society’s mitigation, adaptation and vulnerabilities to climate change. Pursuing policies that are considered to be consistent with the 1.5 °C aim will not completely remove the risk of global temperatures being much higher or of some regional extremes reaching dangerous levels for ecosystems and societies over the coming decades

    Accuracy of the electronic patient record in a first opinion veterinary practice

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    The use of electronic patient records (EPRs) in veterinary research is becoming more common place. To date no-one has investigated how accurately and completely they represent the clinical interactions that happen between veterinary professionals, and their clients and patients. The aim of this study was to compare data extracted from consultations within EPRs with data gathered by direct observation of the same consultation. A secondary aim was to establish the inter-rater reliability of two researchers who examined the data extracted from the EPRs. A convenience sample of 36 small animal consultations undertaken by 2 veterinary surgeons (83% by one veterinary surgeon) at a mixed veterinary practice in the United Kingdom was studied. All 36 consultations were observed by a single researcher using a standardised data collection tool. The information recorded in the EPRs was extracted from the Practice Management Software (PMS) systems using a validated XML schema. The XML extracted data was then converted into the same format as the observed data by two independent researchers who examined the extracted information and recorded their findings using the same tool as for the observation. The issues discussed and any action taken relating to those problems recorded in the observed and extracted datasets were then compared. In addition the inter-rater reliability of the two researchers who examined the extracted data was assessed. Only 64.4% of the observed problems discussed during the consultations were recorded in the EPR. The type of problem, who raised the problem and at what point in the consultation the problem was raised significantly affected whether the problem was recorded or not in the EPR. Only 58.3% of observed actions taken during the consultations were recorded in the EPR and the type of action significantly affected whether it would be recorded or not. There was moderate agreement between the two researchers who examined the extracted data. This is the first study that examines how much of the activity that occurs in small animal consultations is recorded in the EPR. Understanding the completeness, reliability and validity of EPRs is vital if they are to continue to be used for clinical research and the results to direct clinical care

    Placenta Imaging Workshop 2018 report:Multiscale and multimodal approaches

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    The Centre for Medical Image Computing (CMIC) at University College London (UCL) hosted a two-day workshop on placenta imaging on April 12th and 13th 2018. The workshop consisted of 10 invited talks, 3 contributed talks, a poster session, a public interaction session and a panel discussion about the future direction of placental imaging. With approximately 50 placental researchers in attendance, the workshop was a platform for engineers, clinicians and medical experts in the field to network and exchange ideas. Attendees had the chance to explore over 20 posters with subjects ranging from the movement of blood within the placenta to the efficient segmentation of fetal MRI using deep learning tools. UCL public engagement specialists also presented a poster, encouraging attendees to learn more about how to engage patients and the public with their research, creating spaces for mutual learning and dialogue
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