Anti-oesophageal cancer activity in extracts of deep-water Marion Island sponges

Oesophageal cancer is one of the most common causes of cancer-related deaths in South African black males. The limited efficacy of chemotherapeutic agents to treat this disease has prompted a search for potential new chemical entities with anticancer properties. We report here on the evidence for anti-oesophageal cancer activity in the methanolic extracts of five species of sponges dredged from a depth of approximately 100 m in the vicinity of Marion Island in the Southern Ocean during the autumn of 2004

Captivating a captive audience : a quality improvement project increasing participation in intradialytic exercise across five renal dialysis units

Acknowledgements The authors would like to thank Anne Bisset-Smith, Clinical Specialist Physiotherapist, for her support in planning and undertaking the project; Siobhan Crichton, King’s College London, for her assistance with the statistical analyses and Dr Jacky Jones, Head of Physiotherapy Guy’s & St. Thomas’ NHS Foundation Trust, for reviewing the manuscript. Due acknowledgement is given to Ros Tibbles, Service Improvement Nurse, and Debra Mundle, Clinical Nurse Manager Satellite Haemodialysis, for their assistance in planning the project. In addition, we thank the staff and patients at all the dialysis units for their participation. This study received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.Peer reviewedPublisher PD

Beliefs about back pain and pain management behaviours, and their associations in the general population : a systematic review

This work was supported by the Arthritis Research UK/Medical Research Council Centre for Musculoskeletal Health and Work (grant number: 20665).Peer reviewedPublisher PD

The design and application of a 50 K SNP chip for a threatened Aotearoa New Zealand passerine, the hihi

Next-generation sequencing has transformed the fields of ecological and evolutionary genetics by allowing for cost-effective identification of genome-wide variation. Single nucleotide polymorphism (SNP) arrays, or “SNP chips”, enable very large numbers of individuals to be consistently genotyped at a selected set of these identified markers, and also offer the advantage of being able to analyse samples of variable DNA quality. We used reduced representation restriction-aided digest sequencing (RAD-seq) of 31 birds of the threatened hihi (Notiomystis cincta; stitchbird) and low-coverage whole genome sequencing (WGS) of 10 of these birds to develop an Affymetrix 50 K SNP chip. We overcame the limitations of having no hihi reference genome and a low quantity of sequence data by separate and pooled de novo assembly of each of the 10 WGS birds. Reads from all individuals were mapped back to these de novo assemblies to identify SNPs. A subset of RAD-seq and WGS SNPs were selected for inclusion on the chip, prioritising SNPs with the highest quality scores whose flanking sequence uniquely aligned to the zebra finch (Taeniopygia guttata) genome. Of the 58,466 SNPs manufactured on the chip, 72% passed filtering metrics and were polymorphic. By genotyping 1,536 hihi on the array, we found that SNPs detected in multiple assemblies were more likely to successfully genotype, representing a cost-effective approach to identify SNPs for genotyping. Here, we demonstrate the utility of the SNP chip by describing the high rates of linkage disequilibrium in the hihi genome, reflecting the history of population bottlenecks in the species

FReD: the Floral Reflectance Database - a web portal for analyses of flower colour

Background: Flower colour is of great importance in various fields relating to floral biology and pollinator behaviour. However, subjective human judgements of flower colour may be inaccurate and are irrelevant to the ecology and vision of the flower's pollinators. For precise, detailed information about the colours of flowers, a full reflectance spectrum for the flower of interest should be used rather than relying on such human assessments. Methodology/Principal Findings: The Floral Reflectance Database (FReD) has been developed to make an extensive collection of such data available to researchers. It is freely available at http://www.reflectance.co.uk. The database allows users to download spectral reflectance data for flower species collected from all over the world. These could, for example, be used in modelling interactions between pollinator vision and plant signals, or analyses of flower colours in various habitats. The database contains functions for calculating flower colour loci according to widely-used models of bee colour space, reflectance graphs of the spectra and an option to search for flowers with similar colours in bee colour space. Conclusions/Significance: The Floral Reflectance Database is a valuable new tool for researchers interested in the colours of flowers and their association with pollinator colour vision, containing raw spectral reflectance data for a large number of flower species

Cannabinoid use among Americans with MS : Current trends and gaps in knowledge

Acknowledgements: The National Multiple Sclerosis Society (NMSS) provided participant recruitment support. The Michigan Institute for Clinical & Health Research (MICHR:NIH award number UL1TR002240) provided participant recruitment support through UMHealthResearch.org. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or NMSS. The investigators thank Shubha Kulkarni for her assistance with data collection.Peer reviewedPublisher PD

Genetic Variation in the TP53 Pathway and Bladder Cancer Risk. A Comprehensive Analysis

Introduction: Germline variants in TP63 have been consistently associated with several tumors, including bladder cancer, indicating the importance of TP53 pathway in cancer genetic susceptibility. However, variants in other related genes, including TP53 rs1042522 (Arg72Pro), still present controversial results. We carried out an in depth assessment of associations between common germline variants in the TP53 pathway and bladder cancer risk. Material and Methods: We investigated 184 tagSNPs from 18 genes in 1,058 cases and 1,138 controls from the Spanish Bladder Cancer/EPICURO Study. Cases were newly-diagnosed bladder cancer patients during 1998–2001. Hospital controls were age-gender, and area matched to cases. SNPs were genotyped in blood DNA using Illumina Golden Gate and TaqMan assays. Cases were subphenotyped according to stage/grade and tumor p53 expression. We applied classical tests to assess individual SNP associations and the Least Absolute Shrinkage and Selection Operator (LASSO)-penalized logistic regression analysis to assess multiple SNPs simultaneously. Results: Based on classical analyses, SNPs in BAK1 (1), IGF1R (5), P53AIP1 (1), PMAIP1 (2), SERINPB5 (3), TP63 (3), and TP73 (1) showed significant associations at p-value#0.05. However, no evidence of association, either with overall risk or with specific disease subtypes, was observed after correction for multiple testing (p-value$0.8). LASSO selected the SNP rs6567355 in SERPINB5 with 83% of reproducibility. This SNP provided an OR = 1.21, 95%CI 1.05–1.38, p-value = 0.006, and a corrected p-value = 0.5 when controlling for over-estimation. Discussion: We found no strong evidence that common variants in the TP53 pathway are associated with bladder cancer susceptibility. Our study suggests that it is unlikely that TP53 Arg72Pro is implicated in the UCB in white Europeans. SERPINB5 and TP63 variation deserve further exploration in extended studies.This work was supported by the Fondo de Investigacion Sanitaria, Spain (grant numbers 00/0745, PI051436, PI061614, G03/174); Red Tematica de Investigacion Cooperativa en Cancer (grant number RD06/0020-RTICC), Spain; Marato TV3 (grant number 050830); European Commission (grant numbers EU-FP7-HEALTH-F2-2008-201663-UROMOL; US National Institutes of Health (grant number USA-NIH-RO1-CA089715); and the Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute at the National Institutes of Health, USA; Consolider ONCOBIO (Ministerio de Economia y Competitividad, Madrid, Spain). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

X-exome sequencing of 405 unresolved families identifies seven novel intellectual disability genes

X-linked intellectual disability (XLID) is a clinically and genetically heterogeneous disorder. During the past two decades in excess of 100 X-chromosome ID genes have been identified. Yet, a large number of families mapping to the X-chromosome remained unresolved suggesting that more XLID genes or loci are yet to be identified. Here, we have investigated 405 unresolved families with XLID. We employed massively parallel sequencing of all X-chromosome exons in the index males. The majority of these males were previously tested negative for copy number variations and for mutations in a subset of known XLID genes by Sanger sequencing. In total, 745 X-chromosomal genes were screened. After stringent filtering, a total of 1297 non-recurrent exonic variants remained for prioritization. Co-segregation analysis of potential clinically relevant changes revealed that 80 families (20%) carried pathogenic variants in established XLID genes. In 19 families, we detected likely causative protein truncating and missense variants in 7 novel and validated XLID genes (CLCN4, CNKSR2, FRMPD4, KLHL15, LAS1L, RLIM and USP27X) and potentially deleterious variants in 2 novel candidate XLID genes (CDK16 and TAF1). We show that the CLCN4 and CNKSR2 variants impair protein functions as indicated by electrophysiological studies and altered differentiation of cultured primary neurons from Clcn4−/− mice or after mRNA knock-down. The newly identified and candidate XLID proteins belong to pathways and networks with established roles in cognitive function and intellectual disability in particular. We suggest that systematic sequencing of all X-chromosomal genes in a cohort of patients with genetic evidence for X-chromosome locus involvement may resolve up to 58% of Fragile X-negative cases

A high-density linkage map reveals broad- and fine-scale sex differences in recombination in the hihi (stitchbird; Notiomystis cincta)

Recombination, the process of DNA exchange between homologous chromosomes during meiosis, plays a major role in genomic diversity and evolutionary change. Variation in recombination rate is widespread despite recombination often being essential for progression of meiosis. One such variation is heterochiasmy, where recombination rates differ between sexes. Heterochiasmy has been observed across broad taxonomic groups, yet it remains an evolutionary enigma. We used Lep-MAP3, a pedigree-based software that is efficient in handling large datasets, to generate linkage maps for the hihi or stitchbird (Notiomystis cincta), utilising information from >36 K SNPs and 36 families. We constructed 29 linkage maps, including for the previously unscaffolded Z chromosome. The hihi is an endangered passerine endemic to Aotearoa New Zealand that is sexually dimorphic and exhibits high levels of sexual conflict, including sperm competition. Patterns in recombination in the hihi are consistent with those in other birds, including higher recombination rates in micro-chromosomes. Heterochiasmy in the hihi is male-biased, in line with predictions of the Haldane-Huxley rule, with the male linkage map being 15% longer. Micro-chromosomes exhibit heterochiasmy to a greater extent, contrary to that reported in other birds. At the intra-chromosomal level, heterochiasmy is higher nearer to chromosome ends and in gene-rich regions. Regions of extreme heterochiasmy are enriched for genes implicated in cell structure. This study adds an important contribution in assessing evolutionary theories of heterochiasmy and provides a framework for future studies investigating fine-scale heterochiasmy

Effect of pain on mood affective disorders in adults with cerebral palsy

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155961/1/dmcn14559_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155961/2/dmcn14559.pd