24 research outputs found
Relationship between domoic acid levels in the blue mussel (Mytilus-edulis) and toxicity in mice
No full textPT: J; CR: 1988, CAN CHEM NEWS, V10, P15 BATES SS, 1988, 57 NAT RES COUNC CAN BIRD CJ, 1988, 56 NAT RES COUNC CAN BRADFORD MM, 1976, ANAL BIOCHEM, V72, P248 COYLE JT, 1984, EXCITOTOXINS, V39, P112 DEBONNEL G, 1989, CAN J PHYSIOL PHARM, V67, P29 FRANSON MA, 1980, STANDARD METHODS EXA IMPELLIZZERI G, 1975, PHYTOCHEMISTRY, V14, P1549 LAWRENCE JF, 1989, J CHROMATOGR, V462, P349 LITCHFIELD JT, 1949, J PHARMACOL EXP THER, V96, P99 MAEDA M, 1987, PESTIC BIOCHEM PHYS, V28, P85 QUILLIAM MA, 1988, 55 NAT RES COUNC CAN RAO DVS, 1988, CAN J FISH AQUAT SCI, V45, P2076 TAKEMOTO T, 1958, CHEM PHARM BULL, V6, P578 TAKEMOTO T, 1978, KAINIC ACID TOOL NEU, P1 WILLIAMS S, 1984, OFFICIAL METHODS ANA, P344 WRIGHT JLC, 1989, CAN J CHEM, V67, P481; NR: 17; TC: 21; J9: TOXICON; PG: 8; GA: DF893Source type: Electronic(1
A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci.
No full textWe conducted a multi-stage, genome-wide association study of bladder cancer with a primary scan of 591,637 SNPs in 3,532 affected individuals (cases) and 5,120 controls of European descent from five studies followed by a replication strategy, which included 8,382 cases and 48,275 controls from 16 studies. In a combined analysis, we identified three new regions associated with bladder cancer on chromosomes 22q13.1, 19q12 and 2q37.1: rs1014971, (P = 8 × 10⁻¹²) maps to a non-genic region of chromosome 22q13.1, rs8102137 (P = 2 × 10⁻¹¹) on 19q12 maps to CCNE1 and rs11892031 (P = 1 × 10⁻⁷) maps to the UGT1A cluster on 2q37.1. We confirmed four previously identified genome-wide associations on chromosomes 3q28, 4p16.3, 8q24.21 and 8q24.3, validated previous candidate associations for the GSTM1 deletion (P = 4 × 10⁻¹¹) and a tag SNP for NAT2 acetylation status (P = 4 × 10⁻¹¹), and found interactions with smoking in both regions. Our findings on common variants associated with bladder cancer risk should provide new insights into the mechanisms of carcinogenesis
African origin of the malaria parasite Plasmodium vivax.
No full textPlasmodium vivax is the leading cause of human malaria in Asia and Latin America but is absent from most of central Africa due to the near fixation of a mutation that inhibits the expression of its receptor, the Duffy antigen, on human erythrocytes. The emergence of this protective allele is not understood because P. vivax is believed to have originated in Asia. Here we show, using a non-invasive approach, that wild chimpanzees and gorillas throughout central Africa are endemically infected with parasites that are closely related to human P. vivax. Sequence analyses reveal that ape parasites lack host specificity and are much more diverse than human parasites, which form a monophyletic lineage within the ape parasite radiation. These findings indicate that human P. vivax is of African origin and likely selected for the Duffy-negative mutation. All extant human P. vivax parasites are derived from a single ancestor that escaped out of Africa
Next-Generation SINE Compound KPT−8602 Ameliorates Dystrophic Pathology in Zebrafish and Mouse Models of DMD
No full textDuchenne muscular dystrophy (DMD) is a progressive, X-linked childhood neuromuscular disorder that results from loss-of-function mutations in the DYSTROPHIN gene. DMD patients exhibit muscle necrosis, cardiomyopathy, respiratory failure, and loss of ambulation. One of the major driving forces of DMD disease pathology is chronic inflammation. The current DMD standard of care is corticosteroids; however, there are serious side effects with long-term use, thus identifying novel anti-inflammatory and anti-fibrotic treatments for DMD is of high priority. We investigated the next-generation SINE compound, KPT−8602 (eltanexor) as an oral therapeutic to alleviate dystrophic symptoms. We performed pre-clinical evaluation of the effects of KPT−8602 in DMD zebrafish (sapje) and mouse (D2-mdx) models. KPT−8602 improved dystrophic skeletal muscle pathologies, muscle architecture and integrity, and overall outcomes in both animal models. KPT−8602 treatment ameliorated DMD pathology in D2-mdx mice, with increased locomotor behavior and improved muscle histology. KPT−8602 altered the immunological profile of the dystrophic mice, and reduced circulating osteopontin serum levels. These findings demonstrate KPT−8602 as an effective therapeutic in DMD through by promotion of an anti-inflammatory environment and overall improvement of DMD pathological outcomes
Emily Brontë : the mind of a visionary
No full textBibliography: leaves 216-226.This dissertation is an investigation of the visionary and philosophical aspects of Emily Brontë's works. The first five chapters deal with the visionary process such as visions, spirit guides, dreams, imagination, encounters with the darker side of the self and a union with the divine. There is considerable evidence of these mystical avenues in both her poetry and in Wuthering Heights which have been explored. It is shown how Emily Brontë's mysticism is a direct result of personal experiences which augment her reputation as one of the leading mystics in the world of literature. There are however tensions in her works, such as the cynicism of her own intellect in accepting the visionary experiences as authentic and periods of suffering when her faith is tested. These tensions have been considered within the context of her mystical encounters and philosophy. The remaining four chapters deal with the philosophy of Emily Brontë per se. Her beliefs in respect of heaven and hell, mercy and justice, power and survival, and pantheism are considered in depth. It is argued that she is an unorthodox thinker who does not believe in an eternal hell and that she has drawn inspiration for this idea from Frederick Maurice and Ralph Waldo Emerson. It is also shown how issues of power have been of interest to her from a young age and how this needs to be integrated within her philosophy. To the writer power needs to be tempered by compassion if it is to be of use to society or the individual. Her pantheistic spirit is also investigated and related to the mystical ideas
Divergent evolutionary processes associated with colonization of offshore islands
No full textWe dedicate this article to Michel Pascal, our outstanding co-author, who died on 5 January 2013, and to Anne Brundle, who gave us access to much archaeological material and who died in 2012. We acknowledge receipt of a Marie Curie Intra European Fellowship (to N.M.), support from the Swiss National Science Foundation (projects 31003A-127377, 3100A0-112072 and 3100-126074) to L.E. and G.H., funding from SYNTHESYS2 made available by the European Community Research Infrastructure under FP7 (‘Synthesis of Systematic Resources’, 226506-CP-CSA-Infra) to S.B., a Wellcome Trust University award to K.M.D. (GR071037) and overarching funding from the Arts and Humanities Research Council (project grant 119396). We thank V. Bretille, A. Frantz, M. Fuster, N. Gould, J. Herman, E. Jones, S. Martínek, R. Marwick, J. Michaux, S. Montuire, J. Pauperio, C. Scott, C. Tougard, B. Walther and N. Wheale for field specimens, T. White for assistance with IMa runs, and A. Ritchie, L. Shepherd and A. Sheridan for archaeological advice. We are grateful to the following for museum and archaeological samples: J. Barrett (MacDonald Institute, University of Cambridge), A. Brundle (Orkney Museum), C. David (Guernsey Museum), A. Ervynck (Flemish Heritage Institute), L. Gordon (Smithsonian Institute), J. Herman (National Museums of Scotland), D. Lee (Orkney College), R. Sabin (British Museum - Natural History, London) and G. Veron (Muséum national d'histoire naturelle, Paris).Peer reviewe
Biocultural perspectives on birth defects in medieval urban and rural English populations.
No full textThe biocultural and epidemiological approaches have been used as investigative methods by which to assess the prevalence of birth defects of the axial skeleton among five English Medieval population samples (Raunds Fumells, Northamptonshire; the hospital/almshouse of St James and St Mary Magdalene, Chichester, West Sussex; St Helen-on-the-Walls, York; Wharram Percy, East Yorkshire, and the Augustinian Friary cemetery, Hull, Humberside).The author hypothesises that Medieval urban populations produced offspring with higher frequencies of skeletal defects because they were subject to the adverse health-mediating effects of higher population density. These include poor quality, frequently overcrowded living conditions, poor sanitation, increased rates of disease threat and transmission, poorer quality food and drink due to pollution and adulteration, and greater levels of industrial-related air and water pollution. The author proposes that this response was a consequence of the impaired interaction between a population-wide compromised nutritional status and a co-existing weakened immune response. It is proposed that rural populations will express significantly lower frequencies of the same skeletal defects, as they are not subject to the same adverse environmental effects of population density and urban living conditions. The results support this hypothesis among the four populations derived from burial grounds associated with residential areas, whilst the Hull population expresses a rural pattern of defect prevalence, raising questions of possibly limited, exclusive access to burial at that site, available to non-urban dwellers. The author suggests that similar reproductive effects may be found today in populations undergoing demographic transition, for example, those experiencing the process of urbanisation in the developing world, or those migrating to the developed West. The author also shows how the results, when viewed alongside the medical literature, may indicate the presence of soft-tissue anomalies which are invisible to those working with dry bone. Keywords: urban, rural, medieval, birth defects, congenital, urbanisation, population density, biocultural, epidemiology, spine, cleft palate, skeleton, archaeology, palaeopathology
Reading Ruth : towards a postmodernist, literary and womanist analysis
No full textBibliography: leaves 132-140.This dissertation examines the book of Ruth from a postmodemist, literary and womanist perspective. The main methodology is postmodemist literary criticism, but it employs intertextual and autobiographical approaches as well. Chapter 1 is an exploration of the plot of Ruth and reveals that in order for the end goal of the plot to be achieved "emptiness has to return to fullness." It is shown that Ruth's action (her decision to return with Naomi) is the catalyst that begins the process that ultimately leads to the denouement of the plot. The fact that it is the two women, Ruth and Naomi, who drive the plot forward, indicates that the Book of Ruth is a woman's story. Chapter 2 demonstrates that the significance of narrative time for any literary analysis lies in the fact that the amount of time allowed for the retelling of the events rarely corresponds to the time it took for the events to happen. Since Ruth is a short story, the choice of what to tell, what to omit as well as how long to dwell on details are indeed significant. In other words it is shown that literary time is only spent on those aspects which are crucial for the advancement of the narrative. Since the reader's main goal is to see how the conflicts are resolved, the literary time spent on the resolution of the conflicts is an indication of where the weight of the story needs to lie. In this case, it is certainly with Ruth and Naomi judging from the amount of time spent on dialogues between the two women. They are therefore the ones that contribute to the resolution of the conflicts of the plot. Chapter 3 reveals that in the book of Ruth the narrative voice or the perspective of attitudes, conceptions and worldview are those of a woman. The fact that the book of Ruth is named after a woman; the fact that at the very outset all the males in the story die and it is the women that take over the narrative; the fact that in the end the women of Bethlehem declare that Ruth is better to Naomi than seven sons are just some of the reasons that substantiate the argument that the narrative voice in the book of Ruth was that of a woman. It is also shown that this narrative voice (whether overt or covert) subverts gender and ethnic expectations. Chapter 4 outlines the way in which biblical characters are portrayed. The subsections of chapter 4 deal with the characterisation of each major character: Naomi, Boaz, and Ruth. Chapter 4 is the longest chapter since it is difficult to evaluate characterisation without engaging the other facets of literary criticism as well, such as plot and dialogue
Efficacy and safety of the RTS,S/AS01 malaria vaccine during 18 months after vaccination : a phase 3 randomized, controlled trial in children and young infants at 11 African sites
No full textA malaria vaccine could be an important addition to current control strategies. We report the safety and vaccine efficacy (VE) of the RTS,S/AS01 vaccine during 18 mo following vaccination at 11 African sites with varying malaria transmission.; 6,537 infants aged 6-12 wk and 8,923 children aged 5-17 mo were randomized to receive three doses of RTS,S/AS01 or comparator vaccine. VE against clinical malaria in children during the 18 mo after vaccine dose 3 (per protocol) was 46% (95% CI 42% to 50%) (range 40% to 77%; VE, p>0.01 across all sites). VE during the 20 mo after vaccine dose 1 (intention to treat [ITT]) was 45% (95% CI 41% to 49%). VE against severe malaria, malaria hospitalization, and all-cause hospitalization was 34% (95% CI 15% to 48%), 41% (95% CI 30% to 50%), and 19% (95% CI 11% to 27%), respectively (ITT). VE against clinical malaria in infants was 27% (95% CI 20% to 32%, per protocol; 27% [95% CI 21% to 33%], ITT), with no significant protection against severe malaria, malaria hospitalization, or all-cause hospitalization. Post-vaccination anti-circumsporozoite antibody geometric mean titer varied from 348 to 787 EU/ml across sites in children and from 117 to 335 EU/ml in infants (per protocol). VE waned over time in both age categories (Schoenfeld residuals p>0.001). The number of clinical and severe malaria cases averted per 1,000 children vaccinated ranged across sites from 37 to 2,365 and from -1 to 49, respectively; corresponding ranges among infants were -10 to 1,402 and -13 to 37, respectively (ITT). Meningitis was reported as a serious adverse event in 16/5,949 and 1/2,974 children and in 9/4,358 and 3/2,179 infants in the RTS,S/AS01 and control groups, respectively.; RTS,S/AS01 prevented many cases of clinical and severe malaria over the 18 mo after vaccine dose 3, with the highest impact in areas with the greatest malaria incidence. VE was higher in children than in infants, but even at modest levels of VE, the number of malaria cases averted was substantial. RTS,S/AS01 could be an important addition to current malaria control in Africa
The Church of Christ in early Bernicia: forerunners and foundation
No full textA firmly multidlsciplinary approach starts from a theological definition of the Church as the Body of Christ, and Christians as empowered by the Holy Spirit, the possibility of miracle, and the reality of warfare with demons are taken seriously, and scholarly belief in them defended. They are made the subject of excursuses. Hagiographic writings are treated with cautious respect. Bernicia, land and people, and its relationship to its neighbours are considered. In a demographic excursus the view that Dark Age life-span was short is rebuffed. Part two discusses the life and mission of the Church in sub-Roman Britain. In our area evidence for this proves to be largely limited to the shadowy activities of Ninian and Kentigern, therefore further evidence of the status of the British church in the fifth and sixth centuries is sought in Patrick’s Confession and Gildas's De Excidlo Britɸmniae. A new model for the latter - the sermon of the protomartyr Stephen - is proposed; as is a new exegesis of D. E. B. c.69, which may have Implications for our understanding of the persistence of Pelagian beliefs. An excursus considers the significance of white stones in association with Christian burial. The origins of the mission of Augustine are considered briefly. Part three considers the mission of Paulinus in detail, in particular the reasons for its collapse; in contrasting it with the Celtic mission misslological principles are cited. A reappraisal of Paulinus's retreat, more favourable to him than that normally held, is reached by invoking wartime experience. The discipline of obstetrics is involved to advance the theory that /Ethelburh's delivery was premature; also earlier to re-examine the Herbert Ian account of Kentigern's conception, where the 'something contrary to sound doctrine' is identified, against the hitherto standard view, as the apparent approval, by Servanus, of extramarital coitus. The final establishment of the Church in Bernicia is seen as occurring principally as the result of Aidan's mission, but with valid contributions from the British and Roman traditions. That Simeon of Durham gave the credit for this foundation to Oswald is found Justifiable. A new genealogical tree of Oswy has been constructed, and maps have been provided
