Genomic organization, complex splicing pattern and expression of a human septin gene on chromosome 17q25.3

The Ov/Br septin gene, which is also a fusion partner of MLL in acute myeloid leukaemia, is a member of a family of novel GTP binding proteins that have been implicated in cytokinesis and exocytosis. In this study, we describe the genomic and transcriptional organization of this gene, detailing seventeen exons distributed over 240 kb of sequence. Extensive database analyses identified orthologous rodent cDNAs that corresponded to new, unidentified 5' splice variants of the Ov/Br septin gene, increasing the total number of such variants to six. We report that splicing events, occurring at non-canonical sites within the body of the 3' terminal exon, remove either 1801 bp or 1849 bp of non-coding sequence and facilitate access to a secondary open reading frame of 44 amino acids maintained near the end of the 3' UTR. These events constitute a novel coding arrangement and represent the first report of such a design being implemented by a eukaryotic gene. The various Ov/Br proteins either differ minimally at their amino and carboxy termini or are equivalent to truncated versions of larger isoforms. Northern analysis with an Ov/Br septin 3' UTR probe reveals three transcripts of 4.4, 4 and 3 kb, the latter being restricted to a sub-set of the tissues tested. Investigation of the identified Ov/Br septin isoforms by RT-PCR confirms a complex transcriptional pattern, with several isoforms showing tissue-specific distribution. To date, none of the other human septins have demonstrated such transcriptional complexity.

Refugial persistence and postglacial recolonization of North America by the cold-tolerant herbaceous plant Orthilia secunda

Previous phylogeographical and palaeontological studies on the biota of northern North America have revealed a complex scenario of glacial survival in multiple refugia and differing patterns of postglacial recolonization. Many putative refugial regions have been proposed both north and south of the ice sheets for species during the Last Glacial Maximum, but the locations of many of these refugia remain a topic of great debate. In this study, we used a phylogeographical approach to elucidate the refugial and recolonization history of the herbaceous plant species Orthilia secunda in North America, which is found in disjunct areas in the west and east of the continent, most of which were either glaciated or lay close to the limits of the ice sheets. Analysis of 596-bp of the chloroplast trnS-trnG intergenic spacer and five microsatellite loci in 84 populations spanning the species' range in North America suggests that O.secunda persisted through the Last Glacial Maximum (LGM) in western refugia, even though palaeodistribution modelling indicated a suitable climate envelope across the entire south of the continent. The present distribution of the species has resulted from recolonization from refugia north and south of the ice sheets, most likely in Beringia or coastal regions of Alaska and British Columbia, the Washington/Oregon region in the northwest USA, and possibly from the region associated with the putative 'ice-free corridor' between the Laurentide and Cordilleran ice sheets. Our findings also highlight the importance of the Pacific Northwest as an important centre of intraspecific genetic diversity, owing to a combination of refugial persistence in the area and recolonization from other refugia.

Replication of association between schizophrenia and ZNF804A in the Irish Case-Control Study of Schizophrenia sample

A recent genome-wide association study reported association between schizophrenia and the ZNF804A gene on chromosome 2q32.1. We attempted to replicate these findings in our Irish Case-Control Study of Schizophrenia (ICCSS) sample (N=1021 cases, 626 controls). Following consultation with the original investigators, we genotyped three of the most promising single-nucleotide polymorphisms (SNPs) from the Cardiff study. We replicate association with rs1344706 (trend test one-tailed P=0.0113 with the previously associated A allele) in ZNF804A. We detect no evidence of association with rs6490121 in NOS1 (one-tailed P=0.21), and only a trend with rs9922369 in RGRIP1L (one-tailed P=0.0515). On the basis of these results, we completed genotyping of 11 additional linkage disequilibrium-tagging SNPs in ZNF804A. Of 12 SNPs genotyped, 11 pass quality control criteria and 4 are nominally associated, with our most significant evidence of association at rs7597593 (P=0.0013) followed by rs1344706. We observe no evidence of differential association in ZNF804A on the basis of family history or sex of case. The associated SNP rs1344706 lies in approximately 30 bp of conserved mammalian sequence, and the associated A allele is predicted to maintain binding sites for the brain-expressed transcription factors MYT1l and POU3F1/OCT-6. In controls, expression is significantly increased from the A allele of rs1344706 compared with the C allele. Expression is increased in schizophrenic cases compared with controls, but this difference does not achieve statistical significance. This study replicates the original reported association of ZNF804A with schizophrenia and suggests that there is a consistent link between the A allele of rs1344706, increased expression of ZNF804A and risk for schizophrenia.

Molecular subtyping of primary prostate cancer reveals specific and shared target genes of different ETS rearrangements

This work aimed to evaluate whether ETS transcription factors frequently involved in rearrangements in prostate carcinomas (PCa), namely ERG and ETV1, regulate specific or shared target genes. We performed differential expression analysis on nine normal prostate tissues and 50 PCa enriched for different ETS rearrangements using exon-level expression microarrays, followed by in vitro validation using cell line models. We found specific deregulation of 57 genes in ERG-positive PCa and 15 genes in ETV1-positive PCa, whereas deregulation of 27 genes was shared in both tumor subtypes. We further showed that the expression of seven tumor-associated ERG target genes (PLA1A, CACNA1D, ATP8A2, HLA-DMB, PDE3B, TDRD1, and TMBIM1) and two tumor-associated ETV1 target genes (FKBP10 and GLYATL2) was significantly affected by specific ETS silencing in VCaP and LNCaP cell line models, respectively, whereas the expression of three candidate ERG and ETV1 shared targets (GRPR, KCNH8, and TMEM45B) was significantly affected by silencing of either ETS. Interestingly, we demonstrate that the expression of TDRD1, the topmost overexpressed gene of our list of ERG-specific candidate targets, is inversely correlated with the methylation levels of a CpG island found at -66 bp of the transcription start site in PCa and that TDRD1 expression is regulated by direct binding of ERG to the CpG island in VCaP cells. We conclude that ETS transcription factors regulate specific and shared target genes and that TDRD1, FKBP10, and GRPR are promising therapeutic targets and can serve as diagnostic markers for molecular subtypes of PCa harboring specific fusion gene rearrangements.

Molecular phylogenetic analysis of a known and a new hydrothermal vent octopod:Their relationships with the genus Benthoctopus (Cephalopoda: Octopodidae)

The resolution of evolutionary relationships among deep-sea incirrate octopuses has been hindered by the paucity of individuals available for morphological studies and by the lack of tissue samples preserved using fixatives compatible with simple DNA extraction techniques. Evolutionary relationships from 11 species of deep-sea incirrate octopuses were investigated using 2392 base pairs (bp) of DNA from four mitochondrial genes (12S rDNA, 16S rDNA, cytochrome c oxidase subunit III, and cytochrome b) and the nuclear gene, rhodopsin. Morphological examination of these species was also undertaken. Molecular analyses distinguish a species of octopus from hydrothermal vents at Manus Basin from the vent octopodid Vulcanoctopus hydrothermalis known from vents on the East Pacific Rise. Both are herein considered members of the clade currently assigned the name Benthoctopus, although taxonomic implications preclude formally naming Vulcanoctopus as a junior synonym. Morphological investigations led to the conclusion that Benthoctopus macrophallus is a junior synonym of Benthoctopus yaquinae. An amended diagnosis of Benthoctopus is provided with additional information on male reproductive characteristics. Copyright © 2009 · Magnolia Press.

Morphological and molecular characters reveal differentiation in a Neotropical social bee, Melipona beecheii (Apidae : Meliponini)

Morphometrics and DNA microsatellites were used to analyse the genetic structure of populations of the stingless bee M. beecheii from two extremes of its geographic range. The results showed that populations from Costa Rica and Yucatan exhibit substantial phenotypic and molecular differentiation. Bees from Yucatan were smaller and paler than those from Costa Rica. The value of multilocus F-ST = 0.280 (P <0.001) confirmed that there were significant molecular genetic differences between the two populations. Populations showed significant deviation from Hardy Weinberg equilibrium and the values of FIS (the inbreeding coefficient) were positive for Costa Rica = 0.416 and the Yucatan Peninsula = 0.193, indicating a lack of heterozygotes in both populations possibly due to inbreeding. The DNA sequence of 678 bp of the mitochondrial gene COI differed between populations by 1.2%. The results of this study should be considered in conservation programmes, particularly with regard to the movement of colonies between regions.

Romanticism and Blackwood's Magazine:'An Unprecedented Phenomenon'

Romanticism and Blackwood's Magazine is inspired by the ongoing critical fascination with Blackwood's Edinburgh Magazine, and the burgeoning recognition of its centrality to the Romantic age. Though the magazine itself was published continuously for well over a century and a half, this volume concentrates specifically on those years when William Blackwood was at the helm, beginning with his founding of the magazine in 1817 and closing with his death in 1834. These were the years when, as Samuel Taylor Coleridge put it in 1832, Blackwood's reigned as 'an unprecedented Phenomenon in the world of letters.' The magazine placed itself at the centre of the emerging mass media, commented decisively on all the major political and cultural issues that shaped the Romantic movement, and published some of the leading writers of the day, including Coleridge, Thomas De Quincey, John Galt, Felicia Hemans, James Hogg, Walter Scott, and Mary Shelley.

'This much-needed volume reminds us not only why Blackwood's was the most influential periodical publication of the time, but also how its writers, writings, and critical agendas continue to shape so many of the scholarly concerns of Romantic studies in the twenty-first century.' - Charles Mahoney, Associate Professor, University of Connecticut, USA

List of Illustrations
Acknowledgements
Abbreviations
Notes on Contributors
'A character so various, and yet so indisputably its own': A Passage to Blackwood's Edinburgh Magazine; R.Morrison & D.S.Roberts
PART I: BLACKWOOD'S AND THE PERIODICAL PRESS
Beginning Blackwood's: The Right Mix of Dulce and Ùtile; P.Flynn
John Gibson Lockhart and Blackwood's: Shaping the Romantic Periodical Press; T.Richardson
From Gluttony to Justified Sinning: Confessional Writing in Blackwood's and the London Magazine; D.Higgins
Camaraderie and Conflict: De Quincey and Wilson on Enemy Lines; R.Morrison
Selling Blackwood's Magazine, 1817-1834; D.Finkelstein
PART II: BLACKWOOD'S CULTURE AND CRITICISM
Blackwood's 'Personalities'; T.Mole
Communal Reception, Mary Shelley, and the 'Blackwood's School' of Criticism; N.Mason
Blackwoodian Allusion and the Culture of Miscellaneity; D.Stewart
Blackwood's Edinburgh Magazine in the Scientific Culture of Early Nineteenth-Century Edinburgh; W.Christie
The Art and Science of Politics in Blackwood's Edinburgh Magazine, c. 1817-1841; D.Kelly
Prosing Poetry: Blackwood's and Generic Transposition, 1820-1840; J.Camlot
PART III: BLACKWOOD'S FICTIONS
Blackwood's and the Boundaries of the Short Story; T.Killick
The Edinburgh of Blackwood's Edinburgh Magazine and James Hogg's Fiction; G.Hughes
'The Taste for Violence in Blackwood's Magazine'; M.Schoenfield
PART IV: BLACKWOOD'S AT HOME
John Wilson and Regency Authorship; R.Cronin
John Wilson and Sport; J.Strachan
William Maginn and the Blackwood's 'Preface' of 1826; D.E.Latané, Jr.
All Work and All Play: Felicia Hemans's Edinburgh Noctes; N.Sweet
PART V: BLACKWOOD'S ABROAD
Imagining India in Early Blackwood's; D.S.Roberts
Tales of the Colonies: Blackwood's, Provincialism, and British Interests Abroad; A.Jarrells
Selected Bibliography
Index

ROBERT MORRISON is Queen's National Scholar at Queen's University, Kingston, Ontario, Canada. His book, The English Opium-Eater: A Biography of Thomas De Quincey was a finalist for the James Tait Black Prize. He has edited writings by Jane Austen, Leigh Hunt, Thomas De Quincey, and John Polidori.
DANIEL SANJIV ROBERTS is Reader in English at Queen's University Belfast, UK. His publications include a monograph, Revisionary Gleam: De Quincey, Coleridge, and the High Romantic Argument (2000), and major critical editions of Thomas De Quincey's Autobiographic Sketches and Robert Southey's The Curse of Kehama; the latter was cited as a Distinguished Scholarly Edition by the MLA. He is currently working on an edition of Charles Johnstone's novel The History of Arsaces, Prince of Betlis for the Early Irish Fiction series.

14C as a tool to trace terrestrial carbon in a complex lake system: implications for food-web structure and carbon cycling

Globally lakes bury and remineralise significant quantities of terrestrial C, and the associated flux of terrestrial C strongly influences their functioning. Changing deposition chemistry, land use and climate induced impacts on hydrology will affect soil biogeochemistry and terrestrial C export¹ and hence lake ecology with potential feedbacks for regional and global C cycling. C and nitrogen stable isotope analysis (SIA) has identified the terrestrial subsidy of freshwater food webs. The approach relies on different ¹³C fractionation in aquatic and terrestrial primary producers, but also that inorganic C demands of aquatic primary producers are partly met by ¹³C depleted C from respiration of terrestrial C, and ‘old’ C derived from weathering of catchment geology. SIA thus fails to differentiate between the contributions of old and recently fixed terrestrial C. Natural abundance ¹⁴C can be used as an additional biomarker to untangle riverine food webs² where aquatic and terrestrial δ ¹³C overlap, but may also be valuable for examining the age and origin of C in the lake. Primary production in lakes is based on dissolved inorganic C (DIC). DIC in alkaline lakes is partially derived from weathering of carbonaceous bedrock, a proportion of which is¹⁴C-free. The low ¹⁴C activity yields an artificial age offset leading samples to appear hundreds to thousands of years older than their actual age. As such, ¹⁴C can be used to identify the proportion of autochthonous C in the food-web. With terrestrial C inputs likely to increase, the origin and utilisation of ‘fossil’ or ‘recent’ allochthonous C in the food-web can also be determined. Stable isotopes and 14C were measured for biota, particulate organic matter (POM), DIC and dissolved organic carbon (DOC) from Lough Erne, Northern Ireland, a humic alkaline lake. Temporal and spatial variation was evident in DIC, DOC and POM C isotopes with implications for the fluctuation in terrestrial export processes. Ramped pyrolysis of lake surface sediment indicates the burial of two C components. ¹⁴C activity (507 ± 30 BP) of sediment combusted at 400˚C was consistent with algal values and younger than bulk sediment values (1097 ± 30 BP). The sample was subsequently combusted at 850˚C, yielding 14C values (1471 ± 30 BP) older than the bulk sediment age, suggesting that fossil terrestrial carbon is also buried in the sediment. Stable isotopes in the food web indicate that terrestrial organic C is also utilised by lake organisms. High winter δ ¹⁵N values in calanoid zooplankton (δ ¹⁵N = 24%¸) relative to phytoplankton and POM (δ ¹⁵N = 6h and 12h respectively) may reflect several microbial trophic levels between terrestrial C and calanoids. Furthermore winter calanoid 14C ages are consistent with DOC from an inflowing river (75 ± 24 BP), not phytoplankton (367 ± 70 BP). Summer calanoid δ ^13C, δ ¹⁵N and ¹⁴C (345 ± 80 BP) indicate greater reliance on phytoplankton.

¹ Monteith, D.T et al., (2007) Dissolved organic carbon trends resulting from changes in atmospheric deposition chemistry. Nature, 450:537-535

² Caraco, N., et al.,(2010) Millennial-aged organic carbon subsidies to a modern river food web. Ecology,91: 2385-2393.

All the World's a Stage: Facilitating Discovery Science and Improved Cancer Care through the Global Alliance for Genomics and Health

The recent explosion of genetic and clinical data generated from tumor genome analysis presents an unparalleled opportunity to enhance our understanding of cancer, but this opportunity is compromised by the reluctance of many in the scientific community to share datasets and the lack of interoperability between different data platforms. The Global Alliance for Genomics and Health is addressing these barriers and challenges through a cooperative framework that encourages "team science" and responsible data sharing, complemented by the development of a series of application program interfaces that link different data platforms, thus breaking down traditional silos and liberating the data to enable new discoveries and ultimately benefit patients.