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.

Analysis of genetic diversity in Portuguese Ceratonia siliqua L. cultivars using RAPD and AFLP markers

Although carob (Ceratonia siliqua L.) is of great economic importance little is still known about the pattern of genetic variation within this species. Morphological characteristics based on 31 fruit and seeds of continuous characters determinant for agro-industrial uses, were compared with RAPD and AFLP markers for assessing genetic distances in 68 accessions of carob trees, from different cultivars, varieties and eco-geographic regions of Algarve. Eighteen selected RAPD primers applied to the 68 accessions produced a total of 235 fragments ranging from 200 to 2000 bp, of which 93 (40%) were polymorphic. Four AFLP selective primer combinations generated a total of 346 amplification fragments of which 110 were polymorphic. The average level of polymorphism based on four primer combinations was 31.8%. The phenetic trees based on RAPD and AFLP analyses gave high co-phenetic correlation values, and were found to be consistent in general with the analysis of morphological data, carried out on the same accessions. A number of RAPD and AFLP markers were found to be diagnostic for ‘Canela’ cultivar and 13 wild ungrafted trees.

Oath of Allegiance to King George III

Transcript (original spelling and grammar retained): We the Commissioned Officers belonging to the Second Regiment of Lincoln Militia - Do sincerely promise and swear that we will be faithful and bear true allegiance to his Majesty King George, and heirs will defend to the utmost of our power against all traitorous conspiracies and attempts whatsoever which shall be made against his Person, Crown or Dignity; and we will do our utmost endeavours to disclose and make them known to his Majesty, His Heirs and successors, all treasons and traitorous conspiracies and attempts, which we shall know to be against Him or them. So help us God. Thomas Clark - Lt. Col. David Secord - Major John Crysler - Capt James Macklin - Capt John [Ross] - [Captain] [Abraham] Bowman - Lieut Gilbert McMicking - Quartmaster John [Misiner] - Ensign Robert Campbell - Capt John [Couke] - Ensign Nicholas Smith - Lieut I certify that the officers who have here [subscribed] the oath took it before me at Chippawa 4 Sept 1812 Thomas Dickson JP

Women’s Literary Club of St. Catharines Fonds

The Women's Literary Club of St. Catharines was founded in 1892 by a local author, Emma Harvey (Mrs. J.G.) Currie (1829-1913) and held its last official meeting on February 19, 1994. The Club developed, flourished and eventually waned. After more than one hundred successful years, the last members deposited the Club's archives at Brock University for the benefit of researchers, scholars and the larger community. The ‘object of the Club’ was established as “the promotion of literary pursuits.” The Club was a non-profit social organization composed of predominantly white, upper middle class women from the St. Catharines and surrounding areas. Club meetings were traditionally held fortnightly from March to December each year. The last meeting of the year was a celebration of their Club anniversary. The early meetings of the Club include papers presented and music performed by Club members. The literary pursuits that would dominate the agendas for the entire life of the Club reflected an interest in selected authors, national and local history, classical history, musical performances and current cultural and newsworthy events. For example in 1893 a typical meeting agendas would contain papers on Henry Wadsworth Longfellow, Hawaii, Brook Farm, Miss Louisa May Alcott and “Education of Women 100 years Ago.” Within the first year of the Club’s existence, detailed minute books became the norm and an annual agenda or program developed. The WLC collection contains a near complete set of meeting minutes from 1892 until 1995 and a comprehensive collection of yearly programs from 1983-1967 which members took great care to publish each year. Mrs. Currie brought together a group of women with a shared interest in literature and history, who wanted to pursue that interest in a formal and structured manner. She was well educated and influenced at an early age by her tutor and mentor William Kirby, local historian, writer and newspaper editor from Niagara-on-the-Lake. While Currie’s private education influenced her love of literature and history, the Club movement of the 1890’s offered a more public forum for her to share knowledge and learning with other women. Mrs. Currie was the wife of St. Catharines lawyer, James G. Currie, who also served as a Member of Parliament for the county of Lincoln. Mrs. W.H. McClive, who was also married to a St. Catharines lawyer, worked closely with Currie and they began research into the possibility of a literary Club in St. Catharines. Currie corresponded with a variety of literary Clubs across North America before she and Mrs.McClive tagged onto the momentum of the Club movement and published “A Clarion call for Women of St. Catharines To Form a Literary Club” in the local paper The St. Catharines Evening Journal. in 1892 and asked like Clubs to publish the news of their new Club. The early years of the WLC set the foundation of how the Club meetings and events would unfold for the next 80 plus years. Photos and minutes from the first ten years reveal an excitement and interest in organized Club outings. One particular event, an annual pilgrimage to the homestead of Laura Secord, became a yearly celebration for the Club. Club President, Mrs. Currie’s own personal work on Laura Secord amplified the Club’s interest in the ‘heroine of 1812’ and she allocated the profits from her publication on Secord in order to create a commemorative plaque/monument in the name of Laura Secord. The Club celebrated this event with a regular pilgrimage to this site. The connection felt by Club members and this memorial would continue until the Club’s last meetings. The majority of members in the early years were of the upper middle classes in the growing city of St. Catharines. Many of the charter members were the wives of merchants, business men, lawyers, doctors, even a hatter. Furthermore, the position of president was most often held by a woman with a comprehensive list of interests. This is particularly the case in Isabel Brighty McComb (1876-1941). Brighty who became a member in 1903, became Club president in 1932 and stayed in her post until her death in 1941. Similar to Mrs. Currie, Brighty was a local historian and published 2 booklets on local history. Her obituary indicates her position in the community as an author and involved community member committed to lifetime memberships in the Imperial Order of Daughters of Empire, I.O.D.E., the National Organization of Women, N.O.W. and the United Empire Loyalist Society, as well as the WLC. She was a locally known ‘teacher of elocution’ and a devoted researcher of Upper Canadian history. In a Club scrapbook dedicated to her, the biographical sketch illustrates the professionalism surrounding Brighty. There is very little personal history mentioned and the focus is on her literary works, her published essay, booklets and poetry. This professional focus, evident in both her obituary and the scrapbook, illustrate the diversity of these women, especially in their roles outside of the home. The WLC collection contains a vast array of essay, lectures clippings and scrapbooks from past meetings. Organized predominantly by topic or author, the folders and scrapbooks offer a substantial amount of research opportunity in the literary history of Canada. The dates, scope of topics and authors covered offer historians an exciting opportunity to examine the consumption of particular literary trends, artists and topics within the context of a midsized industrial city in English Canada. This is especially important because the agenda adhered to by the Club was bent on promoting, discussing and reviewing predominantly Canadian material. By connecting when and what these women were studying, scholars many gain a better understanding of the broader consumption and appreciation of literary and social trends of Canadian women outside of publishing and institutional records. Furthermore, because the agendas were set by and for these women, outside of the constructs of an institutionalized canon or agenda, they offer a fresh and on the ground examination of literary consumption over an extensive length of time.

Office of the City Clerk, St. Catharines Records, 1928-1974, n.d.

The site of present-day St. Catharines was settled by 3000 United Empire Loyalists at the end of the 18th century. From 1790, the settlement (then known as "The Twelve") grew as an agricultural community. St. Catharines was once referred to Shipman's Corners after Paul Shipman, owner of a tavern that was an important stagecoach transfer point. In 1815, leading businessman William Hamilton Merritt abandoned his wharf at Queenston and set up another at Shipman's Corners. He became involved in the construction and operation of several lumber and gristmills along Twelve Mile Creek. Shipman's Corners soon became the principal milling site of the eastern Niagara Peninsula. At about the same time, Merritt began to develop the salt springs that were discovered along the river which subsequently gave the village a reputation as a health resort. By this time St. Catharines was the official name of the village; the origin of the name remains obscure, but is thought to be named after Catharine Askin Robertson Hamilton, wife of the Hon. Robert Hamilton, a prominent businessman. Merritt devised a canal scheme from Lake Erie to Lake Ontario that would provide a more reliable water supply for the mills while at the same time function as a canal. He formed the Welland Canal Company, and construction took place from 1824 to 1829. The canal and the mills made St. Catharines the most important industrial centre in Niagara. By 1845, St. Catharines was incorporated as a town, with the town limits extending in 1854. Administrative and political functions were added to St. Catharines in 1862 when it became the county seat of Lincoln. In 1871, construction began on the third Welland Canal, which attracted additional population to the town. As a consequence of continual growth, the town limits were again extended. St. Catharines attained city status in 1876 with its larger population and area. Manufacturing became increasingly important in St. Catharines in the early 1900s with the abundance of hydro-electric power, and its location on important land and water routes. The large increase in population after the 1900s was mainly due to the continued industrialization and urbanization of the northern part of the city and the related expansion of business activity. The fourth Welland Canal was opened in 1932 as the third canal could no longer accommodate the larger ships. The post war years and the automobile brought great change to the urban form of St. Catharines. St. Catharines began to spread its boundaries in all directions with land being added five times during the 1950s. The Town of Merritton, Village of Port Dalhousie and Grantham Township were all incorporated as part of St. Catharines in 1961. In 1970 the Province of Ontario implemented a regional approach to deal with such issues as planning, pollution, transportation and services. As a result, Louth Township on the west side of the city was amalgamated, extending the city's boundary to Fifteen Mile Creek. With its current population of 131,989, St. Catharines has become the dominant centre of the Niagara region. Source: City of St. Catharines website http://www.stcatharines.ca/en/governin/HistoryOfTheCity.asp (January 27, 2011)

Grant of Permission for lease of military lands from Sir Robert Prescott to Thomas Clark, 1798-1801.

Transcript (original spelling and grammar retained): By His Excellency Robert Prescott Esquire, Captain General and Governor in Chief in and over His Majestys Provinces of Upper and Lower Canada, General and Commander in Chief of all His Majesty’s forces in the Provinces of Upper and Lower Canada, Nova Scotia, New Brunswick and their several Dependencies and in the Island of Newfoundland &ca. &ca. &ca. I do hereby authorise and permit Thomas Clark of Queenstown in the County of Lincoln in the Province of Upper Canada merchant to take possession of all that Lot, piece and parcel of Land (being part of the land reserved by his Majesty for Military purposes) situate, lying and being at Queenstown in the Township of Newark, in the Home District in the said Province of Upper Canada, bounded and abutted as follows, that is to say beginning at the Distance of two Chains and ninety links from the South East End of his Majesty’s Store House, the said distance being measured along the Bank up Stream, thence South thirty nine degrees and an half West one Chain and fifty links thence south fifty degrees and an half East one Chain and thirty links thence North thirty nine degrees and an half East to the Edge of the Bank and from thence along the Bank to the place of beginning, containing thirty one perches and one hundred and twenty five square links and to occupy and hold the said Lot, piece and parcel of Land during pleasure subject nevertheless to the provisoes and Conditions herein after contained, that is to say. First on condition that it shall and may be lawful to and for His Majesty his Heirs and Successors and to and for the Commander in Chief of His Majesty Forces for the time being and to and for the Officer commanding his Majesty’s Forces in Upper Canada for the time being and to and for either of them to determine and make void this present permission to occupy during pleasure the said Lot, Piece or Parcel of Land above described at any time hereafter whenever he or they shall see fit so to do without any compensation or indemnification to the said Thomas Clark or any other Person or Persons whosoever for any Loss Injury or Damage which he the said Thomas Clark or any other Person or Persons whosoever may thereby sustain. Secondly on this further Condition that it shall and may be lawful to and for His Majesty his Heirs and Successors and to and for his and their Officers, Soldiers and Servants at any time hereafter by order of the Commander in Chief of His Majesty’s Forces for the time being or by order of the Officer commanding his Majesty’s forces in Upper Canada for the time being or by order of the Officer of His Majesty’s Corps of Royal Engineers commanding in the said Province of Upper Canada for the time being to enter upon the said Lot Piece and parcel of Land which the said Thomas Clark is hereby permitted to occupy during pleasure or upon any part thereof and to take down and from the said Lot piece and parcel of Land or from any part thereof to remove any dwelling House Store or other Buildings on the said Lot, piece or Parcel of Land or any part thereof erected and to remove any goods or Chattels on the said Lot piece and parcel of Land or on any part thereof or on any such dwelling House Store or other building found or being and that His Majesty his Heirs and Successors or any other Person or Persons whosoever shall not be liable or responsible to the said Thomas Clark or to any other Person or Persons whosoever for any Loss, Injury or Damage which he or they shall or may in such case sustain. Thirdly on this further Condition that the said Thomas Clark shall not erect on the said Lot Piece or Parcel of Land which the said Thomas Clark is hereby permitted to occupy during pleasure or upon any part thereof at any time or times hereafter any dwelling House store or other Building whatsoever of Stone or brick or of any other materials wood only exccepted and that if any dwelling House or Store or other building of Stone or brick or of any other materials except wood shall at any time be erected on the said Lot, piece or parcel of Land or upon any part thereof, then and in such case, this present permission and every Clause and Article thereof shall from thenceforth cease and determine and be absolutely and entirely null and void. And lastly on this further Condition that the said Thomas Clark or any other Person whosoever shall not assign this permission to occupy the said Lot, Piece or Parcel of Land above described to any Person of Persons whosoever, and if any such assignment shall be made by the said Thomas Clark or by any other Person in his right, or on his behalf, that then and in such case such assignment and this permission to occupy during pleasure the said Lot piece and parcel of Land above described, and every Clause and Article thereof shall from thenceforth cease and determine and be absolutely and entirely null and void. Given under my hand at the Castle of St. Lewis in the City of Quebec in the Province of Lower Canada this Ninth day of July in the year of our Lord one thousand seven hundred and ninety eight and in the thirty eighth year of His Majesty’s Reign. [Signed here by Robert Prescott] By Order of the Commander in Chief [Signed here by James Green (Illegible signature)] I the said Thomas Clark above named do hereby accept the above written Permission to occupy during pleasure the said Lot piece and parcel of Land above described upon and subject to the several Provisioes and Conditions above written and each and every of them severally and respectively. In witness whereof I have hereunto set my hand the Sixteenth day of August in the year of our Lord one thousand seven hundred and ninety eight and in the thirty eighth year of His Majesty’s Reign. [Signed here by Thomas Clark] Signed in the presence of [Illegible signature – looks like J. M Donell Lt. Col.] [Illegible – looks like 2d. Battn R. C. Sm?] [Signed here by C. Anderson] Whereas Inconveniences did arise from the peculiar situation of the Ground contiguous to the above described Lot of Land and the occupation thereof, if estimated by the above Limits would prove highly disadvantageous to Mr. Thomas Clark be it known that in consideration thereof we do permit the above Lot to extend one half Chain more in length up stream so as to comprehend the space allowed for the Road between Lots Two + Three, and we do hereby appropriate the said additional space wholly to the use of the said Thomas Clark. In witness whereof we have hereunto subscribed this Thirteenth Day of October in the Year of our Lord one thousand Eight Hundred and one. [Signed here by J. M’Donell Lt. Col] 2d. Battn. R. C. [in?] Com of Fort George + Dependencies Robt. Pilkington Captain Royal Engineers

Lincoln County Records

The County of Lincoln dates back to 1798, when the first Lincoln County was formed. It was comprised of the townships of Clinton, Grimsby, Saltfleet, Barton, Ancaster, Glanford, Binbrook,Gainsborough, Caistor, Newark (Niagara),Grantham, Louth, Stamford, Thorold, Pelham, Bertie, Willoughby, Crowland, Humberstone and Wainfleet. The County boundaries were revised over the years, and the formation of Welland County in 1856 left only 7 townships in Lincoln County (Niagara, Grantham, Louth, Clinton, Gainsborough, Caistor and Grimsby). A County Council was also established at this time, which consisted of a Clerk, Warden, and a representative from each township. In 1862, the County Seat was moved from Niagara-on-the-Lake to St. Catharines. In 1970, Lincoln and Welland Counties were amalgamated to form the Regional Municipality of Niagara.

Province of Upper Canada Land Grant to Ann Cook, 1812

A grant of land to Ann Cook of the Township of Crowland. The land is situated in the township of Wainfleet, in the County of Lincoln, in the district of Niagara. Ann Cook is granted 200 acres in lot no. 32 in the 4th concession in Wainfleet. One of the signatures on the document is illegible but other signatures include: Prideaux Selby, auditor general on April 15, 1812. This is the date that the document was entered into the auditor’s office. Isaac Brock has signed in the upper left hand corner as “Isaac Brock President” which refers to the fact that he was President administering the Government of Upper Canada and Major General commanding the forces within the province. It is also signed on the left hand side by John Macdonell (who is buried at Brock’s Monument). At the time, he was the attorney general.

Probate of Last Will and Testament - William Smith

Probate of Last Will and Testament of William Smith of the township of Lincoln. Mr. Smith was a farmer. His goods and chattels are left to his children and grandchildren. The document was registered May 9, 1865 - instrument no. 15383 and the original date of the document is January 20, 1856.

Indenture of Sale from Adam Hutt and wife Dorothy to Mathias Cairns, 1806

Indenture of bargain and sale from Adam Hutt and his wife Dorothy of Lincoln County regarding 27 acres to Mathias Cairns, of Stamford Township beginning at the northeast angle of Lot 29 of Stamford Township. This was registered on May 16, 1839 in Book U, folio 239 - instrument no. 12448, January 17, 1806.

Indenture of Sale Between David Secord to Jacob Lutz

Indenture of sale between David Secord of Niagara Township to Jacob Lutz of Thorold Township regarding part of Lot no. 90 in the Township of Niagara. Registered for the County of Lincoln and Haldimand in Book J, Folio 817. This was registered July 12, 1825. The instrument no. is 6659, June 30, 1825.