Mutations in known monogenic high bone mass loci only explain a small proportion of high bone mass cases

High bone mass (HBM) can be an incidental clinical finding; however, monogenic HBM disorders (eg, LRP5 or SOST mutations) are rare. We aimed to determine to what extent HBM is explained by mutations in known HBM genes. A total of 258 unrelated HBM cases were identified from a review of 335,115 DXA scans from 13 UK centers. Cases were assessed clinically and underwent sequencing of known anabolic HBM loci: LRP5 (exons 2, 3, 4), LRP4 (exons 25, 26), SOST (exons 1, 2, and the van Buchem's disease [VBD] 52-kb intronic deletion 3'). Family members were assessed for HBM segregation with identified variants. Three-dimensional protein models were constructed for identified variants. Two novel missense LRP5 HBM mutations ([c.518C>T; p.Thr173Met], [c.796C>T; p.Arg266Cys]) were identified, plus three previously reported missense LRP5 mutations ([c.593A>G; p.Asn198Ser], [c.724G>A; p.Ala242Thr], [c.266A>G; p.Gln89Arg]), associated with HBM in 11 adults from seven families. Individuals with LRP5 HBM ( approximately prevalence 5/100,000) displayed a variable phenotype of skeletal dysplasia with increased trabecular BMD and cortical thickness on HRpQCT, and gynoid fat mass accumulation on DXA, compared with both non-LRP5 HBM and controls. One mostly asymptomatic woman carried a novel heterozygous nonsense SOST mutation (c.530C>A; p.Ser177X) predicted to prematurely truncate sclerostin. Protein modeling suggests the severity of the LRP5-HBM phenotype corresponds to the degree of protein disruption and the consequent effect on SOST-LRP5 binding. We predict p.Asn198Ser and p.Ala242Thr directly disrupt SOST binding; both correspond to severe HBM phenotypes (BMD Z-scores +3.1 to +12.2, inability to float). Less disruptive structural alterations predicted from p.Arg266Cys, p.Thr173Met, and p.Gln89Arg were associated with less severe phenotypes (Z-scores +2.4 to +6.2, ability to float). In conclusion, although mutations in known HBM loci may be asymptomatic, they only account for a very small proportion ( approximately 3%) of HBM individuals, suggesting the great majority are explained by either unknown monogenic causes or polygenic inheritance.

Emissões atmosféricas e implicações potenciais sobre a biota terrestre devido as atividades antrópicas na Baía do Almirantado/ Ilha Rei George Antártica

Neste trabalho foi realizado um estudo sobre o impacto sobre a atmosfera e a biota terrestre devido às emissões antrópicas na Baia do Almirantado/Ilha Rei George Antártica. Foram monitoradas as emissões dos compostos orgânicos voláteis e semi-voláteis, tanto nas fontes emissoras como no entorno da Estação Antártica Comandante Ferraz e estimadas as emissões dos navios, dos geradores a diesel e da incineração de lixo. Na avaliação do entorno, coletaram-se amostras de ar, neve e penas de aves. Com os resultados das emissões, do estudo topográfico e da meteorologia, realizou-se uma modelagem de plumas gaussiana para avaliar os impactos. Quatro cenários foram avaliados: dois com a presença dos navios NApOc Ary Rongel e Maximiano apresentaram concentrações máximas de até 356 g m-3 de COV e 18 g m-3 de material particulado, enquanto os demais, sem a presença dos navios, apenas considerando as estações de pesquisa EACF e Arctowski, apresentaram concentrações máximas de até 2,5 g m-3 de COV e 1,3 g m-3 de material particulado. Amostras de COV coletadas foram compatíveis com o cenário mais crítico. O estudo de correlação para carbonilas e HPA atmosférico e Carbono elementar e HPA, depositados em neve, apontaram a EACF como a principal fonte de emissão. As concentrações de levoglucosano detectadas a aproximadamente 2 km da EACF apontaram para a prática de incineração de lixo da EACF. Todas as áreas de interesse biológicos, anteriormente mapeados, dentro da AAEG, são vulneráveis às emissões antrópicas, como sugeriu o modelo de dispersão e a sobreposição dos resultados encontrados.

Sketch of the Life of William Blanchard Towne

Sketch of the life of William Blanchard Towne.

Missionary life among the cannibals : being the life of the Rev. John Geddie, D.D., first missionary to the New Hebrides : with a history of the Nova Scotia Presbyterian mission on that group / by George Patterson.

http://www.archive.org/details/cannibalmission00pattuoft

A Student Composers' Recital, May 7, 1959 8:30pm

Concert program for A Student Composers' Recital, May 7, 1959

Départ de [Georges] Carpentier [de New-York pour revenir en France, de gauche à droite] Harry Pollok, Descamps, Jack Kearns, Carpentier, [William A.] Brady, Jack Curley : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 60168

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

A sermon, preached in Boston, August 20, 1812, the day of humiliation and prayer, appointed by the President of the United States, in consequence of the declaration of war against Great Britain /

Published at the request of the hearers.

Bowslaugh Family fonds, 1860-1861, 1868, 1876-1877, 1880-1882, 1886-1890, 1892-1893, 1895, 1898-1899, n.d.

Edward W. Bowslaugh (1843-1923) was the son of Jacob and Anna (Beamer) Bowslaugh. Edward Bowslaugh married Mary Southward, and the couple had six children, Edgar Morley, Edward Freeman, twins Alfred Malcolm and Alice Mary, Annie Olivia, John Jacob and Mabel Florence. Edward W. Bowslaugh was a farmer, contractor and owner of the Grimsby Planing Mills in Grimsby, Ont. and Bowslaugh’s Planing Mill in Kingsville, Ont. The mills manufactured door and sash trim and other wood related products. Some customers contracted the firm to provide wood products for cottages being built at Grimsby Park, the Methodist camp ground. Some time before 1885 Edward Bowslaugh and his family moved to Kingsville, Ont. to open up a new planing mill and door and sash manufactory. He later sold the Grimsby Planing Mills to Daniel Marsh. The diaries and account books include many names of workers as well as friends and family members residing in the Grimsby and Kingsville areas. James M. Bowslaugh (1841-1882) was the son of Jacob and Anna (Beamer) Bowslaugh. James married first Anna Catharine Merritt and after her death in 1875 he married Mary Gee in 1877. James and Anna had three children, Eliza, James Herbert, George Hiram, all died very young. James and Mary Gee had one son, Charles Leopold Kenneth Frederich Bowslaugh, b. 1881. James Bowslaugh was a farmer and lumberman, much like his younger brother Edward. James’ early diaries often note the activities of himself and his brother Edward. Both Edward and James were heavily involved in the Methodist church, teaching or leading Sunday school and attending prayer meetings. Alfred M. Bowslaugh b. 1873 was the son of Edward W. Bowslaugh and his wife Mary Southward. The school notebook is from his days as a student in Kingsville, Ont.