The origins and early years of the Magnetic and Meteorological department at Greenwich Observatory, 1834-1848*

As one of his first acts upon becoming Astronomer Royal in 1835, George Airy made moves to set up a new observatory at Greenwich to study the Earth’s magnetic field. This paper uses Airy’s correspondence to argue that, while members of the reform movement in British science were putting pressure on the Royal Observatory to branch out into geomagnetism and meteorology, Airy established the magnetic observatory on his own initiative, ahead of Alexander von Humboldt’s request for British participation in the worldwide magnetic charting project that later became known as the ‘Magnetic Crusade’. That the Greenwich magnetic observatory did not become operational until 1839 was due to a series of incidental factors that provide a case study in the technical and political obstacles to be overcome in building a new government observatory. Airy attached less importance to meteorology than he did to geomagnetism. In 1840, he set up a full programme of meteorological observations at Greenwich – and thus turned his magnetic observatory into the ‘Magnetic and Meteorological department’ – only as the price of foiling an attempt by Edward Sabine and others in the London scientific elite to found a rival magnetic and meteorological observatory. Studying the origins of Airy’s Magnetic and Meteorological department highlights how important the context of other institutions and trends in science is to understanding the development of Britain’s national observatory.     

Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes

Genome-wide association (GWA) studies have identified multiple loci at which common variants modestly but reproducibly influence risk of type 2 diabetes (T2D). Established associations to common and rare variants explain only a small proportion of the heritability of T2D. As previously published analyses had limited power to identify variants with modest effects, we carried out meta-analysis of three T2D GWA scans comprising 10,128 individuals of European descent and approximately 2.2 million SNPs (directly genotyped and imputed), followed by replication testing in an independent sample with an effective sample size of up to 53,975. We detected at least six previously unknown loci with robust evidence for association, including the JAZF1 (P = 5.0 x 10(-14)), CDC123-CAMK1D (P = 1.2 x 10(-10)), TSPAN8-LGR5 (P = 1.1 x 10(-9)), THADA (P = 1.1 x 10(-9)), ADAMTS9 (P = 1.2 x 10(-8)) and NOTCH2 (P = 4.1 x 10(-8)) gene regions. Our results illustrate the value of large discovery and follow-up samples for gaining further insights into the inherited basis of T2D.     

Mutations in 15-hydroxyprostaglandin dehydrogenase cause primary hypertrophic osteoarthropathy

Digital clubbing, recognized by Hippocrates in the fifth century BC, is the outward hallmark of pulmonary hypertrophic osteoarthropathy, a clinical constellation that develops secondary to various acquired diseases, especially intrathoracic neoplasm. The pathogenesis of clubbing and hypertrophic osteoarthropathy has hitherto been poorly understood, but a clinically indistinguishable primary (idiopathic) form of hypertrophic osteoarthropathy (PHO) is recognized. This familial disorder can cause diagnostic confusion, as well as significant disability. By autozygosity methods, we mapped PHO to chromosome 4q33-q34 and identified mutations in HPGD, encoding 15-hydroxyprostaglandin dehydrogenase, the main enzyme of prostaglandin degradation. Homozygous individuals develop PHO secondary to chronically elevated prostaglandin E(2) levels. Heterozygous relatives also show milder biochemical and clinical manifestations. These findings not only suggest therapies for PHO, but also imply that clubbing secondary to other pathologies may be prostaglandin mediated. Testing for HPGD mutations and biochemical testing for HPGD deficiency in patients with unexplained clubbing might help to obviate extensive searches for occult pathology.     

Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis

Atopic disease, including atopic dermatitis (eczema), allergy and asthma, has increased in frequency in recent decades and now affects approximately 20% of the population in the developed world. Twin and family studies have shown that predisposition to atopic disease is highly heritable. Although most genetic studies have focused on immunological mechanisms, a primary epithelial barrier defect has been anticipated. Filaggrin is a key protein that facilitates terminal differentiation of the epidermis and formation of the skin barrier. Here we show that two independent loss-of-function genetic variants (R510X and 2282del4) in the gene encoding filaggrin (FLG) are very strong predisposing factors for atopic dermatitis. These variants are carried by approximately 9% of people of European origin. These variants also show highly significant association with asthma occurring in the context of atopic dermatitis. This work establishes a key role for impaired skin barrier function in the development of atopic disease.     

New use of BCG for recombinant vaccines

BCG, a live attenuated tubercle bacillus, is the most widely used vaccine in the world and is also a useful vaccine vehicle for delivering protective antigens of multiple pathogens. Extrachromosomal and integrative expression vectors carrying the regulatory sequences for major BCG heat-shock proteins have been developed to allow expression of foreign antigens in BCG. These recombinant BCG strains can elicit long-lasting humoral and cellular immune responses to foreign antigens in mice.     

龙门山茂汶─汶川变质带构造特征研究

龙门山中段茂汶─汶川韧性剪切带中可见到绿片岩相到角闪岩相的古生界。该地的巴罗型中压变质相相当于松潘—甘孜褶皱带中地壳的绿泥石带，构成了北东—南西向的茂汶—汶川变质带。雪隆包花岗岩体正位于该变质带的中心部位。三次韧性变形作用（Ｄ１～Ｄ３）造就了印支褶皱带，并在三叠纪末末形成了松潘—甘孜褶皱带。Ｄ１变形作用为北东—南西向的挤压作用和冲断作用，形成了大型的等斜褶皱，使古生界缩短和加厚。在持续的Ｄ２北京—南西向挤压作用下，松潘—甘孜褶皱带和稳定的扬子克拉通之间的差异应变由茂汶—汶川剪切带中非同轴左旋剪切作用所容纳。雪隆包花岗岩体是在Ｄ２变形作用的晚期侵入到剪切带的。产生蓝晶石的变质条件也是在Ｄ２或Ｄ２变形作用后出现的。Ｄ３变形作用为北西—南东向挤压，在局部地方形成糜棱岩状的道冲剪切带。这些特征与绿泥石退变质作用有关，揭示出在Ｄ３变形期间茂汶—汶川变质带有较大幅度的隆升。尽管雪隆包岩体在空间上与茂汶—汶川变质带有关，但作者认为其变质作用是岩层加厚引起的热作用重新达到平衡的产物，而不是由侵入作用引起的热接触变质作用。然而，与岩浆作用伴生的高温和活动性流体仍是产生Ｄ３局部变形和雪隆包岩体隆升的原因，这也是局部出现角闪告相