A canine DNM1 mutation is highly associated with the syndrome of exercise-induced collapse

Labrador retrievers are the most common dog breed in the world, with over 200,000 new kennel club registrations per year. The syndrome of exercise-induced collapse (EIC) in this breed is manifested by muscle weakness, incoordination and life-threatening collapse after intense exercise. Using a genome-wide microsatellite marker scan for linkage in pedigrees, we mapped the EIC locus to canine chromosome 9. We then used SNP association and haplotype analysis to fine map the locus, and identified a mutation in the dynamin 1 gene (DNM1) that causes an R256L substitution in a highly conserved region of the protein. This first documented mammalian DNM1 mutation is present at a high frequency in the breed and is a compelling candidate causal mutation for EIC, as the dynamin 1 protein has an essential role in neurotransmission and synaptic vesicle endocytosis.     

Impact of cattle on two isolated fish populations in Pahranagat Valley, Nevada

The presence of cattle at Browning Spring and Ash Springs in Pahranagat Valley, Nevada, impacted fish populations by causing an increase in ammonia (NH 3 ) and nitrite (NO 2 ) levels, an increase in Pseudomonas aeruginosa and Aeromonas hydrophila , and increased, mortality and morbidity. One of the affected fishes, the White River springfish, is listed as endangered by the Department of the Interior. After removal of the cattle from Ash Springs, NH 3 and NO 2 levels decreased and fish populations increased. At Brownie Spring the NH 3 and NO 2 levels are chronically elevated, cattle are still present, and the speckled dace population has not recovered.     

Forecast accuracy and effort: The case of US inflation rates

This paper investigates the relationship between forecast accuracy and effort, where effort is defined as the number of times the model used to generate forecasts is recursively estimated over the full sample period. More specifically, within a framework of costly effort, optimal effort strategies are derived under the assumption that the dynamics of the variable of interest follow an autoregressive‐type process. Results indicate that the strategies are fairly robust over a wide range of linear and nonlinear processes (including structural break processes), and deliver forecasts of transitory, core and total inflation that require less effort to generate and are as accurate as (that is, are insignificantly different from) those produced with maximum effort. Copyright © 2010 John Wiley & Sons, Ltd.     

Loss of Siglec-14 reduces the risk of chronic obstructive pulmonary disease exacerbation

Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality worldwide. COPD exacerbation, or episodic worsening of symptoms, often results in hospitalization and increased mortality rates. Airway infections by new bacterial strains, such as nontypeable Haemophilus influenzae (NTHi), are a major cause of COPD exacerbation. NTHi express lipooligosaccharides that contain sialic acids, and may interact with Siglec-14, a sialic acid recognition protein on myeloid cells that serves as an activating signal transduction receptor. A null allele polymorphism in SIGLEC14 may attenuate the inflammatory responses to NTHi by eliminating Siglec-14 expression. We asked if the loss of Siglec-14 attenuates the inflammatory response by myeloid cells against NTHi, and if the SIGLEC14-null polymorphism has any effect on COPD exacerbation. We found that NTHi interacts with Siglec-14 to enhance proinflammatory cytokine production in a tissue culture model. Inhibitors of the Syk tyrosine kinase suppress this response. Loss of Siglec-14, due to SIGLEC14-null allele homozygosity, is associated with a reduced risk of COPD exacerbation in a Japanese patient population. Taken together, Siglec-14 and its downstream signaling pathway facilitate the “infection–inflammation–exacerbation” axis of COPD disease progression, and may represent promising targets for therapeutic intervention.     

Distribution and three-dimensional structure of AIDS virus envelope spikes

Envelope glycoprotein (Env) spikes on AIDS retroviruses initiate infection of host cells and are therefore targets for vaccine development. Though crystal structures for partial Env subunits are known, the structure and distribution of native Env spikes on virions is obscure. We applied cryoelectron microscopy tomography to define ultrastructural details of spikes. Virions of wild-type human immunodeficiency virus 1 (HIV-1) and a mutant simian immunodeficiency virus (SIV) had approximately 14 and approximately 73 spikes per particle, respectively, with some clustering of HIV-1 spikes. Three-dimensional averaging showed that the surface glycoprotein (gp120) 'head' of each subunit of the trimeric SIV spike contains a primary mass, with two secondary lobes. The transmembrane glycoprotein 'stalk' of each trimer is composed of three independent legs that project obliquely from the trimer head, tripod-like. Reconciling available atomic structures with the three-dimensional whole spike density map yields insights into the orientation of Env spike structural elements and possible structural bases of their functions.     

Biomechanics: a pneumo-hydrostatic skeleton in land crabs

Like their aquatic counterparts, terrestrial crabs repeatedly shed their rigid exoskeleton during moulting. But in the case of land crabs, little water is available to provide a temporary hydrostatic skeleton before the new skeleton hardens, and air does not provide the buoyancy necessary to support the animal. Here we show that whenever its exoskeleton is shed, the blackback land crab Gecarcinus lateralis relies on an unconventional type of hydrostatic skeleton that uses both gas and liquid (a 'pneumo-hydrostat'). To our knowledge, this is the first experimental evidence for a locomotor skeleton that depends on a gas. It establishes a new category of hydrostatic skeletal support and possibly a critical adaptation to life on land for the Crustacea.     

Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease

Several risk factors for Crohn's disease have been identified in recent genome-wide association studies. To advance gene discovery further, we combined data from three studies on Crohn's disease (a total of 3,230 cases and 4,829 controls) and carried out replication in 3,664 independent cases with a mixture of population-based and family-based controls. The results strongly confirm 11 previously reported loci and provide genome-wide significant evidence for 21 additional loci, including the regions containing STAT3, JAK2, ICOSLG, CDKAL1 and ITLN1. The expanded molecular understanding of the basis of this disease offers promise for informed therapeutic development.     

辽宁热河生物群小龙虾化石形态特征及分类之甄别

通过上侏罗统义县组６１块龙虾标本的１２种形态特征统计分析，分别论述了其构造分类意义。利用这些保存良好的新材料，对环足虾科（Ｃｒｉｃｏｉｄｏｓｃｅｌｏｓｉｄａｅ）特征作了重要补充和修订。雄性第１腹足呈棱状，第２腹足无特化现象，是这一科的重要特征。从环足虾（Ｘｒｉｃｏｉｄｏｓｃｅｌｏｓｕｓ）和古Ｌａ蛄属（Ｐａｌａｅｏｃａｍｂａｒｕｓ）雌性都具有腹环沟构造来看，它们与古Ｌａ蛄科的关系最密切。海相的化石原