Rare structural variants disrupt multiple genes in neurodevelopmental pathways in schizophrenia     

Walsh T  McClellan JM  McCarthy SE  Addington AM  Pierce SB  Cooper GM  Nord AS  Kusenda M  Malhotra D  Bhandari A  Stray SM  Rippey CF  Roccanova P  Makarov V  Lakshmi B  Findling RL  Sikich L  Stromberg T  Merriman B  Gogtay N  Butler P  Eckstrand K  Noory L  Gochman P  Long R  Chen Z  Davis S  Baker C  Eichler EE  Meltzer PS  Nelson SF  Singleton AB  Lee MK  Rapoport JL  King MC  Sebat J 《Science (New York, N.Y.)》2008,320(5875):539-543

Schizophrenia is a devastating neurodevelopmental disorder whose genetic influences remain elusive. We hypothesize that individually rare structural variants contribute to the illness. Microdeletions and microduplications >100 kilobases were identified by microarray comparative genomic hybridization of genomic DNA from 150 individuals with schizophrenia and 268 ancestry-matched controls. All variants were validated by high-resolution platforms. Novel deletions and duplications of genes were present in 5% of controls versus 15% of cases and 20% of young-onset cases, both highly significant differences. The association was independently replicated in patients with childhood-onset schizophrenia as compared with their parents. Mutations in cases disrupted genes disproportionately from signaling networks controlling neurodevelopment, including neuregulin and glutamate pathways. These results suggest that multiple, individually rare mutations altering genes in neurodevelopmental pathways contribute to schizophrenia.  相似文献   

Category-specific cortical activity precedes retrieval during memory search     

Polyn SM  Natu VS  Cohen JD  Norman KA 《Science (New York, N.Y.)》2005,310(5756):1963-1966

Here we describe a functional magnetic resonance imaging study of humans engaged in memory search during a free recall task. Patterns of cortical activity associated with the study of three categories of pictures (faces, locations, and objects) were identified by a pattern-classification algorithm. The algorithm was used to track the reappearance of these activity patterns during the recall period. The reappearance of a given category's activity pattern correlates with verbal recalls made from that category and precedes the recall event by several seconds. This result is consistent with the hypothesis that category-specific activity is cueing the memory system to retrieve studied items.  相似文献   

Protective adaptive immunity to Chlamydophila abortus infection and control of ovine enzootic abortion (OEA)     

Rocchi MS  Wattegedera S  Meridiani I  Entrican G 《Veterinary microbiology》2009,135(1-2):112-121

Ovine enzootic abortion (OEA) remains a major problem in sheep-rearing countries despite the availability of protective vaccines. The causative agent, Chlamydophila abortus, is a Gram-negative bacterium that can induce a persistent, subclinical infection in non-pregnant sheep. The development of a new safe, effective and practical vaccine requires a detailed understanding of host-pathogen interactions and the identification of clear correlates of protection. Since disease (abortion) is only observed during pregnancy, the nature of host immunity to C. abortus and the specialised immunological features that permit maternal acceptance of the semi-allogeneic fetus are central to the pathogenesis of OEA. We review the current literature on persistence of C. abortus, host immunity to infection and mechanisms of abortion. We identify the key outstanding questions surrounding OEA and discuss the current knowledge gaps with a view to developing improved control strategies.  相似文献   

Single-dose pharmacokinetics and genotoxicity of metronidazole in cats     

Ivana Sekis  Kerry Ramstead  Mark Rishniw  Wayne S. Schwark  Sean P. McDonough  Richard E. Goldstein  Mark Papich  Kenneth W. Simpson 《Journal of Feline Medicine and Surgery》2009,11(2):60-68

  相似文献   

Changes in distribution,morphology and ultrastructure of chloride cell in Atlantic salmon during an AGD infection     

Yao‐Chung Chang  Harry Hamlin‐Wright  Sean Monaghan  Tharangani Herath  Johanna Baily  Jorge del Pozo  Jamie Downes  Andrew Preston  Lynn Chalmers  Nilantha Jayasuriya  James E. Bron  Alexandra Adams  Sophie Fridman 《Journal of fish diseases》2019,42(10):1433-1446

  相似文献   

Serial exploitation of global sea cucumber fisheries     

Sean C Anderson  Joanna Mills Flemming  Reg Watson  Heike K Lotze 《Fish and Fisheries》2011,12(3):317-339

In recent decades, invertebrate fisheries have expanded in catch and value worldwide. One increasingly harvested group is sea cucumbers (class Holothuroidea), which are highly valued in Asia and sold as trepang or bêche‐de‐mer. We compiled global landings, economic data, and country‐specific assessment and management reports to synthesize global trends in sea cucumber fisheries, evaluate potential drivers, and test for local and global serial exploitation patterns. Although some sea cucumber fisheries have existed for centuries, catch trends of most individual fisheries followed boom‐and‐bust patterns since the 1950s, declining nearly as quickly as they expanded. New fisheries expanded five to six times faster in 1990 compared to 1960 and at an increasing distance from Asia, encompassing a global fishery by the 1990s. Global sea cucumber production was correlated to the Japanese yen at a leading lag. Regional assessments revealed that population declines from overfishing occurred in 81% of sea cucumber fisheries, average harvested body size declined in 35%, harvesters moved from near‐ to off‐shore regions in 51% and from high‐ to low‐value species in 76%. Thirty‐eight per cent of sea cucumber fisheries remained unregulated, and illegal catches were of concern in half. Our results suggest that development patterns of sea cucumber fisheries are largely predictable, often unsustainable and frequently too rapid for effective management responses. We discuss potential ecosystem and human community consequences and urge for better monitoring and reporting of catch and abundance, proper scientific stock assessment and consideration of international trade regulations to ensure long‐term and sustainable harvesting of sea cucumbers worldwide.  相似文献   

Abiotic persistence of atrazine and simazine in water     

Sean D W Comber 《Pest management science》1999,55(7):696-702

Hydrolysis and photolysis experiments have been undertaken to investigate the abiotic persistence of atrazine and simazine in a variety of waters. Hydrolysis only occurs to a significant extent at pH values at the lower limit of those found in the natural aquatic environment (pH 4.0 or less). Photolysis was initiated by a wide range of wavelengths in waters at pH 4.0, but only by more energetic wavelengths of less than 300 nm at higher pH values (pH 6 to 8). Based on these data, the aquatic half-life of atrazine and simazine in well-lit acidic upland waters will be typically six days. In lowland rivers with higher pH (7 to 8.5), these triazines are likely to exhibit half-lives of months rather than days. In groundwaters, atrazine and simazine will have half-lives in the order of years, due to the exceedingly slow rate of hydrolysis. © 1999 Society of Chemical Industry  相似文献   

Survival, growth and osmolality of greenlip abalone Haliotis laevigata (Donovan 1808) when exposed to different ionic profiles of inland saline water     

Ravi Fotedar  Simon Harries  & Sean Savage 《Aquaculture Research》2008,39(5):441-448

Two experiments over 21 days were conducted to assess the effect of different ionic profiles (mainly K⁺) of inland saline water (ISW) on the survival, growth, osmoregulation and moisture content of juvenile greenlip abalone Haliotis laevigata. In experiment I, the juveniles were cultured in five different water types: ocean water (OW) as a control, inland saline water (ISW or ISW K⁺₀), ISW fortified with 33%, 66% and 100% K⁺ as in OW (ISW K⁺₃₃, ISW K⁺₆₆ and ISW K⁺₁₀₀ respectively). In experiment II, five different culture media, 100% OW(control), 75% OW mixed with 25% ISW (ISW₂₅), 50% OW mixed with 50% ISW (ISW₅₀), 25% OW mixed with 75% ISW (ISW₇₅) and 100% ISW (ISW or ISW₁₀₀), were tested. Within 21 days, all of the abalone in ISW (ISW K⁺₀ and ISW₁₀₀; Na⁺/K⁺ ratio of 111 L^?1) died compared with 100% survival in OW. One‐hundred per cent K⁺ fortification of ISW increased the specific growth rate (SGR) and serum osmolality of the surviving juveniles. The 96 h acute LC₅₀ value was between ISW₅₀ and ISW₇₅. The increased proportion of ISW in OW resulted in significantly (P<0.05) lower survival, SGR and serum osmolality of juveniles. The moisture content of the juveniles was not influenced by any water type. The results suggested that abalone cannot survive in raw ISW, but survival can increase when it is fortified with K⁺ and ionic ratios of ISW are brought closer to OW by mixing it with OW. Furthermore, abalone survival is influenced by other ions in ISW besides K⁺.  相似文献   

Conventional fractionated radiotherapy outcomes for young dogs with nephroblastoma of the spinal cord: 5 cases     

Jaeyoung Kim  Michael Sean Kent  Alain Pierre Théon  Amandine Tamara Lejeune  Katherine Sarah Hansen 《Veterinary and comparative oncology》2023,21(3):419-426

Published radiotherapy results for spinal nephroblastomas in dogs are limited. In this retrospective longitudinal study (1/2007–1/2022), five dogs with a median age of 2.8 years received post-operative 3D conformal, conventional fractionated radiotherapy (CFRT) with 2–4 fields (parallel-opposed with or without two hinge-angle fields), for an incompletely resected nephroblastoma. Clinical findings prior to surgery included one or more of the following: pelvic limb paresis (5), faecal incontinence (2), flaccid tail (1), non-ambulatory (2) and deep pain loss (1). All masses were located between T11 and L3 and surgically removed via hemilaminectomy. Dogs received 45–50 Gray (Gy) in 18–20 fractions, and no dogs received chemotherapy post-radiation. At analysis, all dogs were deceased, with none lost to follow-up. The median overall survival (OS) from first treatment to death of any cause was 3.4 years (1234 days; 95% CI 68 days-upper limit not reached; range: 68–3607 days). The median planning target volume was 51.3 cc, with a median PTV dose of 51.4 Gy and median D98 = 48.3 Gy. Late complications or recurrence was difficult to fully determine in this small dataset; however, some degree of ataxia persisted throughout life in all dogs. This study provides preliminary evidence that post-operative radiotherapy may result in prolonged survival times dogs with spinal nephroblastomas.  相似文献