The genome and transcriptome of Japanese flounder provide insights into flatfish asymmetry

Flatfish have the most extreme asymmetric body morphology of vertebrates. During metamorphosis, one eye migrates to the contralateral side of the skull, and this migration is accompanied by extensive craniofacial transformations and simultaneous development of lopsided body pigmentation(1-5). The evolution of this developmental and physiological innovation remains enigmatic. Comparative genomics of two flatfish and transcriptomic analyses during metamorphosis point to a role for thyroid hormone and retinoic acid signaling, as well as phototransduction pathways. We demonstrate that retinoic acid is critical in establishing asymmetric pigmentation and, via cross-talk with thyroid hormones, in modulating eye migration. The unexpected expression of the visual opsins from the phototransduction pathway in the skin translates illumination differences and generates retinoic acid gradients that underlie the generation of asymmetry. Identifying the genetic underpinning of this unique developmental process answers long-standing questions about the evolutionary origin of asymmetry, but it also provides insight into the mechanisms that control body shape in vertebrates.National Natural Science Foundation of China [31130057, 31461163005, 31530078, 31472269, 31472262, 31472273]; State 863 High Technology R&D Project of China [2012AA092203, 2012AA10A408, 2012AA10A403-2]; Education and Research of Guangdong Province [2013B090800017]; Taishan Scholar Climb Project Fund of Shandong of China; Taishan Scholar Project Fund of Shandong of China for Young Scientists; Shanghai Universities First-class Disciplines Project of Fisheries; Program for Professor of Special Appointment (Eastern Scholar) at the Shanghai Institutions of Higher Learning; Shanghai Municipal Science, Special Project on the Integration of Industryinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/publishedVersio

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

Genomic investigations of unexplained acute hepatitis in children

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children

Agricultural Work Exposures and Pulmonary Function Among Hired Farm Workers in California (The MICASA Study)

Despite Californias dependence on hired farm labor, scarce research has been conducted on the respiratory health of hired farm workers. Agricultural exposures to inorganic and organic dusts can adversely affect an individuals respiratory health and differ by farm type and job task. The purpose of the present analysis was to examine associations between agricultural work exposures and pulmonary function among 450 California farm workers. Data were collected as part of the Mexican Immigration to California: Agricultural Safety and Acculturation (MICASA) study, a prospective cohort study examining occupational risk factors and health of hired farm worker families in Mendota, California. Time-weighted self-reported average (TWSRA) dust scores were calculated from assessments of past-12-month agricultural work history. Other dust exposure indicator variables included months worked in agriculture in the past 12 months and years worked in agriculture. Multiple linear regression modeled FEV1 (forced expiratory volume in 1 second), FEF(25-75%) (forced midexpiratory flow rate), FVC (forced vital capacity), FEV6, FEV1/FVC, and FEV1/FEV6 separately. Seventy-six percent of participants had worked in agriculture in the past year. In models conducted for crops and tasks separately, high TWSRA dust score was associated with better FEV6. Crop and task models showed associations between greater months worked in agriculture in the past year and better FEV1, FEF(25-75%), and FEV6. Both models also found greater years worked in agriculture to be associated with worse FEV1/FEV6. Results were generally in the opposite direction as expected given past research but not uncommon. Future research should investigate relationships between pulmonary function and agricultural dust exposure over a lifetime and changes in pulmonary function over time