Transcription profiling by array of gills from Gulf killifish Fundulus grandis collected at three field sites over four time points before and after the arrival of contaminating crude oil spill
ABSTRACT: In this study we characterize the gill transcriptome changes that coincide with the arrival of contaminating oil in field-collected Gulf killifish Fundulus grandis. Gill transcription was contrasted before and after the arrival of oil, and between oil impacted and reference sites. Animals were sampled from field sites at four times. The oil impacted site is Grand Terre Island Louisiana (GT) and the two reference sites are Bay St. Louis Mississippi (BSL) and Bayou La Batre Alabama (BLB). The first timepoint (05/01/2010 to 05/09/2010) was before the arrival of contaminating oil, the second and third timepoints (06/28/2010 to 06/29/2010, and 08/30/2010 to 09/01/2010) were after the arrival of contaminating oil, and the fourth timepoint 08/28/2011) was over a year after the arrival of contaminating oil.
Project description:The Deepwater Horizon oil rig disaster resulted in crude oil contamination along the Gulf coast in sensitive estuaries. Toxicity from exposure to crude oil can affect populations of fish that live or breed in oiled habitats as seen following the Exxon Valdez oil spill. In an ongoing study of the effects of Deepwater Horizon crude oil on fish, Gulf killifish ( Fundulus grandis ) were collected from an oiled site (Grande Terre, LA) and two reference locations (coastal MS and AL) and monitored for measures of exposure to crude oil. Killifish collected from Grande Terre had divergent gene expression in the liver and gill tissue coincident with the arrival of contaminating oil and up-regulation of cytochrome P4501A (CYP1A) protein in gill, liver, intestine, and head kidney for over one year following peak landfall of oil (August 2011) compared to fish collected from reference sites. Furthermore, laboratory exposures of Gulf killifish embryos to field-collected sediments from Grande Terre and Barataria Bay, LA, also resulted in increased CYP1A and developmental abnormalities when exposed to sediments collected from oiled sites compared to exposure to sediments collected from a reference site. These data are predictive of population-level impacts in fish exposed to sediments from oiled locations along the Gulf of Mexico coast.
Project description:Aims/Introduction:? Fulminant type 1 diabetes is a subtype of type 1 diabetes characterized by a remarkably abrupt onset of insulin-deficient hyperglycemia within a few days. The aim of the present study was to clarify characteristic class II HLA genotypes in a large number of patients with fulminant type 1 diabetes to date.? We analyzed the HLA-DRB1 and DQB1 genotypes, and their haplotypes in 207 patients with fulminant type 1 diabetes and 325 control subjects in the Japanese population.? The frequencies of the DRB1*04:05-DQB1*04:01 and DRB1*09:01-DQB1*03:03 haplotypes were significantly higher, and those of the DRB1*01:01-DQB1*05:01, DRB1*15:02-DQB1*06:01 and DRB1*08:03-DQB1*06:01 haplotypes were significantly lower in patients with fulminant type 1 diabetes than in the control subjects. Combination analysis showed that the frequencies of homozygotes with DRB1*04:05-DQB1*04:01 [odds ratio (OR) 7.0] and DRB1*09:01-DQB1*03:03 (OR 9.5) were significantly higher in patients with fulminant type 1 diabetes. Within a limited portion of patients with fulminant type 1 diabetes with antibodies to glutamic acid decarboxylase (GADab; n?=?25), the frequency of DRB1*09:01-DQB1*03:03, but not DRB1*04:05-DQB1*04:01, was significantly higher than in control subjects (44.0% vs 13.7%; Pc?<?0.05, OR 5.0). [Correction to last line of RESULTS, added after online publication 29 July 2011: "OR 5.1" is changed to "OR 5.0".]? Our large-scale study showed the characteristic class II HLA genotypes in fulminant type 1 diabetes, and implicated that genetic contribution to disease susceptibility is distinct between GADab-positive and GADab-negative fulminant type 1 diabetes. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2011.00139.x, 2012).
Project description:NS3/4A protease is an important emerging target for the cure of hepatitis C. There are many inhibitors of HCV NS3/4A protease that are passing through the clinical improvement indicating momentous reduction in the viral infection rate of patients. In this study molecular docking via MOE-Dock program was used to evaluate binding interactions of ligands with HCV NS3/4A protease. The docking and experimental results were found in good correlation. The best conformations of ligands were analyzed for binding interactions with the residues of binding cavity of NS3/4A protease. The valuable binding interactions and docking scores were observed for compounds 01, 05, 06, 07, 08 and 09.
Project description:The biological consequences of the Deepwater Horizon oil spill are unknown, especially for resident organisms. Here, we report results from a field study tracking the effects of contaminating oil across space and time in resident killifish during the first 4 mo of the spill event. Remote sensing and analytical chemistry identified exposures, which were linked to effects in fish characterized by genome expression and associated gill immunohistochemistry, despite very low concentrations of hydrocarbons remaining in water and tissues. Divergence in genome expression coincides with contaminating oil and is consistent with genome responses that are predictive of exposure to hydrocarbon-like chemicals and indicative of physiological and reproductive impairment. Oil-contaminated waters are also associated with aberrant protein expression in gill tissues of larval and adult fish. These data suggest that heavily weathered crude oil from the spill imparts significant biological impacts in sensitive Louisiana marshes, some of which remain for over 2 mo following initial exposures.
Project description:Seasonal influenza causes considerable morbidity and mortality across all age groups, and influenza vaccination was recommended in 2010 for all persons aged 6 months and above. We estimated the averted costs due to influenza vaccination, taking into account the seasonal economic burden of the disease.We used recently published values for averted outcomes due to influenza vaccination for influenza seasons 2005-06, 2006-07, 2007-08, and 2008-09, and age cohorts 6 months-4 years, 5-19 years, 20-64 years, and 65 years and above. Costs were calculated according to a payer and societal perspective (in 2009 US$), and took into account medical costs and productivity losses.When taking into account direct medical costs (payer perspective), influenza vaccination was cost saving only for the older age group (65?) in seasons 2005-06 and 2007-08. Using the same perspective, influenza vaccination resulted in total costs of $US 1.7 billion (95%CI: $US 0.3-4.0 billion) in 2006-07 and $US 1.8 billion (95%CI: $US 0.1-4.1 billion) in 2008-09. When taking into account a societal perspective (and including the averted lost earnings due to premature death) averted deaths in the older age group influenced the results, resulting in cost savings for all ages combined in season 07-08.Influenza vaccination was cost saving in the older age group (65?) when taking into account productivity losses and, in some seasons, when taking into account medical costs only. Averted costs vary significantly per season; however, in seasons where the averted burden of deaths is high in the older age group, averted productivity losses due to premature death tilt overall seasonal results towards savings. Indirect vaccination effects and the possibility of diminished case severity due to influenza vaccination were not considered, thus the averted burden due to influenza vaccine may be even greater than reported.
Project description:Latent autoimmune diabetes in adults (LADA) was recently demonstrated to be the most frequent form of adult-onset autoimmune diabetes mellitus. Case-control studies have investigated the relationship between human leukocyte antigen (HLA)-DQB1 and HLA-DRB1 polymorphisms and LADA risk, but their conclusions are inconsistent. This study aimed to more precisely explore the correlation between these HLA gene variants and LADA development. Eight databases, including PubMed, Embase, and Medline, were systematically searched for relevant studies up to September 15, 2018. We performed this retrospective study using meta-analysis and relative predispositional effect (RPE) methods. The meta-analysis results indicated that DQB1*02 (odds ratio (OR) = 1.685, pc < 0.005) and DQB1*06 (OR = 0.604, pc = 0.010) have opposite effects on susceptibility to LADA, while a significant decrease in LADA risk caused by DQB1*05 (OR = 0.764, pc = 0.100) disappeared upon Bonferroni correction. The RPE method confirmed the roles of DQB1*02 (χ² = 46.475, p < 0.001) and DQB1*06 (χ² = 17.883, p < 0.001) and further suggested protective effects of DQB1*05 (χ² = 16.496, p < 0.001). Additionally, the meta-analysis results showed that DRB1*03 (OR = 2.685, pc < 0.013), DRB1*04 (OR = 1.954, pc < 0.013), and DRB1*09 (OR = 1.346, pc < 0.013) are associated with increased LADA risk, while DRB1*12 (OR = 0.600, pc < 0.013) and DRB1*13 (OR = 0.583, pc < 0.013) carriers have a decreased risk of developing LADA. Furthermore, the RPE method revealed that DRB1*03 (χ² = 98.754, p < 0.001), DRB1*04 (χ² = 94.685, p < 0.001), DRB1*09 (χ² = 40.489, p < 0.001), DRB1*01 (χ² = 12.181, p < 0.001), DRB1*07 (χ² = 10.882, p = 0.001), and DRB1*08 (χ² = 5.000, p = 0.025) play protective roles against LADA. LADA showed a close relationship with genetic polymorphisms of HLA-DQB1 and WHLA-DRB1, which could contribute to a better understanding of disease pathogenesis and the identification of predisposing loci in the diagnosis and treatment of LADA.
Project description:In this study we characterize the gill transcriptome changes in Gulf killifish (Fundulus grandis) that coincide with controlled laboratory-based exposure to various concentrations of experimentally-weathered south Louisiana crude oil. Gill transcription was contrasted between doses and across timepoints following dosing.
Project description:Hepatitis-hydropericardium syndrome (HHS) is a severe disease that causes 20 to 80% mortality in chickens aged 3 to 6 wk. Fowl aviadenovirus serotype 4 (FAdV-4) plays an important role in the etiology of HHS. Since 2015, outbreaks of HHS have been reported in several provinces of China; however, details regarding the FAdV-4 genome properties are lacking. In the present study, the complete genomes of 9 isolates responsible for these outbreaks in Guangxi Province, China, were sequenced. To investigate the molecular characteristics of these FAdV-4 isolates, we compared their genomes with those of other reported pathogenic and nonpathogenic FAdV-4 isolates. A variable number of GA repeats were observed in the isolates of this study. Each of the isolates GX2017-01, GX2017-02, GX2018-08, and GX2019-09 had 11 GA repeats; GX2017-03, GX2017-04, and GX2017-05 each had 10 GA repeats, while GX2017-06 and GX2018-07 each had 8 GA repeats. We observed several deletions and distinct amino acid mutations in the major structural genes of these isolates when compared with non-Chinese isolates. We found 2 novel putative genetic markers in the hexon protein, one present in GX2017-02, in which aspartic acid (D) was changed to tyrosine (Y), and another present in each of isolates GX2018-08 and GX2019-09, in which serine (S) was changed to arginine (R), when compared with selected Chinese and some non-Chinese isolates. Moreover, the phylogenetic analysis revealed that all the isolates of this study were clustered within FAdV-C. We found that these isolates were closely related to other recently isolated Chinese strains. The data presented in this study will not only increase the understanding of the molecular epidemiology and genetic diversity of FAdV-4 isolates in China but also has an important reference value of the major factors that determine the virulence of FAdV-4 strains.
Project description:Background:The high burden of infectious disease and associated antimicrobial use likely contribute to the emergence of antimicrobial resistance in remote Australian Aboriginal communities. We aimed to develop and apply context-specific tools to audit antimicrobial use in the remote primary healthcare setting. Methods:We adapted the General Practice version of the National Antimicrobial Prescribing Survey (GP NAPS) tool to audit antimicrobial use over 2-3 weeks in 15 remote primary healthcare clinics across the Kimberley region of Western Australia (03/2018-06/2018), Top End of the Northern Territory (08/2017-09/2017) and far north Queensland (05/2018-06/2018). At each clinic we reviewed consecutive clinic presentations until 30 presentations where antimicrobials had been used were included in the audit. Data recorded included the antimicrobials used, indications and treating health professional. We assessed the appropriateness of antimicrobial use and functionality of the tool. Results:We audited the use of 668 antimicrobials. Skin and soft tissue infections were the dominant treatment indications (WA: 35%; NT: 29%; QLD: 40%). Compared with other settings in Australia, narrow spectrum antimicrobials like benzathine benzylpenicillin were commonly given and the appropriateness of use was high (WA: 91%; NT: 82%; QLD: 65%). While the audit was informative, non-integration with practice software made the process manually intensive. Conclusions:Patterns of antimicrobial use in remote primary care are different from other settings in Australia. The adapted GP NAPS tool functioned well in this pilot study and has the potential for integration into clinical care. Regular stewardship audits would be facilitated by improved data extraction systems.
Project description:Neurofilament light chain (NfL) is a blood marker for neuroaxonal damage. We assessed the association between serum NfL and cerebral small vessel disease (SVD), which is highly prevalent in elderly individuals and a major cause of stroke and vascular cognitive impairment.Using a cross-sectional design, we studied 53 and 439 patients with genetically defined SVD (Cerebral Autosomal-Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy [CADASIL]) and sporadic SVD, respectively, as well as 93 healthy controls. Serum NfL was measured by an ultrasensitive single-molecule array assay. We quantified magnetic resonance imaging (MRI) markers of SVD, i.e., white matter hyperintensity volume, lacune volume, brain volume, microbleed count, and mean diffusivity obtained from diffusion tensor imaging. Clinical characterization included neuropsychological testing in both SVD samples. CADASIL patients were further characterized for focal neurological deficits (National Institutes of Health stroke scale [NIHSS]) and disability (modified Rankin scale [mRS]).Serum NfL levels were elevated in both SVD samples (P<1e-05 compared with controls) and associated with all SVD MRI markers. The strongest association was found for mean diffusivity (CADASIL, R2=0.52, P=1.2e-09; sporadic SVD, R2=0.21, P<1e-15). Serum NfL levels were independently related to processing speed performance (CADASIL, R2=0.27, P=7.6e-05; sporadic SVD, R2=0.06, P=4.8e-08), focal neurological symptoms (CADASIL, NIHSS, P=4.2e-05) and disability (CADASIL, mRS, P=3.0e-06).We found serum NfL levels to be associated with both imaging and clinical features of SVD. Serum NfL might complement MRI markers in assessing SVD burden. Importantly, SVD needs to be considered when interpreting serum NfL levels in the context of other age-related diseases.