The Function of Fish Cytokines

Peer reviewedPublisher PD

Evolution of Interferons and Interferon Receptors

Peer reviewedPublisher PD

Comparative study of CXC chemokines modulation in brown trout (Salmo trutta) following infection with a bacterial or viral pathogen

Acknowledgements We would like to acknowledge Richard Paley, Tom Hill and Georgina Rimmer for their collaboration during brown trout infection challenges in CEFAS-Weymouth biosecurity facilities. Bartolomeo Gorgoglione, Stephen W. Feist and Nick G. H. Taylor were supported by a DEFRA grant (F1198).Peer reviewedPostprin

Energy Management Optimization for a Hybrid Tracked Vehicle Using the Radau Pseudospectral Method

AbstractThis study explored the feasibility of using the Radau pseudospectral method (RPM) to optimize the energy management strategy for a hybrid tracked vehicle. The engine–generator set and the battery pack of the serial hybrid tracked vehicle were modeled and validated through the bench test. A DC-DC converter was equipped between the battery pack and the DC bus in this hybrid powertrain, which increased the flexibility of energy distribution between the engine–generator set and the battery. The optimal control problem was formulated to minimize the fuel consumption through regulating the power distribution properly between the engine–generator set and battery pack during a typical driving schedule. The RPM was applied to transform the optimal control problem to a finite-dimensional constrained nonlinear programming problem. A comparison of the solutions from RPM and dynamic programming showed that the former offers the higher computation efficiency and better fuel economy

Rheumatoid arthritis-associated polymorphisms are not protective against Alzheimer\u27s disease

BACKGROUND: Rheumatoid arthritis (RA) and Alzheimer\u27s disease (AD) are inversely associated. To test the hypothesis that genetic elements associated with increased RA risk are associated with decreased AD risk, we evaluated RA genetic risk factors recently identified in genome-wide association studies (GWAS) for their association with AD in a two-stage, case-control analysis. RESULTS: In our Stage 1 analysis of ~800 AD and ~1,200 non-AD individuals, three of seventeen RA-associated SNPs were nominally associated with AD (p \u3c 0.05) with one SNP, rs2837960, retaining significance after correction for multiple testing (p = 0.03). The rs2837960_G (minor) allele, which is associated with increased RA risk, was associated with increased AD risk. Analysis of these three SNPs in a Stage 2 population, consisting of ~1,100 AD and ~2,600 non-AD individuals, did not confirm their association with AD. Analysis of Stage 1 and 2 combined suggested that rs2837960 shows a trend for association with AD. When the Stage 2 population was age-matched for the Stage 1 population, rs2837960 exhibited a non-significant trend with AD. Combined analysis of Stage 1 and the age-matched Stage 2 subset showed a significant association of rs2837960 with AD (p = 0.002, OR 1.24) that retained significance following correction for age, sex and APOE (p = 0.02, OR = 1.20). Rs2837960 is near BACE2, which encodes an aspartic protease capable of processing the AD-associated amyloid precursor protein. Testing for an association between rs2837960 and the expression of BACE2 isoforms in human brain, we observed a trend between rs2837960 and the total expression of BACE2 and the expression of a BACE2 transcript lacking exon 7 (p = 0.07 and 0.10, respectively). CONCLUSIONS: RA-associated SNPs are generally not associated with AD. Moreover, rs2837960_G is associated with increased risk of both RA and, in individuals less than 80 years of age, with AD. Overall, these results contest the hypothesis that genetic variants associated with RA confer protection against AD. Further investigation of rs2837960 is necessary to elucidate the mechanism by which rs2837960 contributes to both AD and RA risk, likely via modulation of BACE2 expression

Evaluation of the global association between cholesterol-associated polymorphisms and Alzheimer's disease suggests a role for rs3846662 and HMGCR splicing in disease risk

<p>Abstract</p> <p>Background</p> <p>Recent genome-wide association studies (GWAS) have identified single nucleotide polymorphisms (SNP)s that are essentially unequivocally associated with peripheral cholesterol. Since the alleles of the <it>APOE </it>gene, which modulate peripheral cholesterol metabolism, and midlife plasma cholesterol are both associated with Alzheimer's disease (AD) risk, we have evaluated the hypothesis that SNPs associated with plasma cholesterol are also associated with AD.</p> <p>Results</p> <p>Seventeen non-<it>APOE </it>SNPs reproducibly associated with cholesterol per GWAS were tested for association with AD in ~2,000 AD and ~4,000 non-AD subjects. As a group, these SNPs are associated with AD. Two SNPs in particular, rs3846662 and rs1532085, are associated with AD risk and age-of-onset. Additionally, rs3846662 was associated with <it>HMGCR </it>exon 13 splicing in human liver but not brain, possibly obscured by CNS cell-type heterogeneity. However, rs3846662 was associated with <it>HMGCR </it>exon 13 splicing in liver- and brain-derived cell lines.</p> <p>Conclusions</p> <p>Cholesterol-associated SNPs outside of <it>APOE </it>confer a global risk for AD. Rs3846662 and rs1532085 are associated with both AD risk and age-of-onset. Rs3846662 is associated with <it>HMGCR </it>exon 13 inclusion. Since rs3846662 affects AD risk and age-of-onset as well as statin responsiveness, this SNP may confound clinical trials evaluating the protective effects of statins on AD.</p

Evaluation of the global association between cholesterol-associated polymorphisms and Alzheimer\u27s disease suggests a role for rs3846662 and \u3cem\u3eHMGCR\u3c/em\u3e splicing in disease risk

BACKGROUND: Recent genome-wide association studies (GWAS) have identified single nucleotide polymorphisms (SNP)s that are essentially unequivocally associated with peripheral cholesterol. Since the alleles of the APOE gene, which modulate peripheral cholesterol metabolism, and midlife plasma cholesterol are both associated with Alzheimer\u27s disease (AD) risk, we have evaluated the hypothesis that SNPs associated with plasma cholesterol are also associated with AD. RESULTS: Seventeen non-APOE SNPs reproducibly associated with cholesterol per GWAS were tested for association with AD in ~2,000 AD and ~4,000 non-AD subjects. As a group, these SNPs are associated with AD. Two SNPs in particular, rs3846662 and rs1532085, are associated with AD risk and age-of-onset. Additionally, rs3846662 was associated with HMGCR exon 13 splicing in human liver but not brain, possibly obscured by CNS cell-type heterogeneity. However, rs3846662 was associated with HMGCR exon 13 splicing in liver- and brain-derived cell lines. CONCLUSIONS: Cholesterol-associated SNPs outside of APOE confer a global risk for AD. Rs3846662 and rs1532085 are associated with both AD risk and age-of-onset. Rs3846662 is associated with HMGCR exon 13 inclusion. Since rs3846662 affects AD risk and age-of-onset as well as statin responsiveness, this SNP may confound clinical trials evaluating the protective effects of statins on AD

Rheumatoid arthritis-associated polymorphisms are not protective against Alzheimer's disease

<p>Abstract</p> <p>Background</p> <p>Rheumatoid arthritis (RA) and Alzheimer's disease (AD) are inversely associated. To test the hypothesis that genetic elements associated with increased RA risk are associated with decreased AD risk, we evaluated RA genetic risk factors recently identified in genome-wide association studies (GWAS) for their association with AD in a two-stage, case-control analysis.</p> <p>Results</p> <p>In our Stage 1 analysis of ~800 AD and ~1,200 non-AD individuals, three of seventeen RA-associated SNPs were nominally associated with AD (p < 0.05) with one SNP, rs2837960, retaining significance after correction for multiple testing (p = 0.03). The rs2837960_G (minor) allele, which is associated with increased RA risk, was associated with increased AD risk. Analysis of these three SNPs in a Stage 2 population, consisting of ~1,100 AD and ~2,600 non-AD individuals, did not confirm their association with AD. Analysis of Stage 1 and 2 combined suggested that rs2837960 shows a trend for association with AD. When the Stage 2 population was age-matched for the Stage 1 population, rs2837960 exhibited a non-significant trend with AD. Combined analysis of Stage 1 and the age-matched Stage 2 subset showed a significant association of rs2837960 with AD (p = 0.002, OR 1.24) that retained significance following correction for age, sex and APOE (p = 0.02, OR = 1.20). Rs2837960 is near <it>BACE2</it>, which encodes an aspartic protease capable of processing the AD-associated amyloid precursor protein. Testing for an association between rs2837960 and the expression of <it>BACE2 </it>isoforms in human brain, we observed a trend between rs2837960 and the total expression of <it>BACE2 </it>and the expression of a <it>BACE2 </it>transcript lacking exon 7 (p = 0.07 and 0.10, respectively).</p> <p>Conclusions</p> <p>RA-associated SNPs are generally not associated with AD. Moreover, rs2837960_G is associated with increased risk of both RA and, in individuals less than 80 years of age, with AD. Overall, these results contest the hypothesis that genetic variants associated with RA confer protection against AD. Further investigation of rs2837960 is necessary to elucidate the mechanism by which rs2837960 contributes to both AD and RA risk, likely via modulation of <it>BACE2 </it>expression.</p