Array E Subpack 1 dynamic analysis

This ATM presents the results of the dynamic analyses performed on two different versions of ALSEP Array E - Subpack I. One version contained the Lunar Surface Gravimeter ( LSG) experiment, among others, while the other version contained the Passive Seismic Experiment (PSE) in place of the LSG. The analysis was undertaken to obtain an early estimate of the experiment dynamic environments and dynamic loads in order to compare these with previous Subpack I arrays.prepared by G. B. Min, K. H. Wadleigh.Introduction and summary -- Analysis models -- Computed acceleration responses -- Dynamic loads

Quantitative assay for the detection of the V617F variant in the Janus kinase 2 (JAK2) gene using the Luminex xMAP technology

<p>Abstract</p> <p>Background</p> <p>The availability of clinically valid biomarkers contribute to improve the diagnosis and clinical management of diseases. A valine-to-phenylalanine substitution at position 617 (V617F) in the Janus kinase 2 (JAK2) gene has been recently associated with key signaling abnormalities in the transduction of haemopoietic growth-factor receptors and is now considered as a useful clinical marker of myeloproliferative neoplasms. Several methods have recently been reported to detect the JAK2 V617F point mutation and show variable sensitivity.</p> <p>Methods</p> <p>Using the Luminex xMAP technology, we developed a quantitative assay to detect the JAK2V617F variant. The method was based on polymerase chain reaction (PCR) followed by hybridization to specific probes coupled with internally dyed microspheres. The assay comprises 3 steps: genomic DNA extraction, end point PCR reaction, direct hybridization of PCR fragments and quantification. It has been tested with different sources of nucleic acid.</p> <p>Results</p> <p>Applied to whole blood samples, this quantitative assay showed a limit of detection of 2%. A highly sensitive allele-specific primer extension reaction performed in parallel allowed to validate the results and to identify the specimens with values below 2%.</p> <p>Conclusion</p> <p>Direct hybridization assay using the Luminex xMAP technology allows sensitive quantification of JAK2V617F from blood spots. It is simple and can be easily performed in a clinical setting.</p

Relevance of JAK2V617F positivity to hematological diseases - survey of samples from a clinical genetics laboratory

<p>Abstract</p> <p>Background</p> <p>JAK2V617F is found in the majority of patients with Ph- myeloproliferative neoplasms (MPNs) and has become a valuable marker for diagnosis of MPNs. However, it has also been found in many other hematological diseases, and some studies even detected the presence of JAK2V617F in normal blood samples. This casts doubt on the primary role of JAK2V617F in the pathogenesis of MPNs and its diagnostic value.</p> <p>Methods</p> <p>In the present study, we analyzed JAK2V617F positivity with 232 normal blood samples and 2663 patient blood, bone marrow, and amniotic fluid specimens obtained from a clinical genetics laboratory by using a simple DNA extraction method and a sensitive nested allele-specific PCR strategy.</p> <p>Results</p> <p>We found JAK2V617F present in the majority (78%) of MPN patients and in a small fraction (1.8-8.7%) of patients with other specific hematological diseases but not at all in normal healthy donors or patients with non-hematological diseases. We also revealed associations of JAK2V617F with novel as well as known chromosomal abnormalities.</p> <p>Conclusions</p> <p>Our study suggests that JAK2V617F positivity is associated with specific hematological malignancies and is an excellent diagnostic marker for MPNs. The data also indicate that the nested allele-specific PCR method provides clinically relevant information and should be conducted for all cases suspected of having MPNs as well as for other related diseases.</p

Biochemical warfare on the reef : the role of glutathione transferases in consumer tolerance of dietary prostaglandins

© 2010 The Authors. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in PLoS ONE 5 (2010): e8537, doi:10.1371/journal.pone.0008537.Despite the profound variation among marine consumers in tolerance for allelochemically-rich foods, few studies have examined the biochemical adaptations underlying diet choice. Here we examine the role of glutathione S-transferases (GSTs) in the detoxification of dietary allelochemicals in the digestive gland of the predatory gastropod Cyphoma gibbosum, a generalist consumer of gorgonian corals. Controlled laboratory feeding experiments were used to investigate the influence of gorgonian diet on Cyphoma GST activity and isoform expression. Gorgonian extracts and semi-purified fractions were also screened to identify inhibitors and possible substrates of Cyphoma GSTs. In addition, we investigated the inhibitory properties of prostaglandins (PGs) structurally similar to antipredatory PGs found in high concentrations in the Caribbean gorgonian Plexaura homomalla. Cyphoma GST subunit composition was invariant and activity was constitutively high regardless of gorgonian diet. Bioassay-guided fractionation of gorgonian extracts revealed that moderately hydrophobic fractions from all eight gorgonian species examined contained putative GST substrates/inhibitors. LC-MS and NMR spectral analysis of the most inhibitory fraction from P. homomalla subsequently identified prostaglandin A2 (PGA2) as the dominant component. A similar screening of commercially available prostaglandins in series A, E, and F revealed that those prostaglandins most abundant in gorgonian tissues (e.g., PGA2) were also the most potent inhibitors. In vivo estimates of PGA2 concentration in digestive gland tissues calculated from snail grazing rates revealed that Cyphoma GSTs would be saturated with respect to PGA2 and operating at or near physiological capacity. The high, constitutive activity of Cyphoma GSTs is likely necessitated by the ubiquitous presence of GST substrates and/or inhibitors in this consumer's gorgonian diet. This generalist's GSTs may operate as ‘all-purpose’ detoxification enzymes, capable of conjugating or sequestering a broad range of lipophilic gorgonian compounds, thereby allowing this predator to exploit a range of chemically-defended prey, resulting in a competitive dietary advantage for this species.Financial support for this work was provided by the Ocean Life Institute Tropical Research Initiative Grant (WHOI) to KEW and MEH; the Robert H. Cole Endowed Ocean Ventures Fund (WHOI) to KEW; the National Undersea Research Center - Program Development Proposal (CMRC-03PRMN0103A) to KEW; Walter A. and Hope Noyes Smith, and a National Science Foundation Graduate Research Fellowship to KEW

Association analyses of the interaction between the ADSS and ATM genes with schizophrenia in a Chinese population

<p>Abstract</p> <p>Background</p> <p>The blood-derived RNA levels of the adenylosuccinate synthase (<it>ADSS</it>) and ataxia telangiectasia mutated (<it>ATM</it>) genes were found to be down- and up-regulated, respectively, in schizophrenics compared with controls, and <it>ADSS </it>and <it>ATM </it>were among eight biomarker genes to discriminate schizophrenics from normal controls. ADSS catalyzes the first committed step of AMP synthesis, while ATM kinase serves as a key signal transducer in the DNA double-strand breaks response pathway. It remains unclear whether these changes result from mutations or polymorphisms in the two genes.</p> <p>Methods</p> <p>Six SNPs in the <it>ADSS </it>gene and three SNPs in the <it>ATM </it>gene in a Chinese population of 488 schizophrenics and 516 controls were genotyped to examine their association with schizophrenia (SZ). Genotyping was performed using the Sequenom platform.</p> <p>Results</p> <p>There was no significant difference in the genotype, allele, or haplotype distributions of the nine SNPs between cases and controls. Using the Multifactor Dimensionality Reduction (MDR) method, we found that the interactions among rs3102460 in the <it>ADSS </it>gene and rs227061 and rs664143 in the <it>ATM </it>gene revealed a significant association with SZ. This model held a maximum testing accuracy of 60.4% and a maximum cross-validation consistency of 10 out of 10.</p> <p>Conclusion</p> <p>These findings suggest that the combined effects of the polymorphisms in the <it>ADSS </it>and <it>ATM </it>genes may confer susceptibility to the development of SZ in a Chinese population.</p

Polymorphisms in the interleukin-10 gene cluster are possibly involved in the increased risk for major depressive disorder

<p>Abstract</p> <p>Background</p> <p>Innate immune inflammatory response is suggested to have a role in the pathogenesis of major depressive disorder (MDD). Interleukin (IL)-10 family cytokines IL-10, IL-19, IL-20, and IL-24 are all implicated in the inflammatory processes and polymorphisms in respective genes have been associated with various immunopathological conditions. This study was carried out to investigate whether single-nucleotide polymorphisms (SNPs) in these genes are also associated with MDD.</p> <p>Methods</p> <p>Case-control association study was performed with seven SNPs from the <it>IL10 </it>gene cluster. 153 patients with MDD and 277 healthy control individuals were recruited.</p> <p>Results</p> <p>None of the selected SNPs were individually associated with MDD. The linkage disequilibrium (LD) analysis indicated the existence of two recombination sites in the <it>IL10 </it>gene cluster, thus confirming the formerly established LD pattern of this genomic region. This also created two haplotype blocks, both consisting of three SNPs. Additionally, the haplotype analysis detected a significantly higher frequency of block 2 (<it>IL20 </it>and <it>IL24 </it>genes) haplotype TGC in the patients group compared to healthy control individuals (P = 0.0097).</p> <p>Conclusion</p> <p>Our study established increased risk for MDD related to the <it>IL20 </it>and <it>IL24 </it>haplotype and suggests that cytokines may contribute to the pathogenesis of MDD. Since none of the block 2 SNPs were individually associated with MDD, it is possible that other polymorphisms linked to them contribute to the disease susceptibility. Future studies are needed to confirm the results and to find the possible functional explanation.</p

Increased d-amino acid oxidase expression in the bilateral hippocampal CA4 of schizophrenic patients: a post-mortem study

An important risk gene in schizophrenia is d-amino acid oxidase (DAAO). To establish if expression of DAAO is altered in cortical, hippocampal or thalamic regions of schizophrenia patients, we measured gene expression of DAAO in a post-mortem study of elderly patients with schizophrenia and non-affected controls in both hemispheres differentiating between gray and white matter. We compared cerebral post-mortem samples (granular frontal cortex BA9, middle frontal cortex BA46, superior temporal cortex BA22, entorhinal cortex BA28, sensoric cortex BA1–3, hippocampus (CA4), mediodorsal nucleus of the thalamus) from 10 schizophrenia patients to 13 normal subjects investigating gene expression of DAAO in the gray and white matter of both hemispheres of the above-mentioned brain regions by in situ-hybridization. We found increased expression of DAAO-mRNA in the hippocampal CA4 of schizophrenic patients. Compared to the control group, both hemispheres of the hippocampus of schizophrenic patients showed an increased expression of 46% (right, P = 0.013) and 54% (left, P = 0.019), respectively. None of the other regions examined showed statistically significant differences in DAAO expression. This post-mortem study demonstrated increased gene expression of DAAO in the left and right hippocampus of schizophrenia patients. This increased expression could be responsible for a decrease in local d-serine levels leading to a NMDA-receptor hypofunction that is hypothesized to play a major role in the pathophysiology of schizophrenia. However, our study group was small and results should be verified using larger samples