53 research outputs found

    Gene Structure Evolution of the Na+-Ca2+ Exchanger (NCX) Family

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    <p>Abstract</p> <p>Background</p> <p>The Na<sup>+</sup>-Ca<sup>2+ </sup>exchanger (NCX) is an important regulator of cytosolic Ca<sup>2+ </sup>levels. Many of its structural features are highly conserved across a wide range of species. Invertebrates have a single <it>NCX </it>gene, whereas vertebrate species have multiple <it>NCX </it>genes as a result of at least two duplication events. To examine the molecular evolution of <it>NCX </it>genes and understand the role of duplicated genes in the evolution of the vertebrate <it>NCX </it>gene family, we carried out phylogenetic analyses of <it>NCX </it>genes and compared <it>NCX </it>gene structures from sequenced genomes and individual clones.</p> <p>Results</p> <p>A single <it>NCX </it>in invertebrates and the protochordate <it>Ciona</it>, and the presence of at least four <it>NCX </it>genes in the genomes of teleosts, an amphibian, and a reptile suggest that a four member gene family arose in a basal vertebrate. Extensive examination of mammalian and avian genomes and synteny analysis argue that <it>NCX4 </it>may be lost in these lineages. Duplicates for <it>NCX1</it>, <it>NCX2</it>, and <it>NCX4 </it>were found in all sequenced teleost genomes. The presence of seven genes encoding <it>NCX </it>homologs may provide teleosts with the functional specialization analogous to the alternate splicing strategy seen with the three <it>NCX </it>mammalian homologs.</p> <p>Conclusion</p> <p>We have demonstrated that <it>NCX4 </it>is present in teleost, amphibian and reptilian species but has been secondarily and independently lost in mammals and birds. Comparative studies on conserved vertebrate homologs have provided a possible evolutionary route taken by gene duplicates subfunctionalization by minimizing homolog number.</p

    Postrelease survival, vertical and horizontal movements, and thermal habitats of five species of pelagic sharks in the central Pacific Ocean

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    From 2001 to 2006, 71 pop-up satellite archival tags (PSATs) were deployed on five species of pelagic shark (blue shark [Prionace glauca]; shortfin mako [Isurus oxyrinchus]; silky shark [Carcharhinus falciformis]; oceanic whitetip shark [C. longimanus]; and bigeye thresher [Alopias superciliosus]) in the central Pacific Ocean to determine species-specific movement patterns and survival rates after release from longline fishing gear. Only a single postrelease mortality could be unequivocally documented: a male blue shark which succumbed seven days after release. Meta-analysis of published reports and the current study (n=78 reporting PSATs) indicated that the summary effect of postrelease mortality for blue sharks was 15% (95% CI, 8.5–25.1%) and suggested that catch-and-release in longline fisheries can be a viable management tool to protect parental biomass in shark populations. Pelagic sharks displayed species-specific depth and temperature ranges, although with significant individual temporal and spatial variability in vertical movement patterns, which were also punctuated by stochastic events (e.g., El Niño-Southern Oscillation). Pelagic species can be separated into three broad groups based on daytime temperature preferences by using the unweighted pair-group method with arithmetic averaging clustering on a Kolmogorov-Smirnov Dmax distance matrix: 1) epipelagic species (silky and oceanic whitetip sharks), which spent >95% of their time at temperatures within 2°C of sea surface temperature; 2) mesopelagic-I species (blue sharks and shortfin makos, which spent 95% of their time at temperatures from 9.7° to 26.9°C and from 9.4° to 25.0°C, respectively; and 3) mesopelagic-II species (bigeye threshers), which spent 95% of their time at temperatures from 6.7° to 21.2°C. Distinct thermal niche partitioning based on body size and latitude was also evident within epipelagic species

    Stress Preconditioning of Spreading Depression in the Locust CNS

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    Cortical spreading depression (CSD) is closely associated with important pathologies including stroke, seizures and migraine. The mechanisms underlying SD in its various forms are still incompletely understood. Here we describe SD-like events in an invertebrate model, the ventilatory central pattern generator (CPG) of locusts. Using K+ -sensitive microelectrodes, we measured extracellular K+ concentration ([K+]o) in the metathoracic neuropile of the CPG while monitoring CPG output electromyographically from muscle 161 in the second abdominal segment to investigate the role K+ in failure of neural circuit operation induced by various stressors. Failure of ventilation in response to different stressors (hyperthermia, anoxia, ATP depletion, Na+/K+ ATPase impairment, K+ injection) was associated with a disturbance of CNS ion homeostasis that shares the characteristics of CSD and SD-like events in vertebrates. Hyperthermic failure was preconditioned by prior heat shock (3 h, 45°C) and induced-thermotolerance was associated with an increase in the rate of clearance of extracellular K+ that was not linked to changes in ATP levels or total Na+/K+ ATPase activity. Our findings suggest that SD-like events in locusts are adaptive to terminate neural network operation and conserve energy during stress and that they can be preconditioned by experience. We propose that they share mechanisms with CSD in mammals suggesting a common evolutionary origin

    The association between human endogenous retroviruses and multiple sclerosis: a systematic review and meta-analysis

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    Background: The interaction between genetic and environmental factors is crucial to multiple sclerosis (MS) pathogenesis. Human Endogenous Retroviruses (HERVs) are endogenous viral elements of the human genome whose expression is associated with MS. Objective: To perform a systematic review and meta-analysis and to assess qualitative and quantitative evidence on the expression of HERV families in MS patients. Methods: Medline, Embase and the Cochrane Library were searched for published studies on the association of HERVs and MS. Meta-analysis was performed on the HERV-W family. Odds Ratio (OR) and 95% confidence interval (CI) were calculated for association. Results: 43 reports were extracted (25 related to HERV-W, 13 to HERV-H, 9 to HERV-K, 5 to HRES-1 and 1 to HER-15 family). The analysis showed an association between expression of all HERV families and MS. For HERV-W, adequate data was available for meta-analysis. Results from meta-analyses of HERV-W were OR = 22.66 (95%CI 6.32 to 81.20) from 4 studies investigating MSRV/HERV-W(MS-associated retrovirus) envelope mRNA in peripheral blood mononuclear cells, OR = 44.11 (95%CI 12.95 to 150.30) from 6 studies of MSRV/ HERV-W polymerase mRNA in serum/plasma and OR = 6.00 (95%CI 3.35 to 10.74) from 4 studies of MSRV/HERV-W polymerase mRNA in CSF

    Global respiratory syncytial virus–related infant community deaths

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    Background Respiratory syncytial virus (RSV) is a leading cause of pediatric death, with >99% of mortality occurring in low- and lower middle-income countries. At least half of RSV-related deaths are estimated to occur in the community, but clinical characteristics of this group of children remain poorly characterized. Methods The RSV Global Online Mortality Database (RSV GOLD), a global registry of under-5 children who have died with RSV-related illness, describes clinical characteristics of children dying of RSV through global data sharing. RSV GOLD acts as a collaborative platform for global deaths, including community mortality studies described in this supplement. We aimed to compare the age distribution of infant deaths <6 months occurring in the community with in-hospital. Results We studied 829 RSV-related deaths <1 year of age from 38 developing countries, including 166 community deaths from 12 countries. There were 629 deaths that occurred <6 months, of which 156 (25%) occurred in the community. Among infants who died before 6 months of age, median age at death in the community (1.5 months; IQR: 0.8−3.3) was lower than in-hospital (2.4 months; IQR: 1.5−4.0; P < .0001). The proportion of neonatal deaths was higher in the community (29%, 46/156) than in-hospital (12%, 57/473, P < 0.0001). Conclusions We observed that children in the community die at a younger age. We expect that maternal vaccination or immunoprophylaxis against RSV will have a larger impact on RSV-related mortality in the community than in-hospital. This case series of RSV-related community deaths, made possible through global data sharing, allowed us to assess the potential impact of future RSV vaccines

    Abstracts from the 8th International Conference on cGMP Generators, Effectors and Therapeutic Implications

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    This work was supported by a restricted research grant of Bayer AG
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