1,056 research outputs found

    Comparative structures and evolution of vertebrate lipase H (LIPH) genes and proteins: a relative of the phospholipase A1 gene families

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    Lipase H (LIPH) is a membrane-bound phospholipase generating 2-acyl lysophosphatidic acid (LPA) in the body. LPA is a lipid mediator required for maintaining homeostasis of diverse biological functions and in activating cell surface receptors such as P2Y5, which plays an essential role in hair growth. Bioinformatic methods were used to predict the amino acid sequences, secondary and tertiary structures, and gene locations for LIPH genes and encoded proteins using data from several vertebrate genome projects. Vertebrate LIPH genes contained ten coding exons transcribed on either the positive or negative DNA strands. Evidence is presented for duplicated LIPH genes for the chicken and zebra fish genomes. Vertebrate LIPH protein subunits shared 56–97 % sequence identities and exhibited sequence alignments and identities for key LIPH amino acid residues as well as extensive conservation of predicted secondary and tertiary structures with those previously reported for horse pancreatic lipase (LIPP), with ‘N-signal peptide’, ‘lipase,’ and ‘plat’ structural domains. Comparative studies of vertebrate LIPH sequences with other phospholipase A1-like lipases (LIPI and PS-PLA1), as well as vascular and pancreatic lipases, confirmed predictions for LIPH N-terminal signal peptides (residues 1–18); a conserved vertebrate LIPH N-glycosylation site (66NVT for human LIPH); active site ‘triad’ residues (Ser 154; Asp 178; His 248); disulfide bond residues (233–246; 270–281; 284–292; 427–446), and a ‘short’ 12 residue ‘active site lid’, which is comparable to other phospholipases examined. Phylogenetic analyses demonstrated the relationships and potential evolutionary origins of the vertebrate LIPH family of genes related to, but distinct from other phospholipase A1-like genes (LIPI and PS-PLA1), and from vascular lipase and pancreatic lipase gene families. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s13205-012-0087-z) contains supplementary material, which is available to authorized users

    Opossum carboxylesterases: sequences, phylogeny and evidence for CES gene duplication events predating the marsupial-eutherian common ancestor

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    Background Carboxylesterases (CES) perform diverse metabolic roles in mammalian organisms in the detoxification of a broad range of drugs and xenobiotics and may also serve in specific roles in lipid, cholesterol, pheromone and lung surfactant metabolism. Five CES families have been reported in mammals with human CES1 and CES2 the most extensively studied. Here we describe the genetics, expression and phylogeny of CES isozymes in the opossum and report on the sequences and locations of CES1, CES2 and CES6 'like' genes within two gene clusters on chromosome one. We also discuss the likely sequence of gene duplication events generating multiple CES genes during vertebrate evolution. Results We report a cDNA sequence for an opossum CES and present evidence for CES1 and CES2 like genes expressed in opossum liver and intestine and for distinct gene locations of five opossum CES genes,CES1, CES2.1, CES2.2, CES2.3 and CES6, on chromosome 1. Phylogenetic and sequence alignment studies compared the predicted amino acid sequences for opossum CES with those for human, mouse, chicken, frog, salmon and Drosophila CES gene products. Phylogenetic analyses produced congruent phylogenetic trees depicting a rapid early diversification into at least five distinct CES gene family clusters: CES2, CES1, CES7, CES3, and CES6. Molecular divergence estimates based on a Bayesian relaxed clock approach revealed an origin for the five mammalian CES gene families between 328-378 MYA. Conclusion The deduced amino acid sequence for an opossum cDNA was consistent with its identity as a mammalian CES2 gene product (designated CES2.1). Distinct gene locations for opossum CES1 (1: 446,222,550-446,274,850), three CES2 genes (1: 677,773,395-677,927,030) and a CES6 gene (1: 677,585,520-677,730,419) were observed on chromosome 1. Opossum CES1 and multiple CES2 genes were expressed in liver and intestine. Amino acid sequences for opossum CES1 and three CES2 gene products revealed conserved residues previously reported for human CES1 involved in catalysis, ligand binding, tertiary structure and organelle localization. Phylogenetic studies indicated the gene duplication events which generated ancestral mammalian CES genes predated the common ancestor for marsupial and eutherian mammals, and appear to coincide with the early diversification of tetrapods.Full Tex

    Coalignment of plasma membrane channels and protrusions (fibripositors) specifies the parallelism of tendon

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    The functional properties of tendon require an extracellular matrix (ECM) rich in elongated collagen fibrils in parallel register. We sought to understand how embryonic fibroblasts elaborate this exquisite arrangement of fibrils. We show that procollagen processing and collagen fibrillogenesis are initiated in Golgi to plasma membrane carriers (GPCs). These carriers and their cargo of 28-nm-diam fibrils are targeted to previously unidentified plasma membrane (PM) protrusions (here designated “fibripositors”) that are parallel to the tendon axis and project into parallel channels between cells. The base of the fibripositor lumen (buried several microns within the cell) is a nucleation site of collagen fibrillogenesis. The tip of the fibripositor is the site of fibril deposition to the ECM. Fibripositors are absent at postnatal stages when fibrils increase in diameter by accretion of extracellular collagen, thereby maintaining parallelism of the tendon. Thus, we show that the parallelism of tendon is determined by the late secretory pathway and interaction of adjacent PMs to form extracellular channels

    Stroke genetics: prospects for personalized medicine.

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    Epidemiologic evidence supports a genetic predisposition to stroke. Recent advances, primarily using the genome-wide association study approach, are transforming what we know about the genetics of multifactorial stroke, and are identifying novel stroke genes. The current findings are consistent with different stroke subtypes having different genetic architecture. These discoveries may identify novel pathways involved in stroke pathogenesis, and suggest new treatment approaches. However, the already identified genetic variants explain only a small proportion of overall stroke risk, and therefore are not currently useful in predicting risk for the individual patient. Such risk prediction may become a reality as identification of a greater number of stroke risk variants that explain the majority of genetic risk proceeds, and perhaps when information on rare variants, identified by whole-genome sequencing, is also incorporated into risk algorithms. Pharmacogenomics may offer the potential for earlier implementation of 'personalized genetic' medicine. Genetic variants affecting clopidogrel and warfarin metabolism may identify non-responders and reduce side-effects, but these approaches have not yet been widely adopted in clinical practice

    Pointing control for the SPIDER balloon-borne telescope

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    We present the technology and control methods developed for the pointing system of the SPIDER experiment. SPIDER is a balloon-borne polarimeter designed to detect the imprint of primordial gravitational waves in the polarization of the Cosmic Microwave Background radiation. We describe the two main components of the telescope's azimuth drive: the reaction wheel and the motorized pivot. A 13 kHz PI control loop runs on a digital signal processor, with feedback from fibre optic rate gyroscopes. This system can control azimuthal speed with < 0.02 deg/s RMS error. To control elevation, SPIDER uses stepper-motor-driven linear actuators to rotate the cryostat, which houses the optical instruments, relative to the outer frame. With the velocity in each axis controlled in this way, higher-level control loops on the onboard flight computers can implement the pointing and scanning observation modes required for the experiment. We have accomplished the non-trivial task of scanning a 5000 lb payload sinusoidally in azimuth at a peak acceleration of 0.8 deg/s2^2, and a peak speed of 6 deg/s. We can do so while reliably achieving sub-arcminute pointing control accuracy.Comment: 20 pages, 12 figures, Presented at SPIE Ground-based and Airborne Telescopes V, June 23, 2014. To be published in Proceedings of SPIE Volume 914

    Nut production in Bertholletia excelsa across a logged forest mosaic: implications for multiple forest use

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    Although many examples of multiple-use forest management may be found in tropical smallholder systems, few studies provide empirical support for the integration of selective timber harvesting with non-timber forest product (NTFP) extraction. Brazil nut (Bertholletia excelsa, Lecythidaceae) is one of the world’s most economically-important NTFP species extracted almost entirely from natural forests across the Amazon Basin. An obligate out-crosser, Brazil nut flowers are pollinated by large-bodied bees, a process resulting in a hard round fruit that takes up to 14 months to mature. As many smallholders turn to the financial security provided by timber, Brazil nut fruits are increasingly being harvested in logged forests. We tested the influence of tree and stand-level covariates (distance to nearest cut stump and local logging intensity) on total nut production at the individual tree level in five recently logged Brazil nut concessions covering about 4000 ha of forest in Madre de Dios, Peru. Our field team accompanied Brazil nut harvesters during the traditional harvest period (January-April 2012 and January-April 2013) in order to collect data on fruit production. Three hundred and ninety-nine (approximately 80%) of the 499 trees included in this study were at least 100 m from the nearest cut stump, suggesting that concessionaires avoid logging near adult Brazil nut trees. Yet even for those trees on the edge of logging gaps, distance to nearest cut stump and local logging intensity did not have a statistically significant influence on Brazil nut production at the applied logging intensities (typically 1–2 timber trees removed per ha). In one concession where at least 4 trees ha-1 were removed, however, the logging intensity covariate resulted in a marginally significant (0.09) P value, highlighting a potential risk for a drop in nut production at higher intensities. While we do not suggest that logging activities should be completely avoided in Brazil nut rich forests, when a buffer zone cannot be observed, low logging intensities should be implemented. The sustainability of this integrated management system will ultimately depend on a complex series of socioeconomic and ecological interactions. Yet we submit that our study provides an important initial step in understanding the compatibility of timber harvesting with a high value NTFP, potentially allowing for diversification of forest use strategies in Amazonian PerĂč

    English in product advertisements in non-english speaking countries in western europe: Product image and comprehension of the text

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    Although English has been shown to be the most frequently used foreign language in product advertisements in countries where it is not the native language, little is known about its effects. This article examines the response to advertisements in English compared to the response to the same ad in the local language in Western Europe on members of the target group for which the ad was intended: 715 young, highly educated female consumers. The use of English in a product ad does not appear to have any impact on image and price of the product, but it does affect text comprehension: the meaning of almost 40% of the English phrases was not understood. These results were the same for all countries involved in the study, irrespective of whether the respondents\u27 (self-) reported proficiency in English is high or low. © Taylor & Francis Group, LLC

    A review of nitrogen isotopic alteration in marine sediments

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    Key Points: Use of sedimentary nitrogen isotopes is examined; On average, sediment 15N/14N increases approx. 2 per mil during early burial; Isotopic alteration scales with water depth Abstract: Nitrogen isotopes are an important tool for evaluating past biogeochemical cycling from the paleoceanographic record. However, bulk sedimentary nitrogen isotope ratios, which can be determined routinely and at minimal cost, may be altered during burial and early sedimentary diagenesis, particularly outside of continental margin settings. The causes and detailed mechanisms of isotopic alteration are still under investigation. Case studies of the Mediterranean and South China Seas underscore the complexities of investigating isotopic alteration. In an effort to evaluate the evidence for alteration of the sedimentary N isotopic signal and try to quantify the net effect, we have compiled and compared data demonstrating alteration from the published literature. A >100 point comparison of sediment trap and surface sedimentary nitrogen isotope values demonstrates that, at sites located off of the continental margins, an increase in sediment 15N/14N occurs during early burial, likely at the seafloor. The extent of isotopic alteration appears to be a function of water depth. Depth-related differences in oxygen exposure time at the seafloor are likely the dominant control on the extent of N isotopic alteration. Moreover, the compiled data suggest that the degree of alteration is likely to be uniform through time at most sites so that bulk sedimentary isotope records likely provide a good means for evaluating relative changes in the global N cycle
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