45 research outputs found

    NG peptides: A novel family of neurophysin-associated neuropeptides

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    NOTICE: this is the author’s version of a work that was accepted for publication in GENE. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in GENE, [VOL 458, ISSUE 1-2, (2010)] DOI: 10.1016/j.gene.2010.03.00

    Post-acute Brain Injury Urinary Signature: A New Resource for Molecular Diagnostics

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    Heterogeneity within brain injury presents a challenge to the development of informative molecular diagnostics. Recent studies show progress particularly in cerebrospinal fluid with biomarker assays targeting one or a few structural proteins. Protein-based assays in peripheral fluids, however, have been more challenging to develop in part due to restricted and intermittent barrier access. Further, a greater number of molecular variables may be required to inform on patient status given the multifactorial nature of brain injury. Presented is an alternative approach profiling peripheral fluid for a class of small metabolic by-products rendered by ongoing brain pathobiology. Urine specimens were collected for head trauma subjects upon admission to acute brain injury rehabilitation and nontraumatized matched controls. An innovative data-independent mass spectrometry approach was employed for reproducible molecular quantification across osmolarity-normalized samples. The postacute human traumatic brain injury urinary signature encompassed 2,476 discriminant variables reproducibly measured in specimens for subject classification. Multiple sub-profiles were then discerned in correlation with injury severity per Glasgow Comma Scale and behavioral and neurocognitive function per Patient Competency Rating Scale and Frontal Systems Behavioral Scale. Identified peptide constituents were enriched for outgrowth and guidance, extracellular matrix and post-synaptic density proteins, which were reflective of ongoing post-acute neuroplastic processes demonstrating pathobiological relevance. Taken together, these findings support further development of diagnostics based on brain injury urinary signatures using either combinatorial quantitative models or patternrecognition methods. Particularly, these findings espouse assay development to address unmet diagnostic and theragnostic needs in brain injury rehabilitative medicine

    The evolution of neuropeptide signalling: insights from echinoderms

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    This work was supported by Leverhulme Trust grant RGP-2013-351 and BBSRC grant BB/M001644/1 (awarded to M.R.E.). Dean Semmens has a BSc in Molecular and Cellular Biology (University of Bath, 2011), a PhD in Neurobiology (Queen Mary University of London, 2015) and is a Leverhulme Trust-funded Postdoctoral Fellow. Maurice Elphick studied at Royal Holloway University of London (BSc Biology, 1988; PhD Neurobiology, 1991) and became Professor of Physiology and Neuroscience at Queen Mary University of London in 2004

    Molecular Evolution of the Neuropeptide S Receptor

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    The neuropeptide S receptor (NPSR) is a recently deorphanized member of the G protein-coupled receptor (GPCR) superfamily and is activated by the neuropeptide S (NPS). NPSR and NPS are widely expressed in central nervous system and are known to have crucial roles in asthma pathogenesis, locomotor activity, wakefulness, anxiety and food intake. The NPS-NPSR system was previously thought to have first evolved in the tetrapods. Here we examine the origin and the molecular evolution of the NPSR using in-silico comparative analyses and document the molecular basis of divergence of the NPSR from its closest vertebrate paralogs. In this study, NPSR-like sequences have been identified in a hemichordate and a cephalochordate, suggesting an earlier emergence of a NPSR-like sequence in the metazoan lineage. Phylogenetic analyses revealed that the NPSR is most closely related to the invertebrate cardioacceleratory peptide receptor (CCAPR) and the group of vasopressin-like receptors. Gene structure features were congruent with the phylogenetic clustering and supported the orthology of NPSR to the invertebrate NPSR-like and CCAPR. A site-specific analysis between the vertebrate NPSR and the well studied paralogous vasopressin-like receptor subtypes revealed several putative amino acid sites that may account for the observed functional divergence between them. The data can facilitate experimental studies aiming at deciphering the common features as well as those related to ligand binding and signal transduction processes specific to the NPSR

    The comparative osmoregulatory ability of two water beetle genera whose species span the fresh-hypersaline gradient in inland waters (Coleoptera: Dytiscidae, Hydrophilidae).

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    A better knowledge of the physiological basis of salinity tolerance is essential to understanding the ecology and evolutionary history of organisms that have colonized inland saline waters. Coleoptera are amongst the most diverse macroinvertebrates in inland waters, including saline habitats; however, the osmoregulatory strategies they employ to deal with osmotic stress remain unexplored. Survival and haemolymph osmotic concentration at different salinities were examined in adults of eight aquatic beetle species which inhabit different parts of the fresh-hypersaline gradient. Studied species belong to two unrelated genera which have invaded saline waters independently from freshwater ancestors; Nebrioporus (Dytiscidae) and Enochrus (Hydrophilidae). Their osmoregulatory strategy (osmoconformity or osmoregulation) was identified and osmotic capacity (the osmotic gradient between the animal's haemolymph and the external medium) was compared between species pairs co-habiting similar salinities in nature. We show that osmoregulatory capacity, rather than osmoconformity, has evolved independently in these different lineages. All species hyperegulated their haemolymph osmotic concentration in diluted waters; those living in fresh or low-salinity waters were unable to hyporegulate and survive in hyperosmotic media (> 340 mosmol kg(-1)). In contrast, the species which inhabit the hypo-hypersaline habitats were effective hyporegulators, maintaining their haemolymph osmolality within narrow limits (ca. 300 mosmol kg(-1)) across a wide range of external concentrations. The hypersaline species N. ceresyi and E. jesusarribasi tolerated conductivities up to 140 and 180 mS cm(-1), respectively, and maintained osmotic gradients over 3500 mosmol kg(-1), comparable to those of the most effective insect osmoregulators known to date. Syntopic species of both genera showed similar osmotic capacities and in general, osmotic responses correlated well with upper salinity levels occupied by individual species in nature. Therefore, osmoregulatory capacity may mediate habitat segregation amongst congeners across the salinity gradient

    Genome Sequence of the Pea Aphid Acyrthosiphon pisum

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    Aphids are important agricultural pests and also biological models for studies of insect-plant interactions, symbiosis, virus vectoring, and the developmental causes of extreme phenotypic plasticity. Here we present the 464 Mb draft genome assembly of the pea aphid Acyrthosiphon pisum. This first published whole genome sequence of a basal hemimetabolous insect provides an outgroup to the multiple published genomes of holometabolous insects. Pea aphids are host-plant specialists, they can reproduce both sexually and asexually, and they have coevolved with an obligate bacterial symbiont. Here we highlight findings from whole genome analysis that may be related to these unusual biological features. These findings include discovery of extensive gene duplication in more than 2000 gene families as well as loss of evolutionarily conserved genes. Gene family expansions relative to other published genomes include genes involved in chromatin modification, miRNA synthesis, and sugar transport. Gene losses include genes central to the IMD immune pathway, selenoprotein utilization, purine salvage, and the entire urea cycle. The pea aphid genome reveals that only a limited number of genes have been acquired from bacteria; thus the reduced gene count of Buchnera does not reflect gene transfer to the host genome. The inventory of metabolic genes in the pea aphid genome suggests that there is extensive metabolite exchange between the aphid and Buchnera, including sharing of amino acid biosynthesis between the aphid and Buchnera. The pea aphid genome provides a foundation for post-genomic studies of fundamental biological questions and applied agricultural problems

    Alte Getreidesorten, Natursauerteig und deren Auswirkung auf die Verträglichkeit beim Menschen

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    Intoleranzen, besonders jene gegen Gluten, nehmen fortlaufend zu und billig produzierte Backwaren überhäufen den Markt. Um sich als Bäcker/in weiterhin behaupten zu können muss die Devise Qualität vor Quantität lauten, und dafür ist der Einsatz von Natursauerteig und alten Getreidesorten unerlässlich. Gluten wurde in den letzten Jahren regelrecht verteufelt und der „Glutenfreiboom“ hält weiterhin an. Das Problem, warum immer mehr Menschen Backwaren nicht vertragen ist jedoch zum Großteil nicht das Gluten, sondern die Zeit, welche ihnen meist vorenthalten wird. Problemstoffe wie Fodmaps, ATI oder Phytinsäure können nur über die Zeit abgebaut beziehungsweise aufgespalten werden und der Einsatz von Sauerteig unterstützt diesen Prozess. Auch der Gehalt an Mineralstoffen ist bei Urgetreide deutlich höher als beim modernen Weichweizen, was zur besseren Veträglichkeit beiträgt. Zöliakiepatienten haben keine Wahl und müssen auf glutenhaltige Produkte verzichten. Liegt jedoch trotz Verdauungsproblemen nach dem Verzehr von Brot und Gebäck keine Zöliakiediagnose vor, ist der Schlüssel zur Lösung des Problems meist die Zeit und die richtige Auswahl der Getreidesorten
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