Are infestations of Cymomelanodactylus killing Acropora cytherea in the Chagos archipelago?

Associations between branching corals and infaunal crabs are well known, mostly due to the beneficial effects of Trapezia and Tetralia crabs in protecting host corals from crown-of-thorns starfish (e.g., Pratchett et al. 2000) and/or sedimentation (Stewart et al. 2006). These crabs are obligate associates of live corals and highly prevalent across suitable coral hosts, with 1–2 individuals per colony (Patton 1994). Cymo melanodactylus (Fig. 1) are also prevalent in branching corals, mostly Acropora, and are known to feed on live coral tissue, but are generally found in low abundance (<3 per colony) and do not significantly affect their host corals (e.g., Patton 1994). In the Chagos archipelago, however, infestations of Cymo melanodactylus were found on recently dead and dying colonies of Acropora cytherea

An automated framework for understanding structural variations in the binding grooves of MHC class II molecules

Background: MHC/HLA class II molecules are important components of the immune system and play a critical role in processes such as phagocytosis. Understanding peptide recognition properties of the hundreds of MHC class II alleles is essential to appreciate determinants of antigenicity and ultimately to predict epitopes. While there are several methods for epitope prediction, each differing in their success rates, there are no reports so far in the literature to systematically characterize the binding sites at the structural level and infer recognition profiles from them. Results: Here we report a new approach to compare the binding sites of MHC class II molecules using their three dimensional structures. We use a specifically tuned version of our recent algorithm, PocketMatch. We show that our methodology is useful for classification of MHC class II molecules based on similarities or differences among their binding sites. A new module has been used to define binding sites in MHC molecules. Comparison of binding sites of 103 MHC molecules, both at the whole groove and individual sub-pocket levels has been carried out, and their clustering patterns analyzed. While clusters largely agree with serotypic classification, deviations from it and several new insights are obtained from our study. We also present how differences in sub-pockets of molecules associated with a pair of autoimmune diseases, narcolepsy and rheumatoid arthritis, were captured by PocketMatch(13). Conclusion: The systematic framework for understanding structuralvariations in MHC class II molecules enables large scale comparison of binding grooves and sub-pockets, which is likely to have direct implications towards predicting epitopes and understanding peptide binding preferences

The Tamar Trough revisited: correlations berween sedimentary beds, basalts, their ages and valley evolution, North Tasmania

The Tamar Trough, an Early Palaeogene fault structure, contains sedimentaty beds and interleaved basaltic flows that infill the structure along its 70 km length. These infills represent a complex interplay between sedimentation, channel erosion, eruptive dislocations, and even 'out of trough' diyersions of the ancestral Tamar drainage. Several areas of resistant basalt flows remain in the south, upper, middle and lower Tamar reaches. Although some palynological control was known, radiometric dating of previously untested basalts now allows close integration and age-pegging for observed palynological biozones. The K-Ar and Ar-Ar ages of the basalt bodies indicate eruptive events at 47, 33-37 and 25 Ma, correlating with Proteacidites asperopolus-Malvacipollis diversus, Nothofagites asperus and Proteacidites tuberculatus biozone age sedimentary beds respectively. Basanite, alkali basalt and hawaiite flows dominate basalt lithology with lesser olivine nephelinite, transitional olivine basalt, olivine tholeiite and quartz tholeiite. Basalt geochemistry suggests derivation from different degrees of partial mande melting (from 7 to 35%), with alkaline and tholeiitic basalts being derived from separate source regions. Most alkaline basalts have high-jl (HIMU) related trace element signatures, which are absent in the tholeiitic rocks. A basalt plug on the trough margin at Loira gave a Jurassic age and has Jurassic dolerite-like geochemistry. The Tamar sequence suggests that the initial fluvio-Iacustrine and later channel-fill sedimentation from 65(?) to 24(?) Ma was then punctuated in places by periods of alkaline volcanism between 47 to 33(?) Ma, and alkaline and tholeiitic volcanism between 33 to 24(?) Ma. No Neogene fossils are known, so this later period was probably one of net erosion. These contrasting quiet sedimentary and more volcanic intervals are related here to a tectonic model that involves northerly drift of Victorian and Tasmanian lithosphere over several former Tasman metasomatised mantle plume sources

Identification of putative regulatory upstream ORFs in the yeast genome using heuristics and evolutionary conservation.

BACKGROUND: The translational efficiency of an mRNA can be modulated by upstream open reading frames (uORFs) present in certain genes. A uORF can attenuate translation of the main ORF by interfering with translational reinitiation at the main start codon. uORFs also occur by chance in the genome, in which case they do not have a regulatory role. Since the sequence determinants for functional uORFs are not understood, it is difficult to discriminate functional from spurious uORFs by sequence analysis. RESULTS: We have used comparative genomics to identify novel uORFs in yeast with a high likelihood of having a translational regulatory role. We examined uORFs, previously shown to play a role in regulation of translation in Saccharomyces cerevisiae, for evolutionary conservation within seven Saccharomyces species. Inspection of the set of conserved uORFs yielded the following three characteristics useful for discrimination of functional from spurious uORFs: a length between 4 and 6 codons, a distance from the start of the main ORF between 50 and 150 nucleotides, and finally a lack of overlap with, and clear separation from, neighbouring uORFs. These derived rules are inherently associated with uORFs with properties similar to the GCN4 locus, and may not detect most uORFs of other types. uORFs with high scores based on these rules showed a much higher evolutionary conservation than randomly selected uORFs. In a genome-wide scan in S. cerevisiae, we found 34 conserved uORFs from 32 genes that we predict to be functional; subsequent analysis showed the majority of these to be located within transcripts. A total of 252 genes were found containing conserved uORFs with properties indicative of a functional role; all but 7 are novel. Functional content analysis of this set identified an overrepresentation of genes involved in transcriptional control and development. CONCLUSION: Evolutionary conservation of uORFs in yeasts can be traced up to 100 million years of separation. The conserved uORFs have certain characteristics with respect to length, distance from each other and from the main start codon, and folding energy of the sequence. These newly found characteristics can be used to facilitate detection of other conserved uORFs.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Predicting functional upstream open reading frames in Saccharomyces cerevisiae

<p>Abstract</p> <p>Background</p> <p>Some upstream open reading frames (uORFs) regulate gene expression (i.e., they are functional) and can play key roles in keeping organisms healthy. However, how uORFs are involved in gene regulation is not yet fully understood. In order to get a complete view of how uORFs are involved in gene regulation, it is expected that a large number of experimentally verified functional uORFs are needed. Unfortunately, wet-experiments to verify that uORFs are functional are expensive.</p> <p>Results</p> <p>In this paper, a new computational approach to predicting functional uORFs in the yeast <it>Saccharomyces cerevisiae </it>is presented. Our approach is based on inductive logic programming and makes use of a novel combination of knowledge about biological conservation, Gene Ontology annotations and genes' responses to different conditions. Our method results in a set of simple and informative hypotheses with an estimated sensitivity of 76%. The hypotheses predict 301 further genes to have 398 novel functional uORFs. Three (<it>RPC11</it>, <it>TPK1</it>, and <it>FOL1</it>) of these 301 genes have been hypothesised, following wet-experiments, by a related study to have functional uORFs. A comparison with another related study suggests that eleven of the predicted functional uORFs from genes <it>LDB17</it>, <it>HEM3</it>, <it>CIN8</it>, <it>BCK2</it>, <it>PMC1</it>, <it>FAS1</it>, <it>APP1</it>, <it>ACC1</it>, <it>CKA2</it>, <it>SUR1</it>, and <it>ATH1 </it>are strong candidates for wet-lab experimental studies.</p> <p>Conclusions</p> <p>Learning based prediction of functional uORFs can be done with a high sensitivity. The predictions made in this study can serve as a list of candidates for subsequent wet-lab verification and might help to elucidate the regulatory roles of uORFs.</p

Pain assessment and pain treatment for community-dwelling people with dementia: A systematic review and narrative synthesis.

OBJECTIVES: To describe the current literature on pain assessment and pain treatment for community-dwelling people with dementia. METHOD: A comprehensive systematic search of the literature with narrative synthesis was conducted. Eight major bibliographic databases were searched in October 2018. Titles, abstracts, and full-text articles were sequentially screened. Standardised data extraction and quality appraisal exercises were conducted. RESULTS: 32 studies were included in the review, 11 reporting findings on pain assessment tools or methods, and 27 reporting findings on treatments for pain. In regard to pain assessment, a large proportion of people with moderate to severe dementia were unable to complete a self-report pain instrument. Pain was more commonly reported by informal caregivers than the person with dementia themselves. Limited evidence was available for pain focused behavioural observation assessment. In regard to pain treatment, paracetamol use was more common in community-dwelling people with dementia compared to people without dementia. However, non-steroidal anti-inflammatory drugs (NSAIDs) were used less. For stronger analgesics, community-dwelling people with dementia were more likely to receive strong opioids (e.g. fentanyl) than people without dementia. CONCLUSION: This review identifies a dearth of high quality studies exploring pain assessment and/or treatment for community-dwelling people with dementia, not least into non-pharmacological interventions. The consequences of this lack of evidence, given the current and projected prevalence of the disease, are very serious and require urgent redress. In the meantime, clinicians should adopt a patient and caregiver centred, multi-dimensional, longitudinal approach to pain assessment and pain treatment for this population

SHRIMP ion probe zircon geochronology and Sr and Nd isotope geochemistry for southern Longwood Range and Bluff Peninsula intrusive rocks of Southland, New Zealand

Permian–Jurassic ultramafic to felsic intrusive complexes at Bluff Peninsula and in the southern Longwood Range along the Southland coast represent a series of intraoceanic magmatic arcs with ages spanning a time interval of 110 m.y. New SHRIMP U-Pb zircon data for a quartz diorite from the Flat Hill complex, Bluff Peninsula, yield an age of 259 ± 4 Ma, consistent with other geochronological and paleontological evidence confirming a Late Permian age. The new data are consistent with an age of c. 260 Ma for the intrusive rocks of the Brook Street Terrane. SHRIMP U-Pb zircon ages for the southern Longwood Range confirm that intrusions become progressively younger from east to west across the complex. A gabbro at Oraka Point (eastern end of coastal section) has an age of 245 ± 4 Ma and shows virtually no evidence of zircon inheritance. The age is significantly different from that of the Brook Street Terrane intrusives. Zircon ages from the western parts of the section are younger and more varied (203–227 Ma), indicating more complex magmatic histories. A leucogabbro dike from Pahia Point gives the youngest emplacement age of 142 Ma, which is similar to published U-Pb zircon ages for the Anglem Complex and Paterson Group on Stewart Island

Gastrointestinal-Sparing Effects of Novel NSAIDs in Rats with Compromised Mucosal Defence

Nonsteroidal anti-inflammatory drugs are among the most commonly used prescription and over-the-counter medications, but they often produce significant gastrointestinal ulceration and bleeding, particularly in elderly patients and patients with certain co-morbidities. Novel anti-inflammatory drugs are seldom tested in animal models that mimic the high risk human users, leading to an underestimate of the true toxicity of the drugs. In the present study we examined the effects of two novel NSAIDs and two commonly used NSAIDs in models in which mucosal defence was expected to be impaired. Naproxen, celecoxib, ATB-346 (a hydrogen sulfide- and naproxen-releasing compound) and NCX 429 (a nitric oxide- and naproxen-releasing compound) were evaluated in healthy, arthritic, obese, and hypertensive rats and in rats of advanced age (19 months) and rats co-administered low-dose aspirin and/or omeprazole. In all models except hypertension, greater gastric and/or intestinal damage was observed when naproxen was administered in these models than in healthy rats. Celecoxib-induced damage was significantly increased when co-administered with low-dose aspirin and/or omeprazole. In contrast, ATB-346 and NCX 429, when tested at doses that were as effective as naproxen and celecoxib in reducing inflammation and inhibiting cyclooxygenase activity, did not produce significant gastric or intestinal damage in any of the models. These results demonstrate that animal models of human co-morbidities display the same increased susceptibility to NSAID-induced gastrointestinal damage as observed in humans. Moreover, two novel NSAIDs that release mediators of mucosal defence (hydrogen sulfide and nitric oxide) do not induce significant gastrointestinal damage in these models of impaired mucosal defence

BMP signalling regulates the pre-implantation development of extra-embryonic cell lineages in the mouse embryo.

Pre-implantation development requires the specification and organization of embryonic and extra-embryonic lineages. The separation of these lineages takes place when asymmetric divisions generate inside and outside cells that differ in polarity, position and fate. Here we assess the global transcriptional identities of these precursor cells to gain insight into the molecular mechanisms regulating lineage segregation. Unexpectedly, this reveals that complementary components of the bone morphogenetic protein (BMP) signalling pathway are already differentially expressed after the first wave of asymmetric divisions. We investigate the role of BMP signalling by expressing dominant negative forms of Smad4 and Bmpr2, by downregulating the pathway using RNA interference against BMP ligands and by applying three different BMP inhibitors at distinct stages. This reveals that BMP signalling regulates the correct development of both extra-embryonic lineages, primitive endoderm and trophectoderm, but not the embryonic lineage, before implantation. Together, these findings indicate multiple roles of BMP signalling in the early mouse embryo.This work was supported by a Wellcome Trust programme grant to MZG and an Agency for Science, Technology and Research (A*Star) core research budget to PR.This is the author accepted manuscript. The final version is available from NPG via http://dx.doi.org/10.1038/ncomms666