bluuebunny/crossref_metadata_2025_split huggingface dataset:
Posterior Lamellar Reconstruction of the Lower Eyelid With a Gingivoalveolar Mucosal Graft
Authors: Baltu Yahya 
Published: May 2018

Abstract
The anterior and posterior lamellae should be simultaneously reconstructed to repair the upper and lower eyelid's full thickness defects after resection of a malignant tumor. The author described a gingivoalveolar mucosal graft for posterior lamellar reconstruction of the lower eyelid. Between November 2014 and September 2017, 11 patients (6 women, 5 men; mean age 62.7 years) with 13 posterior lamellar defect of lower eyelid underwent reconstruction with gingivoalveolar mucosal graft. The defects ranged from 10 x 8 mm to 20 x 10 mm. For 11 lower eyelid defects, the anterior lamellar defect was previously reconstructed with an appropriate local flap. The remaining 2 defects were repaired with graft only. The mean follow-up period was 15.3 months. The pathologic diagnoses were squamous cell carcinoma for 8 lower eyelid lesions and basal cell carcinoma for the remaining 5 lower eyelid lesions. No case of necrosis and infection was observed in any flap or graft. Also, there was not observed ectropion or lid laxity at lower eyelids. However, redness developed in 1 eye, but healed in 1 week. Donor areas completely improved with secondary healing with no any complication. Gingivoalveolar mucosal graft is a reliable and easy accessible choice for posterior lamellar reconstruction of eyelid defects. While the gingival mucosal part provides a stable and tight structural support for marginal palpebral area, the alveolar part occupies the conjunctival side without causing corneal irritation.
Global connectivity and function of descending spinal input revealed by 3D microscopy and retrograde transduction
Authors: Wang Zimei , Maunze Brian , Wang Yufang , Tsoulfas Pantelis , Blackmore Murray G. 
Published: May 2018

ABSTRACTThe brain communicates with the spinal cord through numerous axon tracts that arise from discrete nuclei, transmit distinct functions, and often collateralize to facilitate the coordination of descending commands. In efforts to restore supraspinal connectivity after injury or disease, this complexity presents a major challenge to interpreting functional outcomes, while the wide distribution of supraspinal nuclei complicates the delivery of therapeutics. Here we harness retrograde viral vectors to overcome these challenges. We demonstrate highly efficient retrograde transduction by AAV2-Retro in adult female mice, and employ tissue clearing to visualize descending tracts and create a mesoscopic projectome for the spinal cord. Moreover, chemogenetic silencing of supraspinal neurons with retrograde vectors results in complete and reversible forelimb paralysis, illustrating effective modulation of supraspinal function. Retrograde efficacy persists even after spinal injury, highlighting therapeutic potential. These data provide a global view of supraspinal connectivity and illustrate the potential of retrograde vectors to parse the functional contributions of supraspinal inputs.
Intersection of phosphate transport, oxidative stress and TOR signalling inCandida albicansvirulence
Authors: Liu Ning-Ning , Uppuluri Priya , Broggi Achille , Besold Angelique , Ryman Kicki , Kambara Hiroto , Solis Norma , Lorenz Viola , Qi Wanjun , Acosta-Zaldivar Maikel , Emami S. Noushin , Bao Bin , An Dingding , Bonilla Francisco A. , Sola-Visner Martha , Filler Scott G. , Luo Hongbo R. , Engström Ylva , Ljungdahl Per Olof , Culotta Valeria C. , Zanoni Ivan , Lopez-Ribot Jose L. , Köhler Julia R. 
Published: May 2018

AbstractPhosphate is an essential macronutrient required for cell growth and division. Pho84 is the major high-affinity cell-surface phosphate importer ofSaccharomyces cerevisiaeand a crucial element in the phosphate homeostatic system of this model yeast. We found that loss ofCandida albicansPho84 attenuated virulence inDrosophilaand murine oropharyngeal and disseminated models of invasive infection, and conferred hypersensitivity to neutrophil killing. Susceptibility of cells lacking Pho84 to neutrophil attack depended on reactive oxygen species (ROS):pho84-/-cells were no more susceptible than wild typeC. albicansto neutrophils from a patient with chronic granulomatous disease, or to those whose oxidative burst was pharmacologically inhibited or neutralized.pho84-/-mutants hyperactivated oxidative stress signalling. They accumulated intracellular ROS in the absence of extrinsic oxidative stress, in high as well as low ambient phosphate conditions. ROS accumulation correlated with diminished levels of the unique superoxide dismutase Sod3 inpho84-/-cells, whileSOD3overexpression from a conditional promoter substantially restored these cells’ oxidative stress resistance in vitro. Repression ofSOD3expression sharply increased their oxidative stress hypersensitivity. Neither of these oxidative stress management effects of manipulatingSOD3transcription was observed inPHO84wild type cells. Sod3 levels were not the only factor driving oxidative stress effects onpho84-/-cells, though, because overexpressingSOD3did not ameliorate these cells’ hypersensitivity to neutrophil killing ex vivo, indicating Pho84 has further roles in oxidative stress resistance and virulence. Measurement of cellular metal concentrations demonstrated that diminished Sod3 expression was not due to decreased import of its metal cofactor manganese, as predicted from the function ofS. cerevisiaePho84 as a low-affinity manganese transporter. Instead of a role of Pho84 in metal transport, we found its role in TORC1 activation to impact oxidative stress management: overexpression of the TORC1-activating GTPase Gtr1 relieved the Sod3 deficit and ROS excess inpho84-/-null mutant cells, though it did not suppress their hypersensitivity to neutrophil killing or hyphal growth defect. Pharmacologic inhibition of Pho84 by small molecules including the FDA-approved drug foscarnet also induced ROS accumulation. Inhibiting Pho84 could hence support host defenses by sensitizingC. albicansto oxidative stress.
Neutrophil microvesicles drive atherosclerosis by deliveringmiR-155to atheroprone endothelium
Authors: Gomez Ingrid , Ward Ben , Souilhol Celine , Recarti Chiara , Ariaans Mark , Johnston Jessica , Burnett Amanda , Mahmoud Marwa , Luong Le Anh , West Laura , Long Merete , Parry Sion , Woods Rachel , Hulston Carl , Benedikter Birke , Bazaz Rohit , Francis Sheila , Kiss-Toth Endre , Zandvoort Marc van , Schober Andreas , Hellewell Paul , Evans Paul C. , Ridger Victoria 
Published: May 2018

AbstractNeutrophils have been implicated in the pathogenesis of atherosclerosis, a lipid-driven disease of arteries, but they are seldom found in atherosclerotic plaques. To resolve this longstanding paradox, we investigated whether neutrophil-derived microvesicles may influence arterial pathophysiology. Clinical and pre-clinical studies revealed that levels of circulating neutrophil microvesicles were enhanced by exposure to a high fat diet, a known risk factor for atherosclerosis. Neutrophil microvesicles accumulated at disease-prone regions of arteries that are exposed to complex flow patterns, and they promoted vascular inflammation and atherosclerosis in a murine model. Using cultured endothelial cells exposed to disturbed flow, it was demonstrated that neutrophil microvesicles promoted inflammatory gene expression by delivering a microRNA (miR-155) that enhanced NF-κB activation. Similary, neutrophil microvesicles increased miR-155 and enhanced NF-κB at disease-prone sites of disturbed flow in arteries of mice. We conclude that delivery of microvesicles carrying miR-155 to disease-prone regions of arteries provides a novel mechanism by which neutrophils contribute to vascular inflammation and atherogenesis.
Neuronal morphologies built for reliable physiology in a rhythmic motor circuit
Authors: Otopalik Adriane G. , Marder Eve 
Published: May 2018

AbstractThe neurons of the crustacean stomatogastric ganglion (STG) exhibit highly-conserved firing patterns, voltage waveforms, and circuit functions despite quantifiable animal-to-animal variability in their neuronal morphologies. In recent work, we showed that one neuron type, the Gastric Mill (GM) neuron, is electrotonically compact and operates much like a single compartment, despite having thousands of branch points and a total cable length on the order of 10 mm. Here, we explore how STG neurite morphology shapes voltage signal propagation and summation in four STG neuron types. We use focal glutamate photo-uncaging in tandem with somatic intracellular recordings to examine passive electrotonic structure and voltage signal summation in the GM neuron and three additional STG neuron types: Lateral Pyloric (LP), Ventricular Dilator (VD), and Pyloric Dilator (PD) neurons. In each neuron, we measured the amplitudes and apparent reversal potentials (Erevs) of inhibitory responses evoked with focal glutamate photo-uncaging at more than 20 sites varying in their distance (100–800 μm) from the somatic recording site in the presence of TTX. Apparent Erevs were relatively invariant (mean CVs = 0.04, 0.06, 0.05, and 0.08 for 5–6 GM, LP, PD, VD neurons, respectively), suggesting that all four neuron types are similarly electrotonically uniform and compact. We then characterized the directional sensitivity and arithmetic of voltage summation (with fast sequential activation of 4–6 sites) in individual STG neurites. All four neuron types showed no directional bias in voltage signal summation and linear voltage summation. We motivate these experiments with a proof-of-concept computational model that suggests the immense tapering of STG neurite diameters: from 10–20 μm to sub-micron diameters at the terminal tips, may explain the uniform electrotonic structures experimentally observed and contribute to the robust nature of this central pattern-generating circuit.
Using set theory to reduce redundancy in pathway sets
Authors: Stoney Ruth , Schwartz Jean-Mark , Robertson David L , Nenadic Goran 
Published: May 2018

1.Abstract1.01BackgroundThe consolidation of pathway databases, such as KEGG[1], Reactome[2]and ConsensusPathDB[3], has generated widespread biological interest, however the issue of pathway redundancy impedes the use of these consolidated datasets. Attempts to reduce this redundancy have focused on visualizing pathway overlap or merging pathways, but the resulting pathways may be of heterogeneous sizes and cover multiple biological functions. Efforts have also been made to deal with redundancy in pathway data by consolidating enriched pathways into a number of clusters or concepts. We present an alternative approach, which generates pathway subsets capable of covering all of genes presented within either pathway databases or enrichment results, generating substantial reductions in redundancy.1.02ResultsWe propose a method that uses set cover to reduce pathway redundancy, without merging pathways. The proposed approach considers three objectives: removal of pathway redundancy, controlling pathway size and coverage of the gene set. By applying set cover to the ConsensusPathDB dataset we were able to produce a reduced set of pathways, representing 100% of the genes in the original data set with 74% less redundancy, or 95% of the genes with 88% less redundancy. We also developed an algorithm to simplify enrichment data and applied it to a set of enriched osteoarthritis pathways, revealing that within the top ten pathways, five were redundant subsets of more enriched pathways. Applying set cover to the enrichment results removed these redundant pathways allowing more informative pathways to take their place.1.03ConclusionOur method provides an alternative approach for handling pathway redundancy, while ensuring that the pathways are of homogeneous size and gene coverage is maximised. Pathways are not altered from their original form, allowing biological knowledge regarding the data set to be directly applicable. We demonstrate the ability of the algorithms to prioritise redundancy reduction, pathway size control or gene set coverage. The application of set cover to pathway enrichment results produces an optimised summary of the pathways that best represent the differentially regulated gene set.
Bivariate GWAS scan identifies six novel loci associated with lipid levels and coronary artery disease
Authors: Siewert Katherine M. , Voight Benjamin F. 
Published: May 2018

AbstractBackgroundPlasma lipid levels are heritable and genetically associated with risk of coronary artery disease (CAD). However, genome-wide association studies (GWAS) routinely analyze these traits independently of one another. Joint GWAS for two related phenotypes can lead to a higher-powered analysis to detect variants contributing to both traits.Methods and ResultsWe performed a bivariate GWAS to discover novel loci associated with heart disease, using a CAD Meta-Analysis (122,733 cases and 424,528 controls), and lipid traits, using data from the Global Lipid Genetics Consortium (188,577 subjects). We identified six previously unreported loci at genome-wide significance (P < 5 × 10−8), three which were associated with Triglycerides and CAD, two which were associated with LDL cholesterol and CAD, and one associated with Total Cholesterol and CAD. At several of our loci, the GWAS signals jointly localize with genetic variants associated with expression level changes for one or more neighboring genes, indicating that these loci may be affecting disease risk through regulatory activity.ConclusionsWe discovered six novel variants individually associated with both lipids and coronary artery disease.
Large-scale RNA editing profiling in different adult chicken tissues
Authors: Shafiei Hamid , Bakhtiarizadeh Mohammad Reza , Salehi Abdolreza 
Published: May 2018

AbstractRNA editing is a post-transcription maturation process that diversifies genomically encoded information and can lead to diversity and complexity of transcriptome, especially in the brain. Thanks to next-generation sequencing technologies, a large number of editing sites have been identified in different species, especially in human, mouse and rat. While this mechanism is well described in mammals, only a few studies have been performed in the chicken. Here, we developed a rigorous computational strategy to identify RNA editing sites in eight different tissues of the chicken (brain, spleen, colon, lung, kidney, heart, testes and liver), based on RNA sequencing data alone. We identified 68 A-to-G editing sites in 46 genes. Only two of these were previously reported in chicken. We found no C-to-U sites, attesting the lack of this type of editing mechanism in the chicken. Similar to mammals, the editing sites were enriched in non-coding regions, rarely resulted in change of amino acids, showed a critical role in nervous system and had a low guanosine level upstream of the editing site and some enrichment downstream from the site. Moreover, in contrast to mammals, editing sites were weakly enriched in interspersed repeats and the frequency and editing ratio of non-synonymous sites were higher than those of synonymous sites.Interestingly, we found several tissue-specific edited genes including GABRA3, SORL1 and HTR1D in brain and RYR2 and FHOD3 in heart that were associated with functional processes relevant to the corresponding tissue. This finding highlighted the importance of the RNA editing in several chicken tissues, especially the brain. This study extends our understanding of RNA editing in chicken tissues and establish a foundation for further exploration of this process.
Bacteria are required for regeneration of the Xenopus tadpole tail
Authors: Bishop Thomas F. , Beck Caroline W. 
Published: May 2018

AbstractThe impressive regenerative capabilities of amphibians have been studied for over a century. Although we have learnt a great deal about regenerative processes, the factors responsible for the initiation of regeneration have remained elusive. A previous study implicated reactive oxygen species (ROS) and the ROS-generator, NADPH oxidase (Nox), in Xenopus tadpole tail regeneration. In this study we suggest that Nox is expressed as a consequence of NF-κB transcription factor activity and that ROS produced by Nox, in turn, help to maintain the activity of NF-κB, forming a positive-feedback loop. Microorganisms were found to be required for regeneration through binding to toll-like receptors (TLR). NF-κB is a downstream component of TLR pathways and its activation through TLR stimulation could jump-start the positive-feedback loop. These findings provide potential targets for the activation of regeneration in non-regenerative animals.
Baculovirus-inducing fast-acting innate immunity killsPlasmodiumliver stages
Authors: Emran Talha Bin , Iyori Mitsuhiro , Ono Yuki , Amelia Fitri , Yusuf Yenni , Islam Ashekul , Alam Asrar , Ogawa Ryohei , Matsuoka Hiroyuki , Yamamoto Daisuke , Yoshida Shigeto 
Published: May 2018

ABSTRACTBaculovirus (BV), an enveloped insect virus with a circular double-stranded DNA genome, possesses unique characteristics that induce strong innate immune responses in mammalian cells. Here, we show that BV administration not only sterilely protects BALB/c mice for at least 7 days from subsequentPlasmodium bergheisporozoite infection but also eliminates existing liver-stage parasites completely, effects superior to those of primaquine, and does so in a TLR9-independent manner. Six hours post-BV administration, IFN-α and IFN-γ were robustly produced in serum, and RNA transcripts of interferon-stimulated genes were drastically upregulated in the liver. Thein vivopassive transfer of post-BV administration serum effectively eliminated liver-stage parasites, and IFN-α neutralization abolished this effect, indicating that the BV liver-stage parasite killing mechanism is downstream of the type I IFN signaling pathway. Our results demonstrate that BV is a potent IFN-inducing prophylactic and therapeutic agent with great potential for further development as a new malaria vaccine and/or anti-hypnozoite drug.
The Evolution and Sequence Diversity of FhuA inSalmonellaandEscherichia
Authors: Wang Yejun , Chen Xiongbin , Zhu Guoqiang , White Aaron P. , Köster Wolfgang 
Published: May 2018

ABSTRACTThefhuACDBoperon, present in a number ofEnterobacteriaceae, encodes components essential for the uptake of ferric hydroxamate type siderophores. FhuA acts not only as transporter for physiologically important chelated ferric iron, but also as receptor for various bacteriophages, toxins and antibiotics, which are pathogenic to bacterial cells. In this research, thefhuAgene distribution and sequence diversity were investigated inEnterobacteriaceae, especiallySalmonellaandEscherichia. Comparative sequence analysis resulted in afhuAphylogenetic tree that did not match the expected phylogeny based on housekeeping sequence analysis or trees offhuCDBgenes. ThefhuAsequences showed a unique mosaic-clustering pattern. On the other hand, the gene sequences showed high conservation for strains from the same serovar or serotype. In total, six clusters were identified from FhuA proteins inSalmonellaandEscherichia, among which typical peptide fragment variations could be defined. Six fragmental insertions / deletions and two substitution fragments were discovered, which could well classify the different clusters. Structure modeling demonstrated that all the six featured insertions/deletions and one substitution fragment are located at the apexes of the long loops of FhuA external pocket. These frequently mutated regions are likely under high selection pressure, and bacterial strains could have escaped from phage infection or toxin / antibiotics attack viafhuAgene mutations while maintaining the siderophore uptake activity essential for bacterial survival. The unusualfhuAclustering suggests that high frequency exchange offhuAgenes has occurred between enterobacterial strains after distinctive species were established.IMPORTANCEThe enterobacterialfhuACDBoperon encodes proteins which mediate the uptake of siderophores to supply the cells with iron essential for bacterial survival. Here we show different evolutionary patterns for thefhugenes within the same operon. ThefhuAhas a phylogenetic tree that does not match the species phylogeny, whereas the rest of thefhugenes do. ThefhuAgenes showed inter-species sequence convergence and conservation within specific serovars and serotypes. Nearly all of the significant sequence differences among FhuA clusters are located in potential ligand-binding sites on the extracellular surface of fhuA-encoding receptors. The unusualfhuAclustering suggests the frequent recombination and exchange offhuAgenes between enterobacterial strains in the evolutionary state after distinctive species were established.Our findings suggested either a new evolutionary mechanism or local gene recombination infhuAthat is in contrast to previous evolutionary hypotheses that have formed under the assumption of no recombination.
The genetic architecture of hair colour in the UK population
Authors: Morgan Michael D. , Pairo-Castineira Erola , Rawlik Konrad , Canela-Xandri Oriol , Rees Jonathan , Sims David , Tenesa Albert , Jackson Ian J. 
Published: May 2018

AbstractWe have extensively mapped the genes responsible for hair colour in the UK population. MC1R mutations are well established as the principal genetic cause of red hair colour, but with variable penetrance. We find variation at genes encoding its agonist (POMC), inverse agonist (ASIP) and other loci contribute to red hair and demonstrate epistasis between MC1R and some of these loci. Blonde hair is associated with over 200 loci, and we find a genetic continuum from black through dark and light brown to blonde. Many of the associated genes are involved in hair growth or texture, emphasising the cellular connections between keratinocytes and melanocytes in the determination of hair colour.