Medicine by Sfakianakis Alexandros: 02/04/16

Πέμπτη 4 Φεβρουαρίου 2016

Genetic Mapping of Resistance to Meloidogyne arenaria in Arachis stenosperma: A New Source of Nematode Resistance for Peanut

Root-knot nematodes (RKN; Meloidogyne sp.) are a major threat to crops in tropical and subtropical regions worldwide. The use of resistant crop varieties is the preferred method of control because nematicides are expensive, and hazardous to humans and the environment. Peanut (Arachis hypogaea) is infected by four species of RKN, the most damaging being M. arenaria, and commercial cultivars rely on a single source of resistance. In this study, we genetically characterize RKN resistance of the wild Arachis species A. stenosperma using a population of 93 recombinant inbred lines developed from a cross between A. duranensis and A. stenosperma. Four quantitative trait loci (QTL) located on linkage groups 02, 04, and 09 strongly influenced nematode root galling and egg production. Drought-related, domestication and agronomically relevant traits were also evaluated, revealing several QTL. Using the newly available Arachis genome sequence, easy-to-use KASP (kompetitive allele specific PCR) markers linked to the newly identified RKN resistance loci were developed and validated in a tetraploid context. Therefore, we consider that A. stenosperma has high potential as a new source of RKN resistance in peanut breeding programs.

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argyle: An R Package for Analysis of Illumina Genotyping Arrays

Genotyping microarrays are an important and widely-used tool in genetics. I present argyle, an R package for analysis of genotyping array data tailored to Illumina arrays. The goal of the argyle package is to provide simple, expressive tools for nonexpert users to perform quality checks and exploratory analyses of genotyping data. To these ends, the package consists of a suite of quality-control functions, normalization procedures, and utilities for visually and statistically summarizing such data. Format-conversion tools allow interoperability with popular software packages for analysis of genetic data including PLINK, R/qtl and DOQTL. Detailed vignettes demonstrating common use cases are included as supporting information. argyle bridges the gap between the low-level tasks of quality control and high-level tasks of genetic analysis. It is freely available at http://ift.tt/1IeTaQL and has been submitted to Bioconductor.

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Tying Down Loose Ends in the Chlamydomonas Genome: Functional Significance of Abundant Upstream Open Reading Frames

The Chlamydomonas genome has been sequenced, assembled, and annotated to produce a rich resource for genetics and molecular biology in this well-studied model organism. The annotated genome is very rich in open reading frames upstream of the annotated coding sequence ('uORFs'): almost three quarters of the assigned transcripts have at least one uORF, and frequently more than one. This is problematic with respect to the standard 'scanning' model for eukaryotic translation initiation. These uORFs can be grouped into three classes: class 1, initiating in-frame with the coding sequence (CDS) (thus providing a potential in-frame N-terminal extension); class 2, initiating in the 5' untranslated sequences (5UT) and terminating out-of-frame in the CDS; and class 3, initiating and terminating within the 5UT. Multiple bioinformatics criteria (including analysis of Kozak consensus sequence agreement and BLASTP comparisons to the closely related Volvox genome, and statistical comparison to cds and to random sequence controls) indicate that of ~4000 class 1 uORFs, approximately half are likely in vivo translation initiation sites. The proposed resulting N-terminal extensions in many cases will sharply alter the predicted biochemical properties of the encoded proteins. These results suggest significant modifications in ~2000 of the ~20,000 transcript models with respect to translation initiation and encoded peptides. In contrast, class 2 uORFs may be subject to purifying selection, and the existent ones (surviving selection) are likely inefficiently translated. Class 3 uORFs are found in more than half of transcripts, frequently multiple times per transcript; however, they are remarkably similar to random sequence expectations with respect to size, number, and composition, and therefore may in most cases be selectively neutral.

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SAGA DUB-Ubp8 Deubiquitylates Centromeric Histone Variant Cse4

Aneuploidy, the unbalanced segregation of chromosomes during cell division, is recurrent in many tumors and the cause of birth defects and genetic diseases. Centromeric chromatin represents the chromosome attachment site to the mitotic spindle, marked by specialized nucleosomes containing a specific histone variant, CEN-H3/Cse4, in yeast. Mislocalization of Cse4 outside the centromere is deleterious and may cause aberrant chromosome behavior and mitotic loss. For this reason, ubiquitylation by the E3-ubiquitin ligase Psh1 and subsequent proteolysis tightly regulates its restricted localization. Among multiproteic machineries, the SAGA complex is not merely engaged in acetylation but also directly involved in deubiquitylation. In this study, we investigated the role of SAGA-DUB's Ubp8-driven deubiquitylation of the centromeric histone variant Cse4 in budding yeast. We found that Ubp8 works in concert with the E3-ubiquitin ligase Psh1, and that its loss causes defective deubiquitylation and the accumulation of a short ubiquitin oligomer on Cse4. We also show that lack of Ubp8 and defective deubiquitylation increase mitotic instability, cause faster Cse4 proteolysis and induce mislocalization of the centromeric histone outside the centromere. Our data provide evidence for a fundamental role of DUB-Ubp8 in deubiquitylation and the stability of the centromeric histone in budding yeast.

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Back to Acid Soil Fields: The Citrate Transporter SbMATE Is a Major Asset for Sustainable Grain Yield for Sorghum Cultivated on Acid Soils

Aluminum (Al) toxicity damages plant roots and limits crop production on acid soils, which comprise up to 50% of the world's arable lands. A major Al tolerance locus on chromosome 3, Alt_SB, controls aluminum tolerance in sorghum [Sorghum bicolor (L.) Moench] via SbMATE, an Al-activated plasma membrane transporter that mediates Al exclusion from sensitive regions in the root apex. As is the case with other known Al tolerance genes, SbMATE was cloned based on studies conducted under controlled environmental conditions, in nutrient solution. Therefore, its impact on grain yield on acid soils remains undetermined. To determine the real world impact of SbMATE, multi-trait quantitative trait loci (QTL) mapping in hydroponics, and, in the field, revealed a large-effect QTL colocalized with the Al tolerance locus Alt_SB, where SbMATE lies, conferring a 0.6 ton ha^–1 grain yield increase on acid soils. A second QTL for Al tolerance in hydroponics, where the positive allele was also donated by the Al tolerant parent, SC283, was found on chromosome 9, indicating the presence of distinct Al tolerance genes in the sorghum genome, or genes acting in the SbMATE pathway leading to Al-activated citrate release. There was no yield penalty for Alt_SB, consistent with the highly localized Al regulated SbMATE expression in the root tip, and Al-dependent transport activity. A female effect of 0.5 ton ha^–1 independently demonstrated the effectiveness of Alt_SB in hybrids. Al tolerance conferred by Alt_SB is thus an indispensable asset for sorghum production and food security on acid soils, many of which are located in developing countries.

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The wavy Mutation Maps to the Inositol 1,4,5-Trisphosphate 3-Kinase 2 (IP3K2) Gene of Drosophila and Interacts with IP3R to Affect Wing Development

Inositol 1,4,5-trisphosphate (IP₃) regulates a host of biological processes from egg activation to cell death. When IP₃-specific receptors (IP3Rs) bind to IP₃, they release calcium from the ER into the cytoplasm, triggering a variety of cell type- and developmental stage-specific responses. Alternatively, inositol polyphosphate kinases can phosphorylate IP₃; this limits IP3R activation by reducing IP₃ levels, and also generates new signaling molecules altogether. These divergent pathways draw from the same IP₃ pool yet cause very different cellular responses. Therefore, controlling the relative rates of IP3R activation vs. phosphorylation of IP₃ is essential for proper cell functioning. Establishing a model system that sensitively reports the net output of IP₃ signaling is crucial for identifying the controlling genes. Here we report that mutant alleles of wavy (wy), a classic locus of the fruit fly Drosophila melanogaster, map to IP₃ 3-kinase 2 (IP3K2), a member of the inositol polyphosphate kinase gene family. Mutations in wy disrupt wing structure in a highly specific pattern. RNAi experiments using GAL4 and GAL80^ts indicated that IP3K2 function is required in the wing discs of early pupae for normal wing development. Gradations in the severity of the wy phenotype provide high-resolution readouts of IP3K2 function and of overall IP₃ signaling, giving this system strong potential as a model for further study of the IP₃ signaling network. In proof of concept, a dominant modifier screen revealed that mutations in IP3R strongly suppress the wy phenotype, suggesting that the wy phenotype results from reduced IP₄ levels, and/or excessive IP3R signaling.

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Comparative Phylogenomics of Pathogenic and Nonpathogenic Species

The Ascomycete Onygenales order embraces a diverse group of mammalian pathogens, including the yeast-forming dimorphic fungal pathogens Histoplasma capsulatum, Paracoccidioides spp. and Blastomyces dermatitidis, the dermatophytes Microsporum spp. and Trichopyton spp., the spherule-forming dimorphic fungal pathogens in the genus Coccidioides, and many nonpathogens. Although genomes for all of the aforementioned pathogenic species are available, only one nonpathogen had been sequenced. Here, we enhance comparative phylogenomics in Onygenales by adding genomes for Amauroascus mutatus, Amauroascus niger, Byssoonygena ceratinophila, and Chrysosporium queenslandicum—four nonpathogenic Onygenales species, all of which are more closely related to Coccidioides spp. than any other known Onygenales species. Phylogenomic detection of gene family expansion and contraction can provide clues to fungal function but is sensitive to taxon sampling. By adding additional nonpathogens, we show that LysM domain-containing proteins, previously thought to be expanding in some Onygenales, are contracting in the Coccidioides-Uncinocarpus clade, as are the self-nonself recognition Het loci. The denser genome sampling presented here highlights nearly 800 genes unique to Coccidiodes, which have significantly fewer known protein domains and show increased expression in the endosporulating spherule, the parasitic phase unique to Coccidioides spp. These genomes provide insight to gene family expansion/contraction and patterns of individual gene gain/loss in this diverse order—both major drivers of evolutionary change. Our results suggest that gene family expansion/contraction can lead to adaptive radiations that create taxonomic orders, while individual gene gain/loss likely plays a more significant role in branch-specific phenotypic changes that lead to adaptation for species or genera.

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Quantitative Trait Locus and Genetical Genomics Analysis Identifies Putatively Causal Genes for Fecundity and Brooding in the Chicken

Life history traits such as fecundity are important to evolution because they make up components of lifetime fitness. Due to their polygenic architectures, such traits are difficult to investigate with genetic mapping. Therefore, little is known about their molecular basis. One possible way toward finding the underlying genes is to map intermediary molecular phenotypes, such as gene expression traits. We set out to map candidate quantitative trait genes for egg fecundity in the chicken by combining quantitative trait locus mapping in an advanced intercross of wild by domestic chickens with expression quantitative trait locus mapping in the same birds. We measured individual egg fecundity in 232 intercross chickens in two consecutive trials, the second one aimed at measuring brooding. We found 12 loci for different aspects of egg fecundity. We then combined the genomic confidence intervals of these loci with expression quantitative trait loci from bone and hypothalamus in the same intercross. Overlaps between egg loci and expression loci, and trait–gene expression correlations identify 29 candidates from bone and five from hypothalamus. The candidate quantitative trait genes include fibroblast growth factor 1, and mitochondrial ribosomal proteins L42 and L32. In summary, we found putative quantitative trait genes for egg traits in the chicken that may have been affected by regulatory variants under chicken domestication. These represent, to the best of our knowledge, some of the first candidate genes identified by genome-wide mapping for life history traits in an avian species.

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Genetic Determinants of RNA Editing Levels of ADAR Targets in Drosophila melanogaster

RNA editing usually affects only a fraction of expressed transcripts and there is a vast amount of variation in editing levels of ADAR (adenosine deaminase, RNA-specific) targets. Here we explore natural genetic variation affecting editing levels of particular sites in 81 natural strains of Drosophila melanogaster. The analysis of associations between editing levels and single-nucleotide polymorphisms allows us to map putative cis-regulatory regions affecting editing of 16 A-to-I editing sites (cis-RNA editing quantitative trait loci or cis-edQTLs, P < 10^–8). The observed changes in editing levels are validated by independent molecular technique. All identified regulatory variants are located in close proximity of modulated editing sites. Moreover, colocalized editing sites are often regulated by same loci. Similar to expression and splicing QTL studies, the characterization of edQTLs will greatly expand our understanding of cis-regulatory evolution of gene expression.

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The Extent of mRNA Editing Is Limited in Chicken Liver and Adipose, but Impacted by Tissular Context, Genotype, Age, and Feeding as Exemplified with a Conserved Edited Site in COG3

RNA editing is a posttranscriptional process leading to differences between genomic DNA and transcript sequences, potentially enhancing transcriptome diversity. With recent advances in high-throughput sequencing, many efforts have been made to describe mRNA editing at the transcriptome scale, especially in mammals, yielding contradictory conclusions regarding the extent of this phenomenon. We show, by detailed description of the 25 studies focusing so far on mRNA editing at the whole-transcriptome scale, that systematic sequencing artifacts are considered in most studies whereas biological replication is often neglected and multi-alignment not properly evaluated, which ultimately impairs the legitimacy of results. We recently developed a rigorous strategy to identify mRNA editing using mRNA and genomic DNA sequencing, taking into account sequencing and mapping artifacts, and biological replicates. We applied this method to screen for mRNA editing in liver and white adipose tissue from eight chickens and confirm the small extent of mRNA recoding in this species. Among the 25 unique edited sites identified, three events were previously described in mammals, attesting that this phenomenon is conserved throughout evolution. Deeper investigations on five sites revealed the impact of tissular context, genotype, age, feeding conditions, and sex on mRNA editing levels. More specifically, this analysis highlighted that the editing level at the site located on COG3 was strongly regulated by four of these factors. By comprehensively characterizing the mRNA editing landscape in chickens, our results highlight how this phenomenon is limited and suggest regulation of editing levels by various genetic and environmental factors.

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G4 DNA in ras genes and its potential in cancer therapy

Publication date: Available online 4 February 2016
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Susanna Cogoi, Luigi E. Xodo
It is now well established that in the human genome the canonical double helix coexists with folded G-quadruplex structures that are known to have important biological functions. In this review we summarize the current knowledge on quadruplex formation in the promoters of the ras genes that are mutated in about 30% of all human cancers. We describe the nuclear proteins that recognize these unusual DNA structures and discuss their function in transcription. We also examine the formation of G-quadruplexes in the 5′-untranslated region of the ras transcripts and conclude this review by reporting strategies that use either ras G-quadruplexes or proteins recognizing the ras G-quadruplexes as targets of anticancer small molecules.

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Pure white-light and color-tuning of Eu3+-Gd3+-containing metallopolymer

Chem. Commun., 2016, Accepted Manuscript
DOI: 10.1039/C5CC09946C, Communication

Zhao Zhang, Yani Hui, Lin Liu, Xingqiang Lv, Xunjin Zhu, Wai-Kwok Wong, Mei Pan, Chengyong Su
Direct white-light (CIE coordinate of x = 0.333, y = 0.335, CCT of 5455 K and CRI of 82) with a high luminous efficiency (18.4%) was achieved in the first...
The content of this RSS Feed (c) The Royal Society of Chemistry

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Deadly pressure pneumothorax after withdrawal of misplaced feeding tube: a case report

Background: Many patients have a nasogastric feeding tube inserted during admission; however, misplacement is not uncommon. In this case report we present, to the best of our knowledge, the first documented fatality from pressure pneumothorax following nasogastric tube withdrawal.Case presentationAn 84-year-old Caucasian woman with dysphagia and at risk of aspiration underwent routine insertion of a nasogastric feeding tube; however, shortly after insertion she developed respiratory distress. A chest X-ray showed the tube had been misplaced into our patient's right lung. The tube was removed, but our patient died less than an hour after withdrawal. The autopsy report stated that cause of death was tension pneumothorax, which developed following withdrawal of the misplaced feeding tube. Conclusions: The indications for insertion of nasogastric feeding tubes are many and the procedure is considered harmless; however, if the tube is misplaced there is good reason to be cautious on removal as this can unmask puncture of the pleura eliciting pneumothorax and, as this case report shows, result in an ultimately deadly tension pneumothorax.

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Evaluation of treatment results of orthovoltage X-rays for a selection of previously untreated favorable basal cell carcinomas (BCC) in the head and neck area concerning local control, cosmetic and functional outcome, and toxicity profile.

Methods

A consecutive series of patients with primarily treated BCCs who were irradiated by means of orthovoltage X-rays in the Netherlands Cancer Institute in Amsterdam between January 2000 and February 2015 were retrospectively evaluated.

Results

Two hundred fifty-three BCCs in 232 patients were primarily treated with orthovoltage X-rays. The local control rates at 1, 3, and 5 years for this selection of basal cell carcinomas were 98.9%, 97.5%, and 96.3%, respectively. Tumor size was the only significant predictor for local control because BCCs < 20 mm had a significantly higher 5-year local control rate than lesions ≥ 20 mm (96.8% vs. 89.4%, P = 0.041). Acute toxicity healed spontaneously without medical intervention, and late toxicity rates were low. Functional impairments were negligible, and the cosmetic outcome was excellent.

Conclusion

Orthovoltage therapy for well-selected favorable BCCs in the head and neck area resulted in excellent local control rates, a low toxicity profile, and apparently satisfactory functional and cosmetic outcomes. Orthovoltage irradiation is a good alternative for surgery for BCCs with favorable histologic prognosis at locations that are at risk for postoperative functional or cosmetic changes, such as the nose or canthus.

Level of Evidence

4. Laryngoscope, 2016

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Are leeches effective in local/regional skin flap salvage?

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Effets de l’activité physique sur le syndrome de sevrage et le craving à l’arrêt du tabac

Publication date: Available online 3 February 2016
Source:Revue des Maladies Respiratoires
Author(s): M. Underner, J. Perriot, G. Peiffer, J.-C. Meurice
Un fumeur sur deux qui poursuit sa consommation de tabac jusqu'à la fin de son existence décédera d'une maladie en lien avec cet usage. Le tabagisme est à l'origine d'une forte dépendance qui rend l'arrêt du tabac difficile du fait de l'apparition d'un syndrome de sevrage avec craving (désir impérieux de fumer sans délai). Cette revue s'est attachée à évaluer les effets de l'activité physique sur le craving lors de l'arrêt du tabac. Elle a rassemblé 18 études randomisées contrôlées comprenant une activité physique. Dix-sept des 18 essais mettent en évidence l'efficacité de l'activité physique pour diminuer le craving tabagique. La concordance de ces résultats constitue un élément de preuve solide de l'intérêt de l'activité physique pour réduire le craving à l'arrêt du tabac. La pratique d'une activité physique doit donc être conseillée pour aider l'arrêt du tabac et devrait être intégrée dans les protocoles de sevrage tabagique.One in two people who smoke for their whole lifetime will die from a disease related to tobacco use. The smoking habit is sustained by nicotine dependence, which makes smoking cessation very difficult because of withdrawal syndrome and craving (urge to smoke without delay). The aim of this review was to evaluate the impact of physical activity interventions to reduce tobacco craving in smoking cessation. It included 18 randomized controlled trials, which incorporated physical activity. Seventeen of the 18 trials demonstrate the effectiveness of the physical activity in reducing tobacco craving. The consistency of these results constitutes solid evidence of the importance of physical activity as an aid to smoking cessation. Advice to increase physical activity should therefore be given during quit attempts and should be incorporated into smoking cessation programs.

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Atteinte des voies aériennes distales et immunodépression

Publication date: Available online 4 February 2016
Source:Revue des Maladies Respiratoires
Author(s): P.-R. Burgel, A. Bergeron, C. Knoop, D. Dusser
IntroductionLes immunodépressions congénitales et acquises peuvent se compliquer d'atteintes respiratoires touchant les voies aériennes distales. L'objectif de cet article est de faire une mise au point sur les atteintes des voies aériennes distales rencontrées lors des principales causes d'immunodépression.État des connaissancesLes déficits immunitaires communs d'expression variable se compliquent fréquemment d'atteintes bronchiolaires et de dilatations des bronches d'origine infectieuse. Des bronchiolites folliculaires ou granulomateuses d'étiologie non infectieuse peuvent également survenir. La bronchiolite oblitérante est la première cause de mortalité après la première année post-greffe chez les patients ayant eu une transplantation pulmonaire. Elle peut survenir chez les patients ayant eu une allogreffe de cellules souches hématopoïétiques, en particulier en cas de réaction du greffon contre l'hôte.Perspectives et conclusionsLes atteintes des voies aériennes distales ont une expression et une physiopathologie variables selon la cause de l'immunodépression. Une meilleure compréhension de ces pathologies pourrait permettre le développement de thérapeutiques ciblées.IntroductionInnate or acquired immune deficiency may show respiratory manifestations, often characterized by small airway involvement. The purpose of this article is to provide an overview of small airway disease across the major causes of immune deficiency.BackgroundIn patients with common variable immune deficiency, recurrent lower airway infections may lead to bronchiolitis and bronchiectasis. Follicular and/or granulomatous bronchiolitis of unknown origin may also occur. Bronchiolitis obliterans is the leading cause of death after the first year in patients with lung transplantation. Bronchiolitis obliterans also occurs in patients with allogeneic haematopoietic stem cell transplantation, especially in the context of systemic graft-versus-host disease.Viewpoint and conclusionSmall airway diseases have different clinical expression and pathophysiology across various causes of immune deficiency. A better understanding of small airways disease pathogenesis in these settings may lead to the development of novel targeted therapies.

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Functional connectivity density and balance in young patients with traumatic axonal injury

Abstract Our previous study provided some evidence for the relationship between abnormal structural connectivity and poor balance performance in young traumatic axonal injury (TAI) patients. An enhanced understanding of the functional connectivity following TAI may allow targeted treatments geared toward improving brain function and postural control. Twelve patients with TAI and 28 normally developing children (aged 9-19 years) performed the sensory organization test (SOT) protocol of the EquiTest (Neurocom). All participants were scanned using resting-state functional magnetic resonance imaging series along with anatomical scans. We applied "functional connectivity density mapping" (FCDM), a voxel-wise data-driven method that calculates individual functional connectivity maps to obtain both short-range and long-range FCD. Findings revealed that the TAI group scored generally lower than the control group on the SOT, especially when proprioceptive feedback was compromised. Between-group maps noted significantly decreased long-range FCD in the TAI group in frontal and subcortical regions and significantly increased short-range FCD in frontal regions, left inferior parietal, and cerebellar lobules. Moreover, lower balance levels in TAI patients were associated with a lower long-range FCD in left putamen and cerebellar vermis. These findings suggest that long-range connections may be more vulnerable to TAI than short-range connections. Moreover, higher values of short-range FCD may suggest adaptive mechanisms in the TAI group. Finally, this study supports the view that FCDM is a valuable tool for selectively predicting functional motor deficits in TAI patients.

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Human dimensions of ecological restoration. Integrating science, nature and culture. D. Egan, E. E. Hjerpe and J. Abrams (eds.). Island Press, Washington, DC, 2011

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Increased plant growth from nitrogen addition should conserve phosphorus in terrestrial ecosystems

Inputs of available nitrogen (N) to ecosystems have grown over the recent past. There is limited general understanding of how increased N inputs affect the cycling and retention of other potentially limiting nutrients. Using a plant-soil nutrient model, and by explicitly coupling N and phosphorus (P) in plant biomass, we examine the impact of increasing N supply on the ecosystem cycling and retention of P, assuming that the main impact of N is to increase plant growth. We find divergent responses in the P cycle depending on the specific pathway by which nutrients are lost from the ecosystem. Retention of P is promoted if the relative propensity for loss of plant available P is greater than that for the loss of less readily available organic P. This is the first theoretical demonstration that the coupled response of ecosystem-scale nutrient cycles critically depends on the form of nutrient loss. P retention might be lessened, or reversed, depending on the kinetics and size of a buffering reactive P pool. These properties determine the reactive pool's ability to supply available P. Parameterization of the model across a range of forest ecosystems spanning various environmental and climatic conditions indicates,that enhanced plant growth due to increased N should trigger increased P conservation within ecosystems while leading to more dissolved organic P loss. We discuss how the magnitude and direction of the effect of N may also depend on other processes.

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All the essentials of ecology?

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Contents: (Adv. Healthcare Mater. 3/2016)

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Masthead: (Adv. Healthcare Mater. 3/2016)

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Ultrathin Injectable Sensors: Ultrathin Injectable Sensors of Temperature, Thermal Conductivity, and Heat Capacity for Cardiac Ablation Monitoring (Adv. Healthcare Mater. 3/2016)

On page 373, I. R. Efimov, J. A. Rogers, and co-workers report classes of ultrathin injectable sensors for spatiotemporal determination of temperature, thermal conductivity, and heat capacity of biological tissues. These flexible devices provide unique capabilities in monitoring of depth-dependent changes in the properties of myocardial tissue that result from cardiac ablation therapy. The materials and mechanical designs provide minimally invasive, biocompatible operation.

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Stem Cell Mechanobiology: 3D Micropillars Guide the Mechanobiology of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes (Adv. Healthcare Mater. 3/2016)

On page 335, M. Münzenberg, M. Delcea, and co-workers report on the use of 3D micropillars generated by photolithography as a platform to probe by atomic force microscopy the mechanodynamics of human induced pluripotent stem cell-derived cardiomyocytes. The results indicate that 3D micropillars guide subcellular cytoskeletal modifications of cardiomyocytes and lead to biochemical changes altering beating rate, stiffness, and calcium dynamics of the cells.

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Controlled Release: Photocleavable Hydrogels for Light-Triggered siRNA Release (Adv. Healthcare Mater. 3/2016)

"On-demand" release of genetic material for regulation of cell gene expression to control cell behavior is an innovative strategy for disease therapeutics and tissue regeneration. On page 305, E. Alsberg and co-workers explore a photolabile hydrogel system that can be used to actively tune the release of siRNA via the application of external UV light. The cover image illustrates how external UV light drives hydrogel degradation, and this accelerates the release of siRNA to ultimately alter gene expression of recipient cells.

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Osteogenic Differentiation: Periodic Nanoneedle and Buffer Zones Constructed on a Titanium Surface Promote Osteogenic Differentiation and Bone Calcification In Vivo (Adv. Healthcare Mater. 3/2016)

On page 364, C. Ning and co-workers present the effects of constructing functionalized microscale zones on titanium bone implants on osteogenesis. Periodic microscale nanoneedle zones and buffer zones on titanium implants surface promote osteoblast proliferation, modulate zonal protein adsorption and apatite deposition capacities, as well as induce mechanotransduction, leading to effective bone regeneration.

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Development of 3D Microvascular Networks Within Gelatin Hydrogels Using Thermoresponsive Sacrificial Microfibers

A 3D microvascularized gelatin hydrogel is produced using thermoresponsive sacrificial poly(N-isopropylacrylamide) microfibers. The capillary-like microvascular network allows constant perfusion of media throughout the thick hydrogel, and significantly improves the viability of human neonatal dermal fibroblasts encapsulated within the gel at a high density.

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ssDNA Functionalized Nanoceria: A Redox Active Aptaswitch for Biomolecular Recognition

Quantification of biomolecular binding events is a critical step for the development of biorecognition assays for diagnostics and therapeutic applications. This paper reports the design of redox active switches based on aptamer conjugated nanoceria for detection and quantification of biomolecular recognition. It is shown that the conformational transition state of the aptamer on nanoceria, combined with the redox properties of these particles can be used to create surface based structure switchable aptasensing platforms. Changes in the redox properties at the nanoceria surface upon binding of the ssDNA and its target analyte enables rapid and highly sensitive measurement of biomolecular interactions. This concept is demonstrated as a general applicable method to the colorimetric detection of DNA binding events. An example of a nanoceria aptaswitch for the colorimetric sensing of Ochratoxin A (OTA) and applicability to other targets is provided. The system can sensitively and selectivity detect as low as 0.15 × 10⁻⁹m OTA. This novel assay is simple in design and does not involve oligonucleotide labeling or elaborate nanoparticle modification steps. The proposed mechanism discovered here opens up a new way of designing optical sensing methods based on aptamer recognition. This approach can be broadly applicable to many bimolecular recognition processes and related applications.

A nanoceria based colorimetric aptaswitch for probing bimolecular recognition events is reported. The method capitalizes on a newly discovered phenomenon involving reversible, target tunable electrostatic and steric repulsion of single-stranded DNA aptamers to the surface of nanoceria. The results demonstrate that redox active nanoceria can be used as a universal platform to quantify biomolecular targets by measuring changes in the redox properties at the nanoparticle surface upon binding of the DNA and its target analyte.

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Impaired Neurite Contact Guidance in Ubiquitin Ligase E3a (Ube3a)-Deficient Hippocampal Neurons on Nanostructured Substrates

Recent discoveries indicate that during neuronal development the signaling processes that regulate extracellular sensing (e.g., adhesion, cytoskeletal dynamics) are important targets for ubiquitination-dependent regulation, in particular through E3 ubiquitin ligases. Among these, Ubiquitin E3a ligase (UBE3A) has a key role in brain functioning, but its function and how its deficiency results in the neurodevelopmental disorder Angelman syndrome is still unclear. Here, the role of UBE3A is investigated in neurite contact guidance during neuronal development, in vitro. The microtopography sensing of wild-type and Ube3a-deficient hippocampal neurons is studied by exploiting gratings with different topographical characteristics, with the aim to compare their capabilities to read and follow physical directional stimuli. It is shown that neuronal contact guidance is defective in Ube3a-deficient neurons, and this behavior is linked to an impaired activation of the focal adhesion signaling pathway. Taken together, the results suggest that the neuronal contact sensing machinery might be affected in Angelman syndrome.

The performance of neurite contact guidance and adhesion signaling is addressed in Ubiquitin ligase E3a (Ube3a)-deficient hippocampal neurons (Angelman syndrome model). By using nanogrooved substrates, impairments in the contact guidance and neurite polarization of Ube3aKO neurons in response to pure topographical signals are demonstrated and this behavior is linked to the impaired activation of focal adhesion pathway.

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pH-Responsive Fe(III)–Gallic Acid Nanoparticles for In Vivo Photoacoustic Imaging-Guided Photothermal Therapy

pH-responsive biocompatible Fe(III)–gallic acid nanoparticles with strong near-infrared absorbance are very stable in mild acidic conditions, but easily decomposed in neutral conditions, which enables the nanoparticles to be stable in a tumor and easily metabolized in other organs, thus providing a safe nanoplatform for in vivo photoacoustic imaging/photothermal therapy theranostic applications.

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The Role of Surface Nanotopography and Chemistry on Primary Neutrophil and Macrophage Cellular Responses

Synthetic materials employed for enhancing, replacing, or restoring biological functionality may be compromised by the host immune responses that they evoke. Surface modification has attracted substantial attention as a tool to modulate the host response to synthetic materials; however, how surface nanotopography combined with chemistry affects immune effector cell responses is still poorly understood. To address this open question, a unique set of model surfaces with controlled surface nanotopography in the range of 16, 38, and 68 nm has been generated. Tailored outermost surface chemistry that was amine, carboxyl, or methyl group rich has been provided. The combinations of these properties yield 12 surface types that are subject to functional assays assessing key immune effector cells, namely, primary neutrophil and macrophage responses in vitro. The data demonstrate that surface nanotopography leads to enhanced matrix metalloproteinase-9 production from primary neutrophils, and a decrease in pro-inflammatory cytokine secretion from primary macrophages. Together, these results are the first to directly compare the immunomodulatory effects of the cooperative interplay between surface nanotopography and chemistry.

Innate immune effector cells can differentially respond to the controlled surface nanotopography in the range of 16, 38, and 68 nm. Additional overcoating of these surfaces with amine, carboxyl, or methyl group rich chemistries demonstrates that surfaces with hydrophillic anionic overcoated 68 nm gold nanoparticles can modulate neutrophil and macrophage functionality.

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Coxiella burnetii Seroprevalence and Risk Factors in Cattle Farmers and Farm Residents in Three Northeastern Provinces and Inner Mongolia Autonomous Region, China

Little is known about Coxiella burnetii infection among cattle farmers and farm residents in China. Thus, the present study was conducted to detect the seroprevalence of C. burnetii infection and estimate associated risk factors among cattle farmers and farm residents in China. A cross-sectional study was designed, and sera of 362 people living or working on 106 cattle farms were tested for C. burnetii IgG and IgM antibodies by immunofluorescence assay. Overall C. burnetii seroprevalence was 35.6% (129/362, 95% CI: 30.70–40.57), and 112 participants had experienced a past infection and seventeen (4.7%) had experienced a relatively recent infection. In the final combined multilevel model, the following activities were significantly associated with presence of antibodies against C. burnetii: milking cattle, providing general healthcare to cattle, providing birth assistance, contact dead-born animals, urbanization, and presence of mice and/or rats in the stable. Moreover, presence of disinfection equipment was a significant protective factor. This is the first study addressing the seroprevalence and risk factors of C. burnetii infection in cattle farmers and farm residents in three northeastern provinces and Inner Mongolia Autonomous Region, China.

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Gradient-based quantitative image reconstruction in ultrasound-modulated optical tomography: first harmonic measurement type in a linearised diffusion formulation

Powell, S; Arridge, SR; Leung, TS; (2016) Gradient-based quantitative image reconstruction in ultrasound-modulated optical tomography: first harmonic measurement type in a linearised diffusion formulation. IEEE Transactions on Medical Imaging , 35 (2) pp. 456-467. 10.1109/TMI.2015.2478742 . Green open access

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The stress regulator FKBP51 drives chronic pain by modulating spinal glucocorticoid signaling

Geranton, SM; Maiarù, M; Tochiki, KK; Cox, MB; Annan, LV; Bell, CG; Feng, X; Geranton, SM; Maiarù, M; Tochiki, KK; Cox, MB; Annan, LV; Bell, CG; Feng, X; Hausch, F; - view fewer (2016) The stress regulator FKBP51 drives chronic pain by modulating spinal glucocorticoid signaling.

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In situ performance of various metal doped catalysts in micro-pyrolysis and continuous fast pyrolysis

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On the aspect of deverbal nominals: a corpus study of perception nominalizations in Spanish

Nominalizations have mainly been studied from a theoretical point of view and consequently, elaborate corpus studies on this category are hard to find. Moreover, apart from some recent interest in psychological nouns, literature has generally focused on prototypical instances, i.e. deverbal nominalizations derived from verbs with an agentive subject (e.g. construction, translation). This paper fills up these gaps by examining the aspectual behaviour of a fairly neglected class, namely perception nominals in Spanish (e.g. vista, mirada, escucha). Corpus data of different nature are used to show that the aspectual complexity of these nominals is comparable to the heterogeneity of the related class of perception verbs.

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Modelled effects of rising CO2 concentration and climate change on native perennial grass and sown grass-legume pastures

Native perennial grass and sown grass-legume pastures are an important agricultural and environmental resource. We investigated the impact of rising carbon dioxide concentration ([CO2]) and projected climate changes on these pasture ecosystems in southeastern Tasmania, Australia, using a biophysical simulation model, EcoMod. The model consists of interdependent modules that describe soil physicochemical and hydrological characteristics, and pasture growth and senescence, with fluxes described by empirical and mechanistic equations. Our simulations showed that in native pastures, projected climate change increased the biomass of C-4 grasses, with limited impact upon C-3 grasses, a trend reversed by rising [CO2]. In sown pastures, projected climate change decreased the biomass of perennial rye grass Lolium perenne and total biomass markedly by 2070, whilst subterranean clover Trifolium subterraneum biomass increased. Subterranean clover biomass changed little with increased [CO2] alone, whereas perennial rye grass biomass increased. Responses across pastures reflected species' tolerances to environmental factors, with projected climate change generally having more of an impact on biomass than rising [CO2]. Changes in both [CO2] and climate led to a reduction in protein content and digestibility. Soil inorganic nutrient concentrations decreased with increasing [CO2] and increased with projected climate change. Further simulations should investigate whether these patterns are robust for different sites and alternative environmental futures. Our results reinforce the need to pursue adaptation strategies in response to environmental change in order to maintain productive pasture ecosystems.

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Removing phosphorus from ecosystems through nitrogen fertilization and cutting with removal of biomass

High amounts of phosphorus (P) are in soil of former farmland due to previous fertilizer additions. Draining these residues would provide conditions for grassland plant species diversity restoration amongst other ecosystem benefits. Nitrogen (N) fertilization followed by cutting with subsequent removal of biomass has been suggested as a P residue removal method. We present a general model of N and P ecosystem cycling with nutrients coupled in plant biomass. We incorporate major P pools and biological and physico-chemical fluxes around the system together with transfers into and out of the system given several decades of management. We investigate conditions where N addition and cutting accelerate fertilizer P draining. Cutting does not generally accelerate soil P depletion under short-term management because the benefits of biomass removal through decreased P mineralization occur on too long a timescale compared to cutting's impact on the ability of plants to deplete nutrients. Short-term N fertilization lowers soil fertilizer P residues, provided plant growth remains N limited. In such situations, N fertilization without biomass removal increases soil organic P. Some scenarios show significant reductions in available P following N addition, but many situations record only marginal decreases in problematic soil P pools compared to the unfertilized state. We provide explicit conditions open to experimental testing. Cutting might have minimal adverse impacts, but will take time to be successful. N fertilization either alone or in combination with cutting is more likely to bring about desired reductions in P availability thus allowing grassland restoration, but might have undesired ecosystem consequences.

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Climate change impacts on Australian grazing systems: whole farming systems analysis and tools for the Australian and New Zealand grazing industries project report

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Aquaculture of fish and shrimp in tropical areas

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Time To ‘Walk Away’ From Next-Generation Sequencing?

Lately, it feels like a day doesn't go by without hearing about the vision of self-driving cars in newspapers, on TV, radio news and in the blogosphere. And now, just this month, the government pledged $4 billion over the next 10 years to make this vision a reality. Highlighted among the promises of this technology Read the rest of this article

The post Time To 'Walk Away' From Next-Generation Sequencing? appeared first on Accelerating Science.

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Can Plastic Beads Cause Mardi Gras Misfortune?

Beads are a colorful symbol of Mardi Gras and are thrown from the many Krewes participating in the yearly parades. According to Mardi Gras Day, "the bead phenomena is a relatively new one considering that while the first Mardi Gras parade in New Orleans occurred in the 1830s, it wasn't until the Rex parade threw Read the rest of this article

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They Won’t Be Throwing Louisiana Opal Beads at Mardi Gras

There's no doubt that Mardi Gras is a colorful celebration. Although the 'official colors' of the celebration are purple for justice, gold for power and green for faith, every color of the rainbow can be seen in headdresses, costumes, masks, and banners on the streets of New Orleans. So it is appropriate that the Louisiana Read the rest of this article

The post They Won't Be Throwing Louisiana Opal Beads at Mardi Gras appeared first on Accelerating Science.

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The Wrought Iron Balconies of New Orleans

If you happen to be in New Orleans during Mardi Gras season, make sure you look up at all the beautiful wrought iron balconies or at the detailed garden gates that can be found throughout the city. Those ornamental gates, fences, and windows along St. Charles Avenue and the decorative balconies in the French Quarter Read the rest of this article

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