bluuebunny/crossref_metadata_2025 huggingface dataset:
A method for the efficient and selective identification of 5-hydroxymethyluracil in genomic DNA
Authors: Bullard Whitney , Kieft Rudo , Sabatini Robert
Published: December 2016

Recently, 5-hydroxymethyluracil (5hmU) was identified in mammalian genomic DNA as an oxidative product of thymine by the ten-eleven translocation (TET) proteins. While the biological role of this modification remains unclear, identifying its genomic location will assist in elucidating function. Here we present a rapid and robust method to selectively tag and enrich genomic regions containing 5hmU. This method involves the selective glucosylation of 5hmU residues by the base J glucosyltransferase from trypanosomes creating glucosylhydroxymethyluracil (base J). The base J can then be efficiently and selectively pulled down by antibodies against base J or by J-binding protein 1. DNA that is enriched is suitable for analysis by quantitative PCR or sequencing. We utilized this tagging reaction to provide proof of concept for the enrichment of 5hmU containing DNA from a pool that contains modified and unmodified DNA. Furthermore, we demonstrate that the base J pull-down assay identifies 5hmU at specific regions of the trypanosome genome involved in transcriptional repression. The method described here will allow for a greater understanding of the functional role and dynamics of 5hmU in biology.
MetaMap Lite: an evaluation of a new Java implementation of MetaMap
Authors: Demner-Fushman Dina , Rogers Willie J , Aronson Alan R
Published: December 2016

MetaMap is a widely used named entity recognition tool that identifies concepts from the Unified Medical Language System Metathesaurus in text. This study presents MetaMap Lite, an implementation of some of the basic MetaMap functions in Java. On several collections of biomedical literature and clinical text, MetaMap Lite demonstrated real-time speed and precision, recall, and F1 scores comparable to or exceeding those of MetaMap and other popular biomedical text processing tools, clinical Text Analysis and Knowledge Extraction System (cTAKES) and DNorm.
A new era of quality measurement in rheumatology: electronic clinical quality measures and national registries
Authors: Tonner Chris , Schmajuk Gabriela , Yazdany Jinoos
Published: December 2016

Purpose of review

This article reviews the evolution of quality measurement in rheumatology, highlighting new health-information technology infrastructure and standards that are enabling unprecedented innovation in this field.

Recent findings

Spurred by landmark legislation that ties physician payment to value, the widespread use of electronic health records, and standards such as the Quality Data Model, quality measurement in rheumatology is rapidly evolving. Rather than relying on retrospective assessments of care gathered through administrative claims or manual chart abstraction, new electronic clinical quality measures (eCQMs) allow automated data capture from electronic health records. At the same time, qualified clinical data registries, like the American College of Rheumatology's Rheumatology Informatics System for Effectiveness registry, are enabling large-scale implementation of eCQMs across national electronic health record networks with real-time performance feedback to clinicians. Although successful examples of eCQM development and implementation in rheumatology and other fields exist, there also remain challenges, such as lack of health system data interoperability and problems with measure accuracy.

Quality measurement and improvement is increasingly an essential component of rheumatology practice. Advances in health information technology are likely to continue to make implementation of eCQMs easier and measurement more clinically meaningful and accurate in coming years.
Factors modulating the inflammatory response in acute gouty arthritis
Authors: Cleophas Maartje C. , Crişan Tania O. , Joosten Leo A.B.
Published: December 2016

Purpose of review

Gout is a common debilitating form of arthritis and despite our extensive knowledge on the pathogenesis its prevalence is still rising quickly. In the current review, we provide a concise overview of recent discoveries in factors tuning the inflammatory response to soluble uric acid and monosodium urate crystals.

Recent findings

It appears that soluble uric acid has a much larger role to play than just being a risk factor for gout. It may have widespread consequences for systemic inflammation and the development of metabolic syndrome. Additionally, a specific gout-related gut microbiome might not only provide us with a new diagnostic tool, but also highlights possible new therapeutic targets. Furthermore, several recent publications further elucidated the roles of mitochondrial dysfunction, production of reactive oxygen species, autophagy, and AMP-dependent protein kinase in monosodium urate-induced NLRP3 inflammasome activation. Finally, neutrophils have been shown to be involved in both the promotion and resolution of gouty inflammation. A new alpha-1-antitrypsin fusion protein may limit the proinflammatory effects of neutrophil-derived serine proteases.

Together, these studies provide us with many new insights in the pathogenesis of gout, important new treatment targets, and a rationale to further study the role of soluble uric acid in inflammatory diseases.
Mesenchymal stem cells for the management of rheumatoid arthritis: immune modulation, repair or both?
Authors: Ansboro Sharon , Roelofs Anke J. , De Bari Cosimo
Published: December 2016

Purpose of review

Mesenchymal stromal/stem cells (MSCs) have potent anti-inflammatory and immunomodulatory properties, in addition to their ability to form cartilage and bone. The purpose of this review is to highlight recent developments and current knowledge gaps in our understanding of the protective effects of MSCs against inflammatory arthritis, and to discuss their clinical exploitation for the treatment of rheumatoid arthritis (RA).

Recent findings

The weight of evidence for protective mechanisms of exogenously administered MSCs is on immunomodulatory effects, including inhibition of dendritic cell maturation, polarization of macrophages to an anti-inflammatory phenotype, and activation of regulatory T cells, thereby dampening inflammation and preventing joint damage. Evidence for direct effects on tissue repair is scant. Recent studies have identified MSC subsets in vivo and an important question is whether MSCs in their native tissues have similar immunoregulatory functions. Recent proof-of-concept clinical studies have shown a satisfactory safety profile of allogeneic MSC therapy in RA patients with promising trends for clinical efficacy.

Allogeneic MSCs could be effective in RA. Larger, multicentre clinical studies are needed to provide robust evidence, and MSC treatment at early stages of RA should be explored to ‘reset’ the immune system.
Safety and efficacy of sublaminar bands and Ponte osteotomies in rigid deformity: preliminary results in a prospective series of 20 neuromuscular scoliosis patients
Authors: Canavese Federico , Charles Yann Philippe , Samba Antoine , Dimeglio Alain
Published: December 2016

This prospective cohort study investigated radiographic outcomes and complications over time in patients with rigid neuromuscular scoliosis treated with sublaminar bands and Ponte osteotomies. Twenty consecutive patients with neuromuscular scoliosis were treated with sublaminar bands in addition to Ponte osteotomies at and around the apex of the deformity and prospectively included. All curves were rigid, with less than 30% reduction on preoperative bending films. Cobb angle, pelvic obliquity, and shoulder obliquity were significantly corrected (P<0.01). Normal thoracic kyphosis was achieved for 85% of patients at the last follow-up. No intraoperative complications were observed. The association between Ponte osteotomies and sublaminar bands appears to be efficient for the management of rigid neuromuscular deformities in children and adolescents. No death and no permanent neurological impairment, as well as no sublaminar bands associated events were recorded.
Use of Phenylacetonitrile Plus Acetic Acid to MonitorPandemis pyrusana(Lepidoptera: Tortricidae) in Apple
Authors: Knight A. L. , Basoalto E. , Judd G. J. R. , Hilton R. , Suckling D. M. , El-Sayed A. M.
Published: December 2016

A recent discovery have demonstrated that herbivore induced plant volatile compounds from apple tree infested with leafrollers were highly attractive to con-specific adult male and female leafrollers. However, this work has been conducted in New Zealand and Canada testing only low doses of kairomone. This study has been conducted in US to assess the attractiveness of higher doses of the six apple volatiles provisory identified in apple trees infested by tortricid larvaeto the leafroller,Pandemis pyrusanaKearfott. These volatiles included, β-caryophyllene, germacrene D, benzyl alcohol, phenylacetonitrile, (E)-nerolidol, and indole. No volatiles were attractive toP. pyrusanawhen used alone. However, traps baited with phenylacetonitrile plus acetic acid caught both sexes ofP. pyrusana. Traps baited with the other volatiles plus acetic acid caught zero to only incidental numbers of moths, ≤ 1.0. Adding phenylacetonitrile to traps baited with pear ester, ethyl (E,Z)-2,4-decadienoate plus acetic acid significantly reduced catches of codling moth,Cydia pomonella(L.). However, adding phenylacetonitrile to traps baited with codling moth sex pheromone, pear ester, and acetic acid did not similarly reduce moth catches ofC. pomonella. Interestingly, traps baited with phenylacetonitrile plus acetic acid caught significantly moreP. pyrusanathan traps baited with a commercial sex pheromone lure. The evaporation rate of the acetic acid co-lure was an important factor affecting catches ofP. pyrusanawith phenylacetonitrile, and studies are needed to optimize the emission rates of both lure components. Further studies are warranted to develop phenylacetonitrile and possibly other aromatic plant volatiles as bisexual lures for the range of tortricid pests attacking horticultural crops.
Interpreting short tandem repeat variations in humans using mutational constraint
Authors: Gymrek Melissa , Willems Thomas , Reich David , Erlich Yaniv
Published: December 2016

Identifying regions of the genome that are depleted of mutations can reveal potentially deleterious variants. Short tandem repeats (STRs), also known as microsatellites, are among the largest contributors ofde novomutations in humans and are implicated in a variety of human disorders. However, because of the challenges STRs pose to bioinformatics tools, per-locus studies of STR mutations have been limited to highly ascertained panels of several dozen loci. Here, we harnessed bioinformatics tools and a novel analytical framework to estimate mutation parameters for each STR in the human genome by correlating STR genotypes with local sequence heterozygosity. We applied our method to obtain robust estimates of the impact of local sequence features on mutation parameters and used this to create a framework for measuring constraint at STRs by comparing observed vs. expected mutation rates. Constraint scores identified known pathogenic variants with early onset effects. Our constraint metrics will provide a valuable tool for prioritizing pathogenic STRs in medical genetics studies.
Evidence for Philopatry and Homing in a New World Elapid Snake
Authors: Hall Alexander S. , Vázquez-Quinto Abigail M. K. , Ramírez-Velázquez Antonio , Smith Eric N.
Published: December 2016

Animal navigation allows individuals to efficiently find and use best available habitats. Despite the long history of research into well-studied taxa (e.g., pigeons, salmon, sea turtles), we know relatively little about squamate navigational abilities. Among snakes, documented philopatry (range maintenance) in a non-colubrid species has been rare. In this study, we document the first example of philopatry and homing in a new world elapid snake,Micrurus apiatus. Our data come from the first multi-year mark-recapture study of this species at the open urban preserveZoológico Regional Miguel Álvarez del Toro, in Tuxtla Gutiérrez, Chiapas, Mexico. We show that on average snakes returned to within 144 m of their last capture point. By releasing snakes in one location, we noted that recaptured individuals preferentially returned to their last capture location, compared to a distribution of random locations in the park. We conclude with a preliminary discussion of the evolution of snake homing and potential mechanisms.
Detecting ancient positive selection in humans using extended lineage sorting
Authors: Peyrégne Stéphane , James Boyle Michael , Dannemann Michael , Prüfer Kay
Published: December 2016

Natural selection that affected modern humans early in their evolution has likely shaped some of the traits that set present-day humans apart from their closest extinct and living relatives. The ability to detect ancient natural selection in the human genome could provide insights into the molecular basis for these human-specific traits. Here, we introduce a method for detecting ancient selective sweeps by scanning for extended genomic regions where our closest extinct relatives, Neandertals and Denisovans, fall outside of the present-day human variation. Regions that are unusually long indicate the presence of lineages that reached fixation in the human population faster than expected under neutral evolution. Using simulations we show that the method is able to detect ancient events of positive selection and that it can differentiate those from background selection. Applying our method to the 1000 Genomes dataset, we find evidence for ancient selective sweeps favoring regulatory changes and present a list of genomic regions that are predicted to underlie positively selected human specific traits.
Using social media to quantify spatial and temporal dynamics of nature-based recreational activities
Authors: Mancini Francesca , Coghill George M. , Lusseau David
Published: December 2016

Big data offer a great opportunity for nature-based recreation (NbR) mapping and evaluation. However, it is important to determine when and how it is appropriate to use this resource. We used Scotland as a case study to validate the use of data from Flickr as an indicator of NbR on a national scale and at several regional spatial and temporal resolutions. We compared Flickr photographs to visitor statistics in the Cairngorms National Park (CNP) and determined whether temporal variability in photo counts could be explained by known annual estimates of CNP visitor numbers. We then used a unique recent national survey of nature recreation in Scotland to determine whether the spatial distribution of Flickr photos could be explained by known spatial variability in nature use. Following this validation work, we used Flickr data to identify hotspots of wildlife watching in Scotland and investigated how they changed between 2005 and 2015.We found that spatial and temporal patterns in Flickr count are explained by measures of visitation obtained through surveys and that this relationship is reliable down to a 10 Km scale resolution. Our findings have implications for planning and management of NbR as they suggest that photographs uploaded on Flickr reflect patterns of NbR at spatial and temporal scales that are relevant for ecosystem management.
Fitness Landscapes Reveal Simple Strategies for Steering Evolution to Minimize Antibiotic Resistance
Authors: Smith Maria , Cobey Sarah
Published: December 2016

The evolution of antibiotic resistance presents a practical and theoretical challenge: the design of strategies that limit the risk of evolved resistance while effectively treating current patients. Sequentially cycling antibiotics has been proposed as a way to slow the evolution of resistance by reducing the extent of adaptation to a given drug, and clinical trials have demonstrated its effectiveness in some settings. Empirical fitness landscapes in theory allow the sequence of drugs to be refined to maximize tradeoffs between drugs and thereby slow adaptation even further. Using the measured growth rates of 16 genotypes ofEscherichia coliin the presence ofβ-lactam antibiotics, we test an adaptive strategy, based on a Markov chain transition matrix, to select drug sequences that continuously minimize resistance. Cycling is never selected over the long term. Instead, monotherapy with the antibiotic that permits the least growth in its landscape’s absorbing state is rapidly selected from different starting conditions. Analysis of a synthetic fitness landscape shows that cycling drugs that induce sensitivity to one other could, in theory, outperform monotherapy. These results underscore the importance of considering the specific topologies of fitness landscape in determining whether to cycle drugs and suggest a general computational approach to identify high performing, practical strategies to manage resistance.
Cell-to-cell variability in the yeast pheromone response: high throughput screen identifies genes with different effects on transmitted signal and response
Authors: Pesce C. G. , Peria W. , Zdraljevic S. , Rockwell D. , Yu R. C. , Colman-Lerner A. , Brent R.
Published: December 2016

Populations of isogenic cells often respond coherently to signals despite differences in protein abundance and cell state. Our previous work in theSaccharomyces cerevisiaepheromone response system (PRS) uncovered processes that reduced cell-to-cell variation in signal and response. To understand these and other processes that controlled variation, we generated a whole-genome collection of haploid strains with deletions in non-essential genes and used high-throughput flow cytometry to screen more than 1000. We identified 50 “variation genes” required for normal cell-to-cell variability in signal and response. Some genes affected only signal variability, signal strength, or system output, defining these quantities as separable “axes” of system behavior. Two genes affected cytoplasmic microtubule function.
Comparing Bayesian and non-Bayesian accounts of human confidence reports
Authors: Adler William T. , Ma Wei Ji
Published: December 2016

Humans can meaningfully report their confidence in a perceptual or cognitive decision. It is widely believed that these reports reflect the Bayesian probability that the decision is correct, but this hypothesis has not been rigorously tested against non-Bayesian alternatives. We use two perceptual categorization tasks in which Bayesian confidence reporting requires subjects to take sensory uncertainty into account in a specific way. We find that subjects do take sensory uncertainty into account when reporting confidence, suggesting that brain areas involved in reporting confidence can access low-level representations of sensory uncertainty. However, behavior is not fully consistent with the Bayesian hypothesis and is better described by simple heuristic models. Both conclusions are robust to changes in the uncertainty manipulation, task, response modality, model comparison metric, and additional flexibility in the Bayesian model. Our results suggest that adhering to a rational account of confidence behavior may require incorporating implementational constraints.
Microbial Genome-Wide Association Studies: Lessons from Human GWAS
Authors: Power Robert A. , Parkhill Julian , de Oliveira Tulio
Published: December 2016

The reduced costs of sequencing have led to the availability of whole genome sequences for a large number of microorganisms, enabling the application of microbial genome wide association studies (GWAS). Given the successes of human GWAS in understanding disease aetiology and identifying potential drug targets, microbial GWAS is likely to further advance our understanding of infectious diseases. By building on the success of GWAS, microbial GWAS have the potential to rapidly provide important insights into pressing global health problems, such as antibiotic resistance and disease transmission. In this review, we outline the methodologies of GWAS, the state of the field of microbial GWAS today, and how lessons from GWAS can direct the future of the field.
A phosphorylation–deubiquitination cascade regulates the BRCA2–RAD51 axis in homologous recombination
Authors: Luo Kuntian , Li Lei , Li Yunhui , Wu Chenming , Yin Yujiao , Chen Yuping , Deng Min , Nowsheen Somaira , Yuan Jian , Lou Zhenkun
Published: December 2016

Homologous recombination (HR) is one of the major DNA double-strand break (DSB) repair pathways in mammalian cells. Defects in HR trigger genomic instability and result in cancer predisposition. The defining step of HR is homologous strand exchange directed by the protein RAD51, which is recruited to DSBs by BRCA2. However, the regulation of the BRCA2–RAD51 axis remains unclear. Here we report that ubiquitination of RAD51 hinders RAD51–BRCA2 interaction, while deubiquitination of RAD51 facilitates RAD51–BRCA2 binding and RAD51 recruitment and thus is critical for proper HR. Mechanistically, in response to DNA damage, the deubiquitinase UCHL3 is phosphorylated and activated by ATM. UCHL3, in turn, deubiquitinates RAD51 and promotes the binding between RAD51 and BRCA2. Overexpression of UCHL3 renders breast cancer cells resistant to radiation and chemotherapy, while depletion of UCHL3 sensitizes cells to these treatments, suggesting a determinant role of UCHL3 in cancer therapy. Overall, we identify UCHL3 as a novel regulator of DNA repair and reveal a model in which a phosphorylation–deubiquitination cascade dynamically regulates the BRCA2–RAD51 pathway.
The RNA-induced transcriptional silencing complex targets chromatin exclusively via interacting with nascent transcripts
Authors: Shimada Yukiko , Mohn Fabio , Bühler Marc
Published: December 2016

Small RNAs regulate chromatin modification and transcriptional gene silencing across the eukaryotic kingdom. Although these processes have been well studied, fundamental mechanistic aspects remain obscure. Specifically, it is unclear exactly how small RNA-loaded Argonaute protein complexes target chromatin to mediate silencing. Here, using fission yeast, we demonstrate that transcription of the target locus is essential for RNA-directed formation of heterochromatin. However, high transcriptional activity is inhibitory; thus, a transcriptional window exists that is optimal for silencing. We further found that pre-mRNA splicing is compatible with RNA-directed heterochromatin formation. However, the kinetics of pre-mRNA processing is critical. Introns close to the 5′ end of a transcript that are rapidly spliced result in a bistable response whereby the target either remains euchromatic or becomes fully silenced. Together, our results discount siRNA–DNA base pairing in RNA-mediated heterochromatin formation, and the mechanistic insights further reveal guiding paradigms for the design of small RNA-directed chromatin silencing studies in multicellular organisms.
Knowledge management and total quality management: a reciprocal relationship
Authors: Honarpour Amir , Jusoh Ahmad , Long Choi Sang
Published: December 2016

Purpose

This research is an effort to conceptualize the relationship between total quality management (TQM) and knowledge management in a new way. While some researchers considered knowledge management as a facilitator of TQM other scholars concerned TQM as an antecedent for knowledge management. The purpose of this paper is to propose a reciprocal causation between TQM and knowledge management.

Design/methodology/approach

The main focus of literature review is focusing on common practices of TQM and knowledge management. In the next step, joint variance analysis method is used to reanalyze the results of the empirical studies linking TQM to knowledge management. This approach aims to divide the multiple correlation squared and demonstrate what portion is distinctly connected to predictor variables and what portion is on account of common variance among predictors.

Findings

The result indicates that nearly half of all explained variances in empirical studies that considered the relationship between TQM and knowledge management disregarding the criteria are accounted for the joint variance of TQM and knowledge management processes. Therefore a reciprocal causation between TQM and knowledge management can be formulated.

Originality/value

This research is one of the first studies which explores the diverse results of the relationship between TQM and knowledge management from a methodological perspective.
Involvement of high mobility group box‐1 in imiquimod‐induced psoriasis‐like mice model
Authors: Chen Tao , Fu Li‐xin , Guo Zai‐pei , Yin Bin , Cao Na , Qin Sha
Published: December 2016

In the previous work, we have indicated that HMGB1, a pro‐inflammatory cytokine, is closely associated with the pathogenesis of psoriasis. To further clarify the role of HMGB1 in the pathogenesis of psoriasis, we investigated the direct function of HMGB1 application and HMGB1 blockade in imiquimod (IMQ)‐induced psoriatic mouse model in this study. Mice were treated with imiquimod (IMQ) to induce psoriasis‐like inflammation, and consecutively injected with recombinant HMGB1 or phosphate‐buffered saline (PBS) i.d. Abundant cytoplasmic expression of HMGB1 was observed in lesional skin from IMQ‐treated skin. The injection of HMGB1 into the IMQ‐treated skin further aggravated the psoriasis‐like disease, enhanced the infiltration of CD3+ T cells, myeloperoxidase+ neutrophils and CD11c+ dendritic cells, increased the number of γδ T cells, and upregulated the mRNA expression of interleukin (IL)‐6, tumor necrosis factor (TNF)‐α, interferon (IFN)‐γ and IL‐17 compared with the PBS injection. Finally, by using anti‐HMGB1 monoclonal antibody or HMGB1 inhibitor glycyrrhizin, we indicated that HMGB1 blockade reduced the number of γδ T cells, suppressed the mRNA expression of IL‐6, TNF‐α, IFN‐γ and IL‐17, and moderated clinical and histological evolvement in the IMQ‐treated skin. Our data suggest that HMGB1 may act as a pro‐inflammatory cytokine, and contribute to the development of IMQ‐induced psoriasis‐like inflammation. HMGB1 blockade may represent a new direction in the suppression of psoriasis.
Invasive plant removal: assessing community impact and recovery from invasion
Authors: Guido Anaclara , Pillar Valério D.
Published: December 2016

Invasive species spread on natural ecosystems is one of the most important causes of biodiversity loss. To disentangle the invasive plant impact on communities it is essential to combine experimental and observation approaches, which enable the correct interpretations of results and lead to the right decisions for management.

We examined the invasion of southern Brazil's grasslands by Eragrostis plana, which is currently the most problematic invasive species in the region. By means of an experiment on invaded communities complemented by observation of non‐invaded communities, we assessed E. plana impact on vegetation, evaluated community response to its removal and discussed the effectiveness of removal methods. Fifty permanent 1 × 1 m plots were located on natural grassland that was partially invaded by E. plana. Removal was done annually from 2012 to 2015 and consisted of five treatments (n = 10): (i) clipping above‐ground biomass on one occasion; (ii) clipping above‐ground biomass periodically; (iii) herbicide and (iv) hand‐pulling, plus (v) control treatment with no‐removal. In addition, 10 plots located in an adjacent non‐invaded area were monitored.

All removal treatments reduced E. plana cover across years, but were not enough to eradicate it. Our results revealed not only differences between invaded and non‐invaded communities, but also an effect of E. plana removal on resident species richness and total cover.

At the local scale, we demonstrated the impact of E. plana invasion on grassland vegetation, suggesting a reduction in resident species richness and total cover. Invasive species removal changed communities differently from invaded ones, but not resembling non‐invaded references, suggesting that community recovery may need more time for reestablishment or that some restoration strategies are required.

Synthesis and applications. This study demonstrated the impact on vegetation of the most important invasive species in southern Brazil's natural grasslands. We highlighted the advantages of combining observations of non‐invaded communities and experimental studies on invaded communities, with and without invasive removal, to help infer causal relationships in ecological invasion research.
Phenotypic plasticity in freshwater picocyanobacteria
Authors: Huber Paula , Diovisalvi Nadia , Ferraro Marcela , Metz Sebastián , Lagomarsino Leonardo , Llames María Eugenia , Royo‐Llonch Marta , Bustingorry José , Escaray Roberto , Acinas Silvia G. , Gasol Josep M. , Unrein Fernando
Published: December 2016

Picocyanobacteria can occur as single‐cell (Pcy) or as colonies (CPcy). Published evidence suggests that some Pcy strains have the capability to aggregate under certain culture conditions, however this has not been demonstrated to occur in natural environments. We investigated whether the Pcy and CPcy belong to the same species (i.e. phylotype), and the factors that determine their morphological and genetic variability in a hypertrophic shallow lake dominated by picocyanobacteria. Six main different morphologies and >30 phylotypes were observed. All sequences retrieved belonged to the ‘Anathece + Cyanobium’ clade (Synechococcales) that are known to have the capability of aggregation/disaggregation. The temporal variation of picocyanobacteria morphotype composition was weakly correlated with the DGGE temporal pattern, and could be explained by the composition of the zooplankton assemblage. Laboratory experiments confirmed that the small cladoceran Bosmina favoured the dominance of CPcy, i.e. Cyanodictyon doubled the size of the colonies when present, most likely through the aggregation of single‐cell picocyanobacteria into colonies. Flow cytometry cell sorting and 16S rRNA + ITS sequencing of the Pcy and CPcy cytometrically‐defined populations revealed that some phylotypes could be found in both sorted populations, suggesting phenotypic plasticity in which various Synechococcales phylotypes could be found in situ either as single‐cells or as colonies.
Characterization of the first cultured representative of a Bacteroidetes clade specialized on the scavenging of cyanobacteria
Authors: Ben Hania Wajdi , Joseph Manon , Bunk Boyke , Spröer Cathrin , Klenk Hans‐Peter , Fardeau Marie‐Laure , Spring Stefan
Published: December 2016

The anaerobic, mesophilic and moderately halophilic strain L21‐Spi‐D4T was recently isolated from the suboxic zone of a hypersaline cyanobacterial mat using protein‐rich extracts of Arthrospira (formerly Spirulina) platensis as substrate. Phylogenetic analyses based on 16S rRNA genes indicated an affiliation of the novel strain with the Bacteroidetes clade MgMjR‐022, which is widely distributed and abundant in hypersaline microbial mats and heretofore comprised only sequences of uncultured bacteria. Analyses of the complete genome sequence of strain L21‐Spi‐D4T revealed a possible specialization on the degradation of cyanobacterial biomass. Besides genes for enzymes degrading specific cyanobacterial proteins a conspicuous transport complex for the polypeptide cyanophycin could be identified that is homologous to typical polysaccharide utilization loci of Bacteroidetes. A distinct and reproducible co‐occurrence pattern of environmental 16S rRNA gene sequences of the MgMjR‐022 clade and cyanobacteria in the suboxic zone of hypersaline mats points to a specific dependence of members of this clade on decaying cyanobacteria. Based on a comparative analysis of phenotypic, genomic and ecological characteristics we propose to establish the novel taxa Salinivirga cyanobacteriivorans gen. nov., sp. nov., represented by the type strain L21‐Spi‐D4T, and Salinivirgaceae fam. nov., comprising sequences of the MgMjR‐022 clade.
Impact of Christmas on bowel preparation for endoscopic examination of the lower gastrointestinal tract
Authors: Sutton Paul A. , Burley Natalie M.Y. , Glover Jane , Titu Liviu V.
Published: December 2016

Aim

The aim of the present study was to evaluate the impact of Christmas on the efficacy of bowel cleansing performed prior to endoscopic examination of the lower gastrointestinal tract.

Patients and methods

A retrospective review of contemporaneous endoscopy reports at a single institution was undertaken. The quality of bowel preparation in patients undergoing lower gastrointestinal endoscopy over a period of 7 days immediately following 25 December in 2013, 2014 and 2015 was compared to the unit average for the corresponding year.

Results

The proportion of patients with poor bowel preparation was significantly higher in each of the Christmas weeks compared to the unit average for the corresponding year, specifically 36.6 per cent vs 21.1 per cent in 2013 (
P
 = 0.032), 22 per cent vs 17.8 per cent in 2014 (
P
 = 0.011) and 24.4 per cent vs 17.4 per cent in 2015 (
P
 = 0.008). Pooling data over the study period suggested that the incidence of poor preparation between Christmas and New Year was 26.4 per cent vs 18.7 per cent for the remainder of the year (
P
 = 0.006).

Conclusion

Christmas results in a higher proportion of poor bowel preparation. While causality cannot be determined in the present study, we suggest that the residue from Christmas dinner combined with poor compliance with bowel preparation due to satiety from overconsumption are likely to be responsible. Endoscopy units should consider providing additional and specific dietary advice to patients who are undergoing examination during the festive period.
UV reflectance is associated with environmental conditions in Palaearctic Pieris napi (Lepidoptera: Pieridae)
Authors: Stella David , Pecháček Pavel , Meyer‐Rochow Victor Benno , Kleisner Karel
Published: December 2016

The subject of our investigation was the visual features of wing color with special focus on the UV reflectance in the green‐veined white butterfly (Pieris napi). Previous studies had concluded that UV reflectance on dorsal wing surfaces is found only in the female P. napi. Based on UV sensitive photography, we analyzed a correlation between 12 geographic and environmental factors and UV reflectance patterns on 3 patches on the forewings of 407 P. napi specimens from the Palaearctic region. Results had shown that females significantly differ from males: they exhibit a 25% higher UV reflectance. To investigate whether and how UV reflectance levels on the forewings and hindwings of both sexes are influenced by the environment, we performed a principal component analysis (PCA) with several environmental variables. For several variables (in particular, latitude and longitude, mean annual temperature and precipitation, and temperature annual range and altitude), the generalized linear model (GLM) model revealed a significant correlation in both sexes. This suggests a link between UV reflectance levels and the environment and distribution of P. napi. We found that stronger UV reflectance is associated with generally more hostile environments and concluded that large‐scale environmental factors influence the UV reflectance on the forewings of both male and female green‐veined white butterflies.
HLA‐DRB1shared epitope alleles in patients with rheumatoid arthritis: relation to autoantibodies and disease severity in a south Indian population
Authors: Konda Mohan Vasanth , Ganesan Nalini , Gopalakrishnan Rajasekhar , Venkatesan Vettriselvi
Published: December 2016

Aim

To investigate the presence of the ‘shared epitope’ (SE) in theHLA‐DRB1alleles in patients withRAand to ascertain the frequency of theHLA‐DRB1alleles with autoantibodies (anti‐cyclic citrullinated peptide [anti‐CCP] rheumatoid factor [RF]) and disease severity.

Methods

A total of 200RApatients and 200 apparently healthy subjects participated in the study.HLA‐DRB1were genotyped using polymerase chain reaction with sequence‐specific primer (PCR‐SSP). Anti‐CCPandRFin serum were determined byin vitroquantitative enzyme‐linked immunosorbent assay (ELISA) method. Erythrocyte sedimentation rate (ESR) was measured by Westergren method. Disease activity was assessed by using the disease activity score‐28 (DAS‐28). Chi‐square test and Student'st‐test were used in the statistical analysis.

Results

A significant increase in the frequency ofHLA‐DRB1*01, *04, *10 and *14 were identified inRApatients and showed a strong association with the disease susceptibility. While the frequencies ofHLA‐DRB1*03, *07, *11 and *13 were significantly lower inRApatients than in controls. The otherHLA‐DRB1alleles *08, *09, *12, *15 and *16 showed no significant difference. The frequency of anti‐CCPandRFantibodies did not showed significant difference inSE‐positive patients compared withSE‐negative patients.DAS‐28 values ofRApatients showed no significant difference betweenSE‐positive andSE‐negative groups.

Conclusion

Our results indicate thatHLA‐DRB1*01, *04, *10 and *14 alleles are related withRA, whileHLA‐DRB1*03, *07, *11 and *13 protect againstRAin our population. On the other hand, we failed to provide evidence for the association of the autoantibodies andDAS‐28 withSE‐positiveRApatients.
Smokers and ex‐smokers have shared differences in the neural substrates for potential monetary gains and losses
Authors: Nestor Liam J. , McCabe Ella , Jones Jennifer , Clancy Luke , Garavan Hugh
Published: December 2016

Despite an increased understanding of nicotine addiction, there is a scarcity of research comparing the neural correlates of non‐drug reward between smokers and ex‐smokers. Long‐term changes in reward‐related brain functioning for non‐drug incentives may elucidate patterns of functioning that potentially contribute to ongoing smoking behaviour in current smokers. Similarly, examining the effects of previous chronic nicotine exposure during a period of extended abstinence may reveal whether there are neural correlates responsible for non‐drug reward processing that are different from current smokers. The current study, therefore, sets out to examine the neural correlates of reward and loss anticipation, and their respective outcomes, in smokers, ex‐smokers and matched controls using a monetary incentive delay task during functional magnetic resonance imaging. Here, we report that in the absence of any significant behavioural group differences, both smokers and ex‐smokers showed a significantly greater activation change in the lateral orbitofrontal/anterior insular cortex compared with smokers when anticipating both potential monetary gains and losses. We further report that ex‐smokers showed a significantly greater activation change in the ventral putamen compared with both controls and smokers and in the caudate compared with controls during the anticipation of potential monetary losses only. The results suggest that smoking may sensitize striato‐orbitofrontal circuitry subserving motivational processes for loss avoidance and reward gain in nicotine addiction.
Local or global policy? Thinking about policy mobility with assemblage and topology
Authors: Prince Russell
Published: December 2016

The policy mobility literature is haunted by the local–global binary and the problem of understanding the extent to which a particular policy is ‘local’ or ‘global’. This paper argues that while an assemblage perspective is already prominent in the literature, its use can be extended to more effectively engage with this problem. Proceeding from the recognition that what makes mobile policy possible is first and foremost the existence of separate policy territories, through a focus on the kinds of assemblages that territorialise separate but interconnected territories, and a more thoroughgoing account of the topologies contained by those assemblages, we can account for how mobile policy is an outcome of this work of assemblage. It is through such assemblages that our ideas of what is global and what is local are produced. The example of the technocracy is used to illustrate the argument.
Statin potency and the risk of hospitalization for community‐acquired pneumonia
Authors: Shin Ju‐Young , Eberg Maria , Ernst Pierre , Filion Kristian B.
Published: December 2016

Aim

Previous studies suggest that statins may have beneficial respiratory effects. However, it is unclear if these purported benefits vary with statin potency. Our objective was to determine if higher potency statins, compared with lower potency statins, were associated with a reduced risk of hospitalization for community‐acquired pneumonia (HCAP).

Methods

We conducted a nested case–control analysis of a retrospective, population‐based cohort of new users of statins using data extracted from the UK's Clinical Practice Research Datalink and Hospital Episode Statistics. For each HCAP case, we used risk set sampling to randomly select up to 10 controls, matched on sex, age, cohort entry date and follow‐up duration. We used conditional logistic regression with high‐dimensional propensity scores to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for HCAP with current use of higher potency statin vs. lower potency statins.

Results

A total of 217 721 patients entered the cohort on a lower potency statin and 130 707 entered on a higher potency statin; these patients resulted in 2251 cases of HCAP during 561 886 person‐years of observation (rate: 4.0 HCAP per 1000 persons per year, 95% CI: 3.8–4.2). The analysis included 22 178 matched controls. Compared with lower potency statins, higher potency statins were associated with an increased rate of HCAP (HR: 1.14, 95% CI: 1.03–1.27). Higher potency statins were also associated with an increased rate of fatal HCAP (HR: 1.29, 95% CI: 1.04–1.59).

Conclusions

Higher potency statins were not associated with a decreased risk of HCAP compared with lower potency statins.
The Bothnian Sea ice stream: early Holocene retreat dynamics of the south‐central Fennoscandian Ice Sheet
Authors: Greenwood Sarah L. , Clason Caroline C. , Nyberg Johan , Jakobsson Martin , Holmlund Per
Published: December 2016

The Gulf of Bothnia hosted a variety of palaeo‐glaciodynamic environments throughout the growth and decay of the last Fennoscandian Ice Sheet, from the main ice‐sheet divide to a major corridor of marine‐ and lacustrine‐based deglaciation. Ice streaming through the Bothnian and Baltic basins has been widely assumed, and the damming and drainage of the huge proglacial Baltic Ice Lake has been implicated in major regional and hemispheric climate changes. However, the dynamics of palaeo‐ice flow and retreat in this large marine sector have until now been inferred only indirectly, from terrestrial, peripheral evidence. Recent acquisition of high‐resolution multibeam bathymetry opens these basins up, for the first time, to direct investigation of their glacial footprint and palaeo‐ice sheet behaviour. Here we report on a rich glacial landform record: in particular, a palaeo‐ice stream pathway, abundant traces of high subglacial meltwater volumes, and widespread basal crevasse squeeze ridges. The Bothnian Sea ice stream is a narrow flow corridor that was directed southward through the basin to a terminal zone in the south‐central Bothnian Sea. It was activated after initial margin retreat across the Åland sill and into the Bothnian basin, and the exclusive association of the ice‐stream pathway with crevasse squeeze ridges leads us to interpret a short‐lived stream event, under high extension, followed by rapid crevasse‐triggered break‐up. We link this event with a c. 150‐year ice‐rafted debris signal in peripheral varved records, at c. 10.67 cal. ka BP. Furthermore, the extensive glacifluvial system throughout the Bothnian Sea calls for considerable input of surface meltwater. We interpret strongly atmospherically driven retreat of this marine‐based ice‐sheet sector.
Innovations in Practice: Using clinician‐rated outcomes to support improved service decision making in a Child and Adolescent Mental Health Service
Authors: Fuggle Peter , Cleridou Kalia
Published: December 2016

Background

Clinical outcomes are now routinely collected in most services. However, there is a need to make full use of the information collected in order to improve the use of limited Child and Adolescent Mental Health Service (CAMHS) resources. This paper describes a method of improving service decision making by making the interpretation of outcomes data accessible to frontline staff.

Method

Clinician ratings of child outcomes for 2876 cases were routinely collected between 2009 and 2013 in a single CAMHS service. These outcomes were assessed against seven ‘point of entry’ and ‘treatment’ variables.

Results

Older children, referred by social care and presenting with multiple problems were associated with worse treatment outcomes than other service users. These findings were used to create an accessible Service Evaluation Chart of outcomes, to support discussion and decision making within the service. This process enabled the identification of a group who had particularly poor outcomes and resulted in consideration about service changes to try to improve outcomes for this specific group.

Conclusions

Providing clinicians with accessible information about outcomes promotes the likelihood of outcomes being used in service decision making.
Proinflammatory cytokine interferon-γ and microbiome-derived metabolites dictate epigenetic switch between forkhead box protein 3 isoforms in coeliac disease
Authors: Serena G , Yan S , Camhi S , Patel S , Lima R S , Sapone A , Leonard M M , Mukherjee R , Nath B J , Lammers K M , Fasano A
Published: December 2016

Coeliac disease (CD) is an autoimmune enteropathy triggered by gluten and characterized by a strong T helper type 1 (Th1)/Th17 immune response in the small intestine. Regulatory T cells (Treg) are CD4+CD25++forkhead box protein 3 (FoxP3+) cells that regulate the immune response. Conversely to its counterpart, FoxP3 full length (FL), the alternatively spliced isoform FoxP3 Δ2, cannot properly down-regulate the Th17-driven immune response. As the active state of CD has been associated with impairments in Treg cell function, we aimed at determining whether imbalances between FoxP3 isoforms may be associated with the disease. Intestinal biopsies from patients with active CD showed increased expression of FOXP3 Δ2 isoform over FL, while both isoforms were expressed similarly in non-coeliac control subjects (HC). Conversely to what we saw in the intestine, peripheral blood mononuclear cells (PBMC) from HC subjects did not show the same balance between isoforms. We therefore hypothesized that the intestinal microenvironment may play a role in modulating alternative splicing. The proinflammatory intestinal microenvironment of active patients has been reported to be enriched in butyrate-producing bacteria, while high concentrations of lactate have been shown to characterize the preclinical stage of the disease. We show that the combination of interferon (IFN)-γ and butyrate triggers the balance between FoxP3 isoforms in HC subjects, while the same does not occur in CD patients. Furthermore, we report that lactate increases both isoforms in CD patients. Collectively, these findings highlight the importance of the ratio between FoxP3 isoforms in CD and, for the first time, associate the alternative splicing process mechanistically with microbial-derived metabolites.