bluuebunny/crossref_metadata_2025 huggingface dataset:
Crystal structure of the catalytic domain of a GH16 β-agarase from a deep-sea bacterium, Microbulbifer thermotolerans JAMB-A94
Authors: Takagi Emiko , Hatada Yuji , Akita Masatake , Ohta Yukari , Yokoi Gaku , Miyazaki Takatsugu , Nishikawa Atsushi , Tonozuka Takashi
Published: December 2014

A deep-sea bacterium, Microbulbifer thermotolerans JAMB-A94, has a β-agarase (MtAgaA) belonging to the glycoside hydrolase family (GH) 16. The optimal temperature of this bacterium for growth is 43–49 °C, and MtAgaA is stable at 60 °C, which is one of the most thermostable enzymes among GH16 β-agarases. Here, we determined the catalytic domain structure of MtAgaA. MtAgaA consists of a β-jelly roll fold, as observed in other GH16 enzymes. The structure of MtAgaA was most similar to two β-agarases from Zobellia galactanivorans, ZgAgaA, and ZgAgaB. Although the catalytic cleft structure of MtAgaA was similar to ZgAgaA and ZgAgaB, residues at subsite −4 of MtAgaA were not conserved between them. Also, an α-helix, designated as α4′, was uniquely located near the catalytic cleft of MtAgaA. A comparison of the structures of the three enzymes suggested that multiple factors, including increased numbers of arginine and proline residues, could contribute to the thermostability of MtAgaA.
SNPlice: variants that modulate Intron retention from RNA-sequencing data
Authors: Mudvari Prakriti , Movassagh Mercedeh , Kowsari Kamran , Seyfi Ali , Kokkinaki Maria , Edwards Nathan J. , Golestaneh Nady , Horvath Anelia
Published: December 2014

Rationale: The growing recognition of the importance of splicing, together with rapidly accumulating RNA-sequencing data, demand robust high-throughput approaches, which efficiently analyze experimentally derived whole-transcriptome splice profiles.

Results: We have developed a computational approach, called SNPlice, for identifying cis-acting, splice-modulating variants from RNA-seq datasets. SNPlice mines RNA-seq datasets to find reads that span single-nucleotide variant (SNV) loci and nearby splice junctions, assessing the co-occurrence of variants and molecules that remain unspliced at nearby exon–intron boundaries. Hence, SNPlice highlights variants preferentially occurring on intron-containing molecules, possibly resulting from altered splicing. To illustrate co-occurrence of variant nucleotide and exon–intron boundary, allele-specific sequencing was used. SNPlice results are generally consistent with splice-prediction tools, but also indicate splice-modulating elements missed by other algorithms. SNPlice can be applied to identify variants that correlate with unexpected splicing events, and to measure the splice-modulating potential of canonical splice-site SNVs.

Availability and implementation: SNPlice is freely available for download from https://code.google.com/p/snplice/ as a self-contained binary package for 64-bit Linux computers and as python source-code.

Contact: pmudvari@gwu.edu or horvatha@gwu.edu

Supplementary information: Supplementary data are available at Bioinformatics online.
Improved gene tree error correction in the presence of horizontal gene transfer
Authors: Bansal Mukul S. , Wu Yi-Chieh , Alm Eric J. , Kellis Manolis
Published: December 2014

Motivation: The accurate inference of gene trees is a necessary step in many evolutionary studies. Although the problem of accurate gene tree inference has received considerable attention, most existing methods are only applicable to gene families unaffected by horizontal gene transfer. As a result, the accurate inference of gene trees affected by horizontal gene transfer remains a largely unaddressed problem.

Results: In this study, we introduce a new and highly effective method for gene tree error correction in the presence of horizontal gene transfer. Our method efficiently models horizontal gene transfers, gene duplications and losses, and uses a statistical hypothesis testing framework [Shimodaira–Hasegawa (SH) test] to balance sequence likelihood with topological information from a known species tree. Using a thorough simulation study, we show that existing phylogenetic methods yield inaccurate gene trees when applied to horizontally transferred gene families and that our method dramatically improves gene tree accuracy. We apply our method to a dataset of 11 cyanobacterial species and demonstrate the large impact of gene tree accuracy on downstream evolutionary analyses.

Availability and implementation: An implementation of our method is available at http://compbio.mit.edu/treefix-dtl/

Contact: mukul@engr.uconn.edu or manoli@mit.edu

Supplementary information: Supplementary data are available at Bioinformatics online.
flowCL: ontology-based cell population labelling in flow cytometry
Authors: Courtot Mélanie , Meskas Justin , Diehl Alexander D. , Droumeva Radina , Gottardo Raphael , Jalali Adrin , Taghiyar Mohammad Jafar , Maecker Holden T. , McCoy J. Philip , Ruttenberg Alan , Scheuermann Richard H. , Brinkman Ryan R.
Published: December 2014

Motivation: Finding one or more cell populations of interest, such as those correlating to a specific disease, is critical when analysing flow cytometry data. However, labelling of cell populations is not well defined, making it difficult to integrate the output of algorithms to external knowledge sources.

Results: We developed flowCL, a software package that performs semantic labelling of cell populations based on their surface markers and applied it to labelling of the Federation of Clinical Immunology Societies Human Immunology Project Consortium lyoplate populations as a use case.

Conclusion: By providing automated labelling of cell populations based on their immunophenotype, flowCL allows for unambiguous and reproducible identification of standardized cell types.

Availability and implementation: Code, R script and documentation are available under the Artistic 2.0 license through Bioconductor (http://www.bioconductor.org/packages/devel/bioc/html/flowCL.html).

Contact:  rbrinkman@bccrc.ca

Supplementary information:  Supplementary data are available at Bioinformatics online.
ICMA: an integrated cardiac modeling and analysis platform
Authors: Hussan Jagir R. , Hunter Peter J. , Gladding Patrick A. , Greenberg Neil , Christie Richard , Wu Alan , Sorby Hugh , Thomas James D.
Published: December 2014

Summary: ICMA, a software framework to create 3D finite element models of the left ventricle from cardiac ultrasound or magnetic resonance imaging (MRI) data, has been made available as an open-source code. The framework is hardware vendor independent and uses speckle tracking (endocardial border detection) on ultrasound (MRI) imaging data in the form of DICOM. Standard American Heart Association segment-based strain analysis can be performed using a browser-based interface. The speckle tracking, border detection and model fitting methods are implemented in C++ using open-source tools. They are wrapped as web services and orchestrated via a JBOSS-based application server.

Availability and implementation: The source code for ICMA is freely available under MPL 1.1 or GPL 2.0 or LGPL 2.1 license at https://github.com/ABI-Software-Laboratory/ICMA and a standalone virtual machine at http://goo.gl/M4lJKH for download.

Contact:  r.jagir@auckland.ac.nz

Supplementary information:  Supplementary materials are available at Bioinformatics online.
The Geography of Interstate Resource Wars *
Authors: Caselli Francesco , Morelli Massimo , Rohner Dominic
Published: December 2014

We establish a theoretical and empirical framework to assess the role of resource endowments and their geographic location in interstate conflict. The main predictions of the theory are that conflict is more likely when at least one country has natural resources, when the resources in the resource-endowed country are closer to the border, and, in the case where both countries have natural resources, when the resources are located asymmetrically vis-à-vis the border. We test these predictions on a novel data set featuring oilfield distances from bilateral borders. The empirical analysis shows that the presence and location of oil are significant and quantitatively important predictors of interstate conflicts after World War II.
Plant-Influenced Gene Expression in the Rice Endophyte Burkholderia kururiensis M130
Authors: Coutinho Bruna G. , Licastro Danilo , Mendonça-Previato Lucia , Cámara Miguel , Venturi Vittorio
Published: December 2014

Burkholderia kururiensis M130 is one of the few rice endophytic diazotrophic bacteria identified thus far which is able to enhance growth of rice. To date, very little is known of how strain M130 and other endophytes enter and colonize plants. Here, we identified genes of strain M130 that are differentially regulated in the presence of rice plant extract. A genetic screening of a promoter probe transposon mutant genome bank and RNAseq analysis were performed. The screening of 10,100 insertions of the genomic transposon reporter library resulted in the isolation of 61 insertions displaying differential expression in response to rice macerate. The RNAseq results validated this screen and indicated that this endophytic bacterium undergoes major changes in the presence of plant extract regulating 27.7% of its open reading frames. A large number of differentially expressed genes encode membrane transporters and secretion systems, indicating that the exchange of molecules is an important aspect of bacterial endophytic growth. Genes related to motility, chemotaxis, and adhesion were also overrepresented, further suggesting plant–bacteria interaction. This work highlights the potential close signaling taking place between plants and bacteria and helps us to begin to understand the adaptation of an endophyte in planta.
Up-regulation of CX3CL1 via Nuclear Factor-κB–dependent Histone Acetylation Is Involved in Paclitaxel-induced Peripheral Neuropathy
Authors: Li Dai , Huang Zhen-Zhen , Ling Yun-Zhi , Wei Jia-You , Cui Yu , Zhang Xiang-Zhong , Zhu He-Quan , Xin Wen-Jun
Published: December 2014

AbstractAbstract

Using a rat model of paclitaxel-induced neuropathy, both pharmacological and small interfering RNA–based techniques showed that CX3CL1 supports allodynia in this model. Chromatin immunoprecipitation experiments demonstrated that an epigenetic mechanism controls CX3CL1 expression in the spinal neurons of neuropathic rats.

Background:

Up-regulation of CX3CL1 has been revealed to be involved in the neuropathic pain induced by nerve injury. However, whether CX3CL1 participates in the paclitaxel-induced painful peripheral neuropathy remains unknown. The aim of the current study was to elucidate the involvement of transcriptional factors nuclear factor-κB (NF-κB) and its causal interaction with CX3CL1 signaling in the paclitaxel-induced painful peripheral neuropathy.

Methods:

Painful peripheral neuropathy induced by paclitaxel treatment was established in adult male Sprague-Dawley rats. The von Frey test were performed to evaluate neuropathic pain behavior, and real-time quantitative reverse transcription polymerase chain reaction, chromatin immunoprecipitation, Western blot, immunohistochemistry, and small interfering RNA were performed to understand the molecular mechanisms.

Results:

The application of paclitaxel induced an up-regulation of CX3CL1 expression in the spinal neurons, which is reduced significantly by NF-κB inhibitor ammonium pyrrolidinedithiocarbamate or p65 small interfering RNA. Blockade of either CX3CL1 (n = 12 each) or NF-κB (n = 12 each) signaling pathway attenuated mechanical allodynia induced by paclitaxel. Chromatin immunoprecipitation further found that paclitaxel induced an increased recruitment of nuclear factor-κB (NF-κB)p65 to the Cx3cl1 promoter region. Furthermore, an increased acetylation level of H4, but not H3, in Cx3cl1 promoter region in spinal neurons was detected after paclitaxel treatment, which was reversed by inhibition of NF-κB with ammonium pyrrolidinedithiocarbamate or p65 small interfering RNA.

Conclusions:

These findings suggest that up-regulation of CX3CL1 via NF-κB–dependent H4 acetylation might be critical for paclitaxel-induced mechanical allodynia.
Reclassification of Ruminococcus obeum as Blautia
obeum comb. nov.
Authors: Lawson Paul A. , Finegold Sydney M.
Published: December 2014

During our previous studies we reclassified

Clostridium coccoides

and a number of misclassified ruminococci into a novel genus

Blautia

within the family

Lachnospiraceae

. However, the Rules of the Bacteriological Code currently require that the types of all species and subspecies with new names (including new combinations) be deposited in two different collections in two different countries. The type strain of

Ruminococcus obeum

was, at that period in time, only deposited in the American Type Culture Collection (ATCC) and a second independent deposit, as required by the Code, was not available. Consequently, the transfer of this species to the genus

Blautia

could not be made, because the resulting species name would not conform to the Rules governing the valid publication of species names and deposit of type material (Rules 27 and 30) and consequently would not be considered to be validly published. This resulted in a nomenclatural and taxonomic anomaly with

R. obeum

being phylogenetically placed among members of the genus

Blautia

with 16S rRNA gene sequence similarities of between 91.8 and 96.6 %. In order to rectify this unsatisfactory situation, through our discussions with the ATCC, the deposit of strain

R. obeum

ATCC 29174T to the DSMZ as strain number DSM 25238T was completed. Hence, the transfer of

R. obeum

to the genus

Blautia

as Blautia obeum comb. nov. is now proposed. The type strain is ATCC 29174T ( = DSM 25238T = KCTC 15206T).
Reclassification of Gemmobacter changlensis to a new genus as Cereibacter changlensis gen. nov., comb. nov.
Authors: Suresh G. , Sasikala Ch. , Ramana Ch. V.
Published: December 2014

We propose a new genus to accommodate the phototrophic bacterium

Gemmobacter changlensis

[Chen W. M., Cho, N. T., Huang, W. C., Young, C. C. & Sheu, S. Y. (2013) Int J Syst Evol Microbiol 63, 470–478] based on multiple strain analysis. Differences in the major diagnostic properties such as ability to grow phototrophically, the presence of internal photosynthetic membranes, the light harvesting complexes, fatty acids, carotenoids, bacterial chlorophylls, polar lipid composition and some other phenotypic properties warrant the creation of a new genus, designated Cereibacter gen. nov., to accommodate the phototrophic members of the genus

Gemmobacter

, as represented by the type species Cereibacter changlensis comb. nov.
Flavicella marina gen. nov., sp. nov., a carotenoid-producing bacterium from surface seawater
Authors: Teramoto Maki , Nishijima Miyuki
Published: December 2014

A Gram-stain-negative, non-motile, mesophilic, aerobic, rod-shaped or spherical bacterium, strain 2A-7T, was isolated from surface seawater at Muroto city, Kochi prefecture, Japan. The strain produced a pigment(s), the absorption spectrum of which closely resembled that of β-carotene. Phylogenetic analyses based on 16S rRNA gene sequences showed that the strain fell within the family

Flavobacteriaceae

and clustered distantly with the type strains of species of the genus

Lutibacter

(up to 93.9 % similarity). The DNA G+C content was 34.1 mol%. The major fatty acids were summed feature 3 (iso-C15 : 0 2-OH and/or C16 : 1ω7c), iso-C17 : 0 3-OH and iso-C15 : 0 3-OH. The major polar lipids were phosphatidylethanolamine and three unidentified lipids. Menaquinone 6 was detected as the sole isoprenoid quinone. On the basis of phenotypic, genotypic and chemotaxonomic data, strain 2A-7T represents a novel genus and species, for which the name Flavicella marina gen. nov., sp. nov. is proposed. The type strain of Flavicella marina is 2A-7T ( = NBRC 110145T = KCTC 42197T).
Catenisphaera adipataccumulans gen. nov., sp. nov., a member of the family Erysipelotrichaceae isolated from an anaerobic digester
Authors: Kanno Manabu , Katayama Taiki , Morita Naoki , Tamaki Hideyuki , Hanada Satoshi , Kamagata Yoichi
Published: December 2014

An obligately anaerobic bacterium, designated strain GK12T, was isolated from an anaerobic digester in Fukagawa, Hokkaido Prefecture, Japan. The cells of strain GK12Twere non-motile, non-spore-forming cocci that commonly occurred in chains. 16S rRNA gene sequence analysis revealed that strain GK12Twas affiliated with the familyErysipelotrichaceaein the phylumFirmicutesand showed 91.8 % sequence similarity to the most closely related species,Faecalicoccus acidiformans. The strain grew at 30–50 °C (optimally at 40 °C) and at pH 5.5–8.5 (optimally at pH 7.5). The main end product of glucose fermentation was lactate. Yeast extract was required for growth. The strain contained C14 : 0, C14 : 01,1-dimethoxyalkane (DMA), C16 : 0DMA and C18 : 0DMA as the major cellular fatty acids (>10 % of the total). The polar lipid profile was composed of phosphatidylglycerol, phosphatidylinositol and an unidentified phospholipid. The whole-cell sugars were galactose, rhamnose and ribose. The cell-wall murein contained alanine, glutamic acid, lysine, serine and threonine, but not diaminopimelic acid. The G+C content of the genomic DNA was 47.7 mol%. Based on phenotypic, phylogenetic and chemotaxonomic properties, a novel genus and species,Catenisphaera adipataccumulansgen. nov., sp. nov., is proposed to accommodate strain GK12T( = NBRC 108915T = DSM 25799T).
Seed-associated subspecies of the genus Clavibacter are clearly distinguishable from Clavibacter michiganensis subsp. michiganensis
Authors: Yasuhara-Bell Jarred , Alvarez Anne M.
Published: December 2014

The genusClavibactercontains one recognized species,Clavibacter michiganensis.Clavibacter michiganensisis subdivided into subspecies based on host specificity and bacteriological characteristics, withClavibacter michiganensissubsp.michiganensiscausing bacterial canker of tomato.Clavibacter michiganensissubsp.michiganensisis often spread through contaminated seed leading to outbreaks of bacterial canker in tomato production areas worldwide. The frequent occurrence of non-pathogenicClavibacter michiganensissubsp.michiganensis-like bacteria (CMB) is a concern for seed producers becauseClavibacter michiganensissubsp.michiganensisis a quarantine organism and detection of a non-pathogenic variant may result in destruction of an otherwise healthy seed lot. A thorough biological and genetic characterization of these seed-associated CMB strains was performed using standard biochemical tests, cell wall analyses, metabolic profiling using Biolog, and single-gene and multilocus sequence analyses. Combined, these tests revealed two distinct populations of seed-associated members of the genusClavibacterthat differed from each other, as well as from all other described subspecies ofClavibacter michiganensis. DNA–DNA hybridization values are 70 % or higher, justifying placement into the single recognized species,C. michiganensis, but other analyses justify separate subspecies designations. Additionally, strains belonging to the genusClavibacterisolated from pepper also represent a distinct population and warrant separate subspecies designation. On the basis of these data we propose subspecies designations for separate non-pathogenic subpopulations ofClavibacter michiganensis:Clavibacter michiganensissubsp.californiensissubsp. nov. andClavibacter michiganensissubsp.chilensissubsp. nov. for seed-associated strains represented by C55T( = ATCC BAA-2691T = CFBP 8216T) and ZUM3936T( = ATCC BAA-2690T = CFBP 8217T), respectively. Recognition of separate subspecies is essential for improved international seed testing operations.
Genome sequencing defines phylogeny and spread of methicillin-resistant Staphylococcus aureus in a high transmission setting
Authors: Tong Steven Y.C. , Holden Matthew T.G. , Nickerson Emma K. , Cooper Ben S. , Köser Claudio U. , Cori Anne , Jombart Thibaut , Cauchemez Simon , Fraser Christophe , Wuthiekanun Vanaporn , Thaipadungpanit Janjira , Hongsuwan Maliwan , Day Nicholas P. , Limmathurotsakul Direk , Parkhill Julian , Peacock Sharon J.
Published: December 2014

Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of nosocomial infection. Whole-genome sequencing of MRSA has been used to define phylogeny and transmission in well-resourced healthcare settings, yet the greatest burden of nosocomial infection occurs in resource-restricted settings where barriers to transmission are lower. Here, we study the flux and genetic diversity of MRSA on ward and individual patient levels in a hospital where transmission was common. We repeatedly screened all patients on two intensive care units for MRSA carriage over a 3-mo period. All MRSA belonged to multilocus sequence type 239 (ST 239). We defined the population structure and charted the spread of MRSA by sequencing 79 isolates from 46 patients and five members of staff, including the first MRSA-positive screen isolates and up to two repeat isolates where available. Phylogenetic analysis identified a flux of distinct ST 239 clades over time in each intensive care unit. In total, five main clades were identified, which varied in the carriage of plasmids encoding antiseptic and antimicrobial resistance determinants. Sequence data confirmed intra- and interwards transmission events and identified individual patients who were colonized by more than one clade. One patient on each unit was the source of numerous transmission events, and deep sampling of one of these cases demonstrated colonization with a “cloud” of related MRSA variants. The application of whole-genome sequencing and analysis provides novel insights into the transmission of MRSA in under-resourced healthcare settings and has relevance to wider global health.
Asymmetric nucleosomes flank promoters in the budding yeast genome
Authors: Ramachandran Srinivas , Zentner Gabriel E. , Henikoff Steven
Published: December 2014

Nucleosomes in active chromatin are dynamic, but whether they have distinct structural conformations is unknown. To identify nucleosomes with alternative structures genome-wide, we used H4S47C-anchored cleavage mapping, which revealed that 5% of budding yeast (Saccharomyces cerevisiae) nucleosome positions have asymmetric histone-DNA interactions. These asymmetric interactions are enriched at nucleosome positions that flank promoters. Micrococcal nuclease (MNase) sequence-based profiles of asymmetric nucleosome positions revealed a corresponding asymmetry in MNase protection near the dyad axis, suggesting that the loss of DNA contacts around H4S47 is accompanied by protection of the DNA from MNase. Chromatin immunoprecipitation mapping of selected nucleosome remodelers indicated that asymmetric nucleosomes are bound by the RSC chromatin remodeling complex, which is required for maintaining nucleosomes at asymmetric positions. These results imply that the asymmetric nucleosome-RSC complex is a metastable intermediate representing partial unwrapping and protection of nucleosomal DNA on one side of the dyad axis during chromatin remodeling.
Pepper Heat Shock Protein 70a Interacts with the Type III Effector AvrBsT and Triggers Plant Cell Death and Immunity
Authors: Kim Nak Hyun , Hwang Byung Kook
Published: December 2014

Heat shock proteins (HSPs) function as molecular chaperones and are essential for the maintenance and/or restoration of protein homeostasis. The genus Xanthomonas type III effector protein AvrBsT induces hypersensitive cell death in pepper (Capsicum annuum). Here, we report the identification of the pepper CaHSP70a as an AvrBsT-interacting protein. Bimolecular fluorescence complementation and coimmunoprecipitation assays confirm the specific interaction between CaHSP70a and AvrBsT in planta. The CaHSP70a peptide-binding domain is essential for its interaction with AvrBsT. Heat stress (37°C) and Xanthomonas campestris pv vesicatoria (Xcv) infection distinctly induce CaHSP70a in pepper leaves. Cytoplasmic CaHSP70a proteins significantly accumulate in pepper leaves to induce the hypersensitive cell death response by Xcv (avrBsT) infection. Transient CaHSP70a overexpression induces hypersensitive cell death under heat stress, which is accompanied by strong induction of defense- and cell death-related genes. The CaHSP70a peptide-binding domain and ATPase-binding domain are required to trigger cell death under heat stress. Transient coexpression of CaHSP70a and avrBsT leads to cytoplasmic localization of the CaHSP70a-AvrBsT complex and significantly enhances avrBsT-triggered cell death in Nicotiana benthamiana. CaHSP70a silencing in pepper enhances Xcv growth but disrupts the reactive oxygen species burst and cell death response during Xcv infection. Expression of some defense marker genes is significantly reduced in CaHSP70a-silenced leaves, with lower levels of the defense hormones salicylic acid and jasmonic acid. Together, these results suggest that CaHSP70a interacts with the type III effector AvrBsT and is required for cell death and immunity in plants.
The Arabidopsis Cellulose Synthase Complex: A Proposed Hexamer of CESA Trimers in an Equimolar Stoichiometry
Authors: Hill Joseph L. , Hammudi Mustafa B. , Tien Ming
Published: December 2014

Cellulose is the most abundant renewable polymer on Earth and a major component of the plant cell wall. In vascular plants, cellulose synthesis is catalyzed by a large, plasma membrane-localized cellulose synthase complex (CSC), visualized as a hexameric rosette structure. Three unique cellulose synthase (CESA) isoforms are required for CSC assembly and function. However, elucidation of either the number or stoichiometry of CESAs within the CSC has remained elusive. In this study, we show a 1:1:1 stoichiometry between the three Arabidopsis thaliana secondary cell wall isozymes: CESA4, CESA7, and CESA8. This ratio was determined utilizing a simple but elegant method of quantitative immunoblotting using isoform-specific antibodies and 35S-labeled protein standards for each CESA. Additionally, the observed equimolar stoichiometry was found to be fixed along the axis of the stem, which represents a developmental gradient. Our results complement recent spectroscopic analyses pointing toward an 18-chain cellulose microfibril. Taken together, we propose that the CSC is composed of a hexamer of catalytically active CESA trimers, with each CESA in equimolar amounts. This finding is a crucial advance in understanding how CESAs integrate to form higher order complexes, which is a key determinate of cellulose microfibril and cell wall properties.
Integrated Network Analysis Identifies Fight-Club Nodes as a Class of Hubs Encompassing Key Putative Switch Genes That Induce Major Transcriptome Reprogramming during Grapevine Development
Authors: Palumbo Maria Concetta , Zenoni Sara , Fasoli Marianna , Massonnet Mélanie , Farina Lorenzo , Castiglione Filippo , Pezzotti Mario , Paci Paola
Published: December 2014

We developed an approach that integrates different network-based methods to analyze the correlation network arising from large-scale gene expression data. By studying grapevine (Vitis vinifera) and tomato (Solanum lycopersicum) gene expression atlases and a grapevine berry transcriptomic data set during the transition from immature to mature growth, we identified a category named “fight-club hubs” characterized by a marked negative correlation with the expression profiles of neighboring genes in the network. A special subset named “switch genes” was identified, with the additional property of many significant negative correlations outside their own group in the network. Switch genes are involved in multiple processes and include transcription factors that may be considered master regulators of the previously reported transcriptome remodeling that marks the developmental shift from immature to mature growth. All switch genes, expressed at low levels in vegetative/green tissues, showed a significant increase in mature/woody organs, suggesting a potential regulatory role during the developmental transition. Finally, our analysis of tomato gene expression data sets showed that wild-type switch genes are downregulated in ripening-deficient mutants. The identification of known master regulators of tomato fruit maturation suggests our method is suitable for the detection of key regulators of organ development in different fleshy fruit crops.
Monitoring the thin film formation during sputter deposition of vanadium carbide
Authors: Kaufholz Marthe , Krause Bärbel , Kotapati Sunil , Köhl Martin , Mantilla Miguel F. , Stüber Michael , Ulrich Sven , Schneider Reinhard , Gerthsen Dagmar , Baumbach Tilo
Published: December 2014

The thin film formation of magnetron sputtered polycrystalline coatings was monitored byin situX-ray reflectivity measurements. The measured intensity was analyzed using the Parratt algorithm for time-dependent thin film systems. Guidelines for the on-line interpretation of the data were developed. For thick coatings, the experimental resolution needs to be included in the data evaluation in order to avoid misinterpretations. Based on a simple layer model, the time-dependent mean electron density, roughness and growth velocity were extracted from the data. As an example, the method was applied to the hard coating material vanadium carbide. Both instantaneous and slowly varying changes of the coating could be detected. It was shown that the growth velocity is proportional to the DC power. Significant changes of the microstructure induced by the working gas pressure are mainly driven by the chemical composition.
Unsupervised home use of an overnight closed‐loop system over 3–4 weeks: a pooled analysis of randomized controlled studies in adults and adolescents with type 1 diabetes
Authors: Thabit H. , Elleri D. , Leelarathna L. , Allen J. M. , Lubina‐Solomon A. , Stadler M. , Walkinshaw E. , Iqbal A. , Choudhary P. , Wilinska M. E. , Barnard K. D. , Heller S. R. , Amiel S. A. , Evans M. L. , Dunger D. B. , Hovorka R.
Published: December 2014

Aims

To compare overnight closed‐loop and sensor‐augmented pump therapy in patients with type 1 diabetes by combining data collected during free‐living unsupervised randomized crossover home studies.

Methods

A total of 40 participants with type 1 diabetes, of whom 24 were adults [mean ± standard deviation (s.d.) age 43 ± 12 years and glycated haemoglobin (HbA1c) 8.0 ± 0.9%] and 16 were adolescents (mean ± s.d. age 15.6 ± 3.6 years and HbA1c 8.1 ± 0.8%), underwent two periods of sensor‐augmented pump therapy in the home setting, in combination with or without an overnight closed‐loop insulin delivery system that uses a model predictive control algorithm to direct insulin delivery. The order of the two interventions was random; each period lasted 4 weeks in adults and 3 weeks in adolescents. The primary outcome was time during which sensor glucose readings were in the target range of 3.9–8.0 mmol/l.

Results

The proportion of time when sensor glucose was in the target range (3.9–8.0 mmol/l) overnight (between 24:00 and 08:00 hours) was 18.5% greater during closed‐loop insulin delivery than during sensor‐augmented therapy (p < 0.001). Closed‐loop therapy significantly reduced mean overnight glucose levels by 0.9 mmol/l (p < 0.001), with no difference in glycaemic variability, as measured by the standard deviation of sensor glucose. Time spent above the target range was reduced (p = 0.001), as was time spent in hypoglycaemia (<3.9 mmol/l; p = 0.014) during closed‐loop therapy. Lower mean overnight glucose levels during closed‐loop therapy were brought about by increased overnight insulin delivery (p < 0.001) without changes to the total daily delivery (p = 0.84).

Conclusion

Overnight closed‐loop insulin therapy at home in adults and adolescents with type 1 diabetes is feasible, showing improvements in glucose control and reducing the risk of nocturnal hypoglycaemia.
Collective empowerment: A comparative study of community work in Mumbai and Stockholm
Authors: Sjöberg Stefan , Rambaree Komalsingh , Jojo Bipin
Published: December 2014

Mumbai and Stockholm are worlds apart in terms of public services, infrastructures and standard of living. However, both cities have known common problems of social exclusion and marginalisation related to neo‐liberal globalisation. Social workers are facing similar challenges regarding collective empowerment as a strategy for community work. This comparative study explored how collective empowerment is undertaken by community workers. The research participants were 13 informants from community‐work organisations in the two settings. Semi‐structured interviews were used and were analysed with the help of Atlas‐ti 6.2 (ATLAS.ti Scientific Software Development GmbH D‐10623 Berlin Germany). Social work in Mumbai is in a context of extreme poverty and mainly within the informal sector, whereas in Stockholm most social work is done in relation to a public welfare model. In Stockholm, interventions are aimed towards strengthening social networks, without direct aim at social change. In Mumbai, community workers organise people for collective empowerment to strengthen marginalised groups and achieve social change.
Non‐dominated “trade‐off” solutions in television scheduling optimization
Authors: Lupo Toni
Published: December 2014

The main approaches for the television scheduling design are commonly based on the ratings or revenues maximization objective, and thus, only a single optimal solution can be obtained, corresponding to the best result for the considered objective. Therefore, these approaches lead up to the alternative solutions loss which, even if less effective from the ratings or revenues maximization viewpoint, may be more suitable for the decision maker because of better compromise in relation to factors influencing the decision process. Specifically, such a compromise could be achieved through a suitable “trade‐off” between these factors, with reference to the decision context in which the decision maker has to operate. The present study concerns the development of a multi‐objective approach for the television scheduling design in which ratings and costs are the considered objectives to optimize, because these are the main factors influencing the decision process. In particular, an integer mathematical programming model is formulated and solved, considering as input data forecasted values of show‐parts ratings and costs obtained by a suitable forecast engine. Finally, in order to show the employment of the proposed approach, a case study concerning the television scheduling optimization for an Italian TV channel is conducted with detailed practical considerations.
SPATIAL ADMINISTRATIVE STRUCTURE AND INTRA‐METROPOLITAN TAX COMPETITION
Authors: Kauder Björn
Published: December 2014

I investigate whether the spatial administrative structure of agglomerations is associated with local business tax rates in core cities of agglomerations. Using data for German municipalities, I define agglomerations based on distances and based on cumulative population densities. The results show that the population share of the core in its agglomeration is positively associated and the number of surrounding municipalities is negatively associated with the tax rate of the core. When municipalities consolidate, the core has the opportunity to increase the tax rate.
Synergistic antibacterial activity of the combination of the alkaloid sanguinarine with EDTA and the antibiotic streptomycin against multidrug resistant bacteria
Authors: Hamoud Razan , Reichling Jürgen , Wink Michael
Published: December 2014

Objectives

Drug combinations consisting of the DNA intercalating benzophenanthridine alkaloid sanguinarine, the chelator EDTA with the antibiotic streptomycin were tested against several Gram-positive and Gram-negative bacteria, including multi-resistant clinical isolates.

Methods

Microdilution, checkerboard and time kill curve methods were used to investigate the antibacterial activity of the individual drugs and the potential synergistic activity of combinations.

Key findings

Sanguinarine demonstrated a strong activity against Gram-positive and Gram-negative bacteria (minimum inhibitory concentrations, MIC = 0.5–128 μg/ml), while streptomycin was active against Gram-negative strains (MIC = 2–128 μg/ml). EDTA showed only bacteriostatic activity. Indifference to synergistic activity was seen in the two-drug combinations sanguinarine + EDTA and sanguinarine + streptomycin (fractional inhibitory concentration index = 0.1–1.5), while the three-drug combination of sanguinarine + EDTA + streptomycin showed synergistic activity against almost all the strains (except methicillin-resistant Staphylococcus aureus), as well as a strong reduction in the effective doses (dose reduction index = 2–16 times) of sanguinarine, EDTA and streptomycin. In time kill studies, a substantial synergistic interaction of the three-drug combination was detected against Escherichia coli and Klebsiella pneumoniae.

Conclusions

The combination of drugs, which interfere with different molecular targets, can be an important strategy to combat multidrug resistant bacteria.
Immunoproteomic characterisation of M
ycoplasma mycoides subspecies capri by mass spectrometry analysis of two-dimensional electrophoresis spots and western blot
Authors: Churchward Colin P , Rosales Rubén S , Gielbert Adriana , Domínguez Mercedes , Nicholas Robin A J , Ayling Roger D
Published: December 2014

Objectives

M ycoplasma mycoides subspecies capri is one of the causative agents of contagious agalactia in goats. The disease is characterised by mastitis, pneumonia, arthritis, keratitis and in acute cases septicaemia. No vaccine is currently available that has been demonstrated to prevent disease.

Methods

This study used two-dimensional electrophoresis to separate proteins from whole-cell preparations and tandem mass spectrometry to identify them.

Key findings

In total, 145 spots were successfully identified corresponding to 74 protein identities. Twenty of these proteins were found to be immunogenic by western blot analysis using a pooled serum sample from experimentally infected goats.

Conclusions

Six proteins were found to have a less than 95% amino acid similarity to a closely related Mycoplasma species showing that they warrant further evaluation in development of diagnostic tests. These proteins were a dihydrolipoamide acetyltransferase component of the pyruvate dehydrogenase complex, phosphoglycerate kinase, pyrimidine-nucleoside phosphorylase, 30S ribosomal protein S6, ribulose-phosphate 3-epimerase and D-lactate dehydrogenase.
Particulate inorganic adjuvants: recent developments and future outlook
Authors: Maughan Charlotte N , Preston Stephen G , Williams Gareth R
Published: December 2014

Objectives

To review the state of the art and assess future potential in the use of inorganic particulates as vaccine adjuvants.

Key findings

An adjuvant is an entity added to a vaccine formulation to ensure that robust immunity to the antigen is inculcated. The inclusion of an adjuvant is typically vital for the efficacy of vaccines using inactivated organisms, subunit and DNA antigens. With increasing research efforts being focused on subunit and DNA antigens because of their improved safety profiles, the development of appropriate adjuvants is becoming ever more crucial. Despite this, very few adjuvants are licensed for use in humans (four by the FDA, five by the European Medicines Agency). The most widely used adjuvant, alum, has been used for nearly 90 years, yet its mechanism of action remains poorly understood. In addition, while alum produces a powerful antibody Th2 response, it does not provoke the cellular immune response required for the elimination of intracellular infections or cancers. New adjuvants are therefore needed, and inorganic systems have attracted much attention in this regard.

In this review, the inorganic adjuvants currently in use are considered, and the efforts made to date to understand their mechanisms of action are summarised. We then move on to survey the literature on inorganic particulate adjuvants, focusing on the most interesting recent developments in this area and their future potential.
One Medicine One Science: a framework for exploring challenges at the intersection of animals, humans, and the environment
Authors: Travis Dominic A. , Sriramarao P. , Cardona Carol , Steer Clifford J. , Kennedy Shaun , Sreevatsan Srinand , Murtaugh Michael P.
Published: December 2014

Characterizing the health consequences of interactions among animals, humans, and the environment in the face of climatic change, environmental disturbance, and expanding human populations is a critical global challenge in today's world. Exchange of interdisciplinary knowledge in basic and applied sciences and medicine that includes scientists, health professionals, key sponsors, and policy experts revealed that relevant case studies of monkeypox, influenza A, tuberculosis, and HIV can be used to guide strategies for anticipating and responding to new disease threats such as the Ebola and Chickungunya viruses, as well as to improve programs to control existing zoonotic diseases, including tuberculosis. The problem of safely feeding the world while preserving the environment and avoiding issues such as antibiotic resistance in animals and humans requires cooperative scientific problem solving. Food poisoning outbreaks resulting from Salmonella growing in vegetables have demonstrated the need for knowledge of pathogen evolution and adaptation in developing appropriate countermeasures for prevention and policy development. Similarly, pesticide use for efficient crop production must take into consideration bee population declines that threaten the availability of the two‐thirds of human foods that are dependent on pollination. This report presents and weighs the objective merits of competing health priorities and identifies gaps in knowledge that threaten health security, to promote discussion of major public policy implications such that they may be decided with at least an underlying platform of facts.
Language‐Games and Relativism: On Cora Diamond's Reading of Peter Winch
Authors: Ahlskog Jonas , Lagerspetz Olli
Published: December 2014

We will look critically at three essays by Cora Diamond concerning Peter Winch's views on the possibility of communication and criticism between language‐games. We briefly present our understanding of Winch's approach to philosophy. Then, we argue that Diamond misidentifies Winch's views, taking them to imply language‐game relativism or linguistic idealism. When she does raise valid criticisms against language‐game relativism, her critical points mainly coincide with things that Winch has already stressed in his own work. That leaves us with the question what their real disagreement amounts to. Finally, we suggest that at the bottom of Diamond's objections lies her failure to appreciate Winch's insights about the place of logic in human intercourse.
Point‐of‐Dispensing Location and Capacity Optimization via a Decision Support System
Authors: Ramirez‐Nafarrate Adrian , Lyon Joshua D. , Fowler John W. , Araz Ozgur M.
Published: December 2014

Dispensing of mass prophylaxis can be critical to public health during emergency situations and involves complex decisions that must be made in a short period of time. This study presents a model and solution approach for optimizing point‐of‐dispensing (POD) location and capacity decisions. This approach is part of a decision support system designed to help officials prepare for and respond to public health emergencies. The model selects PODs from a candidate set and suggests how to staff each POD so that average travel and waiting times are minimized. A genetic algorithm (GA) quickly solves the problem based on travel and queuing approximations (QAs) and it has the ability to relax soft constraints when the dispensing goals cannot be met. We show that the proposed approach returns solutions comparable with other systems and it is able to evaluate alternative courses of action when the resources are not sufficient to meet the performance targets.
Subtherapeutic ganciclovir (GCV) levels and GCV‐resistant cytomegalovirus in lung transplant recipients
Authors: Gagermeier J.P. , Rusinak J.D. , Lurain N.S. , Alex C.G. , Dilling D.F. , Wigfield C.H. , Love R.B.
Published: December 2014

Background

Cytomegalovirus (CMV) infection results in significant morbidity and mortality in lung transplant recipients. Ganciclovir (GCV) has dramatically reduced complications caused by CMV infections. Unfortunately, GCV resistance is identified in 5–10% of CMV‐infected patients. Mismatched CMV status and ongoing replication due to immunosuppression are risk factors for drug resistance. Whether subtherapeutic GCV levels contribute to resistance remains unknown.

Methods

A retrospective review was conducted in all 51 patients who underwent lung transplantation between March 2007 and June 2008 at Loyola University Medical Center. GCV resistance and outcome data of CMV‐infected patients were analyzed to identify variables that may contribute to suboptimal response to CMV infection.

Results

During the 16‐month period, CMV infection was identified in 21 of 51 lung transplant recipients. Ten of 21 patients (47.6%) had CMV infection with early response to GCV, and 11 patients (52.4%) had CMV infection with suboptimal response to GCV. GCV levels were obtained in the 11 CMV‐infected patients with suboptimal response. In 6 patients, GCV levels were therapeutic; all 6 had delayed response to GCV. In 5 patients, GCV levels were subtherapeutic; each had persistent suboptimal response to GCV. Genotyping documented GCV‐resistant (GCV‐R) CMV in all 5 patients. Cystic fibrosis as the diagnosis requiring lung transplantation was associated with GCV‐R CMV infection (P = 0.01).

Conclusion

In our lung transplant recipient cohort, GCV levels were subtherapeutic in all patients with persistent suboptimal response to GCV, each of whom had GCV‐R CMV infection. In contrast, GCV levels were therapeutic in CMV‐infected patients with delayed GCV response.
Storage of RBCs results in an increased susceptibility for complement‐mediated degradation
Authors: Kamhieh‐Milz J. , Bartl B. , Sterzer V. , Kamhieh‐Milz S. , Salama A.
Published: December 2014

Objective

The objective of this study was to elucidate whether complement activation occurs during the storage of RBCs in newly formulated PAGGS‐M storage medium.

Background

The reason for red blood cell (RBC) storage lesions is not yet fully understood. The contribution of complement to RBC storage lesion has not been extensively characterised.

Study design and methods

We investigated the surface expression of CD35, CD55, CD59 and CD47, as well as deposition of C3d, using flow cytometry over a storage period of up to 42 days on a weekly basis. C3d and the immunoglobulins IgG, IgM and IgA were additionally investigated via the direct antiglobulin test (DAT). The effect of contact with homologous serum for 30 min at 37 °C was also performed for C3d and CD35 and is subsequently termed as a ‘transfusion simulation (TS)’.

Results

A weak but significant increase of C3d was observed prior to TS (anova P = 0·0103), whereas a stronger increase from 74·0 ± 12·4 to 101·2 ± 9·7 was observed post‐TS (anova; P < 0·0001). These findings were confirmed by the DAT. CD35, CD55 and CD47 demonstrated a decrease in their expression over storage time (anova; P < 0·0001 each). The majority of changes occurred following 14 days. There was neither a decrease of CD59 observed nor an increase of IgG, IgM and IgA.

Conclusion

RBCs are becoming increasingly susceptible to spontaneous complement deposition following TS, which might be associated with the decrease of C35 and CD55 by proteolytic cleavage and vesiculation during storage. As the impact of storage lesions is rather controversial, institutions involved in blood collection and administration of blood products should focus on carrying out research on the prevention of storage lesions.