bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oligomeric states in sodium ion–dependent regulation of cyanobacterial histidine kinase-2
Authors: Ibrahim Iskander M. , Wang Liang , Puthiyaveetil Sujith , Krauß Norbert , Nield Jon , Allen John F. 
Published: May 2017

ABSTRACTTwo-component signal transduction systems (TCSs) consist of sensor histidine kinases and response regulators. TCSs mediate adaptation to environmental changes in bacteria, plants, fungi, and protists. Histidine kinase 2 (Hik2) is a sensor histidine kinase found in all known cyanobacteria and as chloroplast sensor kinase in eukaryotic algae and plants. Sodium ions have been shown to inhibit the autophosphorylation activity of Hik2 that precedes phosphoryl transfer to response regulators, but the mechanism of inhibition has not been determined. We report on the mechanism of Hik2 activation and inactivation probed by chemical crosslinking and size exclusion chromatography together with direct visualisation of the kinase using negative-stain transmission electron microscopy of single particles. We show that the functional form of Hik2 is a higher order oligomer such as a hexamer or octamer. Increased NaCl concentration converts the active hexamer into an inactive tetramer. Furthermore, the action of NaCl appears to be confined to the Hik2 kinase domain.IMPORTANCEBacteria sense change and respond to it by means of two-component regulatory systems. The sensor component is a protein that becomes covalently modified by a phosphate group on a histidine side chain. The response regulator accepts the phosphate group onto an aspartate, with structural and functional consequences, often for gene transcription. Histidine kinase 2 is a sensor of sodium ion concentration and redox potential, regulating transcription of genes for light-harvesting and reaction center proteins of photosynthesis in cyanobacteria and chloroplasts of algae and plants. Using radiolabeling, chemical crosslinking, chromatography and electron microscopy, we find that sodium ion concentration governs the oligomeric state of Histidine Kinase 2 and its phosphorylation by ATP.
Identification of jellyfish neuropeptides that act directly as oocyte maturation inducing hormones
Authors: Takeda Noriyo , Kon Yota , Quiroga Artigas Gonzalo , Lapébie Pascal , Barreau Carine , Koizumi Osamu , Kishimoto Takeo , Tachibana Kazunori , Houliston Evelyn , Deguchi Ryusaku 
Published: May 2017

AbstractOocyte meiotic maturation is a critical process for sexually reproducing animals, and its core cytoplasmic regulators are highly conserved between species. In contrast, the few known Maturation Inducing Hormones (MIHs) that act on oocytes to initiate this process have highly variable molecular natures. Using the hydrozoan jellyfish speciesClytiaandCladonema, which undergo oocyte maturation in response to dark-light and light-dark transitions respectively, we deduced from gonad transcriptome data amidated tetrapeptide sequences and found that synthetic peptides could induce maturation of isolated oocytes at nanomolar concentrations. Antibody preabsorption experiments conclusively demonstrated that these W/RPRPamide-related neuropeptides account for endogenous MIH activity produced by isolated gonads. We further showed that the MIH peptides are synthesised by neural-type cells in the gonad, are released following dark-light / light-dark transitions, and probably act on the oocyte surface. They are produced by male as well as female jellyfish and can trigger both sperm and egg release, suggesting a role in spawning coordination. We propose an evolutionary link between hydrozoan MIH and the neuropeptide hormones that regulate reproduction upstream of MIH in bilaterian species.
In vivophenotyping of Parkinson-specific stem cells reveals increased a-Synuclein levels but no spreading
Authors: Hemmer Kathrin , Smits Lisa M. , Bolognin Silvia , Schwamborn Jens C. 
Published: May 2017

AbstractParkinson′s disease is a progressive age-associated neurological disorder. One of the major neuropathological hallmarks of Parkinson’s disease is the appearance of protein aggregates, mainly consisting of the protein alpha-Synuclein. These aggregates have been described both in genetic as well as idiopathic forms of the disease. Currently, Parkinson’s disease patient-specific induced pluripotent stem cells (iPSCs) are mainly used forin vitrodisease modeling or for experimental cell replacement approaches. Here, we demonstrate that these cells can be used forin vivodisease modeling. We show that Parkinson’s disease patient-specific, iPSC-derived neurons carrying the LRRK2-G2019S mutation show an upregulation of alpha-Synuclein after transplantation in the mouse brain. However, further investigations indicate that the increased human alpha-Synuclein levels fail to induce spreading or aggregation in the mouse brain. We therefore conclude that grafting of these cells into the mouse brain is suitable for cell autonomousin vivodisease modeling but has strong limitations beyond that. Furthermore, our results support the hypothesis that there might be a species barrier between human to mouse concerning alpha-Synuclein spreading.
The resistome of common human pathogens
Authors: Munck Christian , Hashim Ellabaan Mostafa M. , Klausen Michael Schantz , Sommer Morten O.A. 
Published: May 2017

AbstractGenes capable of conferring resistance to clinically used antibiotics have been found in many different natural environments. However, a concise overview of the resistance genes found in common human bacterial pathogens is lacking, which complicates risk ranking of environmental reservoirs. Here, we present an analysis of potential antibiotic resistance genes in the 17 most common bacterial pathogens isolated from humans. We analyzed more than 20,000 bacterial genomes and defined a clinical resistome as the set of resistance genes found across these genomes. Using this database, we uncovered the co-occurrence frequencies of the resistance gene clusters within each species enabling identification of co-dissemination and co-selection patterns. The resistance genes identified in this study represent the subset of the environmental resistome that is clinically relevant and the dataset and approach provides a baseline for further investigations into the abundance of clinically relevant resistance genes across different environments. To facilitate an easy overview the data is presented at the species level atwww.resistome.biosustain.dtu.dk.
Ccr4 and Pop2 control poly(A) tail length inSaccharomyces cerevisiae
Authors: Balagopal Vidya , Bolisetty Mohan , Al Husaini Najwa , Coller Jeff , Graveley Brenton R. 
Published: May 2017

ABSTRACTMessenger RNA degradation is an important aspect of post-transcriptional gene regulation and shortening the poly(A) tail is suggested to be the rate-limiting step in mRNA degradation. InSaccharomyces cerevisiae, the Ccr4-Not complex is the major deadenylase and contains two subunits with exoribonuclease domains, Ccr4 and Pop2. Although the role of Ccr4 and Pop2 in deadenylation has previously been studied using individual reporter mRNAs, their activity has not been studied transcriptome-wide. Here, we describe END-seq, a method to accurately measure poly(A) tail lengths of individual mRNAs transcriptome-wide, and have used this assay to examine the impact of deleting or mutatingCCR4andPOP2on steady state poly(A) tail length. We found that Ccr4 and Pop2 have differential effects on the poly(A) tail lengths of individual mRNAs. Additionally, though Pop2 has previously been reported to have exonuclease activity, mutations that render it catalytically inactive have no effect on steady-state poly(A) tail lengths. Furthermore, mutations that disrupt the interaction between Ccr4 and Pop2 result in longer poly(A) tails. We also observe an inverse correlation between codon optimality and poly(A) tail length – transcripts containing predominantly optimal codons display fewer changes in poly(A) tail length upon deletion of Ccr4 or Pop2 than those containing less optimal codons. Together, these results indicate that Pop2 modulates poly(A) tail length, at least partially, via its association with Ccr4 and that Pop2 improves the function of Ccr4 in regulating poly(A) tail length. These data provide important insights into poly(A) tail length dynamics in yeast and demonstrate that END-seq is an efficient and accurate method to study poly(A) tail length.
A gonad-expressed opsin mediates light-induced spawning in the jellyfishClytia
Authors: Quiroga Artigas Gonzalo , Lapébie Pascal , Leclère Lucas , Takeda Noriyo , Deguchi Ryusaku , Jékely Gáspár , Momose Tsuyoshi , Houliston Evelyn 
Published: May 2017

AbstractAcross the animal kingdom, environmental light cues are widely involved in regulating gamete release, but the molecular and cellular bases of the photoresponsive mechanisms are poorly understood. In hydrozoan jellyfish, spawning is triggered by dark-light or light-dark transitions acting on the gonad, and is mediated by oocyte maturation-inducing neuropeptide hormones (MIHs) released from the ectoderm. We determined inClytia hemisphaericathat blue-cyan light triggers spawning in isolated gonads. A candidate opsin (Opsin9) was found co-expressed with MIH within specialised ectodermal cells.Opsin9knockout jellyfish generated by CRISPR/Cas9 failed to undergo oocyte maturation and spawning, a phenotype reversible by synthetic MIH. Gamete maturation and release inClytiais thus regulated by gonadal photosensory-neurosecretory cells that secrete MIH in response to light via Opsin9. Similar cells in ancestral eumetazoans may have allowed tissue-level photo-regulation of diverse behaviours, a feature elaborated in cnidarians in parallel with expansion of the opsin gene family.
Interactive phenotyping of large-scale histology imaging data with HistomicsML
Authors: Nalisnik Michael , Amgad Mohamed , Lee Sanghoon , Halani Sameer H. , Vega Jose Velazquez , Brat Daniel J , Gutman David A , Cooper Lee AD 
Published: May 2017

ABSTRACTWhole-slide imaging of histologic sections captures tissue microenvironments and cytologic details in expansive high-resolution images. These images can be mined to extract quantitative features that describe histologic elements, yielding measurements for hundreds of millions of objects. A central challenge in utilizing this data is enabling investigators to train and evaluate classification rules for identifying objects related to processes like angiogenesis or immune response. Here we present HistomicsML, an interactive machine-learning framework for large whole-slide imaging data. HistomicsML uses active learning direct user feedback, making classifier training efficient and scalable in datasets containing 108+ histologic objects. We demonstrate how HistomicsML can be used to phenotype microvascular structures in gliomas to predict survival, and to explore the molecular pathways associated with these phenotypes. Our approach enables researchers to unlock phenotypic information from digital pathology datasets to investigate prognostic image biomarkers and genotype-phenotype associations.
An inference approach combines spatial and temporal gene expression data to predict gene regulatory networks in Arabidopsis stem cells
Authors: de Luis Balaguer Maria Angels , Fisher Adam P. , Clark Natalie M. , Fernandez-Espinosa Maria Guadalupe , Möller Barbara K. , Weijers Dolf , Lohmann Jan U. , Williams Cranos , Lorenzo Oscar , Sozzani Rosangela 
Published: May 2017

AbstractIdentifying the transcription factors (TFs) and associated networks involved in stem cell regulation is key for understanding the initiation and growth of plant tissues and organs. Although many TFs have been shown to have a role in the Arabidopsis root stem cells, a comprehensive view of the transcriptional signature of the stem cells is lacking. In this work, we used spatial and temporal transcriptomic data to predict interactions among the genes involved in stem cell regulation. For this, we transcriptionally profiled several stem cell populations and developed a gene regulatory network (GRN) inference algorithm that combines clustering with Dynamic Bayesian Network (DBN) inference. We leveraged the topology of our networks to infer potential key regulators. The results presented in this work show that our combination of molecular biology approaches, computational biology and mathematical modeling was key to identify candidate factors that function in the stem cells. Specifically, through experimental validation and mathematical modeling, we identifiedPERIANTHIA (PAN)as an important molecular regulator of quiescent center (QC) function.
Daam2 Driven Degradation of VHL Promotes Gliomagenesis
Authors: Zhu Wenyi , Krishna Saritha , Garcia Cristina , John Lin Chia-Ching , Scott Ken , Mohila Carrie A , Creighton Chad J , Yoo Seung-Hee , Lee Hyun Kyoung , Deneen Benjamin 
Published: May 2017

AbstractVon Hippel-Landau (VHL) protein is a potent tumor suppressor regulating numerous pathways that drive cancer, but mutations in VHL are restricted to limited subsets of malignancies. Here we identified a novel mechanism for VHL suppression in tumors that do not have inactivating mutations. Using developmental processes to uncover new pathways contributing to tumorigenesis, we found that Daam2 promotes glioma formation. Protein expression screening identified an inverse correlation between Daam2 and VHL expression across a host of cancers, including glioma. Thesein silicoinsights guided corroborating functional studies, which revealed that Daam2 promotes tumorigenesis by suppressing VHL expression. Furthermore, biochemical analyses demonstrate that Daam2 associates with VHL and facilitates its ubiquitination and degradation. Together, these studies are the first to define an upstream mechanism regulating VHL suppression in cancer and describe the role of Daam2 in tumorigenesis.Statement of SignificanceWe found that the glial developmental factor Daam2 promotes glioma tumorigenesis by suppressing VHL expression. Our studies show, for the first time, a regulatory mechanism that operates upstream of VHL in cancer and provides an explanation for how VHL expression is extinguished in tumors that do not have inactivating mutations.
Service quality, perceived value, satisfaction and intention to pay
Authors: Londoño Beatriz , Prado Yesica , Salazar Viviana 
Published: May 2017

ObjectiveThe purpose of this paper is to examine the relations between the concepts of service quality, perceived value, satisfaction and intention to pay in the context of theatrical services in the city of Medellín, Colombia.Design/methodologyQuantitative research was carried out on a sample of 274 individuals who had attended the theatre at least once in the previous year. The information was gathered in October 2014 using an online survey. Confirmatory factor analysis was used to test the validity and reliability of the measurement scales, and a structural equations model was developed to test the hypotheses.FindingsSatisfaction with overall service and with the central service (i.e. with the performance itself) was the major predictors of consumer intention to pay.Limitations/implications of the researchFuture research could replicate the analysis presented here for other cultural services and different geographical contexts.Practical implicationsTheatres should focus their efforts on offering a basic service (a theatrical presentation) that meets the cultural and artistic expectations of the public, but should also bear in mind that audiences expect to be treated well when they go out and want to feel comfortable.Originality/valueThis paper contributes to understand the factors that influence theatre clients’ intention to pay by taking into account the factors that affect satisfaction and perceived value of the theatregoing experience. It also contributes to academic reflections on the cultural consumption in the field of the theatrical arts in the Latin American region, where this is a new field of research.
Development, implementation and evaluation of nurse-led integrated, person-centred care with long-term conditions
Authors: Harvey Clare Lynette , Sibley Jonathan , Palmer Janine , Phillips Andrew , Willis Eileen , Marshall Robert , Thompson Shona , Ward Susanne , Forrest Rachel , Pearson Maria 
Published: May 2017

Purpose
The purpose of this paper is to outline a conceptual plan for innovative, integrated care designed for people living with long-term conditions (LTCs).

Design/methodology/approach
The conceptual plan delivers a partnership between the health system, the person with LTCs (chronic), their family, and the community. The partnership aims to support people at home with access to effective treatment, consistent with the New Zealand Government Health Strategy. This concept of people-owned care is provided by nurses with advanced practice skills, who coordinate care across services, locations and multiple LTCs.

Findings
With the global increase in numbers of people with multiple chronic conditions, health services are challenged to deliver good outcomes and experience. This model aims to demonstrate the effective use of healthcare resources by supporting people living with a chronic condition, to increase their self-efficacy and resilience in accordance with personal, cultural and social circumstance. The aim is to have a model of care that is replicable and transferable across a range of health services.

Social implications
People living with chronic conditions can be empowered to manage their health and well-being, whilst having access to nurse-led care appropriate to individual needs.

Originality/value
Although there are examples of case management and nurse-led coordination, this model is novel in that it combines a liaison nursing role that works in partnership with patients, whilst ensuring that care across a number of primary and secondary care services is truly integrated and not simply interfaced.
Imaging and Peritoneal Dialysis Catheters
Authors: Ash Stephen , Sequeira Adrian , Narayan Rajeev 
Published: May 2017

AbstractThe placement of a peritoneal dialysis (PD) catheter by interventionalists demands not only procedural skill but also an ability to decipher real‐time ultrasonographic and fluoroscopic images. In this article, we discuss how imaging assists in PD placement and recognition of complications. To aid this endeavor, we have provided images and video clips that should assist interventionalists. Compared with the fluoroscopic technique, peritoneoscopic PD catheter placement provides direct visual imaging to also aid placement of the initial trocar and the peritoneal catheter.
Development of Multiwell-Plate Methods Using Pure Cultures of Methanogens To Identify New Inhibitors for Suppressing Ruminant Methane Emissions
Authors: Weimar M. R. , Cheung J. , Dey D. , McSweeney C. , Morrison M. , Kobayashi Y. , Whitman W. B. , Carbone V. , Schofield L. R. , Ronimus R. S. , Cook G. M. 
Published: May 2017

ABSTRACT

Hydrogenotrophic methanogens typically require strictly anaerobic culturing conditions in glass tubes with overpressures of H
2
and CO
2
that are both time-consuming and costly. To increase the throughput for screening chemical compound libraries, 96-well microtiter plate methods for the growth of a marine (environmental) methanogen
Methanococcus maripaludis
strain S2 and the rumen methanogen
Methanobrevibacter
species AbM4 were developed. A number of key parameters (inoculum size, reducing agents for medium preparation, assay duration, inhibitor solvents, and culture volume) were optimized to achieve robust and reproducible growth in a high-throughput microtiter plate format. The method was validated using published methanogen inhibitors and statistically assessed for sensitivity and reproducibility. The Sigma-Aldrich LOPAC library containing 1,280 pharmacologically active compounds and an in-house natural product library (120 compounds) were screened against
M. maripaludis
as a proof of utility. This screen identified a number of bioactive compounds, and MIC values were confirmed for some of them against
M. maripaludis
and
M.
AbM4. The developed method provides a significant increase in throughput for screening compound libraries and can now be used to screen larger compound libraries to discover novel methanogen-specific inhibitors for the mitigation of ruminant methane emissions.

IMPORTANCE
Methane emissions from ruminants are a significant contributor to global greenhouse gas emissions, and new technologies are required to control emissions in the agriculture technology (agritech) sector. The discovery of small-molecule inhibitors of methanogens using high-throughput phenotypic (growth) screening against compound libraries (synthetic and natural products) is an attractive avenue. However, phenotypic inhibitor screening is currently hindered by our inability to grow methanogens in a high-throughput format. We have developed, optimized, and validated a high-throughput 96-well microtiter plate assay for growing environmental and rumen methanogens. Using this platform, we identified several new inhibitors of methanogen growth, demonstrating the utility of this approach to fast track the development of methanogen-specific inhibitors for controlling ruminant methane emissions.
Iron-Dependent Enzyme Catalyzes the Initial Step in Biodegradation of
N
-Nitroglycine by Variovorax sp. Strain JS1663
Authors: Mahan Kristina M. , Zheng Hangping , Fida Tekle T. , Parry Ronald J. , Graham David E. , Spain Jim C. 
Published: May 2017

ABSTRACT

Nitramines are key constituents of most of the explosives currently in use and consequently contaminate soil and groundwater at many military facilities around the world. Toxicity from nitramine contamination poses a health risk to plants and animals. Thus, understanding how nitramines are biodegraded is critical to environmental remediation. The biodegradation of synthetic nitramine compounds such as hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) has been studied for decades, but little is known about the catabolism of naturally produced nitramine compounds. In this study, we report the isolation of a soil bacterium,
Variovorax
sp. strain JS1663, that degrades
N
-nitroglycine (NNG), a naturally produced nitramine, and the key enzyme involved in its catabolism.
Variovorax
sp. JS1663 is a Gram-negative, non-spore-forming motile bacterium isolated from activated sludge based on its ability to use NNG as a sole growth substrate under aerobic conditions. A single gene (
nnlA
) encodes an iron-dependent enzyme that releases nitrite from NNG through a proposed β-elimination reaction. Bioinformatics analysis of the amino acid sequence of NNG lyase identified a PAS (Per-Arnt-Sim) domain. PAS domains can be associated with heme cofactors and function as signal sensors in signaling proteins. This is the first instance of a PAS domain present in a denitration enzyme. The NNG biodegradation pathway should provide the basis for the identification of other enzymes that cleave the N—N bond and facilitate the development of enzymes to cleave similar bonds in RDX, nitroguanidine, and other nitramine explosives.

IMPORTANCE
The production of antibiotics and other allelopathic chemicals is a major aspect of chemical ecology. The biodegradation of such chemicals can play an important ecological role in mitigating or eliminating the effects of such compounds.
N
-Nitroglycine (NNG) is produced by the Gram-positive filamentous soil bacterium
Streptomyces noursei
. This study reports the isolation of a Gram-negative soil bacterium,
Variovorax
sp. strain JS1663, that is able to use NNG as a sole growth substrate. The proposed degradation pathway occurs via a β-elimination reaction that releases nitrite from NNG. The novel NNG lyase requires iron(II) for activity. The identification of a novel enzyme and catabolic pathway provides evidence of a substantial and underappreciated flux of the antibiotic in natural ecosystems. Understanding the NNG biodegradation pathway will help identify other enzymes that cleave the N—N bond and facilitate the development of enzymes to cleave similar bonds in synthetic nitramine explosives.