bluuebunny/crossref_metadata_2025 huggingface dataset:
Recapitulation and Retrospective Prediction of Biomedical Associations Using Temporally-enabled Word Embeddings
Authors: Park Jiho , Marquez Agustin Lopez , Puranik Arjun , Rajasekharan Ajit , Aravamudan Murali , Garcia-Rivera Enrique
Published: May 2019

The recent explosion of biomedical knowledge presents both a major opportunity and challenge for scientists tackling complex problems in healthcare. Here we present an approach for synthesizing biomedical knowledge based on a combination of word-embeddings and select cooccurrences. We evaluated our ability to recapitulate and retrospectively predict disease-gene associations from the Online Mendelian Inheritance in Man (OMIM) resource. Our metrics achieved an area under the curve (AUC) value of 0.981 at the recapitulation task for 2,400 disease-gene associations. At the most stringent cutoff, our metrics predicted 13.89% of these associations before their first cooccurrence in the literature, with a median time of 4 years between prediction and first cooccurrence. Finally, our literature metrics can be combined with human genetics data to retrospectively predict disease-gene associations, IL-6 and Giant Cell Arteritis provided as an example. We believe this framework can provide robust biomedical hypotheses at a much faster pace than current standard practices.
RUNX1/RUNX1T1 controls alternative splicing in the t(8;21)-positive acute myeloid leukemia cells
Authors: Grinev Vasily , Ilyushonak Ilia , Clough Richard , Nakjang Sirintra , Smink Job , Martinez-Soria Natalia , Ramanouskaya Tatsiana , Bonifer Constanze , Heidenreich Olaf
Published: May 2019

The fusion oncogene RUNX1/RUNX1T1 encodes an aberrant transcription factor, which plays a key role in the initiation and maintenance of the t(8;21)-positive acute myeloid leukemia. Here we show that this oncogene is a regulator of the alternative RNA splicing for a sub-set of genes in the leukemia cells. We found two primary mechanisms underlying changes in the production of RNA isoforms: (i) RUNX1/RUNX1T1-mediated regulation of alternative transcription start sites selection in target genes, and (ii) direct or indirect control of the expression of the genes encoding splicing factors. The first mechanism leads to the expression of RNA isoforms with alternative structure of the 5’-UTR regions. The second mechanism generates alternative transcripts with new junctions between internal cassettes and constitutive exons. We also show that RUNX1/RUNX1T1-mediated differential splicing affects several functional groups of genes and produces proteins with unique conserved domain structures. In summary, this study reveals a novel layer of RUNX1/RUNX1T1-dependent transcriptome organization in t(8;21)-positive acute myeloid leukemia.
DEN-IM: Dengue Virus identification from shotgun and targeted metagenomics
Authors: Mendes C I , Lizarazo E , Machado M P , Silva D N , Tami A , Ramirez M , Couto N , Rossen J W A , Carriço J A
Published: May 2019

Dengue virus (DENV) represents a public health and economic burden in affected countries. The availability of genomic data is key to understand viral evolution and dynamics, supporting improved control strategies. Currently, the use of High Throughput Sequencing (HTS) technologies, which can be applied both directly to patient samples (shotgun metagenomics) and to PCR amplified viral sequences (targeted metagenomics), is the most informative approach to monitor the viral dissemination and genetic diversity.

Despite many advantages, these technologies require bioinformatics expertise and appropriate infrastructure for the analysis and interpretation of the resulting data. In addition, the many software solutions available can hamper reproducibility and comparison of results.

Here we present DEN-IM, a one-stop, user-friendly, containerised and reproducible workflow for the analysis of DENV sequencing data, both from shotgun and targeted metagenomics approaches. It is able to infer DENV coding sequence (CDS), identify serotype and genotype, and generate a phylogenetic tree. It can easily be run on any UNIX-like system, from local machines to high-performance computing clusters, performing a comprehensive analysis without the requirement of extensive bioinformatics expertise.

Using DEN-IM, we successfully analysed two DENV datasets. The first comprised 25 shotgun metagenomic sequencing samples of varying serotype and genotype, including a spiked sample containing the existing four serotypes. The second dataset consisted of 106 targeted metagenomics samples of DENV 3 genotype III where DEN-IM allowed detection of the intra-genotype diversity.

The DEN-IM workflow, parameters and execution configuration files, and documentation are freely available athttps://github.com/B-UMMI/DEN-IM.
Protein Expression Patterns in ovarian cancer cells Associated with Monofunctional Platinums Treatment
Authors: Arzuman Laila , Moni Mohammad Ali , Beale Philip , Yu Jun Q. , Molloy Mark , Quinn Julian M.W. , Huq Fazlul
Published: May 2019

Platinum drugs cisplatin and carboplatin, given in combination with paclitaxel, constitute the standard chemotherapy against ovarian cancer (OC). Oc chemoresistance is a major obstacle to effective treatment, but knowledge of the mechanisms that underlie it remains incomplete. We thus sought to discover key proteins associated with platinum resistance by comparing A2780 OC cells with A2780cisR cells (resistant cells derived from the A2780 line) to identify proteins with markedly altered expression levels in the resistant cells. We also determined which proteins in these cells had altered expression in response to treatment with either designed monofunctional platinum alone or a combination with cisplatin with selected phytochemical therapeutic agents.

We thus performed proteomic analysis using 2D-gel electrophoresis A2780 and A2780cisR to identify proteins with differential expression; these were eluted and analysed by mass spectrometry to identify them. A total of 122 proteins were found to be differentially expressed between A2780 and A2780cisR cell lines in the absence of any drug treatment. Among them, levels of 27 proteins in A2780cisR cell line were further altered (up-or down-regulated) in response to one or more of the drug treatments. We then investigated primary OC tissue RNA expression levels (compared to l ovarian tissue) of genes coding for these candidate 27 proteins using publically available datasets (The Cancer Genome Atlas). We assessed how expression of these genes in OC tissue associates with patient survival using Cox Proportional Hazard (PH) regression models to determine relative risk of death associated with each factor. Our Cox PH regression-based machine learning method confirmed a significant relationship of mortality with altered expression of ARHGDIA, CCT6A and HISTIH4F genes. This indicated that these genes affect OC patient survival, i.e., provided mechanistic evidence, in addition to that of the clinical traits, that these genes may be critical mediators of the processes that underlie OC progression and mortality.

Thus, we identified differentially expressed proteins that are implicated in platinum-based chemotherapy resistance mechanisms which may serve as resistance biomarkers. These drug resistance associated proteins may also serve as potential OC therapeutic targets whose blockade may enhance the effectiveness of platinum based drugs.
Different energetic diets affect the maintenance of Apis mellifera L. colonies during off-season
Authors: de Oliveira Gabriela Pinto , Kadri Samir Moura , Emilio Benaglia Bruno Giovane , Martins Ribolla Paulo Eduardo , de Oliveira Orsi Ricardo
Published: May 2019

The aim of this study wasto evaluate the best energetic foodforuse in the maintenance of honey bee colonies during the off-season. To do this, 20Apis mellifera beehives were used(with five beehives per treatment): CTL,control (without feeding); SJ,sugarcane juice; SS,sugar syrup; and IS,inverted sugar. We evaluated the food consumption, population development, and physiological state (expression of vitellogenin and hexamerin 70agenes)of eachcolony.The results showed that the supplementation of colonieswith sugar syrup resulted in an intermediateconsumption and thebetter development of the colony.In addition, this diet ensured that the colonies were in a good physiological state,as beesfed this diet presentedthe highest relative expression levels of vitellogenin and hexamerin 70ameasuredamong all thediets tested.Therefore, sugar syrup was concluded to be the best artificial energetic food for use in thesupplementation of honey bee colonies during the off-season.
Model-based control of individual finger movements for prosthetic hand function
Authors: Blana Dimitra , van den Bogert Antonie J. , Murray Wendy M. , Ganguly Amartya , Krasoulis Agamemnon , Nazarpour Kianoush , Chadwick Edward K.
Published: May 2019

Prosthetic devices for hand difference have advanced considerably in recent years, to the point where the mechanical dexterity of a state-of-the-art prosthetic hand approaches that of the natural hand. Control options for users, however, have not kept pace, meaning that the new devices are not used to their full potential. Promising developments in control technology reported in the literature have met with limited commercial and clinical success. We have previously described a biomechanical model of the hand that could be used for prosthesis control. In this study, we report on three key elements of the biomechanical simulations relevant to prosthesis control: we show the performance of the model in replicating recorded hand kinematics and find average correlations of 0.89 between modelled and recorded motions; we show that the computational performance of the simulations is fast enough to achieve real-time control with a robotic hand in the loop; and we describe the use of the model for controlling object gripping. Despite some limitations in accessing sufficient driving signals, the model performance shows promise as a controller for prosthetic hands when driven with recorded EMG signals. We identify areas for future work to address these limitations.
The L1 stalk is required for efficient export of nascent large ribosomal subunits in yeast
Authors: Musalgaonkar Sharmishtha , Black Joshua J. , Johnson Arlen W.
Published: May 2019

The ribosomal protein Rpl1 (uL1 in universal nomenclature) is essential in yeast and constitutes part of the L1 stalk which interacts with E site ligands on the ribosome. Structural studies of nascent pre-60S complexes in yeast have shown that a domain of the Crm1-dependent nuclear export adapter Nmd3, binds in the E site and interacts with Rpl1, inducing closure of the L1 stalk. Based on this observation, we decided to reinvestigate the role of the L1 stalk in nuclear export of pre-60S subunits despite previous work showing that Rpl1-deficient ribosomes are exported from the nucleus and engage in translation. Large cargoes, such as ribosomal subunits, require multiple export factors to facilitate their transport through the nuclear pore complex. Here, we show that pre-60S subunits lacking Rpl1 or truncated for the RNA of the L1 stalk are exported inefficiently. Surprisingly, this is not due to a measurable defect in recruitment of Nmd3 but appears to result from inefficient recruitment of the Mex67-Mtr2 heterodimer.
Rapid functionalisation and detection of viruses via a novel Ca2+-mediated virus-DNA interaction
Authors: Robb Nicole C. , Taylor Jonathan M. , Kent Amy , Pambos Oliver J. , Gilboa Barak , Kapanidis Achillefs N.
Published: May 2019

Current virus detection methods often take significant time or can be limited in sensitivity and specificity. The increasing frequency and magnitude of viral outbreaks in recent decades has resulted in an urgent need for diagnostic methods that are facile, sensitive, rapid and inexpensive. Here, we describe and characterise a novel, calcium-mediated interaction of the surface of enveloped viruses with DNA, that can be used for the functionalisation of intact virus particles via chemical groups attached to the DNA. Using DNA modified with fluorophores, we have demonstrated the rapid and sensitive labelling and detection of influenza and other viruses using single-particle tracking and particle-size determination. With this method, we have detected clinical isolates of influenza in just one minute, significantly faster than existing rapid diagnostic tests. This powerful technique is easily extendable to a wide range of other enveloped pathogenic viruses and holds significant promise as a future diagnostic tool.
Noncanonical scaffolding of Gαiand β-arrestin by G protein-coupled receptors
Authors: Smith Jeffrey S. , Pack Thomas F. , Inoue Asuka , Lee Claudia , Xiong Xinyu , Zheng Kevin , Kahsai Alem W. , Choi Issac , Ma Zhiyuan , Levitan Ian M. , Rochelle Lauren K. , Staus Dean P. , Snyder Joshua C. , Caron Marc G. , Rajagopal Sudarshan
Published: May 2019

G-protein-coupled receptors (GPCRs) enable cells to sense and respond appropriately to hormonal and environmental signals, and are a target of ~30% of all FDA-approved medications. Canonically, each GPCR couples to distinct Gαproteins, such as Gαs, Gαi, Gαqor Gα12/13, as well as β-arrestins. These transducer proteins translate and integrate extracellular stimuli sensed by GPCRs into intracellular signals through what are broadly considered separable signalling pathways. However, the ability of Gαproteins to directly interact with β-arrestins to integrate signalling has not previously been appreciated. Here we show a novel interaction between Gαiprotein family members and β-arrestin. Gαi:β-arrestin complexes were formed by all GPCRs tested, regardless of their canonical G protein isoform coupling, and could bind both GPCRs as well as the extracellular signal-regulated kinase (ERK). This novel paradigm of Gαi:β-arrestin scaffolds enhances our understanding of GPCR signalling.
PROMO: An interactive tool for analyzing clinically-labeled multi-omic cancer datasets
Authors: Netanely Dvir , Stern Neta , Laufer Itay , Shamir Ron
Published: May 2019

Background

Analysis of large genomic datasets along with their accompanying clinical information has shown great promise in cancer research over the last decade. Such datasets typically include thousands of samples, each measured by one or several high-throughput technologies (‘omics’) and annotated with extensive clinical information. While instrumental for fulfilling the promise of personalized medicine, the analysis and visualization of such large datasets is challenging and necessitates programming skills and familiarity with a large array of software tools to be used for the various steps of the analysis.

Results

We developed PROMO (Profiler of Multi-Omic data), a friendly, fully interactive stand-alone software for analyzing large genomic cancer datasets together with their associated clinical information. The tool provides an array of built-in methods and algorithms for importing, preprocessing, visualizing, clustering, clinical label enrichment testing and survival analysis that can be performed on a single or multi-omic dataset. The tool can be used for quick exploration and for stratification of tumor samples taken from patients into clinically significant molecular subtypes. Identification of prognostic biomarkers and generation of simple subtype classifiers are additional important features. We review PROMO’s main features and demonstrate its analysis capabilities on a breast cancer cohort from TCGA.

Conclusions

PROMO provides a single integrated solution for swiftly performing a complete analysis of cancer genomic data for subtype discovery and biomarker identification without writing a single line of code, and can, therefore, make the analysis of these data much easier for cancer biologists and biomedical researchers. PROMO is freely available for download at http://acgt.cs.tau.ac.il/promo/.
Calcium entry does not drive fast mechanotransduction adaptation in cochlear hair cells
Authors: Caprara Giusy A. , Mecca Andrew A. , Wang Yanli , Ricci Anthony J. , Peng Anthony W.
Published: May 2019

Sound detection in auditory sensory hair cells depends on the deflection of the stereocilia hair bundle, which opens mechano-electric transduction (MET) channels. Adaptation is hypothesized to be a critical property of MET that contributes to the wide dynamic range and sharp frequency selectivity of the auditory system. Historically, adaptation was hypothesized to have multiple mechanisms, all of which require calcium entry through MET channels. Our recent work using a stiff probe to displace hair bundles showed that the fastest adaptation mechanism (fast adaptation) does not require calcium entry. Using a fluid-jet stimulus, others obtained data showing only a calcium-dependent fast adaptation response. Here, we identified the source of this discrepancy. Because the hair cell response to a hair bundle stimulus depends critically on the magnitude and time course of the hair bundle deflection, we developed a high-speed imaging technique to quantify this deflection. The fluid jet delivers a force stimulus, and step-like force stimuli lead to a complex time course of hair bundle displacement (mechanical creep), which affects the hair cell’s macroscopic MET current response by masking the time course of the fast adaptation response. Modifying the fluid-jet stimulus to generate a step-like hair bundle displacement produced rapidly adapting currents that did not depend on membrane potential. This indicated that fast adaptation does not depend on calcium entry. We also confirmed the presence of a calcium-dependent slow adaptation process. These results confirm the existence of multiple adaptation processes: a fast adaptation that is not driven by calcium entry and a slower calcium-dependent process.

Significance Statement

Mechanotransduction by sensory hair cells represents a key first step for the sound sensing ability in vertebrates. The sharp frequency tuning and wide dynamic range of sound sensation are hypothesized to require a mechanotransduction adaptation mechanism. For decades, it had been accepted that all adaptation mechanisms require calcium entry into hair cells. However, more recent work indicated that the apparent calcium dependence of the fastest adaptation differs with the method of cochlear hair cell stimulation. Here, we reconcile existing data and show that calcium entry does not drive the fastest adaptation process, independent of the stimulation method.
A highly-selective chloride microelectrode based on a mercuracarborand anion carrier
Authors: DiFranco Marino , Quinonez Marbella , Dziedzic Rafal M. , Spokoyny Alexander M. , Cannon Stephen C.
Published: May 2019

The chloride gradient plays an important role in regulating cell volume, membrane potential, pH, secretion, and the reversal potential of inhibitory GABAA receptors. Measurement of intracellular chloride activity, , using liquid membrane ion-selective microelectrodes (ISM), however, has been limited by the physiochemical properties of Cl ionophores which have caused poor stability, drift, sluggish response times, and interference from other biologically relevant anions. Most importantly, intracellular HCO3− may be up to 4 times more abundant than Cl− (e.g. skeletal muscle) which places severe constraints on the required selectivity of a Cl – sensing ISM.

Previously, a sensitive and highly-selective Cl sensor was developed in a polymeric membrane electrode (Badr et al. 1999) using a trinuclear Hg(II) complex containing carborane-based ligands, [9]-mercuracarborand-3, or MC3 for short. Here, we have adapted the use of the MC3 anion carrier in a liquid membrane ion-selective microelectrode and show the MC3-ISM has a linear Nernstian response over a wide range of aCl (0.1 mM to 100 mM), is highly selective for Cl over other biological anions or inhibitors of Cl transport, and has a response time of less than 5 sec. Importantly, over the physiological range of aCl (1 mM to 100 mM) the potentiometric response of the MC3-ISM is insensitive to HCO3− or changes in pH. Finally, we demonstrate the biological application of an MC3-ISM by measuring intracellular aCl, and the response to an external Cl-free challenge, for an isolated skeletal muscle fiber.
Variable prediction accuracy of polygenic scores within an ancestry group
Authors: Mostafavi Hakhamanesh , Harpak Arbel , Conley Dalton , Pritchard Jonathan K , Przeworski Molly
Published: May 2019

Fields as diverse as human genetics and sociology are increasingly using polygenic scores based on genome-wide association studies (GWAS) for phenotypic prediction. However, recent work has shown that polygenic scores have limited portability across groups of different genetic ancestries, restricting the contexts in which they can be used reliably and potentially creating serious inequities in future clinical applications. Using the UK Biobank data, we demonstrate that even within a single ancestry group, the prediction accuracy of polygenic scores depends on characteristics such as the age or sex composition of the individuals in which the GWAS and the prediction were conducted, and on the GWAS study design. Our findings highlight both the complexities of interpreting polygenic scores and underappreciated obstacles to their broad use.
Relationships between MA-RNA binding in cells and suppression of HIV-1 Gag mislocalization to intracellular membranes
Authors: Thornhill Dishari , Olety Balaji , Ono Akira
Published: May 2019

The HIV-1 Gag matrix (MA) domain mediates localization of Gag to the plasma membrane (PM), the site for infectious virion assembly. The MA highly basic region (HBR) interacts with phosphatidylinositol-(4,5)-bisphosphate [PI(4,5)P2], a PM-specific acidic lipid. MA-HBR also binds RNAs. To test whether acidic lipids alone determine PM-specific localization of Gag or whether MA-RNA binding also plays a role, we compared a panel of MA-HBR mutants that contain two types of substitutions at MA residues 25/26 or 29/31: Lys->Arg (KR) (25/26KR and 29/31KR) and Lys->Thr (KT) (25/26KT and 29/31KT). Consistent with the importance of the HBR charge in RNA binding, both KT mutants failed to bind RNA via MA efficiently unlike the corresponding KR mutants. Both 25/26KT Gag-YFP and 29/31KT Gag-YFP bound non-specifically to PM and intracellular membranes, presumably via the myristoyl moiety and remaining MA basic residues. In contrast, 25/26KR Gag-YFP bound specifically to the PM, suggesting a role for the total positive charge and/or MA-bound RNA in navigating Gag to the PM. Unlike 29/31KT Gag-YFP, 29/31KR Gag-YFP was predominantly cytosolic and showed little intracellular membrane binding despite having a higher HBR charge. Therefore, it is likely that MA-RNA binding blocks promiscuous Gag membrane binding in cells. Notably, introduction of a heterologous multimerization domain restored PI(4,5)P2-dependent PM-specific localization for 29/31KR Gag-YFP, suggesting that the blocking of PM binding is more readily reversed than that of intracellular membrane binding. Altogether, these cell-based data support a model in which MA-RNA binding ensures PM-specific localization of Gag via suppression of non-specific membrane binding.

IMPORTANCE

The PM-specific localization of HIV-1 Gag is a crucial early step in the infectious progeny production. The interaction between the MA highly basic region (HBR) of Gag and the PM-specific lipid PI(4,5)P2 is critical for Gag localization to the PM. Additionally,in vitroevidence has indicated that MA-RNA binding prevents non-specific binding of Gag to non-PI(4,5)P2-containing membranes. However, cell-based evidence supporting a role for HIV-1 MA-RNA binding in PM-specific subcellular localization has been scarce; thus, it remained possible that in cells, just the high basic charge or the PI(4,5)P2-binding ability is sufficient for MA to direct Gag specifically to the PM. The current study revealed for the first time an excellent correlation between RNA binding of MA-HBR and inhibition of promiscuous Gag localization, both within the cells, and thereby provided cell-based evidence supporting a mechanism in which HIV-1 MA binding to RNA ensures specific localization of Gag to the PM.
Acquisition of cross-resistance to Bedaquiline and Clofazimine following treatment for Tuberculosis in Pakistan
Authors: Ghodousi Arash , Rizvi Alamdar Hussain , Baloch Aurangzaib Quadir , Ghafoor Abdul , Khanzada Faisal Masood , Qadir Mehmood , Borroni Emanuele , Trovato Alberto , Tahseen Sabira , Cirillo Daniela Maria
Published: May 2019

We report on the first six cases of acquired resistance to bedaquiline in Pakistan. Seventy sequential culture isolates from 30 drug-resistant tuberculosis patients on bedaquiline-containing regimen were tested for minimum inhibitory concentration (MIC) and whole genome sequencing. An increase in MICs associated with cross-resistance to clofazimine and appearance of specific mutations was documented in six cases. The study underlines that appropriate monitoring is mandatory for the introduction of new drugs.
AI on animals: AI-assisted animal-borne logger never misses the moments that biologists want
Authors: Korpela Joseph M. , Suzuki Hirokazu , Matsumoto Sakiko , Mizutani Yuichi , Samejima Masaki , Maekawa Takuya , Nakai Junichi , Yoda Ken
Published: May 2019

Animal-borne data loggers, i.e., biologgers, allow researchers to record a variety of sensor data from animals in their natural environments (Hussey et al. 2015; Kays et al. 2015). This data allows biologists to observe many aspects of the animals’ lives, including their behavior, physiology, social interactions, and external environment. However, the need to limit the size of these devices to a small fraction of the animal’s size imposes strict limits on the devices’ hardware and battery capacities (Kays et al. 2015). Here we show how AI can be leveraged on board these devices to intelligently control their activation of costly sensors, e.g., video cameras, allowing them to make the most of their limited resources during long deployment periods. Our method goes beyond previous works that have proposed controlling such costly sensors using simple threshold-based triggers, e.g., depth-based (Watanuki et al. 2007; Volpov et al. 2015) and acceleration-based (Nishiumi et al. 2018; Brown et al. 2012) triggers. Using AI-assisted biologgers, biologists can focus their data collection on specific complex target behaviors such as foraging activities, allowing them to automatically record video that captures only the moments they want to see. By doing so, the biologger can reserve its battery power for recording only those target activities. We anticipate our work will provide motivation for more widespread adoption of AI techniques on biologgers, both for intelligent sensor control and intelligent onboard data processing. Such techniques can not only be used to control what is collected by such devices, but also what is transmitted off the devices, such as is done by satellite relay tags (Cox et al. 2018).
A genetically validated approach to detect inorganic polyphosphates in plants
Authors: Zhu Jinsheng , Loubéry Sylvain , Broger Larissa , Lorenzo-Orts Laura , Utz-Pugin Anne , Young-Tae Chang , Hothorn Michael
Published: May 2019

Inorganic polyphosphates (polyPs) are linear polymers of orthophosphate units linked by phosphoanhydride bonds. PolyPs represent important stores of phosphate and energy, and are abundantly found in many pro- and eukaryotic organisms. In plants, the existence of polyPs has been established using microscopy and biochemical extraction methods that are now known to produce artifacts. Here we use a polyP-specific dye and a polyP binding domain to detect polyPs in plant and algal cells. To develop the staining protocol, we induced polyP granules inNicotiana benthamianaand Arabiopsis cells by heterologous expression ofE. colipolyphosphate kinase 1 (PPK1). Over-expression of PPK1 but not of a catalytically impaired version of the enzyme lead to severe growth phenotypes, suggesting that ATP-dependent synthesis and accumulation of polyPs in the plant cytosol is toxic. We next crossed stable PPK1 expressing Arabidopsis lines with plants expressing the polyP-binding domain ofE. coliexopolyphosphatase (PPX1c), which co-localized with PPK1-generated polyP granules. These granules were stained by the polyP-specific dye JC-D7 and appeared as electron dense structures in transmission electron microscopy (TEM) sections. Using the polyP staining protocol derived from these experiments, we screened for polyP stores in different organs and tissues of both mono- and dicotyledonous plants. While we could not detect polyP granules in higher plants, we could visualize the polyP-rich acidocalicisomes in the green algaeChlamydomonas reinhardtii.Together, our experiments suggest that higher plants may not contain large polyPs stores.

Significance Statement

A chemical dye and an inorganic polyphosphate binding domain are shown to specifically label inorganic polyphosphate granules in transgenic Arabidopsis lines and Chlamydomonas acidocalcisomes. Using these tools, we show that in contrast to many prokaryotic and eukaryotic organisms, higher plants do not seem to contain large inorganic polyphosphate stores.
Amplification of genomic regions harbouring genes with dose-limiting effects provides selection pressure for acquiring aberrant epigenetic silencing in ovarian cancer
Authors: Bonito Nair , Eringyte Ieva , Masrour Nahal , Wilhelm-Benartzi Charlotte , Brown Robert , Curry Edward
Published: May 2019

High-grade serous ovarian cancer (HGSOC) feature widespread genomic rearrangements that alter the copy number of genes. Genes for which elevated expression is detrimental to growth may be passengers in rearrangements that increase the copy number of strongly selective driver genes. There would then be selection pressure for compensatory epigenetic silencing of such passenger genes, such as through promoter DNA methylation.

We have used two independent cohorts of primary HGSOC tumour samples to provide evidence of consistent dosage-compensating promoter methylation (DCPM) genome-wide. Mapping CpG methylation to genomic copy number, we show that bias due to variable tumour cellularity of tissue samples results in false positive associations between methylation and copy number. Adjusting for this bias, we found that approximately 5-10% of all measured promoter CpGs with copy number gain showed a statistically significant increase in methylation. DCPM nullifies the association between increased copy number and increased gene expression. We confirmed a functional basis for selective pressure against over-expressing two candidate passenger genes in the 3q12 locus, as overexpressing either gene reduced spheroid formation efficiency in two HGSOC cell lines. DCPM represents a novel class of specific functional interactions between genetic and epigenetic landscapes of cancers.
Genetic variation regulates the activation and specificity of Restriction-Modification systems in Neisseria gonorrhoeae
Authors: Sánchez-Busó Leonor , Golparian Daniel , Parkhill Julian , Unemo Magnus , Harris Simon R.
Published: May 2019

Restriction-Modification systems (RMS) are one of the main mechanisms of defence against foreign DNA invasion and can have an important role in the regulation of gene expression. The obligate human pathogen Neisseria gonorrhoeae carries one of the highest loads of RMS in its genome; between 13 to 15 of the three main types. Previous work has described their organization in the reference genome FA1090 and has experimentally inferred the associated methylated motifs. Here, we studied the structure of RMS and target methylated motifs in 25 gonococcal strains sequenced with Single Molecule Real-Time (SMRT) technology, which provides data on DNA modification. The results showed a variable picture of active RMS in different strains, with phase variation switching the activity of Type III RMS, and both the activity and specificity of a Type I RMS. Interestingly, the Dam methylase was found in place of the NgoAXI endonuclease in two of the strains, despite being previously thought to be absent in the gonococcus. We also identified the real methylation target of NgoAX as 5’-GCAGA-3’, different from that previously described. Results from this work give further insights into the diversity and dynamics of RMS and methylation patterns in N. gonorrhoeae.
Transactional sex among men who have sex with men participating in the CohMSM prospective cohort study in West Africa
Authors: Kounta Cheick Haïballa , Sagaon-Teyssier Luis , Coulaud Pierre-Julien , Mora Marion , Maradan Gwenaelle , Bourrelly Michel , keita Abdoul Aziz , Yoro Stéphane-Alain Babo , Anoma Camille , Coulibaly Christian , Tiero Dah Elias Ter , Agbomadji Selom , Mensah Ephrem , Bernier Adeline , Couderc Clotilde , Keita Bintou Dembélé , Laurent Christian , Spire Bruno ,   the CohMSM Study Group
Published: May 2019

Men who have sex with men (MSM) are at much greater risk of HIV infection in Africa. Little is known about their involvement in transactional sex (TS). We aimed to characterize MSM reporting TS (MSM-TS) and to identify factors associated with their sexual practices using data from the prospective cohort study CohMSM conducted in Burkina Faso, Côte d’Ivoire, Mali and Togo. Our study focused on HIV-negative MSM, recruited between 06/2015 and 01/2018 by a team of trained peer educators. Scheduled study visits at 6, 12 and 18 months included medical examinations, HIV screening, risk-reduction counselling and face-to-face interviews to collect information on their sociodemographic characteristics, sexual behaviours, and HIV risk-reduction strategies. Three stigmatization sub-scores were constructed. The generalized estimating equation method was used for data analysis. Of the 630 HIV-negative participants recruited at baseline, 463, 410 and 244 had a follow-up visit at 6- and 12- and 18-months, respectively. Over a total of 1747 visits, 478 TS encounters were reported by 289 MSM-TS (45.9%). Of the latter, 91 participants reported systematic TS (31.5%), 55 (19.0 %) stopped reporting TS after baseline, and 53 (18.3%) reported TS after baseline. Ninety participants (31.1 %) reported occasional TS. After adjusting for country of study and follow-up visits, the following factors, reported for the previous 6 months, were associated with a greater likelihood of TS: younger age, an educational level <high-school diploma, satisfaction with current sex life, group sex with men, multiple male sexual partners, condomless anal sex, receptive or versatile anal sex with male sexual partners, giving benefits in exchange for sex with a man, alcohol consumption and drug use during sex, and experiencing stigmatization. The majority of MSM in this study who received benefits in exchange for sex had high-risk HIV infection exposure practices and were characterized by socioeconomic difficulties.
Network governance and the contemporary opium problem in northern Thailand
Authors: Jongruck Patamawadee
Published: May 2019

Purpose

The purpose of this paper is to explore the current approach that the Thai Government has employed to manage “wicked problems,” using the case of opium in northern Thailand, and analyzing how the network governance approach can contribute to sustainable upland community development.

Design/methodology/approach

A case study was employed for this research. The data collection was based upon a qualitative research approach, namely in-depth interviews, participatory observation and document research, were all conducted.

Findings

The study found that the strategy of the Thai Government to manage the opium problem in the upland periphery has changed over time. The recent approach could be illustrated as a form of network governance albeit solely within the governmental realm, which was found to be different from the network governance stratagem currently defined in the dominant literature. This paper suggests that in order to achieve a sustainable solution for upland community development, the mode of network governance should shift toward self-governing networks. In other words, non-state stakeholders should be actively engaged in the network and empowered to manage their problems for sustainable upland community development.

Originality/value

This paper contributes to the current corpus of network governance literature by introducing an empirical case study from Thailand. In terms of policy implication, this paper provides policy suggestions for governments, especially in Asia, who are actively seeking to resolve “wicked problems” and achieving sustainable community development.
The effect of social and economic transitions on the meaning of work
Authors: Sharabi Moshe , Polin Brian , Yanay-Ventura Galit
Published: May 2019

Purpose

The purpose of this paper is to examine the impact of social and economic changes, particularly the transition from a collectivistic to an individualistic society, on the meaning of work (MOW) in Israel.

Design/methodology/approach

A questionnaire probing the MOW domains (economic orientation, intrinsic orientation, interpersonal relations, entitlement and obligation norms and job satisfaction) was conducted on a representative sample of the Israeli labor force in 1981 (n=973) and 2006 (n=898).

Findings

A comparison between the results of the 1981 and 2006 surveys shows a significant increase in economic and intrinsic orientation, and a significant decrease in interpersonal relations orientation, job satisfaction and obligation and entitlement norms. Work centrality remained stable. The demographic factors, especially education, have some impact on the MOW domains.

Practical implications

The transformation of work values reflects the changes in employees’ expectations and needs. Therefore, organizations are compelled to find new material and non-material reward systems and methods to maintain employee commitment, motivation and satisfaction. Various implications for organizations and management are discussed.

Originality/value

This cross-sectional study explores how the combination of economic and social changes is reflected in employees’ job satisfaction and other work values. Furthermore, the study examines the impact of the main demographic factors on the MOW and offers suggestions to gain employees loyalty and commitment based on all the findings.
Adolescents’ learning and experiences of solving the need for dietary supplementation through socioscientific issue (SSI) method
Authors: Kärkkäinen Sirpa , Hartikainen-Ahia Anu , Elorinne Anna-Liisa , Hokkanen Johanna , Hämeen-Anttila Katri
Published: May 2019

Purpose

The purpose of this paper is to assess the socioscientific issue (SSI) method as a way of improving seventh graders’ nutrition know-how on dietary supplements (DS), and to describe how students experience learning nutritional issues through the SSI method.

Design/methodology/approach

Participants were seventh graders from three different classes (n=43). Health education intervention lasted 7 h and it embodied the three-staged model: the scenario, the inquiry and the decision-making stages. The study was qualitative in nature. The data were collected through a questionnaire before and after the intervention. The data were analyzed using summative content analysis.

Findings

Intervention tended to deepen students’ know-how on vitamins and rational use of DS. Students’ experiences of learning nutritional issues through the SSI method were generally positive. The scenario stage was considered current and authentic. The inquiry stage and decision-making stage helped in understanding the societal connections between the study task and the rational use of DS.

Practical implications

SSI method enhances students’ knowledge about the rational use of DS. E-learning environment gave students possibilities to work collaboratively. Especially, possibilities to discuss with peers and share own experiences supported learning.

Originality/value

To solve the need of dietary supplements (DS) is a complex nutritional issue for society and for individuals. Since consumption of special diets has increased among adolescents, the rational consumption of DS is relevant and interesting learning topic at secondary school.
A survey on VV&A of large-scale simulations
Authors: Wang Yanan , Li Jianqiang , Hongbo Sun , Li Yuan , Akhtar Faheem , Imran Azhar
Published: May 2019

Purpose

Simulation is a well-known technique for using computers to imitate or simulate the operations of various kinds of real-world facilities or processes. The facility or process of interest is usually called a system, and to study it scientifically, we often have to make a set of assumptions about how it works. These assumptions, which usually take the form of mathematical or logical relationships, constitute a model that is used to gain some understanding of how the corresponding system behaves, and the quality of these understandings essentially depends on the credibility of given assumptions or models, known as VV&A (verification, validation and accreditation). The main purpose of this paper is to present an in-depth theoretical review and analysis for the application of VV&A in large-scale simulations.

Design/methodology/approach

After summarizing the VV&A of related research studies, the standards, frameworks, techniques, methods and tools have been discussed according to the characteristics of large-scale simulations (such as crowd network simulations).

Findings

The contributions of this paper will be useful for both academics and practitioners for formulating VV&A in large-scale simulations (such as crowd network simulations).

Originality/value

This paper will help researchers to provide support of a recommendation for formulating VV&A in large-scale simulations (such as crowd network simulations).
Hybrid impedance control of a knee joint orthosis
Authors: Alouane Mohamed Amine , Rifai Hala , Kim Kwangtaek , Amirat Yacine , Mohammed Samer
Published: May 2019

Purpose

This paper aims to deal with the design of new hybrid approach for the assistance of the flexion extension movement of the knee joint.

Design/methodology/approach

The control approach combines the use of a knee joint orthosis along with functional electrical stimulation (FES) within an assist-as-needed paradigm. An active impedance controller is used to assist the generation of muscular stimulation patterns during the extension sub-phase of the knee joint movement. The generated FES patterns are appropriately tailored to achieve flexion/extension movement of the knee joint, which allows providing the required assistance by the subject through muscular stimulation. The generated torque through stimulation is tracked by a non-linear disturbance observer and fed to the impedance controller to generate the desired trajectory that will be tracked using a standard proportional derivative controller.

Findings

The approach was tested in experiments with two healthy subjects. Results show satisfactory performances in terms of estimating the knee joint torque, as well as in terms of cooperation between the FES and the orthosis actuator during the execution of the knee joint flexion/extension movements.

Originality/value

The authors designed a new hybrid approach for the assistance of the flexion extension movement of the knee joint, which has not been studied yet. The control approach combines the use of a knee joint orthosis along with FES within an assist-as-needed paradigm.
Displacing Informality: Rights and Legitimacy in Belo Horizonte, Brazil
Authors: Nogueira Mara
Published: May 2019

This article compares two cases of displacement suffered by informal workers and informal residents in the Brazilian city of Belo Horizonte, both connected to the hosting of the 2014 FIFA World Cup. It asks the following question: considering that the right to work and the right to housing are both enshrined in the Brazilian Constitution, why do claims upon space based on those constitutional rights have different degrees of legitimacy? Two cases are analysed in detail. The first one concerns a group of informal workers displaced from their workspace for the modernization of the local stadium. The second one tells the story of an informal settlement where 90 families were displaced due to the construction of a flyover designed to improve access to the football stadium. This article engages with current postcolonial debates around urban informality, tackling two points that have been absent from these discussions. First, it compares two ways of informally occupying urban space—for work and for housing—revealing the distinct degrees of legitimacy embedded in such practices due to pre‐existing institutional arrangements. Second, it emphasizes the connection between work and home through the life strategies and place‐making practices of the urban poor.
Gradual Evolution from Fluvial Dominated to Tide Dominated Deltas and Channel Type Transformation: A Case Study of MPE3 Block in the Orinoco Heavy Oil Belt of the Eastern Venezuelan Basin
Authors: HUANG Wensong , CHEN Heping , XU Fang , MENG Zheng , ZHANG Fanqin , WU Suwei
Published: May 2019

Based on the data of core description and sporopollen analysis, the gradual evolution of deltas in vertical direction and transition of channel types in the MPE3 block of the eastern Venezuela Basin have been surveyed by seismic phase and well logging facies interpretation. The results show that due to the great sea level rise, the sedimentary system of the Miocene Oficina Formation in the MPE3 block shifted from the distal‐source sandy braided river delta to tide‐affected delta, and eventually to tide‐dominated delta. Vertically, during the early stage of sedimentation of Oficina Formation, the distributary channels of the delta were dominated by braided river channels. While in the later stage, as the tidal effect was gradually intensified, the channel changed from braided channel to meandering channel. On plane, as a result of differential transgression, sedimentary framework and distribution of sand bodies vary across the study area. Compared with the eastern part, the western part has more braided channels, larger channel bars, less developments of distributary bay and higher ratio of sand to mud. Whereas the braided channels in the south are larger than those in the north. It is the first time we pointed out the impact of marine transgression differences on the sedimentary facies distribution and river type transition in the study area. Factors like the structural and paleogeomorphological change, sea level variation, supply of sediments have strong influence on the evolution of sedimentary system and distribution of sandbodies. It is predicted that the major sandbody is more developed in the central south, which can guide the subsequent horizontal well development.