bluuebunny/crossref_metadata_2025 huggingface dataset:
Prominent features of the amino acid mutation landscape in cancer
Authors: Szpiech Zachary A. , Strauli Nicolas B. , White Katharine A. , Ruiz Diego Garrido , Jacobson Matthew P. , Barber Diane L. , Hernandez Ryan D.
Published: May 2017

Cancer can be viewed as a set of different diseases with distinctions based on tissue origin, driver mutations, and genetic signatures. Accordingly, each of these distinctions have been used to classify cancer subtypes and to reveal common features. Here, we present a different analysis of cancer based on amino acid mutation signatures. Non-negative Matrix Factorization and principal component analysis of 29 cancers revealed six amino acid mutation signatures, including four signatures that were dominated by either arginine to histidine (Arg>His) or glutamate to lysine (Glu>Lys) mutations. Sample-level analyses reveal that while some cancers are heterogeneous, others are largely dominated by one type of mutation. Using a non-overlapping set of samples from the COSMIC somatic mutation database, we validate five of six mutation signatures, including signatures with prominent arginine to histidine (Arg>His) or glutamate to lysine (Glu>Lys) mutations. This suggests that our classification of cancers based on amino acid mutation patterns may provide avenues of inquiry pertaining to specific protein mutations that may generate novel insights into cancer biology.
Genome-wide Association Study Of Plasma Proteins Identifies Putatively Causal Genes, Proteins, And Pathways For Cardiovascular Disease
Authors: Yao Chen , Chen George , Song Ci , Mendelson Michael , Huan Tianxiao , Laser Annika , Wu Hongsheng , Ho Jennifer E. , Courchesne Paul , Lyass Asya , Larson Martin G. , Gieger Christian , Graumann Johannes , Johnson Andrew D. , Hwang Shih-Jen , Liu Chunyu , Suhre Karsten , Levy Daniel
Published: May 2017

Identifying genetic variants associated with circulating protein concentrations (pQTLs) and integrating them with variants from genome-wide association studies (GWAS) may illuminate the proteome’s causal role in disease and bridge a GWAS knowledge gap for hitherto unexplained SNP-disease associations. We conducted GWAS of 71 high-value proteins for cardiovascular disease in 6,861 Framingham Heart Study participants followed by external replication. We comprehensively mapped thousands of pQTLs, including functional annotations and clinical-trait associations, and created an integrated plasma-protein-QTL searchable database. We next identified 15 proteins with pQTLs coinciding with coronary heart disease (CHD)-related variants from GWAS or tested causal for CHD by Mendelian randomization; most of these proteins were associated with new-onset cardiovascular disease events in Framingham participants with long-term follow-up. Identifying pQTLs and integrating them with GWAS results yields insights into genes, proteins, and pathways that may be causally associated with disease and can serve as therapeutic targets for treatment and prevention.
A simple representation of three-dimensional molecular structure
Authors: Axen Seth D. , Huang Xi-Ping , Cáceres Elena L. , Gendelev Leo , Roth Bryan L. , Keiser Michael J.
Published: May 2017

Statistical and machine learning approaches predict drug-to-target relationships from 2D small-molecule topology patterns. One might expect 3D information to improve these calculations. Here we apply the logic of the Extended Connectivity FingerPrint (ECFP) to develop a rapid, alignment-invariant 3D representation of molecular conformers, the Extended Three-Dimensional FingerPrint (E3FP). By integrating E3FP with the Similarity Ensemble Approach (SEA), we achieve higher precision-recall performance relative to SEA with ECFP on ChEMBL20, and equivalent receiver operating characteristic performance. We identify classes of molecules for which E3FP is a better predictor of similarity in bioactivity than is ECFP. Finally, we report novel drug-to-target binding predictions inaccessible by 2D fingerprints and confirm three of them experimentally with ligand efficiencies from 0.442 - 0.637 kcal/mol/heavy atom.
A novel reporter allele for monitoringDll4expression within the embryonic and adult mouse
Authors: Herman Alexander M. , Rhyner Alexander M. , Devine W. Patrick , Marrelli Sean P. , Bruneau Benoit G. , Wythe Joshua D.
Published: May 2017

Canonical Notch signaling requires the presence of a membrane bound ligand and a corresponding transmembrane Notch receptor. Receptor engagement induces multiple proteolytic cleavage events culminating in the nuclear accumulation of the Notch intracellular domain and its binding to a transcriptional co-factor to mediate gene expression. Notch signaling networks are essential regulators of vascular patterning and angiogenesis, as well as myriad other biological processes.Delta-like 4(Dll4) encodes the earliest Notch ligand detected in arterial cells, and is enriched in sprouting endothelial tip cells.Dll4expression has often been inferred by proxy using alacZknockin reporter allele. This is problematic, as a single copy ofDll4is haploinsufficient. Additionally, Notch activity regulatesDll4transcription, making it unclear whether these reporter lines accurately reflectDll4expression. Accordingly, accurately definingDll4expression is essential for determining its role in development and disease. To address these limitations, we generated a novel BAC transgenic allele with a nuclear-localized β-galactosidase reporter (Dll4-BAC-nlacZ). Through a comparative analysis, we show the BAC line overcomes previous issues of haploinsufficiency, it recapitulatesDll4expressionin vivo, and allows superior visualization and imaging. As such, this novelDll4reporter is an important addition to the growing Notch toolkit.

Summary Statement:

We have developed a novel reporter line, free from complicating factors associated with previous alleles, for monitoringDll4expression, at a cellular resolution, in the developing and adult mouse.
Scc2/Nipbl hops between chromosomal cohesin rings after loading
Authors: Rhodes James D.P. , Mazza Davide , Nasmyth Kim A. , Uphoff Stephan
Published: May 2017

The cohesin complex mediates DNA-DNA interactions both between (sister chromatid cohesion) and within chromosomes (DNA looping) via a process thought to involve entrapment of DNAs within its tripartite ring. It has been suggested that intra- chromosome loops are generated through processive extrusion of DNAs through the lumen of cohesin’s ring. Scc2 (Nipbl) is essential for loading cohesin onto chromosomes but not for maintaining sister chromatid cohesion following DNA replication. It has therefore been assumed that Scc2 is involved exclusively in the cohesin loading process. However, it is possible that the stimulation of cohesin’s ABC-like ATPase by Scc2 also has a post-loading function, for example driving loop extrusion. Using fluorescence recovery after photobleaching (FRAP) and single-molecule tracking, we show that Scc2 binds dynamically to chromatin, principally through an association with cohesin. Scc2’s movement within chromatin is consistent with a “stop-and-go” or “hopping” motion. We suggest that a low diffusion coefficient, a low stoichiometry relative to cohesin, and a high affinity for chromosomal cohesin enables Scc2 to move rapidly from one chromosomal cohesin complex to another, performing a function distinct from loading.
Active mode of excretion across digestive tissues predates the origin of excretory organs
Authors: Andrikou Carmen , Thiel Daniel , Ruiz-Santiesteban Juan A. , Hejnol Andreas
Published: May 2017

Most bilaterian animals excrete toxic metabolites through specialized organs, such as nephridia and kidneys, which share morphological and functional correspondences. In contrast, the excretory mechanisms in non-nephrozoans are largely unknown, and therefore the reconstruction of ancestral excretory mechanisms is problematic. Here, we investigated the excretory mode of members of the Xenacoelomorpha, the sister group to Nephrozoa, and Cnidaria, the sister group to Bilateria. By combining gene expression, inhibitor experiments and exposure to varying environmental ammonia conditions we show that both, Xenacoelomorpha and Cnidaria, are able to excrete across digestive-associated tissues. Based on these results we propose that digestive-associated tissues functioned as excretory sites before the evolution of specialized organs in nephrozoans. We conclude that diffusion was likely the ancestral mode of excretion, whilst the emergence of a compact, multiple-layered bilaterian body plan necessitated the evolution of active transport excretory mechanisms that was later recruited into the specialized excretory organs.
Global phylogenetic analysis of Escherichia coli and plasmids carrying the mcr-1 gene indicates bacterial diversity but plasmid restriction
Authors: Matamoros Sébastien , van Hattem Jarne M. , Arcilla Maris S. , Willemse Niels , Melles Damian C. , Penders John , Nguyen Vinh Trung , Hoa Ngo Thi , de Jong Menno D. , Schultsz Constance , Bootsma Martin C.J. , van Genderen Perry J. , Goorhuis Abraham , Grobusch Martin P. , Molhoek Nicky , Oude Lashof Astrid M.L. , Stobberingh Ellen E. , Verbrugh Henri A.
Published: May 2017

To understand the dynamics behind the worldwide spread of the mcr-1 gene, we determined the population structure of Escherichia coli and of mobile genetic elements (MGEs) carrying the mcr-1 gene. After a systematic review of the literature we included 65 E. coli whole genome sequences (WGS), adding 6 recently sequenced travel related isolates, and 312 MLST profiles. We included 219 MGEs described in 7 Enterobacteriaceae species isolated from human, animal and environmental samples. Despite a high overall diversity, 2 lineages were observed in the E. coli population that may function as reservoirs of the mcr-1 gene, the largest of which was linked to ST10, a sequence type known for its ubiquity in human faecal samples and in food samples. No genotypic clustering by geographical origin or isolation source was observed. Amongst a total of 13 plasmid incompatibility types, the Incl2, lncX4 and IncHI2 plasmids accounted for more than 90% of MGEs carrying the mcr-1 gene. We observed significant geographical clustering with regional spread of lncHI2 plasmids in Europe and Incl2 in Asia. These findings point towards promiscuous spread of the mcr-1 gene by efficient horizontal gene transfer dominated by a limited number of plasmid incompatibility types.
Neurophysiological Correlates of the Rubber Hand Illusion in Evoked and Oscillatory Brain Activity
Authors: Rao Isa S. , Kayser Christoph
Published: May 2017

The rubber hand illusion (RHI) allows insights into how the brain resolves conflicting multisensory information regarding body position and ownership. Previous neuroimaging studies have reported a variety of neurophysiological correlates of illusory hand ownership, with conflicting results likely originating from differences in experimental parameters and control conditions. Here, we overcome these limitations by using a fully automated and precisely-timed visuo-tactile stimulation setup to record evoked responses and oscillatory responses in the human EEG. Importantly, we relied on a combination of experimental conditions to rule out confounds of attention, body-stimulus position and stimulus duration, and on the combination of two control conditions to identify neurophysiological correlates of illusory hand ownership. In two separate experiments we observed a consistent illusion-related attenuation of ERPs around 330 ms over frontocentral electrodes, as well as decreases of frontal alpha and beta power during the illusion that could not be attributed to changes in attention, body-stimulus position or stimulus duration. Our results reveal neural correlates of illusory hand ownership in late and likely higher-order rather than early sensory processes, and support a role of premotor and possibly intraparietal areas in mediating illusory body ownership.
Systematic Functional Characterization of Human 21st Chromosome Orthologs inCaenorhabditis elegans
Authors: Nordquist Sarah K. , Smith Sofia R. , Pierce Jonathan T.
Published: May 2017

Individuals with Down syndrome have neurological and muscle impairments due to an additional copy of the human 21stchromosome (HSA21). Only a few of ~200 HSA21 genes encoding protein have been linked to specific Down syndrome phenotypes, while the remainder are understudied. To identify poorly characterized HSA21 genes required for nervous system function, we studied behavioral phenotypes caused by loss-of-function mutations in conserved HSA21 orthologs in the nematodeCaenorhabditis elegans. We identified ten HSA21 orthologs that are required for neuromuscular behaviors:cle-1(COL18A1),cysl-2(CBS),dnsn-1(DONSON),eva-1(EVA1C),mtq-2(N6ATM1),ncam-1(NCAM2),pad-2(POFUT2),pdxk-1(PDXK),rnt-1(RUNX1), andunc-26(SYNJ1). We also found that three of these genes are required for normal release of the neurotransmitter acetylcholine. This includes a known synaptic geneunc-26(SYNJ1), as well as uncharacterized genespdxk-1(PDXK) andmtq-2(N6ATM1). As the first systematic functional analysis of HSA21 orthologs, this study may serve as a platform to understand genes that underlie phenotypes associated with Down syndrome.

ARTICLE SUMMARY

Down syndrome causes neurological and muscle dysfunction due to an extra 21stchromosome. This chromosome has over 200 genes, most of which are understudied. To address this, we studied whether reducing function of these gene equivalents in the wormC. eleganscaused neuronal or muscle defects. We identified ten genes conserved between human and worm that mediate function of behaviors. Among these, we show the uncharacterized genesmtq-2andpdxk-1are important for synaptic transmission and are exclusively expressed in nervous system. Our analysis may reveal functions of poorly studied genes that affect nervous system function in Down syndrome.
Quantifying spontaneous metastasis in a syngeneic mouse melanoma model using real time PCR
Authors: Deng Wentao , McLaughlin Sarah L. , Klinke David J.
Published: May 2017

Modeling metastasis in vivo with animals is a priority for both revealing mechanisms of tumor dissemination and developing therapeutic methods. While conventional intravenous injection of tumor cells provides an efficient and consistent system for studying tumor cell extravasation and colonization, studying spontaneous metastasis derived from orthotopic tumor sites has the advantage of modeling more aspects of the metastatic cascade, but is challenging as it is difficult to detect small numbers of metastatic cells. In this work, we developed an approach for quantifying spontaneous metastasis in the syngeneic mouse B16 system using real time PCR. We first transduced B16 cells with lentivirus expressing firefly luciferaseLuc2gene for bioluminescence imaging. Next, we developed a real time quantitative PCR (qPCR) method for the detection of luciferase-expressing, metastatic tumor cells in mouse lungs and other organs. To illustrate the approach, we quantified lung metastasis in both spontaneous and experimental scenarios using B16F0 and B16F10 cells in C57BL/6Ncrl and NOD-Scid Gamma (NSG) mice. We tracked B16 melanoma metastasis with both bioluminescence imaging and qPCR, which were found to be self-consistent. Using this assay, we can quantitatively detect one Luc2 positive tumor cells out of 104tissue cells, which corresponds to a metastatic burden of 1.8x104metastatic cells per whole mouse lung. More importantly, the qPCR method was at least a factor of 10 more sensitive in detecting metastatic cell dissemination and should be combined with bioluminescence imaging as a high-resolution, end-point method for final metastatic cell quantitation. Given the rapid growth of primary tumors in many mouse models, assays with improved sensitivity can provide better insight into biological mechanisms that underpin tumor metastasis.
Response-time behaviors of intercellular communication network motifs
Authors: Thurley Kevin , Wu Lani F , Altschuler Steven J
Published: May 2017

Cell-to-cell communication networks have critical roles in diverse organismal processes, such as coordinating tissue development or immune cell response. However, compared to intracellular signal transduction networks, the function and engineering principles of cell-to-cell communication networks are far less understood. Here, we study cell-to-cell communication networks using a framework that models the input-to-output relationship of intracellular signal transduction networks with a single function—the response-time distribution. We identify a prototypic response-time distribution—the gamma distribution—arising in both experimental data sets and mathematical models of signal-transduction pathways. We find that simple cell-to-cell communication circuits can generate bimodal response-time distributions, and can control synchronization and delay of cell-population responses independently. We apply our modeling approach to explain otherwise puzzling data on cytokine secretion onset times in T cells. Our approach can be used to predict communication network structure using experimentally accessible input-to-output measurements and without detailed knowledge of intermediate steps.
Ionic current correlations are ubiquitous across phyla
Authors: Tran Trinh , Unal Cagri T. , Zaborszky Laszlo , Rotstein Horacio , Kirkwood Alfredo , Golowasch Jorge
Published: May 2017

Ionic currents, whether measured as conductance amplitude or as ion channel transcript levels, can vary many-fold within a population of identified neurons. This variability has been observed in multiple invertebrate neuronal types, but they do so in a coordinated manner such that their magnitudes are correlated. These conductance correlations are thought to reflect a tight homeostasis of cellular excitability that enhances the robustness and stability of neuronal activity over long stretches of time. Notably, although such ionic current correlations are well documented in invertebrates, they have not been reported in vertebrates. Here we demonstrate with two examples, identified mouse hippocampal granule cells and cholinergic basal forebrain neurons, that ionic current correlations is a ubiquitous phenomenon expressed by a number of species across phyla.
Detecting molecular basis of phenotypic convergence
Authors: Chabrol Olivier , Royer-Carenzi Manuela , Pontarotti Pierre , Didier Gilles
Published: May 2017

Convergence is the process by which several species independently evolve similar traits. This evolutionary process is not only strongly related to fundamental questions such as the predictability of evolution and the role of adaptation, its study also may provide new insights about genes involved in the convergent character. We focus on this latter question and aim to detect molecular basis of a given phenotypic convergence. After pointing out a number of concerns about detection methods based on ancestral reconstruction, we propose a novel approach combining an original measure of the extent to which a site supports a phenotypic convergence, with a statistical framework for selecting genes from the measure of their sites. First, our measure of “convergence level” outperforms two previous ones in distinguishing simulated convergent sites from non-convergent ones. Second, by applying our detection approach to the well-studied case of convergent echolocation between dolphins and bats, we identified a set of genes which is very significantly annotated with audition-related GO-terms. This result constitutes an indirect evidence that genes involved in a phenotypic convergence can be identified with a genome-wide approach, a point which was highly debated, notably in the echolocation case (the latest articles published on this topic were quite pessimistic). Our approach opens the way to systematic studies of numerous examples of convergent evolution in order to link (convergent) phenotype to genotype.
De novoannotation and characterization of the translatome with ribosome profiling data
Authors: Xiao Zhengtao , Huang Rongyao , Chen Yuling , Deng Haiteng , Yang Xuerui
Published: May 2017

By capturing and sequencing the RNA fragments protected by translating ribosomes, ribosome profiling sketches the landscape of translation at subcodon resolution. We developed a new method, RiboCode, which uses ribosome profiling data to assess the translation of each RNA transcript genome-wide. As shown by multiple tests with simulated data and cell type-specific QTI-seq and mass spectrometry data, RiboCode exhibits superior efficiency, sensitivity, and accuracy forde novoannotation of the translatome, which covers various types of novel ORFs in the previously annotated coding and non-coding regions and overlapping ORFs. Finally, to showcase its application, we applied RiboCode on a published ribosome profiling dataset and assembled the context-dependent translatomes of yeast under normal condition, heat shock, and oxidative stress. Comparisons among these translatomes revealed stress-activated novel upstream and downstream ORFs, some of which are associated with potential translational dysregulations of the main protein coding ORFs in response to the stress signals.
Easyml: Easily Build and Evaluate Machine Learning Models
Authors: Ahn Woo-Young , Hendricks Paul , Haines Nathaniel
Published: May 2017

Theeasyml(easymachinelearning) package lowers the barrier to entry to machine learning and is ideal for undergraduate/graduate students, and practitioners who want to quickly apply machine learning algorithms to their research without having to worry about the best practices of implementing each algorithm. The package provides standardized recipes for regression and classification algorithms in R and Python and implements them in a functional, modular, and extensible framework. This package currently implements recipes for several common machine learning algorithms (e.g., penalized linear models, random forests, and support vector machines) and provides a unified interface to each one. Importantly, users can run and evaluate each machine learning algorithmwith a single line of coding.Each recipe is robust, implements best practices specific to each algorithm, and generates a report with details about the model, its performance, as well as journal-quality visualizations. The package’s functional, modular, and extensible framework also allows researchers and more advanced users to easily implement new recipes for other algorithms.
Protein features identification for machine learning-based prediction of protein-protein interactions
Authors: Raza Khalid
Published: May 2017

The long awaited challenge of post-genomic era and systems biology research is computational prediction of protein-protein interactions (PPIs) that ultimately lead to protein functions prediction. The important research questions is how protein complexes with known sequence and structure be used to identify and classify protein binding sites, and how to infer knowledge from these classification such as predicting PPIs of proteins with unknown sequence and structure. Several machine learning techniques have been applied for the prediction of PPIs, but the accuracy of their prediction wholly depends on the number of features being used for training. In this paper, we have performed a survey of protein features used for the prediction of PPIs. The open research challenges and opportunities in the area have also been discussed.
Inducible and reversible phenotypes in a novel mouse model of Friedreich’s Ataxia
Authors: Chandran Vijayendran , Gao Kun , Swarup Vivek , Versano Revital , Dong Hongmei , Jordan Maria C. , Geschwind Daniel H.
Published: May 2017

Friedreich’s ataxia (FRDA), the most common inherited ataxia, is caused by recessive mutations that reduce the levels of frataxin (FXN), a mitochondrial iron binding protein. We developed an inducible mouse model ofFxndeficiency that enabled us to control the onset and progression of disease phenotypes by the modulation ofFxnlevels. Systemic knockdown ofFxnin adult mice led to multiple phenotypes paralleling those observed in human patients across multiple organ systems. By reversing knockdown after clinical features appear, we were able to determine to what extent observed phenotypes represent reversible cellular dysfunction. Remarkably, upon restoration of near wild-type FXN levels, we observed significant recovery of function, associated pathology and transcriptomic dysregulation even after substantial motor dysfunction and pathology were observed. This model will be of broad utility in therapeutic development and in refining our understanding of the relative contribution of reversible cellular dysfunction at different stages in disease.
Cellular responses to proteostasis perturbations reveal non-optimal feedback in chaperone networks
Authors: Ghosh Asmita , Gangadharan Abhilash , Das Sarada , Verma Monika , Matai Latika , Dash Debasis , Mapa Koyeli , Chakraborty Kausik
Published: May 2017

The proteostasis network (PN) comprises a plethora of proteins that are dedicated to aid in protein folding; some with over-lapping functions. Despite this, there are multiple pathophysiological states associated with depletion of chaperones. This is counter-intuitive assuming cells have the ability to re-program transcriptional outputs in accordance with its proteostasic limitations. To this effect, we have usedS. cerevisiaeto understand the route a cell takes as a response when challenged with different proteostasis impairments. Using 14 single deletion strains of genes of Protein Quality Control (PQC) system, we quantify their proteostasis impairment and the transcriptional response. In most cases cellular response was incapable of restoring proteostasis. The response did not activate proteostasis components or pathways that could complement the function of the missing PQC gene. Over-expression of alternate machineries, could restore part of the proteostasis defect in deletion strains. We posit that epistasis guided synthetic biology approaches may be helpful in realizing the true potential of the cellular chaperone machinery.
Inferring Genetic Interactions From Comparative Fitness Data
Authors: Crona Kristina , Gavryushkin Alex , Greene Devin , Beerenwinkel Niko
Published: May 2017

Abstract

Darwinian fitness is a central concept in evolutionary biology. In practice, however, it is hardly possible to measure fitness for all genotypes in a natural population. Here, we present quantitative tools to make inferences about epistatic gene interactions when the fitness landscape is only incompletely determined due to imprecise measurements or missing observations. We demonstrate that genetic interactions can often be inferred from fitness rank orders, where all genotypes are ordered according to fitness, and even from partial fitness orders. We provide a complete characterization of rank orders that imply higher order epistasis. Our theory applies to all common types of gene interactions and facilitates comprehensive investigations of diverse genetic interactions. We analyzed various genetic systems comprising HIV-1, the malaria-causing parasitePlasmodium vivax, the fungusAspergillus niger, and the TEM-family ofβ-lactamase associated with antibiotic resistance. For all systems, our approach revealed higher order interactions among mutations.
Behavioural outcomes of adult female offspring following maternal stress and perinatal fluoxetine exposure
Authors: Kiryanova Veronika , Meunier Sara J. , Dyck Richard H.
Published: May 2017

Depression, anxiety, and stress are common in pregnant women. One of the primary pharmacological treatments for anxiety and depression is the antidepressant fluoxetine (Flx). Maternal stress, depression, and Flx exposure are known to effect neurodevelopment of the offspring, however, their combined effects have been scarcely studied, especially in female offspring. The present study investigated the combined effects of maternal stress during pregnancy and perinatal exposure to Flx on the behaviour of female mice as adults. METHODS: Mouse dams were exposed to either chronic unpredictable stress (embryonic (E) day 7 to E18), or FLX (E15-postnatal day 12), or a combination of stress and FLX or left untreated. At two months of age, the female offspring went through a comprehensive behavioural test battery. RESULTS: Maternal stress led to increased activity and alterations of prepulse inhibition in the adult female offspring. Maternal treatment with Flx had a potentially beneficial effect on spatial memory. The combination of prenatal stress and perinatal Flx exposure did not interact in their effects. These results suggest that gestational Flx exposure may have a limited negative impact on female offspring.
Genome-wide association study reveals genetic link between diarrhea-associatedEntamoeba histolyticainfection and inflammatory bowel disease
Authors: Wojcik Genevieve L , Marie Chelsea , Abhyankar Mayuresh M , Yoshida Nobuya , Watanabe Koji , Mychaleckyj Josyf , Kirkpatrick Beth D , Rich Stephen S , Concannon Patrick , Haque Rashidul , Tsokos George C. , Petri William A , Duggal Priya
Published: May 2017

Diarrhea is the second leading cause of death for children globally, causing 760,000 deaths each year in children under the age of 5. Amoebic dysentery contributes significantly to this burden, especially in developing countries. We hypothesize that genetic variation contributes to susceptibility to diarrhea-associatedEntamoeba histolyticainfection in Bangladeshi infants; thus, we conducted a genome-wide association study (GWAS) in two independent birth cohorts of diarrhea-associatedE. histolyticainfection. Cases were defined as children with at least one diarrheal episode positive forE. histolyticathrough either PCR or ELISA within the first year of life. Controls were children without any episodes positive forE. histolyticain the same time frame. Meta-analyses under a fixed-effects inverse variance weighting model identified variants in two neighboring genes on chromosome 10:CUL2(cullin 2) andCREM(cAMP responsive element modulator) associated withE. histolyticainfection, with SNP rs58000832 achieving genome-wide significance (Pmeta=4.2x10−10). Each additional risk allele (an intergenic insertion betweenCREMandCCNY) of rs58000832 conferred 2.5 increased odds of a diarrhea-associatedE. histolyticainfection. The most associated SNP within a gene was in an intron ofCREM(rs58468685, Pmeta=2.3x10−9), which withCUL2, has been implicated as a susceptibility locus for Inflammatory Bowel Disease (IBD) and Crohn’s Disease. Gene expression resources suggest these loci are related to the higher expression ofCREM, but notCUL2. IncreasedCREMexpression is also observed in earlyE. histolyticainfection. Further,CREM-/-mice were more susceptible toE. histolyticaamebic colitis. These genetic associations reinforce the pathological similarities observed in gut inflammation betweenE. histolyticainfection and IBD.
Maximum Entropy Framework For Inference Of Cell Population Heterogeneity In Signaling Networks
Authors: Dixit Purushottam D. , Lyashenko Eugenia , Niepel Mario , Vitkup Dennis
Published: May 2017

Predictive models of signaling networks are essential tools for understanding cell population heterogeneity and designing rational interventions in disease. However, using network models to predict signaling dynamics heterogeneity is often challenging due to the extensive variability of signaling parameters across cell populations. Here, we describe aMaximumEntropy-based fRamework for Inference of heterogeneity inDynamics of sIgAlingNetworks (MERIDIAN). MERIDIAN allows us to estimate the joint probability distribution over signaling parameters that is consistent with experimentally observed cell-to-cell variability in abundances of network species. We apply the developed approach to investigate the heterogeneity in the signaling network activated by the epidermal growth factor (EGF) and leading to phosphorylation of protein kinase B (Akt). Using the inferred parameter distribution, we also predict heterogeneity of phosphorylated Akt levels and the distribution of EGF receptor abundance hours after EGF stimulation. We discuss how MERIDIAN can be generalized and applied to problems beyond modeling of heterogeneous signaling dynamics.
3′-(4-Chlorophenyl)-4′-phenyl-3H,4′H-spiro[benzo[b]thiophene-2,5′-isoxazol]-3-one
Authors: Bakhouch Mohamed , El Yazidi Mohamed , Al Houari Ghali , Saadi Mohamed , El Ammari Lahcen
Published: May 2017

The molecule of the title compound, C22H14ClNO2S, is built up from an isoxazole ring linked to a benzothiophene ring system with additional phenyl and 4-chlorophenyl substituents. The benzothiophene system is virtually planar with the largest deviation from the mean plane being 0.041 (2) Å, while the isoxazole ring adopts an envelope conformation. The plane of the benzothiophene ring system is almost perpendicular to those of the phenyl and the 4-chlorophenyl rings, with dihedral angles of 64.76 (10) and 82.81 (10)°, respectively, between them. The phenyl ring is inclined by 85.76 (12)° to the plane of the 4-chlorophenyl ring, which in turn lies close to the plane of the isoxazole ring. In the crystal, molecules are linked by weak C—H...O hydrogen bonds and offset π–π interactions between the aromatic rings of adjacent benzothiophene ring systems. These combine to form a three-dimensional network structure.
The effect of social spending on reducing poverty
Authors: Celikay Ferdi , Gumus Erdal
Published: May 2017

Purpose

The purpose of this paper is to provide new empirical evidence on the relationship between social expenditure and poverty in Turkey.

Design/methodology/approach

There are voluminous studies in the literature and many of which contain condradictory results. The authors use panel error correction models and employ Turkish statistical territorial units data (26 regions) covering the period 2004-2011 in the analysis.

Findings

The authors have found that in the short run, there is a negative relationship between social expenditure and poverty, as expected. In the long run, however, there exists a positive relation between them. The authors utilize expenditure on education as one component of social expenditure, and the authors obtain a negative relationship between education expenditure and poverty, both in the short run and in the long run.

Social implications

Poverty is an important social problem that more studies on this subject should examine various aspects and find policies to alleviate it.

Originality/value

Literature on poverty and social spending are growing and their results are contradictory. However, this paper clearly and significantly provides new empirical evidence on the effect of social spending on reducing poverty using Turkish data. This kind of study is hardly found for developing countries like Turkey. It contributes to the literature.
Twelve methods of money laundering
Authors: Teichmann Fabian Maximilian Johannes
Published: May 2017

Purpose

This paper aims to discuss how feasible it is for intelligent criminals to circumvent existing anti-money laundering mechanisms.

Design/methodology/approach

Based upon ten informal interviews with money launderers and their advisers; 18 formal, semi-standardized expert interviews with selected anti-money laundering specialists; and a quantitative survey of 181 compliance officers, 12 effective methods to launder money have been developed.

Findings

It has been found that gold, jewellery, raw diamonds, antiquities, art, real estate projects, consulting firms, mergers and acquisitions, banks in Dubai, deposit boxes, private cash deals and currency exchange offices continue to be extraordinarily suitable tools for money laundering.

Originality/value

The identification of gaps in anti-money laundering mechanisms is meant to provide both compliance officers and legislators with valuable insights. While the existing literature focuses on estimating the volume of money laundered in certain geographical areas and on the improvement of anti-money laundering mechanisms, this paper describes how money launderers proceed to avoid getting caught.
Engagement platforms in the sharing economy
Authors: Breidbach Christoph F. , Brodie Roderick J.
Published: May 2017

Purpose

The purpose of this paper is to identify and delineate research directions that guide future empirical studies exploring how engagement platforms facilitate value co-creation and actor engagement in the context of the sharing economy.

Design/methodology/approach

The authors adopt a midrange theorizing approach with service-dominant logic as the integrating meta-theoretical perspective to develop a theoretical framework about service platforms, engagement platforms, and actor engagement in information communication technology (ICT) mediated environments. The authors then contextualize the framework for the sharing economy.

Findings

The authors introduce 20 unique research questions to guide future studies related to service ecosystems, engagement platforms, and actor engagement practices in the context of the sharing economy.

Research limitations/implications

The sharing economy is an emerging phenomenon that is driven by the development and proliferation of engagement platforms. The engagement platform concept therefore provides a novel perspective for exploration of how ICT can be utilized to facilitate value co-creation and engagement amongst interdependent economic actors in a service ecosystem.

Practical implications

The purpose of this paper is to guide future academic research, rather than managerial practice. Future research based on the framework can help guide decision-makers to implement and use engagement platforms more effectively.

Originality/value

This paper offers new insight into the important intersection of ICT and service research, and guides future studies exploring the role of engagement platforms in the context of the sharing economy.
Altered expression of four miRNA (miR‐1238‐3p, miR‐202‐3p, miR‐630 and miR‐766‐3p) and their potential targets in peripheral blood from vitiligo patients
Authors: Shang Zhiwei , Li Hongwen
Published: May 2017

Vitiligo is an acquired skin disease with pigmentary disorder. Autoimmune destruction of melanocytes is thought to be major factor in the etiology of vitiligo. miRNA‐based regulators of gene expression have been reported to play crucial roles in autoimmune disease. Therefore, we attempt to profile the miRNA expressions and predict their potential targets, assessing the biological functions of differentially expressed miRNA. Total RNA was extracted from peripheral blood of vitiligo (experimental group, n = 5) and non‐vitiligo (control group, n = 5) age‐matched patients. Samples were hybridized to a miRNA array. Box, scatter and principal component analysis plots were performed, followed by unsupervised hierarchical clustering analysis to classify the samples. Quantitative reverse transcription polymerase chain reaction (RT–PCR) was conducted for validation of microarray data. Three different databases, TargetScan, PITA and microRNA.org, were used to predict the potential target genes. Gene ontology (GO) annotation and pathway analysis were performed to assess the potential functions of predicted genes of identified miRNA. A total of 100 (29 upregulated and 71 downregulated) miRNA were filtered by volcano plot analysis. Four miRNA were validated by quantitative RT–PCR as significantly downregulated in the vitiligo group. The functions of predicted target genes associated with differentially expressed miRNA were assessed by GO analysis, showing that the GO term with most significantly enriched target genes was axon guidance, and that the axon guidance pathway was most significantly correlated with these miRNA. In conclusion, we identified four downregulated miRNA in vitiligo and assessed the potential functions of target genes related to these differentially expressed miRNA.
Higher viral load and genetic diversity of HIV‐1 in seminal compartments than in blood of seven Chinese men who have sex with men and have early HIV‐1 infection
Authors: Jiao Yan‐Mei , Chen Guang‐Lei , Zhu Wei‐Jun , Huang Hui‐huang , Fu Jun‐liang , Chen Wei‐wei , Shi Ming , Zhang Tong , Wu Hao , Wang Fu‐Sheng
Published: May 2017

To date, there have been no reports characterizing HIV‐1 in the semen of Chinese men who have sex with men (MSM) with early infection. In this study, genetic diversity and viral load of HIV‐1 in the seminal compartments and blood of Chinese MSM with early HIV‐1 infection were examined. Viral load and genetic diversity of HIV‐1 in paired samples of semen and blood were analyzed in seven MSM with early HIV‐1 infection. HIV‐1 RNA and DNA were quantitated by real‐time PCR assays. Through sequencing the C2‐V5 region of the HIV‐1 env gene, the HIV‐1 genotype and genetic diversity based on V3 loop amino acid sequences were determined by using Geno2pheno and PSSM programs co‐receptor usage. It was found that there was more HIV‐1 RNA in seminal plasma than in blood plasma and total, and more 2‐LTR circular and integrated HIV‐1 DNA in seminal cells than in peripheral blood mononuclear cells from all seven patients with early HIV‐infection. There was also greater HIV‐1 genetic diversity in seminal than in blood compartments. HIV‐1 in plasma displayed higher genetic diversity than in cells from the blood and semen. In addition, V3 loop central motifs, which present some key neutralizing antibody epitopes, varied between blood and semen. Thus, virological characteristics in semen may be more representative when evaluating risk of transmission in persons with early HIV infection.
Bordetella effector BopN is translocated into host cells via its N‐terminal residues
Authors: Abe Akio , Nishimura Ryutaro , Kuwae Asaomi
Published: May 2017

Bordetella bronchiseptica infects a wide variety of mammals, and the type III secretion system (T3SS) is involved in long‐term colonization by Bordetella in the trachea and lung. T3SS translocates virulence factors (commonly referred to as effectors) into host cells, leading to alterations in the host's physiological function. The Bordetella effectors BopN and BteA are known to have roles in up‐regulation of IL‐10 and cytotoxicity, respectively. Nevertheless, the mechanism by which BopN is translocated into host cells has not been examined in sufficient detail. Therefore, to determine the precise mechanisms of the BopN translocation into host cells, we built truncated derivatives of BopN and evaluated the derivatives’ ability to translocation into host cells by adenylate cyclase‐mediated translocation assay. It was found that N‐terminal amino acid (aa) residues 1–200 of BopN are sufficient for its translocation into host cells. Interestingly, BopN translocation was completely blocked by deletion of the N‐terminal aa residues 6–50, indicating that the N‐terminal region is critical for BopN translocation. Furthermore, BopN appears to play an auxiliary role in BteA‐mediated cytotoxicity. Thus, BopN can apparently translocate into host cells and may facilitate activity of BteA.
Association Between Staphylococcus aureus Bacteremia and Hospital Mortality in Hemodialysis Patients With Bloodstream Infection: A Multicenter Cohort From Japanese Tertiary Care Centers
Authors: Imaizumi Takahiro , Hasegawa Takeshi , Nomura Atsushi , Sasaki Sho , Nishiwaki Hiroki , Ozeki Takaya , Shimizu Hideaki , Minatoguchi Shun , Yamakawa Taishi , Yazawa Masahiko , Uchida Daisuke , Kawarazaki Hiroo , Miyamoto Masahito , Suzuki Tomo , Koitabashi Ken'ichiro , Furusho Masahide , Fujita Yoshiro
Published: May 2017

Multiple studies have shown that Staphylococcus aureus bacteremia (SAB) has been a major cause of death in hemodialysis patients. We examined whether SAB is a risk for mortality among chronic hemodialysis patients in Japan where the standard vascular access is arteriovenous fistula (AVF). This was a multicenter, retrospective study of maintenance hemodialysis patients with bloodstream infection (BSI) from 2011 to 2013 at tertiary care centers in Japan. The endpoint was hospital mortality. Our cohort contained 32 SAB cases (14 MRSA and 18 MSSA) and 42 non‐SAB cases. Hospital mortality was higher among SAB cases than non‐SAB cases (46.9% vs. 23.8%, P = 0.038). In patients with BSI, SAB was significantly associated with hospital mortality after adjustment for potential confounders, including type of vascular access (OR 3.26). S. aureus was the leading cause of BSI and hospital mortality among this cohort. Therefore, initial empiric treatment should cover for S. aureus.
Response of Drosophila suzukii (Diptera: Drosophilidae) to extreme heat and dryness
Authors: Eben Astrid , Reifenrath Maria , Briem Felix , Pink Sebastian , Vogt Heidrun
Published: May 2017

Drosophila suzukii Matsumura (Diptera) is a polyphagous herbivore native to East Asia that develops in cultivated and wild fruits. In 2011, it appeared in Germany. In 2012, economic damage was recorded and, in 2014, the harvest of stone and soft fruits was lost in some regions. By contrast, during 2015, populations remained lower. Record temperatures and dryness might have impeded population growth during that year.

To test this hypothesis, flies were exposed to a 4‐day simulation. We evaluated the effect of fluctuating temperature and humidity on mortality and reproduction of D. suzukii from three age classes (average age: class 1: 3 days; class 2: 11 days; class 3: 20 days). Maximum temperatures were 27, 33 and 39 °C. Relative humidity oscillated between 18% and 85%.

Fly mortality through heat stress ranged from 50% to 80%. Higher rates died of oldest flies and females. Offspring per female did not differ between heat stressed and control groups.

Flies of both sexes were not sterilized through heat and dryness. Prior acclimation reduced any negative effects.

We concluded that heat waves and extreme dryness during 2015 were one cause of the low population densities of D. suzukii observed under field conditions.
Telomere length and fetal programming: A review of recent scientific advances
Authors: Whiteman Valerie E. , Goswami Anjali , Salihu Hamisu M.
Published: May 2017

We sought to synthesize a comprehensive literature review comprising recent research linking fetal programming to fetal telomere length. We also explored the potential effects fetal telomere length shortening has on fetal phenotypes. Utilizing the PubMed database as our primary search engine, we retrieved and reviewed 165 articles of published research. The inclusion criteria limited the articles to those that appeared within the last ten years, were pertinent to humans, and without restriction to language of publication. Our results showed that socio‐demographic factors like age, sex, genetic inheritance, and acquired disease impact telomere length. Further, we found several maternal characteristics to be associated with fetal telomere length shortening, and these include maternal chemical exposure (eg, tobacco smoke), maternal stress during pregnancy, maternal nutritional and sleeping disorders during pregnancy as well as maternal disease status. Due to paucity of data, our review could not synthesize evidence directly linking fetal phenotypes to telomere length shortening. Although the research summarized in this review shows some association between determinants of intrauterine programming and fetal telomere length, there is still significant work that needs to be done to delineate the direct relationship of telomere attrition with specific fetal phenotypes.