bluuebunny/crossref_metadata_2025 huggingface dataset:
The enemy from within: a prophage ofRoseburia intestinalissystematically turns lytic in the mouse gut, driving bacterial adaptation by CRISPR spacer acquisition
Authors: Cornuault Jeffrey K. , Moncaut Elisabeth , Loux Valentin , Mathieu Aurélie , Sokol Harry , Petit Marie-Agnès , Paepe Marianne De
Published: March 2019

Despite an overall stability in time of the human gut microbiota at the phylum level, strong temporal variations in species abundance have been observed. We are far from a clear understanding of what promotes or disrupts the stability of microbiome communities. Environmental factors, like food or antibiotic use, modify the gut microbiota composition, but their overall impacts remain relatively low. Phages, the viruses that infect bacteria, might constitute important factors explaining temporal variations in species abundance. Gut bacteria harbour numerous prophages, or dormant viruses. A breakdown of prophage dormancy can evolve through the selection of ultravirulent phage mutants, potentially leading to important bacterial death. Whether such phenomenon occurs in the mammal’s microbiota has been largely unexplored.

Here we studied temperate phage-bacteria coevolution in gnotoxenic mice colonised withEscherichia coliandRoseburia intestinalis, a dominant symbiont of the human gut microbiota. We show thatR. intestinalisharbors two active prophages, Jekyll and Shimadzu, and observed the systematic evolution of ultravirulent Shimadzu phage mutants, leading to a collapse ofR. intestinalispopulation. In a second step, phage infection drove the fast evolution of host phage-resistance mainly through phage-derived spacer acquisition in a Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) array. Alternatively, phage resistance was conferred by a prophage originating from an ultravirulent phage with a restored ability to lysogenize.

Our results demonstrate that prophages are the potential source of ultravirulent phages that can successfully infect most of the susceptible bacteria. This suggests that prophages can play important roles in the short-term temporal variations observed in the composition of the gut microbiota.
Multi-enhancer transcriptional hubs confer phenotypic robustness
Authors: Tsai Albert , Alves Mariana RP , Crocker Justin
Published: March 2019

We had previously shown inDrosophila melanogasterembryos that low-affinity Ultrabithorax (Ubx)-responsiveshavenbaby(svb) enhancers drive robust expression using localized transcriptional environments and that activesvbenhancers tended to colocalize, even when placed on different chromosomes (Tsai et al., 2017). Here, we test the hypothesis that these multi-enhancer “hubs” improve robustness by increasing transcription factor retention near transcription sites. Deleting a redundant enhancer from thesvblocus led to reduced trichome numbers in embryos raised at elevated temperatures. Using high-resolution fluorescence microscopy, we observed lower Ubx concentration and transcriptional output in this deletion allele. Transcription sites of the fullsvb cis-regulatory region inserted into a different chromosome colocalized with thesvblocus, increasing Ubx concentration, the transcriptional output ofsvb, and partially rescuing the phenotype. Thus, multiple enhancers could reinforce a local transcriptional hub to buffer against environmental stresses and genetic perturbations, providing a mechanism for phenotypical robustness.

Impact statement

Multiple enhancers in physical proximity can reinforce shared transcriptional “hubs” to retain transcription factors, providing a buffer during environmental stresses and genetic perturbations to preserve phenotypic robustness.
Optimisation of rapid STR analysis using a standard DNA forensic pipeline
Authors: Gammon Katharine , Mayers Carl
Published: March 2019

Previous studies in published literature have reported on various alterations to STR mastermixes, protocols and instrumentation in order to reduce the time taken to generate forensic DNA profiles from reference and casework type samples. In this study, we demonstrate how altering default PCR amplification and capillary electrophoresis protocols in our existing DNA profiling pipeline can reduce the overall time taken to generate a DNA profile from buccal cell reference samples. GlobalFiler Express STR mastermix was used with direct PCR from FTA cards, run on altered PCR protocols and CE settings, and results compared to the standard evaluated settings used in our laboratories. This study demonstrated that full DNA profiles could be recovered in less than 80 minutes in comparison to our standard time of 97 – 102 minutes whilst utilising existing reagent kits and instrumentation, with only minor modifications to protocols.
Hierarchical temporal prediction captures motion processing from retina to higher visual cortex
Authors: Singer Yosef , Willmore Ben D. B. , King Andrew J. , Harper Nicol S.
Published: March 2019

Visual neurons respond selectively to specific features that become increasingly complex in their form and dynamics from the eyes to the cortex. Retinal neurons prefer localized flashing spots of light, primary visual cortical (V1) neurons moving bars, and those in higher cortical areas, such as middle temporal (MT) cortex, favor complex features like moving textures. Whether there are general computational principles behind this diversity of response properties remains unclear. To date, no single normative model has been able to account for the hierarchy of tuning to dynamic inputs along the visual pathway. Here we show that hierarchical application of temporal prediction - representing features that efficiently predict future sensory input from past sensory input - can explain how neuronal tuning properties, particularly those relating to motion, change from retina to higher visual cortex. This suggests that the brain may not have evolved to efficiently represent all incoming information, as implied by some leading theories. Instead, the selective representation of sensory inputs that help in predicting the future may be a general neural coding principle, which when applied hierarchically extracts temporally-structured features that depend on increasingly high-level statistics of the sensory input.
‘%svy_logistic_regression: A generic SAS® macro for simple and multiple logistic regression and creating quality publication-ready tables using survey or non-survey data
Authors: Muthusi Jacques , Mwalili Samuel , Young Peter
Published: March 2019

Introduction

Reproducible research is increasingly gaining interest in the research community. Automating the production of research manuscript tables from statistical software can help increase the reproducibility of findings. Logistic regression is used in studying disease prevalence and associated factors in epidemiological studies and can be easily performed using widely available software including SAS, SUDAAN, Stata or R. However, output from these software must be processed further to make it readily presentable. There exists a number of procedures developed to organize regression output, though many of them suffer limitations of flexibility, complexity, lack of validation checks for input parameters, as well as inability to incorporate survey design.

Methods

We developed a SAS macro,%svy_logistic_regression, for fitting simple and multiple logistic regression models. The macro also creates quality publication-ready tables using survey or non-survey data which aims to increase transparency of data analyses. It further significantly reduces turn-around time for conducting analysis and preparing output tables while also addressing the limitations of existing procedures.

Results

We demonstrate the use of the macro in the analysis of the 2013-2014 National Health and Nutrition Examination Survey (NHANES), a complex survey designed to assess the health and nutritional status of adults and children in the United States. The output presented here is directly from the macro and is consistent with how regression results are often presented in the epidemiological and biomedical literature, with unadjusted and adjusted model results presented side by side.

Conclusions

The SAS code presented in this macro is comprehensive, easy to follow, manipulate and to extend to other areas of interest. It can also be incorporated quickly by the statistician for immediate use. It is an especially valuable tool for generating quality, easy to review tables which can be incorporated directly in a publication.
Doberman pinschers present autoimmunity associated with functional autoantibodies: a model to study the autoimmune background of human dilated cardiomyopathy
Authors: Wess Gerhard , Wallukat Gerd , Fritscher Anna , Becker Niels-Peter , Wenzel Katrin , Müller Johannes , Schimke Ingolf
Published: March 2019

Background

Autoimmunity associated with autoantibodies directed against the β1-adrenergic receptor (β1-AAB) is increasingly accepted as driving human dilated cardiomyopathy (DCM). Unfortunately, animal models of DCM are lacking, preventing our knowledge about β1-AAB autoimmunity in DCM from being extended and hindering the development of related treatment strategies.

Objectives

To introduce an animal model, we studied Doberman pinschers, which develop cardiomyopathy (DoCM), with similarities to human DCM, with regard to their β1-AAB autoimmunity.

Methods

Eighty-seven DP with DoCM and 31 (at enrolment) healthy controls were analyzed for β1-AAB; the receptor binding site and sensitivity to inhibition were determined. In controls who developed cardiomyopathy during the follow-up, β1-AAB were analyzed during the DoCM progress.

Results

Fifty-nine (67.8%) DoCM dogs and 19 (61.3%) controls were β1-AAB positive. Excluding the 9 controls who developed DoCM in the follow-up, β1-AAB positivity tended to be more pronounced in DoCM.

From the controls who developed DoCM, 8 were β1-AAB positive (p=0.044 vs. dogs remaining healthy); their β1-AAB level increased with the cardiomyopathy progress. Overall mortality and mortality exclusively due to cardiac reasons during the study period, were higher (p=0.002; p=0037) in β1-AAB positive dogs. The dogs’ β1-AAB targeted a specific epitope centralized on the second extracellular receptor and were sensitive to inhibition by drugs already successful tested for the corresponding human autoantibody.

Conclusions

Doberman pinschers presented β1-AAB associated autoimmunity similar to that driving the pathogenesis of human DCM. Consequently, DP could remove the lack of animal models available for studying β1-AAB autoimmunity in DCM.
What’s in Your Body of Water? Reducing the Psychological Distance of Pharmaceutical Pollution through Metaphoric Framing in Risk Communication (A Pilot Study)
Authors: Millarhouse Alexandra Z. , Vatovec Christine , Niles Meredith T. , Ivakhiv Adrian
Published: March 2019

Aquatic pharmaceutical pollution poses ecotoxicological risks to the environment and human health. Consumer behaviors represent a significant source of pharmaceutical compounds found in water. Thus, understanding public perceptions of aquatic pharmaceutical pollution and developing effective risk communication techniques are critical to engaging society in the type of widespread change necessary for addressing the presence of pharmaceuticals in water. This mixed-methods pilot study applies conceptual metaphor theory in conjunction with construal level theory of psychological distance to assess the relationship of metaphoric framing to perceptions of aquatic pharmaceutical contamination across four principal dimensions of psychological distance (geographic, social, and temporal distance, and uncertainty). Additionally, this study assesses the direct impact of metaphor use on concern and willingness to act, which are positively associated with perceived psychological distance. Data were collected from a convenience sample (n = 20) of university students in Burlington, Vermont using cognitive interviewing. Results indicate that participants initially perceived pharmaceutical pollution as socially and geographically distant, temporally both distant and proximal, and agreed that the issue is certain. Representing aquatic pharmaceutical contamination through metaphor significantly reduced perceived social and geographic distance, suggesting a relationship between metaphoric framing and psychological distance warranting additional research. Metaphor use did not directly nor significantly impact concern or willingness to act. Additionally, participants preferred the metaphorically-framed visual intervention to the non-metaphor visual intervention. Theoretical and practical implications of metaphor use in risk communications are discussed.
Acetylcholine release inhibits distinct excitatory inputs onto hippocampal CA1 pyramidal neurons via different cellular and network mechanisms
Authors: Goswamee Priyodarshan , McQuiston A. Rory
Published: March 2019

In hippocampal CA1, muscarinic acetylcholine (ACh) receptor (mAChR) activation via exogenous application of cholinergic agonists has been shown to presynaptically inhibit Schaffer collateral (SC) glutamatergic inputs in stratum radiatum (SR), and temporoammonic (TA) and thalamic nucleus reuniens (RE) glutamatergic inputs in stratum lacunosum-moleculare (SLM). However, steady-state uniform mAChR activation may not mimic the effect of ACh release in an intact hippocampal network. To more accurately examine the effect of ACh release on glutamatergic synaptic efficacy, we measured electrically evoked synaptic responses in CA1 pyramidal cells (PCs) following the optogenetic release of ACh in genetically modified mouse brain slices. The ratio of synaptic amplitudes in response to paired-pulse SR stimulation (stimulus 2/stimulus 1) was significantly reduced by the optogenetic release of ACh, consistent with a postsynaptic decrease in synaptic efficacy. The effect of ACh release was blocked by the M3 receptor antagonist 4-DAMP, the GABAB receptor antagonist CGP 52432, inclusion of GDP-β-S, cesium, QX314 in the intracellular patch clamp solution, or extracellular barium. These observations suggest that ACh release decreased SC synaptic transmission through an M3 muscarinic receptor-mediated increase in inhibitory interneuron excitability, which activate GABAB receptors and inwardly rectifying potassium channels on CA1 pyramidal cells. In contrast, the ratio of synaptic amplitudes in response to paired-pulse stimulation in the SLM was increased by ACh release, consistent with presynaptic inhibition. ACh-mediated effects in SLM were blocked by the M2 receptor antagonist AF-DX 116, presumably located on presynaptic terminals. Therefore, our data indicate that ACh release differentially modulates excitatory inputs in SR and SLM of CA1 through different cellular and network mechanisms.
Frequent birth ofde novogenes in the compact yeast genome
Authors: Blevins William R. , Ruiz-Orera Jorge , Messeguer Xavier , Blasco-Moreno Bernat , Villanueva-Cañas José Luis , Espinar Lorena , Díez Juana , Carey Lucas B. , Mar Albà M.
Published: March 2019

Evidence has accumulated that some genes originate directly from previously non-genic sequences, orde novo, rather than by the duplication or fusion of existing genes. However, howde novogenes emerge and eventually become functional is largely unknown. Here we perform the first study onde novogenes that uses transcriptomics data from eleven different yeast species, all grown identically in both rich media and in oxidative stress conditions. The genomes of these species are densely-packed with functional elements, leaving little room for the co-option of genomic sequences into new transcribed loci. Despite this, we find that at least 213 transcripts (~5%) have arisende novoin the past 20 million years of evolution of baker’s yeast-or approximately 10 new transcripts every million years. Nearly half of the total newly expressed sequences are generated from regions in which both DNA strands are used as templates for transcription, explaining the apparent contradiction between the limited ‘empty’ genomic space and high rate ofde novogene birth. In addition, we find that 40% of thesede novotranscripts are actively translated and that at least a fraction of the encoded proteins are likely to be under purifying selection. This study shows that even in very highly compact genomes,de novotranscripts are continuously generated and can give rise to new functional protein-coding genes.
CMKLR1-targeting peptide tracers for PET/MR imaging of breast cancer
Authors: Erdmann Sarah , Niederstadt Lars , Koziolek Eva Jolanthe , Castillo Gómez Juan Daniel , Prasad Sonal , Wagener Asja , von Hacht Jan Lennart , Hallmann Sandy , Exner Samantha , Bandholtz Sebastian , Beindorff Nicola , Brenner Winfried , Grötzinger Carsten
Published: March 2019

Molecular targeting remains to be a promising approach in cancer medicine. Knowledge about molecular properties such as overexpression of G protein-coupled receptors (GPCRs) is thereby offering a powerful tool for tumor-selective imaging and treatment of cancer cells. We utilized chemerin-based peptides for CMKLR1 receptor targeting in a breast cancer xenograft model. By conjugation with radiolabeled chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), we obtained a family of highly specific and affine tracers for hybridin vivoimaging with positron emission tomography (PET)/ magnetic resonance (MR) and concomitant biodistribution studies.

Methods

We developed five highly specific and affine peptide tracers targeting CMKLR1 by linker-based conjugation of chemerin peptide analogs (CG34 and CG36) with radiolabeled (68Ga) chelator DOTA. Our established xenograft model with target-positive DU4475 and negative A549 tumors in immunodeficient nude mice enabled CMKLR1-specific imagingin vivo. Therefore, we acquired small animal PET/MR images, assessed biodistribution byex vivomeasurements and investigated the tracer specificity by blocking experiments.

Results

The family of five CMKLR1-targeting peptide tracers demonstrated high biological activity and affinityin vitrowith EC50and IC50values being below 2 nM. Our target-positive (DU4475) and target-negative (A549) xenograft model could be confirmed byex vivoanalysis of CMKLR1 expression and binding. After preliminary PET imaging, the three most promising tracers68Ga-DOTA-AHX-CG34,68Ga-DOTA-KCap-CG34 and68Ga-DOTA-ADX-CG34 with apparent DU4475 tumor uptake were further analyzed. Hybrid PET/MR imaging along with concomitant biodistribution studies revealed distinct CMKLR1-specific uptake (5.1% IA/g, 4.5% IA/g and 6.2% IA/g 1 h post-injection) of our targeted tracers in DU4475 tumor tissue. More strikingly, the tumor uptake could be blocked by excess of unlabeled peptide (6.4-fold, 7.2-fold and 3.4-fold 1 h post-injection) and further confirmed the CMKLR1 specificity. As our five tracers, each with particular degree of hydrophobicity, showed different results regarding tumor uptake and organ distribution, we identified these three tracers with moderate, balanced properties to be the most potent in receptor-mediated tumor targeting.

Conclusion

With the breast cancer cell line DU4475, we established a model endogenously expressing our target CMKLR1 to evaluate our chemerin-based peptide tracers as highly affine and specific targeting agents. Eventually, we demonstrated the applicability of our68Ga-labeled tracers by visualizing CMKLR1-positive breast cancer xenografts in PET/MR imaging and thus developed promising theranostics for tumor treatment.
Estimating relatedness between malaria parasites
Authors: Taylor Aimee R. , Jacob Pierre E. , Neafsey Daniel E. , Buckee Caroline O.
Published: March 2019

1.

Understanding the relatedness of individuals within or between populations is a common goal in biology. Increasingly, relatedness features in genetic epidemiology studies of pathogens. These studies are relatively new compared to those in humans and other organisms, but are important for designing interventions and understanding pathogen transmission. Only recently have researchers begun to routinely apply relatedness to apicomplexan eukaryotic malaria parasites, and to date have used a range of different approaches on an ad hoc basis. It remains unclear how to compare different studies, therefore, and which measures to use. Here, we systematically compare measures based on identity-by-state and identity-by-descent using a globally diverse data set of malaria parasites,Plasmodium falciparumandPlasmodium vivax, and provide marker requirements for estimates based on identity-by-descent. We formally show that the informativeness of polyallelic markers for relatedness inference is maximised when alleles are equifrequent. Estimates based on identity-by-state are sensitive to allele frequencies, which vary across populations and by experimental design. For portability across studies, we thus recommend estimates based on identity-by-descent. To generate reliable estimates, we recommend approximately 200 biallelic or 100 polyallelic markers. Confidence intervals illuminate inference across studies based on different sets of markers. These marker requirements, unlike many thus far reported, are immediately applicable to haploid malaria parasites and other haploid eukaryotes. This is the first attempt to provide rigorous analysis of the reliability of, and requirements for, relatedness inference in malaria genetic epidemiology, and will provide a basis for statistically informed prospective study design and surveillance strategies.
Nbs1 Mediates Assembly and Activity of the Mre11 complex
Authors: Kim Jun Hyun , Penson Alexander , Taylor Barry S. , Petrini John H.J.
Published: March 2019

We derived a mouse model in which a mutant form of Nbs1 (Nbs1mid8) exhibits severely impaired binding to the Mre11-Rad50 core of the Mre11 complex. TheNbs1mid8allele was expressed exclusively in hematopoietic lineages (inNbs1-/mid8vavmice). UnlikeNbs1flox/floxvavmice, which are Nbs1 deficient in the bone marrow,Nbs1-/mid8vavmice were viable.Nbs1-/mid8vavhematopoiesis was profoundly defective, exhibiting reduced cellularity of thymus and bone marrow, and stage specific blockage of B cell development. Within six months,Nbs1-/mid8mice developed highly penetrant T cell leukemias.Nbs1-/mid8vavleukemias recapitulated mutational features of human T-ALL, containing mutations inNotch1, Trp53, Bcl6, Bcor, andIkzf1, suggesting thatNbs1mid8mice may provide a venue to examine the relationship between the Mre11 complex and oncogene activation in the hematopoietic compartment. Genomic analysis ofNbs1-/mid8vavmalignancies showed focal amplification of 9qA2, causing overexpression ofMRE11andCHK1. We propose that overexpression compensates for the meta-stable Mre11-Nbs1mid8interaction, and that selection pressure for overexpression reflects the essential role of Nbs1 in promoting assembly and activity of the Mre11 complex.
Looking for a reference for large datasets: relative reliability of visual and automatic sleep scoring
Authors: Berthomier C. , Muto V. , Schmidt C. , Vandewalle G. , Jaspar M. , Devillers J. , Gaggioni G. , Chellappa S. L. , Meyer C. , Phillips C. , Salmon E. , Berthomier P. , Prado J. , Benoit O. , Brandewinder M. , Mattout J. , Maquet J.
Published: March 2019

Study Objectives

New challenges in sleep science require to describe fine grain phenomena or to deal with large datasets. Beside the human resource challenge of scoring huge datasets, the inter- and intra-expert variability may also reduce the sensitivity of such studies. Searching for a way to disentangle the variability induced by the scoring method from the actual variability in the data, visual and automatic sleep scorings of healthy individuals were examined.

Methods

A first dataset (DS1, 4 recordings) scored by 6 experts plus an autoscoring algorithm was used to characterize inter-scoring variability. A second dataset (DS2, 88 recordings) scored a few weeks later was used to investigate intra-expert variability. Percentage agreements and Conger’s kappa were derived from epoch-by-epoch comparisons on pairwise, consensus and majority scorings.

Results

On DS1 the number of epochs of agreement decreased when the number of expert increased, in both majority and consensus scoring, where agreement ranged from 86% (pairwise) to 69% (all experts). Adding autoscoring to visual scorings changed the kappa value from 0.81 to 0.79. Agreement between expert consensus and autoscoring was 93%. On DS2 intra-expert variability was evidenced by the kappa systematic decrease between autoscoring and each single expert between datasets (0.75 to 0.70).

Conclusions

Visual scoring induces inter- and intra-expert variability, which is difficult to address especially in big data studies. When proven to be reliable and if perfectly reproducible, autoscoring methods can cope with intra-scorer variability making them a sensible option when dealing with large datasets.

Statement of Significance

We confirmed and extended previous findings highlighting the intra- and inter-expert variability in visual sleep scoring. On large datasets those variability issues cannot be completely addressed by neither practical nor statistical solutions such as group training, majority or consensus scoring.

When an automated scoring method can be proven to be as reasonably imperfect as visual scoring but perfectly reproducible, it can serve as a reliable scoring reference for sleep studies.
PINK1 and parkin shape the organism-wide distribution of a deleterious mitochondrial genome
Authors: Ahier Arnaud , Cummins Nadia , Dai Chuan-Yang , Götz Jürgen , Zuryn Steven
Published: March 2019

In multiple species, certain tissue types are prone to acquiring greater loads of mitochondrial genome (mtDNA) mutations relative to others, however the mechanisms that drive these heteroplasmy differences are unknown. We found that the conserved PTEN-induced putative kinase (PINK1/PINK-1) and the E3 ubiquitin-protein ligase parkin (PDR-1), which are required for mitochondrial autophagy (mitophagy), underlie stereotyped differences in heteroplasmy of a deleterious mitochondrial genome mutation (ΔmtDNA) between major somatic tissues types in Caenorhabditis elegans. We demonstrate that tissues prone to accumulating ΔmtDNA have lower mitophagy responses than those with low mutation levels, such as neurons. Moreover, we show that ΔmtDNA heteroplasmy increases when proteotoxic species that are associated with neurodegenerative disease and mitophagy inhibition are overexpressed in the nervous system. Together, these results suggest that PINK1 and parkin drive organism-wide patterns of heteroplasmy and provide evidence of a causal link between proteotoxicity, mitophagy, and mtDNA mutation levels in neurons.
Neural measures of subsequent memory reflect endogenous variability in cognitive function
Authors: Weidemann Christoph T. , Kahana Michael J.
Published: March 2019

Human cognition exhibits a striking degree of variability: Sometimes we rapidly forge new associations whereas at other times new information simply does not stick. Correlations between neural activity during encoding and subsequent retrieval performance have implicated such “subsequent memory effects” (SMEs) as important for understanding the neural basis of memory formation. Uncontrolled variability in external factors that also predict memory performance, however, confounds the interpretation of these effects. By controlling for a comprehensive set of external variables, we investigated the extent to which neural correlates of successful memory encoding reflect variability in endogenous brain states. We show that external variables that reliably predict memory performance have relatively small effects on electroencephalographic (EEG) correlates of successful memory encoding. Instead, the brain activity that is diagnostic of successful encoding primarily reflects fluctuations in endogenous neural activity. These findings link neural activity during learning to endogenous states that drive variability in human cognition.
A subset of lung cancer cases shows robust signs of homologous recombination deficiency associated genomic mutational signatures
Authors: Diossy Miklos , Sztupinszki Zsofia , Borcsok Judit , Krzystanek Marcin , Tisza Viktoria , Spisak Sandor , Rusz Orsolya , Timar Jozsef , Csabai István , Moldvay Judit , Pedersen Anders Gorm , Szuts David , Szallasi Zoltan
Published: March 2019

Background

Consistent with their assumed mechanism of action, PARP inhibitors show significant therapeutic efficacy in breast, ovarian and prostate cancer, which are the solid tumor types most often associated with the loss of function of key homologous recombination genes. It remains unknown, however, how frequent homologous recombination deficiency (HRD) is in other solid tumor types. Since it is well established, that HRD induces specific DNA aberration profiles and genomic scars that can be captured by various next-generation sequencing (NGS) based biomarkers, it is possible to assess the presence or absence of this DNA repair pathway aberration in any given tumor biopsy.

Methods

We derived the various HRD associated mutational signatures from whole genome and whole exome sequencing data in the lung adenocarcinoma (LUAD) and lung squamous carcinoma (LUSC) cases from TCGA, in a patient of ours with stage IVA lung cancer with exceptionally good response to platinum-based therapy and in lung cancer cell lines.

Results

We have found evidence that a subset of the investigated cases shows robust signs of HR deficiency, some of which exhibiting similar patterns to those with a complete loss of function of either BRCA1 or BRCA2 genes, however, without any signs of genetic alterations being present in either of those genes. The extreme platinum responder case also showed a robust HRD associated genomic mutational profile. HRD associated mutational signatures were also associated with PARP inhibitor sensitivity in lung cancer cell lines.

Conclusions

Lung cancer cases with high levels of HRD associated mutational signatures could be candidates for PARP inhibitor treatment, and in general, the prioritization of patients for clinical trials might be achieved using the combined analysis of the HRD-related next-generation sequencing-based mutational signatures.
Visual recognition of the female body axis drives spatial elements of male courtship in Drosophila melanogaster
Authors: McKinney Ross M , Ben-Shahar Yehuda
Published: March 2019

Like other mating behaviors, the courtship ritual exhibited by male Drosophila towards a virgin female is comprised of spatiotemporal sequences of innate behavioral elements. Yet, the specific stimuli and neural circuits that determine when and where males release individual courtship elements are not well understood. Here, we investigated the role of visual object recognition in the release of specific behavioral elements during bouts of male courtship. By using a computer vision and machine learning based approach for high-resolution analyses of the male courtship ritual, we show that the release of distinct behavioral elements occur at stereotyped locations around the female and depends on the ability of males to recognize visual landmarks present on the female. Specifically, we show that independent of female motion, males utilize unique populations of visual projection neurons to recognize the eyes of a target female, which is essential for the release of courtship behaviors at their appropriate spatial locations. Together, these results provide a mechanistic explanation for how relatively simple visual cues could play a role in driving both spatially- and temporally-complex social interactions.
Characterization and repurposing of the endogenous Type I-F CRISPR-Cas system ofZymomonas mobilisfor genome engineering
Authors: Zheng Yanli , Han Jiamei , Liang Wenyao , Li Runxia , Hu Xiaoyun , Wang Baiyang , Shen Wei , Ma Xiangdong , Ma Lixin , Yi Li , Yang Shihui , Peng Wenfang
Published: March 2019

Establishment of production platform organisms through prokaryotic engineering represents an efficient means to generate alternatives for yielding renewable biochemicals and biofuels from sustainable resources.Zymomonas mobilis, a natural facultative anaerobic ethanologen, possesses many attractive physiological attributes, making it an important industrial microorganism. To facilitate the broad applications of this strain for biorefinery, an efficient genome engineering toolkit forZ. mobiliswas established in this study by repurposing the endogenous Type I-F CRISPR-Cas system upon its functional characterization, and further updated. This toolkit includes a series of genome engineering plasmids, each carrying an artificial self-targeting CRISPR and a donor DNA for the recovery of recombinants. Using the updated toolkit, genome engineering purposes were achieved with efficiencies of up to 100%, including knockout ofcas3gene, replacement ofcas3with the mCherry-encodingrfpgene, nucleotide substitutions incas3, and deletion of two large genomic fragments up to 10 kb. This study established thus far the most efficient, straightforward and convenient genome engineering toolkit forZ. mobilis, and laid a foundation for further native CRISPRi studies inZ.mobilis, which extended the application scope of CRISPR-based technologies, and could also be applied to other industrial microorganisms with unexploited endogenous CRISPR-Cas systems.
Effects of dietary taurine level on visual function in European sea bass (Dicentrarchus labrax)
Authors: Brill Richard W. , Horodysky Andrij Z. , Place Allen R. , Larkin Mary E.M. , Reimschuessel Renate
Published: March 2019

Dietary insufficiencies have been well documented to decrease growth rates and survival (and therefore overall production) in fish aquaculture. By contrast, the effects of dietary insufficiencies on the sensory biology of cultured fish remains largely unstudied. Diets based solely on plant protein sources could have advantages over fish-based diets, because of the cost and ecological effects of the latter, but lack the amino acid taurine. Adequate levels of taurine are, however, necessary for the development of a fully functional visual system in mammals. As part of ongoing studies to determine the suitability of plant-based diets, we investigated the effects of normal and reduced taurine dietary levels on retinal anatomy and function in European sea bass (Dicentrarchus labrax). We could not demonstrate any effects of dietary taurine level on retinal anatomy, nor the functional properties of luminous sensitivity or temporal resolution (measured as flicker fusion frequency). We did, however, find an effect on spectral sensitivity. The peak of spectral sensitivity of individuals fed a 5% taurine diet was rightward shifted (i.e., towards longer wavelengths) relative to that of fish fed a 0% or 1.5 % taurine diet. This difference in in spectral sensitivity was due to a relatively lower level of middle wavelength pigment (maximum absorbance ≈500 nm) in fish fed a 5% taurine diet. Changes in spectral sensitivity resulting from diets containing different taurine levels are unlikely to be detrimental to fish destined for market but could be in fishes that are being reared for stock enhancement programs.
Crystal defects responsible for mechanical behaviors of a WC–Co composite at room and high temperatures – a simulation study
Authors: Fang Jing , Liu Xuemei , Lu Hao , Liu Xingwei , Song Xiaoyan
Published: March 2019

The microstructure evolution and changes in the structures of crystal defects of the nanocrystalline WC–Co composite in the process of uniaxial compression were studied by simulations at both room and high temperatures. The deformation processes were demonstrated as a function of stress and temperature for the stages prior to and after yielding of the composite. The Peierls stresses were evaluated for Co and WC dislocations with increasing temperature. The deformation mechanisms for each stage of the stress–strain curve were disclosed, in which the effect of temperature was clarified. It was found that with the increase of stress, from elastic deformation to plastic deformation then to yielding of the composite, the dominant mechanisms are grain boundary migration, formation and motion of dislocations in Co, concurrent motion and reaction of dislocations in Co and WC, and then rotation of WC grains in combination with motion of Co and WC dislocations. At the yielding stage, sliding of WC grain boundaries plays an increasingly important role in the contribution to plastic deformation at high temperatures. With strain the proportion of mobile dislocations decreases, and dislocations pile up at triple junctions of WC grains, WC/WC grain boundaries and WC/Co phase boundaries in priority order, leading to the nucleation and propagation of microcracks in these regions.
Substrate-analogue complex structure of Mycobacterium tuberculosis decaprenyl diphosphate synthase
Authors: Ko Tzu-Ping , Xiao Xiansha , Guo Rey-Ting , Huang Jian-Wen , Liu Weidong , Chen Chun-Chi
Published: March 2019

Decaprenyl diphosphate synthase from Mycobacterium tuberculosis (MtDPPS, also known as Rv2361c) catalyzes the consecutive elongation of ω,E,Z-farnesyl diphosphate (EZ-FPP) by seven isoprene units by forming new cis double bonds. The protein folds into a butterfly-like homodimer like most other cis-type prenyltransferases. The starting allylic substrate EZ-FPP is bound to the S1 site and the homoallylic substrate to be incorporated, isopentenyl diphosphate, is bound to the S2 site. Here, a 1.55 Å resolution structure of MtDPPS in complex with the substrate analogues geranyl S-thiodiphosphate (GSPP) and isopentenyl S-thiodiphosphate bound to their respective sites in one subunit clearly shows the active-site configuration and the magnesium-coordinated geometry for catalysis. The ligand-binding mode of GSPP in the other subunit indicates a possible pathway of product translocation from the S2 site to the S1 site, as required for the next step of the reaction. The preferred binding of negatively charged effectors to the S1 site also suggests a promising direction for inhibitor design.
The effect of organizational culture on supply chain management in uncertain environments
Authors: Sung Hyunjung , Kim Seogsoo
Published: March 2019

Purpose

The purpose of this paper is to investigate the impact of environmental uncertainty (EU) on supply chain management (SCM) in Korea, and assess the moderating role of organizational culture.

Design/methodology/approach

Quantitative data analysis was conducted on data that were collected from 125 Korean manufacturing firms listed on the Korean Stock Exchange. First, structural equation modeling was employed to test the hypothesized paths. Second, multi-group analysis was used to explore the possibility of differences between groups with diverse organizational cultures. Before testing the measurement model, confirmatory factor analysis was run to test the reliability and validity of the measurement items.

Findings

The findings indicate that all the hypotheses on the relationships between EU, SCM antecedents and SCM activities are supported except the relationship between commitment and cooperation. The outcome of the multi-group analysis shows that the impact of EU on SCM antecedents varies across organizational cultures.

Originality/value

This study proposes managerial guidelines for implementing effective SCM in response to EU and emphasize that these are consistent with organizational culture.
Relation between Chinese consumers’ ethical perceptions and purchase intentions
Authors: Javed Muhammad Kashif , Degong Ma , Qadeer Talat
Published: March 2019

Purpose

Most business-related studies on ethics focus on consumers in developed western economies but ignore developing economies. Therefore, to fill this void in the literature and address the concerns of prior studies, the purpose of this paper is to examine the ethical perceptions of Chinese consumers as an example of effective and efficient management of company/brand strategies in an economy experiencing rapid socioeconomic growth.

Design/methodology/approach

This study examines 328 Chinese consumers’ purchase intentions based on their ethical perceptions toward Apple and P&G through mediating (i.e. consumer–corporate identification (CCI) and brand trust) and moderating (i.e. consumer gender, age, education and residence) effects. Structural equation modeling is used to analyze the constructs and overall model.

Findings

The ethical perceptions of consumers translate into purchase intentions, both at the corporate and product brand levels. Similarly, a significant direct relationship between CCI and brand trust reveals that corporate-level ethical identification is a trivial matter to customers, although these perceptions do apply to product brands under a corporate umbrella. Furthermore, to identify target groups of Chinese consumers who are receptive to ethical appeals, moderating variables were found to be useful.

Originality/value

The results confirm that the mediating role of CCI is more influential in the context of Chinese consumers’ ethical perceptions, followed by brand trust. In relation to demographics, ethical perceptions affect CCI and brand trust more positively in females and highly educated consumers in China. Similarly, the relationship between consumers’ ethical perception and their trust in brand is revealed more influential in urban residents than they do in rural. This broadens the applications and contexts of this research model. The results provide managerial guidance on enhancing potential ethical perceptions.
The framework for designing new logistics service product: a multi-case investigation in China
Authors: Liu Weihua , Wang Di , Zhao Xuan , Si Cheng , Tang Ou
Published: March 2019

Purpose

The purpose of this paper is to analyze the influencing factors of new logistics service product design (NLSPD) in China to establish a theoretical framework for the future development of the logistics industry.

Design/methodology/approach

The paper adopts the multi-case study method based on a sample of four Chinese logistics enterprises, in which the authors consider the logistics service maturity (LSM), a distinct characteristic of logistics enterprises.

Findings

NLSPD is directly related to the degree of supply–demand matching (SDM) and LSM. Customer demand, service capability and peer competition influence the performance of NLSPD through the SDM degree, whereas LSM moderates these influencing mechanisms. Moreover, the degree of SDM has a positive impact on LSM.

Practical implications

The findings can help the managers of logistics enterprises and practitioners in the logistics industry understand the complexity of NLSPD. First, they should broaden and deepen their service offering to enhance the degree of LSM. Second, they should pay attention to the factors that affect SDM systematically. Finally, it is vital to balance the relationship between LSM and SDM.

Originality/value

NLSPD has become an important tool affecting the competitiveness and sustainability of logistics service enterprises. This is the first paper to propose a theoretical framework for NLSPD that considers the characteristic of the logistics industry. It clarifies the mechanisms of influencing factors, and contributes to the literature by filling the research gap.
Consumer attitudes and buying behavior for green food products
Authors: Woo Eunju , Kim Yeong Gug
Published: March 2019

Purpose

The purpose of this paper is to apply the multidimensional construct of green perceived value (GPV) to the buying behavior of green food products to enhance the understanding of consumer behavior intentions and explain the formation of the intention to buy green food products.

Design/methodology/approach

This study adopted four GPVs (i.e. functional value, conditional value, social value and emotional value) and explored the relationships among GPV, attitudes and purchase intention. A total of 300 self-administered questionnaires were distributed, from which 253 usable responses were obtained.

Findings

The relationships between six constructs and 20 indicators were measured using structural equation modeling. All the underlying dimensions had a significant effect on consumers’ attitudes, significantly affecting their purchase intention.

Originality/value

Implications for future research and marketing strategies in the field of purchasing behaviors of green food products are discussed.
Consumer awareness and acceptance of irradiated foods: the case of Italian consumers
Authors: Galati Antonino , Moavero Pietro , Crescimanno Maria
Published: March 2019

Purpose

The purpose of this paper is to investigate consumers’ willingness to accept irradiated food and the major factors related both to socio-demographic characteristics and to the perceived risk of consumers about the assumption of foods treated with novel technologies and irradiation, in particular, affecting their behavior. Consumers’ need for information has been investigated.

Design/methodology/approach

An online survey, involving 392 consumers living in Italy, was carried out to respond to the aim of the study. A Probit model was performed in order to identify major factors affecting the probability to accept food treated with ionizing radiation.

Findings

Findings show that the acceptability of irradiated foods is mainly affected by the consumers’ perceived risk to health consequent to their consumption. Equally influent are the socio-economic characteristics such as age, monthly income and geographical area in which consumers live.

Research limitations/implications

This study provides some interesting suggestions both for policy makers and managers, primarily related to the need to start an effective promotion campaign aimed to familiarize the consumers about the principles, aims and benefits of irradiation technology.

Originality/value

Very few empirical studies have been carried out in order to evaluate the acceptability of foods products treated with ionizing radiation in Italy, where exist a growing problem related to the food loss and waste, and the need for information among consumers about the irradiated foods.
Assessing mobile application components in providing library services
Authors: Mansouri Ali , Soleymani Asl Nooshin
Published: March 2019

Purpose

This study aims to investigate the essential components needed to develop a practical mobile application for providing library services to its users.

Design/methodology/approach

The study was conducted in a descriptive-survey format. The statistical population constituted the libraries worldwide using mobile applications to provide library services to the users of academic and public libraries. The data were collected through the content-analysis method, World Wide Web and checklists.

Findings

It was found that services such as search, ask a librarian, database, renew, circulation and library hours were frequently used at academic libraries, while the services of search, search through barcode scanners and database were mostly common at public libraries. According to the users of academic and public libraries, circulation and renew, search, ask a librarian and library hours were considered as the most essential services to be included in library mobile applications.

Practical implications

Most libraries usually use mobile apps subjectively. Thus, it is important to identify the most important components of their usage and present them in a suitable pattern. The findings of this study identified the most important components in the design and development of mobile apps and proposed the right model for their integration into libraries.

Originality/value

The practical mobile application proposed here for library services is applicable to all types of libraries and provides an appropriate pattern for mobile application designers.