bluuebunny/crossref_metadata_2025 huggingface dataset:
Flexible Learning-Free Segmentation and Reconstruction for Sparse Neuronal Circuit Tracing
Authors: Shahbazi Ali , Kinnison Jeffery , Vescovi Rafael , Du Ming , Hill Robert , Joesch Maximilian , Takeno Marc , Zeng Hongkui , Costa Nuno Macarico da , Grutzendler Jaime , Kasthuri Narayanan , Scheirer Walter J.
Published: March 2018

Imaging is a dominant strategy for data collection in neuroscience, yielding stacks of images that often scale to gigabytes of data for a single experiment. Machine learning algorithms from computer vision can serve as a pair of virtual eyes that tirelessly processes these images, automatically constructing more complete and realistic circuits. In practice, such algorithms are often too error-prone and computationally expensive to be immediately useful. We address these shortcomings with a new fast, flexible, learning-free method for sparse segmentation and reconstruction of neural volumes. Unlike learning methods, our Flexible Learning-free Reconstruction of Imaged Neural volumes (FLoRIN) pipeline exploits structure-specific contextual clues and requires no training. This approach generalizes across different modalities, including serially-sectioned scanning electron microscopy (sSEM) of genetically labeled and contrast enhanced processes, spectral confocal reflectance (SCoRe) microscopy, and high-energy synchrotron X-ray microtomography (μCT) of large tissue volumes. We deploy the FLoRIN pipeline on newly published and novel mouse datasets, demonstrating the high biological fidelity of the pipeline’s reconstructions, which are of sufficient quality for preliminary biological study. Compared to existing supervised learning methods, it is both significantly faster (up to several orders of magnitude) and produces high-quality reconstructions that are robust to noise and artifacts.
Physiology and lipid accumulation capacity of differentYarrowia lipolyticaandRhodosporidium toruloidesstrains on glycerol
Authors: Azambuja Suellen Patricia Held , Bonturi Nemailla , Miranda Everson Alves , Gombert Andreas Karoly
Published: March 2018

Objective

To compare physiological and process parameters, as well as lipid accumulation capacity, of six strains ofYarrowia lipolyticaand two strains ofRhodosporidium toruloidesin media containing glycerol as the main carbon and energy source.

Results

The strainsY. lipolyticaIMUFRJ 50678, Po1g, W29 and CCT 5443 displayed very similar physiological parameters, with µmax,andaverage values of 0.31 h−1, 0.53 (g DW/g S), 0.60 (g S/g DW.h) and 0.46 (g DW/g S), respectively. The two strains ofR. toruloidespresented physiological and process parameters with no significant difference, with average values of 0.084 h−1, 0.53 (g DW/g S), 0.17 (g S/g DW.h) and 0.44 (g DW/g S). Among allY. lipolyticastrains,Y. lipolyticaCCT 5443 strain presented the highestYLip/S, 0.054 (g Lip/g S), andPLipof 0.040 (g Lip/l.h). Among all investigated strains (Y. lipolyticaandR. toruloides), the yeastR. toruloidesCCT 7815 displayed the highest lipid accumulation capacity, withYLip/Sequal to 0.11 (g Lip/g S) andPLipequal to 0.10 (g Lip/l.h).

Conclusion

Among all strains investigated in our study, the yeast strainR. toruloidesCCT 7815 presents the most promising characteristics for industrial single cell oil production.

List of abbreviations

DW

dry weight (g/l)

Lip

lipid (g/l)

PLip

lipid productivity (g Lip/l.h)

maximum specific substrate consumption rate (g S/g DW.h)

S

substrate (g/l)

YLip/S

lipid yield on substrate (g Lip/g S)

biomass yield on substrate during the exponential growth phase (g DW/g S)

global biomass yield on substrate (g DW/g S)

µmax

maximum specific growth rate (h−1)
Species- and C-terminal linker-dependent variations in the dynamic behavior of FtsZ on membranesin vitro
Authors: Sundararajan Kousik , Vecchiarelli Anthony , Mizuuchi Kiyoshi , Goley Erin D.
Published: March 2018

Bacterial cell division requires the assembly of FtsZ protofilaments into a dynamic structure called the ‘Z-ring’. The Z-ring recruits the division machinery and directs local cell wall remodeling for constriction. The organization and dynamics of protofilaments within the Z-ring coordinate local cell wall synthesis during cell constriction, but their regulation is largely unknown. The disordered C-terminal linker (CTL) region ofCaulobacter crescentusFtsZ (CcFtsZ) regulates polymer structure and turnover in solutionin vitro, and regulates Z-ring structure and activity of cell wall enzymesin vivo. To investigate the contributions of the CTL to the polymerization properties of FtsZ on its physiological platform, the cell membrane, we reconstitutedCcFtsZ polymerization on supported lipid bilayers (SLB) and visualized polymer dynamics and structure using total internal reflection fluorescence microscopy. UnlikeE. coliFtsZ protofilaments that organized into large, bundled patterns,CcFtsZ protofilaments assembled into small, dynamic clusters on SLBs. Moreover,CcFtsZ lacking its CTL formed large networks of straight filament bundles that underwent slower turnover than the dynamic clusters of wildtype FtsZ. Ourin vitrocharacterization provides novel insights into species- and CTL-dependent differences between FtsZ assembly properties that are relevant to Z-ring assembly and function on membranesin vivo.
Epidermal YAP Activity Drives Canonical WNT16/β-catenin Signaling to Promote Keratinocyte Proliferation in vitro and in the Murine Skin
Authors: Mendoza-Reinoso Veronica , Beverdam Annemiek
Published: March 2018

The skin constantly self-renews throughout adult life. Wnt/β-catenin signaling plays a key role in promoting keratinocyte proliferation in the hair follicles and in the interfollicular epidermis. A recent report demonstrated that epidermal YAP activity drives β-catenin activation to promote keratinocyte proliferation in the murine skin. However, it remains unclear whether this is caused by paracrine activation of canonical Wnt signaling or through other YAP/β-catenin regulatory interactions. In the present study, we found that XAV939-inhibition of canonical WNT signaling in skin of YAP2-5SA-ΔC mice resulted in diminished β-catenin activation, reduced keratinocyte proliferation, and a mitigation of the hyperplastic abnormalities in the interfollicular epidermis, signifying a canonical WNT ligand-dependent mechanism. Our subsequent analyses determined that WNT16 is produced in response to YAP activity in keratinocytes both in vitro and in vivo, and that WNT16 drives HaCaT keratinocyte proliferation via canonical WNT16/β-catenin signaling. We conclude that under normal physiological conditions WNT16 is the paracrine WNT ligand secreted in response to epidermal YAP activity that promotes cell proliferation in the interfollicular epidermis. This study delineates a fundamental YAP-driven mechanism that controls normal skin regeneration, and that may be perturbed in human regenerative disease displaying increased YAP and WNT signaling activity.
DeepProfile: Deep learning of cancer molecular profiles for precision medicine
Authors: Dincer Ayse Berceste , Celik Safiye , Hiranuma Naozumi , Lee Su-In
Published: March 2018

We present the DeepProfile framework, which learns a variational autoencoder (VAE) network from thousands of publicly available gene expression samples and uses this network to encode a low-dimensional representation (LDR) to predict complex disease phenotypes. To our knowledge, DeepProfile is the first attempt to use deep learning to extract a feature representation from a vast quantity of unlabeled (i.e, lacking phenotype information) expression samples that are not incorporated into the prediction problem. We use Deep-Profile to predict acute myeloid leukemia patients’ in vitro responses to 160 chemotherapy drugs. We show that, when compared to the original features (i.e., expression levels) and LDRs from two commonly used dimensionality reduction methods, DeepProfile: (1) better predicts complex phenotypes, (2) better captures known functional gene groups, and (3) better reconstructs the input data. We show that DeepProfile is generalizable to other diseases and phenotypes by using it to predict ovarian cancer patients’ tumor invasion patterns and breast cancer patients’ disease subtypes.
AIControl: Replacing matched control experiments with machine learning improves ChIP-seq peak identification
Authors: Hiranuma Nao , Lundberg Scott M. , Lee Su-In
Published: March 2018

ChIP-seq is a technique to determine binding locations of transcription factors, which remains a central challenge in molecular biology. Current practice is to use a “control” dataset to remove background signals from a immunoprecipitation (IP) target dataset. We introduce the AlControl framework, which eliminates the need to obtain a control dataset and instead identifies binding peaks by estimating the distributions of background signals from many publicly available control ChIP-seq datasets. We thereby avoid the cost of running control experiments while simultaneously increasing the accuracy of binding location identification. Specifically, AIControl can (1) estimate background signals at fine resolution, (2) systematically weigh the most appropriate control datasets in a data-driven way, (3) capture sources of potential biases that may be missed by one control dataset, and (4) remove the need for costly and time-consuming control experiments. We applied AIControl to 410 IP datasets in the ENCODE ChIP-seq database, using 440 control datasets from 107 cell types to impute background signal. Without using matched control datasets, AIControl identified peaks that were more enriched for putative binding sites than those identified by other popular peak callers that used a matched control dataset. We also demonstrated that our framework identifies binding sites that recover documented protein interactions more accurately.
Reverse-engineering flow-cytometry gating strategies for phenotypic labelling and high-performance cell sorting
Authors: Becht Etienne , Simoni Yannick , Coustan-Smith Elaine , Evrard Maximilien , Cheng Yang , Ng Lai Guan , Campana Dario , Newell Evan
Published: March 2018

Motivation

Recent flow and mass cytometers generate 1,000,000 single cell datasets of dimensions 20 to 40. Many tools facilitate the discovery of new cell populations associated with diseases or physiology. These discoveries require the identification of new gating strategies, but gating strategies become exponentially harder to optimize when dimensionality increases. To facilitate this step we developed Hypergate, an algorithm which given a cell population of interest identifies a gating strategy optimized for high yield and purity.

Results

Hypergate achieves higher yield and purity than human experts, Support Vector Machines and Random-Forests on public datasets. We use it to revisit some established gating strategies for the identification of Innate lymphoid cells, which identifies concise and efficient strategies that allow gating these cells with fewer parameters but higher yield and purity than the current standards. For phenotypic description, Hypergate’s outputs are consistent with fields’ knowledge and sparser than those from a competing method.

Availability and Implementation

Hypergate is implemented in R and available at http://github.com/ebecht/hypergate under an Open Source Initiative-compliant licence.
Bees use anthropogenic habitats despite strong natural habitat preferences
Authors: Collado Miguel Á. , Sol Daniel , Bartomeus Ignasi
Published: March 2018

Habitat loss and alteration is widely considered one of the main drivers of the current loss of pollinator diversity. Unfortunately, we still lack a comprehensive analysis of habitat importance, use and preference for major groups of pollinators. Here, we address this gap analysing a large dataset of 15,762 bee specimens (more than 400 species) across northeast USA. We found that natural habitats sustain the highest bee diversity, with many species strongly depending on such habitats. By characterizing habitat use and preference for the 45 most abundant species, we also show that many bee species can use human-altered habitats despite exhibiting strong and clear preferences for forested habitats. However, only a few species appear to do well when the habitat has been drastically modified. We conclude that although altered environments may harbor a substantial number of species, preserving natural areas is still essential to guarantee the conservation of bee biodiversity.
Integration and segregation in Autism Spectrum Disorders modulated by age, disease, and interaction: A graph theoretic study of intrinsic functional connectivity
Authors: Harlalka Vatika , Naik Shruti , Bapi Raju S. , Vinod P.K. , Roy Dipanjan
Published: March 2018

Autism spectrum disorder (ASD) is a neurodevelopmental disorder affecting 1 in 50 children between the ages of 6 and 17 years. Brain connectivity and graph theoretic methods have been particularly very useful in shedding light on the differences between high functioning autistic children compared to typically developing (TD) ones. However, very recent developments in network measures raise a cautionary note by highlighting gross under- and over-connectivity in ASD may be an oversimplified hypothesis. Thus the primary aim of our study is to investigate these notions in functional connectomics of ASD versus TD by subjecting the data to reproducibility experiments using two independent datasets.

Further, we tested the hypothesis of alteration in network segregation and integration in the ASD subjects. We have analyzed the resting-state functional magnetic resonance imaging (rs-fMRI) and diffusion tensor imaging (DTI) data from the University of California Los Angeles (UCLA) multimodal connectivity database (n=42 ASD, n=37 TD) and rs-fMRI data from the Autism Brain Imaging Data Exchange (ABIDE) (n=187 ASD, n=176 TD) dataset. We assessed the differences in connection strength between TD and ASD subjects. We also performed graph theoretical analysis to analyze the effect of disease on various network measures. Further, using the larger ABIDE dataset, we performed two-factor ANOVA test, to study the effect of age, disease and their interaction by classifying the TD and ASD participants into two cohorts: children (9-12 years, n=73 TD and n=87 ASD) and adolescents (13-16 years, n=103 TD and n=100 ASD). In ASD, we show the existence of atypical connectivity within and between functional networks as compared to TD. We also found in ASD both hypo-and hyper-connectivity within functional networks such as the default mode network (DMN). Further, graph theoretic analysis showed that there is significant effect of age and disease on modularity, clustering coefficient, and local efficiency. We also identified specific areas within the DMN, sensorimotor, visual and attention networks that are affected by age, disease and their interaction. Overall, our findings suggest that maturation, disease and their interaction are critical for unraveling the biological basis and developmental trajectory in ASD and other neuropsychiatric disorders.
Decomposing the subclonal structure of tumors with two-way mixture models on copy number aberrations
Authors: Tai An-Shun , Peng Chien-Hua , Peng Shih-Chi , Hsieh Wen-Ping
Published: March 2018

Multistage tumorigenesis is a dynamic process characterized by the accumulation of mutations. Thus, a tumor mass is composed of genetically divergent cell subclones. With the advancement of next-generation sequencing (NGS), mathematical models have been recently developed to decompose tumor subclonal architecture from a collective genome sequencing data. Most of the methods focused on single-nucleotide variants (SNVs). However, somatic copy number aberrations (CNAs) also play critical roles in carcinogenesis. Therefore, further modeling subclonal CNAs composition would hold the promise to improve the analysis of tumor heterogeneity and cancer evolution. To address this issue, we developed a two-way mixture Poisson model, named CloneDeMix for the deconvolution of read-depth information. It can infer the subclonal copy number, mutational cellular prevalence (MCP), subclone composition, and the order in which mutations occurred in the evolutionary hierarchy. The performance of CloneDeMix was systematically assessed in simulations. As a result, the accuracy of CNA inference was nearly 93% and the MCP was also accurately restored. Furthermore, we also demonstrated its applicability using head and neck cancer samples from TCGA. Our results inform about the extent of subclonal CNA diversity, and a group of candidate genes that probably initiate lymph node metastasis during tumor evolution was also discovered. Most importantly, these driver genes are located at 11q13.3 which is highly susceptible to copy number change in head and neck cancer genomes. This study successfully estimates subclonal CNAs and exhibit the evolutionary relationships of mutation events. By doing so, we can track tumor heterogeneity and identify crucial mutations during evolution process. Hence, it facilitates not only understanding the cancer development but finding potential therapeutic targets. Briefly, this framework has implications for improved modeling of tumor evolution and the importance of inclusion of subclonal CNAs.
The neuronal ceroid lipofuscinosis protein Cln7 regulates neural development from the post-synaptic cell
Authors: Connolly Kyle J. , O’Hare Megan B. , Mohammed Alamin , Aitchison Katelyn M. , Anthoney Niki C. , Taylor Matthew J. , Stewart Bryan A. , Tuxworth Richard I. , Tear Guy
Published: March 2018

The neuronal ceroid lipofuscinoses (NCLs) are a group of fatal, monogenic neurodegenerative disorders with an early onset in infancy or childhood. Despite identification of the genes disrupted in each form of the disease, their normal cellular role and how their deficits lead to disease pathology is not fully understood. Cln7, a major facilitator superfamily domain-containing protein, is affected in a late infantile-onset form of NCL. Using the Drosophila larval neuromuscular junction as a model to study neural development, we demonstrate that Cln7 is required for the normal growth of synapses. In a Cln7 mutant, synapses fail to develop fully leading to reduced function and behavioral changes with dysregulation of TOR activity. Cln7 expression is restricted to the post-synaptic cell and the protein localizes to vesicles immediately adjacent to the post-synaptic membrane. Our data suggest an involvement for Cln7 in regulating trans-synaptic communication.
The role of stochastic sequestration dynamics for intrinsic noise filtering in signaling network motifs
Authors: Paul Debdas , Radde Nicole
Published: March 2018

The relation between design principles of signaling network motifs and their robustness against intrinsic noise still remains illusive. In this work we investigate the role of cascading for coping with intrinsic noise due to stochasticity in molecular reactions. We use stochastic approaches to quantify fluctuations in the terminal kinase of phosphorylation-dephosphorylation cascade motifs and demonstrate that cascading highly affects these fluctuations. We show that this purely stochastic effect can be explained by time-varying sequestration of upstream kinase molecules. In particular, we discuss conditions on time scales and parameter regimes which lead to a reduction of output fluctuations. Our results are put into biological context by adapting rate parameters of our modeling approach to biologically feasible ranges for general binding-unbinding and phosphorylation-dephosphorylation mechanisms. Overall, this study reveals a novel role of stochastic sequestration for dynamic noise filtering in signaling cascade motifs.
DNA methylation age acceleration and risk factors for Alzheimer’s disease
Authors: McCartney Daniel L , Stevenson Anna J , Walker Rosie M , Gibson Jude , Morris Stewart W , Campbell Archie , Murray Alison D , Whalley Heather C , Porteous David J , McIntosh Andrew M , Evans Kathryn L , Deary Ian J , Marioni Riccardo E
Published: March 2018

INTRODUCTION

The ‘epigenetic clock’ is a DNA methylation-based estimate of biological age and is correlated with chronological age – the greatest risk factor for Alzheimer’s disease (AD). Genetic and environmental risk factors exist for AD, several of which are potentially modifiable. Here, we assess the relationship associations between the epigenetic clock and AD risk factors.

METHODS

Linear mixed modelling was used to assess the relationship between age acceleration (the residual of biological age regressed onto chronological age) and AD risk factors relating to cognitive reserve, lifestyle, disease, and genetics in the Generation Scotland study (n=5,100).

RESULTS

We report significant associations between the epigenetic clock and BMI, total:HDL cholesterol ratios, socioeconomic status, and smoking behaviour (Bonferroni-adjusted P<0.05).

DISCUSSION

Associations are present between environmental risk factors for AD and age acceleration. Measures to modify such risk factors might improve the risk profile for AD and the rate of biological ageing. Future longitudinal analyses are therefore warranted.
Variational algorithms for analyzing noisy multi-state diffusion trajectories
Authors: Lindén Martin , Elf Johan
Published: March 2018

Single particle tracking offers a non-invasive high-resolution probe of biomolecular reactions inside living cells. However, efficient data analysis methods that correctly account for various noise soures are needed to realize the full quantitative potential of the method. We report new algorithms for hidden Markov based analysis of single particle tracking data, which incorporate most sources of experimental noise, including heterogeneuous localization errors and missing positions. Compared to previous implementations, the algorithms offer significant speed-ups, support for a wider range of inference methods, and a simple user interface. This will enable more advanced and exploratory quantitative analysis of single particle tracking data.
Can Actin Depolymerization Actually Result in Increased Plant Resistance to Pathogens?
Authors: Krutinová Hana , Trdá Lucie , Kalachova Tetiana , Lamparová Lucie , Pospíchalová Romana , Dobrev Petre I. , Malínská Kateřina , Burketová Lenka , Valentová Olga , Janda Martin
Published: March 2018

Introductory paragraph

The integrity of the actin cytoskeleton is essential for plant immune signalling1. Consequently, it is generally assumed that actin disruption reduces plant resistance to pathogen attack2-4. However, in a previous study, it was shown that actin depolymerisation triggers the salicylic acid (SA) signalling pathway5, which is interesting because increased SA is associated with enhanced plant resistance to pathogen attack6,7. Here, we attempt to resolve this seeming inconsistency by showing that the relationship between actin depolymerization and plant resistance is more complex than currently thought. We investigate the precise nature of this relationship using two completely different plant pathosystems: i) a model plant (Arabidopsis thaliana) and a bacterial pathogen (Pseudomonas syringae), and ii) an important crop (Brassica napus) and a fungal pathogen (Leptosphaeria maculans). We demonstrate that actin depolymerization induces a dramatic increase in SA levels and that the increased SA is biosynthesized by the isochorismate synthase pathway. In both pathosystems, this phenomenon leads to increased plant resistance.
Mobile genetic element-encoded hypertolerance to copper protectsStaphylococcus aureusfrom killing by host phagocytes
Authors: Zapotoczna Marta , Pelicioli-Riboldi Gus , Moustafa Ahmed M , Dickson Elizabeth , Narechania Apurva , Morrissey Julie A. , Planet Paul J. , Holden Matthew T.G. , Waldron Kevin J. , Geoghegan Joan A.
Published: March 2018

Pathogens are exposed to toxic levels of copper during infection and copper tolerance may be a general virulence mechanism used by bacteria to resist host defences. In support of this, inactivation of copper-exporter genes has been found to reduce the virulence of bacterial pathogensin vivo. Here we investigate the role of copper-hypertolerance in methicillin resistantStaphylococcus aureus. We show that a copper-hypertolerance locus (copB-mco), carried on a mobile genetic element, is prevalent in a collection of invasiveS. aureusstrains and more widely among clonal complex 22, 30 and 398 strains. ThecopBandmcogenes encode a copper efflux pump and a multicopper oxidase, respectively. Isogenic mutants lackingcopBormcohad impaired growth in subinhibitory concentrations of copper. Transfer of acopB-mcoencoding plasmid to a naive clinical isolate resulted in a gain of copper hypertolerance and enhanced bacterial survival inside primed macrophages. ThecopBandmcogenes were upregulated within infected macrophages and their expression was dependent on the copper sensitive operon repressor CsoR. IsogeniccopBandmcomutants were impaired in their ability to persist intracellularly in macrophages and were less resistant to phagocytic killing in human blood than the parent strain. The importance of copper-regulated genes in resistance to phagocytic killing was further elaborated using mutants expressing a copper-insensitive variant of CsoR. Our findings suggest that the gain of mobile genetic elements carrying copper-hypertolerance genes contributes to the evolution of virulent strains ofS. aureus, better equipped to resist killing by host immune cells.
Extraction of a recombinant full-length NADPH-cytochrome P450 oxidoreductase from bacterial membranes: effect of detergents and additives
Authors: Arafeh Sara A. , Galiakhmetov Azamat R. , Kovrigina Elizaveta A. , Fellin Eric , Kovrigin Evgenii L.
Published: March 2018

NADPH-cytochrome P450 oxidoreductase (POR) is a membrane protein in the endoplasmic reticulum of eukaryotic cells. POR is as a key reducing partner for a number of cytochrome P450 proteins involved in different metabolic degradation and signaling pathways. Preparation of the full-length recombinant POR expressed in bacteria has been reported and, typically, involved the use of Triton X-100 detergent for extraction of the overexpressed POR from bacterial membranes. However, extraction efficiency is always relatively low hindering structural studies, particularly—the NMR spectroscopy requiring isotopic enrichment. In this paper, we assessed the effect of a variety of detergents and additives on the efficiency of the membrane-extraction step in POR preparation protocol. We evaluated non-ionic detergents with the variable hydrophobicity (Triton X-100, X-114, and X-405) and structure (Triton X-100, TWEEN-20, Brij-35), a zwitterionic/non-ionic detergent combination (Triton X-100 and CHAPS), as well as a range of alkylamines and polyamines as additives to the conventional extraction buffer containing Triton X-100. None of the detergents or detergent-additive combinations yielded better extraction efficiency than the conventional protocol with the Triton X-100. Lack of variation of the extraction yield allows to hypothesize that the conventional protocol extracts all of the available natively-folded monomeric POR while the remaining fraction is possibly an unfolded aggregated POR, which did not insert in the membranes during expression. We propose that the yield of soluble POR may be increased by a careful optimization of expression conditions while monitoring the distribution of POR between soluble and insoluble fractions in the detergent extraction step.
Multi-study inference of regulatory networks for more accurate models of gene regulation
Authors: Castro Dayanne M. , de Veaux Nicholas R. , Miraldi Emily R. , Bonneau Richard
Published: March 2018

Gene regulatory networks are composed of sub-networks that are often shared across biological processes, cell-types, and organisms. Leveraging multiple sources of information, such as publicly available gene expression datasets, could therefore be helpful when learning a network of interest. Integrating data across different studies, however, raises numerous technical concerns. Hence, a common approach in network inference, and broadly in genomics research, is to separately learn models from each dataset and combine the results. Individual models, however, often suffer from under-sampling, poor generalization and limited network recovery. In this study, we explore previous integration strategies, such as batch-correction and model ensembles, and introduce a new multitask learning approach for joint network inference across several datasets. Our method initially estimates the activities of transcription factors, and subsequently, infers the relevant network topology. As regulatory interactions are context-dependent, we estimate model coefficients as a combination of both dataset-specific and conserved components. In addition, adaptive penalties may be used to favor models that include interactions derived from multiple sources of prior knowledge including orthogonal genomics experiments. We evaluate generalization and network recovery using examples fromBacillus subtilisandSaccharomyces cerevisiae, and show that sharing information across models improves network reconstruction. Finally, we demonstrate robustness to both false positives in the prior information and heterogeneity among datasets.
Epoxide hydrolysis as a model system for understanding flux through a branched reaction scheme
Authors: Janfalk Carlsson Åsa , Bauer Paul , Dobritzsch Doreen , Kamerlin Shina C. L. , Widersten Mikael
Published: March 2018

The epoxide hydrolase StEH1 catalyzes the hydrolysis oftrans-methylstyrene oxide to 1-phenylpropane-1,2-diol. The (S,S)-epoxide is exclusively transformed into the (1R,2S)-diol, while hydrolysis of the (R,R)-epoxide results in a mixture of product enantiomers. In order to understand the differences in the stereoconfigurations of the products, the reactions were studied kinetically during both the pre-steady-state and steady-state phases. A number of closely related StEH1 variants were analyzed in parallel, and the results were rationalized by structure–activity analysis using the available crystal structures of all tested enzyme variants. Finally, empirical valence-bond simulations were performed in order to provide additional insight into the observed kinetic behaviour and ratios of the diol product enantiomers. These combined data allow us to present a model for the flux through the catalyzed reactions. With the (R,R)-epoxide, ring opening may occur at either C atom and with similar energy barriers for hydrolysis, resulting in a mixture of diol enantiomer products. However, with the (S,S)-epoxide, although either epoxide C atom may react to form the covalent enzyme intermediate, only thepro-(R,S) alkylenzyme is amenable to subsequent hydrolysis. Previously contradictory observations from kinetics experiments as well as product ratios can therefore now be explained for this biocatalytically relevant enzyme.
Crystal structure of bis(diisopropylammonium) cis-diiodidobis(oxolato-κ2
O
1,O
2)stannate(IV)
Authors: Sarr Bougar , Diop Cheikh Abdoul Khadir , Sidibé Mamadou , Rousselin Yoann
Published: March 2018

In the title compound, (iPr2NH2)2[SnI2(C2O4)2], which was prepared by reacting (
i
Pr2NH2
+)2·C2O4
2− with SnI4 in a 2:1 molar ratio in a mixed ethanol–acetonitrile solvent, the Sn atom is coordinated by two chelating oxalate ions and two iodide ions, with the latter in a cis configuration. In the crystal, the cations are linked to the anions by N—H...O and bifurcated N—H...(O,O) hydrogen bonds, generating [10-1] chains.
1-Benzyl-3-methylquinoxalin-2(1H)-one
Authors: Ramli Youssef , El Bakri Youness , El Ghayati L'houssaine , Essassi El Mokhtar , Mague Joel T.
Published: March 2018

The asymmetric unit of the title compound, C16H14N2O, contains three independent molecules differing primarily in the orientations of the benzyl groups. Each independent molecule forms inversion related dimersviaoffset π-stacking interactions. For two of these dimers, stacks are formed approximately along thea-axis direction by a combinations of C—H...N and C—H...π(ring) contacts, in addition to the offset π-stacking interactions. The third set of dimers are also stacked in the same direction but only by pairwise C—H...N hydrogen bonds.
Coordinate transformation uncertainty analysis and reduction using hybrid reference system for aircraft assembly
Authors: Deng Zhengping , Li Shuanggao , Huang Xiang
Published: March 2018

Purpose

In aircraft assembly, standard reference points with nominal coordinates are commonly applied for coordinate transformation between multiple measurement stations and the assembly coordinate system. For several reasons in practical application, these points often fail to envelop the key assembly space, which leads to large transformation uncertainty. This paper aims to analyze and further reduce the coordinate transformation uncertainty by introducing a new hybrid reference system (HRS).

Design/methodology/approach

Several temporary extension points without known coordinates are added to enhance the tightness between different stations, especially at the weakness area in the network, thus constituting an HRS together with the existing standard reference points. The coordinate transformation model of the HRS-based measurement network is established based on an extend Gauss–Markov model. By using the geometrical differential property and variance-covariance propagation law, the covariance matrixes in the transformation model are calculated, and the analytical solution of the uncertainties of transformation parameters are ultimately derived. The transformation uncertainty of each check points is presented by Helmert error expression.

Findings

The proposed analytical solution of transformation uncertainty is verified using the state-of-the-art Monte Carlo simulation method, but the solution process is simpler and the computation expenses are much less.

Practical implications

The HRS with three temporary extension points is practically applied to a tail boom in-site measurement for assembly. The average transformation uncertainty has been reduced by 26 per cent to less than 0.05 mm.

Originality/value

The hybrid coordinate transformation model is proposed for the first time. The HRS method for transformation uncertainty reduction is more economical and practical than increasing the number of standard reference points.
Gender differences in growth of Spanish university spin-offs
Authors: Rodríguez-Gulías María Jesús , Fernández-López Sara , Rodeiro-Pazos David
Published: March 2018

Purpose

The purpose of this paper is to explore the hypothesis that the female-owned university spin-off organizations (USOs) have a similar resource endowment and, as a consequence, growth rates similar to the male-owned USOs.

Design/methodology/approach

A unique and original longitudinal data set, which is an unbalanced panel, consisting of 120 Spanish USOs over the period 2001-2010 has been constructed. The methodology includes the analysis of mean differences (t-test) and dynamic panel data models.

Findings

The results confirmed that there are no gender differences in either the firms’ initial resource endowment or in the preference for industries. There is no gender effect on the USOs’ growth, but the initial endowment resources matter. Thus the financial, human and technological resources have a positive effect on the USOs’ growth. This evidence suggests that the USOs’ context may mitigate the initial resource endowment of the female-owned firms and their preferences for traditional industries, showing similar rates of growth than male-owned USOs.

Research limitations/implications

Owners’ gender has been used as a proxy for founders’ gender. Also, only USOs included in the SABI database have been considered as part of the sample; the significant number of USOs that did not reveal information about their owners have been discarded.

Practical implications

It is important to continue supporting academic entrepreneurship, as in the university context, firm growth is not affected by gender differences. However, given that the percentage of female owners in university entrepreneurship is still lower compared to entrepreneurship in general, the universities’ entrepreneur programmes targeting women must adopt a gendered perspective.

Originality/value

Literature on USOs has traditionally analyzed the firm-specific characteristics that impact their growth without considering the influence of the owners’ gender. In this paper, an attempt to fill this gap has been made using a sample of 120 Spanish USOs and by applying the dynamic panel data methodology. In particular, it has been argued that the university context from which USOs emerge allows female-owned USOs to have a similar resource endowment and, as a consequence, a similar growth when compared to male-owned USOs.
An ethnocentric perspective of foreign multi-brand retail in India
Authors: Banerji Diptiman , Mishra Prashant
Published: March 2018

Purpose

The purpose of this paper is to understand the ethnocentric tendencies of Indian consumers towards foreign multi-brand retailers (FMBRs), and the influence that such ethnocentrism has on their attitudes towards, and future purchasing behaviour from, these international retailers.

Design/methodology/approach

The paper used a mall intercept method with a randomised data collection process to secure data from 119 organised retail shoppers in a major metropolitan Indian city. The analysis was carried out using analysis of covariance, bootstrapping mediation, multiple regression analysis, and Johnson’s relative weight analysis.

Findings

Two main results are as follows: concern for livelihoods of small retailers and a perception that earnings of foreign retailers are unjust are revealed as the most significant drivers of negative attitude towards FMBRs, and although high ethnocentric customers have a strong negative attitude towards FMBRs, they are open to the idea of making future purchases of goods that are not available with small retailers, from the foreign retail outlets.

Research limitations/implications

The study sample is from a single metropolitan city, albeit one which serves as a miniature version of the Indian society. As a limitation, the results might not be generalisable to small, non-metropolitan Indian towns.

Practical implications

These results provide valuable input regarding the marketing strategy and sustainability of foreign retailers planning to launch operations in India. For example, FMBRs should position themselves as not being in competition with existing small retail shops by offering a different array of products. Further, younger and more educated Indians are the least ethnocentric towards FMBRs, thus making them an attractive target segment.

Originality/value

Extant research has studied consumer ethnocentrism of Indian consumers towards foreign brands and products, but not towards FMBRs. This paper attempts to fill that research gap.
The use of social media by South African organisations
Authors: Dlamini Nomusa Nomhle , Johnston Kevin
Published: March 2018

Purpose

The purpose of this paper is to present how organisations in South Africa are using social media. The paper further explores the value of social media to South African organisations and if it is important for an organisation to have a social media presence.

Design/methodology/approach

The study used quantitative research methods to answer the main research question and sub-questions.

Findings

The data collected revealed that most organisations in South Africa are using social media for free advertising, CRM and marketing. The popular social media sites used by these organisations are Facebook and Twitter, with LinkedIn increasing in popularity. The data further revealed that social media is important in organisations for relationship building, contact keeping advertising, marketing, attracting customers, brand management and information gathering.

Research limitations/implications

The role of social media is changing, it was initially a marketing tool, but the findings revealed that majority of organisations are using social media for free advertising, CRM and marketing. Social media is an easy CRM tool that offers effective and efficient capabilities.

Practical implications

It is important to use integrate social media with the organisations processes to market and advertise new products, it is an instant and cost-saving way of communicating with customers, and helps in reaching and attracting new customers.

Social implications

Social media is important for keeping contact and building relationships with customers, advertising and marketing, way to attract customers, brand management tool and gathering information.

Originality/value

The study provides guidance to how organisation can use social media, identifying the value of using social media and highlighting the importance of social media in an organisation in the South African context.
Corporate financial structure and firm’s decision to export
Authors: Miravitlles Paloma , Mora Toni , Achcaoucaou Fariza
Published: March 2018

Purpose

The purpose of this paper is to analyse the decision to export in relation to financial issues, specifically the impact of corporate financial structure on a firm’s export propensity (the likelihood of a firm becoming an exporter) by firm size.

Design/methodology/approach

A multivariate probit model is applied to a sample of 8,019 Spanish manufacturing firms drawn from the Iberian Balance Sheet Analysis System (SABI). The analysis is performed separately for small, medium and large firms.

Findings

The paper evidences, by firm size, a positive link between ownership concentration and export propensity, although for SMEs if shareholder concentration is very high it can be counterproductive. In addition, a high degree of liquidity influences the probability of entering export markets, while those firms that face high costs as result of their export activity may need to become indebted in order to secure the necessary financial resources. However, the strength of these latter effects differs in SMEs.

Originality/value

This paper broadens the understanding of the relationship between firms’ export propensity and their financial health and ownership concentration, an internal factor not previously considered in the international business literature despite its relevance for firm’s decision to export. The paper highlights that their influence is not uniform but affects firms of different sizes in different ways. This is of interest and value to scholars, investors and policy makers worldwide, since handling corporate financial structure and international strategies needs to be addressed in today’s global business environment.
A horizontally gene transferred copper resistance locus confers hyper‐resistance to antibacterial copper toxicity and enables survival of community acquired methicillin resistant Staphylococcus aureus USA300 in macrophages
Authors: Purves Joanne , Thomas Jamie , Riboldi Gustavo P. , Zapotoczna Marta , Tarrant Emma , Andrew Peter W. , Londoño Alejandra , Planet Paul J. , Geoghegan Joan A. , Waldron Kevin J. , Morrissey Julie A.
Published: March 2018

Excess copper is highly toxic and forms part of the host innate immune system's antibacterial arsenal, accumulating at sites of infection and acting within macrophages to kill engulfed pathogens. We show for the first time that a novel, horizontally gene transferred copper resistance locus (copXL), uniquely associated with the SCCmec elements of the highly virulent, epidemic, community acquired methicillin resistant Staphylococcus aureus (CA‐MRSA) USA300, confers copper hyper‐resistance. These genes are additional to existing core genome copper resistance mechanisms, and are not found in typical S. aureus lineages, but are increasingly identified in emerging pathogenic isolates. Our data show that CopX, a putative P1B‐3‐ATPase efflux transporter, and CopL, a novel lipoprotein, confer copper hyper‐resistance compared to typical S. aureus strains. The copXL genes form an operon that is tightly repressed in low copper environments by the copper regulator CsoR. Significantly, CopX and CopL are important for S. aureus USA300 intracellular survival within macrophages. Therefore, the emergence of new S. aureus clones with the copXL locus has significant implications for public health because these genes confer increased resistance to antibacterial copper toxicity, enhancing bacterial fitness by altering S. aureus interaction with innate immunity.
Genomes of ubiquitous marine and hypersaline Hydrogenovibrio, Thiomicrorhabdus and Thiomicrospira spp. encode a diversity of mechanisms to sustain chemolithoautotrophy in heterogeneous environments
Authors: Scott Kathleen M. , Williams John , Porter Cody M. B. , Russel Sydney , Harmer Tara L. , Paul John H. , Antonen Kirsten M. , Bridges Megan K. , Camper Gary J. , Campla Christie K. , Casella Leila G. , Chase Eva , Conrad James W. , Cruz Mercedez C. , Dunlap Darren S. , Duran Laura , Fahsbender Elizabeth M. , Goldsmith Dawn B. , Keeley Ryan F. , Kondoff Matthew R. , Kussy Breanna I. , Lane Marannda K. , Lawler Stephanie , Leigh Brittany A. , Lewis Courtney , Lostal Lygia M. , Marking Devon , Mancera Paola A. , McClenthan Evan C. , McIntyre Emily A. , Mine Jessica A. , Modi Swapnil , Moore Brittney D. , Morgan William A. , Nelson Kaleigh M. , Nguyen Kimmy N. , Ogburn Nicholas , Parrino David G. , Pedapudi Anangamanjari D. , Pelham Rebecca P. , Preece Amanda M. , Rampersad Elizabeth A. , Richardson Jason C. , Rodgers Christina M. , Schaffer Brent L. , Sheridan Nancy E. , Solone Michael R. , Staley Zachery R. , Tabuchi Maki , Waide Ramond J. , Wanjugi Pauline W. , Young Suzanne , Clum Alicia , Daum Chris , Huntemann Marcel , Ivanova Natalia , Kyrpides Nikos , Mikhailova Natalia , Palaniappan Krishnaveni , Pillay Manoj , Reddy T.B.K. , Shapiro Nicole , Stamatis Dimitrios , Varghese Neha , Woyke Tanja , Boden Rich , Freyermuth Sharyn K. , Kerfeld Cheryl A.
Published: March 2018

Chemolithoautotrophic bacteria from the genera Hydrogenovibrio, Thiomicrorhabdus and Thiomicrospira are common, sometimes dominant, isolates from sulfidic habitats including hydrothermal vents, soda and salt lakes and marine sediments. Their genome sequences confirm their membership in a deeply branching clade of the Gammaproteobacteria. Several adaptations to heterogeneous habitats are apparent. Their genomes include large numbers of genes for sensing and responding to their environment (EAL‐ and GGDEF‐domain proteins and methyl‐accepting chemotaxis proteins) despite their small sizes (2.1–3.1 Mbp). An array of sulfur‐oxidizing complexes are encoded, likely to facilitate these organisms' use of multiple forms of reduced sulfur as electron donors. Hydrogenase genes are present in some taxa, including group 1d and 2b hydrogenases in Hydrogenovibrio marinus and H. thermophilus MA2‐6, acquired via horizontal gene transfer. In addition to high‐affinity cbb3 cytochrome c oxidase, some also encode cytochrome bd‐type quinol oxidase or ba3‐type cytochrome c oxidase, which could facilitate growth under different oxygen tensions, or maintain redox balance. Carboxysome operons are present in most, with genes downstream encoding transporters from four evolutionarily distinct families, which may act with the carboxysomes to form CO2 concentrating mechanisms. These adaptations to habitat variability likely contribute to the cosmopolitan distribution of these organisms.