bluuebunny/crossref_metadata_2025 huggingface dataset:
TransgeneR: a one-stop tool for transgene integration and rearrangement discovery using sequencing data
Authors: Meng Guofeng
Published: November 2018

Genetically modified organisms are widely used in lifescience research, agriculture and in commercial products. However, in most cases, the genetic modification in the host genome is often less well characterized with respect to integration location, copy number and host gene expression. The application of next generation sequencing technologies has enabled the characterization of transgene events but still limited by the lack of computational tools. We present a one-stop R tool, transgeneR, as a general computational tool for discovering transgene integration and rearrangement in the host genome. It especially considers the properties of transgene events, such as the homologous transgene sequences, complex genetic structure and multiple copies of transgene insertion. Using this tool, we have successfully mapped the chromosomal transgene integration loci and transgene rearrangements in an artificially simulated MAPT transgene mice genome as well as in a newly generated human tau (MAPT, 0N4R) transgene mice. When unbiased sequencing data such as the whole genome sequencing data, were provided as input, transgeneR integrated multiple information, including integration location, direction, split- and nonsplit-reads, to predict the transgene fragments and their copy number. Overall, our initial evaluation indicates that the transgeneR package is an effective tool for the identification and characterization of transgene integration and rearrangements events, especially in transgene genome with complex genetic structure. TransgeneR is publicly available: https://github.com/menggf/transgeneR
High levels of antibiotic resistance gene expression among birds living in a wastewater treatment plant
Authors: Marcelino Vanessa R. , Wille Michelle , Hurt Aeron C. , González-Acuña Daniel , Klaassen Marcel , Eden John-Sebastian , Shi Mang , Iredell Jonathan R. , Sorrell Tania C. , Holmes Edward C.
Published: November 2018

Antibiotic resistance is rendering common bacterial infections untreatable. Wildlife can incorporate and disperse antibiotic resistant bacteria in the environment, such as water systems, which in turn serve as reservoirs of resistance genes for human pathogens. We used bulk RNA-sequencing (meta-transcriptomics) to assess the diversity and expression levels of functionally active resistance genes in the microbiome of birds with aquatic behavior. We sampled birds across a range of habitats, from penguins in Antarctica to ducks in a wastewater treatment plant in Australia. This revealed 81 antibiotic resistance genes in birds from all localities, including β-lactam, tetracycline and chloramphenicol resistance in Antarctica, and genes typically associated with multidrug resistance plasmids in areas with high human impact. Notably, birds feeding at a wastewater treatment plant carried the greatest resistance gene burden, suggesting that human waste, even if it undergoes treatment, contributes to the spread of antibiotic resistance genes to the wild. Differences in resistance gene burden also reflected the birds’ ecology, taxonomic group and microbial functioning. Ducks, which feed by dabbling, carried a higher abundance and diversity of resistance genes than turnstones, avocets and penguins, that usually prey on more pristine waters. In sum, this study helps to reveal the complex factors explaining the distribution of resistance genes and their exchange routes between humans and wildlife.
Structure and function of a bacterial gap junction analog
Authors: Weiss Gregor L. , Kieninger Ann-Katrin , Maldener Iris , Forchhammer Karl , Pilhofer Martin
Published: November 2018

Multicellular lifestyle requires cell-cell connections. In multicellular cyanobacteria, septal junctions enable molecular exchange between sister cells and are required for cellular differentiation. The structure of septal junctions is poorly understood and it is unknown whether they regulate intercellular communication.

Here we resolved thein situarchitecture of septal junctions by electron cryotomography of cryo-focused ion beam-milled cyanobacteria. Septal junctions consisted of a tube traversing the septal peptidoglycan. Each tube end comprised a plug that was covered by a cytoplasmic cap. Fluorescence recovery after photobleaching showed that intercellular communication was blocked upon stress. This gating was accompanied by a conformational change of the septal junctions, mediated by the proteins FraC/D.

We provide the mechanistic framework for a cell junction that predates eukaryotic gap junctions by a billion years. The conservation of a gated dynamic mechanism across different domains of life emphasizes the importance of controlling molecular exchange, e.g. upon injury.
Inter-organ growth coordination is mediated by the Xrp1/Dilp8 axis in Drosophila
Authors: Boulan Laura , Andersen Ditte , Colombani Julien , Boone Emilie , Léopold Pierre
Published: November 2018

How organs scale with other body parts is not mechanistically understood. We have addressed this question using the Drosophila imaginal disc model. When growth of one disc domain is perturbed, other parts of the disc and other discs slow down their growth, maintaining proper inter-disc and intra-disc proportions. We show here that the relaxin-like Dilp8 is required for this inter-organ coordination. Our work also reveals that the stress-response transcription factor Xrp1 plays a key role upstream of dilp8 in linking organ growth status with non-autonomous/systemic growth response. In addition, we show that the small ribosomal subunit protein RpS12 is required to trigger Xrp1-dependent non-autonomous response. Our work demonstrates that RpS12, Xrp1 and Dilp8 constitute a new, independent regulatory module that ensures intra- and inter-organ growth coordination during development.
Retinal microvasculature and cerebral small vessel disease in the Lothian Birth Cohort 1936 and Mild Stroke Study
Authors: McGrory Sarah , Ballerini Lucia , Doubal Fergus N. , Staals Julie , Allerhand Mike , Valdes-Hernandez Maria del C. , Wang Xin , MacGillivray Thomas J. , Doney Alex S.F. , Dhillon Baljean , Starr John M. , Bastin Mark E. , Trucco Emanuele , Deary Ian J. , Wardlaw Joanna M.
Published: November 2018

Research has suggested that the retinal vasculature may act as a surrogate marker for diseased cerebral vessels. Retinal vascular parameters were measured using Vessel Assessment and Measurement Platform for Images of the Retina (VAMPIRE) software in two cohorts: (i) community-dwelling older subjects of the Lothian Birth Cohort 1936; and (ii) patients with recent minor ischaemic stroke of the Mild Stroke Study. Imaging markers of small vessel disease (SVD) (white matter hyperintensities [WMH] on structural MRI, visual scores and volume; perivascular spaces; lacunes and microbleeds), and vascular risk measures were assessed in both cohorts. We assessed associations between retinal and brain measurements using structural equation modelling and regression analysis. In the Lothian Birth Cohort 1936 arteriolar fractal dimension accounted for 4% of the variance in WMH load. In the Mild Stroke Study lower arteriolar fractal dimension was associated with deep WMH scores (odds ratio [OR] 0.53; 95% CI, 0.32-0.87). No other retinal measure was associated with SVD. Reduced fractal dimension, a measure of vascular complexity, is related to SVD imaging features in older people. The results provide some support for the use of the retinal vasculature in the study of brain microvascular disease.
Periodically driven force protein translocation through a α-hemolysin biological nano-pore
Authors: Shahzad M. A.
Published: November 2018

We study the translocation of protein pulled under the action of time periodically external driving force through α-hemolysin nano-pore using Langevin molecular dynamical simulation. We observe that time depended external pulling force could enhance to more efficient translocation process as compared to protein translocation driven by constant external pulling force. We characterized the time depended force driven translocation mechanism by studying the gain in translocation as a function of frequency. We also present Golestanian plot which shows the modulated evolutions of number of translocation peptides, and of the probability distribution function with frequency as a results of the transmission of force oscillation to translocation dynamics.
Prolonged quiescence delays somatic stem cell-like division inCaenorhabditis elegansand is controlled by insulin signalling
Authors: Olmedo María , Mata-Cabana Alejandro , Rodríguez-Palero María Jesús , García-Sánchez Sabas , Fernández-Yañez Antonio , Merrow Martha , Artal-Sanz Marta
Published: November 2018

Cells can enter quiescence in adverse conditions and resume proliferation when the environment becomes favourable. Prolonged quiescence comes with a cost, reducing proliferation potential and survival. Interestingly, cellular quiescence also occurs in normal development, with many cells spending most of their lifetime at this state. Elucidating the mechanisms involved in surviving long-term quiescence and in maintenance of cellular proliferation potential will contribute to a better understanding of the process of tissue regeneration. Developmental arrest ofC. elegansat the L1 stage is an emerging model for the study of cellular quiescence and reactivation. During arrest, L1 larvae undergo a process that shares phenotypic hallmarks with the ageing of the adult. Interestingly, insulin signalling, a prominent pathway in the regulation of ageing, also balances cell proliferation and activation of stress resistance pathways during quiescence, becoming a candidate regulator of proliferation potential. Here we report that prolonged L1 quiescence delays reactivation of blast cell divisions inC. elegans, leading to a delay in the initiation of postembryonic development. This delay is accompanied by increased inter-individual variability. We propose that the delay in cell division results from the decline that animals suffer during L1 arrest. To that end, we show that insulin signalling modulates the rate of L1 ageing, affecting proliferative potential after quiescence. These findings support that the insulin signalling pathway has a comparable role in L1 arrest to that in ageing adults. Furthermore, we show that variable yolk provisioning to the embryos as a consequence of maternal age is one of the sources of inter-individual variability in recovery after quiescence of genetically identical animals. Taken together, these results support the relevance of L1 arrest as a model to studyin vivoproliferation after quiescence and to understand the mechanisms for maintenance of proliferation potential.
Stress-induced neuron remodeling reveals differential interplay between neurexin and environmental factors
Authors: Hart Michael P.
Published: November 2018

Neurexins are neuronal adhesion molecules important for synapse maturation, function, and plasticity. Neurexins have been genetically associated with neurodevelopmental disorders including autism spectrum disorders (ASDs) and schizophrenia, but can have variable penetrance and phenotypic severity. Heritability studies indicate that a significant percentage of risk for ASD and schizophrenia includes environmental factors, highlighting the poorly understood interplay between genetic and environmental factors in pathogenesis of these disorders. The singularC. elegansortholog of human neurexins,nrx-1, controls experience-dependent morphologic remodeling of a GABAergic neuron in adult males. Here I show that this GABAergic neuron’s morphology is altered in response to each of three environmental stressors (nutritional, heat, or genotoxic stress) applied during sexual maturation, but not during adulthood. Increased outgrowth of axon-like neurites following adolescent stress results from an altered morphologic plasticity that occurs upon entry into adulthood. Despite axonal remodeling being induced by each of the three stressors, only nutritional stress (starvation) impacts behavior and is dependent on neurexin/nrx-1. Heat or genotoxic stress during sexual maturation did not alter behavior despite inducing GABAergic neuron remodeling, and this remodeling was independent of neurexin/nrx-1. Remodeling induced by starvation stress was found be dependent on neuroligin/nlg-1, the canonical binding partner for neurexin/nrx-1, as well as the stress signaling transcription factorsFOXO/daf-16andHSF1/hsf-1, each of which was also found to have unique roles in remodeling induced by heat and UV stress. The differential molecular mechanisms underlying GABAergic neuron remodeling in response to different stressors, and the disparate effects of stressors on behavior, is a novel paradigm for understanding how genetics, environmental exposures, and plasticity may contribute to brain dysfunction in ASDs and schizophrenia.
Bridging the translational gap: Implementation of multimodal small animal imaging strategies for tumor burden assessment in a co-clinical trial
Authors: Blocker S.J. , Mowery Y.M. , Holbrook M. D. , Qi Y. , Kirsch D.G. , Johnson G.A. , Badea C.T.
Published: November 2018

In designing co-clinical cancer studies, preclinical imaging brings unique challenges that emphasize the gap between man and mouse. Our group is developing quantitative imaging methods for the preclinical arm of a co-clinical trial studying immunotherapy and radiotherapy in a soft tissue sarcoma model. In line with treatment for patients enrolled in the clinical trial SU2C-SARC032, primary mouse sarcomas are imaged with multi-contrast micro-MRI (T1 weighted, T2 weighted, and T1 with contrast) before and after immune checkpoint inhibition and pre-operative radiation therapy. Similar to the patients, after surgery the mice will be screened for lung metastases with micro-CT using respiratory gating. A systems evaluation was undertaken to establish a quantitative baseline for both the MR and micro-CT systems against which others systems might be compared. We have constructed imaging protocols which provide clinically-relevant resolution and contrast in a genetically engineered mouse model of sarcoma. We have employed tools in 3D Slicer for semi-automated segmentation of both MR and micro-CT images to measure tumor volumes efficiently and reliably in a large number of animals. Assessment of tumor burden in the resulting images was precise, repeatable, and reproducible. Furthermore, we have implemented a publicly accessible platform for sharing imaging data collected during the study, as well as protocols, supporting information, and data analyses. In doing so, we aim to improve the clinical relevance of small animal imaging and begin establishing standards for preclinical imaging of tumors from the perspective of a co-clinical trial.
eUTOPIA: Solution for omics data preprocessing and analysis
Authors: Marwah Veer Singh , Scala Giovanni , Kinaret Pia Anneli Sofia , Serra Angela , Alenius Harri , Fortino Vittorio , Greco Dario
Published: November 2018

Application of microarrays in omics technologies enables quantification of many biomolecules simultaneously. It is widely applied to observe the positive or negative effect on biomolecule activity in perturbed versus the steady state by quantitative comparison. Community resources, such as Bioconductor and CRAN, host tools based on R that have become standard for high-throughput analytics. However, there is a need for intuitive and easy-to-use platform to process omics data, visualize, and interpret results, which is computational skill neutral. We propose an integrated software solution, eUTOPIA, that implements a set of essential processing steps as a guided workflow presented to the user as an R Shiny application. eUTOPIA allows researchers to perform preprocessing and analysis of microarray data via a simple and intuitive graphical interface while using state of the art methods. eUTOPIA is free for academic use and can be obtained from the GitHub repository https://github.com/Greco-Lab/eUTOPIA.
Establishment and characteristic of an orthotopic implantation model of human hepatocellular carcinoma with Luc-GFP-labeled in nude mice
Authors: Zhang Jing-jing , Xu Min-hua , Wang Jie , Jin Xiao-bao , Ma Yan
Published: November 2018

Aim

To construct Luc-GFP-labeled human hepatocellular carcinoma (HCC) cell line with high metastatic potential. And to establish a spontaneous metastasis and conveniently monitored orthotopic model of hepatocellular carcinoma in nude mice. Methods: HCCLM3-Luc-GFP cell line stably expressing luciferase (Luc) and green fluorescent protein (GFP) was constructed by lentivirus transfection. The orthotopic xenograft model was established though cell suspension injection method and tumor fragment implanted method. The growth and metastasis of the tumors were observed by in vivo imaging and pathology. Results: HCCLM3-Luc-GFP, a highly metastatic HCC cell line with GFP expression and Luc activity, was obtained. The tumorigenic rates both of two approaches were 100%, but the lung metastatic rate was higher the former than the latter. Conclusion: The orthotopic model of highly metastatic and Luc-GFP-labeled HCC in nude mice was successfully established by above approaches, called as cell suspension injection method and tumor fragment implanted method, respectively. This study provides a new and effective means to monitor the growth of tumors in vivo and to evaluate the efficacy of anti-metastatic drugs against HCC.
STAT6 mRNA and protein knockdown using multiple siRNA sequences inhibits proliferation and induces apoptosis of the human colon adenocarcinoma cell line, HT-29
Authors: Salguero-Aranda C. , Sancho-Mensat D. , Sultan S. , Reginald A. , Chapman L.
Published: November 2018

The transcription factor STAT6 is strongly expressed in various tumours and is most highly expressed in malignant lymphomas and pancreatic, colorectal, prostate and breast cancers. STAT6 expression in colorectal cancer is associated with an increased malignancy, poor prognosis and poor survival rates. Colorectal cancer has an incidence of approximately 1,361,000 patientsper annumworldwide and approximately 60% of those cancers show STAT6 expression. Techniques aimed at reducing or blocking STAT6 expression may be useful in treating colorectal cancers. Celixir’s four proprietary STAT6 specific small interfering RNA (siRNA) sequences were testedin vitrousing the human colon adenocarcinoma cell line, HT-29. The four sequences were introduced individually and in combination into HT-29 cells at different concentrations (10 to 200 nM). Decreases in STAT6 mRNA and protein levels were analysed to confirm the transfection was successful. STAT6 knockdown effects were measured by analysing cell proliferation and apoptosis. Results showed that 100nM siRNA concentration was the most effective and all four individual sequences knocked-down STAT6 mRNA and protein by more than 50%. Although all individual sequences were capable of significantly inhibiting cell proliferation, STAT6.1 and STAT6.4 were the best. STAT6 silencing also significantly induced late and total apoptotic events. In conclusion, these results demonstrate that STAT6 siRNA sequences are capable of inhibiting the proliferation, and inducing late apoptosis, of HT-29 colon cancer cells and, in some instances, halving the number of cancer cells. These experiments will be repeated using xenografts of STAT6-expressing colon cancer cells in immunocompromised mice and the STAT6 siRNA sequences will be tested in other cancers in which STAT6 is expressed. The STAT6 siRNA sequences therefore represent a potential treatment for the most serious colorectal cancers and a wide variety of STAT6-expressing cancers.
A more physiological approach to lipid metabolism alterations in cancer: CRC-like organoids assessment
Authors: Cruz-Gil Silvia , Sanchez-Martinez Ruth , Wagner-Reguero Sonia , Stange Daniel , Schölch Sebastian , Werner Kristin , Ramirez de Molina Ana
Published: November 2018

Precision medicine might be the response to the recent questioning of the use of metformin as an anticancer drug in colorectal cancer (CRC). Thus, in order to establish properly its benefits, its application need to be assayed on the different progression stages of CRC. In this way, organoids imply a more physiological tool, representing a new therapeutic opportunity for CRC personalized treatment to assay tumor stage-dependent drugs effects. Since the lipid metabolism-related axis, ACSL/SCD, stimulates colon cancer progression and Metformin is able to rescuing the invasive and migratory phenotype conferred to cancer cells upon this axis overexpression; we checked ACSL/SCD status, its regulatory miRNAs and the effect of Metformin treatment in organoids as a model for specific and personalized treatment. Despite ACSL4 expression is upregulated in CRC-like organoids, Metformin is able to downregulate it, especially in the first stages. Besides, organoids are clearly more sensitive in this first stage (Apc mutated) to Metformin than current chemotherapeutic drugs such as fluorouracil (5-FU). Metformin performs an independent “Warburg effect” blockade to cancer progression and is able to reduce crypt stem cell markers expression such as Lgr5+. These results suggest a putative increased efficiency of the use of Metformin in the first stages of CRC than in advanced disease.
The spermidine acetyltransferase SpeG regulates transcription of the small RNA RprA
Authors: Hu Linda I. , Filippova Ekaterina V. , Dang Joseph , Pshenychnyi Sergii , Ruan Jiapeng , Kiryukhina Olga , Anderson Wayne F. , Kuhn Misty L. , Wolfe Alan J.
Published: November 2018

SpermidineN-acetyltransferase (SpeG) acetylates and thus neutralizes toxic polyamines. Studies indicate that SpeG plays an important role in virulence and pathogenicity of many bacteria, which have evolved SpeG-dependent strategies to control polyamine concentrations and survive in their hosts. InEscherichia coli, the two-component response regulator RcsB is reported to be subject to Nε-acetylation on several lysine residues, resulting in reduced DNA binding affinity and reduced transcription of the small RNArprA; however, the physiological acetylation mechanism responsible for this behavior has not been fully determined. Here, we performed an acetyltransferase screen and found that SpeG inhibitsrprApromoter activity in an acetylation-independent manner. Surface plasmon resonance analysis revealed that SpeG can physically interact with the DNA-binding carboxyl domain of RcsB. We hypothesize that SpeG interacts with the DNA-binding domain of RcsB and that this interaction might be responsible for SpeG-dependent inhibition of RcsB-dependentrprAtranscription. This work provides a model for SpeG as a modulator ofE. colitranscription through its ability to interact with the transcription factor RcsB. This is the first study to provide evidence that an enzyme involved in polyamine metabolism can influence the function of the global regulator RcsB, which integrates information concerning envelope stresses and central metabolic status to regulate diverse behaviors.
Phylogeny of the AustralianSolanum dioicumgroup using seven nuclear genes: Testing Symon’s fruit and seed dispersal hypotheses
Authors: Martine Christopher T. , Jordon-Thaden Ingrid E. , McDonnell Angela J. , Cantley Jason T. , Hayes Daniel S. , Roche Morgan D. , Frawley Emma S. , Gilman Ian S. , Tank David C.
Published: November 2018

The dioecious and andromonoeciousSolanumtaxa (previously described as the “S. dioicumgroup”) of the Australian Monsoon Tropics have been the subject of phylogenetic and taxonomic study for decades, yet much of their basic biology is still unknown. This is especially true for plant-animal interactions, including the influence of fruit form and calyx morphology on seed dispersal. We combine field/greenhouse observations and specimen-based study with phylogenetic analysis of seven nuclear regions obtained via a microfluidic PCR-based enrichment strategy and high-throughput sequencing, and present the first intron-containing nuclear gene dataset in the genusSolanumand the first species-tree hypothesis for theS. dioicumgroup. Our results suggest that epizoochorous trample burr seed dispersal (strongly linked to calyx accrescence) is far more common among AustralianSolanumthan previously thought and support the hypothesis that the combination of large fleshy fruits and endozoochorous dispersal represents a reversal in this study group. The general lack of direct evidence related to biotic dispersal (epizoochorous or endozoochorous) may be a function of declines and/or extinctions of vertebrate dispersers. Because of this, some taxa might now rely on secondary dispersal mechanisms (e.g. shakers, tumbleweeds, rafting) as a means to maintain current populations and establish new ones.
Neural mechanisms of perceptive and affective processing of body stimuli in Anorexia nervosa – are there developmental effects?
Authors: Horndasch Stefanie , Roesch Julie , Kratz Oliver , Vogel Anne , Heinrich Hartmut , Graap Holmer , Moll Gunther H. , Dörfler Arnd , Forster Clemens
Published: November 2018

Objective

Different components of body image processing seem to be reflected by different neural mechanisms. A core symptom of Anorexia nervosa (AN) is a disturbance of body image with correlates found on a neural level. The present study focusses at the neural processing of visual body stimuli of different weight categories in adolescent and adult AN patients.

Method

33 adolescents aged 12–18 years (15 AN patients, 18 control participants) and 36 adult women (19 AN patients, 17 control participants) underwent functional magnetic resonance imaging (fMRI) while performing a perceptive and an affective body image task involving photographic stimuli of women belonging to different BMI categories.

Results

Differential effects on activation depending on the BMI of the women shown in the pictures were found in frontal brain regions, the thalamus, caudate and the fusiform gyrus. Group effects differentiating between AN patients and control participants were seen mainly in the caudate and insula.

Discussion

During a perceptive task, diminished activation of regions involved in perceptive and evaluative functions as well as emotional reasoning was seen in AN. During evaluation of the neural processing in an affective task there was a tendency towards activation differences reflecting reduced ability of size estimation and impaired integration of visual and body perception with emotions.
Decades of native bee biodiversity surveys at Pinnacles National Park highlight the importance of monitoring natural areas over time
Authors: Meiners Joan M. , Griswold Terry L. , Carril Olivia Messinger
Published: November 2018

Thousands of species of bees are in global decline, yet research addressing the ecology and status of these wild pollinators lags far behind work being done to address similar impacts on the managed honey bee. This knowledge gap is especially glaring in natural areas, despite knowledge that protected habitats harbor and export diverse bee communities into nearby croplands where their pollination services have been valued at over $3 billion per year. Surrounded by ranches and farmlands, Pinnacles National Park in the Inner South Coast Range of California contains intact Mediterranean chaparral shrubland. This habitat type is among the most valuable for bee biodiversity worldwide, as well as one of the most vulnerable to agricultural conversion, urbanization and climate change. Pinnacles National Park is also one of a very few locations where extensive native bee inventory efforts have been repeated over time. This park thus presents a valuable and rare opportunity to monitor long-term trends and baseline variability of native bees in natural habitats. Fifteen years after a species inventory marked Pinnacles as a biodiversity hotspot for native bees, we resurveyed these native bee communities over two flowering seasons using a systematic, plot-based design. Combining results, we report a total of 450 bee species within this 109km2natural area of California, including 48 new species records as of 2012 and 95 species not seen since 1999. As far as we are aware, this species richness marks Pinnacles National Park as one of the most densely diverse places known for native bees. We explore patterns of bee diversity across this protected landscape, compare results to other surveyed natural areas, and highlight the need for additional repeated inventories in protected areas over time amid widespread concerns of bee declines.
Fatty acid profiles in adipose tissues and liver differ between horses and ponies
Authors: Adolph Stephanie , Schedlbauer Carola , Blaue Dominique , Schöniger Axel , Gittel Claudia , Brehm Walter , Fuhrmann Herbert , Vervuert Ingrid
Published: November 2018

Fatty acids, as key components of cellular membranes and complex lipids, may play a central role in endocrine signalling and the function of adipose tissue and liver. Thus, the lipid fatty acid composition may play a role in health and disease status in the equine. This study aimed to investigate the fatty acid composition of different tissues and liver lipid classes by comparing Warmblood horses and Shetland ponies under defined conditions. We hypothesized that ponies show different lipid patterns than horses in adipose tissue, liver and plasma. Six Warmblood horses and six Shetland ponies were housed and fed under identical conditions. Tissue and blood sampling were performed following a standardized protocol. A one-step lipid extraction, methylation and trans-esterification method with subsequent gas chromatography was used to analyse the total lipid content and fatty acid profile of retroperitoneal, mesocolon and subcutaneous adipose tissue, liver and plasma. In the adipose tissues, saturated fatty acids (SFAs) and n-9 monounsaturated fatty acids (n-9 MUFAs) were most present in ponies and horses. N-6 polyunsaturated fatty acids (n-6 PUFAs), followed by SFAs, were most frequently found in liver tissue and plasma in all animals. Horses, in comparison to ponies, had significantly higher n-6 PUFA levels in all tissues and plasma. In liver tissue, horses had significantly lower hepatic iso-branched-chain fatty acids (iso-BCFAs) than ponies. The hepatic fatty acid composition of selected lipid classes was different between horses and ponies. In the polar PL fraction, horses had low n-9 MUFA and n-3 PUFA contents but higher n-6 PUFA contents than ponies. Furthermore, iso-BCFAs are absent in several hepatic lipid fractions of horses but not ponies. The differences in fatty acid lipid classes between horses and ponies provide key information on the species- and location-specific regulation of FA metabolism, thus affecting health and disease risk.
Comparative analysis of sequencing technologies platforms for single-cell transcriptomics
Authors: Natarajan Kedar Nath , Miao Zhichao , Jiang Miaomiao , Huang Xiaoyun , Zhou Hongpo , Xie Jiarui , Wang Chunqing , Qin Shishang , Zhao Zhikun , Wu Liang , Li Bo , Hou Yong , Liu Shiping , Teichmann Sarah A.
Published: November 2018

All single-cell RNA-seq protocols and technologies require library preparation prior to sequencing on a platform such as Illumina. Here, we present the first report to utilize the BGISEQ-500 platform for scRNA-seq, and compare the sensitivity and accuracy to Illumina sequencing. We generate a scRNA-seq resource of 468 unique single-cells and 1,297 matched single cDNA samples, performing SMARTer and Smart-seq2 protocols on mESCs and K562 cells with RNA spike-ins. We sequence these libraries on both BGISEQ-500 and Illumina HiSeq platforms using single- and paired-end reads. The two platforms have comparable sensitivity and accuracy in terms of quantification of gene expression, and low technical variability. Our study provides a standardised scRNA-seq resource to benchmark new scRNA-seq library preparation protocols and sequencing platforms.
Emotionotopy in the Human Right Temporo-Parietal Cortex
Authors: Lettieri Giada , Handjaras Giacomo , Ricciardi Emiliano , Leo Andrea , Papale Paolo , Betta Monica , Pietrini Pietro , Cecchetti Luca
Published: November 2018

Humans use emotions to decipher complex cascades of internal events. However, which mechanisms link descriptions of affective states to brain activity is unclear, with evidence supporting either local or distributed processing. A biologically favorable alternative is provided by the notion of gradient, which postulates the isomorphism between functional representations of stimulus features and cortical distance. Here, we use fMRI activity evoked by an emotionally charged movie and continuous ratings of the perceived emotion intensity to reveal the topographic organization of affective states. Results show that three orthogonal and spatially overlapping gradients encode the polarity, complexity and intensity of emotional experiences in right temporo-parietal territories. The spatial arrangement of these gradients allows the brain to map a variety of affective states within a single patch of cortex. As this organization resembles how sensory regions represent psychophysical properties (e.g., retinotopy), we propose emotionotopy as a principle of emotion coding.
Valid post-clustering differential analysis for single-cell RNA-Seq
Authors: Zhang Jesse M. , Kamath Govinda M. , Tse David N.
Published: November 2018

Single-cell computational pipelines involve two critical steps: organizing cells (clustering) and identifying the markers driving this organization (differential expression analysis). State-of-the-art pipelines perform differential analysis after clustering on the same dataset. We observe that because clustering forces separation, reusing the same dataset generates artificially low p-values and hence false discoveries. We introduce a valid post-clustering differential analysis framework which corrects for this problem. We provide software at https://github.com/jessemzhang/tn_test.
Technical efficiency of private sector hospitals in India using data envelopment analysis
Authors: Gandhi Aradhana Vikas , Sharma Dipasha
Published: November 2018

Purpose

The purpose of this paper is to ascertain the performance of Indian hospitals in recent past and derive meaningful insights for policy makers and practicing managers in this area.

Design/methodology/approach

This paper analyses the technical efficiency of select Indian private hospitals using three related methodologies: data envelopment analysis (DEA), Malmquist Productivity Index (MPI) and Tobit regression. Two output variables (i.e. total income and profit after tax) and four input variables (i.e. cost of labour, net fixed assets, current assets and other operating expenses) were selected for the purpose of the study.

Findings

DEA analysis has shown that 14 out of 37 hospitals are found to be efficient under the Cooper and Rhodes model of DEA and 20 out of 37 hospitals are efficient under the Banker, Charles and Cooper model of DEA. The empirical results pertaining to MPI indicate an overall productivity progress in the private Indian hospital industry during the study period, which is largely due to technological advancement in the industry. Tobit regression demonstrates that chain affiliated, specialized and multi-city located hospitals exhibit a higher technical efficiency.

Research limitations/implications

This study has a limitation with reference to the unavailability of data on the input and output parameters of the model. The data related to the number of beds, number of doctors, number of nurses, etc., were not available for the period under consideration.

Originality/value

This study seems to be one of the few studies applying productivity and performance analysis using DEA, MPI and Tobit regression for the Indian private hospital industry.
Benchmarking model for factors influencing creation of negative electronic word of mouth
Authors: Kumar Sushant , Purbey Shankar
Published: November 2018

Purpose

The purpose of this paper is to develop a structural framework for factors influencing the creation of negative electronic word of mouth (WOM) at online forums, review portals, social networking sites or any other internet-based platform. Consumers frequently talk about consumption through WOM. With the unprecedented progress in digitalization of world, consumers usually tell stories about a product or service experience online. The study aims to identify the antecedents for negative electronic WOM (EWOM) and develop a structural model with different levels of factors.

Design/methodology/approach

Literature review and group judgment techniques are used to identify the factors responsible for negative WOM. The study uses interpretive structural modeling approach to develop a structural model representing interrelationships among factors. The model also represents the factors at different levels along with most and least dominant factors responsible for EWOM.

Findings

Seven factors responsible for negative electronic WOM are identified which are spread over three levels. First level of factors includes anxiety reduction, advice seeking, exertion of power (over companies) and social benefits (received), whereas the second level of factors includes altruism (negative WOM) and economic rewards. The most dominant factor identified is vengeance, which is at level three.

Practical implications

The study identified three levels of factors responsible for negative EWOM. Companies can strategies their resources to ensure that no consumer reaches beyond level one. Beyond level one, the involved factors may jeopardize the brand value and brand image of the company.

Originality/value

The study contributes to the literature by providing a structural model for negative EWOM. This model identifies the most and least dominant factors and guides managers to take necessary action to prevent negative EWOM.
Contextualising mainstreaming of disaster resilience concepts in the construction process
Authors: Amaratunga Dilanthi , Malalgoda Chamindi Ishara , Keraminiyage Kaushal
Published: November 2018

Purpose

Construction industry and the built environment professions play an important role in contributing to society’s improved resilience. It is therefore important to improve their knowledgebase to strengthen their capacities. This paper aims to identify gaps in the knowledgebase of construction professionals that are undermining their ability to contribute to the development of a more disaster resilient society. The paper also provides a series of recommendations to key actors in the built environment on how to more effectively mainstream disaster resilience in the construction process.

Design/methodology/approach

The paper reports the findings of 87 stakeholder interviews with: national and local government organisations; the community; non-governmental organisations, international non-governmental organisation and other international agencies; academia and research organisations; and the private sector, which were supplemented by a comprehensive analysis of key policies related to disaster resilience and management. The findings were validated using focus group discussions that were conducted as part of six organised stakeholder workshops.

Findings

The primary and secondary data generated a long list of needs and skills. Finally, the identified needs and skills were combined “like-for-like” to produce broader knowledge gaps. Some of the key knowledge gaps identified are: governance, legal frameworks and compliance; business continuity management; disaster response; contracts and procurement; resilience technologies, engineering and infrastructure; knowledge management; social and cultural awareness; sustainability and resilience; ethics and human rights; innovative financing mechanisms; multi stakeholder approach, inclusion and empowerment; post disaster project management; and multi hazard risk assessment. The study also identifies a series of recommendations to key actors in the built environment on how to more effectively mainstream disaster resilience in the construction process. The recommendations are set out in five key themes: education, policy, practice, research and cross-cutting.

Research limitations/implications

This study is part of an EU funded research project that is seeking to develop innovative and timely professional education that will update the knowledge and skills of construction professionals in the industry and enable them to contribute more effectively to disaster resilience building efforts.

Originality/value

The paper provides an extensive analysis of the gaps in the knowledgebase of construction professionals that are undermining their ability to contribute to the development of a more disaster resilient society. Accordingly, the paper recommends major changes in construction education, research, policy and practice with respect to mainstreaming disaster resilience within the construction process.
How entrepreneurial resilience generates resilient SMEs
Authors: Branicki Layla Jayne , Sullivan-Taylor Bridgette , Livschitz Sarah Rachael
Published: November 2018

Purpose

The purpose of this paper is to investigate how entrepreneurial behaviors support small and medium-sized enterprise (SME) resilience, refine the concept of entrepreneurial resilience, and identify how SME resilience might be promoted.

Design/methodology/approach

Qualitative data were collected in the UK via 11 focus groups which provided a sub-sample of 19 SME participants.

Findings

Because of their experience operating in uncertain environments, their direct experience of adversity, and the informal organizational settings they inhabit, entrepreneurs are often highly resilient and possess capabilities that enable SMEs to be resilient. Entrepreneurial resilience provides a basis for SME resilience that differs significantly from best practices as understood in larger firms.

Research limitations/implications

Exploratory qualitative research on a small sample (n=19) limits the generalizability of this work. Further research could quantitatively test the paper’s findings and/or examine the link between entrepreneurial resilience and the resilience of larger firms.

Practical implications

Rather than encouraging formal planning and redundancy, policy and practice designed to promote the resilience of SMEs should pay greater attention to building capacities to cope with uncertainty, generating and leveraging personal relationships, and activating the ability to experiment and think creatively in response to crises.

Originality/value

This paper draws on organizational psychology research to refine understanding of entrepreneurial resilience and to empirically examine and inductively theorize the multi-level relationships between entrepreneurial resilience and SME resilience.
The value propositions of multi-, cross-, and omni-channel retailing
Authors: Yrjölä Mika , Saarijärvi Hannu , Nummela Henrietta
Published: November 2018

Purpose

This study examines how retailers leverage multiple-channel strategies in relation to their customer value propositions (CVPs). More specifically, the purpose of this paper is to identify and analyze how multi-, cross- and omni-channel CVPs differ in terms of how they create value and which types of shopping motivations they aim to satisfy.

Design/methodology/approach

This conceptual paper presents and synthesizes three theoretical discussions pertaining to consumer shopping motivations, CVPs and multiple-channel retailing strategies into a tentative conceptual framework. Nine case examples are used to illustrate three different channel strategies: multi-channel, cross-channel and omni-channel retailing.

Findings

A tentative framework for understanding retailers’ channel strategies is suggested.

Practical implications

Retailers will benefit from a structured and synthesized understanding of the differences between multiple-channel strategies and their links to CVPs.

Originality/value

This paper introduces and integrates the concept of CVPs with the literature on multi-channel retailing strategies.
Applied spatial modelling for retail planning in tourist resorts
Authors: Newing Andy , Clarke Graham , Clarke Martin
Published: November 2018

Purpose

The purpose of this paper is to demonstrate that applied spatial modelling can inform the planning, delivery and evaluation of retail services, offering improvements over traditional retail impact assessment (RIA), especially within localities which experience seasonal fluctuations in demand.

Design/methodology/approach

The paper first describes a new theoretically informed tourist-based spatial interaction model (SIM) which has been custom-built and calibrated to capture the dynamics of the grocery sector in Cornwall, UK. It tests the power of the model to predict store performance for stores not used in the original calibration process, using client data for a new store development. The model is operationalised for the evaluation of various retail development schemes, demonstrating its contribution across a full suite of location decision making application areas.

Findings

The paper demonstrates that this highly disaggregate modelling framework can provide considerable insight into the local economic and social impacts of new store developments, rarely addressed in the retail location modelling literature.

Practical implications

Whilst SIMs have been widely used in retail location research by the private sector, the paper shows that such a model can have considerable value for public sector retail planning, a sector which seemed to have abandoned such models from the 1980s onwards, replacing them with often very limited and crude RIA.

Originality/value

The ability to review the forecasting capabilities of a model (termed post-investment review) are very rare in academic research. This paper offers new evidence that SIMs can support the RIA process.
How managers experience situations involving employee mental ill-health
Authors: Martin Angela , Woods Megan , Dawkins Sarah
Published: November 2018

Purpose

Mental health conditions such as depression are prevalent in working adults, costly to employers, and have implications for legal liability and corporate social responsibility. Managers play an important role in determining how employees’ and organizations’ interests are reconciled in situations involving employee mental ill-health issues. The purpose of this paper is to explore these situations from the perspective of managers in order to develop theory and inform practice in workplace mental health promotion.

Design/methodology/approach

Semi-structured interviews were conducted with 24 Australian managers who had supervised an employee with a mental health issue. Interview transcripts were content analyzed to explore themes in managers’ experiences.

Findings

Managing an employee with a mental health issue involves becoming aware of the issue, taking action to understand the situation and develop an action response, implementing the response and managing the ongoing situation. Each of these tasks had a range of positive and negative aspects to them, e.g., managing the situation can be experienced as both a source of stress for the manager but also as an opportunity to develop greater management skills.

Practical implications

Understanding line managers’ experiences is critical to successful implementation of HR policies regarding employee health and well-being. HR strategies for dealing with employee mental health issues need to consider implementation support for managers, including promotion of guiding policies, training, emotional support and creating a psychosocial safety climate in their work units or teams.

Originality/value

The insights gained from this study contribute to the body of knowledge regarding psychosocial safety climate, an emergent theoretical framework concerned with values, attitudes and philosophy regarding worker psychological health. The findings also have important implications for strategic human resource management approaches to managing mental health in the workplace.