bluuebunny/crossref_metadata_2025 huggingface dataset:
The N-Glycome regulates the endothelial-to-hematopoietic transition
Authors: Kasper Dionna M. , Hintzen Jared , Wu Yinyu , Ghersi Joey J. , Mandl Hanna K. , Salinas Kevin E. , Armero William , He Zhiheng , Sheng Ying , Xie Yixuan , Heindel Daniel W. , Park Eon Joo , Sessa William C. , Mahal Lara K. , Lebrilla Carlito , Hirschi Karen K. , Nicoli Stefania
Published: April 2019

Hematopoietic stem and progenitor cells (HSPCs) that establish and maintain the blood system in adult vertebrates arise from the transdifferentiation of hemogenic endothelial cells (hemECs) during embryogenesis. This endothelial-to-hematopoietic transition (EHT) is tightly regulated, but the mechanisms are poorly understood. Here, we show that microRNA (miR)-223-mediated regulation of N-glycan biosynthesis in endothelial cells (ECs) regulates EHT. Single cell RNA-sequencing revealed that miR-223 is enriched in hemECs and in oligopotent nascent HSPCs. miR-223 restricts the EHT of lymphoid/myeloid lineages by suppressing the expression of mannosyltransferase alg2 and sialyltransferase st3gal2, two enzymes involved in N-linked protein glycosylation. High-throughput glycomics of ECs lacking miR-223 showed a decrease of high mannose versus sialylated complex/hybrid sugars on N-glycoproteins involved in EHT such as the metalloprotease Adam10. Endothelial-specific expression of an N-glycan Adam10 mutant or of the N-glycoenzymes phenocopied the aberrant HSPC production of miR-223 mutants. Thus, the N-glycome plays a previously unappreciated role as an intrinsic regulator of EHT, with specific mannose and sialic acid modifications serving as key endothelial determinants of their hematopoietic fate.

One Sentence Summary

The N-glycan “sugar code” governs the hematopoietic fate of endothelial cells and regulates blood stem cell production in vivo.
Composition of the holdfast polysaccharide fromCaulobacter crescentus
Authors: Hershey David M. , Porfírio Sara , Jaehrig Bernhard , Heiss Christian , Azadi Parastoo , Fiebig Aretha , Crosson Sean
Published: April 2019

Surface colonization is central to the lifestyles of many bacteria. Exploiting surface niches requires sophisticated systems for sensing and attaching to solid materials.Caulobacter crescentussynthesizes a polysaccharide-based adhesin known as the holdfast at one of its cell poles, which enables tight attachment to exogenous surfaces. The genes required for holdfast biosynthesis have been analyzed in detail, but an inability to isolate sufficient quantities of holdfast has limited efforts to characterize its composition and structure. In this report we describe a method to extract the holdfast fromC. crescentuscultures and present a survey of its carbohydrate content. Glucose, 3-O-methylglucose, mannose, N-acetylglucosamine and xylose were detected in our extracts. Our results suggest that the holdfast contains a 1,4-linked backbone of glucose, mannose, N-acetylglucosamine and xylose that is decorated with branches at the C-6 positions of glucose and mannose. By defining the monosaccharide components in the polysaccharide, our work establishes a framework for characterizing enzymes in the holdfast pathway and provides a broader understanding of how polysaccharide adhesins are built.
Dorsoventral dissociation of Hox gene expression underpins the diversification of molluscs
Authors: Huan Pin , Wang Qian , Tan Sujian , Liu Baozhong
Published: April 2019

Unlike the Hox genes in arthropods and vertebrates, those in molluscs show diverse expression patterns and, with some exceptions, have generally been described as lacking the canonical staggered pattern along the anterior-posterior (AP) axis. This difference is unexpected given that almost all molluscs share highly conserved early development. Here, we show that molluscan Hox expression can undergo dynamic changes, which may explain why previous research observed different expression patterns. Moreover, we reveal that a key character of molluscan Hox expression is that the dorsal and ventral expression is dissociated. We then deduce a generalized molluscan Hox expression model, including conserved staggered Hox expression in the neuroectoderm on the ventral side and lineage-specific dorsal expression that strongly correlates with shell formation. This generalized model clarifies a long-standing debate over whether molluscs possess staggered Hox expression and it can be used to explain the diversification of molluscs. In this scenario, the dorsoventral dissociation of Hox expression allows lineage-specific dorsal and ventral patterning in different clades, which may have permitted the evolution of diverse body plans in different molluscan clades.
Joint species distribution modelling with HMSC-R
Authors: Tikhonov Gleb , Opedal Øystein , Abrego Nerea , Lehikoinen Aleksi , Ovaskainen Otso
Published: April 2019

Joint Species Distribution Modelling (JSDM) is becoming an increasingly popular statistical method for analyzing data in community ecology. JSDM allow the integration of community ecology data with data on environmental covariates, species traits, phylogenetic relationships, and the spatio-temporal context of the study, providing predictive insights into community assembly processes from non-manipulative observational data of species communities. Hierarchical Modelling of Species Communities (HMSC) is a general and flexible framework for fitting JSDMs, yet its full range of functionality has remained restricted to Matlab users only.

To make HMSC accessible to the wider community of ecologists, we introduce HMSC-R 3.0, a user-friendly R implementation of the framework described in Ovaskainen et al (Ecology Letters, 20 (5), 561-576, 2017) and further extended in several later publications.

We illustrate the use of the package by providing a series of five vignettes that apply HMSC-R 3.0 to simulated and real data. HMSC-R applications to simulated data involve single-species models, models of small communities, and models of large species communities. They demonstrate the estimation of species responses to environmental covariates and how these depend on species traits, as well as the estimation of residual species associations. They further demonstrate how HMSC-R can be applied to normally distributed data, count data, and presence-absence data. The real data consist of bird counts in a spatio-temporally structured dataset, environmental covariates, species traits and phylogenetic relationships. The vignettes demonstrate how to construct and fit many kinds of models, how to examine MCMC convergence, how to examine the explanatory and predictive powers of the models, how to assess parameter estimates, and how to make predictions.

The package, along with the extended vignettes, makes JSDM fitting and post-processing easily accessible to ecologists familiar with R.
First report of reference guided genome assembly of Black Bengal goat (Capra hircus)
Authors: Siddiki Amam Z. , Baten A. , Billah M. , Alam MAU. , Shawrob KSM. , Saha S. , Chowdhury M. , Rahman A.H. , Stear M. , Miah G. , Kumkum M. , Hossain M.A. , Mollah AKM. , Islam M.S. , Khan MKI.
Published: April 2019

Objectives

Black Bengal goat (Capra hircus), a member of the Bovidae family with the unique traits of high prolificacy, skin quality and low demand for food is the most socioeconomically significant goat breed in Bangladesh. Furthermore, the aptitude of adaptation and disease resistance capacity of it is highly notable which makes its whole genome information an area of research interest.

Data description

The genomic DNA of local (Chittagong, Bangladesh) healthy Black Bengal goat (Capra hircus) was extracted and then sequenced. The de novo assembly and structural annotations are being presented here. Sequencing was done using Illumina sequencing platform and the draft genome assembled is about 3.04 Gb. 26458 Genes were annotated using Maker gene annotations tool which predicted BUSCO Gene models. Universal Single Copy Orthologs refer 82.5% completeness of the assembled genome.
Local parasite pressures and host genotype may modulate epigenetic diversity in a mixed-mating fish
Authors: Berbel-Filho Waldir M. , de Leaniz Carlos Garcia , Morán Paloma , Cable Jo , Lima Sergio M. Q. , Consuegra Sofia
Published: April 2019

Parasite-mediated selection is one of the main drivers of genetic variation in natural populations. The persistence of asexual reproduction and self-fertilization, however, challenges the notion that low genetic variation and inbreeding compromise the host’s ability to respond to pathogens. DNA methylation represents a potential mechanism for generating additional adaptive variation under low genetic diversity. We compared genetic diversity (microsatellites and AFLPs), variation in DNA methylation (MSAFLPs), and parasite loads in three populations of Kryptolebias hermaphroditus, a unique mixed-mating (partially self-fertilising) fish, to analyse the potential adaptive value of DNA methylation in relation to genetic diversity and parasite loads. We found strong genetic population structuring, as well as differences in parasite loads and methylation levels among sampling sites and selfing lineages. Globally, the interaction between parasites and inbreeding with selfing lineages influenced DNA methylation, but parasites seemed more important in determining methylation levels at the local scale.
Identification of target candidate in Polycystic ovarian syndrome and invitro evaluation of therapeutic activity of the designed RNA Aptamer
Authors: Subramanian Manibalan , Ayyachamy Shobana , Manickam Kiruthika , Madasamy Swathi , Renganathan Venkatalakshmi , Achary Anant , Kandasamy Thirukumaran , Suhasini K , Roopathy Sharon
Published: April 2019

Prevalence of poly cystic ovary syndrome has been gradually increasing among adult females and Laparoscopy drilling on the ovary is only available temporary solution with high incidence of reoccurrence. Confidential gene disease association studies combined with various graph theory analysis on the biological protein interaction network of this syndrome has resulted, the 15 genes are overexpressed as central nodes among 434 proteins of disease specific proteome network. Through the Intensive Structural and functional prioritization analysis we have identified S100A8, calprotectin is the ideal drug target protein. In this research, we have constructed RNA library of consensus DNA sequence of Glucocorticoid Response Element (GRE) and screened the best RNA Aptamer fragment which competitively binds with minimal energy to inhibit the cell migration activity of S100A8. In order to prove this computational research, Lipofectamine mediated RNA aptamer delivered and Wound scrap assay in cell lines confirms that the synthesized 18mer oligo has significant molecular level inhibition activity toward cyst formation and spreading in poly cystic condition in ovary.
High-Throughput Single-Molecule Analysis via Divisive Segmentation and Clustering
Authors: White David S. , Goldschen-Ohm Marcel P. , Goldsmith Randall H. , Chanda Baron
Published: April 2019

Single-molecule approaches provide insight into the dynamics of biomolecules, yet analysis methods have not scaled with the growing size of data sets acquired in high-throughput experiments. We present a new analysis platform (DISC) that uses divisive clustering to accelerate unsupervised analysis of single-molecule trajectories by up to three orders of magnitude with improved accuracy. Using DISC, we reveal an inherent lack of cooperativity between cyclic nucleotide binding domains from HCN pacemaker ion channels embedded in nanophotonic zero-mode waveguides.
Exploring the lower thermal limits for transmission of human malaria, Plasmodium falciparum
Authors: Waite Jessica L. , Suh Eunho , Lynch Penelope A. , Thomas Matthew B.
Published: April 2019

The rate of malaria transmission is strongly determined by parasite development time in the mosquito, known as the extrinsic incubation period (EIP), since the quicker parasites develop, the greater the chance that the vector will survive long enough for the parasite to complete development and be transmitted. EIP is known to be temperature dependent but this relationship is surprisingly poorly characterized. There is a single degree-day model for EIP of Plasmodium falciparum that derives from a limited number of poorly controlled studies conducted almost a century ago. Here, we show that the established degree-day model greatly underestimates the rate of development of P. falciparum in both Anopheles stephensi and An. gambiae mosquitoes at temperatures in the range of 17-20°C. We also show that realistic daily temperature fluctuation further speeds parasite development. These novel results challenge one of the longest standing models in malaria biology and have potentially important implications for understanding the impacts of climate change.
Generative network models identify biological mechanisms of altered structural brain connectivity in schizophrenia
Authors: Zhang Xiaolong , Braun Urs , Harneit Anais , Zang Zhenxiang , Geiger Lena S. , Betzel Richard F. , Chen Junfang , Schweiger Janina , Schwarz Kristina , Reinwald Jonathan Rochus , Fritze Stefan , Witt Stephanie , Rietschel Marcella , Nöthen Markus M. , Degenhardt Franziska , Schwarz Emanuel , Hirjak Dusan , Meyer-Lindenberg Andreas , Bassett Danielle S. , Tost Heike
Published: April 2019

Background

Alterations in the structural connectome of schizophrenia patients have been widely characterized, but the mechanisms leading to those alterations remain largely unknown. Generative network models have recently been introduced as a tool to test the biological underpinnings of the formation of altered structural brain networks.

Methods

We evaluated different generative network models to investigate the formation of structural brain networks in healthy controls (n=152), schizophrenia patients (n=66) and their unaffected first-degree relatives (n=32), and we identified spatial and topological factors contributing to network formation. We further investigated the association of these factors to cognition and to polygenic risk for schizophrenia.

Results

Structural brain networks can be best accounted for by a two-factor model combining spatial constraints and topological neighborhood structure. The same wiring model explained brain network formation for all groups analyzed. However, relatives and schizophrenia patients exhibited significantly lower spatial constraints and lower topological facilitation compared to healthy controls. The model parameter for spatial constraint was correlated with the polygenic risk for schizophrenia and predicted reduced cognitive performance.

Conclusions

Our results identify spatial constraints and local topological structure as two interrelated mechanisms contributing to normal brain development as well as altered connectomes in schizophrenia. Spatial constraints were linked to the genetic risk for schizophrenia and general cognitive functioning, thereby providing insights into their biological basis and behavioral relevance.
Chromatin co-accessibility is highly structured, spans entire chromosomes, and mediates long range regulatory genetic effects
Authors: Young Greenwald William W. , D’Antonio-Chronowska Agnieszka , Benaglio Paola , Matsui Hiroko , Smith Erin N. , D’Antonio Matteo , Frazer Kelly A.
Published: April 2019

Chromatin accessibility identifies active regions of the genome, often at transcription factor (TF) binding sites, enhancers, and promoters, and contains regulatory genetic variation. Functionally related accessible sites have been reported to be co-accessible; however, the prevalence and range of co-accessibility is unknown. We perform ATAC-seq in induced pluripotent stem cells from 134 individuals and integrate it with RNA-seq, WGS, and ChIP-seq, providing the first long-range chromosome-length analysis of co-accessibility. We show that co-accessibility is highly connected, with sites having a median of 24 co-accessible partners up to 250Mb away. We also show that co-accessibility can de novo identify known and novel co-expressed genes, and co-regulatory TFs and chromatin states. We perform a cis and trans-caQTL, a trans-eQTL, and examine allelic effects of co-accessibility, identifying tens of thousands of trans-caQTLs, and showing that trans genetic effects can be propagated through co-accessibility to gene expression for cell-type and disease relevant genes.
Start from Scratch: Precisely Identify Massive Active Enhancers by Sequencing
Authors: Zhu Xiusheng , Huang Lei , Li Qing , Zhang Yubo
Published: April 2019

Enhancer loci identified by ChIP-Seq or other experimental methods occupy hundreds of base pairs on the genome. It is the paradox comparing with the motif analysis, which usually contains only a few or tens nucleotides, achieved by bioinformatics analysis. To address this issue, we develop an experimental method, termed as massive active enhancer sequencing (MAE-Seq), to designate active enhancer sequences from arbitrary sources of 25bp random DNA libraries. These sequences are constructed in a mini-promoter vector with fluorescent reporter. After transfection, positive cells are sorted out and for sequencing. With the results, we successfully identify hundreds known accurate active enhancer sequences as expected. Besides that, large amounts of unmarked regulatory elements (UREs) without epigenetic features are also been spotted. In conclusion, MAE-Seq would be useful to refine enhancer sequences and precisely annotate the genome in eukaryotes.
A high-fat diet induces a microbiota-dependent increase in stem cell activity in the Drosophila intestine
Authors: von Frieling Jakob , Faisal Muhammed Naeem , Sporn Femke , Pfefferkorn Roxana , Nolte Stella Solveig , Sommer Felix , Rosenstiel Philip , Roeder Thomas
Published: April 2019

Over-consumption of high-fat diets (HFDs) is associated with several pathologies. Although the intestine is the organ that comes into direct contact with all diet components, the impact of HFD has mostly been studied in organs that are linked to obesity and obesity related disorders. We used Drosophila as a simple model to disentangle the effects of a HFD on the intestinal structure and physiology from the plethora of other effects caused by this nutritional intervention. Here, we show that a HFD triggers activation of intestinal stem cells in the Drosophila midgut. This stem cell activation was transient and preceded by induction of JNK signaling in enterocytes. JNK (basket) within enterocytes was essential for activation of stem cells in response to a HFD. Moreover, this nutritional intervention leads to upregulation of the cytokine upd3 in enterocytes, a reaction that is known to trigger STAT signaling in intestinal stem cells followed by their activation. We also showed that the indigenous microbiota was essential for HFD-induced stem cell activation because this response was blunted in germ-free flies lacking a microbiota. Moreover, chronic HFD feeding of flies markedly altered both the microbiota composition and bacterial load. Although HFD-induced stem cell activity was transient, long-lasting changes to the cellular composition, including a substantial increase in the number of enteroendocrine cells, were observed. Taken together, a HFD enhances stem cell activity in the Drosophila gut and this effect is completely reliant on the indigenous microbiota and also dependent on JNK signaling within intestinal enterocytes.

Author summary

High-fat diets have been associated with a plethora of morbidities. The major research focus has been on its effects on obesity related disorders, mostly omitting the intestine, although it is the organ that makes the first contact with all diet components. Here, we aimed to understand the direct effects of HFD on the intestine itself. Using Drosophila as a model, we showed that HFD induced a transient activation of intestinal stem cells. This response completely depended on JNK signaling in enterocytes. Mechanistically, we found that HFD induces JNK signaling in enterocytes, which triggers production of the cytokine upd3. This, in turn activates STAT signaling in intestinal stem cells, leading to their activation. Surprisingly, we found that a HFD triggered induced stem cell activation critically depends on the indigenous microbiota, as in germ free flies this reaction was completely abolished. Moreover, HFD changed both, composition and abundance of the microbiota. As fecal transfer experiments failed to recapitulate the HFD phenotype, we assume that the increased bacterial load is the major cause for the HFD triggered stem cell activation in the intestine.
Host developmental stage is associated with shifts in the exosphere microbiome of urban-farmed Asian green leafy vegetables
Authors: Pavagadhi Shruti , Bandla Aditya , Hong Miko Poh Chin , Umashankar Shivshankar , Ting Yeap Yoon , Swarup Sanjay
Published: April 2019

Green leafy vegetables (GLV’s) comprise a significant part of urban South-East Asian (SEA) diets and are intensively farmed in SEA cities, including Singapore. Urban farming practices and urban-adapted vegetable cultivars likely select for specific above- and below-ground microbial communities – microbiomes – that assemble in close proximity to the plant tissues – the exosphere. A healthy exosphere microbiome is important for plant growth and safe human consumption. Using 16S rDNA gene amplicon sequencing compositional analyses, we show here that the exosphere microbiome of two commonly-consumed GLV’s – Choy Sum (Brassica oleracea Alboglabra Group) and Gai Lan (Brassica chinensis var. parachinensis) – dominated by Gammaproteobacteria, Alphaproteobacteria, Bacteroidia and Actinobacteria. Shifts in exosphere microbiome composition were strongly associated with plant developmental stage. Finally, microbial taxa consistently detected in the exosphere comprise a small subset, which are predicted to harbour plant-beneficial traits.

Significance

Among plant crops, GLVs form an integral part of the Asian diet, especially so in Southeast Asia. Some of these GLVs have short life-cycles (∽30-45 days), which makes them suitable for urban farms in terms of cost advantage as short cycle crops are preferred in urban farms. From a food-security perspective, GLVs forms an important target food group and efforts are being made to increase its productivity to meet the increasing food demands. Current farming practices often place lot of importance on chemical fertilizers and nutrient inputs to improve the fertility of non-arable urban lands to increase the crop productivity. Furthermore, farms in urban settings are also associated with anthropogenic inputs and eutrophic conditions. These together, contribute to negative environmental externalities questioning the sustainability and eco-sustenance of urban farming. Microbial based management systems can not only resolve these challenging issues, but can also enhance plant growth, nutrient use efficiency and disease tolerance. However, their use as microbial adjuncts to agricultural practices is currently limited in urban environments, which could possibly be due to the restricted knowledge-base on these urban phytobiomes.
ATM and ATR Influence Meiotic Crossover Formation Through Antagonistic and Overlapping Functions inC. elegans
Authors: Li Wei , Yanowitz Judith
Published: April 2019

During meiosis, formation of double-strand breaks (DSBs) and repair by homologous recombination between homologs creates crossovers (COs) that facilitate chromosome segregation. CO formation is tightly regulated to ensure the integrity of this process. The DNA damage response kinases, Ataxia-telangiectasia mutated (ATM) and RAD3-related (ATR) have emerged as key regulators of CO formation in yeast, flies, and mice, influencing DSB formation, repair pathway choice, and cell cycle progression. The molecular networks that ATM and ATR influence during meiosis are still being resolved in other organisms. Here we show thatCaenorhabditis elegansATM and ATR homologs, ATM-1 and ATL-1 respectively, act at multiple steps in CO formation to ultimately ensure that COs are formed on all chromosomes. We show a role for ATM-1 in regulating the choice of repair template, biasing use of the homologous chromosome instead of the sister chromatid. Our data suggests a model in which ATM-1 and ATL-1 have antagonistic roles in very early repair processing, but are redundantly required for accumulation of the RAD-51 recombinase at DSB sites. We propose that these features of ATM-1 and ATL-1 ensure both CO formation on all chromosomes and accurate repair of additional DSBs.

Article Summary

Crossovers formed during meiosis connect homologs and properly align them for cell division. The central importance of crossovers is underscored by the existence of extensive regulatory processes that ensures the proper execution of these events. This paper explores the evolutionary conserved roles of the central DNA damage response kinases, ATM and ATR, in crossover formation. The authors show that these kinases function together as rheostats to promote timely formation of crossovers on all chromosomes but to limit extensive DNA damage. This work provides a platform for identifying conserved meiotic targets of ATM and ATR that affect fertility across species.
Dynamic changes in the urine proteome in two ovarian cancer rat models
Authors: Li Yuqiu , Zhang Linpei , Meng Wenshu , Gao Youhe
Published: April 2019

Ovarian cancer is the most lethal gynecological malignancy in women, and it is likely to metastasize and has a poor prognosis. The early and reliable diagnosis and monitoring of ovarian cancer is very important. Without a homeostasis mechanism, urine can reflect early systemic changes in the body and has a great potential to be used for the early detection of cancer. This study tested whether early changes could be detected in two ovarian cancer rat models. Two rat models were established by either intraperitoneal (i.p.) or orthotopic (o.t.) injection of NuTu-19 ovarian cancer cells in female Fischer344 rats. Urine samples from ovarian cancer rats were collected at five time points during cancer development, and urinary proteins from the rats were profiled by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Compared with pre-injection samples, 49 differential proteins that have human orthologues were significantly changed in the orthotopically injected model. Among them, 24 of the differential proteins have previously been reported to be associated with ovarian cancer, six of which were reported to be biomarkers of ovarian cancer. On the 7th day after orthotopic injection, four differential proteins (APOA1, OX2G, CHMP5, HEXB) were identified before obvious metastases appeared. In the intraperitoneal injection model, 76 differential proteins were changed during the course of ovarian cancer development. The results show that urine proteins could enable the early detection and monitoring of ovarian cancer progression and could lay a foundation for further exploration of the biomarkers of ovarian cancer.
Post-ictal neuronal network remodeling and Wnt pathway dysregulation in the intra-hippocampal kainate mouse model of temporal lobe epilepsy
Authors: Gupta Kunal , Schnell Eric
Published: April 2019

Mouse models of mesial temporal lobe epilepsy recapitulate aspects of human epilepsy, which is characterized by neuronal network remodeling in the hippocampal dentate gyrus. Observational studies suggest that this remodeling is associated with altered Wnt pathway signaling, although this has not been experimentally examined. We used the well-characterized mouse intrahippocampal kainate model of temporal lobe epilepsy to examine associations between post-seizure hippocampal neurogenesis and altered Wnt signaling. Tissue was analyzed using immunohistochemistry and confocal microscopy, and transcriptome analysis was performed on RNA extracted from anatomically micro-dissected dentate gyri. Seizures increased neurogenesis and dendritic arborization of newborn hippocampal dentate granule cells in peri-ictal regions, and decreased neurogenesis in the ictal zone, 2-weeks after kainate injection. Interestingly, administration of the novel canonical Wnt pathway inhibitor XAV939 daily for 2-weeks after kainate injection further increased dendritic arborization in peri-ictal regions after seizure, without an effect on baseline neurogenesis in control animals. Transcriptome analysis of dentate gyri demonstrated significant canonical Wnt gene dysregulation in kainate-injected mice across all regions for Wnt3, 5a and 9a. Intriguingly, certain Wnt genes demonstrated differential patterns of dysregulation between the ictal and peri-ictal zones, most notably Wnt5B, 7B and DKK-1. Together, these results demonstrate regional variation in Wnt pathway dysregulation in the early post-ictal period, and surprisingly, suggest that some Wnt-mediated effects might actually temper aberrant neurogenesis after seizures. The Wnt pathway may therefore provide suitable targets for novel therapies that prevent network remodeling and the development of epileptic foci in high-risk patients.
Targeting against HIV/HCV Co-infection using Machine Learning-based multitarget-quantitative structure-activity relationships (mt-QSAR) Methods
Authors: Wei Yu , Li Wei , Du Tengfei , Hong Zhangyong , Lin Jianping
Published: April 2019

Co-infection between HIV-1 and HCV is common today in certain populations. However, treatment of co-infection is full of challenges with special consideration for potential hepatic safety and drug-drug interactions. Multitarget inhibitors with less toxicity may provide a promising therapeutic strategy for HIV/HCV co-infection. However, identification of one molecule acting on multiple targets simultaneously by experimental evaluation is costly and time-consuming. In silico target prediction tools provide more opportunities for the development of multitarget inhibitors. In this study, by combining naive Bayesian (NB) and support vector machine (SVM) algorithms with two types of molecular fingerprints (MACCS and ECFP6), 60 classification models were constructed to predict the active compounds toward 11 HIV-1 targets and 4 HCV targets based on the multitarget-quantitative structure-activity relationships (mt-QSAR). 5-fold cross-validation and test set validation was performed to confirm the performance of 60 classification models. Our results show that 60 mt-QSAR models appeared to have high classification accuracy in terms of ROC-AUC values ranging from 0.83 to 1 with a mean value of 0.97 for HIV-1 models, and ROC-AUC values ranging from 0.84 to 1 with a mean value of 0.96 for HCV. Furthermore, the 60 models were applied to comprehensively predict the potential targets for additional 46 compounds including 27 approved HIV-1 drugs, 10 approved HCV drugs and 9 selected compounds known to be active on one or more targets of HIV-1 or those of HCV. Finally, 18 hits including 7 HIV-1 approved drugs, 4 HCV approved drugs and 7 compounds were predicted to be HIV/HCV co-infection multitarget inhibitors. The reported bioactivity data confirmed that 7 compounds actually interacted with HIV-1 and HCV targets simultaneously with diverse binding affinities. Of those remaining predicted hits and chemical-protein interaction pairs involving the potential ability to suppress HIV/HCV co-infection deserve further investigation by experiments. This investigation shows that the mt-QSAR method is available to predict chemical-protein interaction for discovering multitarget inhibitors and provide a unique perspective on HIV/HCV co-infection treatment.
Resistance toCandidatusLiberibacter solanacearum in tomato landraces from Mexico
Authors: Garzón-Tiznado José A. , López-Orona Carlos A. , Castro-Espinoza Luciano , Velarde-Félix Sixto , Figueroa-Pérez Marely G. , Retes-Manjarrez Jesús E.
Published: April 2019

CandidatusLiberibacter solanacearum (CLso) is an economically important plant-pathogen of tomato (Solanum lycopersicum) crops in the United States, Mexico, Central America, and New Zealand. Currently, there are no reports of resistance toCLsoin tomato cultivars. Identification and development ofCLso-resistant cultivars may offer the most efficient way to manage this tomato disease. Resistance of 46 tomato landraces collected in different regions of Mexico, representing a wide range of genetic variability from this country was evaluated. Two assays were done in consecutively years to assess the resistance toCLsounder greenhouse conditions. Plants from both tests were inoculated withCLsothrough 20Bactericera cockerelliinsects per plant. In the first trial, landraces FC22 and FC44 showed a significantly higher proportion of resistant plants, less symptoms severity, and longer incubation time, followed by landraces FC40 and FC33 compared with the rest of the 42 landraces and 2 susceptible cultivars 60 days post inoculation (dpi). In the second assay, only landraces FC22 and FC44 had again significantly higher proportion of resistant plants, less symptoms severity, relative lowerCLsotiters, and longer incubation time in comparison with landraces FC40 and FC33 and the two susceptible cultivars 60 dpi, corroborating their resistance toCLso. Presence ofCLsoDNA in all resistant plants from both assays discards scape plants and indicates that the methodology used was adequate to discriminate between resistant and susceptible plants. These results confirm that landraces FC22 and FC44 are promising resistant sources for the development ofCLso-resistant cultivars of tomato.

Author summary

The bacterium “CandidatusLiberibacter solanacearum” (CLso) is an important plant-pathogen of tomato crops in the United States, Mexico, Central America, and New Zealand. Tomato growers are lacking of cultivars with resistance to this pathogen and the development of resistant cultivars of this crop would make a sustainable business for these growers and healthy tomato consumption for humans. Tomato landraces from countries that are center of domestication of cultivated crops like Mexico, are potentially sources of resistance to plant-pathogens. Therefore, two tests were done looking for resistance sources to this pathogen and we found two tomato landraces (FC22 and FC44) showing high level of resistance toCLsobecause they had significantly higher resistant plants, less symptoms severity, lowerCLsoDNA concentration, and delay of the first symptoms in the inoculated plants in comparison with the two commercial cultivars and 44 tomato landraces collected from Mexico 60 days post infection. These landraces are promising resistant sources for the development ofCLso-resistant cultivars of tomato.
Generic pulse width modulation model, based on generalized inverses and applied to voltage source inverters
Authors: Paul-Etienne Vidal , Cailhol Simon , Rotella Frédéric , Fadel Maurice
Published: April 2019

Purpose

This paper aims to develop a method for a unified model of pulse width modulation (PWM) voltage source inverters (VSI). This generic method, based on a common and easy-to-use carrier-based modulation, allows to generate the exhaustive solution set for a given PWM-VSI.

Design/methodology/approach

The use of the generalized inverse theory is developed to express the PWM solution set for the duty cycle. Indeed, the infinite number of PWM solutions is demonstrated. To explore this solution set, the unified model described exhibits degrees of freedom. The admissible margins to set the degree of freedom are highlighted. Some experimental results are presented.

Findings

It is demonstrated how the degree of freedom can be directly connected with efficiency indicators such as common mode voltage, inverter linearity and switching losses. The expression of the PWM solution set boundaries is clearly expressed.

Research limitations/implications

Further studies should explore how the degree of freedom can be connected with parameters associated with the current (and not the voltage as described in this paper).

Practical implications

The paper includes implications for the development of a more generic approach for PWM multilevel VSI.

Originality/value

This paper fulfils a mathematical frame to ease the expression of PWM scheme.
Characteristics extraction and numerical analysis of the rough surface macro-morphology
Authors: Sun Qingchao , Mu Xiaokai , Yuan Bo , Xu Jiawen , Sun Wei
Published: April 2019

Purpose

This paper aims to distinguish the relationship between the morphology characteristics of different scales and the contact performance of the mating surfaces. Also, an integrated method of the spectrum analysis and the wavelet transform is used to separate the morphology characteristics of the actual machined parts.

Design/methodology/approach

First, a three-dimensional (3D) surface profilometer is used to obtain the surface morphology data of the actual machined parts. Second, the morphology characteristics of different scales are realized by the wavelet analysis and the power spectral density. Third, the reverse modeling engineering is used to construct the 3D contact models for the macroscopic characteristics. Finally, the finite element method is used to analyze the contact stiffness and the contact area of the 3D contact model.

Findings

The contact area and the nominal contact pressure Pn have a nonlinear relationship in the whole compression process for the 3D contact model. The percentage of the total contact area of the macro-scale mating surface is about 70 per cent when the contact pressure Pn is in the range of 0-100 MPa, and the elastic contact area accounts for the vast majority. Meanwhile, when the contact pressure Pn is less than 10MPa, the influence factor (the relative error of contact stiffness) is larger than 50 per cent, so the surface macro-scale morphology has a weakening effect on the normal contact stiffness of the mating surfaces.

Originality/value

This paper provides an effective method for the multi-scale separation of the surface morphology and then lays a certain theoretical foundation for improving the surface quality of parts and the morphology design.
Co-creation and co-destruction of service quality through customer-to-customer interactions
Authors: Luo Jiaqi (Gemma) , Wong IpKin Anthony , King Brian , Liu Matthew Tingchi , Huang GuoQiong
Published: April 2019

Purpose

This study draws on the service-dominant (S-D) logic paradigm to examine value co-creation and co-destruction. As these phenomena are driven by positive and negative “customer-to-customer” (C2C) interactions, this paper aims to examine their influence on tourist perceptions of service quality and how they shape affective responses toward tourism and hospitality services and brand loyalty.

Design/methodology/approach

Following a comprehensive literature review, the authors used convenience sampling to gather a large sample of tourists at Shanghai Disneyland, a recently opened and already popular international tourism attraction. Structural equation modeling was used to test for direct and moderated relationships.

Findings

The findings indicated that positive and negative C2C interactions have significant though differential impacts on customer responses. Furthermore, it was found that visitor arousal mediated the relationship between service quality and brand loyalty. Prior experience was identified as a moderator in the co-creation and co-destruction process during service encounters.

Practical implications

This paper is one of the first to examine the concept of co-destruction in the tourism and hospitality context. It contributes to the literature by demonstrating the merits of proactive service provision by tourism operators, taking account of both the co-creation and co-destruction of value.

Originality/value

The study extends the literature by taking account of both positive and negative C2C interactions when examining co-creation and co-destruction in the context of service encounters. It also contributes to knowledge by assessing the asymmetry of such interactions in the context of the customer experience.
Testing for detection of crack in rotor using vibration analysis: an experimental approach
Authors: Shah Bhumi Ankit , Vakharia Dipak P.
Published: April 2019

Purpose

Many incidents of rotor failures are reported due to the development and propagation of the crack. Condition monitoring is adopted for the identification of symptoms of the crack at very early stage in the rotating machinery. Identification requires a reliable and accurate vibration analysis technique for achieving the objective of the study. The purpose of this paper is to detect the crack in the rotating machinery by measuring vibration parameters at different measurement locations.

Design/methodology/approach

Two different types of cracks were simulated in these experiments. Experiments were conducted using healthy shaft, crack simulated shaft and glued shaft with and without added unbalance to observe the changes in vibration pattern, magnitude and phase. Deviation in vibration response allows the identification of crack and its location. Initial data were acquired in the form of time waveform. Run-up and coast-down measurements were taken to find the critical speed. The wavelet packet energy analysis technique was used to get better localization in time and frequency zone.

Findings

The presence of crack changes the dynamic behavior of the rotor. 1× and 2× harmonic components for steady-state test and critical speed for transient test are important parameters in condition monitoring to detect the crack. To separate the 1× and 2× harmonic component in the different wavelet packets, original signal is decomposed in nine levels. Wavelet packet energy analysis is carried out to find the intensity of the signal due to simulated crack.

Originality/value

Original signals obtained from the experiment test set up may contain noise component and dominant frequency components other than the crack. Wavelet packets contain the crack-related information that are identified and separated in this study. This technique develops the condition monitoring procedure more specific about the type of the fault and accurate due to the separation of specific fault features in different wavelet packets. From the experiment end results, it is found that there is significant rise in a 2× energy component due to crack in the shaft. The intensity of a 1× energy component depends upon the shaft crack and unbalance orientation angle.
Category-based or piecemeal-based processing? A dual model of web-mobile service extension behavior
Authors: Gong Xiang , Zhang Kem Z.K. , Chen Chongyang , Zhao Sesia J. , Lee Matthew K.O.
Published: April 2019

Purpose

The advancements of mobile technologies and devices have greatly facilitated the extension of online services from web to mobile environments. Drawing on the categorization theory, the purpose of this paper is to explore the impact of perceived entitativity on users’ web-mobile service extension behavior. The research model considers how perceived entitativity serves as a category cue to link the category- and piecemeal-based processing and shape users’ adoption of extended mobile services.

Design/methodology/approach

An online survey (n=552) was conducted to empirically test the model. The data were analyzed by structural equation modeling approach.

Findings

The results offer two major findings. First, performance expectancy, perceived controllability and subjective norm are important antecedents of users’ usage intention. Second, perceived entitativity has three types of effects on usage intention: it exerts a direct and positive influence on usage intention; it indirectly facilitates usage intention through increasing PE and perceived controllability; and it moderates the relationship between subjective norm and usage intention.

Originality/value

This study contributes to the literature by taking into account the interplay of category- and piecemeal-based processing to understand consumers’ web-mobile service extension behavior.
The influence of senior executive support informatization on radical innovation performance
Authors: Li Chao , Han Shuihua , Kumar Sameer , Feng Wei-Xi
Published: April 2019

Purpose

The purpose of this paper is to define the conceptualization and measurement of informatization according to a capability perspective reflected in three aspects: IT managerial capability, IT-enabled capability and IT infrastructure capability.

Design/methodology/approach

Manufacturing enterprises in China’s Northeast and Pearl River Delta regions in China were selected to empirically examine, using structural equation modeling, the association between a firm’s senior executive support informatization and radical innovation performance.

Findings

Results show a significant positive relationship between senior executive support and IT-enabled capability. However, there are no significant positive influences uncovered between senior executive support and IT managerial capability and IT infrastructure capability. The authors find significant positive effects of IT managerial capability, IT-enabled capability and IT infrastructure capability on radical innovation performance. Lastly, the joint effect of senior executive support and external institutional environment has no significant influence on informatization.

Originality/value

This study offers improved understanding for enterprises and academia about the effect of senior executive support informatization on radical innovation performance. It also suggests taking effective measures to highlight the management level and enterprises’ radical innovation performance.
Complexity and performance measurement for retail supply chains
Authors: Ekinci Esra , Baykasoğlu Adil
Published: April 2019

Purpose

The purpose of this paper is to present how complexity on retail supply chains should be recognized and its relationship with the performance. Different supply chain structures and planning horizons have been analyzed to support practitioners taking action on the short, mid and long terms. Confronted complexity in the supply chain has been categorized as system, perceived and value adding. This would also help practitioners to understand the sources of the complexity and if the complexity is useful for the system or not.

Design/methodology/approach

Three different retail supply chain scenarios – each concentrating on different planning horizons – have been simulated on system dynamics software STELLA. Using the new classification scheme for complexity and suggested performance metrics, a multi-perspective analysis has been performed on the STELLA output.

Findings

The results and the methodology can be easily applicable in practice to support decision-making process and to answer “what-if” type scenario analysis on systems design and configuration. Using the selected complexity metrics, complexity of the system considering time factor – static and dynamic – and different information levels – system, perceived and value adding – has been evaluated. Used complexity metrics indicate the problematic areas in the systems to be distinguished.

Originality/value

This paper uses system dynamics modeling in retail supply chains to derive insight about dynamic behavior and to represent the complex interactions and a new classification scheme for system complexity.