bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential proteomic analysis by SWATH-MS unravels the most dominant mechanisms underlying yeast adaptation to non-optimal temperatures under anaerobic conditions
Authors: Pinheiro Tânia , Lip Ka Ying Florence , García-Ríos Estéfani , Querol Amparo , Teixeira José , van Gulik Walter , Guillamón José Manuel , Domingues Lucília
Published: January 2020

Elucidation of temperature tolerance mechanisms in yeast is essential for enhancing cellular robustness of strains, providing more economically and sustainable processes. We investigated the differential responses of three distinctSaccharomyces cerevisiaestrains, an industrial wine strain, ADY5, a laboratory strain, CEN.PK113-7D and an industrial bioethanol strain, Ethanol Red, grown at sub- and supra-optimal temperatures under chemostat conditions. We employed anaerobic conditions, mimicking the industrial processes. The proteomic profile of these strains was performed by SWATH-MS, allowing the quantification of 997 proteins, data available via ProteomeXchange (PXD016567). Our analysis demonstrated that temperature responses differ between the strains; however, we also found some common responsive proteins, revealing that the response to temperature involves general stress and specific mechanisms. Overall, sub-optimal temperature conditions involved a higher remodeling of the proteome. The proteomic data evidenced that the cold response involves strong repression of translation-related proteins as well as induction of amino acid metabolism, together with components related to protein folding and degradation while, the high temperature response mainly recruits amino acid metabolism. Our study provides a global and thorough insight into how growth temperature affects the yeast proteome, which can be a step forward in the comprehension and improvement of yeast thermotolerance.
Correlation-based and feature-driven mutation signature analyses to identify genetic features associated with DNA mutagenic processes in cancer genomes
Authors: Jeong Hye Young , Yoo Jinseon , Kim Hyunwoo , Kim Tae-Min
Published: January 2020

Mutation signatures represent unique sequence footprints of somatic mutations resulting from specific DNA mutagenic and repair processes; however, their causal associations and potential utility for genome research remain largely unknown. In this study, we performed PanCancer-scale correlative analyses to identify the genomic features associated with tumor mutation burdens (TMB) and individual mutation signatures. We observed that TMB was correlated with tumor purity, ploidy, and the level of aneuploidy, as well as with the expression of cell proliferation-related genes representing genomic covariates in evaluating TMB. Correlative analyses of mutation signature levels with genes belonging to DNA damage-repair processes revealed that deficiencies ofNHEJ1andALKBH3may elevate TMB levels in cancer genomes accompanying APOBEC overactivity and DNA mismatch repair deficiency, respectively. We further employed a strategy to identify feature-driven,de novomutation signatures and demonstrated they can be reconstructed using known causal features such as APOBEC overexpression, MLH1 underexpression,POLEmutations, and the level of homologous recombination deficiency. We further demonstrated, that tumor hypoxia-related mutation signatures are similar to those associated with APOBEC suggesting that APOBEC-related mutagenic activity mediates hypoxia-related mutational consequences in cancer genomes, and also, that mutation signatures can be further used to predict hypoxic tumors. Taken together, our study advances mutation signature-level mechanistic insights in cancer genomes, extending categories of cancer-relevant mutation signatures and their potential biological implications.

Author summary

Mutation signature analysis is powerful in deciphering the causative mutagenic events and their contributions in individual cancer genomes, but the causal relationship of individual mutation signatures are still largely unknown. PanCancer-scaled correlative analysis revealed mutation resource candidates in cancer genomes such asNHEJ1andALKBH3deficiencies that may facilitate the accumulation of mutations in the setting of APOBEC overactivity and DNA mismatch repair deficiency, respectively. A feature-driven mutation discovery approach was employed to identify the mutation signatures representing homologous recombination deficiency and tumor hypoxia, the extent of which may serve as mutation-based phenotypic measures, previously estimated by DNA copy number alterations and mRNA expression signatures, respectively. Our study advances our understanding into the mechanistic insights of mutation signatures and proposes a method to utilize somatic mutations as a molecular proxy in terms of mutation signatures.
Multidrug resistance and high prevalence of class 1 integrons inEscherichia coliisolated from waters and vegetables in Nsukka and Enugu, Nigeria
Authors: Chigor Chinyere B. , Ibangha Ini-Abasi I. , Nweze Nkechinyere O. , Ozochi Chizoba A. , Onuora Valentino C. , Titilawo Yinka , Chernikova Tatyana N. , Golyshin Peter N. , Chigor Vincent N.
Published: January 2020

In spite of treated wastewater presenting itself as an attractive alternative to scarce quality water in the developing countries, the associated contamination of fresh produce by irrigation waters leading to outbreak of foodborne illnesses is on the rise. Horizontal transfer of integrons play important role in the spread and maintenance of antimicrobial resistance among strains ofEscherichia coli. This study assessed the effluents from the University of Nigeria, Nsukka Wastewater Treatment Plant (UNN-WWTP) as well as vegetables irrigated with the effluent, and vegetables sold in selected markets from Nsukka and Enugu cities for the presence ofE. coliand determined the prevalence integrons in multidrug-resistant isolates. Isolation ofE. coliwas done using eosin methylene blue agar and isolates subjected to Gram staining for identification of presumptive colonies. Confirmation ofE. coliwas achieved by polymerase chain reaction (PCR) technique, targeting beta-glucuronidase (uidA). Resistance to antibiotics was determined using the Bauer-Kirby disk diffusion assay and the Clinical and Laboratory Standard Institute criteria. Integrons were detected by multiplex PCR using primers specific for class 1 and 2 integrons. A total of 178E. coliisolates were obtained from WWTP effluent (41), and vegetables from greenhouse (46), farms (55) and market (36). Multi-drug resistance was detected in all the isolates, ranging from five-drug resistance in a single isolate to 16-drug resistance patterns in two different isolates. Of the total isolates, class 1 integrons were abundantly detected in 175 (98.3%) and class 2 in 5 (2.8%). All the class 2 integrons were found in isolates that were positive for class 1. The high detection ofE. coliin the studied effluent and vegetables pose potential public health hazards heightened by observed multidrug resistance in all the isolates and the high prevalence of class 1 integron. It is concluded that the vegetable samples are significant reservoirs for potentially pathogenicE. coli.Therefore, vegetable irrigation farming with unsafe water should be discontinued, while appropriate improvement strategies to ensure compliance should be facilitated without further delay.
The conserved herpesviral kinase ORF36 activates B2 retrotransposons during murine gammaherpesvirus infection
Authors: Schaller Aaron M. , Tucker Jessica , Willis Ian , Glaunsinger Britt A.
Published: January 2020

Short interspersed nuclear elements (SINEs) are RNA polymerase III (RNAPIII) transcribed, retrotransposable noncoding RNA (ncRNA) elements ubiquitously spread throughout mammalian genomes. While normally silenced in healthy somatic tissue, SINEs can be induced during infection with DNA viruses, including the model murine gammaherpesvirus MHV68. Here, we explored the mechanisms underlying MHV68 activation of SINE ncRNAs. We demonstrate that lytic MHV68 infection of B cells, macrophages and fibroblasts leads to robust activation of the B2 family of SINEs in a cell autonomous manner. B2 ncRNA induction requires neither host innate immune signaling factors nor involvement of the RNAPIII master regulator Maf1. However, we identify MHV68 ORF36, the conserved herpesviral kinase, as playing a key role in B2 induction during lytic infection. SINE activation is linked to ORF36 kinase activity and can also be induced by HDAC1/2 inhibition, which is one of the known ORF36 functions. Collectively, our data suggest that ORF36-mediated changes in chromatin modification contribute to B2 activation during MHV68 infection, and that this activity is conserved in other herpesviral protein kinase homologs.

AUTHOR SUMMARY

Viral infection dramatically changes the levels of many types of RNA in a cell. In particular, certain oncogenic viruses activate expression of repetitive genes called retrotransposons, which are normally silenced due to their ability to copy and spread throughout the genome. Here, we established that infection with the gammaherpesvirus MHV68 leads to a dramatic induction of a class of noncoding retrotransposons called B2 SINEs in multiple cell types. We then explored how MHV68 activates B2 SINEs, revealing a role for the conserved herpesviral protein kinase ORF36. Both ORF36 kinase-dependent and kinase-independent functions contribute to B2 induction, perhaps through ORF36 targeting of proteins involved in controlling the accessibility of chromatin surrounding SINE loci. Understanding features underlying induction of these elements following MHV68 infection should provide insight into core elements of SINE regulation, as well as dis-regulation of SINE elements associated with disease.
Lipid-specific labeling of enveloped viruses with quantum dots for single-virus tracking
Authors: Zhang Li-Juan , Wang Shaobo , Xia Li , Lv Cheng , Tang Hong-Wu , Xiao Gengfu , Pang Dai-Wen
Published: January 2020

Quantum dots (QDs) possess optical properties of superbright fluorescence, excellent photostability, narrow emission spectra, and optional colors. Labeled with QDs, single molecules/viruses can be rapidly and continuously imaged for a long time, providing more detailed information than labeled with other fluorophores. While they are widely used to label proteins in single-molecule tracking studies, QDs have rarely been used to study virus infection, mainly due to lack of accepted labeling strategies. Here, we report a general method to mildly and readily label enveloped viruses with QDs. Lipid-biotin conjugates were used to recognize and mark viral lipid membranes, and streptavidin (SA)-QD conjugates were used to light them up. Such a method allowed enveloped viruses to be labeled in 2 hours with specificity and efficiency up to 99% and 98%. The intact morphology and the native infectivity of viruses could be furthest preserved. With the aid of this QD labeling method, we lit wild-type (WT) and mutant Japanese encephalitis virus (JEV) up, tracked their infection in living Vero cells, and found that H144A and Q258A substitutions in the envelope (E) protein didn’t affect the virus intracellular trafficking. The lipid-specific QD labeling method described in this study provides a handy and practical tool to readily “see” the viruses and follow their infection, facilitating the widespread use of single-virus tracking and the uncovering of complex infection mechanisms.

Author summary

Virus infection in host cells is a complex process comprising a large number of dynamic molecular events. Single-virus tracking is a versatile technique to study these events. To perform this technique, viruses must be fluorescently labeled to be visible to fluorescence microscopes. Quantum dot is a kind of fluorescent tags that has many unique optical properties. It has been widely used to label proteins in single-molecule tracking studies, but rarely used to study virus infection, mainly due to lack of accepted labeling method. In this study, we developed a lipid-specific method to readily, mildly, specifically, and efficiently label enveloped viruses with quantum dots by recognizing viral envelope lipids with lipid-biotin conjugates and recognizing these lipid-biotin conjugates with streptavidin-quantum dot conjugates. Such a method is superior to the commonly used DiD/DiO labeling and the other QD labeling methods. It is not only applicable to normal viruses, but also competent to label the key protein-mutated viruses and the inactivated high virulent viruses, providing a powerful tool for single-virus tracking.
Myosin X interaction with KIF13B, a crucial pathway for Netrin-1-induced axonal development
Authors: Yu Hua-Li , Peng Yun , Zhao Yang , Lan Yong-Sheng , Wang Bo , Zhao Lu , Sun Dong , Pan Jin-Xiu , Dong Zhao-Qi , Mei Lin , Ding Yu-Qiang , Zhu Xiao-Juan , Xiong Wen-Cheng
Published: January 2020

Myosin X (Myo X) transports cargos to the tip of filopodia for cell adhesion, migration, and neuronal axon guidance. Deleted in Colorectal Cancer (DCC) is one of Myo X cargos essential for Netrin-1-regulated axon pathfinding. Myo X’s function in axon development in vivo and the underlying mechanisms remain poorly understood. Here, we provide evidence for Myo X’s function in Netrin-1-DCC regulated axon development in mouse neocortex. Knocking-out (KO) or knocking-down (KD) Myo X in embryonic cortical neurons impairs axon initiation and contralateral branching/targeting. Similar axon deficits are detected in Netrin-1-KO or DCC-KD cortical neurons. Myo X interacts with KIF13B (a kinesin family motor protein), which is induced by Netrin-1. Netrin-1 promotes anterograde transportation of Myo X into axons in KIF13B dependent manner. KIF13B-KD cortical neurons exhibit similar axon deficits. These results suggest Myo X-KIF13B as a critical pathway for Netrin-1 promoted axon initiation and branching/targeting.
Resolving brain organoid heterogeneity by mapping single cell genomic data to a spatial reference
Authors: Fleck Jonas Simon , He Zhisong , Boyle Michael James , Camp J. Gray , Treutlein Barbara
Published: January 2020

Self-organizing tissues resembling brain regions grown in vitro from human stem cells (so-called organoids or spheroids) offer exciting possibilities to study human brain development, disease, and evolution. Brain organoids or spheroids are complex and can contain cells at various stages of differentiation from different brain structures. Single-cell genomic methods provide powerful approaches to explore cell composition, differentiation trajectories, gene regulation, and genetic perturbations in brain organoid systems. However, it remains a major challenge to understand the cellular heterogeneity observed within and between individual organoids. Here, we have developed a computational approach (VoxHunt) to assess brain organoid patterning, developmental state, and cell composition through systematic comparisons to three-dimensionalin situhybridization data from the Allen Brain Atlas. Cellular transcriptomes as well as accessible chromatin landscapes can be compared to spatial transcript patterns in the developing mammalian brain, which enables characterization and visualization of organoid cell compositions. VoxHunt will be useful to assess novel organoid engineering protocols and to annotate cell fates that emerge in organoids during genetic and environmental perturbation experiments.
Structure and mechanism of human diacylglycerol acyltransferase 1
Authors: Wang Lie , Qian Hongwu , Nian Yin , Han Yimo , Ren Zhenning , Zhang Hanzhi , Hu Liya , Prasad B. V. Venkataram , Yan Nieng , Zhou Ming
Published: January 2020

Human diacylglycerol O-acyltransferase-1 (hDGAT1) synthesizes triacylglycerides and is required for dietary fat absorption and fat storage. The lack of 3-dimensional structure has limited our understanding of substrate recognition and mechanism of catalysis, and hampers rational targeting of hDGAT1 for therapeutic purposes. Here we present the structure of hDGAT1 in complex with a substrate oleoyl Coenzyme A at 3.1 Å resolution. hDGAT1 forms a homodimer and each protomer has nine transmembrane helices that carve out a hollow chamber in the lipid bilayer. The chamber encloses highly conserved catalytic residues and has separate entrances for the two substrates fatty acyl Coenzyme A and diacylglycerol. The N-terminus of hDGAT1 makes extensive interactions with the neighboring protomer, and is required for enzymatic activity.
Controlling brain state prior to stimulation of parietal cortex prevents deterioration of sustained attention
Authors: Edwards Grace , Contò Federica , Bucci Loryn K. , Battelli Lorella
Published: January 2020

Sustained attention is a limited resource which declines during daily tasks. Such decay is exacerbated in clinical and aging populations. Recent research has demonstrated that inhibition of the intraparietal sulcus (IPS) using low-frequency transcranial magnetic stimulation (LF-rTMS) can lead to an upregulation of functional communication within the attention network. Attributed to functional compensation for the inhibited node, this boost outlasts the stimulation for tens of minutes. Despite the neural change, no behavioral correlate has been found in healthy subjects, a necessary direct evidence of functional compensation. To understand the functional significance of neuromodulatory induced fluctuations on attention, we sought to boost the impact of LF-rTMS through controlling neural excitability prior to LF-rTMS, with the goal to impact behavior. Brain state was controlled using high-frequency transcranial random noise stimulation (HF-tRNS), shown to increase and stabilizes neuronal excitability. Using fMRI-guided stimulation protocols combining HF-tRNS and LF-rTMS, we tested the post-stimulation impact on sustained attention via a multiple object tracking task (MOT). Whilst attention deteriorated across time in the control conditions, HF-tRNS followed by LF-rTMS maintained attention performance up to 94 minutes, doubling the length of successful sustained attention. Multimethod stimulation was also more effective when targeting right IPS, supporting the notion of specialized attention processing in the right hemisphere. Used in a cognitive domain dependent on network-wide neural activity, this tool may be effective in causing lasting neural compensation important for clinical rehabilitation.
Soybean CHX protein GmSALT3 confers leaf Na+exclusion via a root derived mechanism, and Cl−exclusion via a shoot derived process
Authors: Qu Yue , Guan Rongxia , Bose Jayakumar , Henderson Sam W. , Wege Stefanie , Qiu Lijuan , Gilliham Matthew
Published: January 2020

Soybean (Glycine max) yields are threatened by multiple stresses including soil salinity.GmSALT3confers net shoot exclusion for both Na+ and Cl−and improves salt tolerance of soybean; however, how the ER-localised GmSALT3 achieves this is unknown. Here, GmSALT3’s function was investigated in heterologous systems and near-isogenic lines that contained the full-lengthGmSALT3(NIL-T; salt-tolerant) or a truncated transcriptGmsalt3(NIL-S; salt-sensitive). GmSALT3 restored growth of K+-uptake-defectiveE. coliand contributed toward net influx and accumulation of Na+, K+, and Cl−inXenopus laevisoocytes, whileGmsalt3was non-functional. A time-course analysis of the NILs confirmed that shoot Cl−exclusion breaks down prior to Na+ exclusion, while grafting showed that shoot Na+exclusion occurs via a root xylem-based mechanism. In contrast, NIL-T plants exhibited significantly greater Cl−content in both the stem xylem and phloem sap compared to NIL-S, indicating that shoot Cl−exclusion likely depends upon novel phloem-based Cl−recirculation. NIL-T shoots grafted on NIL-S roots contained low shoot Cl−, which confirmed that Cl−recirculation is dependent on the presence of GmSALT3 in shoots. Overall, these findings provide new insights on GmSALT3’s impact on salinity tolerance and reveal a novel mechanism for shoot Cl– exclusion in plants.

Highlight

GmSALT3 improves soybean salt tolerance. Here, using heterologous expression, we found GmSALT3 is a functional ion transporter, and,in plantathat it confers shoot salt exclusion through root-based Na+xylem exclusion and shoot-based Cl−exclusion via phloem derived Cl-recirculation.
Antimicrobial activity of the quinoline derivative HT61, effective against non-dividing cells, inStaphylococcus aureusbiofilms
Authors: Frapwell C.J. , Skipp P.J. , Howlin R.P. , Angus E.M. , Hu Y. , Coates A.R.M. , Allan R.N. , Webb J.S.
Published: January 2020

Staphylococcus aureusis an opportunistic pathogen responsible for a wide range of chronic infections. Disease chronicity is often associated with biofilm formation, a phenotype that confers enhanced tolerance towards antimicrobials, a trait which can be attributed to a dormant, non-dividing subpopulation within the biofilm. Development of antibiofilm agents that target these populations could therefore improve treatment success. HT61 is a quinoline derivative that has demonstrated efficacy towards non-dividing planktonicStaphylococcus spp. and therefore, in principal, could be effective against staphylococcal biofilms. In this study HT61 was tested on matureS. aureusbiofilms, assessing both antimicrobial efficacy and characterising the cellular response to treatment. HT61 was found to be more effective than vancomycin in killingS. aureusbiofilms (minimum bactericidal concentrations: HT61; 32 mg/L, vancomycin; 64 mg/L), and in reducing biofilm biomass. Scanning electron microscopy of HT61-treated biofilms also revealed disrupted cellular structure and biofilm architecture. HT61 treatment resulted in increased expression of proteins associated with the cell wall stress stimulon anddcwcluster, implying global changes in peptidoglycan and cell wall biosynthesis. Altered expression of metabolic and translational proteins following treatment also confirm a general adaptive response. These findings suggest that HT61 represents a new treatment forS. aureusbiofilm-associated infections that are otherwise tolerant to conventional antibiotics targeting actively dividing cells.
Supervised Adversarial Alignment of Single-Cell RNA-seq Data
Authors: Ge Songwei , Wang Haohan , Alavi Amir , Xing Eric , Bar-Joseph Ziv
Published: January 2020

Dimensionality reduction is an important first step in the analysis of single cell RNA-seq (scRNA-seq) data. In addition to enabling the visualization of the profiled cells, such representations are used by many downstream analyses methods ranging from pseudo-time reconstruction to clustering to alignment of scRNA-seq data from different experiments, platforms, and labs. Both supervised and unsupervised methods have been proposed to reduce the dimension of scRNA-seq. However, all methods to date are sensitive to batch effects. When batches correlate with cell types, as is often the case, their impact can lead to representations that are batch rather than cell type specific. To overcome this we developed a domain adversarial neural network model for learning a reduced dimension representation of scRNA-seq data. The adversarial model tries to simultaneously optimize two objectives. The first is the accuracy of cell type assignment and the second is the inability to distinguish the batch (domain). We tested the method by using the resulting representation to align several different datasets. As we show, by overcoming batch effects our method was able to correctly separate cell types, improving on several prior methods suggested for this task. Analysis of the top features used by the network indicates that by taking the batch impact into account, the reduced representation is much better able to focus on key genes for each cell type.
Scanning electron microscopy preparation of the cellular actin cortex: a quantitative comparison between critical point drying and hexamethyldisilazane drying
Authors: Schu M. , Terriac E. , Koch M. , Paschke S. , Lautenschläger F. , Flormann D.A.D.
Published: January 2020

The cellular cortex is an approximately 200-nm-thick actin network that lies just beneath the cell membrane. It is responsible for the mechanical properties of cells, and as such, it is involved in many cellular processes, including cell migration and cellular interactions with the environment. To develop a clear view of this dense structure, high-resolution imaging is essential. As one such technique, electron microscopy, involves complex sample preparation procedures. The final drying of these samples has significant influence on potential artifacts, like cell shrinkage and the formation of artifactual holes in the actin cortex. In this study, we compared the three most used final sample drying procedures: critical-point drying (CPD), CPD with lens tissue (CPD-LT), and hexamethyldisilazane drying. We show that both hexamethyldisilazane and CPD-LT lead to fewer artifactual mesh holes within the actin cortex than CPD. Moreover, CPD-LT leads to significant reduction in cell height compared to hexamethyldisilazane and CPD. We conclude that the final drying procedure should be chosen according to the reduction in cell height, and so CPD-LT, or according to the spatial separation of the single layers of the actin cortex, and so hexamethyldisilazane.
A simple, cost-effective, and robust method for rRNA depletion in RNA-sequencing studies
Authors: Culviner Peter H. , Guegler Chantal K. , Laub Michael T.
Published: January 2020

The profiling of gene expression by RNA-sequencing (RNA-seq) has enabled powerful studies of global transcriptional patterns in all organisms, including bacteria. Because the vast majority of RNA in bacteria is ribosomal RNA (rRNA), it is standard practice to deplete the rRNA from a total RNA sample such that the reads in an RNA-seq experiment derive predominantly from mRNA. One of the most commonly used commercial kits for rRNA depletion, the Ribo-Zero kit from Illumina, was recently discontinued. Here, we report the development a simple, cost-effective, and robust method for depleting rRNA that can be easily implemented by any lab or facility. We first developed an algorithm for designing biotinylated oligonucleotides that will hybridize tightly and specifically to the 23S, 16S, and 5S rRNAs from any species of interest. Precipitation of these oligonucleotides bound to rRNA by magnetic streptavidin beads then depletes rRNA from a complex, total RNA sample such that ~75-80% of reads in a typical RNA-seq experiment derive from mRNA. Importantly, we demonstrate a high correlation of RNA abundance or fold-change measurements in RNA-seq experiments between our method and the previously available Ribo-Zero kit. Complete details on the methodology are provided, including open-source software for designing oligonucleotides optimized for any bacterial species or metagenomic sample of interest.

Importance

The ability to examine global patterns of gene expression in microbes through RNA-sequencing has fundamentally transformed microbiology. However, RNA-seq depends critically on the removal of ribosomal RNA from total RNA samples. Otherwise, rRNA would comprise upwards of 90% of the reads in a typical RNA-seq experiment, limiting the reads coming from messenger RNA or requiring high total read depth. A commonly used, kit for rRNA subtraction from Illumina was recently discontinued. Here, we report the development of a ‘do-it-yourself’ kit for rapid, cost-effective, and robust depletion of rRNA from total RNA. We present an algorithm for designing biotinylated oligonucleotides that will hybridize to the rRNAs from a target set of species. We then demonstrate that the designed oligos enable sufficient rRNA depletion to produce RNA-seq data with 75-80% of reads comming from mRNA. The methodology presented should enable RNA-seq studies on any species or metagenomic sample of interest.
Acto-myosin network geometry defines centrosome position
Authors: Jimenez Ana Joaquina , de Pascalis Chiara , Letort Gaelle , Vianay Benoit , Goldman Robert D. , Bornens Michel , Piel Matthieu , Blanchoin Laurent , Théry Manuel
Published: January 2020

The centrosome is the main organizer of microtubules and as such, its position is a key determinant of polarized cell functions. As the name says, the default position of the centrosome is considered to be the cell geometrical center. However, the mechanism regulating centrosome positioning is still unclear and often confused with the mechanism regulating the position of the nucleus to which it is linked. Here we used enucleated cells plated on adhesive micropatterns to impose regular and precise geometrical conditions to centrosome-microtubule networks. Although frequently observed there, the equilibrium position of the centrosome is not systematically at the cell geometrical center and can be close to cell edge. Centrosome positioning appears to respond accurately to the architecture and anisotropy of the actin network, which constitutes, rather than cell shape, the actual spatial boundary conditions the microtubule network is sensitive to. We found that the contraction of the actin network defines a peripheral margin, in which microtubules appeared bent by compressive forces. The disassembly of the actin network away from the cell edges defines an inner zone where actin bundles were absent and microtubules were more radially organized. The production of dynein-based forces on microtubules places the centrosome at the center of this inner zone. Cell adhesion pattern and contractile forces define the shape and position of the inner zone in which the centrosome-microtubule network is centered.
Tumoral and immune heterogeneity in an anti-PD-1-responsive glioblastoma: a case study
Authors: Restrepo Paula , Yong Raymund , Laface Ilaria , Tsankova Nadejda , Nael Kambiz , Akturk Guray , Sebra Robert , Gnjatic Sacha , Hormigo Adilia , Losic Bojan
Published: January 2020

Clinical benefit of immune checkpoint blockade in glioblastoma (GBM) is rare, and we hypothesize that tumor clonal evolution and the immune microenvironment are key determinants of response. Here, we present a detailed molecular characterization of the intratumoral and immune heterogeneity in an IDH wild-type, MGMT-negative GBM patient who plausibly benefited from anti-PD-1 therapy with an unusually long 25-mo overall survival time. We leveraged multiplex immunohistochemistry, RNA-seq, and whole-exome data from the primary tumor and three resected regions of recurrent disease to survey regional tumor-immune interactions, genomic instability, mutation burden, and expression profiles. We found significant regional heterogeneity in the neoantigenic and immune landscape, with a differential T-cell signature among recurrent sectors, a uniform loss of focal amplifications in EGFR, and a novel subclonal EGFR mutation. Comparisons with recently reported correlates of checkpoint blockade in GBM and with TCGA-GBM revealed appreciable intratumoral heterogeneity that may have contributed to a differential PD-1 blockade response.
Understanding co-editing mechanism of wiki-based digital humanities projects
Authors: Deng Weihua , Lv Pei , Yi Ming , Liu Ming
Published: January 2020

Purpose

The purpose of this paper is to reveal the co-editing mechanism aiming at content creation, and an entry of online encyclopedia is taken as a case, for the purpose of promoting and enhancing the development of wiki-based digital humanities projects (WDHPs), specifically, the projects that focus on gathering contextual information in the culture heritage domain.

Design/methodology/approach

An exploratory study was conducted by three steps. A representative entry’s editorial records were reorganized to obtain a data set of discussion statements (n=608), based on which linked-structures were built, and PageRank algorithm was used to analyze the co-editing process. Skewness statistic was applied to measure the consensus of co-editing, and consensus evolution over time was explored. Linear or curve fitting was performed to analyze the correlation between consensus evolution and its influential factors.

Findings

In WDHPs, co-editing activity of content creation can be considered as a large-scale group discussion, consensus can evaluate the efficiency of co-editing, which evolves with time and is influenced by the number of statements, breadth and depth of argumentation structure. Taking “Mogao Grottoes” as an example, group discussions around 15 key issues dominate the content creating process, consensus is on a rise with time, finally reaches a relatively high level, and consensus evolution is more influenced by breadth than by depth of argumentation structure, which indicates that co-editing efficiency of “Mogao Grottoes” is fine and more argumentation in a depth manner should be guided.

Practical implications

For researchers of WDHPs, it is beneficial to apply online encyclopedia platform combining with consensus analysis to develop WDHPs. For designers of WDHPs, the elements related to argumentation structure can be absorbed into the design to promote co-editing in an effective manner. For DH researchers, the analytic procedure can be beneficial of revealing the interest of contributors in a specific DH field.

Originality/value

This research is novel in comprehensively understanding co-editing mechanism of content creation in WDHPs, resulting in a three-step analytic procedure of presenting co-editing process, evaluating and improving co-editing efficiency.
Search optimal control of induction heating modes for a moving workpiece
Authors: Smolyanov Ivan Alexandrovich , Tarasov Fedor
Published: January 2020

Purpose

This paper aims to create mathematical models and control algorithms allowing the authors to study and form effective modes of operation of multi-inductor system of electrical heating of moving hollow cylindrical blanks.

Design/methodology/approach

The developed mathematical models were based on the finite-difference method, the control volume method and their combination. The reliability of the results obtained was verified by comparing the calculated results with the experimental ones. The temperature control system was synthesized using methods of the object management theory with distributed parameters.

Findings

A set of mathematical instruments has been created that allow modelling the operation modes of installation for induction heating of moving hollow cylindrical blanks. Recommendations were given on the formation of an automatic control system that provides heating of a moving hollow cylindrical billet to the required temperature with simultaneous equalization of temperature along the length of the billet in case of highly uneven initial temperature along the length of the billet.

Practical implications

Part of the paper will be used by the industrial plant for the purpose of heat treatment of iron alloys workpiece. Particularly, a control system will be basically formed based on the models.

Originality/value

The scientific novelty of the paper is to create control algorithms and mathematical models for the induction heating system of tubular workpieces allowing to explore interrelated electromagnetic and thermal processes taking into account nonlinearities and design features of the system, as well as to form effective modes of its operation based on transfer functions and methods of the object management theory with distributed parameters.
Effective methods for optimal design of induction coils on example of surface hardening
Authors: Pleshivtseva Yuliya , Baldan Marco , Popov Anton , Nikanorov Alexander , Rapoport Edgar , Nacke Bernard
Published: January 2020

Purpose

This paper aims to describe main ideas and demonstrates results of the research activities carried out by the authors in the field of optimal design concepts for induction heater for surface hardening. The main goal of the research studies is the application of different optimization methods and numerical finite element method (FEM) codes for field analysis to solve the optimal design problem that is mathematically formulated in terms of the one of the most important optimization criteria for surface hardening technology, e.g. maximum temperature uniformity within the hardening surface layer.

Design/methodology/approach

Evolutionary algorithm based on Adaptive Gaussian Process-Assisted Differential Evolution for MEMS Design Optimization (AGDEMO) and alternance method of parametric optimization based on optimal control theory are applied as effective tools for the practice-oriented problem for optimization of induction heater design based on non-linear coupled electromagnetic and temperature field analysis. Different approaches are used for combining FEM codes for interconnected field analysis and optimization algorithms into automated optimization procedure.

Findings

Optimization procedures are tested and investigated for optimal design problem solution on the examples of induction hardening of steel cylindrical billet.

Practical implications

Solved problems are based on the design of practical industrial applications. The developed optimization procedures are planned to be applied to the wide range of real-life problems of the optimal design of different electromagnetic devices and systems.

Originality/value

This paper describes main ideas and results of the research activities carried out by the authors in the field of optimal design of induction heaters for hardening based on numerical coupled electromagnetic and temperature field analysis. The implementation of the automated procedure that combines a numerical FEM code for coupled field analysis with an optimization algorithm and its subsequent application for designing induction heaters makes the proposed approach specific and original. This paper also demonstrates that different optimization strategies used (evolutionary algorithm based on AGDEMO and alternance method of optimal control theory) are effective for real-life industrial applications for optimization of induction heaters design.
Influence of vessel dimensions on particles homogenization and heat removing in TMF stirrer
Authors: Evgeny Shvidkiy , Sokolov Igor , Bolotin Kirill , Zakharov Valery
Published: January 2020

Purpose

The purpose of this paper is to determine how the shape of the container affects the efficiency of a traveling magnetic field (TMF) stirring.

Design/methodology/approach

The modeling approach is based on finite element software Comsol which includes harmonic electromagnetic (EM), transient CFD and particle tracing modules. For evaluating efficiency of stirring the particle, homogenization parameter is used.

Findings

It has been determined that the use of an elliptical cylinder-shaped vessel allows better heat removal from the side surface and, at the same time, the stirring efficiency does not drop significantly.

Practical implications

The results of the work can be used in the design of EM stirring installations in which exothermic reactions occur.

Originality/value

The transient simulation of particle transport in a TMF-driven melt flow gives the opportunity to estimate the efficiency of stirring process in different vessel shapes.
Occupational health and safety performance evaluation of countries based on MAIRCA
Authors: Can Gülin Feryal , Kıran Muzaffer Bertan
Published: January 2020

Purpose

The purpose of this paper is to develop an approach to compare occupational health and safety (OHS) performances of countries. Additionally, another aim is to debate the impacts of using recorded data and ratios for OHS performance evaluations.

Design/methodology/approach

The number of fatal accidents (NFAs), fatal accident rates (FARs), numbers of lost days (NLDs) and accident severity rates (ASRs) are determined as main criteria and six economic activity areas (EAAs) are considered as sub-criteria. Two different initial decision matrices are used as the initial decision matrix, the first of which consists of recorded data of countries related to NFAs and NLDs, and the second consists of FAR and ASR values as ratios. Importance weights of main and sub-criteria regarding the recorded data and ratios are determined using four different weighting ways. Countries are ranked via utilizing Multi-Attributive Ideal-Real Comparative Analysis considering two different initial decision matrices.

Findings

It can be stated that an evaluation based on ratios for comparison of OHS performance provides more realistic results. Additionally, increasing the effect of the FAR values using the 6,000 equivalent lost days factor is also important in terms of differentiating the data of the countries in question.

Originality/value

To the best of the authors’ knowledge, there is no study in literature that discusses the ranking of countries by means of recorded data and ratios considering different criteria. Additionally, this study is a first in terms of the number of countries evaluated and the comparison of these countries according to their respective EAAs.
Research on spatial positioning of online inspection robots for vertical storage tanks
Authors: Huang Zhiqiang , He Lei , Gao ZhaoXin , Jia Yingqi , Kang Yewei , Xie Dou , Fu Chunli
Published: January 2020

Purpose

This paper aims to introduce a new acoustic positioning method to solve the problem of space positioning for online inspection robots within the storage tank.

Design/methodology/approach

The proposed positioning system comprises two acoustic signal emitters and two receivers. Emitters are brought by the robot into the storage tank. Receivers are mounted on the external edge of the storage tank floor. The spatial coordinate values and motion directions of the robot in the storage tank are calculated by using the proposed acoustic positioning algorithm.

Findings

The experiment results and positioning error analysis indicate that the method can obtain the data of robotic space coordinates and motion orientation, while the positioning error of the method can be less than 20 cm. The accuracy reaches the positioning technology level of other tank online inspection robots.

Originality/value

This method not only expands the positioning of the inspection robots from 2D plane to 3D space but also significantly reduces the number of positioning sensors carried by a robot and improves the safety of a robot in the tank.
The role of public markets in urban habitability and competitiveness
Authors: Balsas Carlos J.L.
Published: January 2020

Purpose

The purpose of this paper is to examine public market functions in three different continents (Europe, North America and Asia) and to identify a set of planning implications for their use in contexts of urban regeneration.

Design/methodology/approach

The paper presents a comparative analysis of four downtown market functions based on the LABiMAAM framework: [L]ocation; [A]ccessibility; [B]uilding; [i]nternal structure; [M]ain trading area; [A]menities and services; [A]nimation program; and [M]anagement structure.

Findings

The lessons learned suggest that centrally located public markets possess: social functions aimed at guaranteeing food security, urban development goals that prevent the leap-frog suburbanization of the territory, walkability goals that reduce automobile dependence and welfare goals that support disenfranchised, usually minority, populations.

Research limitations/implications

Positive and dire implications are identified. The former are structured in terms of these five categories, namely, social, financial, macro-spatial, environmental and public space; while the latter tend to result mostly from the abandonment of the public good orientation associated with having a public market function in a central location.

Originality/value

This study results from the realization of increasing developmental pressures and widespread tendencies to multiply specialized retail offers in both traditional, and especially, innovative commercial formats. The findings comprise the identification of public policies aimed at augmenting the relevance of commercial urbanism and urban regeneration strategies.
Cognitive psychology and tourism – surfing the “cognitive wave”: a perspective article
Authors: Scott Noel
Published: January 2020

Purpose

This paper aims to provide a personal perspective on the application of psychological theory in tourism studies and the importance of cognitive science for future research.

Design/methodology/approach

Empirical findings and theoretical ideas from cognitive science provide insights useful for tourism researchers. The slow uptake of these ideas provides a means to probe systematic weaknesses in the tourism academy’s research practice.

Findings

Theories derived from psychology are applied in tourism research, but these same theories are not reassessed after they are discredited, and new approaches emerge. Instead, “old” ideas continue to be used resulting in a moribund theoretical environment. Further, concepts from different paradigms are often adopted in the same study resulting in a confused and confusing literature.

Originality/value

This paper challenges theoretically conservative “social science”-based tourism researchers to adopt current best practice ideas from cognitive psychology. It highlights the value of cognitive psychology and neuroscience research for understanding social science phenomena.
Investigation of brain functional connectivity to assess cognitive control over cue‐processing in Alcohol Use Disorder
Authors: Strosche Alicia , Zhang Xiaochu , Kirsch Martina , Hermann Derik , Ende Gabriele , Kiefer Falk , Vollstädt‐Klein Sabine
Published: January 2020

Alcohol Use Disorder has been associated with impairments of functional connectivity between neural networks underlying reward processing and cognitive control. Evidence for aberrant functional connectivity between the striatum, insula, and frontal cortex in alcohol users exists at rest, but not during cue‐exposure. In this study, we investigated functional connectivity changes during a cue‐reactivity task across different subgroups of alcohol consumers. Ninety‐six participants (ranging from light social to heavy social drinkers and nonabstinent dependent to abstinent dependent drinkers) were examined. A functional magnetic resonance imaging cue‐reactivity paradigm was administered, during which alcohol‐related and neutral stimuli were presented. Applying psychophysiological interaction analyses, we found: (a) Abstinent alcohol‐dependent patients compared with non‐abstinent dependent drinkers showed a greater increase of functional connectivity of the ventral striatum and anterior insula with the anterior cingulate cortex and dorsolateral prefrontal cortex during the presentation of alcohol cues compared with neutral cues. (b) Subjective craving correlated positively with functional connectivity change between the posterior insula and the medial orbitofrontal cortex and negatively with functional connectivity change between the ventral striatum and the anterior cingulate cortex, dorsolateral prefrontal cortex, and lateral orbitofrontal cortex. (c) Compulsivity of alcohol use correlated positively with functional connectivity change between the dorsolateral prefrontal cortex and the ventral striatum, anterior insula, and posterior insula. Results suggest increased cognitive control over cue‐processing in abstinent alcohol‐dependent patients, compensating high levels of cue‐provoked craving and compulsive use.

Clinical trial registration details: ClinicalTrials.gov ID: NCT00926900