bluuebunny/crossref_metadata_2025_split huggingface dataset:
A mathematical model of flagellar gene regulation and construction inSalmonella enterica
Authors: Utsey Kiersten , Keener James P. 
Published: January 2020

AbstractMillions of people worldwide develop foodborne illnesses caused bySalmonella enterica(S. enterica) every year. The pathogenesis ofS. entericadepends on flagella, which are appendages that the bacteria use to move through the environment. Interestingly, populations of genetically identical bacteria exhibit heterogeneity in the number of flagella. To understand this heterogeneity and the regulation of flagella quantity, we propose a mathematical model that connects the flagellar gene regulatory network to flagellar construction. A regulatory network involving more than 60 genes controls flagellar assembly. The most important member of the network is the master operon,flhDC, which encodes the FlhD4C2protein. FlhD4C2controls the construction of flagella by initiating the production of hook basal bodies (HBBs), protein structures that anchor the flagella to the bacterium. By connecting a model of FlhD4C2regulation to a model of HBB construction, we investigate the roles of various feedback mechanisms. Analysis of our model suggests that a combination of regulatory mechanisms at the protein and transcriptional levels induce bistable FlhD4C2levels and heterogeneous numbers of flagella. Also, the balance of regulatory mechanisms that become active following HBB construction is sufficient to provide a counting mechanism for controlling the total number of flagella produced.Author summarySalmonellacauses foodborne illnesses in millions of people worldwide each year. Flagella, which are appendages that the bacteria use to move through the environment, are a key factor in the infection process. Populations of genetically identical bacteria have been observed to contain both motile cells, generally with 6–10 flagella, and nonmotile cells, with no flagella. In this paper, we use mathematical models of the gene network that regulates flagellar construction to explore how the bacteria controls the number of flagella produced. We suggest that a bacterium must accumulate a threshold amount of a master regulator protein to initiate flagella production and failure to reach the threshold results in no flagella. Downstream mechanisms that impact the amount of master regulator protein are sufficient to determine how many flagella are produced.
Parental investment and immune dynamics in sex-role reversed pipefishes
Authors: Keller Isabel S. , Roth Olivia 
Published: January 2020

AbstractParental care elevates reproductive success by allocating resources into the upbringing of the offspring. However, it also imposes strong costs for the care giving parent and can foster sexual dimorphism. Trade-offs between the reproductive system and the immune system may result in differential immunological capacities between the care-providing and the non-care-providing parent. Usually, providing care is restricted to the female sex making it impossible to study a sex-independent influence of parental investment on sexual immune dimorphism. The decoupling of sex-dependent parental investment and their influences on the parental immunological capacity, however, is possible in syngnathids, which evolved the unique male pregnancy on a gradient ranging from a simple carrying of eggs on the trunk (Nerophinae, low paternal investment) to full internal pregnancy (Syngnathus, high paternal investment). In this study, we compared candidate gene expression between females and males of different gravity stages in three species of syngnathids (Syngnathus typhle,Syngnathus rostellatusandNerophis ophidion) with different male pregnancy intensities to determine how parental investment influences sexual immune dimorphism. While our data failed to detect sexual immune dimorphism in the subset of candidate genes assessed, we show a parental care specific resource-allocation trade-off between investment into pregnancy and immune defense when parental care is provided.
Wing Metric Variation inAedes aegyptiEffect of Altitude on Wing Metric Variation ofAedes aegypti(Diptera: Culicidae) in a Region of the Colombian Central Andes
Authors: Leyton-Ramos Luis M. , Aguirre-Obando Oscar Alexander , Duque Jonny Edward , García-Merchán Víctor Hugo 
Published: January 2020

AbstractIn mosquitoes of medical importance, wing shape and size can vary with altitude, an aspect that can influence dispersion and, consequently, their vector capacity. Using geometric morphometry analysis,Aedes aegyptiwing size and shape variation of males and females was studied in four altitudes in the second-smallest department in Colombia: 1.200 m (Tebaida), 1.400 m (Armenia), 1.500 m (Calarcá), and 1.700 m (Filandia). Wing shape in males (P < 0.001) and females (P < 0.001) was significantly different through the altitudinal gradient; in turn, wing size in males followed the altitudinal gradient (Males R2= 0.04946, P = 0.0002), Females (R2= 0.0011, P = 0.46). Wing allometry for males (P < 0.001) and females (P < 0.001) was significant. Likewise, the shape and size of the wings of males (P < 0.001) and females (P < 0.001) had significant fluctuating asymmetry. It is concluded that, in a small scale with an altitudinal variation of 500 meters, it is detected that the size and shape of the wings varied inA. aegypti, principal vector of dengue, chikungunya, and Zika. The fluctuating asymmetry is present in the individuals studied and could be associated with environmental effects caused by vector control campaigns present in some sampling locations.
Transposon mobilization in the human fungal pathogenCryptococcus deneoformansis mutagenic during infection and promotes drug resistancein vitro
Authors: Gusa Asiya , Williams Jonathan D. , Cho Jang-Eun , Floyd-Averette Anna , Sun Sheng , Shouse Eva Mei , Heitman Joseph , Alspaugh J. Andrew , Jinks-Robertson Sue 
Published: January 2020

ABSTRACTWhen transitioning from the environment, pathogenic microorganisms must adapt rapidly to survive in hostile host conditions. This is especially true for environmental fungi that cause opportunistic infections in immunocompromised patients since these microbes are not well adapted human pathogens.Cryptococcusspecies are yeast-like fungi that cause lethal infections, especially in HIV-infected patients. UsingCryptococcus deneoformansin a murine model of infection, we examined contributors to drug resistance and demonstrated that transposon mutagenesis drives the development of 5-fluoroorotic acid (5FOA) resistance. Inactivation of target genesURA3orURA5primarily reflected the insertion of two transposable elements (TEs): the T1 DNA transposon and the TCN12 retrotransposon. Consistent within vivoresults, increased rates of mutagenesis and resistance to 5FOA and the antifungal drugs rapamycin/FK506 and 5-fluorocytosine (5FC) were found whenCryptococcuswas incubated at 37° compared to 30°in vitro, a condition that mimics the temperature shift that occurs during the environment-to-host transition. Inactivation of the RNAi pathway, which suppresses TE movement in many organisms, was not sufficient to elevate TE movement at 30° to the level observed at 37°. We propose that temperature-dependent TE mobilization inCryptococcusis an important mechanism that enhances microbial adaptation and promotes pathogenesis and drug resistance in the human host.SIGNIFICANCE STATEMENTThe incidence of infections due to fungal pathogens has dramatically increased in the past few decades with similar increases in human populations with weakened or suppressed immune systems. Understanding the mechanisms by which organisms rapidly adapt during human infection to enhance virulence and evolve drug resistance is important for developing effective treatments. We find that transposon mobilization in the human pathogenCryptococcuscauses genomic mutations in a murine model of infection and promotes resistance to antifungal drugsin vitro. Thermotolerance is a key virulence determinant for pathogenic fungi during the environment-to-host transition, and we demonstrate that a temperature increase is sufficient to trigger transposon mobilizationin vitro. The link between temperature stress and transposon-associated mutations may significantly impact adaptation to the host during infection, including the acquisition of drug resistance.
Dynamic chromatin accessibility landscape changes following interleukin-1 stimulation
Authors: Barter Matt J. , Cheung Kathleen , Falk Julia , Panagiotopoulos Andreas C. , Cosimini Caitlin , O’Brien Siobhan , Teja-Putri Karina , Neill Graham , Deehan David J. , Young David A. 
Published: January 2020

AbstractGenome-wide methods for examining chromatin modification provide detailed information on regulatory regions of the genome. Dynamic modifications of chromatin allow rapid access of the gene regulatory machinery to condensed genomic regions facilitating subsequent gene expression. Inflammatory cytokine stimulation of cells can cause rapid gene expression changes through direct signalling pathway-mediated transcription factor activation and regulatory element binding.Here we used the Assay for Transposase Accessible Chromatin with high-throughput sequencing (ATAC-seq) to assess regions of the genome that are differentially accessible following treatment of cells with interleukin-1 (IL-1). We identified 126,483 open chromatin regions, with 241 regions significantly differentially accessible following stimulation, with 64 and 177 more or less accessible, respectively. These differentially accessible regions predominantly correspond to regions of the genome marked as enhancers. Motif searching identified an overrepresentation of a number of transcription factors, most notably RelA in the regions becoming more accessible, with analysis of ChIP-seq data confirmed RelA binding to these regions. A significant correlation in differential chromatin accessibility and gene expression was also observed.Functionality in regulating gene expression was confirmed using CRISPR/Cas9 genome-editing to delete regions for that became more accessible following stimulation in the genesMMP13,IKBKEandC1QTNF1. These same regions were also accessible for activation using a dCas9-transcriptional activator and showed enhancer activity in a cellular model.Together, these data describe and functionally validate a number of dynamically accessible chromatin regions involved in inflammatory signalling.
Evolution from adherent to suspension – systems biology of HEK293 cell line development
Authors: Malm Magdalena , Saghaleyni Rasool , Lundqvist Magnus , Giudici Marco , Chotteau Veronique , Field Raymond , Varley Paul , Hatton Diane , Grassi Luigi , Svensson Thomas , Uhlen Mathias , Nielsen Jens , Rockberg Johan 
Published: January 2020

AbstractThe need for new safe and efficacious therapies has led to an increased focus on biologics produced in mammalian cells. The human cell line HEK293 has bio-synthetic potential for human-like production and is today used for manufacturing of several therapeutic proteins and viral vectors. Despite this increasing popularity there is still limited knowledge of the detailed genetic and composition of derivatives of this strain. Here we present a genomic, transcriptomic and metabolic gene analysis of six of the most widely used HEK293 cell lines. Changes in gene copy and expression between industrial progeny cell lines and the original HEK293 were associated with cellular component organization, cell motility and cell adhesion. Changes in gene expression between adherent and suspension derivatives highlighted switching in cholesterol biosynthesis and expression of five key genes (RARG, ID1, ZIC1, LOX and DHRS3), a pattern validated in 63 human adherent or suspension cell lines of other origin.
Convolutional neural network MRI segmentation for fast and robust optimization of transcranial electrical current stimulation of the human brain
Authors: Sendra-Balcells Carla , Salvador Ricardo , Pedro Juan B. , Biagi M C , Aubinet Charlène , Manor Brad , Thibaut Aurore , Laureys Steven , Lekadir Karim , Ruffini Giulio 
Published: January 2020

AbstractThe segmentation of structural MRI data is an essential step for deriving geometrical information about brain tissues. One important application is in transcranial electrical stimulation (e.g., tDCS), a non-invasive neuromodulatory technique where head modeling is required to determine the electric field (E-field) generated in the cortex to predict and optimize its effects. Here we propose a deep learning-based model (StarNEt) to automatize white matter (WM) and gray matter (GM) segmentation and compare its performance withFreeSurfer, an established tool. Since good definition of sulci and gyri in the cortical surface is an important requirement for E-field calculation,StarNEtis specifically designed to output masks at a higher resolution than that of the original input T1w-MRI.StarNEtuses a residual network as the encoder (ResNet) and a fully convolutional neural network with U-net skip connections as the decoder to segment an MRI slice by slice. Slice vertical location is provided as an extra input. The model was trained on scans from 425 patients in the open-access ADNI+IXI datasets, and usingFreeSurfersegmentation as ground truth. Model performance was evaluated using the Dice Coefficient (DC) in a separate subset (N=105) of ADNI+IXI and in two extra testing sets not involved in training. In addition,FreeSurferandStarNEtwere compared to manual segmentations of the MRBrainS18 dataset, also unseen by the model. To study performance in real use cases, first, we created electrical head models derived from theFreeSurferandStarNEtsegmentations and used them for montage optimization with a common target region using a standard algorithm (Stimweaver) and second, we usedStarNEtto successfully segment the brains of minimally conscious state (MCS) patients having suffered from brain trauma, a scenario whereFreeSurfertypically fails. Our results indicate thatStarNEtmatchesFreeSurferperformance on the trained tasks while reducing computation time from several hours to a few seconds, and with the potential to evolve into an effective technique even when patients present large brain abnormalities.
Characterization ofEscherichia coliExbD protein modificationin vivo
Authors: Kumar Aruna , Postle Kathleen 
Published: January 2020

ABSTRACTThe TonB system ofEscherichia colicouples the protonmotive force of the cytoplasmic membrane to active transport of nutrients across the outer membrane. In the cytoplasmic membrane, this system consists of three known proteins, TonB, ExbB, and ExbD. ExbB and ExbD appear to harvest the protonmotive force and transmit it to TonB, which then makes direct physical contact with TonB-dependent active transport proteins in the outer membrane. Using two-dimensional gel electrophoresis, we found that ExbD exists as two different species with the same apparent molecular mass but with different pIs. The more basic ExbD species was consistently present, while the more acidic species arose when cells were starved for iron by the addition of iron chelators. The cause of the modification was, however, more complex than simple iron starvation. Absence of either TonB or ExbB protein also gave rise to modified ExbD under iron-replete conditions where the wild-type strain exhibited no ExbD modification. The effect of thetonBorexbBmutations were not entirely due to iron limitation since an equally iron-limitedaroBmutation did not replicate the ExbD modification. This constitutes the first report ofin vivomodification for any of the TonB system proteins.
Pervasive promoter hypermethylation of silencedTERTalleles in human cancers
Authors: Esopi D , Graham MK , Brosnan-Cashman J , Meyers J , Vaghasia A , Gupta A , Kumar B , Haffner MC , Heaphy CM , De Marzo AM , Meeker AK , Nelson WG , Wheelan SJ , Yegnasubramanian S 
Published: January 2020

ABSTRACTIn cancers, maintenance of telomeres often occurs through activation of the catalytic subunit of telomerase, encoded byTERT. Yet, most cancers show only modest levels of telomerase gene expression, even in the context of activating hotspot promoter mutations (C228T and C250T). The role of epigenetic mechanisms, including DNA methylation, in regulating telomerase gene expression in cancer cells is not fully understood. Here, we have carried out the most comprehensive characterization to date ofTERTpromoter methylation using ultra-deep bisulfite sequencing spanning the CpG island surrounding the coreTERTpromoter in 96 different human cell lines. In general, we observed that immortalized and cancer cell lines were hypermethylated in a region upstream of the recurrent C228T and C250TTERTpromoter mutations, while non-malignant primary cells were comparatively hypomethylated in this region. However, at the allele-level, we generally observe hypermethylation of promoter sequences in cancer cells is associated with repressed expression, and the remaining unmethylated alleles marked with open chromatin are largely responsible for the observedTERTexpression in cancer cells. Our findings suggest that hypermethylation of theTERTpromoter alleles signals transcriptional repression of those alleles, leading to the attenuation ofTERTactivation in cancer cells.SIGNIFICANCEHypermethylation of theTERTpromoter alleles to attenuateTERTactivation in cancer cells may account for the modest activation ofTERTexpression in most cancers.
Quantifying influences on intragenomic mutation rate
Authors: Simon Helmut , Huttley Gavin 
Published: January 2020

ABSTRACTWe report work to quantify the impact on the probability of human genome polymorphism both of recombination and of sequence context at different scales. We use population-based analyses of data on human genetic variants obtained from the public Ensembl database. For recombination, we calculate the variance due to recombination and the probability that a recombination event causes a mutation. We employ novel statistical procedures to take account of the spatial auto-correlation of recombination and mutation rates along the genome. Our results support the view that genomic diversity in recombination hotspots arises from a direct effect of recombination on mutation rather than from the effect of selective sweeps. We also use the statistic of variance due to context to compare the effect on the probability of polymorphism of contexts of various sizes. We find that when the 12 point mutations are considered separately, variance due to context increases significantly as we move from 3-mer to 5-mer and from 5-mer to 7-mer contexts. However, when all mutations are considered in aggregate, these differences are outweighed by the effect of interaction between the central base and its immediate neighbors. This interaction is itself dominated by the transition mutations, including, but not limited to, the CpG effect. We also demonstrate strand-asymmetry of contextual influence in intronic regions, which is hypothesized to be a result of transcription coupled DNA repair. We consider the extent to which the measures we have used can be used to meaningfully compare the relative magnitudes of the impact of recombination and context on mutation.
A Systematic Evaluation of Single-cell RNA-sequencing Imputation Methods
Authors: Hou Wenpin , Ji Zhicheng , Ji Hongkai , Hicks Stephanie C. 
Published: January 2020

ABSTRACTThe rapid development of single-cell RNA-sequencing (scRNA-seq) technology, with increased sparsity compared to bulk RNA-sequencing (RNA-seq), has led to the emergence of many methods for preprocessing, including imputation methods. Here, we systematically evaluate the performance of 18 state-of-the-art scRNA-seq imputation methods using cell line and tissue data measured across experimental protocols. Specifically, we assess the similarity of imputed cell profiles to bulk samples as well as investigate whether methods recover relevant biological signals or introduce spurious noise in three downstream analyses: differential expression, unsupervised clustering, and inferring pseudotemporal trajectories. Broadly, we found significant variability in the performance of the methods across evaluation settings. While most scRNA-seq imputation methods recover biological expression observed in bulk RNA-seq data, the majority of the methods do not improve performance in downstream analyses compared to no imputation, in particular for clustering and trajectory analysis, and thus should be used with caution. Furthermore, we find that the performance of scRNA-seq imputation methods depends on many factors including the experimental protocol, the sparsity of the data, the number of cells in the dataset, and the magnitude of the effect sizes. We summarize our results and provide a key set of recommendations for users and investigators to navigate the current space of scRNA-seq imputation methods.
Variance constrained trajectory tracking for tandem-rotor helicopters
Authors: Sal Firat 
Published: January 2020

Purpose
This paper aims to present novel results for trajectory tracking of tandem-rotor helicopters via variance-constrained controllers.

Design/methodology/approach
Regarding these purposes, linearized tandem-rotor helicopter models are benefitted.

Findings
Variance-constrained controllers are very beneficial for trajectory tracking of tandem-rotor helicopters while there exists variance bounds on outputs of interest.

Practical implications
Variance-constrained controllers can be used for cheaper tandem-rotor helicopter operations with high trajectory tracking quality.

Originality/value
Applying variance-constrained control strategy for tandem-rotor helicopters during trajectory tracking. This also causes less fuel consumption and green environment, and good trajectory tracking quality.
Craft beer mon amour: an exploration of Italian craft consumers
Authors: Carbone Anna , Quici Luisangela 
Published: January 2020

PurposeThe purpose of this paper is to contribute understanding tendencies of the Italian demand for craft beer. More in details, it seeks at exploring consumers’ awareness about craft beer, their attitudes, habits and behaviors. It also aims at assessing the impact of each and all these features on consumers’ choice. At last, the paper frames different consumers’ profiles.Design/methodology/approachThe analysis is based on an online survey associated with a choice experiment designed for assessing willingness to buy (WTB) and willingness to pay (WTP) for craft vs industrial beer. Factors influencing consumers’ expenditure for craft beer are explored via an OLS estimation of a simple regression model. Afterwards, different consumers’ profiles are depicted via cluster analysis.FindingsThe survey shows that, overall, Italian consumers appreciate craft beers and are interested in this market. Socio-demographic characteristics impact this inclination but have no significant influence on the results of the choice experiment. Market knowledge, preferences and consumption habits influence consumer spending. Five different consumer profiles emerge.Originality/valueThe research proposes a combined original methodology for assessing beer consumers’ features and their impacts on beer WTB and WTP. The complementary perspectives adopted provide new insights on craft beer demand. Results are of interest for craft brewery managers and for the design of policies aimed at promoting and expanding the sector. Enlarging the sample and improving its representativeness would allow for more general results.