bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plasmodium falciparum Acetyl-CoA Synthetase is essential for parasite intraerythrocytic development and chromatin modification
Authors: Prata Isadora Oliveira , Galindo Cubillos Eliana Fernanda , Barbosa Deibs , Martins Joaquim , Setubal João Carlos , Wunderlich Gerhard 
Published: June 2021

AbstractThe malaria parasite Plasmodium falciparum possesses a unique Acetyl-CoA Synthetase (PfACS) which provides acetyl moieties for different metabolic and regulatory cellular pathways. We characterized PfACS and studied its role focusing on epigenetic modifications using the var gene family as reporter genes. For this, mutant lines to modulate plasmodial ACS expression by degron-mediated protein degradation or ribozyme induced transcript decay were created. Additionally, an ACS inhibitor was tested for its effectiveness and specificity in interfering with PfACS. The knockdown of PfACS or its inhibition led to impaired parasite growth. Decreased levels of PfACS also led to differential histone acetylation patterns, altered variant gene expression and concomitantly decreased cytoadherence of infected red blood cells containing knocked-down parasites. Further, ChIP analysis revealed the presence of PfACS in many loci in ring stage parasites, underscoring its involvement in the regulation of chromatin. Due to its significant differences to human ACS, PfACS seems an interesting target for drug development.
Proliferation maintains the undifferentiated status of stem cells: the role of the planarian cell cycle regulator Cdh1
Authors: Sato Yuki , Umesono Yoshihiko , Kuroki Yoshihito , Agata Kiyokazu , Hashimoto Chikara 
Published: June 2021

AbstractThe coincidence of cell cycle arrest and differentiation has been described in a wide variety of stem cells and organisms for decades, but the causal relationship is still unclear due to the complicated regulation of the cell cycle. Here, we used the planarian Dugesia japonica since it possesses a quite simple cell cycle regulation in which cdh1 is the only factor that arrests the cell cycle. When cdh1 was functionally inhibited, the planarians could not maintain their tissue homeostasis and could not regenerate their missing body parts. While the ablation of cdh1 caused pronounced propagation of the stem cells, the progenitor and differentiated cells were decreased. Further analysis indicated that the stem cells without cdh1 expression did not undergo differentiation even though they received ERK signaling activation as an induction signal. These results suggested that stem cells could not acquire differentiation competence without cell cycle arrest. Thus, we propose that cell cycle regulation determines the differentiation competence and that cell cycle exit to G0 enables stem cells to undergo differentiation.Summary statementBy using planarians, which have quite simple cell cycle regulation, we revealed that stem cells with cell cycle progression could not undergo differentiation even though an induction signal was activated.
Preterm birth is associated with xenobiotics and predicted by the vaginal metabolome
Authors: Kindschuh William F. , Baldini Federico , Liu Martin C. , Gerson Kristin D. , Liao Jingqiu , Lee Harry H. , Anton Lauren , Gajer Pawel , Ravel Jacques , Levy Maayan , Elovitz Michal A. , Korem Tal 
Published: June 2021

AbstractSpontaneous preterm birth (sPTB) is a leading cause of maternal and neonatal morbidity and mortality, yet both its prevention and early risk stratification are limited. The vaginal microbiome has been associated with PTB risk, possibly via metabolic or other interactions with its host. Here, we performed untargeted metabolomics on 232 vaginal samples, in which we have previously profiled the microbiota using 16S rRNA gene sequencing. Samples were collected at 20-24 weeks of gestation from women with singleton pregnancies, of which 80 delivered spontaneously before 37 weeks of gestation. We find that the vaginal metabolome correlates with the microbiome and separates into six clusters, three of which are associated with spontaneous preterm birth (sPTB) in Black women. Furthermore, while we identify five metabolites that associate with sPTB, another five associate with sPTB only when stratifying by race. We identify multiple microbial correlations with metabolites associated with sPTB, including intriguing correlations between vaginal bacteria that are considered sub-optimal and metabolites that were enriched in women who delivered at term. We propose that several sPTB-associated metabolites may be exogenous, and investigate another using metabolic models. Notably, we use machine learning models to predict sPTB risk using metabolite levels, weeks to months in advance, with high accuracy. We show that these predictions are more accurate than microbiome-based and maternal covariates-based models. Altogether, our results demonstrate the potential of vaginal metabolites as early biomarkers of sPTB and highlight exogenous exposures as potential risk factors for prematurity.
Insights into rRNA processing and modification mapping in Archaea using Nanopore-based RNA sequencing
Authors: Grünberger Felix , Jüttner Michael , Knüppel Robert , Ferreira-Cerca Sébastien , Grohmann Dina 
Published: June 2021

AbstractSimilar to its bacterial and eukaryotic counterparts, ribosomal RNA maturation in archaea is a multi-step process requiring well-defined endo- and exoribonuclease activities. However, the detailed rRNA processing pathway in archaea remained elusive. Here, we employed long-read direct cDNA and direct RNA Nanopore-based sequencing to study rRNA maturation in three archaeal model organisms, namely the EuryarchaeaHaloferax volcaniiandPyrococcus furiosusand the CrenarchaeonSulfolobus acidocaldarius. Compared to standard short-read protocols, nanopore sequencing facilitates simultaneous readout of 5’- and 3’-positions, which is required for the classification of rRNA processing intermediates. More specifically, we i) accurately detect and describe rRNA maturation stages by analysis of terminal read positions of cDNA reads and thereupon ii) explore the stage-dependent installation of the KsgA-mediated dimethylations inHaloferax volcaniiusing basecalling and signal characteristics of direct RNA reads. Due to the single-molecule sequencing capacity of nanopore sequencing, we could detect hitherto unknown intermediates with high confidence revealing details about the maturation of archaea-specific circular rRNA intermediates. Taken together, our study delineates common principles and unique features of rRNA processing in euryarchaeal and crenarchaeal representatives, thereby providing a comprehensive picture of rRNA maturation pathways in archaea.
VirClust – a tool for hierarchical clustering, core gene detection and annotation of (prokaryotic) viruses
Authors: Moraru Cristina 
Published: June 2021

AbstractRecent years have seen major changes in the classification criteria and taxonomy of viruses. The current classification scheme, also called “megataxonomy of viruses”, recognizes five different viral realms, defined based on the presence of viral hallmark genes. Within the realms, viruses are classified into hierarchical taxons, ideally defined by their shared genes. Therefore, there is currently a need for virus classification tools based on such shared genes / proteins. Here, VirClust is presented – a novel tool capable of performing i) hierarchical clustering of viruses based on intergenomic distances calculated from their protein cluster content, ii) identification of core proteins and iii) annotation of viral proteins. VirClust groups proteins into clusters both based on BLASTP sequence similarity, which identifies more related proteins, and also based on hidden markow models (HMM), which identifies more distantly related proteins. Furthermore, VirClust provides an integrated visualization of the hierarchical clustering tree and of the distribution of the protein content, which allows the identification of the genomic features responsible for the respective clustering. By using different intergenomic distances, the hierarchical trees produced by VirClust can be split into viral genome clusters of different taxonomic ranks. VirClust is freely available, as web-service (virclust.icbm.de) and stand-alone tool.
Epigenetic features improve TALE target prediction
Authors: Erkes Annett , Mücke Stefanie , Reschke Maik , Boch Jens , Grau Jan 
Published: June 2021

AbstractThe yield of many crop plants can be substantially reduced by plant-pathogenic Xanthomonas bacteria. The infection strategy of many Xanthomonas strains is based on transcription activator-like effectors (TALEs), which are secreted into the host cells and act as transcriptional activators of plant genes that are beneficial for the bacteria.The modular DNA binding domain of TALEs contains tandem repeats, each comprising two hyper-variable amino acids. These repeat-variable diresidues (RVDs) bind to a continuous DNA stretch (a target box) and determine the specificity of a TALE. All available tools for the prediction of TALE targets within the host plant suffer from many false positives. In this paper we propose a strategy to improve prediction accuracy by considering the epigenetic state of the host plant genome in the region of the target box. To this end, we extend our previously published tool PrediTALE by two epigenetic features: (i) We allow for filtering target boxes according to chromatin accessibility and (ii) we allow for considering the methylation state of cytosines within the target box during prediction, since DNA methylation may affect the binding specificity of RVDs. Here, we determine the epigenetic features from publicly available DNase-seq, ATAC-seq, and WGBS-seq data in rice.We benchmark the utility of both epigenetic features separately and in combination, deriving ground-truth from RNA-seq infections studies in rice. We find an improvement for each individual epigenetic feature, but especially the combination of both. Having established an advantage in TALE target predicting considering epigenetic features, we use these data for promoterome and genome-wide scans by our new tool EpiTALE, leading to several novel putative virulence targets.Our results suggest that it would be worthwhile to collect condition-specific chromatin accessibility data and methylation information when studying putative virulence targets of Xan-thomonas TALEs.
Development Of Novel Multiplex PCR For Rapid Diagnosis Of Coinfected Hemo-Parasites In Cattle
Authors: Kumar Pankaj , Kumar Abhay , Sarma Kamal , Sharma Paresh , Kumari Rashmi Rekha , Kumar Manish 
Published: June 2021

ABSTRACTA novel, rapid and specific multiplex polymerase chain reaction has been developed for the diagnosis of hemo-parasitic infection in bovine blood by three of the most common hemo-parasites. The reported method relied on the detection of the three different bovine hemoparasites isolated from red blood cells (RBCs) of cattle by conventional Giemsa stained blood smear (GSBS) and confirmed by multiplex PCR. The designed multiplex primer sets can amplify 205, 313 and 422 bp fragments of apocytochrome b, sporozoite and macroschizont 2 (spm2) and 16S rRNA gene for Babesia bigemina, Theileria annulata and Anaplasma marginale, respectively. This multiplex PCR was sensitive with the ability to detect the presence of 150 ng of genomic DNA. The primers used in this multiplex PCR also showed highly specific amplification of specific gene fragments of each respective parasite DNA without the presence of non-specific and non-target PCR products. This multiplex PCR system was used to diagnose GSBS confirmed blood samples (N=12) found infected or co-infected with hemoparasites. A comparison of the two detection methods revealed that 58.33% of specimens showed concordant diagnoses with both techniques. The specificity, positive predictive value and kappa coefficient of agreement was highest for diagnosis of B. bigemina and lowest for A. marginale. The overall Kappa coefficient for diagnosis based on GSBS for multiple pathogen compared to multiplex PCR was 0.56 slightly behind the threshold of 0.6 of agreement. Therefore, confirmation should always be made based on PCR to rule out false positive due to differences in subjective observations, stain particles and false negative due to low level of parasitaemia. The simplicity and rapidity of this specific multiplex PCR method make it suitable for large-scale epidemiological studies and for follow-up of drug treatments.
EEG-based visual deviance detection in freely behaving mice
Authors: Kat Renate , van den Berg Berry , Perenboom Matthijs JL , Schenke Maarten , van den Maagdenberg Arn MJM , Bruining Hilgo , Tolner Else A , Kas Martien JH 
Published: June 2021

AbstractThe mouse is widely used as an experimental model to study visual processing. To probe how the visual system detects changes in the environment, functional paradigms in freely behaving mice are strongly needed. We developed and validated the first EEG-based method to investigate visual deviance detection in freely behaving mice. Mice with EEG implants were exposed to a visual deviant detection paradigm that involved changes in light intensity as standard and deviant stimuli. By subtracting the standard from the deviant evoked waveform, deviant detection was evident as bi-phasic negativity (starting around 70 ms) in the difference waveform. Additionally, deviance-associated evoked (beta/gamma) and induced (gamma) oscillatory responses were found. We showed that the results were stimulus-independent by applying a “flip-flop” design and the results showed good repeatability in an independent measurement. Together, we put forward a validated, easy-to-use paradigm to measure visual deviance processing in freely behaving mice.
Nash equilibria in human sensorimotor interactions explained by Q-Learning
Authors: Lindig-León Cecilia , Schmid Gerrit , Braun Daniel A. 
Published: June 2021

ABSTRACTThe Nash equilibrium concept has previously been shown to be an important tool to understand human sensorimotor interactions, where different actors vie for minimizing their respective effort while engaging in a multi-agent motor task. However, it is not clear how such equilibria are reached. Here, we compare different reinforcement learning models based on haptic feedback to human behavior in sensorimotor versions of three classic games, including the Prisoners’ Dilemma, and the symmetric and asymmetric matching pennies games. We find that a discrete analysis that reduces the continuous sensorimotor interaction to binary choices as in classical matrix games does not allow to distinguish between the different learning algorithms, but that a more detailed continuous analysis with continuous formulations of the learning algorithms and the game-theoretic solutions affords different predictions. In particular, we find that Q-learning with intrinsic costs that disfavor deviations from average behavior explains the observed data best, even though all learning algorithms equally converge to admissible Nash equilibrium solutions. We therefore conclude that it is important to study different learning algorithms for understanding sensorimotor interactions, as such behavior cannot be inferred from a game-theoretic analysis alone, that simply focuses on the Nash equilibrium concept, as different learning algorithms impose preferences on the set of possible equilibrium solutions due to the inherent learning dynamics.
Three recent sex chromosome-to-autosome fusions in aDrosophila virilisstrain with high satellite content
Authors: Flynn Jullien M. , Hu Kevin B. , Clark Andrew G. 
Published: June 2021

ABSTRACTThe karyotype, or number and arrangement of chromosomes, has varying levels of stability across both evolution and disease. Karyotype changes often originate from DNA breaks near the centromeres of chromosomes, which generally contain long arrays of tandem repeats or satellite DNA.Drosophila virilispossesses among the highest relative satellite abundances of studied species, with almost half its genome composed of three related 7bp satellites. We discovered a strain ofD. virilisthat we infer recently underwent three independent chromosome fusion events involving the X and Y chromosomes, in addition to one subsequent fission event. Here we isolate, characterize and propose a timeline for the chromosome fusions in this strain which we believe demonstrates a remarkable karyotype instability. We discovered that one of the substrains with an X-autosome fusion has a X-to-Y chromosome nondisjunction rate 20x higher than theD. virilisreference strain (21% vs. 1%). Finally, we found an overall higher rate of DNA breakage in the substrain with higher satellite DNA compared to a genetically similar substrain with less satellite DNA. This suggests satellite DNA abundance may play a role in the risk of genome instability. Overall, we introduce a novel system consisting of a single strain with four different karyotypes, which we believe will be useful for future studies of genome instability, centromere function, and sex chromosome evolution.
Serotonergic Neurons Mediate Operant Conditioning in Drosophila Larvae
Authors: Klein Kristina T , Croteau-Chonka Elise C , Narayan Lakshmi , Winding Michael , Masson Jean-Baptiste , Zlatic Marta 
Published: June 2021

AbstractObserved across species, operant conditioning facilitates learned associations between behaviours and outcomes, biasing future action selection to maximise reward and avoid punishment. To elucidate the underlying neural mechanisms, we built a high-throughput tracker for Drosophila melanogaster larvae, combining real-time behaviour detection with closed-loop optogenetic and thermogenetic stimulation capabilities. We demonstrate operant conditioning in Drosophila larvae by inducing a bend direction preference through optogenetic activation of reward-encoding serotonergic neurons. Specifically, we establish that the ventral nerve cord is necessary for this memory formation. Our results extend the role of serotonergic neurons for learning in insects as well as the existence of learning circuits outside the mushroom body. This work supports future studies on the function of serotonin and the mechanisms underlying operant conditioning at both circuit and cellular levels.
Supply chain performance for a traditional shipbuilding industry in Indonesia
Authors: Praharsi Yugowati , Jami'in Mohammad Abu , Suhardjito Gaguk , Reong Samuel , Wee Hui Ming 
Published: June 2021

PurposeStudy in supply chain performance research on the shipbuilding industry is lacking. The purpose of this research is to study and provide guidelines to improve the performance of traditional shipbuilding supply chains in Indonesia.Design/methodology/approachThe paper develops an empirical study gathered from a traditional shipbuilding industry, its suppliers, and customers. This study consists of three sections: the traditional shipbuilding industry, the suppliers, and the individual supplier scores. The internal and external performances in this study are measured using Supply Chain Operations Reference (SCOR) metrics. The SCOR model identifies five performance measurement attributes, including reliability, flexibility, responsiveness, cost and assets. Instead of using “responsiveness,” this study applies the schedule performance index, and supplements “cost” with the cost performance index in order to accurately reflect the traditional shipbuilding supply chains processes.FindingsBy analyzing SCOR metrics in the traditional shipbuilding industry, it has been found that the ideal shipbuilding supply chain metrics are order fulfillment, flexibility, asset turnover and total supply chain costs. The lowest performance metric value in the traditional shipbuilding industry is the cost of goods. Some improvements are proposed to lower the high cost of ship building. An integrated economic ordering system in collaboration with all the suppliers is one of the most effective ways to reduce the cost of the traditional shipbuilding supply chains. The implementation of SCOR metrics enables management to identify the critical issues to improve.Research limitations/implicationsThe study applies SCOR metrics to improve the traditional shipbuilding supply chains performance. The study is limited because the data collected are based on one shipbuilding industry only.Originality/valueTo the author's knowledge, this is the first empirical analysis on the implementation of SCOR metrics to the traditional shipbuilding industry. The analysis to improve the traditional shipbuilding supply chains performance can provide managerial insights to other industries.
Investigating the causes preventing the fulfillment of construction contract requirements
Authors: Fatayer Fadi A. , Issa Amjad Z. , Abunemeh Mohammed , Dwikat Mohammed A.M. 
Published: June 2021

PurposeConstruction contractors in Palestine, as in many other developing countries, suffer from many problems. One of their main problems is their inability to meet contractual requirements, such as completing projects within time, at the agreed cost and to the desired quality. Therefore, this paper aims to investigate the causes of the non-fulfillment of contractual requirements in three different types of projects: building, road and electro-mechanical projects.Design/methodology/approachTwo methods were adopted to collect the data – qualitative and quantitative. In total, 65 causes were identified from the literature and qualitative semi-structured interviews with professional experts. These causes were classified into five categories: managerial, financial, contractor capabilities, regulations and laws and political. In the quantitative approach, a questionnaire was developed and then distributed to 50 professional experts: 20 building experts, 15 road experts and 15 experts in electro-mechanical projects. A five-point Likert scale was used to assess the importance, from the perspective of the subject matter experts, of the causes that had been identified. About 35 responses, which represent a combined response rate of 70%, were received. The quantitative data were analyzed using descriptive statistics, with the mean, standard deviation and degree of importance for each of the identified causes being determined, and the SPSS software platform used to rank them.FindingsThe results reveal that the most important reasons why contractors did not fulfill their contractual requirements in building projects were that contracts were awarded to the contractor offering the lowest price, and the profit margin was low because of intense competition among contractors. In road projects, the most important causes were the poor estimation of the equipment required and a lack of standardized conditions in the construction sector, while in electro-mechanical projects, the most important causes were the inability of the contractor to estimate the cost of the project accurately because of unclear bid documents and a lack of contractor capital.Originality/valueThe results of this study will be useful to stakeholders and Palestinian contractor unions. They can be disseminated to give guidance so that contractors can avoid these problems in future construction projects and enhance their compliance with contractual requirements. Moreover, knowing about these causes may lead to the reduction of conflicts and disputes between contractual parties (owners and contractors), which in turn will be reflected in the work quality and reputation of contractors.