bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identifying potential natural inhibitors of Brucella melitensis Methionyl-tRNA synthetase through an in-silico approach
Authors: Rowaiye Adekunle Babjide , Ogugua Akwoba Joseph , Ibeanu Gordon , Bur Doofan , Ogbeide Osaretin Benjamin , Abraham Emmanuella Oshiorenimeh , Usman Hamzah Bundu 
Published: September 2021

AbstractBackgroundBrucellosis is an infectious disease caused by bacteria of the genus Brucella. Although it is the most common zoonosis worldwide, there are increasing reports of drug resistance and cases of relapse after long term treatment with the existing drugs of choice. This study therefore aims at identifying possible natural inhibitors of Brucella melitensis Methionyl-tRNA synthetase through an in-silico approach.MethodsUsing PyRx 0.8 virtual screening software, the target was docked against a library of natural compounds obtained from edible African plants. The compound, 2-({3-[(3,5-dichlorobenzyl) amino] propyl} amino) quinolin-4(1H)-one (OOU) which is a co-crystallized ligand with the target was used as the reference compound. Screening of the molecular descriptors of the compounds for bioavailability, pharmacokinetic properties, and bioactivity was performed using the SWISSADME, pkCSM, and Molinspiration web servers respectively. The Fpocket and PLIP webservers were used to perform the analyses of the binding pockets and the protein ligand interactions. Analysis of the time-resolved trajectories of the Apo and Holo forms of the target was performed using the Galaxy and MDWeb servers. The lead compounds, Strophanthidin and Isopteropodin are present in Corchorus olitorius and Uncaria tomentosa (cat-claw) plants respectively.ResultsIsopteropodin had a binding affinity score of -8.9 kcal / ml with the target and had 17 anti-correlating residues in pocket 1 after molecular dynamics simulation. The complex formed by Isopteropodin and the target had a total RMSD of 4.408 and a total RMSF of 9.8067. However, Strophanthidin formed 3 hydrogen bonds with the target at ILE21, GLY262 and LEU294, and induced a total RMSF of 5.4541 at Pocket 1.ConclusionOverall, Isopteropodin and Strophanthidin were found to be better drug candidates than OOU and they showed potentials to inhibit the Brucella melitensis Methionyl-tRNA synthetase at Pocket 1, hence abilities to treat brucellosis. In vivo and in vitro investigations are needed to further evaluate the efficacy and toxicity of the lead compounds.Author SummaryStrophanthidin and Isopteropodin showed potentials to inhibit the Brucella melitensis Methionyl-tRNA synthetase at Pocket 1Both compounds can be used to treat brucellosis.Both compounds showed potentials of being safe to use in humans.
A flow-based latent state generative model of neural population responses to natural images
Authors: Bashiri Mohammad , Walker Edgar Y. , Lurz Konstantin-Klemens , Jagadish Akshay Kumar , Muhammad Taliah , Ding Zhiwei , Ding Zhuokun , Tolias Andreas S. , Sinz Fabian H. 
Published: September 2021

AbstractWe present a joint deep neural system identification model for two major sources of neural variability: stimulus-driven and stimulus-conditioned fluctuations. To this end, we combine (1) state-of-the-art deep networks for stimulus-driven activity and (2) a flexible, normalizing flow-based generative model to capture the stimulus-conditioned variability including noise correlations. This allows us to train the model end-to-end without the need for sophisticated probabilistic approximations associated with many latent state models for stimulus-conditioned fluctuations. We train the model on the responses of thousands of neurons from multiple areas of the mouse visual cortex to natural images. We show that our model outperforms previous state-of-the-art models in predicting the distribution of neural population responses to novel stimuli, including shared stimulus-conditioned variability. Furthermore, it successfully learns known latent factors of the population responses that are related to behavioral variables such as pupil dilation, and other factors that vary systematically with brain area or retinotopic location. Overall, our model accurately accounts for two critical sources of neural variability while avoiding several complexities associated with many existing latent state models. It thus provides a useful tool for uncovering the interplay between different factors that contribute to variability in neural activity.
B cell-intrinsic requirement for WNK1 kinase in T cell-dependent antibody responses
Authors: Hayward Darryl , Vanes Lesley , Wissmann Stefanie , Sivapatham Sujana , Hartweger Harald , O’May Joshua Biggs , Boer Leon De , Mitter Richard , Köchl Robert , Stein Jens V. , Tybulewicz Victor L. J. 
Published: September 2021

AbstractMigration and adhesion play critical roles in B cells, regulating recirculation between lymphoid organs, migration within lymphoid tissue and interaction with CD4+ T cells. However, there is limited knowledge of how B cells integrate chemokine receptor and integrin signaling with B cell activation to generate efficient humoral responses. Here we show that the WNK1 kinase, a regulator of migration and adhesion, is essential in B cells for T-dependent antibody responses. We demonstrate that WNK1 transduces signals from the BCR, CXCR5 and CD40, and using intravital imaging we show that WNK1 regulates migration of naive and activated B cells, and their interactions with T cells. Unexpectedly, we show that WNK1 is required for BCR- and CD40-induced proliferation, acting through the OXSR1 and STK39 kinases, and for efficient B cell-T cell collaboration in vivo. Thus, WNK1 is critical for humoral immune responses, by regulating B cell migration, adhesion and T cell-dependent activation.SummaryThe WNK1 kinase is essential in B cells for T-dependent antibody responses because it is activated by signaling from BCR, CXCR5 and CD40 and regulates B cell migration, adhesion, T-dependent activation, and differentiation into germinal center B cells and plasma cells.
SkewDB: A comprehensive database of GC and 10 other skews for over 28,000 chromosomes and plasmids
Authors: Hubert Bert 
Published: September 2021

ABSTRACTGC skew denotes the relative excess of G nucleotides over C nucleotides on the leading versus the lagging replication strand of eubacteria. While the effect is small, typically around 2.5%, it is robust and pervasive. GC skew and the analogous TA skew are a localized deviation from Chargaff’s second parity rule, which states that G and C, and T and A occur with (mostly) equal frequency even within a strand.Most bacteria also show the analogous TA skew. Different phyla show different kinds of skew and differing relations between TA and GC skew.This article introduces an open access database (https://skewdb.org) of GC and 10 other skews for over 28,000 chromosomes and plasmids. Further details like codon bias, strand bias, strand lengths and taxonomic data are also included. The SkewDB database can be used to generate or verify hypotheses. Since the origins of both the second parity rule, as well as GC skew itself, are not yet satisfactorily explained, such a database may enhance our understanding of microbial DNA.
Data cleaning for image-based profiling enhancement
Authors: Rezvani Arghavan , Bigverdi Mahtab , Rohban Mohammad Hossein 
Published: September 2021

AbstractWith the advent of high-throughput assays, a large number of biological experiments can be carried out. Image-based assays are among the most accessible and inexpensive technologies for this purpose. Indeed, these assays have proved to be effective in characterizing unknown functions of genes and small molecules. Image analysis pipelines have a pivotal role in translating raw images that are captured in such assays into useful and compact representation, also known as measurements. CellProfiler is a popular and commonly used tool for this purpose through providing readily available modules for the cell/nuclei segmentation, and making various measurements, or features, for each cell/nuclei. Single cell features are then aggregated for each treatment replica to form treatment “profiles.” However, there may be several sources of error in the CellProfiler quantification pipeline that affects the downstream analysis that is performed on the profiles. In this work, we examined various preprocessing approaches to improve the profiles. We consider identification of drug mechanisms of action as the downstream task to evaluate such preprocessing approaches. Our enhancement steps mainly consist of data cleaning, cell level outlier detection, toxic drug detection, and regressing out the cell area from all other features, as many of them are widely affected by the cell area. We also examined unsupervised and weakly-supervised deep learning based methods to reduce the feature dimensionality, and finally suggest possible avenues for future research.
Auditory Word Comprehension is Less Incremental in Isolated Words
Authors: Gaston Phoebe , Brodbeck Christian , Phillips Colin , Lau Ellen 
Published: September 2021

AbstractPartial speech input is often understood to trigger rapid and automatic activation of successively higher-level representations of words, from sound to meaning. Here we show evidence from magnetoencephalography that this type of incremental processing is limited when words are heard in isolation as compared to continuous speech. This suggests a less unified and automatic word recognition process than is often assumed. We present evidence from isolated words that neural effects of phoneme probability, quantified by phoneme surprisal, are significantly stronger than (statistically null) effects of phoneme-by-phoneme lexical uncertainty, quantified by cohort entropy. In contrast, we find robust effects of both cohort entropy and phoneme surprisal during perception of connected speech, with a significant interaction between the contexts. This dissociation rules out models of word recognition in which phoneme surprisal and cohort entropy are common indicators of a uniform process, even though these closely related information- theoretic measures both arise from the probability distribution of wordforms consistent with the input. We propose that phoneme surprisal effects reflect automatic access of a lower level of representation of the auditory input (e.g., wordforms) while the occurrence of cohort entropy effects is task-sensitive, driven by a competition process or a higher-level representation that is engaged late (or not at all) during the processing of single words.
Widespread roles ofTrypanosoma bruceiATR in nuclear genome function and transmission are linked to R-loops
Authors: Black J.A. , Crouch K. , Briggs E. , Lemgruber L. , Lapsely C. , Tosi L. R. O. , Mottram J. C. , McCulloch R. 
Published: September 2021

AbstractInheritance of aberrant chromosomes can compromise genome integrity and affect cellular fitness. In eukaryotes, surveillance pathways and cell cycle checkpoints monitor for aberrant DNA transmission and the ATR kinase, a regulator of the DNA damage response, plays a pivotal role. Prior work revealed that ATR acts during antigenic variation inTrypanosoma bruceimammal-infective life cycle forms and that its loss is lethal, but how widely ATR operates in genome maintenance is largely unknown. Here, we show that after prolonged ATR depletion by RNAiT. bruceicontinues to synthesise DNA and enters new rounds of cell division, despite increased genome damage. Furthermore, we detect defective chromosome segregation, ‘micronuclei’ formation and disruption of the nuclear architecture. RNA-seq revealed that loss of ATR affects the expression of nearly half the genes in the genome, including both RNA Polymerase I and II transcription. Using ChIP-seq of yH2A and DRIP-seq, we reveal overlapping signals for genome damage and R-loops after ATR depletion in all intergenic regions. In addition, we report reduced R-loop levels and accumulation of yH2A signal within centromeres. Together, our data indicates widespread roles of ATR inT. brucei, including differing roles in R-loop homeostasis during multigene transcription and in chromosome segregation.
Investigation of gating in outer membrane porins provides new perspectives on antibiotic resistance mechanisms
Authors: Vasan Archit Kumar , Haloi Nandan , Ulrich Rebecca Joy , Metcalf Mary Elizabeth , Wen Po-Chao , Metcalf William W. , Hergenrother Paul J. , Shukla Diwakar , Tajkhorshid Emad 
Published: September 2021

AbstractGram-negative bacteria pose a serious public health concern, primarily due to a higher frequency of antibiotic resistance conferred to them as a result of low permeability of their outer membrane (OM). Antibiotics capable of traversing the OM typically permeate through OM porins; thus, understanding the permeation properties of these porins is instrumental to the development of new antibiotics. A common macroscopic feature of many OM porins is their ability to transition between functionally distinct open and closed states that regulate transport properties and rate. To obtain a molecular basis for these processes, we performed tens of microseconds of molecular dynamics simulations of E. coli OM porin, OmpF. We observed that large-scale motion of the internal loop, L3, leads to widening and narrowing of the pore, suggesting its potential role in gating. Furthermore, Markov state analysis revealed multiple energetically stable conformations of L3 corresponding to open and closed states of the porin. Dynamics between these functional states occurs on the time scale of tens of microseconds and are mediated by the movement of highly conserved acidic residues of L3 to form H-bonds with opposing sides of the barrel wall of the pore. To validate our mechanism, we mutated key residues involved in the gating process that alter the H-bond pattern in the open/closed states and performed additional simulations. These mutations shifted the dynamic equilibrium of the pore towards open or closed states. Complementarily, the mutations favoring the open/closed states lead to increased/decreased accumulation of multiple antibiotics in our whole-cell accumulation assays. Notably, porins containing one of the mutations favoring the closed state has previously been found in antibiotic resistant bacterial strains. Overall, our 180 µs of simulation data (wild type and mutants) with concerted experiments suggests that regulation of the dynamic equilibrium between open and closed states of OM porins could be a mechanism by which Gram-negative bacteria acquire antibiotic resistance.
Comparative analysis of L-fucose utilization and its impact on growth and survival of Campylobacter isolates
Authors: Middendorf Pjotr S. , Jacobs-Reitsma Wilma F. , Zomer Aldert L. , Besten Heidy M. W. den , Abee Tjakko 
Published: September 2021

AbstractCampylobacter jejuni and Campylobacter coli were previously considered asaccharolytic, but are now known to possess specific saccharides metabolization pathways, including L-fucose. To investigate the influence of the L-fucose utilization cluster on Campylobacter growth, survival and metabolism, we performed comparative genotyping and phenotyping of the C. jejuni reference isolate NCTC11168 (human isolate), C. jejuni Ca1352 (chicken meat isolate), C. jejuni Ca2426 (sheep isolate), and C. coli Ca0121 (pig manure isolate), that all possess the L-fucose utilization cluster.All isolates showed enhanced survival and prolonged spiral cell morphology in aging cultures up to day seven in L-fucose-enriched MEMα medium (MEMαF) compared to MEMα. HPLC analysis indicated L-fucose utilization linked to acetate, lactate, pyruvate and succinate production, confirming the activation of the L-fucose pathway in these isolates. Highest consumption of L-fucose by C. coli Ca0121, is conceivably linked to its enhanced growth performance up to day 7, reaching 9.3 log CFU/ml compared to approximately 8.3 log CFU/ml for the C. jejuni isolates. Genetic analysis of their respective L-fucose clusters revealed several differences, including a 1 bp deletion in the Cj0489 gene of C. jejuni NCTC11168, causing a frameshift in this isolate resulting in two separate genes, Cj0489 and Cj0490, while no apparent phenotype could be linked to the presumed frameshift in the NCTC11168 isolate. Additionally, we found that the L-fucose cluster of C. coli Ca0121 was most distant from C. jejuni NCTC11168, but confirmation of links to L-fucose metabolism associated phenotypic traits in C. coli versus C. jejuni isolates requires further studies.ImportanceCampylobacter is the leading cause of gastroenteritis in humans worldwide, with increasing incidence and prevalence in recent years. The most prevalent species are Campylobacter jejuni and C. coli with 83% and 10% of all Campylobacter cases, respectively. Previously it was found that the majority of Campylobacter isolates are able to metabolize L-fucose (fuc+ isolates), a sugar that is widely present in the human gut. Putative roles for L-fucose in fuc+ C. jejuni isolates were found in growth, biofilm formation and virulence. Despite this, relatively little is known about L-fucose metabolism and the impact on growth and survival in fuc+ Campylobacter isolates. The results from our comparative genotyping and phenotyping study demonstrate that L-fucose, in both C. jejuni and C. coli fuc+ isolates, is involved in enhanced survival, prolonged spiral cell morphology and changes in the general metabolism. Possible links between phenotypes and differences in respective L-fucose gene clusters are discussed.
The ribbon architecture of the Golgi apparatus is not restricted to vertebrates
Authors: Benvenuto Giovanna , Arnone Maria Ina , Ferraro Francesco 
Published: September 2021

AbstractThe Golgi apparatus plays a central role as a processing and sorting station along the secretory pathway. In multicellular organisms, this organelle displays two structural organizations, whereby its functional subunits, the mini-stacks, are either dispersed throughout the cell or linked into a centralized structure, called Golgi “ribbon”. The Golgi ribbon is considered to be a feature typical of vertebrate cells. Here we report that this is not the case. We show that sea urchin embryonic cells assemble Golgi ribbons during early development. Sea urchins are deuterostomes, the bilaterian animal clade to which chordates, and thus vertebrates, also belong.Far from being a structural innovation of vertebrates, the Golgi ribbon therefore appears to be an ancient cellular feature evolved before the split between echinoderms and chordates. Evolutionary conservation of the ribbon architecture surmises that it must play fundamental roles in the biology of deuterostomes.
pH-dependent polymorphism of the structure of SARS-CoV-2 nsp7
Authors: Lee Yeongjoon , Tonelli Marco , Rahimi Mehdi , Anderson Thomas K. , Kirchdoerfer Robert N. , Henzler-Wildman Katherine , Lee Woonghee 
Published: September 2021

AbstractThe solution structure of SARS-CoV-2 nonstructural protein 7 (nsp7) at pH 7.0 has been determined by NMR spectroscopy. nsp7 is conserved in the coronavirinae subfamily and is an essential co-factor of the viral RNA-dependent RNA polymerase for active and processive replication. Similar to the previously deposited structures of SARS-CoV-1 nsp7 at acidic and basic conditions, SARS-CoV-2 nsp7 has a helical bundle folding at neutral pH. Remarkably, the α4 helix shows gradual dislocation from the core α2-α3 structure as pH increases from 6.5 to 7.5. The protonation state of residue H36 contributes to the change of nsp7’s intramolecular interactions, and thus, to the structural variation near-neutral pH. Spin-relaxation results revealed that all three loop regions in nsp7 possess dynamic properties associated with this structural variation.
Toward diffusion of e-Zakat initiatives amid the COVID-19 crisis and beyond
Authors: Bin-Nashwan Saeed Awadh 
Published: September 2021

Purpose
While the financial relief efforts are struggling to keep up with the COVID-19 outbreak, there is a need for the diffusion of e-Zakat initiatives and work with fintech if governments truly strive to ensure that most vulnerable do not fall behind. The newly launched e-system – popularly known as ZAKATY (e-portal and smartphone application) – in Saudi Arabia is an example worth attention and study on how well people can accept and use the system and Zakat payer-centric e-services, especially amid such uncertain times. The purpose of this study is to explore how an extended unified model of acceptance and use of technology (UTAUT) can induce users to adopt the ZAKATY e-services provided by the General Authority of Zakat and Tax during this unprecedented challenge to pay Zakat online in an easy, fast and reliable way.

Design/methodology/approach
Drawing on a quantitative approach through an online administered survey, a total of 479 usable responses from individual Zakat payers were obtained using snowball sampling and analyzed through smart partial least squares (SmartPLS) software.

Findings
This study confirms the suitability and utility of the UTAUT model used in predicting Zakat payers’ intention to adopt the e-Zakat system and its services, indicating that the model possesses 72% of the predictive capability to explain variance in intentions. It also shows that all UTAUT constructs (i.e. performance expectancy, social influence and facilitating conditions) were statistically significant, except for effort expectancy. Online trust exerted a significant moderating effect on the relationship between UTAUT constructs and users’ intentions to uptake the system’s online services amid COVID-19.

Practical implications
To keep pace with rapid digital transformations amid the pandemic, Zakat institutions, as governmental entities, are likely pursuing to identify the main determinants that influence people’s intentions to engage in adopting e-Zakat services. This could be eventually translated into maximizing the proceeds of Zakat funds by developing ICT-based infrastructure and introducing reliable and efficient e-services that can be adopted by users.

Originality/value
Given the scarce literature on the relevance of e-Zakat systems’ adoption, this work could serve as a building block and springboard for literature and future research by empirically examining an extended framework derived from the UTAUT theory in the Zakat context.