bluuebunny/crossref_metadata_2025 huggingface dataset:
In their sister’s footsteps: Taxonomic divergence obscures substantial functional overlap among the metabolically diverse symbiotic gut communities of adult and larval turtle ants
Authors: Béchade Benoît , Hu Yi , Sanders Jon G. , Cabuslay Christian S. , Łukasik Piotr , Williams Bethany R. , Fiers Valerie J. , Lu Richard , Wertz John T. , Russell Jacob A.
Published: September 2021

Gut bacterial symbionts can support animal nutrition by facilitating digestion and providing valuable metabolites. While the composition of gut symbiont communities shifts with host development in holometabolous insects, changes in symbiotic roles between immature and adult stages are not well documented, especially in ants. Here, we explored the metabolic capabilities of microbiomes sampled from herbivorous turtle ant (Cephalotessp.) larvae and adult workers through genomic and metagenomic screenings and targetedin vitrometabolic assays. We reveal that larval guts harbor bacterial symbionts from the Enterobacteriales, Lactobacillales and Rhizobiales orders, with impressive metabolic capabilities, including catabolism of plant and fungal recalcitrant fibers common in turtle ant diets, and energy-generating fermentation. Additionally, several members of the specialized turtle ant adult gut microbiome, sampled downstream of an anatomical barrier that dams large food particles, show a conserved potential to depolymerize many dietary fibers and other carbohydrates. Symbionts from both life stages have the genomic capacity to recycle nitrogen, synthesize amino acids and B-vitamins, and perform several key aspects of sulfur metabolism. We also document, for the first time in ants, an adult-associated Campylobacterales symbiont with an apparent capacity to anaerobically oxidize sulfide, reduce nitrate, and fix carbon dioxide. With help of their gut symbionts, including several bacteria likely acquired from the environment, turtle ant larvae appear as an important component of turtle ant colony digestion and nutrition. In addition, the conserved nature of the digestive, energy-generating, and nutritive capacities among adult-enriched symbionts suggests that nutritional ecology of turtle ant colonies has long been shaped by specialized, behaviorally-transferred gut bacteria with over 46 million years of residency.
Modular multilevel TMS device with wide output range and ultrabrief pulse capability for sound reduction
Authors: Zeng Zhiyong , Koponen Lari M. , Hamdan Rena , Li Zhongxi , Goetz Stefan M. , Peterchev Angel V.
Published: September 2021

Objective

This article presents a novel transcranial magnetic stimulation (TMS) pulse generator with a wide range of pulse shape, amplitude, and width.

Approach

Based on a modular multilevel TMS (MM-TMS) topology we had proposed previously, we realized the first such device operating at full TMS energy levels. It consists of ten cascaded H-bridge modules, each implemented with insulated-gate bipolar transistors, enabling both novel high-amplitude ultrabrief pulses as well as pulses with conventional amplitude and duration. The MM-TMS device can output pulses including up to 21 voltage levels with a step size of up to 1100 V, allowing relatively flexible generation of various pulse waveforms and sequences. The circuit further allows charging the energy storage capacitor on each of the ten cascaded modules with a conventional TMS power supply.

Main results

The MM-TMS device can output peak coil voltages and currents of 11 kV and 10 kA, respectively, enabling suprathreshold ultrabrief pulses (> 8.25 μs active electric field phase). Further, the MM-TMS device can generate a wide range of near-rectangular monophasic and biphasic pulses, as well as more complex staircase-approximated sinusoidal, polyphasic, and amplitude-modulated pulses. At matched estimated stimulation strength, briefer pulses emit less sound, which could enable quieter TMS. Finally, the MM-TMS device can instantaneously increase or decrease the amplitude from one pulse to the next in discrete steps by adding or removing modules in series, which enables rapid pulse sequences and paired-pulse protocols with variable pulse shapes and amplitudes.

Significance

The MM-TMS device allows unprecedented control of the pulse characteristics which could enable novel protocols and quieter pulses.
Children with amblyaudia show less flexibility in auditory cortical entrainment to periodic non-speech sounds
Authors: Momtaz Sara , Moncrieff Deborah , Ray Meredith A. , Bidelman Gavin M.
Published: September 2021

Objective

We investigated auditory temporal processing in children with amblyaudia (AMB), a subtype of auditory processing disorder, via cortical neural entrainment.

Design and study samples

Evoked responses were recorded to click-trains at slow vs. fast (8.5 vs. 14.9/sec) rates in n=14 children with AMB and n=11 age-matched controls. Source and time-frequency analyses decomposed EEGs into oscillations (reflecting neural entrainment) stemming from the bilateral auditory cortex.

Results

Phase-locking strength in AMB depended critically on the speed of auditory stimuli. In contrast to age-matched peers, AMB responses were largely insensitive to rate manipulations. This rate resistance was seen regardless of the ear of presentation and in both cortical hemispheres.

Conclusion

Children with AMB show a stark inflexibility in auditory cortical entrainment to rapid sounds. In addition to reduced capacity to integrate information between the ears, we identify more rigid tagging of external auditory stimuli. Our neurophysiological findings may account for certain temporal processing deficits commonly observed in AMB and related auditory processing disorders (APDs) behaviorally. More broadly, our findings may inform communication strategies and future rehabilitation programs; increasing the rate of stimuli above a normal (slow) speech rate is likely to make stimulus processing more challenging for individuals with AMB/APD.
Phosphatidylglycerol synthesis facilitates plastid gene expression and light induction of nuclear photosynthetic genes
Authors: Fujii Sho , Kobayashi Koichi , Lin Ying-Chen , Liu Yu-chi , Nakamura Yuki , Wada Hajime
Published: September 2021

Phosphatidylglycerol (PG) is the only major phospholipid in the thylakoid membrane of chloroplasts. PG is essential for photosynthesis and loss of PG in Arabidopsis thaliana results in severe defects of growth and chloroplast development with decreased chlorophyll accumulation, impaired thylakoid formation, and downregulation of photosynthesis-associated genes encoded in nuclear and plastid genomes. However, how the absence of PG affects the gene expression and plant growth remains unclear. To elucidate this mechanism, we investigated the growth and transcriptional profiles of a PG-deficient Arabidopsis mutant pgp1-2 under various light conditions. Microarray analysis demonstrated that reactive oxygen species-responsive genes were upregulated in pgp1-2. Decreased growth light did not alleviated the impaired leaf development and the downregulation of photosynthesis-associated genes in pgp1-2, indicating limited impacts of photooxidative stress on the defects of pgp1-2. Illumination to dark-adapted pgp1-2 triggered downregulation of photosynthesis-associated nuclear-encoded genes (PhANGs), while plastid-encoded genes were constantly suppressed. Overexpression of GOLDEN2-LIKE1 (GLK1), a transcription factor regulating chloroplast development, in pgp1-2 upregulated PhANGs but not plastid-encoded genes along with chlorophyll accumulation. Our data suggest a broad impact of PG biosynthesis on nuclear-encoded genes partially via GLK1 and a specific involvement of this lipid in the plastid gene expression and plant development.
OpenMonkeyChallenge: Dataset and Benchmark Challenges for Pose Tracking of Non-human Primates
Authors: Yao Yuan , Mohan Abhiraj , Bliss-Moreau Eliza , Coleman Kristine , Freeman Sienna M. , Machado Christopher J. , Raper Jessica , Zimmermann Jan , Hayden Benjamin Y. , Park Hyun Soo
Published: September 2021

The ability to automatically track non-human primates as they move through the world is important for several subfields in biology and biomedicine. Inspired by the recent success of computer vision models enabled by benchmark challenges (e.g., object detection), we propose a new benchmark challenge called OpenMonkeyChallenge that facilitates collective community efforts through an annual competition to build generalizable non- human primate pose tracking models. To host the benchmark challenge, we provide a new public dataset consisting of 111,529 annotated (17 body landmarks) photographs of non-human primates in naturalistic contexts obtained from various sources including the internet, three National Primate Research Centers, and the Minnesota Zoo. Such annotated datasets will be used for the training and testing datasets to develop generalizable models with standardized evaluation metrics. We demonstrate the effectiveness of our dataset quantitatively by comparing it with existing datasets based on seven state-of-the-art pose tracking models.
Weight Pulling: A Novel Mouse Model of Human Progressive Resistance Exercise
Authors: Zhu Wenyuan G. , Hibbert Jamie E. , Lin Kuan-Hung , Steinert Nathaniel D. , Lemens Jake L. , Jorgenson Kent W. , Newman Sarah M. , Lamming Dudley W. , Hornberger Troy A.
Published: September 2021

This study describes a mouse model of progressive resistance exercise that utilizes a full-body/multi-joint exercise (weight pulling) along with a training protocol that mimics a traditional human paradigm (3 training sessions per week, ∼8-12 repetitions per set, 2 minutes of rest between sets, ∼2 maximal-intensity sets per session, last set taken to failure, and a progressive increase in loading that is based on the individual’s performance). We demonstrate that weight pulling can induce an increase in the mass of numerous muscles throughout the body. The relative increase in muscle mass is similar to what has been observed in human studies, and it is associated with the same type of long-term adaptations that occur in humans (e.g., fiber hypertrophy, myonuclear accretion, and in some instances a fast-to-slow transition in Type II fiber composition). Moreover, we demonstrate that weight pulling can induce the same type of acute responses that are thought to drive these long-term adaptations (e.g., the activation of signaling through mTORC1 and the induction of protein synthesis at 1 hr post-exercise). Collectively, the results of this study indicate that weight pulling can serve as a highly translatable mouse model of progressive resistance exercise.
Strong and specific connections between retinal axon mosaics and midbrain neurons revealed by large scale paired recordings
Authors: Sibille Jérémie , Gehr Carolin , Benichov Jonathan I. , Balasubramanian Hymavathy , Teh Kai Lun , Lupashina Tatiana , Vallentin Daniela , Kremkow Jens
Published: September 2021

The superior colliculus (SC) is a midbrain structure that plays important roles in visually guided behaviors. Neurons in the SC receive afferent inputs from retinal ganglion cells (RGC), the output cells of the retina, but how SC neurons integrate RGC activityin vivois unknown. SC neurons might be driven by strong but sparse retinal inputs, thereby reliably transmitting specific retinal functional channels. Alternatively, SC neurons could sum numerous but weak inputs, thereby extracting new features by combining a diversity of retinal signals. Here, we discovered that high-density electrodes simultaneously capture the activity and the location of large populations of retinal axons and their postsynaptic SC target neurons, permitting us to investigate the retinocollicular circuit on a structural and functional levelin vivo. We show that RGC axons in the mouse are organized in mosaics that provide a single cell precise representation of the retina as input to SC. This isomorphic mapping between retina and SC builds the scaffold for highly specific wiring in the retinocollicular circuit which we show is characterized by strong connections and limited functional convergence, established in log-normally distributed connection strength. Because our novel method of large-scale paired recordings is broadly applicable for investigating functional connectivity across brain regions, we were also able to identify retinal inputs to the avian optic tectum of the zebra finch. We found common wiring rules in mammals and birds that provide a precise and reliable representation of the visual world encoded in RGCs to neurons in retinorecipient areas.

HIGHLIGHTS

High-density electrodes capture the activity of afferent axons and target neuronsin vivo

Retinal ganglion cells axons are organized in mosaics

Single cell precise isomorphism between dendritic and axonal RGC mosaics

Midbrain neurons are driven by sparse but strong retinal inputs

Functional wiring of the retinotectal circuit is similar in mammals and birds
Joint Registration of Multiple Point Clouds for Fast Particle Fusion in Localization Microscopy
Authors: Wang Wenxiu , Heydarian Hamidreza , Huijben Teun A.P.M. , Stallinga Sjoerd , Rieger Bernd
Published: September 2021

We present a fast particle fusion method for particles imaged with single-molecule localization microscopy. The state-of-the-art approach based on all-to-all registration has proven to work well but its computational cost scales unfavourably with the number of particles N, namely as N2. Our method overcomes this problem and achieves a linear scaling of computational cost with N by making use of the Joint Registration of Multiple Point Clouds (JRMPC) method. Straightforward application of JRMPC fails as mostly locally optimal solutions are found. These usually contain several overlapping clusters, that each consist of well-aligned particles, but that have different poses. We solve this issue by repeated runs of JRMPC for different initial conditions, followed by a classification step to identify the clusters, and a connection step to link the different clusters obtained for different initializations. In this way a single well-aligned structure is obtained containing the majority of the particles.

We achieve reconstructions of experimental DNA-origami datasets consisting of close to 400 particles within only 10 min on a CPU, with an image resolution of 3.2 nm. In addition, we show artifact-free reconstructions of symmetric structures without making any use of the symmetry. We also demonstrate that the method works well for poor data with a low density of labelling and for 3D data.
Differential antibody dynamics to SARS-CoV-2 infection and vaccination
Authors: Chen Yuezhou , Tong Pei , Whiteman Noah B. , Moghaddam Ali Sanjari , Zuiani Adam , Habibi Shaghayegh , Gautam Avneesh , Xiao Tianshu , Cai Yongfei , Chen Bing , Wesemann Duane R.
Published: September 2021

Optimal immune responses furnish long-lasting (durable) antibodies protective across dynamically mutating viral variants (broad). To assess robustness of mRNA vaccine-induced immunity, we compared antibody durability and breadth after SARS-CoV-2 infection and vaccination. While vaccination delivered robust initial virus-specific antibodies with some cross-variant coverage, pre-variant SARS-CoV-2 infection-induced antibodies, while modest in magnitude, showed highly stable long-term antibody dynamics. Vaccination after infection induced maximal antibody magnitudes with enhanced longitudinal stability while infection-naïve vaccinee antibodies fell with time to post-infection-alone levels. The composition of antibody neutralizing activity to variant relative to original virus also differed between groups, with infection-induced antibodies demonstrating greater relative breadth. Differential antibody durability trajectories favored COVID-19-recovered subjects with dual memory B cell features of greater early antibody somatic mutation and cross-coronavirus reactivity. By illuminating an infection-mediated antibody breadth advantage and an anti-SARS-CoV-2 antibody durability-enhancing function conferred by recalled immunity, these findings may serve as guides for ongoing vaccine strategy improvement.
Mechanical and possible auxetic properties of human Achilles tendon during in vitro testing to failure
Authors: Nagelli Christopher V. , Hooke Alexander , Quirk Nicholas , De Padilla Consuelo Lopez , Hewett Timothy E. , van Griensven Martijn , Coenen Michael , Berglund Lawrence , Evans Christopher H. , Müller Sebastian A.
Published: September 2021

The Achilles tendon is the strongest tendon in the human body, but the basis of its high tensile strength has not been elucidated in detail. Here we have loaded healthy, human, Achilles tendons to failure in an anatomically authentic fashion while studying the local three-dimensional deformation and strains in real time, with very high precision, using digital image correlation (DIC). These studies identified a remarkable degree of anisotropic, medio-lateral auxetic behavior, with Poisson’s ratios not exceeding minus 1 in any part of the tendon at any time; under certain loads, discrete areas within the tendon had a Poisson’s ratio below minus 6. Early in the loading cycle, the proximal region of the tendon accumulated high lateral strains while longitudinal strains remained low. This behavior shielded the mid-substance of the tendon, its weakest part, from high longitudinal strains until immediately before rupture. These new insights are of great relevance to understanding the material basis of tendon injuries, designing improved prosthetic replacements, and developing regenerative strategies.
blupADC: An R package and shiny toolkit for comprehensive genetic data analysis in animal and plant breeding
Authors: Mei Quanshun , Fu Chuanke , Li Jieling , Zhao Shuhong , Xiang Tao
Published: September 2021

Genetic analysis is a systematic and complex procedure in animal and plant breeding. With fast development of high-throughput genotyping techniques and algorithms, animal and plant breeding has entered into a genomic era. However, there is a lack of software, which can be used to process comprehensive genetic analyses, in the routine animal and plant breeding program. To make the whole genetic analysis in animal and plant breeding straightforward, we developed a powerful, robust and fast R package that includes genomic data format conversion, genomic data quality control and genotype imputation, breed composition analysis, pedigree tracing, analysis and visualization, pedigree-based and genomic-based relationship matrix construction, and genomic evaluation. In addition, to simplify the application of this package, we also developed a shiny toolkit for users.

Availability and implementation

blupADC is developed primarily in R with core functions written in C++. The development version is maintained athttps://github.com/TXiang-lab/blupADC.

Supplementary information

Supplementary dataare available online
Visualizing the Costs and Benefits of Correcting P-Values for Multiple Hypothesis Testing in Omics Data
Authors: Shuken Steven R. , McNerney Margaret W.
Published: September 2021

The multiple hypothesis testing problem is inherent in high-throughput quantitative genomic, transcriptomic, proteomic, and other “omic” screens. The correction of p-values for multiple testing is a critical element of quantitative omic data analysis, yet many researchers are unfamiliar with the sensitivity costs and false discovery rate (FDR) benefits of p-value correction. We developed models of quantitative omic experiments, modeled the costs and benefits of p-value correction, and visualized the results with color-coded volcano plots. We developed an R Shiny web application for further exploration of these models which we call the Simulator of P-value Multiple Hypothesis Correction (SIMPLYCORRECT). We modeled experiments in which no analytes were truly differential between the control and test group (all null hypotheses true), all analytes were differential, or a mixture of differential and non-differential analytes were present. We corrected p-values using the Benjamini-Hochberg (BH), Bonferroni, and permutation FDR methods and compared the costs and benefits of each. By manipulating variables in the models, we demonstrated that increasing sample size or decreasing variability can reduce or eliminate the sensitivity cost of p-value correction and that permutation FDR correction can yield more hits than BH-adjusted and even unadjusted p-values in strongly differential data. SIMPLYCORRECT can serve as a tool in education and research to show how p-value adjustment and various parameters affect the results of quantitative omics experiments.
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

Background

Brucellosis 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.

Methods

Using 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.

Results

Isopteropodin 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.

Conclusion

Overall, 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 Summary

Strophanthidin and Isopteropodin showed potentials to inhibit the Brucella melitensis Methionyl-tRNA synthetase at Pocket 1

Both 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

We 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

Migration 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.

The 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

GC 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

With 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

Partial 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

Inheritance 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

Gram-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

Campylobacter 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.

Importance

Campylobacter 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

The 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

The 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.
Resolvable polymorphism in an intergrowth of two modifications of tris(diethyldithiocarbamato)antimony
Authors: Ng Seik Weng
Published: September 2021

Tris(diethyldithiocarbamato-κS)antimony(III), [Sb(C5H10NS2)3], is tentatively presumed to comprise a triclinic and a monoclinic polymorph intergrown into each other. The geometry in the triclinic phase is a ψ-capped octahedron and that in the monoclinic phase is a ψ-pentagonal bipyramid. The study also identifies the polyhedral symbols for a reported pair of polymorphs of another SbIII coordination compound, as well as for those of published polymorphic modifications of other BiIII and PbII coordination compounds; the symbols in the pair differ in most of these examples. When differentiating related structures of such classes of coordination compounds, lone-pair stereochemistry may be another informative variable, as stereochemical activity is not always apparent from bond distances and angles only.
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.
Litter decomposition affected by bamboo expansion is modulated by litter‐mixing and microbial composition
Authors: Luan Junwei , Li Siyu , Dong Wei , Liu Yanchun , Wang Yi , Liu Shirong
Published: September 2021

Litter decomposition is a key ecosystem process that drives carbon (C) and nutrient cycling, which could be affected by shifts in plant community composition caused by plant invasion or expansion. However, how changes in leaf litter composition (e.g. litter‐mixing effect) and soil microbial community induced by shift in plant community composition affect decomposition remains elusive.

Here, by deploying 432 litterbags (50‐μm mesh screen), we treated leaf litter of bamboo Phyllostachys edulis and tree species (in a mixture or alone) and decomposed them in forest sites expanded or not expanded by bamboo at three regions, to assess the effects of bamboo expansion on decomposition, microbial community structure and function.

Bamboo expansion reduced microbial C to nitrogen (N) ratio and nutritional stress indicator (cy/pre), which was very likely ascribed to elevated N availability as a result of accelerated litter N release. The N loss of bamboo litter (28.1 ± 3.03%) was more than double of tree species litter (13.2 ± 3.1%), and decomposing litter of bamboo and tree species in a mixture increased litter N loss from 15.3 ± 3.1% to 25.9 ± 3.1% (by 69%). However, no consistent effect of litter type and litter treatment on C loss was observed. The non‐additive litter‐mixing effect is attributable to increased microbial nutrient use efficiency, which is illustrated by the interactive effect between litter treatment and cy/pre on decomposition. Moreover, the forest type interactively affected decomposition with cy/pre as ignoring litter treatment, where higher decay rate and litter N loss at bamboo expanded than non‐expanded sites would be expected when both sites having comparable cy/pre, but the reality is that bamboo expansion tends to have lower cy/pre. These results imply a trade‐off between introduced litter and nutrient use efficiency of local microbial community to drive decomposition.

Our results demonstrate that litter decomposition affected by bamboo expansion was jointly modulated by litter‐mixing and microbial composition, which sheds new insights on predicting changes in soil C and nutrient cycling induced by shifts in plant community composition.

A free plain language summary can be found within the Supporting Information of this article.
Reactivation of hepatitis B virus infection in patients with rheumatoid arthritis receiving tofacitinib
Authors: Wang Sz‐Tsan , Tseng Chih‐Wei , Hsu Chia‐Wen , Tung Chien‐Hsueh , Huang Kuang‐Yung , Lu Ming‐Chi , Lai Ning‐Sheng
Published: September 2021

Objectives

The aim of this study was to investigate hepatitis B virus (HBV) reactivation in patients with rheumatoid arthritis (RA) receiving tofacitinib.

Method

This was a retrospective study performed in a regional teaching hospital in southern Taiwan. During January 2017 and December 2020, patients with a clinician‐confirmed diagnosis of RA using tofacitinib for at least 3 months were enrolled. Serum HBV DNA levels and serum alanine aminotransferase were followed up around every 3 to 6 months to assess HBV reactivation.

Results

A total of 98 patients with RA were enrolled, and eight were hepatitis B surface antigen positive (HBsAg+) (8.1%), 64 were HBsAg‐negative (HBsAg−)/hepatitis B core antibody positive (HBcAb+) (65.3%). In the HBsAg+ patients, two patients received antiviral prophylaxis, and none of them had HBV reactivation or hepatitis flare‐up. The HBV reactivation rate was 33.3% (2/6) in the HBsAg+ RA patient without antiviral prophylaxis. Among the HBsAg−/HBcAb+ patients, the HBV reactivation rate was 3.1% (2/64). The incidence rate of HBV reactivation was 153.8 per 1000 person‐years for overall HBsAg+ patients and 250 per 1000 person‐years after excluding patients receiving antiviral prophylaxis. The incidence rate was 11.2 per 1000 person‐years for HBsAg−/HBcAb+ patients with RA receiving tofacitinib.

Conclusion

Tofacitinib could induce HBV reactivation in both HBsAg+ and HBsAg−/HBcAb+ RA patients. HBsAg+ patients receiving tofacitinib have a high incidence rate of HBV reactivation, which could be prevented by antiviral prophylaxis. Although the risk of reactivation is low in HBsAg−/HBcAb+ patients, closely monitoring HBV DNA and alanine aminotransferase should be suggested.