bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anchors for Time, Distance, and Magnitude in Virtual Movements
Authors: Gladhill Keri Anne , Robinson Eva Marie , Stanfield-Wiswall Candice , Bader Farah , Wiener Martin 
Published: September 2022

AbstractIn order to navigate through the environment, humans must be able to measure both the distance traveled in space, and the interval covered in time. Yet, how these two dimensions are computed and interact across neural systems remains unknown. One possibility is that subjects measure how far and how long they have traveled relative to a known reference point, or anchor. To measure this, we had human participants (n=24) perform a distance estimation task in a virtual environment in which they were cued to attend to either the spatial or temporal interval traveled, while responses were measured with multiband fMRI. We observed that both dimensions evoked similar frontoparietal networks, yet with a striking rostrocaudal dissociation between temporal and spatial estimation. Multivariate classifiers trained on each dimension were further able to predict the temporal or spatial interval traveled, with centers of activation within the supplementary motor area (SMA) and retrosplenial cortex (RSC) for time and space, respectively. Further, a cross-classification approach revealed the right supramarginal gyrus (SMG) and occipital place area (OPA) as regions capable of decoding the general magnitude of the traveled distance. Altogether, our findings suggest the brain uses separate systems for tracking spatial and temporal distances, which are combined together along with amodal estimates.
Practical guide to calculating impact of avidity in models of bispecific antibodies with two membrane-bound targets
Authors: Kareva Irina , Zutshi Anup , Rhoden John , Kabilan Senthil 
Published: September 2022

AbstractHere we present details of the calculation necessary to estimate the impact of avidity in a mathematical model of a bispecific antibody with two membrane-bound targets. The calculation is used to reproduce the results reported in Rhoden et al. (2016) and implemented in Kareva et al. (2018). We reproduce the impact of difference in relative concentration of the two targets on projections of free and bound concentrations of both targets and the antibody and highlight the applicability of this approach for supporting model informed decision making particularly in the early stages of drug discovery and development.
ATF4 Dependent Increase in Mitochondrial-Endoplasmic Reticulum Tethering Following OPA1 Deletion in Skeletal Muscle
Authors: Hinton Antentor , Katti Prasanna , Mungai Margaret , Hall Duane D. , Koval Olha , Shao Jianqiang , Vue Zer , Lopez Edgar Garza , Rostami Rahmati , Neikirk Kit , Ponce Jessica , Streeter Jennifer , Schickling Brandon , Bacevac Serif , Grueter Chad , Marshall Andrea , Beasley Heather K. , Do Koo Young , Bodine Sue C. , Nava Nayeli G. Reyes , Quintana Anita M. , Song Long-Sheng , Grumbach Isabella , Pereira Renata O. , Glancy Brian , Abel E. Dale 
Published: September 2022

SummaryMitochondria and endoplasmic reticulum (ER) contact sites (MERCs) are protein- and lipid-enriched hubs that mediate interorganellar communication by contributing to the dynamic transfer of Ca2+, lipid, and other metabolites between these organelles. Defective MERCs are associated with cellular oxidative stress, neurodegenerative disease, and cardiac and skeletal muscle pathology via mechanisms that are poorly understood. We previously demonstrated that skeletal muscle-specific knockdown (KD) of the mitochondrial fusion mediator optic atrophy 1 (OPA1) induced ER stress and correlated with an induction of Mitofusin-2, a known MERC protein. In the present study, we tested the hypothesis thatOpa1downregulation in skeletal muscle cells alters MERC formation by evaluating multiple myocyte systems, including from mice andDrosophila, and in primary myotubes. Our results revealed that OPA1 deficiency induced tighter and more frequent MERCs in concert with a greater abundance of MERC proteins involved in calcium exchange. Additionally, loss of OPA1 increased the expression of activating transcription factor 4 (ATF4), an integrated stress response (ISR) pathway effector. ReducingAtf4expression prevented the OPA1-loss-induced tightening of MERC structures. OPA1 reduction was associated with decreased mitochondrial and sarcoplasmic reticulum, a specialized form of ER, calcium, which was reversed following ATF4 repression. These data suggest that mitochondrial stress, induced by OPA1 deficiency, regulates skeletal muscle MERC formation in an ATF4-dependent manner.
Imbalanced classification for protein subcellular localisation with multilabel oversampling
Authors: Rana Priyanka , Sowmya Arcot , Meijering Erik , Song Yang 
Published: September 2022

AbstractMotivationSubcellular localisation of human proteins is essential to comprehend their functions and roles in physiological processes, which in turn helps in diagnostic and prognostic studies of pathological conditions and impacts clinical decision making. Since proteins reside at multiple locations at the same time and few subcellular locations host far more proteins than other locations, the computational task for their subcellular localisation is to train a multilabel classifier while handling data imbalance. In imbalanced data, minority classes are underrepresented, thus leading to a heavy bias towards the majority classes and the degradation of predictive capability for the minority classes. Furthermore, data imbalance in multilabel settings is an even more complex problem due to the coexistence of majority and minority classes.ResultsOur studies reveal that based on the extent of concurrence of majority and minority classes, oversampling of minority samples through appropriate data augmentation techniques holds promising scope for boosting the classification performance for the minority classes. We measured the magnitude of data imbalance per class and the concurrence of majority and minority classes in the dataset. Based on the obtained values, we identified minority and medium classes, and a new oversampling method is proposed that includes nonlinear mixup, geometric and colour transformations for data augmentation and a sampling approach to prepare minibatches. Performance evaluation on the Human Protein Atlas Kaggle challenge dataset shows that the proposed method is capable of achieving better predictions for minority classes than existing methods.AvailabilityData used in this study is available at https://www.kaggle.com/competitions/human-protein-atlas-image-classification/data.Contactyang.song1@unsw.edu.auSupplementary informationSupplementary data are available at Bioinformatics online.
Novel Small Molecular Compound AE-848 Showed Potent Inhibitory Activity Against Human Hepatoblastoma Cells
Authors: Wang Juandong , Zhou Qian , Sun Likun , Xu Yaqi , Jiang Yang , Liu Xiaoli , Li Shuo , Li Hui , Zheng Chengyun , Jie Guitao 
Published: September 2022

AbstractPurposeAE-848/33345007, is a novel small molecular compound that was independently synthesized by our laboratory. The aim of the current study was to investigate potential therapeutic effects of the small molecule compound AE-848 on human hepatoblastoma cells.MethodsHuman hepatoblastoma cell line HepG2 was cultured under different concentrations of AE-848. MTT assay was used to detect the inhibitory ability of AE-848 on the activity of this cell line, while flow cytometry was applied to quantify apoptosis. Western-blot technique was used to determine expression levels of signaling pathway-associated molecules. The antitumor in vivo activity of AE-848 against hepatoblastoma was evaluated using hepatoblastoma-bearing nude mice randomly divided into AE-848 (experimental) and saline (control) groups respectively. Changes in survival and tumor sizes were compared between these two groups.ResultsAE-848 significantly inhibited proliferation and induced apoptosis of HepG2 cells, and induced activation of PI3K/Akt/mTOR signaling pathways. More importantly, AE-848 administration significantly inhibited tumor growth and prolonged survival of hepatoblastoma-bearing mice.ConclusionAE-848 had a strong anti-hepatoblastoma activity both in vitro and in vivo, indicating the importance of developing AE-848 as a potential drug for hepatoblastoma treatment.
Immune Isoform Atlas: Landscape of alternative splicing in human immune cells
Authors: Inamo Jun , Suzuki Akari , Ueda Mahoko , Yamaguchi Kensuke , Nishida Hiroshi , Suzuki Katsuya , Kaneko Yuko , Takeuchi Tsutomu , Ishihama Yasushi , Yamamoto Kazuhiko , Kochi Yuta 
Published: September 2022

SummaryAlternative splicing events are a major causal mechanism for complex traits, but they have been understudied due to the limitation of short-read sequencing. Here, we generated a comprehensive full-length isoform annotation of human immune cells, Immune Isoform Atlas, by long-read sequencing for 29 cell subsets. Our atlas contained a number of unannotated transcripts and isoforms such as a read-through transcript of TOMM40-APOE. We profiled functional characteristics of isoforms including encoded domains, inserted repetitive elements, and translational efficiency, and we showed that repetitive elements significantly explained the diversity of unannotated isoforms. Some of the isoforms are expressed in a cell-type specific manner, whose alternative 3’-UTRs usage contributed to their specificity. Further, we identified a number of disease-associated isoforms by isoform switch analysis and by integration of several quantitative trait loci analyses with genome-wide association study data. Our findings will promote the elucidation of the pathomechanism of diseases via alternative splicing.
A novel insertional allele ofCG18135gene is associated with severe mutant phenotypes inDrosophila melanogaster
Authors: Ratiu Attila Cristian , Ionascu Adrian , Ecovoiu Alexandru Al. 
Published: September 2022

AbstractDrosophila melanogasterhas been at the forefront of genetic studies and biochemical modelling for over a century. Yet, the functions of many genes are still unknown mainly because no phenotypic data are available. Herein, we present first evidence data regarding the particular molecular and other quantifiable phenotypes, such as viability and anatomical anomalies, induced by a novelP{lacW}insertional mutant allele ofCG18135gene. So far, theCG18135functions have only been theorized based on electronic annotation and presumptive associations inferred upon high-throughput proteomics or RNA sequencing experiments. The descendants of individuals harboring theCG18135P{lacW}CG18135allele were scored in order to assess mutant embryos, larvae and pupae viability versus Canton Special. Our results revealed that the homozygousCG18135P{lacW}CG18135/CG18135P{lacW}CG18135genotype determines significant lethality both at the inception of larval stage and during pupal development. Few imago escapers that breach the puparium and even more rarely fully exit from it exhibit specific eye depigmentation, wing abnormal unfolding and strong locomotor impairment with apparent spasmodic legs movements. Their maximum lifespan is shorter than two days. When using the quantitative Real-Time PCR (qRT-PCR) method to confirm thatCG18135is indeed upregulated in males compared to females an unexpected gene upregulation was also detected in heterozygous mutants comparative to wild-type flies, probably because of regulatory perturbations induced byP{lacW}transposon. Our work provides the first phenotypic evidence for the essential role ofCG18135, a scenario in accordance with the putative role of this gene in the carbohydrate binding processes.
The dilution effects of healthy lifestyles on the risk of depression attributed to life-course disadvantages among Chinese middle-aged and older adults
Authors: Ren Ziyang , Du Yushan , Lian Xinyao , Zheng Xiaoying , Liu Jufen 
Published: September 2022

AbstractBackgroundLife-course disadvantages and unhealthy lifestyles are well-known to independently induce depression, but their joint effects on depression and whether adopting healthy lifestyles can dilute the depressive risks attributed to life-course disadvantages remain unknown in China.MethodsData were from the China Health and Retirement Longitudinal Study. Life-course (childhood and adulthood) disadvantages were defined using 60 questions and were classified as mild, moderate, and severe by principal component analysis. Healthy lifestyles, including regular exercise, reasonable sleep, never smoking, and no heavy alcohol consumption, were classified as 0/1, 2, 3, and 4. Depression was assessed using CESD-10 with cutoff ≥10. Logistic regression was used to investigate the association of life-course disadvantages and lifestyles with depression and the dilution effects of healthy lifestyles on the depressive risks attributed to life-course disadvantages.ResultsAmong 5724 participants included, sleep and smoking mediated 5.1% and 1.1% the effect of severe life-course disadvantages on depression while exercise mediated - 0.8%. Multiple (vs. 0/1) healthy lifestyles were associated with decreased depressive risks more significantly as the life-course disadvantages increased, with odds ratios (ORs) and 95% confidence intervals (CIs) of 0.44 (0.25-0.80) and 0.33 (0.21-0.53) for 4 healthy lifestyles in participants with mild and severe life-course disadvantages, respectively. Compared to participants with mild life-course disadvantages and 4 healthy lifestyles, those who with severe life-course disadvantages and less than one lifestyles were more than 10 times as significantly associated with depression. Finally, participants with mild/moderate life-course disadvantages but ≤2 healthy lifestyles (vs. severe but 4 lifestyles) were not associated with decreased depressive risks.ConclusionAdopting multiple healthy lifestyles can well-dilute the depressive risks attributed to life-course disadvantages in middle-aged and older Chinese, which is of great importance for reducing the depressive burden and the construction of healthy aging in China.
Interactions between metabolism and growth can determine the co-existence ofStaphylococcus aureusandPseudomonas aeruginosa
Authors: Pajon Camryn , Fortoul Marla C. , Diaz-Tang Gabriela , Meneses Estefania Marin , Mariah Taniya , Toscan Brandon , Marcelin Maili , Lopatkin Allison J. , Eldakar Omar Tonsi , Smith Robert P. 
Published: September 2022

AbstractMost bacteria exist and interact within polymicrobial communities. These interactions produce unique compounds, increased virulence and augmented antibiotic resistance. One community associated with negative healthcare outcomes consists ofPseudomonas aeruginosaandStaphylococcus aureus. When co-cultured, virulence factors secreted byP. aeruginosareduce metabolism and growth inS. aureus. When grownin vitrothis allowsP. aeruginosato driveS. aureustowards extinction. However, when foundin vivo, both species can co-exist. Previous work has noted that this may due to altered gene expression or mutations. However, little is known about how the growth environment could influence co-existence of both species. Using a combination of mathematical modeling and experimentation, we show that changes to bacterial growth and metabolism caused by differences in the growth environment can determine final population composition. We found that changing the carbon source in growth medium affects the ratio of ATP to growth rate for both species, a metric we call absolute growth. We found that as a growth environment increases absolute growth for one species, that species will dominate the co-culture. This is due to interactions between growth, metabolism and metabolism altering virulence factors produced byP. aeruginosa. Finally, we show that the relationship between absolute growth and final population composition can be perturbed by altering the spatial structure in the community. Our results demonstrate that differences in growth environment can account for conflicting observations regarding the co-existence of these bacterial species in the literature, and may offer a novel mechanism to manipulate polymicrobial populations.
A Subtle Balance between Host Selection and Microbial Size Effect Mediates Plant Microbiome Assembly in Mulberry
Authors: He Jintao , Shen Xiaoqiang , Zhang Nan , Muhammad Abrar , Shao Yongqi 
Published: September 2022

AbstractBreeding toward improved ecological plant–microbiome interactions requires improved knowledge of ecological processes/principles underlying microecological patterns, but these remain elusive. Here, we systematically investigated in-planta biogeographic patterns of plant-associated bacteriome and mycobiome along soil– plant and episphere–endosphere continuum in Morus alba. Microecological patterns in diversity, structure, co-occurrence network, species turnover, and assembly process were revealed and varying between bacteriome and mycobiome, possibly driven by multiple factors including host selection, community cohesion, and particularly size-dependent dispersal limitation. Based on these findings, we hypothesized that host selection historically recruits microbiotas, whereas microbial size affects the subsequent turnovers due to the limited dispersal of larger-size microbes. This hypothesis was supported by datasets from other plant species and confirmed by stochastic dispersal experiments showing that smaller-size microbes are more likely to escape/disperse from endosphere niches, contributing to fleeting niches occupied by larger-size microbes. These findings may open new avenues toward an improved understanding of the dynamics of plant microbiome assembly.
Cryo-EM-based structural insights into supramolecular assemblies of γ-Hemolysin from Staphylococcus aureus reveal the pore formation mechanism
Authors: Mishra Suman , Roy Anupam , Dutta Somnath 
Published: September 2022

ABSTRACTγ-hemolysin (γ-HL) is a hemolytic and leukotoxic bicomponent β-pore-forming toxin (β-PFT), a potent virulence factor from Staphylococcus aureus Newman strain. In this study, we performed single particle cryo-EM of γ-HL in a lipid environment. We observed clustering and square lattice packing of octameric HlgAB pores upon membrane bilayer, and an octahedral superassembly of octameric pore complexes, that we resolved at resolution 3.5 Å. Our atomic model further demonstrated the key residues involved in hydrophobic zipping between the rim domains of adjacent octameric pore complexes, thus providing first evidence of additional structural stability in PFTs upon membrane lysis. We also observed lipid densities at the octahedral and octameric interfaces, providing critical insights into the lipid-binding residues involved for both HlgA and HlgB components. Furthermore, the hitherto elusive N-terminal region of HlgA has also been resolved in our cryo-EM map and an overall mechanism of pore formation for bicomponent β-PFTs is proposed.
Systematically attenuating DNA targeting enables CRISPR-driven editing in bacteria
Authors: Collias Daphne , Vialetto Elena , Yu Jiaqi , Co Khoa , Almási Éva d.H. , Rüttiger Ann-Sophie , Achmedov Tatjana , Strowig Till , Beisel Chase L. 
Published: September 2022

ABSTRACTBacterial genome editing commonly relies on chromosomal cleavage with Cas nucleases to counter-select against unedited cells. However, editing normally requires efficient recombination and high transformation efficiencies, which are unavailable in most strains. Here, we show that systematically attenuating DNA targeting activity enables RecA-mediated repair in different bacteria, allowing chromosomal cleavage to drive genome editing. Attenuation can be achieved by altering the format or expression strength of guide (g)RNAs; using nucleases with reduced cleavage activity; or engineering attenuated gRNAs (atgRNAs) with disruptive hairpins, perturbed nuclease scaffolds, non-canonical PAMs, or guide mismatches. These modifications greatly increase cell counts and even improve the efficiency of different types of edits for Cas9 and Cas12a in Escherichia coli and Klebsiella oxytoca. We further applied atgRNAs to restore ampicillin sensitivity in Klebsiella pneumoniae, establishing a new resistance marker for genetic studies. Attenuating DNA targeting thus offers a counterintuitive means to achieve CRISPR-driven editing across bacteria.
Biological and synthetic surfactant exposure increase anti-microbial gene occurrence in a freshwater mixed microbial biofilm environment
Authors: Gill Stephanie P. , Snelling William J. , Dooley James S.G. , Ternan Nigel G. , Banat Ibrahim M. , Arnscheidt Joerg , Hunter William R. 
Published: September 2022

AbstractAquatic habitats are particularly susceptible to chemical pollution from domestic, agricultural, and industrial sources. Antimicrobials are commonly used in medical and industrial environments to reduce harmful bacteria and biofilms. This has led to the rapid increase in the prevalence of antimicrobial resistant (AMR) genes. Alternate remedies to fight pathogenic bacteria and biofilms are in development including synthetic and biological surfactants such as sodium dodecyl sulphate (SDS) and rhamnolipids respectively. In the aquatic environment these surfactants are present as pollutants with potential to affect biofilm formation and AMR gene occurrence; however, there is limited research showing the actual environmental impact of such exposure. We tested the effects of rhamnolipid and SDS on natural aquatic biofilms in a freshwater stream in Northern Ireland. We grew biofilms on contaminant exposure substrata deployed within the stream over four weeks, and then carried out shotgun sequencing to determine microbial community composition, through 16s rRNA analyses (64,678 classifiable reads identified), and AMR gene occurrence (81 instances of AMR genes over 9 AMR gene classes) through a metagenomic analysis. There were no significant changes in community composition within all systems; however, biofilm exposed to rhamnolipid had a greater number of unique taxa as compared to our SDS treatments and controls. AMR gene prevalence was higher in surfactant-treated biofilms, with biofilm exposed to rhamnolipids having the highest presence of AMR genes and classes compared to the control or SDS treatments, in which genes encoding for rifampin resistance were detected. Our results suggest that the presence of rhamnolipid, and to a lesser extent SDS, encourages an increase in the prevalence of AMR genes in biofilms produced in mixed use water bodies.