bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased Risk of Ischemic Stroke in Amyotrophic Lateral Sclerosis: A Nationwide Cohort Study in South Korea
Authors: Kwon Soonwook , Kim Bongseong , Han Kyung-Do , Jung Wonyoung , Cho Eun Bin , Shin Dong Wook , Min Ju-Hong 
Published: August 2023

AbstractBackgroundWe investigated the risk of ischemic stroke in ALS and analyzed the effect of ALS-related physical disability using the Korean National Health Insurance Service database.MethodsA total of 2,252 ALS patients diagnosed between January 1, 2012, and December 31, 2015, and 1:10 age- and sex-matched control populations were included. After selection of cases that participated in the national health check-up programs, 659 ALS patients and 10,927 non-ALS participants were remained. Newly developing ischemic stroke as primary outcome was also defined by the ICD code and the incidence probability was assessed using by the Kaplan– Meier method during the follow-up duration. A Cox hazard regression model was used to examine the hazard ratios (HRs) for ischemic stroke in ALS after adjusting for potential confounders.ResultsALS patients were younger than the control group (60.3 ± 10.2 years vs. 61.4 ± 10.5 years, p = 0.008), and the proportion of male patients was similar between the two groups (61.0% vs. 62.5%, p = 0.447). ALS patients were more likely to have a lower body mass index (23.1 ± 2.92 vs. 24.0 ± 3.00, p < 0.001) and be non-drinkers (64.2% vs. 57.4%, p = 0.002) than the controls. In ALS patients, the incidence of ischemic stroke was 7.8 per 1,000 person-years, and the adjusted HR of ischemic stroke was 3.67 (95% confidence interval 2.02−6.67) compared with the control group. The risk of ischemic stroke did not differ by the presence of disability in ALS patients.ConclusionsOur findings suggest that ALS patients face increased risk of ischemic stroke compared with controls, but the risk did not differ by the presence of disability in ALS.
D-serine- andp-fluorophenylalanine-resistant mutants ofPhyscomitrium patensare defective in amino acid uptake
Authors: Albone Stephen , Cove David J , Ashton Neil W 
Published: August 2023

AbstractTwo amino acid analogue-resistant lines ofPhyscomitrium(formerlyPhyscomitrella)patens, DSR8andPFR4, are resistant to a range of D-amino acids and an inhibitory concentration of L-lysine. Both are defective in the uptake of [35S]-L-methionine. Uptake by the wild-type line is pH-dependent (decreasing with raised external proton concentrations) and is depressed by dinitrophenol and by ammonium ions. We discuss the possible involvement of an active proton-general amino acid antiport pump in the plasma membrane.
Phylogenetic and functional analyses ofN6-methyladenosine RNA methylation factors in the wheat scab fungusFusarium graminearum
Authors: Kim Hyeonjae , Hu Jianzhong , Kang Hunseung , Kim Wonyong 
Published: August 2023

AbstractIn eukaryotes,N6-methyladenosine (m6A) RNA modification plays crucial roles in governing the fate of RNA molecules and has been linked to various developmental processes. However, the phyletic distribution and functions of genetic factors responsible for m6A modification remain largely unexplored in fungi. To get insights into evolution of m6A machineries, we reconstructed global phylogenies of potential m6A writers, readers, and erasers in fungi. Substantial copy number variations were observed, ranging from up to five m6A writers in early-diverging fungi to a single copy in the subphylum Pezizomycotina, which primarily comprises filamentous fungi. To characterize m6A factors in a phytopathogenic fungusFusarium graminearum, we generated knockout mutants lacking potential m6A factors including the sole m6A writerMTA1. However, the resulting knockouts did not exhibit any noticeable phenotypic changes during vegetative and sexual growth stages. As obtaining a homozygous knockout lackingMTA1was likely hindered by its essential role, we generatedMTA1-overexpressing strains (MTA1-OE). TheMTA1-OE5 strain showed delayed conidial germination and reduced hyphal branching, suggesting its involvement during vegetative growth. Consistent with these findings, the expression levels ofMTA1and a potential m6A readerYTH1were dramatically induced in germinating conidia, followed by the expression of potential m6A erasers at later vegetative stages. Several genes including transcription factors, transporters and various enzymes were found to be significantly up- and down-regulated in theMTA1-OE5 strain. Overall, our study highlights the functional importance of the m6A methylation during conidial germination inF. graminearumand provides a foundation for future investigations into m6A modification sites in filamentous fungi.ImportanceN6-methyladenosine (m6A) RNA methylation is a reversible posttranscriptional modification that regulates RNA function and plays a crucial role in diverse developmental processes. This study addresses the knowledge gap regarding phyletic distribution and functions of m6A factors in fungi. The identification of copy number variations among fungal groups enriches our knowledge regarding the evolution of m6A machinery in fungi. Functional characterization of m6A factors in a phytopathogenic filamentous fungusFusarium graminearumprovides insights into the essential role of the m6A writerMTA1in conidial germination and hyphal branching. The observed effects of overexpressingMTA1on fungal growth and gene expression patterns of m6A factors throughout the life cycle ofF. graminearumfurther underscore the importance of m6A modification in conidial germination. Overall, this study significantly advances our understanding of m6A modification in fungi, paving the way for future research into its roles in filamentous growth and potential applications in disease control.
The Electron Transport Chain ofShewanella oneidensisMR-1 can Operate Bidirectionally to Enable Microbial Electrosynthesis
Authors: Ford Kathryne C. , TerAvest Michaela A. 
Published: August 2023

AbstractExtracellular electron transfer (EET) is a process by which bacterial cells can exchange electrons with a redox active material located outside of the cell. InShewanella oneidensis, this process is natively used to facilitate respiration using extracellular electron acceptors such as Fe(III) or an anode. Previously, it was demonstrated that this process can be used to drive microbial electrosynthesis of 2,3-butanediol (2,3-BDO) inS. oneidensisexogenously expressing butanediol dehydrogenase (Bdh). Electrons taken into the cell from a cathode are used to generate NADH, which in turn is used to reduce acetoin to 2,3-BDO via Bdh. However, generating NADH via electron uptake from a cathode is energetically unfavorable, so NADH dehydrogenases couple the reaction to proton motive force. We therefore need to maintain the proton gradient across the membrane to sustain NADH production. This work explores accomplishing this task by bidirectional electron transfer, where electrons provided by the cathode go to both NADH formation and O2reduction by oxidases. We show that oxidases use trace dissolved oxygen in a microaerobic bioelectrical chemical systems (BES), and the translocation of protons across the membrane during O2reduction supports 2,3-BDO generation. Interestingly, this process is inhibited by high levels of dissolved oxygen in this system. In an aerated BES, O2molecules react with the strong reductant (cathode) to form reactive oxygen species, resulting in cell death.ImportanceMicrobial electrosynthesis is increasingly employed for the generation of specialty chemicals such as biofuels, bioplastics, and cancer therapeutics. For these systems to be viable for industrial scale-up, it is important to understand the energetic requirements of the bacteria to mitigate unnecessary costs. This work demonstrates sustained production of an industrially relevant chemical driven by a cathode. Additionally, it optimizes a previously published system by removing any requirement for phototrophic energy, thereby removing the additional cost of providing a light source. We also demonstrate the severe impact of oxygen intrusion into bioelectrochemical systems, offering insight to future researchers aiming to work in an anaerobic environment. These studies provide insight into both the thermodynamics of electrosynthesis and the importance of bioelectrochemical systems design.
Microbial community organization during anaerobic pulp and paper mill wastewater treatment
Authors: Meyer Torsten , Yang Minqing Ivy , Nesbø Camilla , Master Emma , Edwards Elizabeth A. 
Published: August 2023

AbstractAmplicon sequencing data and operating data from anaerobic wastewater treatment plants from three Canadian pulp and paper mills were explored using correlation and network modularization approaches to study the microbial community organization and identify relationships between organisms and operating conditions.Each of the digesters contain two or three modules consisting of organisms that cover all trophic stages of anaerobic digestion. These modules are functioning independently from each other, and their relative abundance changes in response to varying operating conditions.The time delay between a change in digester operation and the change in the abundance of microorganisms was investigated using time-lagged operating parameters. This time delay ranged between two to four days and is likely influenced by the growth rates of the anaerobic microorganisms and the digester hydraulic retention time.Digester upsets due to plant shutdown periods and organic overload caused a drastic increase in the population of acetoclastic methanogens, acidogenic fermenters, and syntrophic acid degraders. As a response to impaired process conditions, the sameMethanothrixamplicon sequence variant (ASV) dominated methanogenesis in the digesters of all three mills. The common characteristics of the organisms represented by this ASV should be further investigated for their role in alleviating the impact of digester upset conditions.Abstract Figure
Unraveling the Half and Full Site Sequence Specificity of theSaccharomyces cerevisiaePdr1p and Pdr3p Transcription Factors
Authors: Buechel Evan R. , Pinkett Heather W. 
Published: August 2023

ABSTRACTThe transcription factors Pdr1p and Pdr3p regulate pleotropic drug resistance (PDR) inSaccharomyces cerevisiae, via the PDR responsive elements (PDREs) to modulate gene expression. However, the exact mechanisms underlying the differences in their regulons remain unclear. Employing genomic occupancy profiling (CUT&RUN), binding assays, and transcription studies, we characterized the differences in sequence specificity between transcription factors. Findings reveal distinct preferences for core PDRE sequences and the flanking sequences for both proteins. While flanking sequences moderately alter DNA binding affinity, they significantly impact Pdr1/3p transcriptional activity. Notably, both proteins demonstrated the ability to bind half sites, showing potential enhancement of transcription from adjacent PDREs. This insight sheds light on ways Pdr1/3 can differentially regulate PDR.
Human STING oligomer function is governed by palmitoylation of an evolutionarily conserved cysteine
Authors: Chan Rebecca , Cao Xujun , Ergun Sabrina L , Njomen Evert , Lynch Stephen R. , Ritchie Christopher , Cravatt Benjamin , Li Lingyin 
Published: August 2023

AbstractThe anti-viral and anti-cancer STING innate immune pathway can exacerbate autoimmune and neurodegenerative diseases when aberrantly activated, emphasizing a key unmet need for STING pathway antagonists. However, no such inhibitors have advanced to the clinic because it remains unclear which mechanistic step(s) of human STING activation are crucial for potent and context-independent inhibition of downstream signaling. Here, we report that C91 palmitoylation, the mechanistic target of a potent tool compound, is not universally necessary for human STING signaling, making it a poor target for drug development. Instead, we discover that evolutionarily conserved C64 is basally palmitoylated and is crucial for preventing unproductive STING oligomerization in the absence of cGAMP stimulation. The effects of palmitoylation at C64 and C91 converge on the control of intra-dimer disulfide bond formation at C148. Importantly, we show for the first time that signaling-competent STING oligomers are composed of a mixture of two species: disulfide-linked STING dimers that stabilize the oligomer, and reduced STING dimers that are phosphorylated to actuate interferon signaling. Given this complex landscape and cell type specificity of palmitoylation modifications, we conclude that robust STING inhibitors must directly inhibit the oligomerization process. Taking inspiration from STING’s natural autoinhibitory mechanism, we identified an eight amino acid peptide that binds a defined pocket at the inter-dimer oligomerization interface as a proof-of-concept human STING inhibitor, setting the stage for future therapeutic development.SummaryWe report that functional STING oligomers require palmitoylation at cysteine 64 and some proportion of reduced dimers, and define the site of autoinhibition that can be targeted to disrupt STING oligomerization and activity.
Comparisons of Auditory Steady State and Auditory Brainstem Response Thresholds in Infants with Normal Hearing and Conductive Hearing Loss
Authors: Valeriote Hope , Small Susan A. 
Published: August 2023

ABSTRACTThis study investigates how well the air- and bone-conduction auditory steady-state response detects mild conductive hearing loss compared to the auditory brainstem response in young infants. Air-bone gap sizes are compared between infants with normal hearing and conductive loss using a two-group cross-sectional design. Twenty-three (500 Hz) and 22 (2000 Hz) infants (0-6 months of age) with normal hearing and 15 (500 Hz) infants with conductive loss were recruited from newborn hearing screening. Thresholds were obtained to frequency-specific air- and bone-conducted stimuli. There were no instances of conductive loss at 2000 Hz. 500 Hz mean thresholds and air-bone gap sizes were compared. Sensitivity and specificity for identifying conductive loss were measured. Overall, mean bone-conduction thresholds were similar between groups, and mean 500-Hz air conduction thresholds were higher with larger air-bone gap size for infants with conductive loss. Sensitivity and specificity for identifying conductive loss was highest for air-conduction auditory brainstem response threshold measurement compared to screening and auditory steady-state response threshold measurements. Compared to the auditory brainstem response, the variability of auditory steady-state response thresholds and air-bone gap size was too great to reliably separate normal hearing from mild conductive loss. More research is needed using infants with varying degrees of hearing loss at multiple frequencies to fully assess the appropriateness of the auditory steady-state response as a clinical diagnostic tool for an infant population.
Whole-Brain Causal Discovery Using fMRI
Authors: Arab Fahimeh , Ghassami AmirEmad , Jamalabadi Hamidreza , Peters Megan A. K. , Nozari Erfan 
Published: August 2023

ABSTRACTDespite significant research, discovering causal relationships from fMRI remains a challenge. Popular methods such as Granger Causality and Dynamic Causal Modeling fall short in handling contemporaneous effects and latent common causes. Methods from causal structure learning literature can address these limitations but often scale poorly with network size and need acyclicity. In this study, we first provide a taxonomy of existing methods and compare their accuracy and efficiency on simulated fMRI from simple topologies. This analysis demonstrates a pressing need for more accurate and scalable methods, motivating the design of Causal discovery for Large-scale Low-resolution Time-series with Feedback (CaLLTiF). CaLLTiF is a constraint-based method that uses conditional independence between contemporaneous and lagged variables to extract causal relationships. On simulated fMRI from the macaque connectome, CaLLTiF achieves significantly higher accuracy and scalability than all tested alternatives. From resting-state human fMRI, CaLLTiF learns causal connectomes that are highly consistent across individuals, show clear top-down flow of causal effect from attention and default mode to sensorimotor networks, exhibit Euclidean distance-dependence in causal interactions, and are highly dominated by contemporaneous effects. Overall, this work takes a major step in enhancing causal discovery from whole-brain fMRI and defines a new standard for future investigations.AUTHOR SUMMARYDiscovering causal relationships from fMRI data is challenging due to contemporaneous effects and latent causes. Popular methods like Granger Causality and Dynamic Causal Modeling struggle with these issues, especially in large networks. To address this, we introduce CaLLTiF, a scalable method that uses both lagged and contemporaneous variables to identify causal relationships. CaLLTiF outperforms various existing techniques in accuracy and scalability on simulated fMRI data. When applied to human resting-state fMRI, it reveals consistent and biologically-plausible patterns across individuals, with a clear top-down causal flow from attention and default mode networks to sensorimotor areas. Overall, this work advances the field of causal discovery in large-scale fMRI studies.
Toxinome - The Bacterial Protein Toxin Database
Authors: Danov Aleks , Segev Ofir , Bograd Avi , Eliyahu Yedidya Ben , Dotan Noam , Kaplan Tommy , Levy Asaf 
Published: August 2023

AbstractProtein toxins are key molecular weapons in biology that are used to attack neighboring cells. Bacteria use protein toxins to kill or inhibit growth of prokaryotic and eukaryotic cells using various modes of action that target essential cellular components. The toxins are responsible for shaping microbiomes in different habitats, for abortive phage infection, and for severe infectious diseases of animals and plants. Although several toxin databases have been developed, each one is devoted to a specific toxin family and they encompass a relatively small number of toxins. Antimicrobial toxins are often accompanied by antitoxins (or immunity proteins) that neutralize the cognate toxins. Here, we combined toxins and antitoxins from many resources and created Toxinome, a comprehensive and updated bacterial protein toxin database. Toxinome includes a total of 1,483,028 toxins and 491,345 antitoxins encoded in 59,475 bacterial genomes across the tree of life. We identified a depletion of toxin and antitoxin genes in bacteria that dwell in extreme temperatures. We defined 5,161 unique Toxin Islands within phylogenetically diverse bacterial genomes, which are loci dense in toxin and antitoxin genes. By focusing on the unannotated genes within these islands, we characterized a number of these genes as toxins or antitoxins. Finally, we developed an interactive Toxinome website (http://toxinome.pythonanywhere.com) that allows searching and downloading of our database. The Toxinome resource will be useful to the large research community interested in bacterial toxins and can guide toxin discovery and function elucidation, and infectious disease diagnosis and treatment.ImportanceMicrobes use protein toxins as important tools to attack neighboring cells, microbial or eukaryotic, and for self-killing when attacked by viruses. These toxins work by different mechanisms to inhibit cell growth or kill cells. Microbes also use antitoxin proteins to neutralize the toxin activities. Here, we developed a comprehensive database called Toxinome of nearly two million toxin and antitoxins that are encoded in 59,475 bacterial genomes. We described the distribution of bacterial toxins and identified that they are depleted from bacteria that live in hot and cold temperatures. We find 5,161 cases in which toxins and antitoxins are densely clustered in bacterial genomes and termed these areas “Toxin Islands”. The Toxinome database is a useful resource for anyone interested in toxin biology and evolution, and it can guide discovery of new toxins.
The identification of expected functional food quality: female consumers' perspective
Authors: Sumaedi Sik , Bakti I Gede Mahatma Yuda , Rakhmawati Tri , Astrini Nidya 
Published: August 2023

PurposeThis study aimed to identify the quality consumers expect from functional food. This study investigated the quality dimensions and indicators female consumers expect in functional food.Design/methodology/approachThis study used a quantitative approach. Data were collected through a survey using a self-administered questionnaire from 149 women aged 17 years and over in the Greater Jakarta area. Data analysis consists of three stages: exploratory factor analysis (EFA), confirmatory factor analysis-structural equation modeling (CFA-SEM) and consumer expectation value analysis. Statistical Package for the Social Sciences (SPSS) and Lisrel software were used to assist the analysis.FindingsThe analysis results showed that women expect functional food products to fulfill the aspects of product presentation, product assurance, convenience, health benefits and safety and sensory characteristics. These five aspects are referred to as the expected quality dimensions. Twenty-one indicators can be used to measure the quality of functional food expected by women.Research limitations/implicationsOther researchers can use this study to understand functional food female consumers' behavior. Furthermore, functional food companies can utilize it to measure consumers' expectations of their products' quality and performance.Originality/valueThis research is believed to be the first study to identify the dimensions of functional food quality expected by female consumers. Most existing research on the perceived quality of functional food measures functional food quality based on performance and ignored the differences in expectations between men and women.
Pyopneumothorax with bronchopleural fistula due to pulmonary infection caused by Porphyromonas gingivalis in a patient with periodontitis
Authors: Sha Jun , Shao Jie , Lu Sheng , Yao Wei , Deng Yimai , Chen Jie , Zhang Jianfeng , Feng Yufeng 
Published: August 2023

AbstractPyopneumothorax with bronchopleural fistula is a rare complication of lung infection. We herein report a case of pyopneumothorax with bronchopleural fistula caused by Porphyromonas gingivalis infection, a common pathogenic pathogen of periodontitis, in a 49‐year‐old man with periodontitis. The patient was admitted with respiratory failure. Pleural puncture yielded a lot of gas continually and foul‐smelling light brown pus, which was found to be caused due to infection with P. gingivalis by the metagenomic next generation sequencing (mNGS) and anaerobic culture.
An exploration of recent trends in the number of British pubs and how these vary by neighbourhood type
Authors: Clark Stephen , Leahy Christopher , Hood Nick 
Published: August 2023

AbstractThe common narrative in the media is that the British public house is in terminal decline and that these losses are having a significant impact on local communities. While it is true that some pubs are closing, it is also true that others are opening. This article examines the quarterly trend of pub numbers over eight years in various neighbourhoods and utilises a multilevel model to estimate and illustrate these trends. City and town centres with a thriving night‐time economy show the most significant increases in pub numbers, whereas suburban areas show a more mixed picture, with pubs in less affluent areas performing better. The areas where reductions are most pronounced are rural locations, especially remote rural communities. The article concludes with an analysis of the reasons behind these trends and suggests avenues for future research.