bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel chemogenomic screening platform for scalable antimalarial drug target identification
Authors: Bower-Lepts Christopher , Rawat Mukul , Keith William Collins , Girling Gareth , Luth Madeline R , Carolino Krypton , Boroviak Katharina , Coyle Rachael , Schwach Frank , Smidt Cindy , Bushell Ellen , Moliner-Cubel Sonia , Gomez-Lorenzo Maria D , Gamo Francisco-Javier , Winzeler Elizabeth A. , Billker Oliver , Lee Marcus C.S. , Rayner Julian C. 
Published: August 2024

SummaryLarge-scale chemical-genetic screening, or chemogenomics, can faciliate rapid and scalable drug target identification. To establish a chemogenomic screen for antimalarial drug target identification, we leveraged ∼600Plasmodium bergheiartificial chromosomes (PbACs) encoding potential drug targets to generate a systematic overexpression library. PbACs were engineered with DNA barcodes, enabling their quantification within mixed pools using next generation sequencing (barcode sequencing or BarSeq). Pooled transfection of PbACs into the highly genetically tractablePlasmodium knowlesidemonstrated efficient vector uptake and transcription of encodedP. bergheigenes. Parasite pools were exposed to antimalarial candidates, with pilot screens probing for known gene-compound associations identifying their targets with high sensitivity. Screening antimalarial inhibitors with unknown mechanisms of action successfully identifiedpi4kas the target for one novel compound, which was subsequently validated usingin vitroevolution inPlasmodium falciparumparasites. This sensitive and scalable chemogenomics platform therefore represents a valuable early-stage tool for antimalarial target identification.
Engineering of ATP synthase for enhancement of proton-to-ATP ratio
Authors: Ueno Hiroshi , Yasuda Kiyoto , Hamaguchi-Suzuki Norie , Marui Riku , Adachi Naruhiko , Senda Toshiya , Murata Takeshi , Noji Hiroyuki 
Published: August 2024

SummaryFoF1-ATP synthase (FoF1) interconverts the energy of the proton motive force (pmf) and that of ATP via mechanical rotation of the rotor complex. The H+/ATP ratio, one of the most crucial parameters in bioenergetics, varies among species due to the different number of H+-bindingc-subunits, resulting in H+/ATP ratios ranging from 2.7 to 5. The present study attempted to enhance the H+/ATP ratio significantly by employing a novel approach that differs from that of nature. We engineered FoF1to form multiple peripheral stalks, each bound to a proton-conductinga-subunit. Engineered FoF1showed an H+/ATP ratio of 5.9, beyond the highest among naturally occurring FoF1s, enabling ATP synthesis at a lowpmf, at which wild-type enzymes are unable to synthesize ATP. Structural analysis showed that the engineered FoF1formed up to three peripheral stalks and thea-subunits. This study not only provides important insights into the H+-transport mechanism of FoF1but also opens the possibility of engineering the foundation of cell bioenergetics.
Optimization of screening methods leads to the discovery of new viruses in black soldier flies (Hermetia illucens)
Authors: Pienaar Robert D. , Herrero Salvador , de Araujo Alexandra Cerqueira , Krupa Frank , Abd-Alla Adly M. M. , Herniou Elisabeth A. 
Published: August 2024

AbstractVirus discovery in mass-reared insects is a growing topic of interest due to outbreak risks and for insect welfare concerns. In the case of black soldier flies (BSF), pioneering bioinformatic studies have uncovered exogenous viruses from the ordersGhabriviralesandBunyavirales, as well as endogenous viral elements from five virus families. This prompted further virome investigation of BSF metagenomes and metatranscriptomes, including from BSF individuals displaying signs and symptoms of disease. In this study, we describe five newly discovered viruses from the familiesDicistroviridae,Iflaviridae,Rhabdoviridae,Solinviviridae, andInseviridae. These viruses were detected in BSF from multiple origins, outlining a diversity of naturally occurring viruses associated with BSF. This viral community may also include BSF pathogens. The growing list of viruses found in BSF allowed the development of molecular detection tools which could be used for viral surveillance, both in mass-reared and wild populations of BSF.
QuICSeedR: An R package for analyzing fluorophore-assisted seed amplification assay data
Authors: Li Manci , Bryant Damani N. , Gresh Sarah , Milstein Marissa , Christenson Peter R. , Lichtenberg Stuart S. , Larsen Peter A. , Oh Sang-Hyun 
Published: August 2024

AbstractSummaryFluorophore-assisted seed amplification assays (F-SAAs), such as real-time quaking-induced conversion (RT-QuIC) and fluorophore-assisted protein misfolding cyclic amplification (F-PMCA), have become indispensable tools for studying protein misfolding in neurodegenerative diseases. However, analyzing data generated by these techniques often requires complex and time-consuming manual processes. Additionally, the lack of standardization in F-SAA data analysis presents a significant challenge to the interpretation and reproducibility of F-SAA results across different laboratories and studies. Here, we present QuICSeedR (pronounced as “quick seeder”), an R package that addresses these challenges by providing a comprehensive toolkit for the automated processing, analysis, and visualization of F-SAA data. Importantly, QuICSeedR also sets up the foundation for building an F-SAA data management and analysis framework, enabling more consistent and comparable results across different research groups.Availability and implementationQuICSeedR source code is freely available at:https://github.com/mancili/QuICSeedR. Data and code used in this manuscript are provided in Supplementary Materials.Supplementary informationSupplementary Materials are available with the manuscript.
Plasmid-bornemcr-1and Replicative Transposition of Episomal and Chromosomal blaNDM-1, blaOXA-69, and blaOXA-23 Carbapenemases in a ClinicalAcinetobacter baumanniiIsolate
Authors: Mmatli Masego , Mbelle Nontombi Marylucy , Osei Sekyere John 
Published: August 2024

AbstractBackgroundA multidrug-resistant clinical A. baumannii isolate with resistance to most antibiotics was isolated from a patient at an intensive care unit. The genetic environment, transcriptome, mobile, and resistome were characterized.MethodThe MicroScan system, disc diffusion, and broth microdilution were used to determine the resistance profile of the isolate. A multiplex PCR assay was also used to screen for carbapenemases and mcr-1 to -5 resistance genes. Efflux-pump inhibitors were used to evaluate efflux activity. The resistome, mobilome, epigenome, and transcriptome were characterized.Results & conclusionThere was phenotypic resistance to 22 of the 25 antibiotics tested, intermediate resistance to levofloxacin and nalidixic acid, and susceptibility to tigecycline, which corresponded to the 27 resistance genes found in the genome, most of which occurred in multiple copies through replicative transposition. A plasmid-borne (pR-B2.MM_C3)mcr-1 and chromosomalblaPER-7, blaOXA-69, blaOXA-23(three copies),blaADC-25,blaTEM-1B, andblaNDM-1were found within composite transposons, ISs, and/or class 1 and 2 integrons on genomic islands. Types I and II methylases and restriction endonucleases were in close synteny to these resistance genes within the genomic islands; chromosomal genomic islands aligned with known plasmids. There was a closer evolutionary relationship between the strain and global strains but not local or regional strains; the resistomes also differed. Significantly expressed/repressed genes (6.2%) included resistance genes, hypothetical proteins, mobile elements, methyltransferases, transcription factors, membrane and efflux proteins.The genomic evolution observed in this strain explains its adaptability and pandrug resistance and shows its genomic plasticity on exposure to antibiotics.
Gene expression and chromatin accessibility comparison in iPSC-derived microglia in African, European, and Amerindian genomes in Alzheimer’s patients and controls
Authors: Moura Sofia , Nasciben Luciana Bertholim , Ramirez Aura M. , Coombs Lauren , Rivero Joe , Van Booven Derek J. , DeRosa Brooke A. , Hamilton-Nelson Kara L. , Whitehead Patrice L. , Adams Larry D. , Starks Takiyah D. , Mena Pedro R. , Illanes-Manrique Maryenela , Tejada Sergio , Byrd Goldie S. , Cornejo-Olivas Mario R. , Feliciano-Astacio Briseida E. , Nuytemans Karen , Wang Liyong , Pericak-Vance Margaret A. , Dykxhoorn Derek M. , Rajabli Farid , Griswold Anthony J. , Young Juan I. , Vance Jeffery M. 
Published: August 2024

AbstractAlzheimer’s disease (AD) risk differs between population groups, with African Americans and Hispanics being the most affected groups compared to non-Hispanic Whites. Genetic factors contribute significant risk to AD, but the genetic regulatory architectures (GRA) have primarily been studied in Europeans. Many AD genes are expressed in microglia; thus, we explored the impact of genetic ancestry (Amerindian (AI), African (AF), and European (EU)) on the GRA in iPSC-derived microglia from 13 individuals (∼4 each with high global ancestry, AD and controls) through ATAC-seq and RNA-seq analyses. We identified several differentially accessible and expressed genes (2 and 10 AD-related, respectively) between ancestry groups. We also found a high correlation between the transcriptomes of iPSC-derived and brain microglia, supporting their use in human studies. This study provides valuable insights into genetically diverse microglia beyond the analysis of AD.
Training Experimentally Naive Seals for Vocal Learning Experiments
Authors: Duengen Diandra , Ravignani Andrea 
Published: August 2024

AbstractHarbor seals (Phoca vitulina) are a common zoo species that show a scientifically valuable propensity for vocal learning. Under human care, the seals can be trained to associate vocalizations with cues. This ability is termed vocal usage learning and is characterized by learning to use a vocalization in a specific context. Among mammals, seals are prime candidates to investigate vocal learning. Yet, only a handful of reports exist on harbor seal vocal learning abilities and even less document how these were trained or tested. Here, we investigate how, and if, two experimentally naive harbor seals under human care, can be trained to participate in scientific experiments. We describe the training and testing of two seals in two basic vocal learning experiments. We trained the animals to vocalize upon the presentation of a discriminative stimuli (SD) through operant conditioning methods and tested their abilities to i) vocalize and refrain from vocalizing on two distinct SD’s, and ii) produce two different vocalizations upon the presentation of two different SD’s. Both seals learned the tasks: the first task was achieved within 118 trials (22 errors to criterion) and 220 trials (40 errors to criterion), the second task within 480 trials (158 errors to criterion) and 380 trials (94 errors to criterion), respectively. Our results confirm that harbor seals are capable of vocal usage learning and further suggest that associating individually distinct vocalizations with different SD’s may be more cognitively demanding than vocalizing and being silent on SD.
Bronchopulmonary Dysplasia with Pulmonary Hypertension Associates with Loss of Semaphorin Signaling and Functional Decrease in FOXF1 Expression
Authors: Shirazi Shawyon P. , Negretti Nicholas M. , Jetter Christopher S. , Sharkey Alexandria L. , Garg Shriya , Kapp Meghan E. , Wilkins Devan , Fortier Gabrielle , Mallapragada Saahithi , Banovich Nicholas E. , Wright Christopher V. E. , Frank David B. , Kropski Jonathan A. , Sucre Jennifer M. S. 
Published: August 2024

AbstractLung injury in preterm infants leads to structural and functional respiratory deficits, with a risk for bronchopulmonary dysplasia (BPD) that in its most severe form is accompanied by pulmonary hypertension (PH). To examine cellular and molecular dynamics driving evolving BPD in humans, we performed single-cell RNA sequencing of preterm infant lungs in early stages of BPD and BPD+PH compared to term infants. Analysis of the endothelium revealed a unique aberrant capillary cell-state primarily in BPD+PH marked byANKRD1expression. Predictive signaling analysis identified deficits in the semaphorin guidance-cue signaling pathway and decreased expression of pro-angiogenic transcription factorFOXF1within the alveolar parenchyma in neonatal lung samples with BPD/BPD+PH. Loss of semaphorin signaling was replicated in a murine BPD model and in humans with alveolar capillary dysplasia (ACDMPV), suggesting a mechanistic link between the developmental programs underlying BPD and ACDMPV and a critical role for semaphorin signaling in normal lung development.
Missing links connect the phylogeographic structure of endangered red pandas, remaining as one species –Ailurus fulgens, and expediting conservation
Authors: Dueck Lucy A. , Uluer Deniz Aygören 
Published: August 2024

AbstractMonitoring biodiversity depends on well-informed taxonomy, reflecting the underlying biology of organisms critical for appropriate conservation management. The taxonomy of red pandas, endangered mammals distributed along a ∼2500km montane range fringing the southern Tibetan Plateau, has been perplexing. Finally resolved as evolutionarily unique Musteloidea, further division ofAilurusinto two geographic variants remains contentious. Red pandas are threatened by extinction from anthropogenic disturbances with consequent population decline; continued gene flow is therefore crucial to maintain adaptive potential. A recent phylogenomic study from sampling range ends and a constrictive species concept split red pandas into two species. Subsequent studies supplied additional data missing from their midrange. We evaluated GenBank mtDNA sequences from 393 animals, plotted sampling locations, and analyzed with and without midrange samples. Two sublineages of monophyleticAiluruswere weakly supported by one method when the midrange was excluded, but not when it was included. Using more stringent analyses,Ailuruswas strongly confirmed as a single species in all circumstances, although the western sublineage (A. f. fulgens) was weakly supported within. Four haplogroups associated with specific regions, suggesting broad phylogeographic patterning and gene flow, with sympatric crossover and a cline bracketing unsampled Bhutan in the midrange. Red pandas are due for IUCN Red List reassessment in 2025; unwarranted taxonomic revision would delay and imperil action needed to prevent extinction. We recommend maintainingAilurusas one species, recognizing and protecting biodiversity at one intraspecific level, allowing for gene flow in conservation management, and extensively investigating intergradation of midrange red pandas.
Cold and lonely: low-abundance microbiota and no core microbiome across a broad geographic sampling of a mosquito species in Greenland
Authors: Rojas-Guerrero Diana , Kolasa Michał , Buczek Mateusz , Prus-Frankowska Monika , Nowak Karol H. , Roslin Tomas , Łukasik Piotr 
Published: August 2024

AbstractMicrobial symbionts play a crucial role in the biology of their insect hosts. In recent years, the mosquito microbiome has emerged as a promising tool for controlling mosquito populations and altering their capacity to transmit diseases. However, while mosquitoes are widespread, most microbiome research focuses on a few model species, leaving many others understudied. In this study, we investigated how temporal and spatial variations influence the microbial abundance and diversity associated withOchlerotatusmosquitoes in Greenland. We did this by conducting high-throughput sequencing of insect and bacterial marker gene amplicons and quantifying bacterial abundance across a large collection of mosquitoes sampled systematically from four regions of Greenland between 2009 and 2023.Analysis of COI data identified two species within our collection: the widely distributedO. nigripesand the less commonO. impiger. Quantitative 16S rRNA amplicon sequencing revealed a highly variable number of bacterial rRNA gene copies per mosquito, with overall microbiota abundance typically lower (Avg = ∼1.2×105, Mdn = 1.04×104) than that estimated for both lab-rearedAedes aegyptiand wildCulex pipiensfrom Poland. Despite identifying diverse bacterial taxa, includingPseudomonas, Wolbachia, andBartonella, we observed significant microbiome variability between individual mosquitoes. Notably, there were no consistent patterns of microbiota distribution across sexes, geographic locations, or sampling years. These findings suggest thatOchlerotatusmosquitoes from the surveyed populations in Greenland may not rely on abundant or specialized microbiota for their reproduction or nutrition, indicating a flexible or minimal relationship with their associated bacterial communities.
The cytokinetic midbody mediates asymmetric fate specification at mitotic exit during neural stem cell division
Authors: LaFoya Bryce , Penkert Rhiannon R , Prehoda Kenneth E. 
Published: August 2024

SummaryAsymmetric cell division (ACD) is a broadly used mechanism for generating cellular diversity. Molecules known as fate determinants are segregated during ACD to generate distinct sibling cell fates, but determinants should not be activated until fate can be specified asymmetrically. Determinants could be activated after cell division but many animal cells complete division long after mitosis ends, raising the question of how activation could occur at mitotic exit taking advantage of the unique state plasticity at this time point. Here we show that the midbody, a microtubule-rich structure that forms in the intercellular bridge connecting nascent siblings, mediates fate determinant activation at mitotic exit in neural stem cells (NSCs) of theDrosophilalarval brain. The fate determinants Prospero (Pros) and Brain tumor (Brat) are sequestered at the NSC membrane at metaphase but are released immediately following nuclear division when the midbody forms, well before cell division completes. The midbody isolates nascent sibling cytoplasms, allowing determinant release from the membrane via the cell cycle phosphatase String, without influencing the fate of the incorrect sibling. Our results identify the midbody as a key facilitator of ACD that allows asymmetric fate determinant activation to be initiated before division.
Association Between Relational Mobility and DNA Methylation in Oxytocin Receptor Gene: A Social Epigenetic Study
Authors: Li Shubing , Yamada Junko , Ishihara Toru , Nishina Kuniyuki , Nishitani Shota , Sasaki Tetsuhiko , Matsuda Tetsuya , Inoue-Murayama Mino , Takagishi Haruto 
Published: August 2024

AbstractDNA methylation is a type of epigenetic modification known to exhibit fluctuations in response to environmental factors. The association of macrosocial factors, such as interpersonal mobility, on methylation has seldom been investigated. This study aimed to examine the association of relational mobility, defined as the extent to which individuals can form and replace social relationships, on the DNA methylation of oxytocin receptor genes. DNA was extracted from the buccal cells of 95 adult participants (50 men and 45 women) and subjected to microarray analysis of DNA methylation using Illumina EPIC v2.0. The findings indicate that the oxytocin receptor gene’s methylation level was higher in individuals residing in low relational mobility social environments. The CpG site associated with relational mobility is an enhancer region, indicating that social environments with low relational mobility exert a suppressive effect on the transcriptional efficiency of the oxytocin receptor gene.Significance StatementThe association between DNA methylation of the oxytocin receptor gene and relational mobility was examined in 95 adults in their 20s to 60s, and found that those living in social environments with lower levels of relationship mobility had higher rates of DNA methylation of the oxytocin receptor gene. This study is a novel approach to a problem discussed in the social sciences using new analytical techniques in epigenomics.
Running on empty: Mitochondria without DNA exhibit differential motility and connectivity
Authors: Chustecki Joanna M. , Schneider Alora Q. , Faber Madeleine H. , Christensen Alan C. 
Published: August 2024

AbstractPlant mitochondria are in continuous motion. While providing ATP to other cellular processes, they also constantly consume ATP to move rapidly within the cell. This movement is in part related to taking up, converting and delivering metabolites and energy to and from different parts of the cell. Plant mitochondria have varying amounts of DNA even within a single cell, from none to the full mitochondrial genome. Because mitochondrial dynamics are altered in anArabidopsismutant with disrupted DNA maintenance, we hypothesised that exchanging DNA templates for repair is one of the functions of their movement and interactions. Here, we image mitochondrial DNA by two distinct methods while tracking mitochondrial position to investigate differences in the behaviour of mitochondria with and without DNA inArabidopsis thaliana. In addition to staining mitochondrial DNA with SYBR Green, we have developed and implemented a fluorescent mitochondrial DNA binding protein that will also enable future understanding of mitochondrial dynamics, genome maintenance and replication. We demonstrate that mitochondria without mtDNA have altered physical behaviour and have a lower immediate connectivity to the rest of the population, further supporting a link between the physical and genetic dynamics of these complex organelles.
NeuroSCAN: Exploring Neurodevelopment via Spatiotemporal Collation of Anatomical Networks
Authors: Koonce Noelle L. , Emerson Sarah E. , Bhaskar Dhananjay , Kuchroo Manik , Moyle Mark W. , Arroyo-Morales Pura , Martínez Nabor Vázquez , Krishnaswamy Smita , Mohler William , Colón-Ramos Daniel 
Published: August 2024

AbstractVolume electron microscopy (vEM) datasets such as those generated for connectome studies allow nanoscale quantifications and comparisons of the cell biological features underpinning circuit architectures. Quantifications of cell biological relationships in the connectome result in rich multidimensional datasets that benefit from data science approaches, including dimensionality reduction and integrated graphical representations of neuronal relationships. We developed NeuroSCAN, an online open-source platform that bridges sophisticated graph analytics from data science approaches with the underlying cell biological features in the connectome. We analyze a series of publishedC. elegansbrain neuropils and demonstrate how these integrated representations of neuronal relationships facilitate comparisons across connectomes, catalyzing new insights on the structure-function relationships of the circuits and their changes during development. NeuroSCAN is designed for intuitive examination and comparisons across connectomes, enabling synthesis of knowledge from high-level abstractions of neuronal relationships derived from data science techniques to the detailed identification of the cell biological features underpinning these abstractions.