bluuebunny/crossref_metadata_2025_split huggingface dataset:
Function and Importance of Marine Bacterial Transporters of Plankton Exometabolites
Authors: Schroer William F. , Kepner Hannah E. , Uchimiya Mario , Mejia Catalina , Rodriguez Lidimarie Trujillo , Reisch Christopher R. , Moran Mary Ann 
Published: January 2023

AbstractMetabolite exchange within marine microbial communities transfers carbon and other major elements through global cycles and forms the basis of microbial interactions. Yet lack of gene annotations and concern about the quality of existing ones remain major impediments to revealing the metabolite-microbial network. We employed an arrayed mutant library of the marine bacteriumRuegeria pomeroyiDSS-3 to experimentally annotate substrates of organic compound transporter systems, using mutant growth and compound drawdown analyses to link transporters to their substrates. Mutant experiments verified substrates for thirteenR. pomeroyitransporters. Four were previously hypothesized based on gene expression data (taurine, glucose/xylose, isethionate, and cadaverine/putrescine/spermidine); five were previously hypothesized based on homology to experimentally annotated transporters in other bacteria (citrate, glycerol,N-acetylglucosamine, fumarate/malate/succinate, and dimethylsulfoniopropionate); and four had no previous annotations (thymidine, carnitine, cysteate, and 3-hydroxybutyrate transporter). These bring the total number of experimentally-verified organic carbon influx transporters to 17 of 126 in theR. pomeroyigenome. In a longitudinal study of a coastal phytoplankton bloom, expression patterns of the experimentally annotated transporters linked them to different stages of the bloom, and also led to the hypothesis that citrate and 3-hydroxybutyrate were among the most highly available bacterial substrates. Improved functional knowledge of these gatekeepers of organic carbon uptake is facilitating better characterization of the surface ocean metabolite network.
Enhanced germination and electrotactic behaviour ofPhytophthora palmivorazoospores in weak electric fields
Authors: Moratto Eleonora , Rothery Stephen , Bozkurt Tolga O. , Sena Giovanni 
Published: January 2023

AbstractSoil-dwelling microorganisms use a variety of chemical and physical signals to navigate their environment. Plant roots produce endogenous electric fields which result in characteristic current profiles. Such electrical signatures are hypothesised to be used by pathogens and symbionts to track and colonise plant roots.The oomycete pathogenPhytophthora palmivoragenerates motile zoospores which swim towards the positive pole when exposed to an external electric fieldin vitro.Here, we provide a quantitative characterization of their electrotactic behaviour in 3D. We found that a weak electric field (0.7 - 1.0 V/cm) is sufficient to induce an accumulation of zoospore at the positive pole, without affecting their encystment rate. We also show that the same external electric field increases the zoospore germination rate and orients the germ tube’s growth. We conclude that several early stages of theP. palmivorainfection cycle are affected by external electric fields.Taken together, our results are compatible with the hypothesis that pathogens use plant endogenous electric fields for host targeting.
Human-gut phages harbor sporulation genes
Authors: Schwartz DA , Rodríguez-Ramos J , Shaffer M , Flynn R , Daly R , Wrighton KC , Lennon Jay T. 
Published: January 2023

ABSTRACTSpore-forming bacteria are prevalent in mammalian guts and have implications for host health and nutrition. The production of dormant spores is thought to play an important role in the colonization, persistence, and transmission of these bacteria. Spore formation also modifies interactions among microorganisms such as infection by phages. Recent studies suggest that phages may counter dormancy-mediated defense through the expression of phage-encoded sporulation genes during infection, which can alter the transitions between active and inactive states. By mining genomes and gut-derived metagenomes, we identified sporulation genes that are preferentially encoded by phages that infect spore-forming bacteria. These included genes involved in chromosome partitioning, DNA damage repair, and cell wall-associated functions. In addition, phages contained homologs of sporulation-specific transcription factors, notablyspo0A, the master regulator of sporulation, which could allow phages to control the complex genetic network responsible for spore development. Our findings suggest that phages could influence the formation of bacterial spores with implications for the health of the human gut microbiome, as well as bacterial communities in other environments.SIGNIFICANCEPhages acquire bacterial genes and use them to alter host metabolism in ways that enhance their fitness. To date, most auxiliary genes replace or modulate enzymes that are used by the host for nutrition or energy production. However, phage fitness is affected by all aspects of host physiology, including decisions that reduce metabolic activity of the cell. Here we focus on endosporulation, a complex and ancient form of dormancy found among the Bacillota that involves hundreds of genes. By coupling homology searches with host classification, we identify 31 phage-encoded homologs of sporulation genes that are mostly limited to phages infecting spore-forming bacteria. Nearly one-third the homologs recovered were regulatory genes suggesting that phages may manipulate host genetic networks by tapping into their control elements. Our findings also suggest a mechanism by which phages can overcome the defensive strategy of dormancy, which may be involved in coevolutionary dynamics of spore-forming bacteria.
Facilitative interaction networks in experimental microbial community dynamics
Authors: Fujita Hiroaki , Ushio Masayuki , Suzuki Kenta , Abe Masato S. , Yamamichi Masato , Okazaki Yusuke , Canarini Alberto , Hayashi Ibuki , Fukushima Keitaro , Fukuda Shinji , Kiers E. Toby , Toju Hirokazu 
Published: January 2023

AbstractUnderstanding potential roles of facilitative interactions between species is one of the major challenges in ecology and microbiology. However, we still have limited knowledge of entangled webs of facilitative interactions in ecosystems. By compiling whole-genome shotgun metagenomic data of an experimental microbial community, we tested the hypothesis that architecture of facilitative interaction networks could change through time. A metabolic modeling approach for estimating dependence between microbial genomes (species) allowed us to infer the network structure of potential facilitative interactions at 13 time points through the 110-day monitoring of experimental microbiomes. We then found that positive feedback loops, which were theoretically predicted to promote cascade breakdown of ecological communities, existed within the inferred networks of metabolic interactions prior to the drastic community-compositional shift observed in the microbiome time-series. We further applied “directed-graph” analyses to pinpoint potential keystone species located at the “upper stream” positions of such feedback loops. These analyses on facilitative interactions will help us understand key mechanisms causing catastrophic shifts in microbial community structure.
Secretory and transcriptomic responses of mantle cells to low pH in the Pacific oyster (Crassostrea gigas)
Authors: Zúñiga-Soto Nicolás , Pinto-Borguero Ingrid , Quevedo Claudio , Aguilera Felipe 
Published: January 2023

AbstractSince the Industrial Revolution, the concentration of atmospheric carbon dioxide (CO2) due to anthropogenic activities has increased at unprecedented rates. One-third of the atmospheric anthropogenic CO2emissions are dissolved in the oceans affecting the chemical equilibrium of seawater, which in turn leads to a decrease in pH and carbonate ion (CO32−) concentration, a phenomenon known as ocean acidification (OA). This chemical disequilibrium can be detrimental to marine organisms (e.g., mollusks) that fabricate mineralized structures based on calcium carbonate (CaCO3). Most studies on the effect of reduced pH in seawater have been conducted on the early developmental stages of shell-building invertebrates, neglecting how adult individuals face OA stress. Here, we evaluate histological, secretory, and transcriptional changes in the mantle of adult oysters (Crassostrea gigas) exposure to ambient (8.0 ± 0.2) and reduced (7.6 ± 0.2) pH during 20 days. Most histological observations did not show differences in terms of mantle cell morphology. However, Alcian Blue/PAS staining revealed significant differences in the number of Alcian Blue positive cells in the mantle edge, suggesting a decrease in the secretory activity in this morphogenetic zone. Transcriptomic analysis revealed 172 differentially expressed genes (DEGs) between mantle tissues from adult oysters kept in normal and reduced pH conditions. Almost 18% of the DEGs encode secreted proteins that are likely to be contributing to shell fabrication and patterning. 17 of 31 DEGs encoding secreted proteins correspond to oyster-specific genes, highlighting the fact that molluscan shell formation is underpinned by a rapidly evolving secretome. The GO analysis of DEGs encoding secreted proteins showed that they are involved in the cellular response to stimulus, response to stress, protein binding, and ion binding, suggesting these biological processes and molecular functions are altered by OA. This study demonstrates that histology and gene expression profiling can advance our understanding of the cellular and molecular mechanisms underlying adult oyster tolerance to low pH conditions.
Widespread Autonomic Physiological Coupling Across the Brain-Body Axis
Authors: Bolt Taylor , Wang Shiyu , Nomi Jason S. , Setton Roni , Gold Benjamin P. , deB.Frederick Blaise , Thomas Yeo B.T. , Jean Chen J. , Picchioni Dante , Spreng R. Nathan , Keilholz Shella D. , Uddin Lucina Q. , Chang Catie 
Published: January 2023

AbstractThe brain is closely attuned to visceral signals from the body’s internal environment, as evidenced by the numerous associations between neural, hemodynamic, and peripheral physiological signals. We show that these brain-body co-fluctuations can be captured by a single spatiotemporal pattern. Across several independent samples, as well as single-echo and multi-echo fMRI data acquisition sequences, we identify widespread co-fluctuations in the low-frequency range (0.01 - 0.1 Hz) between resting-state global fMRI signals, neural activity, and a host of autonomic signals spanning cardiovascular, pulmonary, exocrine and smooth muscle systems. The same brain-body co-fluctuations observed at rest are elicited by arousal induced by cued deep breathing and intermittent sensory stimuli, as well as spontaneous phasic EEG events during sleep. Further, we show that the spatial structure of global fMRI signals is maintained under experimental suppression of end-tidal carbon dioxide (PETCO2) variations, suggesting that respiratory-driven fluctuations in arterial CO2 accompanying arousal cannot explain the origin of these signals in the brain. These findings establish the global fMRI signal as a significant component of the arousal response governed by the autonomic nervous system.
Immigration and seasonal bottlenecks: High inbreeding despite high genetic diversity in an oscillating population of the biting midge,Culicoides sonorensis(Diptera: Ceratopogonidae)
Authors: Shults Phillip , Zhang Xinmi , Moran Megan , Cohnstaedt Lee W. , Gerry Alec C. , Vargo Edward L. , Eyer Pierre-Andre 
Published: January 2023

ABSTRACTMost population genetic studies concern spatial genetic differentiation, but far fewer aim at analyzing the temporal genetic changes that occur within populations. Vector species, including mosquitoes and biting midges, are often characterized by oscillating adult population densities, which may affect their dispersal, selection, and genetic diversity over time. Here, we used a population ofCulicoides sonorensisfrom a single site in California to investigate short-term (intra-annual) and long-term (inter-annual) temporal variation in genetic diversity over a three year period. This biting midge species is the primary vector of several viruses affecting both wildlife and livestock, thus a better understanding of the population dynamics of this species can help inform epidemiological studies. We found no significant genetic differentiation between months or years, and no correlation between adult populations and the inbreeding coefficient (FIS). However, we show that repeated periods of low adult abundance during cooler winter months resulted in recurring bottleneck events. Interestingly, we also found a high number of private and rare alleles, which suggests both a large, stable population, as well as a constant influx of migrants from nearby populations. Overall, we showed that the high number of migrants maintains a high level of genetic diversity by introducing new alleles, while this increased diversity is counterbalanced by recurrent bottleneck events potentially purging unfit alleles each year. These results highlight the temporal influences on population structure and genetic diversity inC. sonorensisand provide insight into factors effecting genetic variation that may occur in other vector species with fluctuating populations.
Oligonucleotide-directed proximity-interactome mapping (O-MAP): A unified method for discovering RNA-interacting proteins, transcripts and genomic lociin situ
Authors: Tsue Ashley F. , Kania Evan E. , Lei Diana Q. , Fields Rose , McGann Christopher D. , Hershberg Elliot , Deng Xinxian , Kihiu Maryanne , Ong Shao-En , Disteche Christine M. , Kugel Sita , Beliveau Brian J. , Schweppe Devin K. , Shechner David M. 
Published: January 2023

ABSTRACTThroughout biology, RNA molecules form complex networks of molecular interactions that are central to their function, but remain challenging to investigate. Here, we introduce Oligonucleotide-mediated proximity-interactome MAPping (O-MAP), a straightforward method for elucidating the biomolecules near an RNA of interest, within its native cellular context. O-MAP uses programmable oligonucleotide probes to deliver proximity-biotinylating enzymes to a target RNA, enabling nearby molecules to be enriched by streptavidin pulldown. O-MAP induces exceptionally precise RNA-localizedin situbiotinylation, and unlike alternative methods it enables straightforward optimization of its targeting accuracy. Using the 47S pre-ribosomal RNA and long noncoding RNAXistas models, we develop O-MAP workflows for unbiased discovery of RNA-proximal proteins, transcripts, and genomic loci. This revealed unexpected co-compartmentalization ofXistand other chromatin-regulatory RNAs and enabled systematic characterization of nucleolar-chromatin interactions across multiple cell lines. O-MAP is portable to cultured cells, organoids, and tissues, and to RNAs of various lengths, abundances, and sequence composition. And, O-MAP requires no genetic manipulation and uses exclusively off-the-shelf parts. We therefore anticipate its application to a broad array of RNA phenomena.
The heme-responsive PrrH sRNA regulatesPseudomonas aeruginosapyochelin gene expression
Authors: Hoang Tra-My , Huang Weiliang , Gans Jonathan , Nowak Evan , Barbier Mariette , Wilks Angela , Kane Maureen A. , Oglesby Amanda G. 
Published: January 2023

AbstractPseudomonas aeruginosais an opportunistic pathogen that requires iron for growth and virulence, yet this nutrient is sequestered by the innate immune system during infection. When iron is limiting,P. aeruginosaexpresses the PrrF1 and PrrF2 small regulatory RNAs (sRNAs), which post-transcriptionally repress expression of non-essential iron-containing proteins thus sparing this nutrient for more critical processes. The genes for the PrrF1 and PrrF2 sRNAs are arranged in tandem on the chromosome, allowing for the transcription of a longer heme-responsive sRNA, termed PrrH. While the functions of PrrF1 and PrrF2 have been studied extensively, the role of PrrH inP. aeruginosaphysiology and virulence is not well understood. In this study, we performed transcriptomic and proteomic studies to identify the PrrH regulon. In shaking cultures, the pyochelin synthesis proteins were increased in two distinctprrHmutants compared to wild type, while the mRNAs for these proteins were not affected byprrHmutation. We identified complementarity between the PrrH sRNA and sequence upstream of thepchEmRNA, suggesting potential for PrrH to directly regulate expression of genes for pyochelin synthesis. We further showed thatpchEmRNA levels were increased in theprrHmutants when grown in static but not shaking conditions. Moreover, we discovered controlling for the presence of light was critical for examining the impact of PrrH onpchEexpression. As such, our study reports on the first likely target of the PrrH sRNA and highlights key environmental variables that will allow for future characterization of PrrH function.ImportanceIn the human host, iron is predominantly in the form of heme, whichPseudomonas aeruginosacan acquire as an iron source during infection. We previously showed that the iron-responsive PrrF sRNAs are critical for mediating iron homeostasis duringP. aeruginosainfection; however the function of the heme-responsive PrrH sRNA remains unclear. In this study, we identified genes for pyochelin siderophore biosynthesis, which mediate uptake of inorganic iron, as a novel target of PrrH regulation. This study therefore highlights a novel relationship between heme availability and siderophore biosynthesis inP. aeruginosa.
VPg impact on Ryegrass mottle virus serine-like 3C protease proteolysis and structure
Authors: Kalnins Gints , Ludviga Rebeka , Kalnciema Ieva , Resevica Gunta , Zeltina Vilija , Bogans Janis , Tars Kaspars , Zeltins Andris , Balke Ina 
Published: January 2023

AbstractSobemoviruses encode serine-like 3C proteases (Pro) that participate in the processing and maturation of other virus-encoded proteins. Itscisandtransactivity is mediated by the naturally unfolded virus-genome-linked protein (VPg). NMR studies show a Pro-VPg complex interaction and VPg tertiary structure; however, information regarding structural changes of the Pro-VPg complex during interaction is lacking. Here, we solved a full Pro-VPg 3D structure of ryegrass mottle virus (RGMoV) that demonstrates the structural changes in three different conformations due to VPg interaction with Pro. We identified a unique site of VPg interaction with Pro that was not observed in other sobemoviruses and observed different conformations of the Pro β2 barrel. This is the first report of a full plant Pro crystal structure with its VPg cofactor. We also confirmed the existence of an unusual previously unmapped cleavage site for sobemovirus Pro in the transmembrane domain: E/A. We demonstrated that RGMoV Proin cisactivity is not regulated by VPg and thatin trans, VPg can also mediate Pro in free form. Additionally, we observed Ca2+and Zn2+inhibitory activities on the Pro cleavage activity.Author summaryThe gRNA of sobemoviruses encodes two polyproteins that are processed by a serine protease. We found that in the bacterial expression system, Pro is activein cisandin trans, where onlyin transactivity is mediated by VPg not only in the fusion form with Pro but also in the free form. Here, we present structural changes in the catalytic and substrate-binding sites of Pro caused by VPg, which can explain thein transactivity and structure of sobemovirus VPg C-terminal peptide. In addition, we confirmed a new cleavage site not previously characterized in sobemoviruses. Additionally, Ca2+and Zn2+decreased Pro cleavage activity. This information could provide a better understanding of a serine protease and their proteolytic mechanisms during viral protein maturation.
Electronic data review, client reminders, and expanded clinic hours for improving cervical cancer screening rates after COVID-19 pandemic shutdowns: a multi-component quality improvement program
Authors: Ghosh Sue , Fantes Jackie , Leschly Karin , Mazul Julio , Perkins Rebecca 
Published: January 2023

AbstractObjectiveTo improve cervical cancer screening (CCS) rates, the East Boston Neighborhood Health Center (EBNHC) implemented a Quality Improvement (QI) initiative from March to August 2021.MethodsStaff training was provided. A 21-provider team validated overdue CCS indicated by electronic medical record data. To improve screening, CCS-only sessions were created during regular clinic hours (n=5) and weekends/evenings (n=8). Patients were surveyed on their experience.Results6126 charts were reviewed. Of the list of overdue patients, outreach was performed to 1375 patients to schedule the 13 sessions. A total of 459 (33%) of patients completed screening, 622 (45%) could not be reached, and 203 (15%) canceled or missed appointments. The proportion of total active patients who were up to date with CCS increased from 68% in March to 73% in August 2021. Survey results indicated high patient satisfaction, and only 42% of patients would have scheduled CCS without outreach.ConclusionsThe creation of a validated patient chart list and extra clinical sessions devoted entirely to CCS improved up-to-date CCS rates. However, high rates of unsuccessful outreach and cancelations limited sustainability. This information can be used by other community health centers to optimize clinical workflows for CCS.FundingAll funding was internal from EBNHC Adult Medicine, Family Medicine, and Women’s Health Departments.
A pivotal study on patients’ selection for BRCA1 and BRCA2 mutations by different models in Libyan breast cancer women
Authors: Elmaihub Eanas , Alhudiri Inas , Elzagheid Adam , Elfagi Fakria , Hassen Elham 
Published: January 2023

AbstractIntroductionThe BRCA mutation spectrum of familial breast cancer in Libya remains unknown. Several genetic models developed to predict the probability of BRCA1/2 mutations have not been applied in Libya, where the NCCN criteria are used for highly penetrating breast cancer susceptibility genes. This study aimed to predict BRCA1/2 mutation probability in familial breast cancer and eligibility for genetic testing by using BOADICEA and BRCAPRO models and NCCN criteria.MethodsBRCA1/2 mutations were retrospectively predicted in 62 unrelated women with familial breast cancer between 2018 and 2021. Logistic regression, ROC analysis, and AUC were used to compare NCCN referral criteria with the BRCAPRO and BOADICEA scores.ResultsOf 62 breast cancer patients, 32 (51.6%) (mean age 43.5±8 years) were predicted by both models as BRCA mutation carriers. BRCAPRO predicted BRCA1 and BRCA2 mutations in 27.4% and 41.9% of the women, respectively. BOADICEA predicted 8% for BRCA1 and 29% for BRCA2. At least one NCCN criterion was met by 50/62 women (80.6%). Three criteria were statistically significant predictors in BRCAPRO and BOADICEA: breast cancer at ≤ 50 years with one or more close blood relatives with breast cancer, breast cancer patient with a close relative of male breast cancer, and triple-negative breast cancer. For the three respective criteria, sensitivity was 0.78, 0.89 and 0.75, specificity was 0.33, 0.39 and 0.22, AUC was 0.72, 0.75 and 0.76, PPV was 78%, 27.5% and 33.3, and NPV was 67%, 97% and 95.5.ConclusionsBODICEA and BRCAPRO models are suitable for recommending genetic testing for BRCA gene mutations. The NCCN criteria are too broad.