bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thermodynamic modeling of Csr/Rsm- RNA interactions capture novel, direct binding interactions across thePseudomonas aeruginosatranscriptome
Authors: Lukasiewicz Alexandra J , Leistra Abigail N , Hoefner Lily , Monzon Erika , Gode Cindy J , Zorn Bryan T , Janssen Kayley H , Yahr Timothy L , Wolfgang Matthew C , Contreras Lydia M 
Published: August 2024

AbstractBackgroundPseudomonas aeruginosa(PA) is a ubiquitous, Gram-negative, bacteria that can attribute its survivability to numerous sensing and signaling pathways; conferring fitness due to speed of response. Post-transcriptional regulation is an energy efficient approach to quickly shift gene expression in response to the environment. The conserved post-transcriptional regulator RsmA is involved in regulating translation of genes involved in pathways that contribute to virulence, metabolism, and antibiotic resistance. Prior high-throughput approaches to map the full regulatory landscape of RsmA have estimated a target pool of approximately 500 genes; however, these approaches have been limited to a narrow range of growth phase, strain, and media conditions. Computational modeling presents a condition-independent approach to generating predictions for binding between the RsmA protein and highest affinity mRNAs. In this study, we draft a two-state thermodynamic model to predict the likelihood of RsmA binding to the 5’ UTR sequence of genes present in the PA genome.ResultsOur modeling approach predicts 1043 direct RsmA-mRNA binding interactions, including 457 novel mRNA targets. We then perform GO term enrichment tests on our predictions that reveal significant enrichment for DNA binding transcriptional regulators. In addition, quorum sensing, biofilm formation, and two-component signaling pathways were represented in KEGG enrichment analysis. We confirm binding predictions usingin vitrobinding assays, and regulatory effects usingin vivotranslational reporters. These reveal RsmA binding and regulation of a broader number of genes not previously reported. An important new observation of this work is the direct regulation of several novel mRNA targets encoding for factors involved in Quorum Sensing and the Type IV Secretion system, such asrsaLandmvaT.ConclusionsOur study demonstrates the utility of thermodynamic modeling for predicting interactions independent of complex and environmentally-sensitive systems, specifically for profiling the post-transcriptional regulator RsmA. Our experimental validation of RsmA binding to novel targets both supports our model and expands upon the pool of characterized target genes in PA. Overall, our findings demonstrate that a modeling approach can differentiate direct from indirect binding interactions and predict specific sites of binding for this global regulatory protein, thus broadening our understanding of the role of RsmA regulation in this relevant pathogen.
Clearing the air on pollutant disruptions of the gut-brain axis: Developmental exposure to Benzo[a]pyrene disturbs zebrafish behavior and the gut microbiome in adults and subsequent generations
Authors: Alexiev Alexandra , Stretch Ebony , Kasschau Kristin D. , Wilson Lindsay B. , Truong Lisa , Tanguay Robyn L. , Sharpton Thomas J. 
Published: August 2024

AbstractDevelopmental exposure to benzo[a]pyrene (BaP), a ubiquitous environmental pollutant, has been linked to various toxic effects, including neurodegenerative disorders and, most recently, multigenerational behavioral impairment. While the specific mechanisms driving BaP neurotoxicity are not fully understood, recent work highlights two important determinants of developmental BaP neurotoxicity: (1) the aryl hydrocarbon receptor (AHR), which is responsible for inducing host metabolism of BaP, and (2) the gut microbiome, which may interact with BaP to affect its metabolism, or be perturbed directly by BaP to yield disruptions to the gut-brain axis. To explore the role of AHR, the gut microbiome, and their interaction on BaP-induced neurotoxicity, we utilized the zebrafish model. We sought to determine (1) how exposure to BaP and developmental expression of AHR2, a key gene in the zebrafish AHR pathway, link to adult zebrafish behavior, (2) how these same variables associated with the structure and function of the adult zebrafish gut metagenome, and (3) whether these associations were multigenerational. This finding revealed a reticulated axis of association between BaP exposure, developmental AHR2 expression, the zebrafish gut metagenome, and behavior. Our results also indicate that AHR2 is a key mediator of how BaP elicits neurotoxicity and microbiome dysbiosis. Additionally, this axis of association manifests inter- and transgenerationally, suggesting that exposure to BaP may yield dysbiotic and neurodevelopmental impacts on subsequent generations. These findings demonstrate the power of utilizing the zebrafish model to study pollutant-metagenome interactions and elucidate the role of specific host genes in the neurotoxicity and dysbiosis.ImportanceBenzo[a]pyrene (BaP) is a toxic chemical that is especially ubiquitous in industrialized nations, as it is produced in large quantities by burning coal, oil, and other organic compounds. Early-life andin uteroexposure to this chemical can induce adverse behavior changes in model animals, like mice and zebrafish. In humans, developmental exposure is linked to symptoms of ADHD, anxiety, and depression. This study found BaP affects zebrafish behavior and the gut microbiome throughout their life and across subsequent generations. We further discovered that a host regulatory pathway called the aryl hydrocarbon receptor is a key component of how benzo[a]pyrene, the gut microbiome, and behavior interconnect. The aryl hydrocarbon receptor binds many toxicants, as well as microbial metabolites associated with maintaining gut homeostasis, and regulates the gut-brain connection. This receptor presents a new potential mechanism of how gut microbiota relate to BaP exposure and behavior for future studies to investigate.
Evaluation of vectors for gene expression inPseudovibriomarine bacteria
Authors: Dai Yitao , Eustáquio Alessandra S. 
Published: August 2024

Abstractα-Proteobacteria belonging to thePseudovibriogenus have been isolated from different marine organisms including marine sponges, corals and algae. This genus was first described in 2004 and has since garnered attention due to the potential ecological relevance and biotechnological application of its metabolites. For instance, we recently reported specialized metabolites we named pseudovibriamides fromPseudovibrio brasiliensisAb134. The pseudovibriamide encodingpppgene cluster is found in two thirds ofPseudovibriogenomes. Pseudovibriamides coordinate motility and biofilm formation, behaviors that are known to be important for host colonization. Although we previously established reverse genetics methods to delete genes via homologous recombination, no self-replicative vectors have been reported forPseudovibrio. We show that plasmid vectors containing two different broad-host-range replicons, RSF1010 and pBBR1, can be used inP. brasiliensis. The efficiency of vector transfer by electroporation averaged ∼ 3 × 103CFU/µg plasmid DNA whereas the conjugation frequency fromE. coliranged from 10-3to 10-6. We then tested the vectors for fluorescent protein expression and consequent labeling, which allowed us to observe their effects on swarming motility and to compare plasmid stability. This study expands the genetic toolbox available forPseudovibriowhich is expected to enable future ecological and biotechnological studies.ImportanceThe genusPseudovibrioof α-Proteobacteria has consistently been isolated from marine sponges and other marine organisms such as corals and algae.Pseudovibriobacteria are a source of antibiotics and other secondary metabolites with the potential to be developed into pharmaceuticals. Moreover, the secondary metabolites they produce are important for their physiology and for interactions with other organisms. Here we expand the genetic tool box available forPseudovibriobacteria by establishing self-replicative vectors that can be used for the expression of e.g., fluorescent proteins. The availability of genetic tools is important to enable us to explore the emerging ecological and biotechnological potential ofPseudovibriobacteria.
Dysbiosis-associated gut bacteriumRuminococcus gnavusvaries at the strain level in ability to utilize key mucin component sialic acid
Authors: Sokolovskaya Olga M. , Uzunovic Jasmina , Peng Yutian , Okumura Mikiko , Wang Lingjue Mike , Zhou Yuhui , Lai Zijuan , Skippington Elizabeth , Tan Man-Wah 
Published: August 2024

AbstractRuminococcus gnavusis a prevalent human gut commensal bacterium with known roles in intestinal mucus degradation, including by catabolism of the terminal mucin sugar sialic acid. WhileR. gnavusis not considered a pathogen, overabundance of this species is correlated with Inflammatory Bowel Disease (IBD), and its sialic acid metabolism may play a role in the dysbiotic state. Interestingly, liberation of mucin-bound sialic acid byR. gnavusyields the distinct product of 2,7-anhydro-N-acetylneuraminic acid (2,7-anhydro-Neu5Ac), in contrast to other known mucin-degrading bacteria, which generate Neu5Ac. This prompted us to look for 2,7-anhydro-Neu5Ac metabolism proteins in the genomes of 77R. gnavusclinical isolates. We found that 2,7-anhydro-Neu5Ac metabolism is sporadically distributed in this species with respect to phylogeny and strain origin. We measured sialic acid-dependent growth of 12 sequenced isolates, finding that the presence of 2,7-anhydro-Neu5Ac catabolism proteins was predictive of growth on this substrate. Our analysis also uncovered “partial” 2,7-anhydro-Neu5Ac catabolism pathways in twoR. gnavusstrains, which we determined constitute the canonical Neu5Ac catabolism pathway, previously unreported in this species. These results reveal a notable diversity of sialic acid catabolism across theR. gnavusspecies, an essential consideration for further investigations into the importance of this metabolism in mucin degradation and in roles ofR. gnavusin IBD and other gut dysbioses.
Effects of short-term isolation on vocal and non-vocal social behaviors in prairie voles
Authors: Madrid Jesus E. , Pranic Nicole M. , Chu Samantha , Bergstrom Johanna J. D. , Singh Rhea , Rabinovich Joclin , Lopez Kaycee Arias , Ophir Alexander G. , Tschida Katherine A. 
Published: August 2024

AbstractSocial isolation affects the brain and behavior in a variety of animals, including humans. Studies in traditional laboratory rodents, including mice and rats, have supported the idea that short-term social isolation promotes affiliative social behaviors, while long-term isolation promotes anti-social behaviors, including increased aggression. Whether the effects of isolation on the social behaviors of mice and rats generalize to other rodents remains understudied. In the current study, we characterized the effects of short-term (3-days) social isolation on the vocal and non-vocal social behaviors of adult prairie voles (Microtus ochrogaster) during same-sex and opposite-sex social interactions. Our experiments revealed that short-term isolation did not affect rates of ultrasonic vocalizations or time spent in non-aggressive social behaviors and huddling. In contrast, short-term isolation affected aggression in a sex- and context-specific manner during male-male interactions. Our findings highlight the importance of comparative work across species and the consideration of social context to understand the diverse ways in which social isolation can impact social behavior.
Genomic and phenotypic characterization of an Oropouche virus strain implicated in the 2023-24 large-scale outbreak in Brazil
Authors: Azevedo Elisa de Almeida Neves , da Silva Alexandre Freitas , da Silva Verônica Gomes , Machado Lais Ceschini , de Lima Gustavo Barbosa , Ishigami Bruno Issao Matos , Silva Keilla Maria Paz e , da Costa Mayara Matias de Oliveira Marques , Falcão Diego Arruda , Vasconcelos Andreza Pâmela , da Silva Clintiano Curvêlo , Naveca Felipe Gomes , Bezerra Matheus Filgueira , de Lima Campos Tulio , Acioli-Santos Bartolomeu , Paiva Marcelo Henrique Santos , Morais Clarice Neuenschwander Lins de , Wallau Gabriel Luz 
Published: August 2024

AbstractTheOrthobunyavirus oropoucheensein a arthropod borne zoonotic pathogen known to infect sylvatic animals and humans by means of biting midges transmission. Several large-scale human outbreaks of Oropouche virus (OROV), primarily confined to the Amazon region, were documented over the decades. However, since 2022, more widespread OROV outbreaks have been unfolding in Brazil and across South America, with cases exported to Cuba, Italy, and Germany. I In Brazil, the virus has reached and established communitary transmission in states from all major regions of the country. Here we isolated, characterized the cytopathic effect and the full genomic sequence of two OROV isolates from the current outbreak. Our data shows that OROV can readily infect and replicate in non-human primate cells, supporting the role of non-human primates as important reservoirs. Phylogenetic data supports a direct introduction of the same lineages causing the 2022-24 outbreak in Brazil from the Amazonas state, the epicenter of the epidemics in Brazil. Lastly, as case counts accumulate in the state and the Northeast region, clear evidence supports established and sustained transmission. Continued studies are critical to understand the transmission cycle in this region, the most important vectors and reservoirs, to appropriately deploy control measures.
Endocytic dynamin deficiency impairs the host colonization of phytopathogenic fungi
Authors: Chen Xin , Chen Xiaomin , Long Yunfei , Fang Zhenyu , Abubakar Yakubu Saddeeq , Zheng Huawei , Wang Zonghua , Zheng Wenhui 
Published: August 2024

AbstractDuring host-pathogen interactions, pathogens employ endolysosomal trafficking to fine-tune host and environmental cues, facilitating disease progression. Inhibiting the functions of the endolysosomal network could be promising for the control of plant fungal diseases. Herein, we showed that inhibition of the endocytic dynamin FgVps1 by the phenothiazines chlorpromazine (CPZ) and prochlorperazine (PCZ) leads to endolysosomal dysfunction. Further analyses revealed that the phenothiazines directly bind the GTPase domain of FgVps1 to inhibit its activity. Moreover, our results showed that FgVps1 is recruited to the endosome by the Rab GTPases FgRab51 and FgRab7 to facilitate the release of retromer- and sorting nexin-coated vesicles, thereby ensuring the proper recycling of some cargos and promoting fungal development and pathogenicity. Direct treatment of the phytopathogensF. graminearum,Magnaporthe oryzaeandFusarium oxysporum f. sp. cubensewith CPZ and PCZ also impairs their growth, development and virulence. These results unveil the underlying mechanisms of endocytic dynamin actions and provide a potential strategy for broad-spectrum control of phytopathogenic fungi.
Membrane bound geranylated RNAs establish a primitive peptide synthesis system
Authors: Chan Chun-Yin , Singer Johannes , Carell Thomas 
Published: August 2024

AbstractThe origin of an RNA-based translation system necessitates a specific interaction of certain RNAs with defined amino acids. This must have happened in a protocellular environment where these molecules were concentrated so that a connection between the encoding RNA and the amino acids could be established that allowed the formation of peptides. A model of how such a system could have evolved does not exist. Here we show that geranylated non-canonical nucleotides that are potential fossils in an early RNA world, allow RNA to anchor to lipid membranes. This creates RNA-geranylating lipids on which a primitive peptide synthesis can then operate with rudimentary chemoselectivity. The system creates a protocellular model of how RNAs and amino acids could have been mutually selected based on their physicochemical properties.
Autophagy disruption and mitochondrial stress precede photoreceptor necroptosis in multiple mouse models of inherited retinal disorders
Authors: Newton Fay , Halachev Mihail , Nguyen Linda , McKie Lisa , Mill Pleasantine , Megaw Roly 
Published: August 2024

AbstractInherited retinal diseases (IRDs) are a leading cause of blindness worldwide. One of the greatest barriers to developing treatments for IRDs is the heterogeneity of these disorders, with causative mutations identified in over 280 genes. It is therefore a priority to find therapies applicable to a broad range of genetic causes. To do so requires a greater understanding of the common or overlapping molecular pathways that lead to photoreceptor death in IRDs and the molecular processes through which they converge. Here, we characterise the contribution of different cell death mechanisms to photoreceptor degeneration and loss throughout disease progression in humanised mouse models of IRDs. Using single-cell transcriptomics, we identify common transcriptional signatures in degenerating photoreceptors. Further, we show that in genetically and functionally distinct IRD models, common early defects in autophagy and mitochondrial damage exist, triggering photoreceptor cell death by necroptosis in later disease stages. These results suggest that, regardless of the underlying genetic cause, these pathways likely contribute to cell death in IRDs. These insights provide potential therapeutic targets for novel, gene-agnostic treatments for IRDs applicable to the majority of patients.
Monoacylglycerol acyltransferase maintains ionotropic receptor expression for cool temperature sensing and avoidance inDrosophila
Authors: Deng Xiangmei , Suito Takuto , Tominaga Makoto , Sokabe Takaaki 
Published: August 2024

AbstractSensory inputs of temperature dynamics in the environment are essential for appropriate physiological outputs. The responsiveness of sensory neurons is maintained by functional thermosensor expression. However, the mechanism by which their expression is regulated is unclear. In this study, we identified a monoacylglycerol acyltransferase-coding gene namedbishu-1that contributes to maintaining the responsiveness of cool temperature sensing neurons inDrosophila.bishu-1mutation led to abnormal thermal avoidance in a cool temperature range. Cooling-induced responses in dorsal organ cool cells were weakened by the absence ofbishu-1, and this was associated with reduced transcription of the ionotropic receptorsIR25aandIR21athrough the transcription factorbroad. Our findings unveil a novel link between lipid metabolism and thermosensor function, thus providing new insights into mechanisms underlying the appropriate maintenance of sensory inputs.
Identification of anthelmintic activity in a small chemical library through random screening using the wormCaenorhabditis elegansas a model helminth
Authors: Gajera Gemini , Kothari Vijay 
Published: August 2024

AbstractParasitic helminths contribute notably to the global infection burden, particularly in developing and underdeveloped nations. Anthelmintic agents currently available for therapeutic purpose are not many in number, and owing to development of resistance against them among parasitic worms, their utility spectrum is also shrinking. Hence, there is an urgent need for discovery of new anthelmintic compounds. This study subjected a small library of 181 compounds to a random screening for identification of compounds with anthelmintic activity against the model wormCaenorhabditis elegans. This screening effort identified 50 compounds capable of killing 100% of the worm population in less than 24 hours, at 25-50 ppm. Further investigation on these ‘hits’ is warranted to identify potential anthelmintic ‘leads’.
Structural mechanism of MUC5AC mucin net-like polymer formation and its SNP variability that affect risk of the lung diseases COPD and IPF
Authors: Trillo-Muyo Sergio , Ermund Anna , Magnusson Jesper M. , Hansson Gunnar C. 
Published: August 2024

ABSTRACTGel-forming mucins MUC5AC and MUC5B constitute the main structural component of the mucus in the respiratory system. Secreted mucins interact specifically with each other and other molecules giving mucus specific properties. We determined the cryoEM structures of the wild type MUC5AC-D3 assembly and the structural SNP variants R996Q and R1201W. Our structures explain the basis of MUC5AC N-terminal non-covalent oligomerization upon secretion. The MUC5AC-D3 assembly forms covalent dimers in two alternative conformations, open and closed. The closed conformation dimers interact through an arginine rich loop in the TIL3 domain forming tetramers. Moreover, we found a positive disease correlation between the SNP (R996Q, rs878913005), Chronic Obstructive Pulmonary Disease (COPD), and Idiopathic Pulmonary Fibrosis (IPF). The well-known MUC5B promotor SNP (rs35705950) association with IPF is much stronger when combined with the MUC5AC SNP. Our study provides a model to explain the formation of MUC5AC net-like structures and how both SNPs will affect mucus organization and increase risk of lung disease.
Word-selective EEG/MEG responses in the English language obtained with Fast Periodic Visual Stimulation (FPVS)
Authors: Hauk O , Marchive M , Volfart A , Schiltz C , Rossion B , Lambon Ralph MA , Lochy A 
Published: August 2024

AbstractFast periodic visual stimulation (FPVS) allows the recording of objective brain responses of human word discrimination (i.e., reproducible word-category-selective responses) with a high signal-to-noise ratio. This approach has been successfully employed over the last decade in a number of scalp electroencephalography (EEG) studies. Three important advances were achieved in this study: (1) robust measures of written word-selective responses with this approach have not been reported in English; (2) responses have only been reported in EEG but not with MEG, and (3) without source localization. Thus, we presented English words periodically (2 Hz) among different types of letter strings (10Hz; consonant strings, non-words, pseudowords) whilst recording simultaneous EEG and MEG in 25 participants who performed a simple non-linguistic color detection task. Data were analyzed in sensor and in source space (L2-minimum-norm estimation, MNE). With only 4 minutes of stimulation we observed a robust word discrimination response in each condition including, importantly, even when words were embedded in word-like pseudowords. This response was larger in nonwords and largest in consonant strings. We observed left-lateralized responses in all conditions in the majority of our participants. Cluster-based permutation tests revealed that these responses were left-lateralized in sensor as well as in source space, with peaks in left posterior regions. Our results demonstrate that the FPVS paradigm can elicit robust English word-discrimination responses in EEG and MEG within only a few minutes of recording time. Together with source estimation, this can provide novel insights into the neural basis of visual word recognition in healthy and clinical populations.