bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardiac neurons expressing a glucagon-like receptor mediate cardiac arrhythmia induced by high-fat diet inDrosophila
Authors: Zhao Yunpo , Duan Jianli , van de Leemput Joyce , Han Zhe 
Published: December 2023

ABSTRACTCardiac arrhythmia leads to increased risks for stroke, heart failure, and cardiac arrest. Arrhythmic pathology is rooted in the cardiac conduction system, but the mechanism is complex and not fully understood. For example, how metabolic diseases, like obesity and diabetes, increase the risk for cardiac arrhythmia. Glucagon regulates glucose production, mobilizes lipids from the fat body, and affects cardiac rate and rhythm, attributes of a likely key player.Drosophilais an established model to study metabolic diseases and cardiac arrhythmias. Since glucagon signaling is highly conserved, we used high-fat diet (HFD)-fed flies to study its effect on heart function. HFD led to increased heartbeat and an irregular rhythm. The HFD-fed flies showed increased levels of adipokinetic hormone (Akh), the functional equivalent to human glucagon. Both genetic reduction of Akh and eliminating the Akh producing cells (APC) rescued HFD-induced arrhythmia, whereas heart rhythm was normal in Akh receptor mutants (AkhRnull). Furthermore, we discovered a pair of cardiac neurons that express high levels of Akh receptor. These are located near the posterior heart, make synaptic connections at the heart muscle, and regulate heart rhythm. Altogether, this Akh signaling pathway provides new understanding of the regulatory mechanisms between metabolic disease and cardiac arrhythmia.HIGHLIGHTSHigh-fat diet activates Akh (glucagon-like)-producing neurons near the esophagus inDrosophilaReducing Akh prevents high-fat diet-induced cardiac arrhythmia in fliesDiscovery of two neurons located at the posterior end of the heart that express the Akh receptor (AkhR) and innervate the heartEliminating one of the two AkhR-expressing cardiac neurons (ACN) results in cardiac arrhythmia, whereas the absence of functional AkhR prevents high-fat diet-induced cardiac arrhythmia in flies
Error-based implicit learning in language: the effect of sentence context and constraint in a repetition paradigm
Authors: Hodapp Alice , Rabovsky Milena 
Published: December 2023

AbstractPrediction errors drive implicit learning in language, but the specific mechanisms underlying these effects remain debated. This issue was addressed in an electroencephalogram (EEG) study manipulating the context of a repeated unpredictable word (repetition of the complete sentence or repetition of the word in a new sentence context) and sentence constraint. For the manipulation of sentence constraint, unexpected words were presented either in high constraint (eliciting a precise prediction) or low constraint sentences (not eliciting any specific prediction). Repetition induced reduction of N400 amplitudes and of power in the alpha/beta frequency band was larger for words repeated with their sentence context as compared to words repeated in a new low constraint context, suggesting that implicit learning happens not only at the level of individual items but additionally improves sentence-based predictions. These processing benefits for repeated sentences did not differ between constraint conditions, suggesting that sentence-based prediction update might be proportional to the amount of unpredicted semantic information, rather than to the precision of the prediction that was violated. Additionally, the consequences of high constraint prediction violations, as reflected in a frontal positivity and increased theta band power, were reduced with repetition. Overall, our findings suggest a powerful and specific adaptation mechanism that allows the language system to quickly adapt its predictions when unexpected semantic information is processed, irrespective of sentence constraint, and to reduce potential costs of strong predictions that were violated.
The P600 and P3 ERP components are linked to the task-evoked pupillary response as a correlate of norepinephrine activity
Authors: Contier Friederike , Wartenburger Isabell , Weymar Mathias , Rabovsky Milena 
Published: December 2023

AbstractDuring language comprehension, anomalies and ambiguities in the input typically elicit the P600 event-related potential component. Although traditionally interpreted as a specific signal of combinatorial operations in sentence processing, the component has alternatively been proposed to be a variant of the oddball-sensitive, domain-general P3 component. In particular, both components might reflect phasic norepinephrine release from the locus coeruleus (LC/NE) to motivationally significant stimuli. In this preregistered study, we tested this hypothesis by relating both components to the task-evoked pupillary response, a putative biomarker of LC/NE activity. 36 participants completed a sentence comprehension task (containing 25% morphosyntactic violations) and a non-linguistic oddball task (containing 20% oddballs), while the EEG and pupil size were co-registered. Our results showed that the task-evoked pupillary response and the ERP amplitudes of both components were similarly affected by both experimental tasks. Crucially, the size of the pupillary response – both pupil size and its temporal derivative – predicted the amplitude of both ERP components on a trial- by-trial basis. This pattern of results supports the idea that both, the P3 and the P600, might rely on a shared neural generator and, more specifically, that they may both be linked to phasic NE release. Generally, our findings further stimulate the debate on whether language- related ERPs are indeed specific to linguistic processes or shared across cognitive domains. In the case of the P600, the present results indicate that anomalies during language comprehension might rather initiate transient NE activity in response to rare and motivationally significant stimuli more generally.
Bosutinib stimulates macrophage survival, phagocytosis and intracellular killing of bacteria
Authors: da Silva Ronni A. G. , Stocks Claudia J. , Hu Guangan , Kline Kimberly A. , Chen Jianzhu 
Published: December 2023

AbstractHost-acting compounds are emerging as potential alternatives to combat antibiotic resistance. Here, we show that bosutinib, an FDA-approved chemotherapeutic for treating chronic myelogenous leukemia, does not possess any antibiotic activity but enhances macrophage responses to bacterial infection.In vitro, bosutinib stimulates murine and human macrophages to kill bacteria more effectively. In a murine wound infection with vancomycin-resistantEnterococcus faecalis, a single intraperitoneal bosutinib injection or multiple topical applications on the wound reduces bacterial load by approximately 10-fold, which is abolished by macrophage depletion. Mechanistically, bosutinib stimulates macrophage phagocytosis of bacteria by upregulating surface expression of bacterial uptake markers Dectin-1 and CD14 and promoting actin remodelling. Bosutinib also stimulates bacterial killing by elevating the intracellular levels of reactive oxygen species. Moreover, bosutinib drives NF-κB activation which protects infected macrophages from dying. Other Src kinase inhibitors such as DMAT and Tirbanibulin also upregulate expression of bacterial uptake markers in macrophages and enhance intracellular bacterial killing. Finally, co-treatment with bosutinib and mitoxantrone, another chemotherapeutic in clinical use, results in an additive effect on bacterial clearancein vitroandin vivo. These results show that bosutinib stimulates macrophage clearance of bacterial infection through multiple mechanisms and could be used to boost host innate immunity to combat drug-resistant bacterial infections.SignificanceThis study shows that bosutinib, an FDA-approved chemotherapeutic, stimulates macrophage responses to antibiotic-resistant bacterial infection by enhancing phagocytosis and intracellular killing of bacteria and promoting survival of infected macrophages. These findings suggest that bosutinib could serve as an adjuvant therapy to combat drug resistant bacterial infections and opens the possibility to target Src kinases to boost innate immunity in general.
Metagenomic assemblies tend to break around antibiotic resistance genes
Authors: Abramova Anna , Karkman Antti , Bengtsson-Palme Johan 
Published: December 2023

AbstractBackgroundAssembly of metagenomic samples can provide essential information about the mobility potential and taxonomic origin of antibiotic resistance genes (ARGs), and inform interventions to prevent further spread of resistant bacteria. However, ARGs typically occur in multiple genomic contexts across different species, representing a considerable challenge for the assembly process. Usually, this results in many fragmented contigs of unclear origin, complicating the risk assessment of ARG detections. To systematically investigate the impact of this issue on detection, quantification and contextualization of ARGs, we evaluated the performance of different assembly approaches, including genomic-, metagenomic- and transcriptomic-specialized assemblers. We quantified recovery and accuracy rates of each tool for ARGs both fromin silicospiked metagenomic samples as well as real samples sequenced using both long- and short-read sequencing technologies.ResultsThe results revealed that none of the investigated tools can accurately capture genomic contexts present in samples of high complexity. The transcriptomic assembler Trinity showed a better performance in terms of reconstructing longer and fewer contigs matching unique genomic contexts, which can be beneficial for deciphering the taxonomic origin of ARGs. The currently commonly used metagenomic assembly tools metaSPAdes and MEGAHIT were able to identify the ARG repertoire but failed to fully recover the diversity of genomic contexts present in a sample. On top of that, in a complex scenario MEGAHIT produced very short contigs, which can lead to considerable underestimation of the resistome in a given sample.ConclusionsOur study shows that metaSPAdes and Trinity would be the preferable tools in terms of accuracy to recover correct genomic contexts around ARGs in metagenomic samples characterized by uneven coverages. Overall, the inability of assemblers to reconstruct long ARG-containing contigs has impacts on ARG quantification, suggesting that directly mapping reads to an ARG database might be necessary, at least as a complementary strategy, to get accurate ARG abundance and diversity measures.
Database size positively correlates with the loss of species-level taxonomic resolution for the 16S rRNA and other prokaryotic marker genes
Authors: Commichaux Seth , Luan Tu , Muralidharan Harihara Subrahmaniam , Pop Mihai 
Published: December 2023

AbstractFor decades, the 16S rRNA gene has been used to taxonomically classify prokaryotic species and to taxonomically profile microbial communities. The 16S rRNA gene has been criticized for being too conserved to differentiate between distinct species. We argue that the inability to differentiate between species is not a unique feature of the 16S rRNA gene. Rather, we observe the gradual loss of species-level resolution for other marker genes as the number of gene sequences increases in reference databases. We demonstrate this effect through the analysis of three commonly used databases of nearly-universal prokaryotic marker genes: the SILVA 16S rRNA gene database, the Genome Taxonomy Database (GTDB), and a set of 40 taxonomically-informative single-copy genes. Our results reflect a more fundamental property of the taxonomies themselves and have broad implications for bioinformatic analyses beyond taxonomic classification. Effective solutions for fine-level taxonomic classification require a more precise, and operationally-relevant, definition of the taxonomic labels being sought, and the use of combinations of genomic markers in the classification process.ImportanceThe use of reference databases for assigning taxonomic labels to genomic and metagenomic sequences is a fundamental bioinformatic task in the characterization of microbial communities. The increasing accessibility of high throughput sequencing has led to a rapid increase in the size and number of sequences in databases. This has been beneficial for improving our understanding of the global microbial genetic diversity. However, there is evidence that as the microbial diversity is more densely sampled, increasingly longer genomic segments are needed to differentiate between distinct species. The scientific community needs to be aware of this issue and needs to develop methods that better account for it when assigning taxonomic labels to metagenomic sequences from microbial communities.
Dynamic protein assembly and architecture of the large solitary membraneless organelle during germline development in the waspNasonia vitripennis
Authors: Kharel Kabita , Tindell Samuel J. , Kemph Allie , Schmidtke Ryan , Alexander Emma , Lynch Jeremy A. , Arkov Alexey L. 
Published: December 2023

AbstractGerm cells in different animals assemble characteristic membraneless organelles referred to as germ granules, which contain RNA and proteins required for germline development. Typically, the germ granules are small spherical or amorphous cytoplasmic granules and often, they assemble around membrane-bound organelles such as nuclei, mitochondria and endoplasmic reticulum. In particular, in egg chambers of the fruit flyDrosophila, nurse cells assemble perinuclear granules, referred to as nuage, along with multiple small germ granules formed at the posterior pole of the oocyte (polar granules). Nuage is assembled in a very similar way in the waspNasonia vitripennis, despite the long evolutionary distance fromDrosophila.In contrast,Nasoniaforms a very different single germ granule, called the oosome, at the posterior, which is about 40 times larger than a homologousDrosophilapolar granule. Here, using molecular and super-resolution imaging approaches, we provide insights into protein assembly and architecture of the oosome during germline development. Interestingly, unlike the fly, the wasp utilizes alternatively spliced RNA-helicase Vasa isoforms during germline development and oosome formation. The isoforms differ by an unstructured region, containing repeats of phenylalanine and glycine, that is similar to functional domains characteristic of nucleoporins. In addition, while other conserved components of germ granules, such as Oskar, Aubergine and Tudor proteins are recruited to the oosome, these polypeptides show a distinct and specific localization within the oosome. Of particular note, Tudor protein forms a shell encapsulating the oosome, while small Oskar/Vasa/Aubergine granules occur inside the oosome core. Also, in surprising contrast toDrosophilaegg chambers, we found that a subset of the wasp nurse cells located in anterior show dramatic DNA damage and assemble higher levels of nuage than their posterior counterparts. The characteristics of two distinct nurse cell populations suggest a mechanistic link between the higher amounts of nuage assembled in anterior nurse cells and their need to silence transposable elements in the presence of double-strand DNA breaks. Our results point to the high degree of plasticity in the assembly of membraneless organelles, which adapt to specific developmental needs of different organisms, and suggest that novel molecular features of conserved proteins result in the unique architecture of the oosome in the wasp.
The leucine-rich repeat receptor kinase QSK1 is a novel regulator of PRR-RBOHD complex and is employed by the bacterial effector HopF2Ptoto modulate plant immunity
Authors: Goto Yukihisa , Kadota Yasuhiro , Mbengue Malick , Lewis Jennifer D , Matsui Hidenori , Maki Noriko , Sklenar Jan , Derbyshire Paul , Shibata Arisa , Ichihashi Yasunori , Guttman David S. , Nakagami Hirofumi , Suzuki Takamasa , Menke Frank L.H. , Robatzek Silke , Desveaux Darrell , Zipfel Cyril , Shirasu Ken 
Published: December 2023

AbstractPlants detect pathogens using cell-surface pattern recognition receptors (PRRs) like EFR and FLS2, which recognize bacterial EF-Tu and flagellin, respectively. These PRRs, belonging to the leucine-rich repeat receptor kinase (LRR-RK) family, activate the production of reactive oxygen species via the NADPH oxidase RBOHD. The PRR-RBOHD complex is tightly regulated to prevent unwarranted or exaggerated immune responses. However, certain pathogenic effectors can subvert these regulatory mechanisms, thereby suppressing plant immunity. To elucidate the intricate dynamics of the PRR-RBOHD complex, we conducted a comparative co-immunoprecipitation analysis using EFR, FLS2, and RBOHD. We identified QSK1, an LRR-RK, as a novel component of the PRR-RBOHD complex. QSK1 functions as a negative regulator of PRR-triggered immunity (PTI) by downregulating the abundance of FLS2 and EFR. QSK1 is targeted by the bacterial effector HopF2Pto, a mono-ADP ribosyltransferase, resulting in the reduction of FLS2 and EFR levels through both transcriptional and transcription-independent pathways, thereby inhibiting PTI. Furthermore, HopF2Ptoreduces transcript levels ofPROSCOOPgenes encoding important stress-regulated phytocytokines and their receptor MIK2. Importantly, HopF2Ptorequires QSK1 for its accumulation and virulence functions within plants. In summary, our results provide novel insights into the mechanism by which HopF2Ptoemploys QSK1 to desensitize plants to pathogen attack.One Sentence SummaryQSK1, a novel component in the plant immune receptor complex, downregulates these receptors and phytocytokines, and is exploited by bacterial effector HopF2Ptoto desensitize plants to pathogen attack.
Function of Cytochrome P450CYP72A1182in Metabolic Herbicide Resistance Evolution inAmaranthus palmeriPopulations
Authors: Rigon Carlos Alberto Gonsiorkiewicz , Küpper Anita , Sparks Crystal , Montgomery Jacob , Peter Falco , Schepp Simon , Perez-Jones Alejandro , Tranel Patrick J. , Beffa Roland , Dayan Franck E. , Gaines Todd A. 
Published: December 2023

ABSTRACTEvolution of metabolic herbicide resistance is a major issue for weed management. Few genes and regulatory mechanisms have been identified, particularly in dicotyledonous weed species. We identified putative causal genes and regulatory mechanism for tembotrione-resistance inAmaranthus palmeri. Cytochrome P450 candidate genes were identified through RNA-seq analysis. We validated their functions using heterologous expression inS. cerevisae. Promoters of the candidate P450 genes were analyzed. We performed QTL mapping to identify genomic regions associated with resistance.CYP72A1182deactivated tembotrione. This gene had increased expression in otherA. palmeripopulations resistant to multiple herbicides, including tembotrione. Resistant plants exhibited polymorphisms in the promoter ofCYP72A1182. We identified QTLs linked to herbicide resistance, including one on chromosome 4 approximately 3 Mb away fromCYP72A1182.CYP72A1182is involved in tembotrione resistance inA. palmeri. Increased expression of this gene could be due tocis-regulation in the promoter, as well astrans-regulation from transcription factors. Further studies are in progress to test this hypothesis. The elucidation of regulatory genes is crucial for developing innovative weed management approaches and target-based novel molecules.HIGHLIGHTSOur study identifies that theCYP72A1182gene has a functional role in metabolic herbicide resistance inAmaranthus palmeriand is linked tocis-regulatory polymorphisms, advancing metabolic resistance understanding in dicots.
Single cell analysis of human CD8+T cells reveals CD45RClow/-TNFR2+CD29lowCD8+Tregs with superior activity
Authors: Sérazin Céline , Flippe Léa , Streitz Mathias , Wendering Désirée-Jacqueline , Schlickeiser Stephan , Heinrich Frederik , Durek Pawel , Guerra Gabriela , Lehmann Katrin , Mashreghi Mir-Farzin , Wajant Harald , Volk Hans Dieter , Anegon Ignacio , David Laurent , Bézie Séverine , Guillonneau Carole 
Published: December 2023

ABSTRACTAlthough described in the 70’s, CD8+regulatory T cells (Tregs) remain incompletely understood and to date, although several markers are used to define them, they remain poorly defined. The identification of reliable and consistent markers, as it was done for CD4+Tregs, remains an urgent task and a challenge to advance our understanding. Herein, we analyzed total CD8+T cells using single cell CITEseq and VDJ T cell receptor sequencing utilizing markers used previously to identify Tregs, in particular CD45RC described by our team and others to divide pro-inflammatory (CD45RChigh) and pro-regulatory (CD45RClow/-) CD8+T cells in rat, mice and human. 7000 freshly isolated, non-stimulated CD8+T lymphocytes of four healthy volunteers were analyzed. Combining at a single cell level transcriptome and protein expression data led for the first time to the characterization and definition of three subsets of regulatory CD8+T cells. Furtherin vitrofunctional analysis based on three markers highlighted the superior suppressive activity of the CD8+CD45RClow/-TNFR2+CD29lowTregs subset.To our knowledge, this is the largest characterization of human CD8+Tregs to date. This data resource will help improve our understanding of CD8+T cells heterogeneity and will help to translate CD8+Tregs to the clinic.
Genomic Revisitation and Reclassification of the GenusProvidencia
Authors: Dong Xu , Jia Huiqiong , Yu Yuyun , Xiang Yanghui , Zhang Ying 
Published: December 2023

AbstractMembers ofProvidencia, although typically opportunistic, can cause severe infections in immunocompromised hosts. Recent advances in genome sequencing provide an opportunity for more precise study of this genus. In this study, we first identified and characterized a novel species namedProvidencia zhijiangensissp. nov. It has ≤88.23% average nucleotide identity (ANI) and ≤31.8% in silico DNA-DNA hybridization (dDDH) values with all knownProvidenciaspecies, which fall significantly below the species-defining thresholds. Interestingly, we found thatProvidencia stuartiiandProvidencia thailandensisactually fall under the same species, evidenced by an ANI of 98.59% and a dDDH value of 90.4%. By fusing ANI with phylogeny, we have reclassified 545 genomes within this genus into 20 species, including seven unnamed taxa (provisionally titled Taxon1-7), which can be further subdivided into 23 lineages. Pangenomic analysis identified 1,550 genus-core genes inProvidencia, with coenzymes being the predominant category at 10.56%, suggesting significant intermediate metabolism activity. Resistance analysis revealed that most lineages of the genus (82.61%, 19/23) carry a high number of antibiotic resistance genes (ARGs) and display diverse resistance profiles. Notably, the majority of ARGs are located on plasmids, underscoring the significant role of plasmids in the resistance evolution within this genus. Three species or lineages (P. stuartii, Taxon 3, andProvidencia hangzhouensisL12) that possess the highest number of carbapenem resistance genes suggest their potential influence on clinical treatment. These findings underscore the need for continued surveillance and study of this genus, particularly due to their role in harboring antibiotic resistance genes.