bluuebunny/crossref_metadata_2025_split huggingface dataset:
Iterative acylation on mature lasso peptides by widespread acetyltransferases for lipolasso production
Authors: Xiong Jiang , Wu Shanquan , Liang Zi-Qi , Fang Shuo , Tao Fen-Yu , Gong Xiao-Tong , Wu Qingfeng , Cui Jiao-Jiao , Gao Kun , Luo Shangwen , Lei Dongsheng , Dong Shi-Hui 
Published: January 2025

AbstractThe biosynthesis of ribosomally synthesized and post-translationally modified peptides (RiPPs) leverages iterative catalysis to enhance structural and biological diversity. Traditionally, iterative enzymes install multiple post-translational modifications (PTMs) on linear peptides, rather than mature RiPPs with intricate three-dimensional structures, which would require complex changes in substrate binding poses. Here, we present a prolific class of GCN5-related N-acetyltransferases (GNATs) that iteratively and consecutively acylate two Lys residues within the loop and ring motifs of lasso peptides, diverging from the typical iterative modification of linear peptides—an unprecedented function for PTM enzymes. Utilizing high-resolution cryo-electron microscopy and enzymatic reconstitution, we mapped the lasso peptide binding pocket of IatT and pinpointed key residues involved in demarcating the two distinct acetylation steps. Structure-based engineering of IatT’s acetyl group recognition site expanded the cavity to accommodate longer-chain acyl groups, leading to the creation of lipolasso peptides, a novel class of ribosomal lipopeptide. This engineering strategy can be applied to any RiPP BGC encoding GNAT, facilitating the efficient diversification of rare ribosomal lipopeptides.Graphic Abstract
Single-cell and spatial transcriptomics uncover the role of B chromosomes in driving plant invasiveness
Authors: Wang Cui , Ord James , Yan Mengxiao , Shao Hongjin , Lin Lele , Salojärvi Jarkko , Liu Lele , Guo Weihua 
Published: January 2025

AbstractInvasive plants can profoundly disrupt native biodiversity, yet the genetic mechanisms underpinning their success remain poorly understood. To date, genomic studies have been conducted on only a limited number of invasive species, and no single-cell level studies have been applied. This research investigates the genetic drivers behind the invasive behavior of the common reed (Phragmites australis), a hardy grass species that became invasive in North America following its introduction from Europe. By integrating whole-genome sequencing with single-cell and spatial transcriptomics, we developed a comprehensive single-cell atlas of the common reed’s shoot system. UMAP analysis identified 19 distinct cell clusters within the shoot system. Gene Ontology (GO) enrichment enabled the annotation of key cell types, including mesophyll, epidermal, bundle sheath, and xylem cells, as well as shoot apical and lateral bud meristems, and auxillary meristems. RNA velocity analysis highlighted the multipotent nature of mesophyll cells, with chlorenchyma in Cluster 3 identified as progenitor cells capable of differentiating into various tissues and Cluster 1 progressing towards aerenchyma formation. Comparative analysis between European and North American invasive populations revealed significant differences in transcriptional activity and gene expression, particularly in clusters associated with the shoot apical meristem. Invasive populations exhibited a higher prevalence of B chromosomes, with three genes IMPA-3, SSC3, and DDE family endonuclease gene consistently upregulated across nearly all clusters, notably near mesophyll and meristematic regions. The fast mutation in IMPA-3 which functions as a major receptor of Resistance (R) gene may have strengthened the adaptability of the invasive population in North America. These findings provide critical insights into the cellular development and genomic diversity underlying the invasiveness of the common reed, offering valuable information to guide ecological management strategies.
Structure of theThomasclavelia ramosaimmunoglobulin A protease reveals a modular and minimizable architecture distinct from other immunoglobulin A proteases
Authors: Tran Norman , Frenette Aaron , Holyoak Todd 
Published: January 2025

AbstractImmunoglobulin A proteases (IgAPs) are a diverse group of enzymes secreted from bacteria that inhabit human mucosal tissues. These enzymes have convergently evolved to cleave human immunoglobulin A as a means of modulating and evading host immunity. Only two of three known IgAP families have been biochemically characterized beyond their initial discovery. Here, we show using solution-scattering, steady-state kinetic, and crystallographic approaches that the protease fromThomasclavelia ramosa, representing the uncharacterized third family, has a truly modular and minimizable protein architecture. This analysis also revealed a unique metal-associated domain that likely functions as a molecular spacer and generated a working hypothesis detailing the structural mechanism behind the enzyme’s high substrate specificity. Our work provides the first in-depth biochemical account of this IgAP family, paving the way for advancing clinically relevant IgAP-related research and our understanding of IgAPs as a whole.
Circuit dynamics of approach-avoidance conflict in humans
Authors: Staveland Brooke R. , Oberschulte Julia , Kim-McManus Olivia , Willie Jon T. , Brunner Peter , Dastjerdi Mohammad , Lin Jack J. , Hsu Ming , Knight Robert T. 
Published: January 2025

AbstractDebilitating anxiety is pervasive in the modern world. Choices to approach or avoid are common in everyday life and excessive avoidance is a cardinal feature of all anxiety disorders. Here, we used intracranial EEG to define a distributed prefrontal-limbic circuit dynamics supporting approach and avoidance. Presurgical epilepsy patients (n=20) performed an approach-avoidance conflict decision-making task inspired by the arcade game Pac-Man, where participants trade-off real-time harvesting rewards with potential losses from attack. As patients approached increasing rewards and threats, we found evidence of a limbic circuit mediated by increased theta power in the hippocampus, amygdala, orbitofrontal cortex (OFC) and anterior cingulate cortex (ACC), which then drops rapidly during avoidance. Theta band connectivity between these regions increases during approach and falls during avoidance, with OFC serving as a connector in this circuit with high theta coherence across limbic regions, but also with regions outside of the limbic system, including the lateral prefrontal cortex. Importantly, the degree of OFC-driven connectivity predicts how long participants approach, with enhanced network synchronicity extending approach times. Finally, under ghost attack, the system dynamically switches to a sustained increase in high-frequency activity (70-150Hz) in the middle frontal gyrus (MFG), marking the retreat from the ghost. The results provide evidence for a distributed prefrontal-limbic circuit, mediated by theta oscillations, underlying approach-avoidance conflict.
Molecular basis for the activation ofPseudomonas aeruginosaMsbA by Zn2+
Authors: Lyu Jixing , Bahramimoghaddam Hanieh , Zhang Tianqi , Yadav Gaya P. , Zhao Minglei , Russell David , Laganowsky Arthur 
Published: January 2025

AbstractProteins involved in the biogenesis of lipopolysaccharide (LPS), a lipid exclusive to Gram-negative bacteria, are promising candidates for drug discovery. Specifically, the ABC transporter MsbA plays a crucial role in translocating an LPS precursor from the cytoplasmic to periplasmic facing leaflet of the inner membrane, and small molecules that inhibit its function exhibit bactericidal activity. Here, we use native mass spectrometry (MS) to determine lipid binding affinities of MsbA fromP. aeruginosa(PaMsbA), a Gram-negative bacteria associated with hospital-acquired infections, in different conformations. We show the ATPase activity of the transporter is stimulated by Zn2+and successfully trapping the protein with vanadate requires Zn2+not Mg2+, which is necessary to trap MsbA fromE. coli. We also present cryogenic-electron microscopy structures of PaMsbA in occluded and open outward-facing conformations determined to a resolution of 2.98 and 2.72 angstroms, respectively. The structures reveal a triad of histidine residues and mutation of these residues abolishes Zn2+stimulation of PaMsbA activity. Together our studies provide detailed insight into PaMsbA structure, lipid binding preferences, and uncover a mechanism through which Zn2+promotes the dimerization of the transporter, resulting in enhanced ATPase activity.
Spore morphology and evolution inIsoetes(Isoetales)
Authors: Larsén Eva , Khodabandeh Anbar , Rydin Catarina 
Published: January 2025

ABSTRACTIsoetes(Isoetaceae, Isoetales) is a cosmopolitan genus with an ancient and diverse evolutionary history that presumably peaked in the Paleozoic. The age of the living clade has never been satisfactorily clarified. With little morphological (and molecular) divergence among species, megaspore morphology may provide valuable information on relationships in the group, not least among extant and extinct forms. We study megaspore ornamentation and surface texture/structure in 74 phylogenetically placed samples representing 59 species ofIsoetesusing SEM, and we discuss evolutionary implications of the results. Ornamentation (classified into 12 categories) and surface structure/texture (10 categories) were mapped onto a phylogeny constructed based on molecular data from the same samples whenever possible. All megaspores of the family are trilete with an outermost siliceous coating. There is ample micromorphological variation, of which some appears clade specific. The megaspores ofIsoetes reticulata, discovered from the late Oligocene to early Miocene of Tasmania, share remarkable similarities with those of extant species in the Australasian clade, in particularIsoetes neoguineensisand partly alsoIsoetes japonica. We argue that this fossil could be used to calibrate the age of the Australasian crown group (clade D) to absolute time (c. 20-25 Ma) in analyses of divergence times of clades based on molecular data.
Ethanol induces craniofacial defects in Bmp mutants independent ofnkx2.3by elevating cranial neural crest cell apoptosis
Authors: Vo Hieu , Lovely C. Ben 
Published: January 2025

AbstractBackgroundFetal Alcohol Spectrum Disorders (FASD) describes a wide range of neurological defects and craniofacial malformations associated with prenatal ethanol exposure. While there is growing evidence for a genetic component to FASD, little is known of the cellular mechanisms underlying these ethanol-sensitive loci in facial development. Endoderm morphogenesis to form lateral protrusions called pouches is one key mechanism in facial development. We have previously shown that multiple members of the Bone Morphogenetic Pathway (Bmp) signaling pathway, a key regulator of pouch formation, interacts with ethanol disrupting facial development. However, ethanol does not directly impact Bmp signaling suggesting that downstream effectors, likenkx2.3may mediate the impact of ethanol on Bmp mutants.MethodsHere we use an ethanol exposure paradigm withnkx2.3knockdown approaches to test if loss ofnkx2.3sensitizes Bmp mutants to ethanol induced facial defects. We then combine a morphometric approach with Hybridization Chain Reaction and immunofluorescence to examine the cellular mechanisms underlying Bmp-ethanol interactions.ResultsWe show that Bmp-ethanol interactions alter morphology of the endodermal pouches, independent ofnkx2.3gene expression. Morpholino knock down ofnkx2.3does not sensitize wild type orbmp4mutant larvae to ethanol-induced facial defects. However, we did observe a significant increase CNCC apoptosis in ethanol-treated Bmp mutants.ConclusionsCollectively, our results suggest that ethanol’s mode of action is independent of downstream Bmp effectors, converging on CNCC cell survival. Ultimately, our work provides a mechanistic paradigm of ethanol-induced facial defects and connects ethanol exposure with concrete cellular events.
Assessment of awareness and attitudes of pregnant women toward labor epidural analgesia and factors influencing the decision to opt for it: A cross-sectional study
Authors: Kassa Adugna A. , Sahle Wossenyeleh A. , Desalew Tsehaynew , Lakew Zufan , Behabtu Tigist 
Published: January 2025

AbstractBackgroundEpidural analgesia is one of the most effective forms of pain relief during various stages of labor. Despite its many advantages, the technique is not routinely practiced in most centers in developing countries. Awareness and attitudes toward it, as well as the reasons for its limited utilization, have not been explored in our setting.Therefore, the aim of this study was to assess the awareness and attitudes of pregnant women toward labor epidurals and to assess the factors influencing their decision to receive labor epidural analgesia (LEA) during labor and delivery.MethodsA cross-sectional study was conducted from June to August 2024 at Hemen Medical Center. A structured questionnaire was used to collect the data. The collected data were analysed via SPSS version 26. Descriptive statistics were used to summarize the descriptive results, and logistic regression was employed to identify factors associated with the decision to receive labor epidural analgesia during delivery. A p value of < 0.05 was used to determine statistical significance.ResultsTwo hundred thirty pregnant women, with a mean age of 30 ± 4.3 years, were included in the analysis. Approximately 78% of the participants had heard of labor epidural analgesia (LEA), although only 6.5% reported healthcare providers as their primary source of information. Approximately 47% believed that LEA was effective for pain relief during labor. However, only 14.3% expressed a willingness to consider using LEA during delivery. Education level, family income, perceived risk to the Fetus, and perceived effectiveness in relieving pain were identified as factors influencing the decision to consider LEA during delivery.ConclusionDespite relatively high basic awareness of LEA, many participants remain hesitant to utilize it during labor and delivery. Comprehensive health education and counselling during antenatal care are essential to address misconceptions and promote informed decision-making regarding LEA.
AA147 Alleviates Symptoms in a Mouse Model of Multiple Sclerosis by Reducing Oligodendrocyte Loss
Authors: Aksu Metin , Kaschke Kevin , Podojil Joseph R. , Chiang MingYi , Steckler Ian , Bruce Kody , Cogswell Andrew C. , Schulz Gwen , Kelly Jeffery , Wiseman R. Luke , Miller Stephen , Popko Brian , Chen Yanan 
Published: January 2025

ABSTRACTInflammation induced oligodendrocyte death and CNS demyelination, are key features of multiple sclerosis (MS). Inflammation-triggered endoplasmic reticulum (ER) stress and oxidative stress promote tissue damage in MS and in its preclinical animal model, experimental autoimmune encephalitis (EAE). Compound AA147 is a potent activator of the ATF6 signaling arm of the unfolded protein response (UPR) that can also induce antioxidant signaling through activation of the NRF2 pathway in neuronal cells. Previous work showed that AA147 protects multiple tissues against ischemia/reperfusion damage through ATF6 and/or NRF2 activation; however, its therapeutic potential in neuroinflammatory disorders remains unexplored. Here, we demonstrate that AA147 ameliorated the clinical symptoms of EAE and reduced ER stress, oligodendrocyte loss, and demyelination. Additionally, AA147 suppressed T cells in the CNS without altering the peripheral immune response. Importantly, AA147 significantly increased the expressions ofGrp78, an ATF6 target gene, in oligodendrocytes, while enhancing levels ofGrp78as well asHo-1, an NRF2 target gene, in microglia. In cultured oligodendrocytes, AA147 promoted nuclear translocation of ATF6, but not NRF2. Intriguingly, AA147 altered the microglia activation profile, possibly by triggering the NRF2 pathway. AA147 was not therapeutically beneficial during the acute EAE stage in mice lacking ATF6 in oligodendrocytes, indicating that protection primarily involves ATF6 activation in these cells. Overall, our results suggest AA147 as a potential therapeutic opportunity for MS by promoting oligodendrocyte survival and regulating microglia status through distinct mechanisms.
Exacerbated salmonellosis in poly(ADP-ribose) polymerase 14 deficient mice
Authors: Vedantham Madhukar , Polari Lauri , Rissanen Tiia , Pulliainen Arto Tapio 
Published: January 2025

ABSTRACTSalmonella entericasubspeciesentericaserovar Typhimurium (S.Typhimurium) is an enteropathogen annually causing millions of acute infections ranging from gastroenteritis to life-threatening invasive systemic disease. Strong mucosal inflammation is characteristic for the infection driven by the innate immune receptor activation but also directly by the invading bacterium. It remains unknown how and at which point the mucosal inflammation turns anti-bacterial and how the tissue homeostasis is restored. Here, we investigated the expression and function of poly(ADP-ribose)polymerase (Parp14), a known cytoplasmic and nuclear regulatory protein of immune cells, in the mouse streptomycin-pretreatment model ofS.Typhimurium infection. In the infected mice, Parp14 expressing cells, some of which were macrophages, were detected throughout the gastrointestinal tract. However, the most strongly Parp14 expressing cells were the epithelial cells. Based on small intestine single cell RNA-Seq analysis of different epithelial cell types, the expression ofparp14was pronounced in the enterocytes and Tuft cells. Mice with a body-wide genetic deficiency of Parp14 suffered from exacerbatedS.Typhimurium colitis. The histopathological analysis of the large intestine revealed increased immune cell infiltration, Goblet cell loss, and epithelial erosion. At the same time lower numbers of viable bacteria were detected. Based on a bulk tissue RNA-Seq analysis, transcriptional signatures either missing or down-regulated in the infected Parp14 deficient mice were detected. These signatures were enriched with genes related to cell adhesion, cell division and cytoskeletal rearrangements, and genes related to infection and immune responses. It appears that Parp14 has potential functions in the regulation of tissue architecture and mucosal inflammation in the large intestine ofS.Typhimurium infected mice.
Investigating sodium homeostasis of structural brain hubs in focal epilepsy using 7T MRI
Authors: Gauer Lucas , Haast Roy AM , Azilinon Mikhael , El Mendili Mohamed Mounir , Scholly Julia , Dary Hugo , Dinkelacker Vera , Ranjeva Jean-Philippe , Zaaraoui Wafaa , Bartolomei Fabrice , Guye Maxime 
Published: January 2025

AbstractBesides their crucial role in cerebral connectivity, brain hubs are regions vulnerable to the energy deficit associated with various brain disorders. Changes in sodium homeostasis of cortical regions have been observed in focal epilepsy and may reflect energy failure. We investigated whether nodal structural connectivity is differently affected within the hub and non-hub regions by ionic perturbations associated with focal epilepsy. Our hypothesis was that the metabolic demands of hub regions may be associated with a distinct ionic profile detectable by sodium MRI and that this profile is altered in focal epilepsy.We recruited 23 patients with drug-resistant focal epilepsy and 21 age- and gender-matched healthy controls. Anatomical, diffusion-weighted, and sodium imaging was performed using a 7 Tesla MRI scanner. Patients underwent pre-surgical work-up, including stereo-electroencephalographic recordings for defining the epileptogenic regions. Anatomical parcellation and multimodal coregistration allowed the use of parcels as nodes of whole-brain structural connectomes, linking structural connectivity measures to epileptogenicity and sodium parameters. Sodium parameters in patients were z-scored concerning homologous parcels in controls to allow comparison across regions of interest.Hub regions had higher total sodium concentration (TSC) than non-hub regions in both patients and controls, and this difference was not observed for sodium signal fraction (f, a proxy of intracellular sodium homeostasis). Compared to controls, patients showed increased TSC in both epileptogenic and non-epileptogenic zones, and this increase in TSC was consistent in both hub and non-hub regions. On the opposite,fwas increased only within the epileptogenic zones and was not affected by the hubness of a region.Our results confirm the whole brain increase in TSC and the local increase of thefvalue within epileptogenic zones previously observed in focal epilepsy patients. Therefore, we propose that that sodium imaging can probe distinct tissue properties: TSC appears sensitive to microstructural alterations, whilefcould reflect homeostatic disruptions specific to epileptogenic regions.
Forecasting invasive mosquito abundance in the Basque Country, Spain using machine learning techniques
Authors: Steindorf Vanessa , Hamna Mariyam K. B. , Stollenwerk Nico , Cevidanes Aitor , Barandika Jesús F. , Vazquez Patricia , García-Pérez Ana L. , Aguiar Maíra 
Published: January 2025

AbstractMosquito-borne diseases cause millions of deaths each year and are increasingly spreading from tropical and subtropical regions into temperate zones, creating significant public health risks. The establishment of mosquito species in new areas increases the risk of local transmission (autochthonous cases), driven by both rising mosquito populations and viremic imported cases, infected travelers who can spark local transmission. Such developments present new challenges for public health systems in non-endemic regions.In Spain, in the Basque Country region, the spread of mosquitoes, driven by changing climatic conditions, has enhanced mosquito adaptation alongside an increase in imported cases of dengue, Zika, and chikungunya. By employing a model that captures the complexities of the mosquito life cycle driven by the interaction with weather variables, including temperature, precipitation, and humidity, and leveraging machine learning techniques, this study aims to predictAedesinvasive mosquito abundance in provinces of the Basque Country, using egg count as a proxy and the weather features as key independent variables.Statistical analyses explored the impact of temperature, precipitation, and humidity on mosquito egg abundance. Using lagged climate variables and ovitrap egg counts, models were evaluated using Root Mean Squared Error (RMSE) and Mean Absolute Error (MAE) metrics. The Random Forest (RF) model demonstrated the highest accuracy, followed by the Seasonal Autoregressive Integrated Moving Average (SARIMAX) model. Lastly, the best models were implemented to forecastAedesinvasive mosquito abundance in the Basque Country provinces. This forecasting tool aids vector control strategies in regions with expanding mosquito populations, highlighting the need for ongoing entomological surveillance to improve mosquito spread assessments.