bluuebunny/crossref_metadata_2025_split huggingface dataset:
Frankia umida sp. nov., isolated from root nodules of Alnus glutinosa L.
Authors: Normand Philippe , Nouioui Imen , Neumann-Schaal Meina , Herrera-Belaroussi Aude , Abrouk Danis , Vemulapally Spandana , Guerra Trina , Hahn Dittmar 
Published: June 2023

Frankia

strain Ag45/Mut15T was isolated from a root nodule of Alnus glutinosa growing in a swamp at lake Grossensee, Germany. The strain forms root nodules on A. glutinosa, in which it produces hyphae and clusters of N2-fixing vesicles. N2-fixing vesicles are also produced in nitrogen-free growth medium, in addition to hyphae and sporangia. The whole-cell hydrolysates of strain Ag45/Mut15T contained meso-diaminopimelic acid in the peptidoglycan and ribose, xylose, mannose, glucose, galactose and a trace of rhamnose as cell-wall sugars. The major polar lipids were phosphatidylglycerol, phosphatidylinositol, diphosphatidylglycerol and glyco-phospholipid. The predominant (>20 %) menaquinones were MK-9(H6) and MK-9(H4). The major fatty acid profile (>10 %) consisted of iso-C16:0, C17 : 1 ω8c and C17 : 0. Pairwise 16S rRNA gene distances showed that strain Ag45/Mut15T was most closely related to

Frankia torreyi

CpI1T and Candidatus Frankia nodulisporulans with 16S rRNA gene similarity values of 0.001335 substitutions per site. An multilocus sequence analysis phylogeny based on atpD, dnaA, ftsZ, pgk and rpoB amino acid sequences positioned the strain within cluster 1 of Alnus- and Myrica-nodulating species, close to Candidatus F. nodulisporulans AgTrST and

F. canadensis

ARgP5T. The digital DNA–DNA hybridization (dDDH) and average nucleotide identity (ANI) values between the studied strain Ag45/Mut15T and all validly named

Frankia

species were below the defined threshold for prokaryotic species demarcation. Candidatus F. nodulisporulans AgTrST, which cannot be cultivated in vitro, was found to be the closest phylogenetic neighbour to strain strain Ag45/Mut15T with dDDH and ANI values of 61.8 and 97 %, respectively. Strain Ag45/Mut15T was not able to sporulate in nodule tissues like strain AgTrST.
Phenotypic, physiological and phylogenomic analyses confirmed the assignment of strain Ag45/Mut15T (=DSM 114737T=LMG 326O1T) to a novel species, with Ag45/Mut15T as type strain, for which the name Frankia umida sp. nov. is proposed.
Gradient boosted decision trees reveal nuances of auditory discrimination behavior
Authors: Griffiths Carla , Lebert Jules , Sollini Joseph , Bizley Jennifer 
Published: June 2023

ABSTRACTAnimal psychophysics can generate rich behavioral datasets, often comprised of many 1000s of trials for an individual subject. Gradient-boosted models are a promising machine learning approach for analyzing such data, partly due to the tools that allow users to gain insight into how the model makes predictions. We trained ferrets to report a target word’s presence, timing, and lateralization within a stream of consecutively presented non-target words. To assess the animals’ ability to generalize across pitch, we manipulated the fundamental frequency (F0) of the speech stimuli across trials, and to assess the contribution of pitch to streaming, we roved the F0 from word token-to-token. We then implemented gradient-boosted regression and decision trees on the trial outcome and reaction time data to understand the behavioral factors behind the ferrets’ decision-making. We visualized model contributions by implementing SHAPs feature importance and partial dependency plots. While ferrets could accurately perform the task across all pitch-shifted conditions, our models reveal subtle effects of shifting F0 on performance, with within-trial pitch shifting elevating false alarms and extending reaction times. Our models identified a subset of non-target words that animals commonly false alarmed to. Follow-up analysis demonstrated that the spectrotemporal similarity of target and non-target words rather than similarity in duration or amplitude waveform was the strongest predictor of the likelihood of false alarming. Finally, we compared the results with those obtained with traditional mixed effects models, revealing equivalent or better performance for the gradient-boosted models over these approaches.AUTHOR SUMMARYThe sorts of listening challenges faced by real-world listeners are rarely captured by most laboratory-based auditory paradigms, particularly those testing animal models. However, many labs are attempting to utilize more realistic experiments, and more complicated behavioral paradigms require more sophisticated approaches to analyzing the resulting data. Here, we used a new behavioral paradigm to test the ability of ferret listeners to identify target speech sounds and assess their ability to generalize across changes in pitch. To make sense of the resulting dataset, we used machine learning algorithms to understand how trained ferrets perform this task. Gradient-boosted regression and decision trees are well-established machine learning methods that do not require users to predetermine interaction effects and are accompanied by visualization methods that allow insights to be gained into how multiple factors ultimately shape behavior. We compare the use of gradient-boosted models to more standard regression approaches and, by applying these methods, we demonstrate key features of ferrets’ performance on this task. Our results suggest that this machine learning approach is ideal for analyzing behavioral data in animal models.
EquiScore: A generic protein-ligand interaction scoring method integrating physical prior knowledge with data augmentation modeling
Authors: Cao Duanhua , Chen Geng , Jiang Jiaxin , Yu Jie , Zhang Runze , Chen Mingan , Zhang Wei , Chen Lifan , Zhong Feisheng , Zhang Yingying , Lu Chenghao , Li Xutong , Luo Xiaomin , Zhang Sulin , Zheng Mingyue 
Published: June 2023

ABSTRACTDeveloping robust methods for evaluating protein-ligand interactions has been a long-standing problem. Here, we propose a novel approach called EquiScore, which utilizes an equivariant heterogeneous graph neural network to integrate physical prior knowledge and characterize protein-ligand interactions in equivariant geometric space. To improve generalization performance, we constructed a dataset called PDBscreen and designed multiple data augmentation strategies suitable for training scoring methods. We also analyzed potential risks of data leakage in commonly used data-driven modeling processes and proposed a more stringent redundancy removal scheme to alleviate this problem. On two large external test sets, EquiScore outperformed 21 methods across a range of screening performance metrics, and this performance was insensitive to binding pose generation methods. EquiScore also showed good performance on the activity ranking task of a series of structural analogs, indicating its potential to guide lead compound optimization. Finally, we investigated different levels of interpretability of EquiScore, which may provide more insights into structure-based drug design.
Place field precision during an episode predicts place field fate across episodes
Authors: Chiu YuHung , Dong Can , Krishnan Seetha , Sheffield Mark E.J. 
Published: June 2023

AbstractSpatial memories are represented by hippocampal place cells during navigation. This spatial code is dynamic, undergoing changes across time – known as drift – and across changes in internal state, even while navigating the same spatial environment with consistent behavior. A dynamic spatial code may be a way for the hippocampus to track distinct episodes that occur at different times or during different internal states and update spatial memories. Changes to the spatial code include place fields that remap to new locations and place fields that vanish, while others are stable. However, what determines place field fate across episodes remains unclear. We measured the lap-by-lap properties of place cells in mice during navigation for a block of trials in a rewarded virtual environment. We then had mice navigate the same spatial environment for another block of trials either separated by a day (a distinct temporal episode) or during the same session but with reward removed to change reward expectation (a distinct internal state episode). We found that, as a population, place cells with remapped place fields across episodes had lower spatial precision during navigation in the initial episode. Place cells with stable or vanished place fields generally had higher spatial precision. We conclude that place cells with less precise place fields have greater spatial flexibility, allowing them to respond to, and track, distinct episodes in the same spatial environment, while place cells with precise place fields generally preserve spatial information when their fields reappear.
The molecular prognostic score, a classifier for risk stratification of high-grade serous ovarian cancer
Authors: Sarkar Siddik , Saha Sarbar Ali , Sarkar Poulomi , Banerjee Sarthak , Mitra Pralay 
Published: June 2023

AbstractThe clinicopathological parameters such as residual tumor, grade, FIGO score are often used to predict the survival of ovarian cancer patients, but the 5-year survival of high grade serous ovarian cancer (HGSOC) still remains around 30%. In recent years, a gene expression based molecular prognostic score (mPS) was developed that showed improved prognosis in several cancers including ovarian cancer.The feature extraction using LASSO-Cox regression was applied on the training data with 10-fold cross validation to obtain 20 predictor genes along with the coefficients to derive mPS. The mPS based prognosis of HGSOC patients was validated using the log-rank test and receiver operator characteristic curve.The AUC of 20 gene-based mPS in predicting the 5-year overall survival was around 0.7 in both the training (n=491) and test datasets (n=491). It was also validated across HGSOC patients (n=7542), data collected from the Ovarian Tumor Tissue Analysis (OTTA) consortium. The mPS showed significant impact (adjusted HR = 6.1, 95% CI of HR= 3.65-10.3; p <0.001) on prognosis of HGSOC. The performance of mPS for the prognosis of survival of HGSOC was substantially better than conventional parameters: FIGO (adjusted HR=1.1, 95% CI=0.97-1.2, p=0.121), residual disease (adjusted HR=1.3, 95% CI= 1.13-1.4, p<0.001), and age (adjusted HR=1.2, 95% CI= 0.98-1.6, p=0.08). It was found that focal-adhesion, Wnt and Notch signaling pathways were significantly (p<0.001) upregulated, whereas antigen processing and presentation (p<0.001) was downregulated in high risk HGSOC cohorts based on mPS stratification.The molecular prognostic score derived from 20-gene signature is found to be the novel robust prognostic marker of HGSOC. It could potentially be harnessed in clinical settings to determine the overall survival of ovarian cancer. The high risk HGSOC patients based on mPS stratification could be benefited from alternative therapies targeting Wnt/ Notch signaling pathways and also immune evasion.Author summaryThe 20-gene signature based molecular prognostic score (mPS) was found to be associated with risk stratification and hence, predicting the overall survival time of HGSOCs. It was applicable in all training HGSOC datasets and across RNA sequencing platforms that also includes the previous reported studies in HGSOC cohorts (Millstein et al., 2020; Talhouk et al., 2020). The 20-gene signature based mPS for the prognosis of overall survival of HGSOC outperformed conventional parameters: age, residual disease and FIGO score. The high or increased risk group of HGSOC based on our mPS stratification was found to have dysregulated pathways of Wnt, Notch, Akt signaling, and antigen presentation. Thus, treatments targeting these pathways might be beneficial for high risk HGSOC and hence anticipated to improve the over-all survival of HGSOC.
Comparative population genomics of manta rays has global implications for management
Authors: Humble Emily , Hosegood Jane , Carvalho Gary , de Bruyn Mark , Creer Simon , Stevens Guy M W , Armstrong Amelia , Bonfil Ramon , Deakos Mark , Fernando Daniel , Froman Niv , Peel Lauren R , Pollett Stephen , Ponzo Alessandro , Poquita Allan L , Stewart Joshua D , Wintner Sabine , Ogden Rob 
Published: June 2023

AbstractUnderstanding population connectivity and genetic diversity is of fundamental importance to conservation. However, in globally threatened marine megafauna, challenges remain due to their elusive nature and wide-ranging distributions. As overexploitation continues to threaten biodiversity across the globe, such knowledge gaps compromise both the suitability and effectiveness of management actions. Here, we use a comparative framework to investigate genetic differentiation and diversity of manta rays, one of the most iconic yet vulnerable groups of elasmobranchs on the planet. Despite their recent divergence, we show how oceanic manta rays (Mobula birostris) display significantly higher heterozygosity than reef manta rays (Mobula alfredi) and thatM. birostrispopulations display higher connectivity worldwide. Through inferring modes of colonisation, we reveal how both contemporary and historical forces have likely influenced these patterns, with important implications for population management. Our findings highlight the potential for fisheries to disrupt population dynamics at both local and global scales and therefore have direct relevance for international conservation of marine species.
PI3K/AKT signalling orchestrates ICM maturation and proper epiblast and primitive endoderm specification
Authors: Geiselmann Anna , Micouin Adèle , Vandormael-Pournin Sandrine , Laville Vincent , Mella Sébastien , Navarro Pablo , Cohen-Tannoudji Michel 
Published: June 2023

AbstractThe inner cell mass (ICM) of early mouse embryos is specified into Epiblast (Epi) and primitive endoderm (PrE) lineages during blastocyst formation. The antagonistic transcription factors (TFs) NANOG and GATA6 in combination with FGF/ERK signalling are central actors in ICM fate choice. However, what initiates the specification of ICM progenitors and whether other factors are involved in this process is not fully understood yet. Here, we show that PI3K/AKT is constitutively active during preimplantation development. Using pharmacological inhibition, we demonstrate that PI3K/AKT enables the formation of a functional ICM capable of giving rise to both the EPI and the PrE: it maintains the expression of the TF NANOG, which specifies the EPI, and confers responsiveness to FGF4, which is essential for PrE specification. Our observations thus identify PI3K/AKT signalling as an upstream regulator orchestrating the molecular events required for both EPI and PrE specification.
Murine Gammaherpesvirus 68 Efficiently Infects Myeloid Cells Resulting In An Atypical, Restricted Form Of Infection
Authors: Vragel Gabrielle , Gomez Brittany D. , Kostelecky Rachael E. , Noell Kyra S. , Tseng Ashley , Cohen Shirli , Dalwadi Manaal , Medina Eva M. , Nail Elizabeth A. , Goodspeed Andrew , Clambey Eric T. , van Dyk Linda F. 
Published: June 2023

AbstractThe gammaherpesviruses (γHVs) establish a lifelong infection in their hosts, with the cellular outcome of infection intimately regulated by target cell type. Murine gammaherpesvirus 68 (MHV68), a small animal model of γHV infection, infects macrophages in vivo, resulting in a range of outcomes, from lytic replication to latent infection. Here, we have further investigated the nature of MHV68 macrophage infection using reductionist and primary in vivo infection studies. While MHV68 readily infected the J774 macrophage cell line, viral gene expression and replication were significantly impaired relative to a fully permissive fibroblast cell line. Lytic replication only occurred in a small subset of MHV68-infected J774 cells, despite the fact that these cells were fully competent to support lytic replication following pre-treatment with interleukin-4, a known potentiator of replication in macrophages. In parallel, we harvested virally-infected macrophages at 16 hours after MHV68 infectionin vivoand analyzed gene expression by single cell RNA-sequencing. Among virally infected macrophages, only rare (0.25%) cells had lytic cycle gene expression, characterized by detection of multiple lytic cycle RNAs. In contrast, ∼50% of virally-infected macrophages were characterized by expression of ORF75A, ORF75B and/or ORF75C, in the absence of other detectable viral RNAs. Selective transcription of the ORF75 locus also occurred in MHV68-infected J774 cells. In total, these studies indicate that MHV68 efficiently infects macrophages, with the majority of cells characterized by an atypical state of restricted viral transcription, and only rare cells undergoing lytic replication.ImportanceThe human gammaherpesviruses Epstein-Barr virus and Kaposi’s sarcoma associated herpesvirus are DNA viruses that cause lifelong infection and are associated with multiple diseases, especially in immunocompromised individuals. Murine gammaherpesvirus 68 (MHV68) is a powerful mouse model that permits close examination of these viruses. Previous studies of MHV68 identified that macrophages are an important in vivo target of infection; how infection within these cells is regulated remains incompletely understood. Here, we demonstrate that MHV68 infection of macrophages is characterized by two divergent outcomes across a population of infected cells: while a small subset of cells undergo lytic replication, to make new virus progeny, the majority of cells are characterized by an atypical, restricted form of infection characterized by a distinct viral gene transcription program not previously reported. These studies highlight important cell-type specific outcomes of gammaherpesvirus infection and identify a potential alternate program by which these viruses usurp macrophages.
Increased error rate and delayed response to negative emotional stimuli in antisaccade task in obsessive-compulsive disorder
Authors: Khayrullina Guzal , Martynova Olga , Panfilova Elizaveta 
Published: June 2023

AbstractAmple evidence links impaired inhibitory control, attentional distortions, emotional dysregulation, and obsessive-compulsive disorder (OCD). However, it remains unclear what underlies the deficit that triggers the OCD cycle. The present study used an antisaccade paradigm with emotional stimuli to compare eye movement patterns reflecting inhibitory control and attention switching in OCD and healthy control groups. Thirty-two patients with OCD and thirty healthy controls performed the antisaccade task with neutral, positive, and negative visual images. The groups differed significantly in the number of errors to negative stimuli. The latency of correct antisaccades varied between valences in OCD group when negative and neutral stimuli served as target ones. The OCD group showed more errors to negative stimuli than the control group and they also performed antisaccades more slowly to negative and neutral stimuli than positive ones. Other patterns, including mean velocity of correct antisaccades and anticipatory saccades, did not differ between groups. The mean velocity of correct antisaccades was higher for negative and positive stimuli than for neutral stimuli; however, there were more anticipatory saccades for neutral stimuli than for negative and positive stimuli in both groups. The peak velocity parameter did not show any differences either between groups or between valences. The findings support a hypothesis that an attentional bias towards threatening stimuli interferes with inhibitory control in OCD.
A transient protein folding response targets aggregation in the early phase of TDP-43-mediated disease
Authors: Gil Rebecca San , Pascovici Dana , Venturato Juliana , Brown-Wright Heledd , Mehta Prachi , Madrid San Martin Lidia , Wu Jemma , Chui Yi Kit , Bademosi Adekunle T. , Swaminathan Shilpa , Luan Wei , Berning Britt A. , Wright Amanda L. , Keating Sean S. , Lee Albert , Morsch Marco , Chung Roger S. , Lisowski Leszek , Mirzaei Mehdi , Walker Adam K. 
Published: June 2023

AbstractUnderstanding the mechanisms that drive TDP-43 pathology is integral to combating neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). To address this, we sought to determine the timeline of proteomic alterations across disease course in TDP-43 proteinopathy. Using longitudinal quantitative proteomics analysis of cortex samples from the cytoplasmic TDP-43 rNLS8 mouse model of ALS and FTLD, we identified several distinct protein subsets characterized by temporal alterations in protein abundance across diverse biological pathways, including protein folding, intracellular transport, myelination, and neuronal synaptic function. Remarkably, neurons in the rNLS8 cortex elicited a transitory response primarily comprising protein-folding factors prior to and in the earliest stages of disease progression. This response included increased levels of DnaJ homolog subfamily B member 5, DNAJB5, and proof-of-concept studies showed that DNAJB5 over-expression decreased TDP-43 aggregation in cell and cortical neuron cultures. Conversely, knockout ofDnajb5exacerbated motor impairments caused by AAV-mediated cytoplasmic TDP-43 expression in the brains and spinal cords of mice. Lastly, the late disease proteomic signatures of rNLS8 mouse cortex strongly correlated with changes in human autopsy-derived TDP-43 proteinopathy tissues, indicating commonality of disease processes. Together, these findings reveal molecular mechanisms that regulate protein levels through distinct stages of ALS and FTLD progression, and suggest that protein folding factors that combat cytoplasmic TDP-43 protein aggregation could be protective in disease.HighlightsThe first longitudinal map of the cortex proteome throughout TDP-43-driven disease in a mouse model of cytoplasmic TDP-43 proteinopathy (rNLS8 mice).Cytoplasmic TDP-43 accumulation drives many dynamic changes to the cortex proteome, including increases in protein folding factors prior to disease onset.The protein folding factor DNAJB5 decreases TDP-43 aggregation in HEK293 cells and primary cortical neurons andDnajb5knockout exacerbates cytoplasmic TDP-43-associated motor impairmentsin vivo.The proteomic signature of the rNLS8 mouse cortex correlates strongly with postmortem brain tissue from human TDP-43 proteinopathies.A new webtool, ‘TDP-map’ (https://shiny.rcc.uq.edu.au/TDP-map/), allows comparison of transcriptomic and proteomic datasets from mouse and human TDP-43 proteinopathy.
Reduced Reverse Replay in Anxious Individuals Impairs Reward Prediction
Authors: Yu Qianqian , Luo Yuejia , Dolan Ray , Ou Jianxin , Huang Chuwen , Wang Haiteng , Xiao Zhibing , Liu Yunzhe 
Published: June 2023

AbstractAnxiety traits can manifest as a tendency to overlook positive information, impacting memory and decision-making. Using EEG-based neural decoding, we examined future reward prediction in participants with varying levels of trait anxiety. In a resting period, following value learning, we found an increase in reverse replay for a task sequence that led to reward. This reward-related replay was significantly reduced within individuals exhibiting higher trait anxiety. Furthermore, this reduction correlated with a distorted neural representation of the reward-predictive sequence, an effect mirrored behaviorally in an attenuated preference for stimuli within the same sequence. These findings indicate that higher trait anxiety may impede formation of reward-predictive representations by reducing offline replay during rest. More broadly, our demonstration of sequential replay using EEG enables examination of offline learning and memory consolidation in wider populations, particularly those with psychopathology.