bluuebunny/crossref_metadata_2025_split huggingface dataset:
SeqTagger, a rapid and accurate tool to demultiplex direct RNA nanopore sequencing datasets
Authors: Pryszcz Leszek P , Diensthuber Gregor , Llovera Laia , Medina Rebeca , Delgado-Tejedor Anna , Cozzuto Luca , Ponomarenko Julia , Novoa Eva Maria 
Published: October 2024

ABSTRACTNanopore direct RNA sequencing (DRS) enables direct measurement of RNA molecules, including their native RNA modifications, without prior conversion to cDNA. However, commercial methods for molecular barcoding of multiple DRS samples are lacking, and community-driven efforts, such as DeePlexiCon, are not compatible with newer RNA chemistry flowcells and the latest-generation GPU cards. To overcome these limitations, we introduce SeqTagger, a rapid and robust method that can demultiplex direct RNA sequencing datasets with 99% precision and 95% recall. We demonstrate the applicability of SeqTagger in both RNA002/R9.4 and RNA004/RNA chemistries and show its robust performance both for long and short RNA libraries, including custom libraries that do not contain standard poly-(A) tails, such as Nano-tRNAseq libraries. Finally, we demonstrate that increasing the multiplexing up to 96 barcodes yields highly accurate demultiplexing models. SeqTagger can be executed in a standalone manner or through the MasterOfPores NextFlow workflow. The availability of an efficient and simple multiplexing strategy improves the cost-effectiveness of this technology and facilitates the analysis of low-input biological samples.
Viewing geometry drives flexible perception of object motion and depth
Authors: Xu Zhe-Xin , Pang Jiayi , Anzai Akiyuki , DeAngelis Gregory C. 
Published: October 2024

1AbstractVision is an active process. We move our eyes and head to acquire useful information and to track objects of interest. While these movements are essential for many behaviors, they greatly complicate the analysis of retinal image motion; the image motion of an object reflects both how that object moves in the world and how the eye moves relative to the scene. Our brain must account for the visual consequences of self-motion to accurately perceive the 3D layout and motion of objects in the scene. Traditionally, compensation for eye movements (e.g., smooth pursuit) has been modeled as a simple vector subtraction process. While these models are effective for pure eye rotations and 2D scenes, we show that they fail to apply to more natural viewing geometries involving combinations of eye rotation and translation to view 3D scenes. We analyze develop theoretical predictions for how perception of object motion and depth should depend on the observer’s inferred viewing geometry. Through psychophysical experiments, we demonstrate novel perceptual biases that manifest when different viewing geometries are simulated by optic flow. Remarkably, these biases occur automatically, without training or feedback, and reflect appropriate context-specific computations. A neural network model trained to perform the same tasks exhibits neural response patterns similar to those observed in macaque area MT, suggesting a possible neural basis for these adaptive computations. Our findings demonstrate that the visual system automatically infers viewing geometry from optic flow and performs appropriate computations to estimate object motion and depth.
Secondary motor cortex tracks decision value and supports behavioral flexibility during non-instructed choice
Authors: Augusto Elisabete , Kouskoff Vladimir , Chenouard Nicolas , Giraudet Margaux , Peltier Léa , de Miranda Aron , Louis Alexy , Alonso Lucille , Gambino Frédéric 
Published: October 2024

ABSTRACTOptimal decision-making relies on interconnected frontal brain regions, which permit animals to adapt their decisions based on their internal state, experience, and environmental context. Among them, the secondary motor cortex (M2) shows earlier decision-related activity required for sensory-guided action selection. However, the role of M2 in adaptive decision-making in the absence of instructive sensory cues remains unclear. Under such conditions, action-selection relies on abstract representations of actions and their values. Usingin vivomicroscopy and modeling, we showed that M2 neurons in mice exhibited persistent activity encoding decision values (DV) predicting the probability of action-selection during a non-cue-guided lever task. This was confirmed by the reduced reversal performance upon M2 optogenetic inhibition prior to action-selection. Furthermore, updates in DV determined the rate at which learning is reversed. Together, these results provide strong evidence of the use of DV by M2 to adapt choice in the absence of instructive sensory cues.Declaration of interestsThe authors declare no competing financial interests.
Medial septum parvalbumin-expressing inhibitory neurons are impaired in a mouse model of Dravet Syndrome
Authors: Zhu Limei , Demetriou Yiannos , Barden Joseph , Disla Juan , Mattis Joanna 
Published: October 2024

SummaryDravet syndrome (DS) is a severe neurodevelopmental disorder caused by pathogenic variants in theSCN1Agene, which encodes the voltage-gated sodium channel Nav1.1 α subunit. Experiments in animal models of DS – including the haploinsufficientScn1a+/-mouse – have identified impaired excitability of interneurons in the hippocampus and neocortex; this is thought to underlie the treatment-resistant epilepsy that is a prominent feature of the DS phenotype. However, additional brain structures, such as the medial septum (MS), also expressSCN1A. The medial septum is known to play an important role in cognitive function and thus may contribute to the intellectual impairment that also characterizes DS. In this study, we employed whole cell patch clamp recordings in acute brain slices to characterize the electrophysiological properties of MS neurons inScn1a+/-mice versus age-matched wild-type littermate controls. We found no discernible genotype-related differences in MS cholinergic (ChAT) neurons, but significant dysfunction within MS parvalbumin-expressing (PV) inhibitory neurons inScn1a+/-mice. We further identified heterogeneity of firing patterns among MS PV neurons, and additional genotype differences in the proportion of subtype representation. These results confirm that the MS is an additional locus of pathology in DS, that may contribute to co- morbidities such as cognitive impairment.
A Protocol for Neuralized Murine Olfactory Organoids
Authors: Ozgun Alp , Suman Priya , Coulombe Josée ,   aSCENT-PD Investigators, Brown Earl G. , Tomlinson Julianna J. , Woulfe John M. , Schlossmacher Michael G. 
Published: October 2024

AbstractChronic olfactory dysfunction can be associated with parkinsonism, dementia, demyelinating disorders and schizophrenia. The olfactory epithelium (OE) represents an interface between the environment and the central nervous system. Mounting evidence implicates environmental factors in neurodegenerative disease processes, necessitating investigations into their interactions with the host’s genome. In Parkinson disease, hyposmia often precedes motor symptoms, raising the possibility that the OE could be involved in disease initiation. We previously demonstrated abundant α-synuclein expression in mammalian OE as well as aggregate formation in the olfactory nerve. Currentin vitromodels of OE are limited, relying primarily on post-mitotic cultures established from biopsies. To address this gap, we present a method for generating olfactory organoids of OE from adult mice. These organoids comprise neuronal and non-neuronal cell types, including sustentacular cells, thus encompassing structural elements of OEin situ. Expression of the olfactory sensory neuron marker OMP and Parkinson’s-linked α-synuclein was also detected in olfactory organoids, highlighting their potential usefulness to mechanistic research. We established OE organoids that were kept in culture for up to 3 weeks. In addition, we inoculated organoids with the neurotropic vesicular stomatitis virus to model infections. We conclude that this olfactory organoid model system offers a new platform for studying airborne environmental factors in their interactions with a genetically defined host; this, to study OE biology and enable the exploration of disease processes within olfactory tissue.
Dickeya ananaesp. nov., pectinolytic bacterium isolated from pineapple (Ananas comosus)
Authors: Dobhal Shefali , Hugouvieux-Cotte-Pattat Nicole , Arizala Dario , Sari Gamze Boluk , Chuang Shu-Cheng , Alvarez Anne M. , Arif Mohammad 
Published: October 2024

ABSTRACTRecently, species clustering withinDickeya zeaehas been identified as complex, encompassing validly published names, includingD. oryzaeandD. parazeae, with some strains potentially delineating new species. In this study, genomes of strains isolated from a bacterial heart rot outbreak in pineapple (Ananas comosusvar.comosus) on Oahu, Hawaii, along with two strains from pineapple in Malaysia, were sequenced. Orthologous average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values among the sequenced genomes ranged from 98.93-99.9% and 91.8-99.9%, respectively, supporting the classification of seven strains within the same species. Comparisons of ANI and dDDH values between these seven strains and type strains ofD. zeae, D. parazeae,andD. oryzaeranged from 94.4-95.9% and 57.2-66.5%, respectively. These values fall below the proposed boundaries for new species designation, supporting the delineation of a novel species. Phylogenetic analyses, including 16S rRNA,gapA, multi-locus sequence analysis (MLSA) of 10 housekeeping genes, whole-genome, and pangenome analyses, were concordant and revealed a distinct monophyletic clade, separating these strains from other members of theD. zeaecomplex, withD. oryzaeas the closest relative. Notably, a nitrogen fixation gene cluster comprising 28 genes, similar to theKlebsiellaspp. nitrogenase gene cluster, was found in the genome of the seven pineapple strains. Based on polyphasic approaches, including ANI, dDDH, biochemical, physiological, and phylogenomic analyses, we propose the reclassification in a new species of the five pineapple strains from Hawaii A5391, A5410T, A5611, A6136, and A6137, together with the two pineapple strains from Malaysia CFBP 1272 and CFBP 1278, previously classified asD. zeae. We propose the nameDickeya ananaesp. nov. for this taxon, represented by the type strain A5410T(= ICMP 25020T= LMG 33197T).
Impaired maturation of wild-type superoxide dismutase 1 associated with neurodegeneration in Parkinson disease brain and a novel murine model
Authors: Abdeen Amr H. , Trist Benjamin G. , Nikseresht Sara , Harwood Richard , Roudeau Stéphane , Rowlands Benjamin D. , Kreilaus Fabian , Cottam Veronica , Mor David , Richardson Miriam , Siciliano Joel , Forkgen Julia , Schaffer Greta , Genoud Sian , Li Anne A. , Proschogo Nicholas , Antonio Bernadeth , Falkenberg Gerald , Brueckner Dennis , Kysenius Kai , Liddell Jeffrey R. , Fat Sandrine Chan Moi , Wu Sharlynn , Fifita Jennifer , Lockwood Thomas E. , Bishop David P. , Blair Ian , Ortega Richard , Crouch Peter J. , Double Kay L. 
Published: October 2024

AbstractAtypical wild-type superoxide dismutase 1 (SOD1) protein misfolding and deposition occurs specifically within the degenerating substantia nigra pars compacta (SNc) in Parkinson disease. Mechanisms driving the formation of this pathology and relationship with SNc dopamine neuron health, are yet to be fully understood. We applied proteomic mass spectrometry and synchrotron-based biometal quantification to post-mortem brain tissues from the SNc of Parkinson disease patients and age-matched controls to uncover key factors underlying the formation of wild-type SOD1 pathology in this disorder. We then engineered brain copper deficiency and upregulated SOD1 protein levels in a novel mouse strain, termed the SOCK mouse, to verify their involvement in the development of Parkinson-like wild-type SOD1 pathology and their impact on dopamine neuron health. Soluble SOD1 protein in the degenerating Parkinson disease SNc exhibited altered post-translational modifications, which may underlie changes to the enzymatic activity and aggregation of the protein in this region. These include decreased copper binding, dysregulation of physiological glycosylation, and atypical oxidation and glycation of key SOD1 amino acid residues. We demonstrated that the biochemical profile introduced in SOCK mice promotes the same post-translational modifications and the development of Parkinson-like wild-type SOD1 pathology in the midbrain and cortex. This pathology accumulates progressively with age and is accompanied by nigrostriatal degeneration and dysfunction, which occur in the absence of α-synuclein deposition. These mice do not exhibit weight loss nor spinal cord motor neuron degeneration, distinguishing them from transgenic mutant SOD1 mouse models. This study provides the firstin vivoevidence that mismetallation and altered post-translational modifications precipitates wild-type SOD1 misfolding, dysfunction and deposition in the Parkinson disease brain, which may contribute to SNc dopamine neuron degeneration. Our data position this pathology as a novel drug target for this disorder, with a particular focus on therapies capable of correcting alterations to SOD1 post-translational modifications.
Mental Rotation is a weak measure of the propensity to visualise
Authors: Arnold Derek H. , Bouyer Loren N. , Saurels Blake W. , Pellicano Elizabeth , Schwarzkopf D. Samuel 
Published: October 2024

ABSTRACTThere is increasing evidence of substantial differences in people’s capacity to voluntarily visualise – with some (Congenital Aphants) asserting they cannot visualise at all. Its been suggested that Congenital Aphants might be mistaken about their inability, as some have performed similarly on tasks purported to measure imagery – including the mental rotation task, where people decide if objects depicted from different viewpoints are the same or different. We examined how the vividness of people’s imagery is related to performance on a ‘mental rotation’ task. People also reported on their response strategies. Mental rotation was an overall superior response strategy relative to non-visualising. However, the vividness of people’s imagery was only weakly associated with viewpoint contingent changes in task performance, and it did not predict changes in reliance on mental rotation as a response strategy. Overall, our data suggest performance on mental rotation tasks is a weak measure of people’s propensity to visualise.
A VersaTile approach to reprogram the specificity of the R2-type tailocin towards different serotypes ofEscherichia coliandKlebsiella pneumoniae
Authors: Dams Dorien , Pas Célia , Latka Agnieszka , Drulis-Kawa Zuzanna , Fieseler Lars , Briers Yves 
Published: October 2024

AbstractPhage tail-like bacteriocins, or tailocins, provide a competitive advantage to producer cells by killing closely related bacteria. Morphologically similar to headless phages, their narrow target specificity is determined by receptor-binding proteins (RBPs). While RBP engineering has been used to alter the host range of a selected R2 tailocin fromPseudomonas aeruginosa, the process is labor-intensive, limiting broader application. We introduce a VersaTile-driven R2 tailocin engineering platform to scale up RBP grafting. This platform achieved three key milestones: (1) engineering R2 tailocins specific toEscherichia coliserogroups O26, O103, O104, O111, O145, O146 and O157; (2) reprogramming R2 tailocins to target for the first time capsule and a new species, specifically the capsular serotype K1 ofE. coliand K11 and K63 ofKlebsiella pneumoniae; (3) creating the first bivalent tailocin with a branched RBP and cross-species activity, effective against bothE. coliK1 andK. pneumoniaeK11. Over 90% of engineered tailocins were effective, with clear pathways for further optimization identified.ImportanceWhile tailocin engineering is a proven and promising concept, the current engineering approach lacks scalability, limiting a vast exploration. This study advances tailocin engineering by increasing its throughput. Implementing a scaled up approach, we have shown the flexibility of the R2 tailocin scaffold to accommodate diverse receptor-binding domains, expanding its functionality to target a new type of receptor (capsule) and a previously untargeted species. In addition, functional tailocins with branched receptor-binding proteins portraying dual, cross-genus activity were produced. This work lays the groundwork for a scalable platform for the development of engineered tailocins, marking an important step towards making R2 tailocins a practical therapeutic tool for targeted bacterial infections.
LC-PLM: Long-context Protein Language Model
Authors: Wang Yingheng , Wang Zichen , Sadeh Gil , Zancato Luca , Achille Alessandro , Karypis George , Rangwala Huzefa 
Published: October 2024

AbstractSelf-supervised training of language models (LMs) has seen great success for protein sequences in learning meaningful representations and for generative drug design. Most protein LMs are based on the Transformer architecture trained on individual proteins with short context lengths. Such protein LMs cannot extrapolate to longer proteins and protein complexes well. They also fail to account for the underlying biological mechanisms carried out by biomolecular interactions and dynamics i.e., proteins often interact with other proteins, molecules, and pathways in complex biological systems. In this work, we proposeLC-PLMbased on an alternative protein LM architecture,BiMamba-S, built off selective structured state-space models, to learn high-quality universal protein representations at the amino acid token level using masked language modeling. We also introduce its graph-contextual variant,LC-PLM-G, which contextualizes protein-protein interaction (PPI) graphs for a second stage of training.LC-PLMdemonstrates favorable neural scaling laws, better length extrapolation capability, and a 7% to 34% improvement on protein downstream tasks than Transformer-based ESM-2.LC-PLM-Gfurther trained within the context of PPI graphs shows promising results on protein structure and function prediction tasks. Our study demonstrates the benefit of increasing the context size with computationally efficient LM architecture (e.g. structured state space models) in learning universal protein representations and incorporating molecular interaction context contained in biological graphs.
15 second assessment of hand and foot motor skill using a smartphone
Authors: Takagi Atsushi , Tabuchi Noriyuki , Ishido Wakana , Kamimukai Chikako , Gomi Hiroaki 
Published: October 2024

AbstractMotor skills are essential for daily functioning and serve as key indicators of healthy development and aging. However, existing assessments of motor skill are inaccessible to the public and do not directly measure the quality of the movement. Here, we developed a convenient and robust measure of motor skill that uses a smartphone app to provide on-the-spot assessment in just 15 seconds. To validate our method, we asked 1675 participants between the ages of three to eighty-eight years old to trace circles at a fixed rhythm with a smartphone, which was either held in the hand or strapped to the ankle. Motor skill was quantified by the smartphone app using an algorithm that calculated the variability in the acceleration’s trajectory. Our assessment revealed significant changes in the skill of the hands and feet with age and practice. The variability of the hands and feet linearly decreased and matured in the mid-teens, but it regressed gradually thereafter. Laterality, or the difference in the motor skill between the left and right limbs, increased with age as the non-dominant hand and foot regressed faster in the elderly. Motor practice affected both skill and laterality as left-handers who were forced to write with their right-hand during childhood had a tell-tale sign of stronger right-handedness and, surprisingly, right-footedness. Our assessment aims to democratize motor skill assessment, making it accessible for professionals and users of all ages.
Antidepressant use during pregnancy and birth outcomes: analysis of electronic health data from the UK, Norway, and Sweden
Authors: Martin Florence Z , Ahlqvist Viktor H , Madley-Dowd Paul , Lundberg Michael , Cohen Jacqueline M , Furu Kari , Rai Dheeraj , Forbes Harriet , Easey Kayleigh , Håberg Siri E , Sharp Gemma C , Magnusson Cecilia , Magnus Maria C 
Published: October 2024

AbstractObjectivesTo explore the association between antidepressant use during pregnancy and birth outcomes.DesignCohort study.SettingElectronic health record data.Participants2 528 916 singleton births from the UK’s Clinical Practice Research Datalink (1996-2018), Norway’s Medical Birth Registry (2009-2020), and Sweden’s Medical Birth Register (2006-2020).Main outcome measuresStillbirth, neonatal death, pre- and post-term delivery, small and large for gestational age, and low Apgar score five minutes post-delivery.ResultsA total of 120 209 (4.8%) deliveries were exposed to maternal antidepressant use during pregnancy. Maternal antidepressant use during pregnancy was associated with increased odds of stillbirth (adjusted pooled OR (aOR) 1.16, 95% CI 1.05 to 1.28), preterm delivery (aOR 1.26, 95% CI 1.23 to 1.30), and Apgar score < 7 at 5 minutes (aOR 1.83, 95% CI 1.75 to 1.91). These findings persisted in the discordant sibling analysis, but with higher uncertainty. The adjusted predicted absolute risk for stillbirth was 0.34% (95% CI 0.33 to 0.35) among the unexposed and 0.40% (95% CI 0.36 to 0.44) in the antidepressant exposed. Restricting to women with depression or anxiety, the association between antidepressant exposure and stillbirth attenuated (aOR 1.07, 95% CI 0.94 to 1.21). Paternal antidepressant use was modestly associated with preterm delivery and low Apgar score. Most antidepressants were associated with preterm delivery (except paroxetine) and Apgar score (except mirtazapine and amitriptyline).ConclusionsMaternal antidepressant use during pregnancy may increase the risk of stillbirth, preterm delivery, and low Apgar score, although the absolute risks remained low. Confounding by severity of indication cannot be ruled out, as the severity of symptoms was not available. The modest association between paternal antidepressant use and both preterm delivery and low Apgar score suggests that residual confounding by familial environment cannot be ruled out.