bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chemosensory modulation of eye-body coordination in larval zebrafish
Authors: Sy Samuel K. H. , Chan Danny C. W. , Zhang Jenny J. , Lyu Jing , Feng Crystal , Wang Kui , Mok Vincent C. T. , Wong Kenneth K. Y. , Mu Yu , Randlett Owen , Hu Yu , Ko Ho 
Published: October 2024

AbstractCoordinated eye-body movements are essential for many animal behaviors, yet the influence of chemosensory inputs on these movements remains underexplored. Here, we enhance the Fish-On-Chips optofluidic platform to reveal that larval zebrafish use coupled saccade-tail flips for chemosensory avoidance, but not pursuit. Spontaneous saccades, which alternate in direction, are closely synchronized with tail flips via anticipatory adjustments in tail flip event rate, directionality, and kinematics. In response to ethologically representative chemosensory cues, this coordination is differentially modulated based on valence. Aversive chemical cues increase saccade frequency and the proportion of saccade-coupled tail flips, while also enhancing the turning intent as the coupling strengthens. Conversely, appetitive chemicals promote more sustained gliding movements without impacting saccades or their tail flip coupling. Brain-wide neuronal activity imaging reveals that the pallium, a cortical homolog in teleosts, strongly represents the sensorimotor transformation of aversive cue-associated coupled saccade-tail flips. Our findings underscore the critical role of chemosensory cues in regulating eye-body coordination in an early vertebrate species, highlighting a deep evolutionary integration of sensory inputs to optimize locomotion.
Revealing mechanisms underlying the collective escape of starling flocks
Authors: Papadopoulou Marina , Hildenbrandt Hanno , Storms Rolf F. , Carere Claudio , Hemelrijk Charlotte K. 
Published: October 2024

AbstractEuropean starlings perform a great diversity of patterns of collective behaviour when hunted by aerial predators; their large flocks are changing shape, size, and internal structure continuously and rapidly, but how these patterns emerge by self-organization is still unknown. Here, we disentangle the emergence of several interconnected patterns of collective escape in starlings. We combine video footage of starling flocks pursued by a robotic predator, the RobotFalcon, with simulations of large flocks in a new data-driven 3-dimentional agent-based model. Our empirical data show that flock members often differ in their evasive manoeuvres and that several patterns of collective escape arise simultaneously at different parts in the flock. In our computational model, we identify what rules of motion, coordination and escape at the individual level lead to the emergence of group density, internal dynamics, and patterns of collective escape similar to real starling flocks. Overall, our results suggest that the emergence and dynamics of simultaneous patterns of collective escape depend on: the speed with which the escape information propagates from one or few initiators, the positions of the escaping flock members in relation to the predator, and the previous state of the flock (hysteresis).
A circuit model for transsaccadic space updating and mislocalization
Authors: Wang Xiao , Tsien Sophia , Goldberg Michael E. , Zhang Mingsha , Qian Ning 
Published: October 2024

AbstractWe perceive a stable, continuous world despite drastic changes of retinal images across saccades. However, whilepersistentobjects in daily life appear stable across saccades, stimuliflashedaround saccades can be grossly mislocalized. We address this puzzle with our recently proposed circuit model for perisaccadic receptive-field (RF) remapping in LIP and FEF. The model uses center/surround connections to store a relevant stimulus’ retinal location in memory as a population activity. This activity profile is updated across each saccade by directional connections gated by the corollary discharge (CD) of the saccade command. The updating is a continuous backward (against the saccade) shift of the population activity (equivalent to continuous forward remapping of the RFs), whose cumulative effect across the saccade is a subtraction of the saccade vector. The model explains forward and backward translational mislocalization for stimuli flashed around the saccade onset and offset, respectively, as insufficient and unnecessary cumulative updating after the saccade, caused by the sluggish CD time course and visual response latency. We confirm the model prediction that for perisaccadic RFs measured with flashes before the saccades, the final forward remapping magnitudes after the saccades are smaller for later flashes. We discuss the possibility that compressive mislocalization results from a brief reduction of attentional remapping and repulsion. Although many models of RF remapping, transsaccadic updating, and perisaccadic mislocalization have been proposed, our work unifies them into a single circuit mechanism and suggests that the brain uses “unaware” decoders which do not distinguish between different origins of neurons’ activities.
Towards a complete phage tail fiber structure atlas
Authors: Klein-Sousa Victor , Roa-Eguiara Aritz , Kielkopf Claudia S. , Sofos Nicholas , Taylor Nicholas M. I. 
Published: October 2024

AbstractBacteriophages use receptor-binding proteins (RBPs) to adhere to bacterial hosts. Understanding the structure of these RBPs can provide insights into their target interactions. Tail fibers, a prominent type of RBP, are typically elongated, flexible, and trimeric proteins, making it challenging to obtain high-resolution experimental data of their full-length structures. Recent advancements in deep learning-based protein structure prediction, such as AlphaFold2-multimer (AF2M) and ESMfold, allow for the generation of high-confidence predicted models of complete tail fibers. In this paper, we introduce RBPseg, a method that combines monomeric ESMfold predictions with a novel sigmoid distance pair (sDp) protein segmentation technique. This method segments the tail fiber sequences into smaller fractions, preserving domain boundaries. These segments are then predicted in parallel using AF2M and assembled into a full fiber model. We demonstrate that RBPseg significantly improves AF2M v2.3.2 in terms of model confidence, running time, and memory usage. To validate our approach, we used single-particle cryo-electron microscopy to analyze five tail fibers from three phages of the BASEL collection. Additionally, we conducted a structural classification of 67 fibers and their domains, which identified 16 well-defined tail fiber classes and 89 domains. Our findings suggest the existence of modular fibers as well as fibers with different sequences and shared structure, indicating possible sequence convergence, divergence, and domain swapping. We further demonstrate that these structural classes account for at least 24% of the known tail fiber universe.
Borrelia burgdorferiloses essential genetic elements and cell proliferative potential during stationary phase in culture but not in the tick vector
Authors: Zhang Jessica , Takacs Constantin N. , McCausland Joshua W. , Mueller Elizabeth A. , Buron Jeline , Thappeta Yashna , Wachter Jenny , Rosa Patricia A. , Jacobs-Wagner Christine 
Published: October 2024

AbstractThe Lyme disease agentBorrelia burgdorferiis a polyploid bacterium with a segmented genome in which both the chromosome and over 20 distinct plasmids are present in multiple copies per cell. This pathogen can survive at least nine months in its tick vector in an apparent dormant state between blood meals, without losing cell proliferative capability when re-exposed to nutrients. CultivatedB. burgdorfericells grown to stationary phase or resuspended in nutrient-limited media are often used to study the effects of nutrient deprivation. However, a thorough assessment of the spirochete’s ability to recover from nutrient depletion has been lacking. Our study shows that starvedB. burgdorfericultures rapidly lose cell proliferative. Loss of genetic elements essential for cell proliferation contributes to the observed proliferative defect in stationary phase. The gradual decline in copies of genetic elements is not perfectly synchronized between chromosomes and plasmids, generating cells that harbor one or more copies of the essential chromosome but lack all copies of one or more non-essential plasmids. This phenomenon likely contributes to the well-documented issue of plasmid loss during in vitro cultivation ofB. burgdorferi. In contrast,B. burgdorfericells from ticks starved for 14 months showed no evidence of reduced cell proliferative ability or plasmid loss. Beyond their practical implications for studyingB. burgdorferi, these findings suggest that the midgut of the tick vector offers a unique environment that supports the maintenance ofB. burgdorferi’s segmented genome and cell proliferative potential during periods of tick fasting.ImportanceBorrelia burgdorfericauses Lyme disease, a prevalent tick-borne illness.B. burgdorferimust survive long periods (months to a year) of apparent dormancy in the midgut of the tick vector between blood meals. Resilience to starvation is a common trait among bacteria. However, this study reveals that in laboratory cultures,B. burgdorferipoorly endures starvation and rapidly loses viability. This decline is linked to a gradual loss of genetic elements required for cell proliferation. These results suggest that the persistence ofB. burgdorferiin nature is likely shaped more by unique environmental conditions in the midgut of the tick vector than by a general innate ability of this bacterium to endure nutrient deprivation.
Synaptic composition, activity, mRNA translation and dynamics in combined single-synapse profiling using multimodal imaging
Authors: Falkovich Reuven , Aryal Sameer , Wang Jasmine , Sheng Morgan , Bathe Mark 
Published: October 2024

AbstractThe function of neuronal circuits, and its perturbation by psychoactive molecules or disease-associated genetic variants, is governed by the interplay between synapse activity and synaptic protein localization and synthesis across a heterogeneous synapse population. Here, we combine in situ measurement of synaptic multiprotein compositions and activation states, synapse activity in calcium traces or glutamate spiking, and local translation of specific genes, across the same individual synapses. We demonstrate how this high-dimensional data enables identification of interdependencies in the multiprotein-activity network, and causal dissection of complex synaptic phenotypes in disease-relevant chemical and genetic NMDAR loss of function that translatein vivo. We show how this method generalizes to other subcellular systems by deriving mitochondrial protein networks, and, using support vector machines, its value in overcoming animal variability in phenotyping. Integrating multiple synapse information modalities enables deep structure-function characterization of synapse populations and their responses to genetic and chemical perturbations.
Cortical Reactivations Modulated by Local Inhibitory Circuits Mediate Memory Consolidation
Authors: Lensjø Kristian Kinden , Nystuen Ingeborg Nymoen , Rogge Frederik Sebastian , Tøndel Kristin , Sugden Arthur , Shurnayte Inga , Grødem Sverre , Malthe-Sørenssen Anders , Hafting Torkel , Andermann Mark L. , Fyhn Marianne 
Published: October 2024

AbstractHighly salient events activate neurons across various brain regions. During subsequent rest or sleep, the activity patterns of these neurons often correlate with those observed during the preceding experience. Growing evidence suggests that these reactivations play a crucial role in memory consolidation, the process by which experiences are solidified in cortical networks for long-term storage.Here, we demonstrate that reactivations in the lateral visual cortex are vital for the consolidation of visual association learning. By employing longitudinal two-photon Ca2+imaging alongside paired LFP recordings in the hippocampus and cortex, we show that targeted manipulation of PV+inhibitory neurons in the lateral visual cortexafterdaily training selectively attenuated cue-specific reactivations and learning, with no apparent effect on normal network function during training. In contrast, reactivations in the control group were biased towards salient cues, aligned with learning process and persisted for hours after training had ended. Overall, our results underscore a crucial role for cortical reactivations in memory consolidation.
The Role of Physical Activity in Mitigating Age-Related Changes in the Neuromuscular Control of Gait
Authors: Nuñez-Lisboa M.N. , Dewolf A.H. 
Published: October 2024

AbstractExercise is known to induce several neural and muscular adaptations, such as increased muscle mass and functional capacity in older adults. In this study, we investigated its impact on the neuromuscular control of gait among young and older adults, divided into two groups: more active (young: n=15; 5185 ± 1471 MET-min/week; old: n=14; 6481 ± 4846 MET-min/week) and less active participants (young: n=14; 1265 ± 965 MET-min/week; old: n=14; 1473 ± 859 MET-min/week). Maximal isometric tests of ankle and knee extension revealed a reduction in force among older adults, with differences associated with the level of physical activity at the ankle level. Gait mechanics revealed no significant differences between young adults and the more active older adults. In contrast, less active older adults exhibited shorter steps, higher mechanical cost, and greater collision at heel strike. These changes cannot be attributed solely to reductions in muscle strength. Instead, they are likely the result of modifications in neuromuscular control and mechanical properties of muscles in less active older adults. Specifically, wider activation (and greater coactivation) of lumbar and sacral motor pools as well as a different timing of activation were observed. Also, their muscle-tendon stiffness was reduced. In conclusion, our findings highlight that the age-related decline in gait efficiency is exacerbated by a sedentary lifestyle. Even modest increases in physical activity appear to preserve neuromuscular control and improve walking performance. This suggests that interventions aiming to enhance physical activity levels could mitigate age-related declines in gait mechanics.
LYCEUM: Learning to call copy number variants on low coverage ancient genomes
Authors: Yılmaz Mehmet Alper , Ceylan Ahmet Arda , Kaynar Gün , Çiçek A. Ercüment 
Published: October 2024

AbstractCopy number variants (CNVs) are pivotal in driving phenotypic variation that facilitates species adaptation. They are significant contributors to various disorders, making ancient genomes crucial for uncovering the genetic origins of disease susceptibility across populations. However, detecting CNVs in ancient DNA (aDNA) samples poses substantial challenges due to several factors: (i) aDNA is often highly degraded; (ii) contamination from microbial DNA and DNA from closely related species introduce additional noise into sequencing data; and finally, (iii) the typically low coverage of aDNA renders accurate CNV detection particularly difficult. Conventional CNV calling algorithms, which are optimized for high coverage read-depth signals, underperform under such conditions. To address these limitations, we introduce LYCEUM, the first machine learning-based CNV caller for aDNA. To overcome challenges related to data quality and scarcity, we employ a two-step training strategy. First, the model is pre-trained on whole genome sequencing data from the 1000 Genomes Project, teaching it CNV-calling capabilities similar to conventional methods. Next, the model is fine-tuned using high-confidence CNV calls derived from only a few existing high-coverage aDNA samples. During this stage, the model adapts to making CNV calls based on the downsampled read depth signals of the same aDNA samples. LYCEUM achieves accurate detection of CNVs even in typically low-coverage ancient genomes. We also observe that the segmental deletion calls made by LYCEUM show correlation with the demographic history of the samples and exhibit patterns of negative selection inline with natural selection. LYCEUM is available athttps://github.com/ciceklab/LYCEUM.
Complex system modelling reveals oxalate homeostasis is driven by diverse oxalate-degrading bacteria
Authors: Mukherjee Sromona D. , Batagello Carlos A. , Adler Ava , Agudelo Jose , Zampini Anna , Suryavanshi Mangesh , Nguyen Andrew , Orr Teri , Dearing Denise , Monga Manoj , Miller Aaron W. 
Published: October 2024

AbstractDecades of research have made clear that host-associated microbiomes touch all facets of health. However, effective therapies that target the microbiome have been elusive given its inherent complexity. Here, we experimentally examined diet-microbe-host interactions through a complex systems framework, centered on dietary oxalate. Using multiple, independent molecular, animal, andin vitroexperimental models, we found that microbiome composition influenced multiple oxalate-microbe-host interfaces. Importantly, administration of the oxalate-degrading specialist,Oxalobacter formigenes,was only effective against a poor oxalate-degrading microbiota background and gives critical new insights into why clinical intervention trials with this species exhibit variable outcomes. Data suggest that, while heterogeneity in the microbiome impacts multiple diet-host-microbe interfaces, metabolic redundancy among diverse microorganisms in specific diet-microbe axes is a critical variable that may impact the efficacy of bacteriotherapies, which can help guide patient and probiotic selection criteria in probiotic clinical trials.
Rhythms and Background (RnB): The Spectroscopy of Sleep Recordings
Authors: Dubé J. , Foti M. , Jaffard S. , Latreille V. , Frauscher B. , Carrier J. , Lina J.M. 
Published: October 2024

AbstractNon-rapid eye movement (NREM) sleep is characterized by the interaction of multiple coupled oscillations essential for various functions such as memory consolidation, alongside a pervasive and dynamic arrhythmic 1/f scale-free background that may also contribute to these functions. Although recent spectral parametrization methods such as FOOOF (Fitting-One-and-Over-f) allowed to dissociate rhythmic and arrhythmic components in the spectral domain, they fail to resolve these processes in the time domain, where instantaneous measures of frequency, amplitude, and phase-amplitude coupling are still confounded by arrhythmic activity. This limitation represents a significant pitfall for studies of NREM sleep, which often rely on phase-based analyses of specific oscillations. To address this limitation, we introduce ‘Rhythms & Background’ (RnB), a novel wavelet-based methodology designed to dynamically denoise time-series data by correcting for arrhythmic interference. This enables the extraction of a purely rhythmic time-series suitable for enhanced time-domain analyses of sleep rhythms. We first validate RnB through simulations, demonstrating its robust performance in accurately estimating spectral profiles of individual and multiple oscillations across a range of arrhythmic conditions. We then apply RnB to publicly available intracranial EEG sleep recordings, showing that it provides an improved spectral and time-domain representation of hallmark NREM rhythms. Finally, we demonstrate that RnB significantly enhances the assessment of phase-amplitude coupling between cardinal NREM oscillations, outperforming traditional methods that conflate rhythmic and arrhythmic components. This methodological advance offers a substantial improvement in the analysis of sleep oscillations, providing greater precision in the study of rhythmic activity critical to NREM sleep functions.SIGNIFICANCE STATEMENTThe Rhythms and Background (RnB) algorithm introduces a novel approach to signal processing in electrophysiology by isolating rhythmic activity from the arrhythmic background at the time-series level. Unlike existing spectral decomposition methods, RnB enables more precise analysis of brain rhythms in both the time and spectral domains, providing clearer insights into cerebral oscillatory processes. This breakthrough has direct applications in studying brain connectivity and oscillation dynamics during sleep. Additionally, its application in clinical populations where pathological changes in arrhythmic activity are common, such as neurodevelopmental and neurodegenerative disorders, will help to better understand abnormal oscillatory processes. By improving the accuracy of rhythmic signal analysis, RnB opens new avenues for understanding brain function and dysfunction in research and clinical settings.
Prostate-specific membrane receptor PPAP facilitatesE. coliinvasion of luminal prostate cells via FimH binding
Authors: Guedes Maria , Joshi Amruta , Dorn Sina , Peters Simon , Beste Tristan , Leipold Alexander M , Rosenfeldt Mathias , Saliba Antoine-Emmanuel , Dobrindt Ulrich , Kalogirou Charis , Aguilar Carmen 
Published: October 2024

ABSTRACTBacterial prostatitis caused by uropathogenicEscherichia coli(UPEC) strains is a highly prevalent and recurrent infection responsible for significant morbidity in men. However, the molecular pathogenesis of prostatitis remains poorly understood, partly due to the lack of comprehensivein-vitromodels. In this study, we introduce a murine prostate organoid model that replicates the cellular heterogeneity of the prostate epithelium with a cell composition and transcriptional signature comparable to the native prostate tissue. Using this model, we uncovered that UPEC preferentially attaches to, invades, and replicates within luminal prostate cells. This selective interaction is mediated by the binding of the bacterial adhesin FimH to the prostate- specific membrane protein PAPP, which is exclusively expressed on luminal prostate cells. Altogether, we identified a new mechanism by which UPEC infects the prostate epithelium, highlighting FimH’s adaptability in engaging host receptors and its potential for targeted therapeutic strategies.
Effect of digital noise-reduction processing on subcortical speech encoding and relationship to behavioral outcomes
Authors: Kim Subong , Schroeder Mary , Bharadwaj Hari M. 
Published: October 2024

AbstractPerceptual benefits from digital noise reduction (NR) vary among individuals with different noise tolerance and sensitivity to distortions introduced in NR-processed speech; however, the physiological bases of the variance are understudied. Here, we developed objective measures of speech encoding in the ascending pathway as candidate measures of individual noise tolerance and sensitivity to NR-processed speech using the brainstem responses to speech syllable /da/. The speech-evoked brainstem response was found to be sensitive to the addition of noise and NR processing. The NR effects on the consonant and vowel portion of the responses were robustly quantified using response-to-response correlation metrics and spectral amplitude ratios, respectively. Further, the f0 amplitude ratios between conditions correlated with behavioral accuracy with NR. These findings suggest that investigating the NR effects on bottom-up speech encoding using brainstem measures is feasible and that individual subcortical encoding of NR-processed speech may relate to individual behavioral outcomes with NR.