Biology subjects

Teng, S.

Publications and source records attributed to Teng, S..

At least 19 recordsLinked to original sources

bioRxiv2026

Hepatitis C Virus Remodels Lipid Droplets to Promote Mitochondrial Fatty Acid Accumulation and Metabolic Activation

Hepatitis C virus (HCV) depends on host lipid metabolism and lipid droplets (LDs) for genome replication, assembly, and particle production, yet how LD structure and lipid utilization change over the course of infection remains incompletely understood. Here, we investigated the temporal remodeling of LD-associated metabolic pathways during HCV JFH-1 infection of human hepatoma Huh7 cells. HCV infection transiently increased LD fluorescence intensity at 24 hours post-infection (hpi), followed by normalization or relative loss of LD signal at later time points. Concomitantly, LDs became progressively clustered and enlargement during late infection, despite reduced protein levels of the canonical LD fusion proteins CIDEA, CIDEB, and CIDEC, suggesting that HCV-induced LD enlargement occurs through CIDE-independent mechanisms. Transcriptomic, RT-qPCR, and immunoblot analyses revealed time-dependent regulation of genes and proteins involved in LD structure, triglyceride synthesis, lipolysis, lipid uptake, and mitochondrial fatty acid utilization. Subcellular fractionation demonstrated preferential accumulation of fatty acids in mitochondrial fractions at 24-72 hpi. This redistribution was accompanied by increased oxygen consumption rate, elevated extracellular acidification, and progressive reactive oxygen species accumulation, indicating infection-associated metabolic activation and oxidative stress. Pharmacological inhibition of DGAT1-dependent LD biogenesis, LIPA-dependent lysosomal lipid hydrolysis, LIPE/HSL-dependent lipolysis, or CPT1-dependent mitochondrial fatty acid transport markedly reduced mitochondrial fatty acid accumulation and suppressed HCV-induced respiratory activity. Inhibition of LIPA or LIPE/HSL reduced both HCV RNA and core protein levels, whereas inhibition of CPT1 or DGAT1 had more pronounced effects on core protein than on viral RNA. Together, these findings support a model in which HCV dynamically remodels LDs, mobilizes LD-associated fatty acids, and redirects them toward mitochondria to support infection-associated metabolism and downstream stages of the viral life cycle. Lipid hydrolysis and mitochondrial fatty acid trafficking therefore represent potential host-directed targets for limiting HCV infection. SIGNIFIGANCEHepatitis C virus depends on host lipid metabolism for replication, assembly, and production of infectious particles, but how it uses lipid droplets over time remains incompletely understood. This study shows that hepatitis C virus dynamically remodels lipid droplets, causing an early increase in lipid storage followed by droplet enlargement and mobilization of fatty acids during later infection. The released fatty acids preferentially accumulate in mitochondria, where they are associated with increased cellular respiration and oxidative stress. Blocking lipid droplet formation, lipid breakdown, or fatty acid transport to mitochondria reduced this metabolic response and decreased viral RNA or core protein accumulation. Inhibition of lysosomal acid lipase and hormone-sensitive lipase suppressed both viral RNA and protein levels. These findings identify lipid droplet breakdown and mitochondrial fatty acid trafficking as important host processes used by hepatitis C virus and as potential targets for host-directed antiviral intervention.

microbiology↗

bioRxiv2026

Modeling human echolocation using a Kalman filter

Some blind individuals use echolocation, a skill that allows them to better navigate their environment using echoes from self-generated mouth clicks reflected off surrounding surfaces. Echolocation involves a complex interplay of sensory accumulation, information processing, dynamic prediction, motor planning and execution in real-time. Computational modeling offers a valuable approach to understanding the cognitive and neural mechanisms underlying echolocation performance, in particular the temporal dynamics of the process. We present a computational model of human echolocation behavior based on a Kalman filter, where we treat the echolocator as an active sensor that maintains an internal belief about the targets location and continuously refines it via echo feedback. The model, based on observations of echolocation in blind human experts, simulates the use of mouth clicks and returning echoes to localize and orient toward a target under varying conditions. In the experiment, the target is placed at a random azimuth in the frontal plane. An echolocator aims a series of mouth clicks in various directions and infers the target azimuth using acoustic information received from the click echoes. The system integrates three major components: (1) a simulation of echoacoustic interaural time differences (ITD) to estimate the relative head-target angle; (2) a Kalman filter that processes these ITDs to iteratively update probabilistic beliefs about target location and associated uncertainty; and (3) a motor control system that modulates head movements with the current belief state. The Kalman filter serves as a representation of the internal state of the observer, where its beliefs drive the direction of head rotation, and its uncertainty estimates drive head velocity adjustments. Model performance demonstrates that simple predictive computational approaches can reproduce key aspects of echo-guided sensorimotor learning, providing a framework that may be leveraged to develop biologically plausible models, advance understanding of best practices, and potentially improve intervention strategies.

neuroscience↗

bioRxiv2026

Sensorimotor dynamics of target acquisition and homing in human echolocation

Blindness imposes constraints on the acquisition of environmental sensory information. To mitigate those constraints, some blind people employ active echolocation, a technique in which self-generated tongue "clicks" produce informative reflections from surrounding surfaces. Practitioners typically produce multiple clicks that guide, and are in turn shaped by, goal-relevant action. What perceptual information is gained in the echoacoustic signal from each click, and how does it inform motor behavior during task performance? To explore these poorly understood dynamics, here we recorded head movements and clicking behavior of an early-blind expert echolocation practitioner who localized and oriented toward a target object positioned at a 1 m distance and random azimuth in the frontal hemifield. Three additional participants, including a blind self-reported echolocator, were unable to perform the task better than chance level. Performance clearly benefited from available echoacoustic information: The larger target was localized with an average absolute angular error of 9.5{degrees} in 9.3 s, vs. 24.6{degrees} in 23.2 s for the smaller target. In a passive control condition prohibiting clicks altogether, no significant convergence on the target was observed, confirming the necessity of active sampling. Clicks were emitted somewhat more rapidly and intensely for small targets, but within-trial emission rate and head kinematics (left-to-right reversals) remained relatively invariant. Angular convergence toward the target was consistent with an exponential decay profile, though only weakly distinguishable from a linear trend for small targets. Pooled across trials within each condition, clicks were unimodally distributed about the target azimuth, suggesting an intensity-maximization strategy. In sum, clicking behavior and target size (therefore sonar strength) strongly influenced the rate and precision of orientation convergence toward the target, suggesting that dynamic interactions between motor-driven head movements, click production, and the resulting echoacoustic feedback accumulate goal-relevant evidence across multiple samples. Together, these results illustrate naturalistic sensorimotor dependencies underlying auditory active sensing in the absence of vision.

neuroscience↗

bioRxiv2026

Lysosomal Expansion Compartments Mediate Zinc and Copper Homeostasis in Caenorhabditis elegans

Zinc is an essential transition metal that participates in many biological processes. In C. elegans, excess zinc is stored in lysosomes in intestinal cells; this process involves increasing the expression of the zinc transporter CDF-2 and remodeling of lysosomes characterized by an increase in the volume of the expansion compartment. To determine if this is a more general property, we investigated other metals. Here we report that lysosomes are remodeled in response to excess copper, manganese, and cadmium, with each metal causing an increase in the volume of the expansion compartment. Mutants with a reduced number of lysosomes were hypersensitive to growth retardation caused by excess copper and manganese, suggesting metal toxicity is prevented by metal sequestration in lysosomes. Using a novel method to analyze isolated lysosomes by X-ray Fluorescence Microscopy we demonstrated that zinc, copper and manganese are detectable in the lumen of lysosomes. To further analyze copper, we examined localization of CUA-1.1, a copper transporter that moves copper into the lumen of lysosomes. Like the zinc transporter CDF-2, CUA-1.1 localizes to both the acidified and expansion compartments in excess copper. These results indicate that the same intestinal lysosomes store zinc, copper and manganese. Lysosome remodeling characterized by an increase in volume of the expansion compartment is not specific to zinc but is a more general phenomenon during metal storage in lysosomes.

molecular biology↗

bioRxiv2025

Integrative Computational and Experimental Analysis of Curly Su Mutations in Drosophila melanogaster

The Curly Su (dMPO) protein, a homolog of the human myeloperoxidase (hMPO), is critical for wing development in Drosophila melanogaster. Like human peroxidases, dMPO is involved in various cellular and physiological processes, producing significant quantities of reactive oxygen species that contribute to both development and immunity in the fruit fly. Given the significant sequence and structural similarities between dMPO and hMPO, dMPO serves an ideal model for studying peroxidase functions and related pathologies. We performed saturated computational mutagenesis on dMPO, analyzing the effects of 11,191 missense mutations on its stability. Notably, the G378W mutation exhibited the greatest destabilizing effect, while the W621R, potentially pathogenic, also reduced dMPO stability. To investigate these effects in vivo, we used genome editing to generate the transgenic Drosophila with G378W, W621R, and deletion of residues 305-687. Remarkably, G378W mutants displayed significant alterations in wing morphology and reduced lifespan. RNA-seq analysis of transgenic and wild-type flies revealed differentially expressed genes (DEGs), as interpreted through gene ontology analysis. Our integrated computational and genetic approach identified dMPO mutations that disrupt protein stability and alter gene expression. These findings offer new insight into how single-point mutations can lead to systemic biological changes. Author SummaryProteins are the molecular machines that drive almost every process in living organisms, and even small genetic changes can disrupt their structure and function. In this study, we focused on Curly Su, a protein in fruit flies that is similar to human myeloperoxidase. We used a computational approach called saturation mutagenesis to model over 11,000 possible single mutations in the Curly Su protein and predict how they would affect its stability. We then used genome editing to introduce several destabilizing and potential disease-causing mutations into flies. These mutant flies developed abnormal wings, had shorter lifespans, and showed widespread changes in gene activity, particularly in metabolism and immune pathways. By combining computational predictions with experimental validation, our work demonstrates a powerful and generalizable strategy for linking specific genetic mutations to whole-organism outcomes. This approach not only sheds light on the biological role of Curly Su but also provides a framework that can be applied to other genes and organisms, offering insights relevant to human health and disease.

bioinformatics↗

bioRxiv2025

Computational and Experimental Identification of Potential Neutralizing Peptides Derived from Human ACE2 Against SARS-CoV-2 Infection

The human angiotensin-converting enzyme 2 (hACE2) is the primary receptor for the entry of SARS-CoV-2. Some human alleles of ACE2 exhibit an improved affinity for the SARS-CoV-2 Spike protein. However, the impact of ACE2 polymorphisms on SARS-CoV-2 infection remains unclear. Our previous study predicted that G431 and S514 in the receptor-binding domain (RBD) od SARS-CoV-2 S1 domain are important for S protein stability, and that S protein residues G496 and F497 and ACE2 residues D355 and Y41 are critical for the RBD-ACE2 interaction (1). In this study, we explored the potential of hACE2-derived neutralizing peptides as a therapeutic strategy against SARS-CoV-2 and investigated how ACE2 polymorphisms affect RBD-ACE2 binding affinity. We applied computational saturation mutagenesis to systematically screen the binding affinity changes among all possible ACE2 missense mutations within the ACE2-Wuhan-S1 complex. Mutations at ACE2 residues D355 and Y41 were predicted to weaken binding affinity, whereas those at N330 and D30 enhanced it. We identified six ACE2 regions (19-49, 65-102, 320-333, 348-359, 378-395, 552-563) to be vital for ACE2-RBD interaction. We synthesized peptides corresponding to these six regions and tested them using a pseudotyped viral particle system and dot blot assay. Three peptides were confirmed to bind with S protein, and four exhibited inhibitory effects. We aligned ACE2-Wuhan-S1 and ACE2-Omicron-S1 complexes, conducted correlation analysis, and observed similar binding patterns, suggesting that these peptides also have potential to neutralize Omicron strains. IMPORTANCESARS-CoV-2 continues its global spread. In this research, we identified six regions within ACE2 that are vital for interaction with the viral S RBD and have potential to neutralize SARS-CoV-2 infection. Among the six peptides derived from ACE2, three were confirmed to bind with S protein of Wuahan strain, and four exhibited inhibitory effects on Wuahn strain SARS-CoV-2. We also found ACE2 residues D355 and Y41 as weakening affinity, and N330 and D30 as enhancing it. We also aligned this complex with the ACE2-Omicron-S1 complex, performed correlation analyses, and compared their patterns of stability changes upon mutations, and obtained similar results, indicating that these peptides may also be effective against Omicron variants. These results provide insight into the role of ACE2 polymorphism in viral entry and suggest that hACE2-derived peptides may offer a promising therapeutic strategy against SARS-CoV-2, demonstrating strong consistency between our computational predictions and experimental outcomes.

microbiology↗

bioRxiv2025

Neural and behavioral correlates of evidence accumulation in human click-based echolocation

Echolocation enables blind individuals to perceive and navigate their environment by emitting clicks and interpreting their returning echoes. While expert blind echolocators demonstrate remarkable spatial accuracy, the behavioral and neural mechanisms supporting the temporal integration of spatial echoacoustic cues remain less explored. Here, we investigated the temporal dynamics of spatial information accumulation in human click-based echolocation using EEG. Blind expert echolocators and novice sighted participants localized virtual spatialized echoes derived from realistic synthesized mouth clicks, with trials presenting trains of 2-11 clicks. Behavioral results showed that blind expert echolocators significantly outperformed sighted controls in spatial localization. For these experts, localization thresholds decreased with more clicks, indicating cumulative integration of spatial cues across repeated samples. EEG decoding analyses revealed that neural representations significantly distinguished echo laterality and predicted overall spatial localization performance from the first click alone. Additionally, brain responses relative to the first click evolved systematically over successive clicks, paralleling psychophysical performance in blind echolocators and providing a possible index of perceptual information accumulation. These findings provide, to our knowledge, the first fine-grained account of temporal neural dynamics underlying click-based echolocation, directly linked to behavioral performance over multiple samples. They reveal how successive echoes are integrated over time into coherent spatial representations. Together, these results advance our understanding of the perceptual and neural mechanisms underlying echolocation and demonstrate adaptive sensory processing in the absence of vision.

neuroscience↗

bioRxiv2025

A transgene harboring the human Glucose Transporter1 (GLUT1) gene locus ameliorates disease in GLUT1 deficiency syndrome model mice.

Proper brain function relies on an adequate supply of energy - mainly glucose - to power neuronal activity. Delivery of this nutrient to the neuropil is mediated by the Glucose Transporter1 (GLUT1) protein. Perturbing glucose supply to the brain is profoundly damaging and exemplified by the neurodevelopmental disorder, GLUT1 deficiency syndrome (GLUT1DS). Resulting from haploinsufficiency of the SLC2A1 (GLUT1) gene, GLUT1DS is characterized by intractable infantile-onset seizures and a disabling movement disorder. Ketogenic diets, which supply the brain with an alternate energy source, ketone bodies, are currently the preferred therapeutic option for Glut1DS patients but do not address the underlying cause - low brain glucose - of the disease. One intuitively appealing therapeutic strategy that does, involves restoring GLUT1 levels to the patient brain. Here, we demonstrate that transgenic expression of the human GLUT1 genomic locus in a mouse model of GLUT1DS raises brain GLUT1 levels and reduces disease burden. Augmenting GLUT1 levels in mutants correspondingly raised cerebrospinal fluid (CSF) glucose levels, improved motor performance and reduced the frequency of seizures characteristically observed in GLUT1DS. Interestingly, the increased GLUT1 in mutants harboring the human GLUT1 locus was at least partly the result of an increase in murine Slc2a1 (Glut1) activity, most likely the effect of a long non-coding RNA (lncRNA) embedded in the human transgene. Collectively, our work has not only shown that repleting human GLUT1 mitigates GLUT1DS but also has yielded transgenic mice that constitute a useful tool to test and optimize clinically promising agents designed to stimulate this gene for therapeutic purposes.

neuroscience↗

bioRxiv2025

A therapeutic role for a regulatory glucose transporter1 (Glut1)-associated natural antisense transcript

The mammalian brain relies primarily on glucose for its energy needs. Delivery of this nutrient to the brain is mediated by the glucose transporter-1 (Glut1) protein. Low Glut1 thwarts glucose entry into the brain, causing an energy crisis and, triggering, in one instance, the debilitating neurodevelopmental condition - Glut1 deficiency syndrome (Glut1DS). Current treatments for Glut1DS are sub-optimal, as none address the root cause - low Glut1 - of the condition. Levels of this transporter must respond rapidly to the brains changing energy requirements. This necessitates fine-tuning its expression. Here we describe a long-noncoding RNA (lncRNA) antisense to Glut1 and show that it is involved in such regulation. Raising levels of the lncRNA had a concordant effect on Glut1 in cultured human cells and transgenic mice; reducing levels elicited the opposite effect. Delivering the lncRNA to Glut1DS model mice via viral vectors induced Glut1 expression, enhancing brain glucose levels to mitigate disease. Direct delivery of such a lncRNA to combat disease has not been reported previously and constitutes a unique therapeutic paradigm. Moreover, considering the importance of maintaining homeostatic Glut1 levels, calibrating transporter expression via the lncRNA could become broadly relevant to the myriad conditions, including Alzheimers disease, wherein Glut1 concentrations are perturbed.

neuroscience↗

bioRxiv2025

Characterization and targeting of the endosomal signaling of the gastrin releasing peptide receptor in pruritus.

Chronic pruritus is a major unmet clinical problem affecting one in four adults. G protein-coupled receptors (GPCRs) are key receptors driving itch signaling and are a therapeutic target for itch relief. The endosomal signaling of GPCRs provides new challenges for understanding how GPCR signaling is regulated, how endosomal signaling of GPCRs contributes to disease states like chronic pruritus and opens new targets for therapeutic development. The Gastrin releasing peptide receptor (GRPR) is a key mediator of pruritus in the spinal cord. Yet, little is known about the molecular mechanisms regulating GRPR signaling in pruritus, if GRPR can signal from endosomes, or the role of endosomal GRPR in the development of pruritus. Here we show the importance of internalization and endosomal signaling of GRPR in pruritus. Agonist induced GRPR internalization and trafficking was quantified using BRET or microscopy while endosomal-mediated ERK signaling was measured using compartmentalized FRET biosensors. Recruitment of G proteins to endosomes was measured with NanoBit BRET. pH sensitive mesoporous silica nanoparticles (MSN) which accumulated in endosomes were used to deliver RC-3095, a GRPR specific antagonist, intracellularly to block endosomal signaling of GRPR. MSN-RC proved more effective than free RC-3095 at inhibiting chloroquine scratching in mice. Our results demonstrate a critical role for GRPR endosomal signaling in itch sensation. These results highlight the ability of endosomally targeted antagonist to inhibit GRPR signaling and provide a new target for developing therapeutics that block GRPR mediated pruritus. Significance StatementGPCRs are dynamic signaling receptors that can continue to signal following internalization and trafficking to endosomes. Using subcellular targeted BRET and FRET based biosensors we can quantify the recruitment of signaling partners like G proteins and arrestins to GRPR from the endosomal compartment. Inhibition of clathrin and dynamin mediated endocytosis allowed to differentiate plasma membrane vs endosomal signaling of GRPR. pH sensitive nanoparticles loaded with the GRPR antagonist RC-3095 are endocytosed to the endosomal network where they specifically target and block endosomal GRPR signaling. Intrathecal injection of RC-3095 loaded nanoparticles blocked chloroquine induced scratching behavior in mice. Thus, intracellular GRPR drives itch sensation and targeted inhibition of intracellular GRPR signaling is a more effective strategy to treat pruritus.

neuroscience↗

bioRxiv2024

A single high-zinc activation enhancer can control two genes oriented head-to-head in C. elegans

Enhancers play critical roles in gene expression, but a full understanding of their complex functions has yet to be defined. The cellular response to excess zinc levels in C. elegans requires the HIZR-1 transcription factor, which binds the high-zinc activation (HZA) enhancer in the promoters of multiple target genes. Cadmium hijacks the excess zinc response by binding and activating HIZR-1. By analyzing the genome-wide transcriptional response to excess zinc and cadmium, we identified two positions in the genome where head-to-head oriented genes are both induced by metals. In both examples, a single predicted HZA enhancer is positioned between the two translational start sites. We hypothesized that a single enhancer can control both head-to-head genes, an arrangement that has not been extensively characterized. To test this hypothesis, we used CRISPR genome editing to precisely delete the HZAmT enhancer positioned between mtl-2 and T08G5.1; in this mutant, both head-to-head genes display severely reduced zinc-activated transcription, whereas zinc-activated transcription of more distant genes was not strongly affected. Deleting the HZAcF enhancer positioned between cdr-1 and F35E8.10 caused both head-to-head genes to display reduced cadmium-activated transcription, whereas cadmium-activated transcription of more distant genes was not strongly affected. These studies rigorously document that a single HZA enhancer can control two head-to-head genes, advancing our understanding of the diverse functions of enhancers. Article SummaryEnhancers are critical for gene expression, but a full understanding their functions has yet to be elucidated. We discovered two positions in the C. elegans genome where a pair of head-to-head oriented genes are both transcriptionally activated by excess zinc and/or cadmium; in both cases, one high-zinc activation (HZA) enhancer is positioned between the translation start sites. When these HZA enhancers were deleted by genome engineering, both head-to-head genes lost metal-activated transcription. These results demonstrate that a single HZA enhancer can control two head-to-head genes, advancing the understanding of enhancer function.

genetics↗

bioRxiv2024

Touch to text: Spatiotemporal evolution of braille letter representations in blind readers

Visual deprivation does not silence the visual cortex, which is responsive to auditory, tactile, and other nonvisual tasks in blind persons. However, the underlying functional dynamics of the neural networks mediating such crossmodal responses remain unclear. Here, using braille reading as a model framework to investigate these networks, we presented sighted (N=13) and blind (N=12) readers with individual visual print and tactile braille alphabetic letters, respectively, during MEG recording. Using time-resolved multivariate pattern analysis and representational similarity analysis, we traced the alphabetic letter processing cascade in both groups of participants. We found that letter representations unfolded more slowly in blind than in sighted brains, with decoding peak latencies [~]200 ms later in braille readers. Focusing on the blind group, we found that the format of neural letter representations transformed within the first 500 ms after stimulus onset from a low-level structure consistent with peripheral nerve afferent coding to high-level format reflecting pairwise letter embeddings in a text corpus. The spatiotemporal dynamics of the transformation suggest that the processing cascade proceeds from a starting point in somatosensory cortex to early visual cortex and then to inferotemporal cortex. Together our results give insight into the neural mechanisms underlying braille reading in blind persons and the dynamics of functional reorganization in sensory deprivation.

neuroscience↗

bioRxiv2024

Imaging the large-scale and cellular cortical response to focal traumatic brain injury in mouse neocortex

Traumatic brain injury (TBI) affects neural function at the local injury site and also at distant, connected brain areas. However, the real-time neural dynamics in response to injury and subsequent effects on sensory processing and behavior are not fully resolved, especially across a range of spatial scales. We used in vivo calcium imaging in awake, head-restrained male and female mice to measure large-scale and cellular resolution neuronal activation, respectively, in response to a mild/moderate TBI induced by focal controlled cortical impact (CCI) injury of the motor cortex (M1). Widefield imaging revealed an immediate CCI-induced activation at the injury site, followed by a massive slow wave of calcium signal activation that traveled across the majority of the dorsal cortex within approximately 30 s. Correspondingly, two-photon calcium imaging in primary somatosensory cortex (S1) found strong activation of neuropil and neuronal populations during the CCI-induced traveling wave. A depression of calcium signals followed the wave, during which we observed atypical activity of a sparse population of S1 neurons. Longitudinal imaging in the hours and days after CCI revealed increases in the area of whisker-evoked sensory maps at early time points, in parallel to decreases in cortical functional connectivity and behavioral measures. Neural and behavioral changes mostly recovered over hours to days in our M1-TBI model, with a more lasting decrease in the number of active S1 neurons. Our results in unanesthetized mice describe novel spatial and temporal neural adaptations that occur at cortical sites remote to a focal brain injury.

neuroscience↗

bioRxiv2024

Sensory and perceptual decisional processes underlying the perception of reverberant auditory environments

Reverberation, a ubiquitous feature of real-world acoustic environments, exhibits statistical regularities that human listeners leverage to self-orient, facilitate auditory perception, and understand their environment. Despite the extensive research on sound source representation in the auditory system, it remains unclear how the brain represents real-world reverberant environments. Here, we characterized the neural response to reverberation of varying realism by applying multivariate pattern analysis to electroencephalographic (EEG) brain signals. Human listeners (12 male and 8 female) heard speech samples convolved with real-world and synthetic reverberant impulse responses and judged whether the speech samples were in a "real" or "fake" environment, focusing on the reverberant background rather than the properties of speech itself. Participants distinguished real from synthetic reverberation with [~]75% accuracy; EEG decoding reveals a multistage decoding time course, with dissociable components early in the stimulus presentation and later in the peri-offset stage. The early component predominantly occurred in temporal electrode clusters, while the later component was prominent in centro-parietal clusters. These findings suggest distinct neural stages in perceiving natural acoustic environments, likely reflecting sensory encoding and higher-level perceptual decision-making processes. Overall, our findings provide evidence that reverberation, rather than being largely suppressed as a noise-like signal, carries relevant environmental information and gains representation along the auditory system. This understanding also offers various applications; it provides insights for including reverberation as a cue to aid navigation for blind and visually impaired people. It also helps to enhance realism perception in immersive virtual reality settings, gaming, music, and film production. SIGNIFICANCEIn real-world environments, multiple acoustic signals coexist, typically reflecting off innumerable surrounding surfaces as reverberation. While reverberation is a rich environmental cue and a ubiquitous feature in acoustic spaces, we do not fully understand how our brains process a signal usually treated as a distortion to be ignored. When asking human participants to make perceptual judgments about reverberant sounds during EEG recordings, we identified distinct, sequential stages of neural processing. The perception of acoustic realism first involves encoding low-level reverberation acoustic features and their subsequent integration into a coherent environment representation. This knowledge provides insights for enhancing realism in immersive virtual reality, music, and film production, and using reverberation to guide navigation for blind and visually impaired people.

neuroscience↗

bioRxiv2024

The transformation of sensory to perceptual braille letter representations in the visually deprived brain

1.Experience-based plasticity of the human cortex mediates the influence of individual experience on cognition and behavior. The complete loss of a sensory modality is among the most extreme such experiences. Investigating such a selective, yet extreme change in experience allows for the characterization of experience-based plasticity at its boundaries. Here, we investigated information processing in individuals who lost vision at birth or early in life by probing the processing of braille letter information. We characterized the transformation of braille letter information from sensory representations depending on the reading hand to perceptual representations that are independent of the reading hand. Using a multivariate analysis framework in combination with fMRI, EEG and behavioral assessment, we tracked cortical braille representations in space and time, and probed their behavioral relevance. We located sensory representations in tactile processing areas and perceptual representations in sighted reading areas, with the lateral occipital complex as a connecting "hinge" region. This elucidates the plasticity of the visually deprived brain in terms of information processing. Regarding information processing in time, we found that sensory representations emerge before perceptual representations. This indicates that even extreme cases of brain plasticity adhere to a common temporal scheme in the progression from sensory to perceptual transformations. Ascertaining behavioral relevance through perceived similarity ratings, we found that perceptual representations in sighted reading areas, but not sensory representations in tactile processing areas are suitably formatted to guide behavior. Together, our results reveal a nuanced picture of both the potentials and limits of experience-dependent plasticity in the visually deprived brain.

neuroscience↗

bioRxiv2023

Genomic insights into post-domestication expansion and selection of body size in ponies

Horses domestication revolutionized human civilization by changing transportation, farming, and warfare patterns. Despite extensive studies on modern domestic horse origins, the intricate demographic history and genetic signatures of pony size demand further exploration. Here, we present a high-quality genome of the Chinese Debao pony and extensively analyzed 385 individuals from 49 horse breeds. We reveal the conservation of ancient components in East Asian horses and close relationships between Asian horses and specific European pony lineages. Genetic analysis uncovers Asian paternal origin for European pony breeds, and these pony-sized horses share a close genetic affinity due to the presence of a potential ancestral ghost pony population. Additionally, we identify promising cis-regulatory elements influencing horse withers height by regulating genes like RFLNA and FOXO1. Overall, our study provides insightful perspectives into the development history and genetic determinants underlying body size in ponies and offers broader implications for horse population management and improvement. TeaserDecoding pony genetics: exploring origins and size determinants sheds light on their historical and biological impacts.

genomics↗

bioRxiv2023

Yeast Ixr1 mediates the DNA replication stress response through it HMGB DNA binding domains and interaction with checkpoint Mrc1

BackgroundHigh mobility group box (HMGB) family protein Ixr1 has been shown to be involved in DNA damage repair, however, its role and mechanism remain largely unclear. MethodsGenes of S. cerevisiae were deleted or tagged with myc, GFP, or mcherry using the lithium acetate method. Sensitivity of strains to hydroxyurea (HU), methyl methanesulfonate (MMS), camptothe-cin (CPT), 4-nitroquinoline N-oxide (4-NQ), or Zeocin was tested. Distribution of GFP or mcherry fusion proteins was visualized with laser scanning confocal microscopy. RNA-seq was used to determine differential gene expression between mutant and control strains. ResultsIxr1 deletion (ixr1{Delta}) mutant strain was sensitive to HU. Additionally, phosphorylation of effector of DNA damage checkpoint kinase Rad53 was lower in ixr1{Delta} than WT. Deletion of DNA damage checkpoint mediators ixr1{Delta} Rad9{Delta} was more sensitive to HU than ixr1{Delta} or Rad9{Delta}, and ixr1{Delta} mrc1{Delta} had similar sensitivity to HU as mrc1{Delta} but stronger than ixr1{Delta}. Deletion of ribonucleotide reductase inhibitors sml1{Delta} or crt10{Delta} didnt reduce the sensitivity of ixr1{Delta} induced by HU. Repli-cation fork nuclease exo1{Delta} ixr1{Delta} or helicase sgs1{Delta} ixr1{Delta} double deletions were more sensitive to HU than single deletion. In addition, laser scanning confocal microscopy imaging indicated that in response to HU, Ixr1 may be in the same pathway as Mrc1, possibly downstream. Gene Ontol-ogy enrichment analysis of differentially expressed genes (DEGs) between ixr1{Delta} and wildtype, untreated and treated with HU, confirmed that Ixr1 plays an important role in regulating the transcription of genes related to DNA replication or DNA damage repair. We also found that, re-gardless of HU exposure, Ixr1 localized to the nucleus and may bind DNA through its two HMG-boxes. ConclusionIxr1 participates in the DNA replication stress response through a DNA damage checkpoint pathway mediated by Mrc1, and regulates expression of genes related to DNA damage repair.

genetics↗

bioRxiv2023

Modulation of infraslow oscillation in the dentate gyrus during Non-REM sleep

Synchronous neuronal activity is organized into neuronal oscillations with various frequency and time domains across different brain areas and brain states. For example, hippocampal theta, gamma and sharp wave oscillations are critical for memory formation and communication between hippocampal subareas and the cortex. In this study, we investigated the neuronal activity of the dentate gyrus (DG) with optical imaging tools during sleep-wake cycles. We found that the activity of major glutamatergic cell populations in the DG is organized into infraslow oscillations (0.01 - 0.03 Hz) during NREM sleep. Although the DG is considered a sparsely active network during wakefulness, we found that 50% of granule cells and about 25% of mossy cells exhibit increased activity during NREM sleep, compared to that during wakefulness. Further experiments revealed that the infraslow oscillation in the DG was correlated with rhythmic serotonin release during sleep, which oscillates at the same frequency but in an opposite phase. Genetic manipulation of 5-HT receptors revealed that this neuromodulatory regulation is mediated by 5-HT1a receptors and the knockdown of these receptors leads to memory impairment. Together, our results provide novel mechanistic insights into how the 5-HT system can influence hippocampal activity patterns during sleep.

neuroscience↗