Biology subjects

Lu, J.

Publications and source records attributed to Lu, J..

At least 181 records · Page 10Linked to original sources

bioRxiv2024

Axo-axonic synaptic input drives homeostatic plasticity by tuning the axon initial segment structurally and functionally

The stability of functional brain network is maintained by homeostatic plasticity, which restores equilibrium following perturbation. As the initiation site of action potentials, the axon initial segment (AIS) of glutamatergic projection neurons (PyNs) undergoes dynamic adjustment that exerts powerful control over neuronal firing properties in response to changes in network states. Although AIS plasticity has been reported to be coupled with the changes of network activity, it is poorly understood whether it involves direct synaptic input to the AIS. Here we show that changes of GABAergic synaptic input to the AIS of cortical PyNs, specifically from chandelier cells (ChCs), are sufficient to drive homeostatic tuning of the AIS within 1-2 weeks, while those from parvalbumin-positive basket cells do not. This tuning is reflected in the morphology of the AIS, the expression level of voltage-gated sodium channels, and the intrinsic neuronal excitability of PyNs. Interestingly, the timing of AIS tuning in PyNs of the prefrontal cortex corresponds to the recovery of changes in social behavior caused by alterations of ChC synaptic transmission. Thus, homeostatic plasticity of the AIS at postsynaptic PyNs may counteract deficits elicited by imbalanced ChC presynaptic input. TeaserAxon initial segment dynamically responds to changes in local input from chandelier cells to prevent abnormal neuronal functions.

neuroscience↗

bioRxiv2024

Inactivation of a non-canonical gp130 signaling arm attenuates chronic systemic inflammation and multimorbidity induced by a high-fat diet.

Interleukin-6 (IL-6) is a major pro-inflammatory cytokine for which the levels in plasma demonstrate a robust correlation with age and body mass index (BMI) as part of the senescence-associated secretory phenotype. IL-6 cytokines also play a crucial role in metabolic homeostasis and regenerative processes, primarily via the canonical STAT3 pathway. Thus, selective modulation of IL-6 signaling may offer a unique opportunity for therapeutic interventions. Recently, we discovered that a non-canonical signaling pathway downstream of tyrosine (Y) 814 within the intracellular domain of gp130, the IL-6 co-receptor, is responsible for the recruitment and activation of SRC family of kinases (SFK). Mice with constitutive genetic inactivation of gp130 Y814 (F814 mice) show accelerated resolution of inflammatory response and superior regenerative outcomes in skin wound healing and posttraumatic models of osteoarthritis. The current study was designed to explore if selective genetic or pharmacological inhibition of the non-canonical gp130-Y814/SFK signaling reduces systemic chronic inflammation and multimorbidity in a high-fat diet (HFD)-induced model of accelerated aging. F814 mice showed significantly reduced inflammatory response to HFD in adipose and liver tissue, with significantly reduced levels of systemic inflammation compared to wild type mice. F814 mice were also protected from HFD-induced bone loss and cartilage degeneration. Pharmacological inhibition of gp130-Y814/SFK in mice on HFD mirrored the effects observed in F814 mice on HFD; furthermore, this pharmacological treatment also demonstrated a marked increase in physical activity levels and protective effects against inflammation-associated suppression of neurogenesis in the brain tissue compared to the control group. These findings suggest that selective inhibition of SFK signaling downstream of gp130 receptor represents a promising strategy to alleviate systemic chronic inflammation. Increased degenerative changes and tissue senescence are inevitable in obese and aged organisms, but we demonstrated that the systemic response and inflammation-associated multi-morbidity can be therapeutically mitigated.

cell biology↗

bioRxiv2024

How short peptides can disassemble ultra-stable tau fibrils extracted from Alzheimers disease brain by a strain-relief mechanism

Reducing fibrous aggregates of protein tau is a possible strategy for halting progression of Alzheimers disease (AD). Previously we found that in vitro the D-peptide D-TLKIVWC disassembles tau fibrils from AD brains (AD-tau) into benign segments with no energy source present beyond ambient thermal agitation. This disassembly by a short peptide was unexpected, given that AD-tau is sufficiently stable to withstand disassembly in boiling SDS detergent. To consider D peptide-mediated disassembly as a potential therapeutic for AD, it is essential to understand the mechanism and energy source of the disassembly action. We find assembly of D-peptides into amyloid-like fibrils is essential for tau fibril disassembly. Cryo-EM and atomic force microscopy reveal that these D-peptide fibrils have a right-handed twist and embrace tau fibrils which have a left-handed twist. In binding to the AD-tau fibril, the oppositely twisted D-peptide fibril produces a strain, which is relieved by disassembly of both fibrils. This strain-relief mechanism appears to operate in other examples of amyloid fibril disassembly and provides a new direction for the development of first-in-class therapeutics for amyloid diseases.

neuroscience↗

bioRxiv2024

Normative growth modeling of brain morphology reveals neuroanatomical heterogeneity and biological subtypes in children with ADHD

BackgroundNeuroimaging studies suggest substantial individual heterogeneity in brain phenotypes in attention-deficit/hyperactivity disorder (ADHD). However, how these individual-level brain phenotypes contribute to the identification of ADHD biotypes and whether these biotypes have different treatment outcomes and neurobiological underpinnings remain largely unknown. MethodsWe collected multisite, high-quality structural magnetic resonance imaging data from 1,006 children aged 6-14 years, including 351 children with ADHD and 655 typically developing children. Normative growth models of cortical thickness were established for 219 regions in the typically developing children. Individual-level deviations from these normal references were quantified and clustered to identify ADHD biotypes. We validated the replicability and generalizability of the ADHD biotypes using two independent datasets and evaluated the associations of the biotypes with symptomatic, cognitive, and gene expression profiles, as well as follow-up treatment outcomes. FindingsNo more than 10% of children with ADHD had extreme deviations in cortical thickness in a single region, suggesting high heterogeneity among individuals with ADHD. On the basis of the brain deviation maps, we discovered two robust ADHD biotypes, an infra-normal subtype with cortical thinning associated with ADHD symptoms and a supranormal subtype with cortical thickening associated with cognition. Patients with the infra-normal subtype responded better to methylphenidate than to atomoxetine, although both subtypes showed treatment efficacy. Brain deviations in the infra-normal subtype were explained by the expression levels of genes enriched in presynaptic and axonal development and polygenic risk of ADHD. InterpretationWe identified anatomically distinct, clinically valuable, and biologically informed ADHD subtypes, providing insight into the neurobiological basis of clinical heterogeneity and facilitating a personalized medication strategy for ADHD patients. Panel: Research in contextO_ST_ABSEvidence before this studyC_ST_ABSSubstantial individual heterogeneity in brain phenotypes in attention-deficit/hyperactivity disorder (ADHD) motivates the need to discover homogeneous biotypes. We searched PubMed for research articles on ADHD biotypes using brain MRI published before December 1, 2023, using the search terms ((attention deficit hyperactivity disorder [Title/Abstract]) OR (ADHD [Title/Abstract])) AND ((subtypes [Title/Abstract]) OR (subgroups [Title/Abstract]) OR (subtyping [Title/Abstract])) AND ((MRI [Title/Abstract]) OR (neuroimaging [Title/Abstract]) OR (brain [Title/Abstract])) without language restrictions. Of the eight included studies, two identified ADHD biotypes using structural morphology, four used functional activity, and two used multimodal features. However, none of these studies considered the developmental effect of the brain phenotypes, examined treatment response, or investigated the genetic correlates of the biotypes. Added value of this studyThis study is the first to use individualized brain measures extracted from normative models to investigate ADHD biotypes in a large sample of more than 1,000 children. We identified two reproducible ADHD biotypes, characterized by distinct symptomatic, cognitive, and gene expression profiles, as well as differential treatment responses. This study advances our understanding of the neurobiological basis underlying the clinical heterogeneity of ADHD and highlights the critical need to discover ADHD biotypes using an unbiased and individualized approach. Implications of all the available evidenceThis study revealed remarkable neuroanatomical heterogeneity in ADHD patients and identified anatomically distinct, clinically valuable, and biologically informed ADHD biotypes. Our findings have potential value for the investigation of data-driven biotypes to evaluate treatment efficacy and facilitate personalized treatment. We also highlight the need for future studies to move beyond the understanding of ADHD solely based on the "average patient" perspective.

neuroscience↗

bioRxiv2024

A brain-to-text framework of decoding natural tonal sentences

Speech brain-computer interfaces (BCIs) directly translate brain activity into speech sound and text, yet decoding tonal languages like Mandarin Chinese poses a significant, unexplored challenge. Despite successful cases in non-tonal languages, the complexities of Mandarin, with its distinct syllabic structures and pivotal lexical information conveyed through tonal nuances, present challenges in BCI decoding. Here we designed a brain-to-text framework to decode Mandarin tonal sentences from invasive neural recordings. Our modular approach dissects speech onset, base syllables, and lexical tones, integrating them with contextual information through Bayesian likelihood and the Viterbi decoder. The results demonstrate accurate tone and syllable decoding under variances in continuous naturalistic speech production, surpassing previous intracranial Mandarin tonal syllable decoders in decoding accuracy. We also verified the robustness of our decoding framework and showed that the model hyperparameters can be generalized across participants of varied gender, age, education backgrounds, pronunciation behaviors, and coverage of electrodes. Our pilot study shed lights on the feasibility of more generalizable brain-to-text decoding of natural tonal sentences from patients with high heterogeneities.

neuroscience↗

bioRxiv2024

Unveiling the Intricate Sinking behavior of Large Diatoms: Insights from Time-Frequency Analysis of Palmerina hardmaniana Sinking under Silicate-Depleted Conditions

Nutrient limits impact diatom sinking in time domain, but response in time-frequency domain is unclear. Studying the response of large diatoms to nutrients exclusively in the time domain fails to fully capture the complete impact of nutrient limitations on sinking behavior due to the absence of crucial information, including period and frequency. Wavelet analysis provides valuable insights into the period and frequency of signals and unveils their positions in the time. This study investigated the sinking behavior response of the large diatom Palmerina hardmaniana to silicate-depleted conditions in the time-frequency domain using wavelet analysis. The results showed that P. hardmaniana was capable of regulating its sinking speed, and this regulation occurred intermittently in time. The predominant frequency of intermittent regulation fell within the range of 0.13-0.50 Hz (equivalent to a period of 2-8 s) for both control and silicate-depleted conditions. The similarity in the frequency range of regulation between the two groups suggests the involvement of shared physiological mechanisms. P. hardmaniana responded to silicate depletion by intensifying the regulation of 0.13-0.50 Hz, which was reflected in the time domain as a change in the proportion of different instantaneous sinking speeds and consequently lead to a significant increase or decrease in the mean sinking speed (p<0.05). Additionally, the regulation of P. hardmaniana sinking behavior was also influenced by the physiological state of the cells. Short-term silicate stress (30 min) enhanced the oscillation power of sinking regulation, while prolonged silicate stress ([≥] 3 d) led to a decline in oscillation power.

plant biology↗

bioRxiv2024

Non-viral Intron Knockins Enable Simplified and Flexible Targeting of Endogenous Genes

Targeting new genetic material to endogenous genes has opened diverse therapeutic and research applications, but current exon-based targeting methods have limited integration sites and are compatible only with complex or harsh selection methods. We present non-viral intron targeting, integrating large synthetic exons into endogenous introns to increase targeting flexibility and simplify selection of successfully edited cells. Engineered control of large synthetic exons splicing behavior further generalizes cell and gene therapy applications of non-viral intron knockins.

bioengineering↗

bioRxiv2024

Ubiquitin-mediated stabilization of SlPsbS regulates low night temperature tolerance in tomatoes

Non-photochemical quenching (NPQ) plays a fundamental role in safely operating photosynthesis under low night temperatures (LNT). PsbS protein is essential for the rapid induction of NPQ, and its stability is often affected by adverse environmental conditions. However, the regulatory mechanism for the stability of PsbS or chloroplast proteins remains to be fully characterized. We showed that LNT decreased NPQ levels and SlPsbS protein abundance in tomato leaves. COP9 signalosome subunit 5A (SlCSN5A) facilitated SlPsbS ubiquitination and degradation in the cytosol. Further, tomato chloroplast vesiculation (SlCV) was activated by LNT. Under LNT, SlCV targeted the chloroplasts and induced the formation of CV-containing vesicles (CCVs) containing SlPsbS, which were exported from the chloroplasts. Subsequently, SlCV and SlPsbS contact SlCSN5A in the cytosol and are ubiquitinated and degraded. Genetic evidence demonstrated that overexpression of SlCV aggravated SlPsbS protein degradation, whereas silencing of SlCSN5 and SlCV delayed LNT-induced NPQ reduction and SlPsbS protein turnover. This study provides evidence that CSN5A is associated with chloroplast proteins, and reveals a ubiquitin-dependent degradation pathway of chloroplast proteins co-mediated by CV and CSN5A, thereby providing new insights into the regulation of chloroplast protein stability under stress conditions.

plant biology↗

bioRxiv2024

Spatially Exploring RNA Biology in Archival Formalin-Fixed Paraffin-Embedded Tissues

Spatial transcriptomics has emerged as a powerful tool for dissecting spatial cellular heterogeneity but as of today is largely limited to gene expression analysis. Yet, the life of RNA molecules is multifaceted and dynamic, requiring spatial profiling of different RNA species throughout the life cycle to delve into the intricate RNA biology in complex tissues. Human disease-relevant tissues are commonly preserved as formalin-fixed and paraffin-embedded (FFPE) blocks, representing an important resource for human tissue specimens. The capability to spatially explore RNA biology in FFPE tissues holds transformative potential for human biology research and clinical histopathology. Here, we present Patho-DBiT combining in situ polyadenylation and deterministic barcoding for spatial full coverage transcriptome sequencing, tailored for probing the diverse landscape of RNA species even in clinically archived FFPE samples. It permits spatial co-profiling of gene expression and RNA processing, unveiling region-specific splicing isoforms, and high-sensitivity transcriptomic mapping of clinical tumor FFPE tissues stored for five years. Furthermore, genome-wide single nucleotide RNA variants can be captured to distinguish different malignant clones from non-malignant cells in human lymphomas. Patho-DBiT also maps microRNA-mRNA regulatory networks and RNA splicing dynamics, decoding their roles in spatial tumorigenesis trajectory. High resolution Patho-DBiT at the cellular level reveals a spatial neighborhood and traces the spatiotemporal kinetics driving tumor progression. Patho-DBiT stands poised as a valuable platform to unravel rich RNA biology in FFPE tissues to study human tissue biology and aid in clinical pathology evaluation.

systems biology↗

bioRxiv2024

Identification and Structural Characterization of a mutant KRAS-G12V specific TCR restricted by HLA-A3

Mutations in KRAS are some of the most common across multiple cancer types and are thus attractive targets for therapy. Recent studies demonstrated that mutant KRAS generates immunogenic neoantigens that can be targeted in adoptive T cell therapy in metastatic diseases. To expand mutant KRAS specific immunotherapies, it is critical to identify additional HLA-I allotypes that can present KRAS neoantigens and their cognate T cell receptors (TCR). Here, we identified a murine TCR specific to a KRAS-G12V neoantigen (7VVVGAVGVGK16) using a vaccination approach with transgenic mice expressing the common HLA-I allotype, HLA-A*03:01 (HLA-A3). This TCR demonstrated exquisite specificity for mutant G12V and not Wt KRAS peptides. To investigate the molecular basis for neoantigen recognition by This TCR, we determined its structure in complex with HLA-A3(G12V). G12V-TCR CDR3{beta} and CDR1 {beta} formed a hydrophobic pocket to interact with p6 Val of the G12V but not Wt KRAS peptide. To improve the tumor sensitivity of This TCR, we designed rational substitutions to improve TCR:HLA-A3 contacts. Two substitutions exhibited modest improvements in TCR binding to HLA-A3 (G12V), but did not sufficiently improve T cell sensitivity for further clinical development. Our study provides mechanistic insight into how TCRs detect neoantigens and reveals the challenges in targeting KRAS-G12V mutations. [203]

immunology↗

bioRxiv2024

Novel metagenomics analysis suggests a Vibrio species is associated with stony coral tissue loss disease

Stony coral tissue loss disease (SCTLD) has devastated coral reefs off the coast of Florida and continues to spread throughout the Caribbean. Although a number of bacterial taxa have consistently been associated with SCTLD, no pathogen has been definitively implicated in the etiology of SCTLD. Previous studies have predominantly focused on the prokaryotic community through 16S rRNA sequencing of healthy and affected tissues. Here, we provide a different analytical approach by applying a bioinformatics pipeline to publicly available metagenomic sequencing samples of SCTLD lesions and healthy tissues from four stony coral species. To compensate for the lack of coral reference genomes, we used data from apparently healthy coral samples to approximate a host genome and healthy microbiome reference. These reads were then used as a reference to which we matched and removed reads from diseased lesion tissue samples, and the remaining reads associated only with disease lesions were taxonomically classified at the DNA and protein levels. For DNA classifications, we used a pathogen identification protocol originally designed to identify pathogens in human tissue samples, and for protein classifications, we used a fast protein sequence aligner. To assess the utility of our pipeline, a species-level analysis of a candidate genus, Vibrio, was used to demonstrate the pipelines effectiveness. Our approach revealed both complementary and unique coral microbiome members compared to a prior metagenome analysis of the same dataset. Article SummaryStudies of stony coral tissue loss disease (SCTLD), a devastating coral disease, have primarily used 16S rRNA sequencing approaches to identify putative pathogens. In contrast, this study applied human tissue pathogen identification protocols to SCTLD metagenomic DNA samples. Diseased samples were filtered of host sequences using a k-mer based method since host genomes were unavailable. DNA and protein-level classifications from this novel approach revealed both complementary and unique microbiome members compared to a prior metagenome analysis of the same dataset.

bioinformatics↗

bioRxiv2023

INHBA/Activin A promotes tumor growth and induces resistance to anti-PD-L1 therapy by suppressing IFN-γ signaling

Inhibin beta A (INHBA) and its homodimer activin A have pleiotropic effects on modulation of immune responses and tumor progression, respectively, but it remains uncertain whether tumors may release activin A to regulate anti-tumor immunity. As evidenced by our RNA-Seq and in vitro results, the interferon-{gamma} (IFN-{gamma}) signaling pathway was significantly down-regulated by tumor intrinsic activin A. Tumor INHBA deficiency led to lower expression of PD-L1 induced by IFN-{gamma}, resulting in poor responsiveness to anti-PD-L1 therapy. On the other hand, decreased secretion of IFN-{gamma}-stimulated chemokines, including C-X-C motif chemokine 9 (CXCL9) and 10 (CXCL10), impaired the infiltration of effector T cells into the tumor microenvironment. Furthermore, the activin A-specific antibody garetosmab improved anti-tumor immunity and its combination with the anti-PD-L1 antibody atezolizumab showed a superior therapeutic effect to monotherapy. Our findings reveal that INHBA/activin A is involved in anti-tumor immunity by inhibiting the IFN-{gamma} signaling pathway and considered to be a potential target to overcome anti-PD-L1 resistance in clinical cancer treatment.

immunology↗

bioRxiv2023

The Myc-Like Mlx Network Impacts Aging and Metabolism

The "Mlx" and "Myc" Networks share many common gene targets. Just as Mycs activity depends upon its heterodimerization with Max, the Mlx Network requires that the Max-like factor Mlx associate with the Myc-like factors MondoA or ChREBP. We show here that body-wide Mlx inactivation, like that of Myc, accelerates numerous aging-related phenotypes pertaining to body habitus and metabolism. The deregulation of numerous aging-related Myc target gene sets is also accelerated. Among other functions, these gene sets often regulate ribosomal and mitochondrial structure and function, genomic stability and aging. Whereas "MycKO" mice have an extended lifespan because of a lower cancer incidence, "MlxKO" mice have normal lifespans and a somewhat higher cancer incidence. Like Myc, Mlx, MondoA and ChREBP expression and that of their target genes, deteriorate with age in both mice and humans, underscoring the importance of life-long and balanced cross-talk between the two Networks to maintain normal aging. TeaserInactivation of the Myc-like "Mlx Network" in mice leads to phenotypic and molecular signs of premature aging and a cancer predisposition.

cancer biology↗

bioRxiv2023

A microfluidic platform with integrated porous membrane cell-substrate impedance spectroscopy (PM-ECIS) for biological barrier assessment

Traditionally, biological barriers are assessed in vitro by measuring trans-endothelial/epithelial electrical resistance (TEER) across a monolayer using handheld chopstick electrodes. Implementation of TEER into organ-on-chip (OOC) setups is a challenge however, due to non-uniform current distribution and interference from biomaterials typically found in such systems. In this work, we address the pitfalls of standard TEER measurement through the application of porous membrane electrical cell-substrate impedance sensing (PM-ECIS) to an OOC setup. Gold leaf electrodes (working electrode diameters = 250, 500, 750 {micro}m) were incorporated onto porous membranes and combined with biocompatible tape to assemble microfluidic devices. PM-ECIS resistance at 4 kHz was not influenced by presence of collagen hydrogel in bottom channels, compared to TEER measurements in same devices, which showed a difference of 1723 {+/-} 381.8 {Omega} (p=0.006) between control and hydrogel conditions. A proof of concept, multi-day co-culture model of the blood-brain barrier was also demonstrated in these devices. PM-ECIS measurements were robust to fluid shear (5 dyn/cm2) in cell-free devices, yet were highly sensitive to flow-induced changes in an endothelial barrier model. Initiation of perfusion (0.06 dyn/cm2) in HUVEC-seeded devices corresponded to significant decreases in impedance at 40 kHz (p<0.01 for 750 and 500 {micro}m electrodes) and resistance at 4 kHz (p<0.05 for all electrode sizes) relative to static control cultures, with minimum values reached at 6.5 to 9.5 hours after induction of flow. Our microfluidic PM-ECIS platform enables sensitive, non-invasive, real-time measurements of barrier function in setups integrating critical OOC features like 3D co-culture, biomaterials and shear stress.

bioengineering↗

bioRxiv2023

Upstream open reading frames dynamically modulate CLOCK protein translation to regulate circadian rhythm and sleep

The circadian rhythm is an evolutionarily conserved mechanism with translational regulation increasingly recognized as pivotal in its modulation. In this study, we found that upstream open reading frames (uORFs) are enriched in circadian rhythm genes, with particularly conserved uORFs present in core circadian clock genes. We demonstrate evidence that the uORFs of the core clock gene, Clock (Clk), rhythmically and substantially attenuate CLK protein translation in Drosophila, with pronounced suppression occurring during daylight hours. Eliminating Clk uORFs results in elevated CLK protein levels during the day and a compressed circadian cycle, along with a broad shift in clock gene expression rhythms. Interestingly, Clk uORF deletion also augments morning sleep by reducing dopaminergic activity. Beyond daily circadian adjustments, Clk uORFs play a role in modulating sleep patterns in response to the varying day lengths of different seasons, inhibiting translation in a day-length contingent manner. Furthermore, the Clk uORFs act as a master regulator to shape the rhythmic expression of a vast array of genes and influence multifaceted physiological outcomes. Collectively, our research sheds light on the intricate ways uORFs dynamically adjust downstream coding sequences to acclimate to environmental shifts.

neuroscience↗

bioRxiv2023

Siderophore Piracy Promotes Dynamical Coexistence in Microbial Community

Niche construction drives ecological dynamics, yet the tragedy of the commons predicts that non-contributing cheaters will undermine cooperation. Here, we studied microbial iron competition by combining dynamic modeling with benefit flow graphs, demonstrating that moderate cheating is not merely tolerated but essential for diversity. In small communities, mutual exploitation forms closed loops enabling steady or dynamic coexistence. In larger communities, we uncovered a paradox: increasing cheating breadth promotes community-level extinction, yet fosters higher biodiversity in surviving communities. We resolve this paradox by mapping ecological dynamics onto the topology of the "Maximal Benefit Transfer Graph", which predicts community fate through its core structure. Broad cheating eliminates the self-loop core that drives competitive exclusion, but increases "terminator" sinks that cause collapse. However, when communities avoid these sinks, cheating aggregates the network and generates cyclic loops to enable coexistence. Thus, structured exploitation acts not as destabilizing vulnerability but as necessary architecture for biodiversity. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/568182v3_ufig1.gif" ALT="Figure 1"> View larger version (42K): org.highwire.dtl.DTLVardef@143f144org.highwire.dtl.DTLVardef@194c2adorg.highwire.dtl.DTLVardef@1792d4aorg.highwire.dtl.DTLVardef@8c96a7_HPS_FORMAT_FIGEXP M_FIG C_FIG How does cheating affect microbial biodiversity? By mapping the strongest benefit flows between species, we discovered a topological rule for survival. While too much cheating creates dead-ends that crash the system, moderate cheating connects species into self-sustaining loops. These "exploitation cycles" act as a scaffold, supporting high diversity and complex population.

systems biology↗

bioRxiv2023

Theta activity discriminates high-level, species-specific body processes

Among social stimuli that trigger rapid reactions, body images occupy a prominent place. Given that bodies carry information about other agents intentions, actions and emotional expressions, a foundational question concerns the neural basis of body processing. Previous fMRI studies have investigated this but were not yet able to clarify the time course and its functional significance. The present EEG study investigated the role of slow oscillatory cortical activity in body processing and species-specificity. Human participants viewed naturalistic images of human and monkey bodies, faces, and objects, along with mosaic-scrambled versions to control for low-level visual features. Analysis of event-related theta power (4 - 7 Hz) combined with data-driven methods revealed a strong, body-evoked neural response that is specific to human bodies and likely originates from a widespread cortical region during a time window of 150 - 550 ms after the onset of the body image. Our results corroborate recent research proposing a widespread, species-specific cortical network of human body processing. We submit that this network may play an essential role in linking body processes to movement intentions.

neuroscience↗

bioRxiv2023

Integrated multi-omics single cell atlas of the human retina

Single-cell sequencing has revolutionized the scale and resolution of molecular profiling of tissues and organs. Here, we present an integrated multimodal reference atlas of the most accessible portion of the mammalian central nervous system, the retina. We compiled around 2.4 million cells from 55 donors, including 1.4 million unpublished data points, to create a comprehensive human retina cell atlas (HRCA) of transcriptome and chromatin accessibility, unveiling over 110 types. Engaging the retina community, we annotated each cluster, refined the Cell Ontology for the retina, identified distinct marker genes, and characterized cis-regulatory elements and gene regulatory networks (GRNs) for these cell types. Our analysis uncovered intriguing differences in transcriptome, chromatin, and GRNs across cell types. In addition, we modeled changes in gene expression and chromatin openness across gender and age. This integrated atlas also enabled the fine-mapping of GWAS and eQTL variants. Accessible through interactive browsers, this multimodal cross-donor and cross-lab HRCA, can facilitate a better understanding of retinal function and pathology.

molecular biology↗