Biology subjects

Hu, J.

Publications and source records attributed to Hu, J..

At least 91 records · Page 5Linked to original sources

bioRxiv2026

Interspecies interactions drive community-level selection in microbial coalescence

It has long been debated in ecology whether communities behave as cohesive units or as loose collections of independent species. Here, we study this question in the context of community coalescence, the mixing of previously isolated communities, using bacterial microcosm experiments combined with ecological modeling. Our results demonstrate that interspecies interaction strength determines whether communities or species are the units of selection during coalescence. When interactions are moderate to strong, one parental community consistently outcompetes the other, indicating community-level selection. In contrast, under weak interactions, species fates are uncorrelated and the two communities contribute equally to the coalesced outcome, indicating the absence of community-level selection. These patterns extend to communities derived from natural samples with greater taxonomic diversity and richness. Furthermore, we identify two distinct regimes underlying community-level selection in experiments with different media conditions: an emergent regime in which collective dynamics shape outcomes that cannot be predicted from species traits alone, and a top-down regime where dominant species determine the winning community. Together, these results reconcile conflicting observations on community-level selection during community coalescence by demonstrating that communities behave as cohesive units only when interactions are sufficiently strong.

ecology↗

bioRxiv2026

Cortex-Wide Cellular Imaging in Freely Locomoting Mice Using Cortex Camera Array Microscope (CortexCAM)

Understanding single-cell neuronal activity across multiple brain regions in the context of ethologically relevant behaviors is a major goal in systems neuroscience. We have engineered the Cortex Camera Array Microscope (CortexCAM), integrating four miniaturized fluorescence imaging microscopes to simultaneously capture cellular activity from contiguous fields of view spanning over 48 mm2 of the dorsal cortex. The CortexCAM is capable of imaging > 9000 individual neurons across much of the primary and secondary motor, somatosensory, visual, retrosplenial, and association cortices across both hemispheres of the dorsal cortex. The compact nature of the CortexCAM allows integration into a passive mechanical gantry system to form the mobile CortexCAM. The mobile CortexCAM allows volitional control of the animals translational motion (x, y) and rotational motion (yaw) in physical behavior arenas. We then use the mobile CortexCAM to perform cortex-wide cellular resolution imaging in freely locomoting mice performing alternating choice tasks, as well as during social interactions. Thus the CortexCAM allows studying cortex-wide cellular dynamics in behaviors that cannot be achieved in headfixed settings.

neuroscience↗

bioRxiv2026

Designing urban green-space heterogeneity across urbanisation gradients to maintain avian richness

Urban expansion drives land cover change and habitat simplification, contributing to biodiversity loss. Urban green spaces can mitigate these impacts, but their effectiveness depends on its configuration and implementation. Here, we examine how three complementary dimensions of environmental heterogeneity--plant species richness, habitat heterogeneity, and foliage-layer richness--shape bird richness along an urbanisation gradient in the Netherlands. Using bird and plant occurrence data, LiDAR-derived vegetation structure, and land-use data, we fitted generalized additive models at three spatial scales (100, 200, and 300 m) to assess how these relationships vary across the urbanisation gradient. Plant species richness showed the strongest and consistent positive effect on bird richness, disregarding urbanization intensities. Habitat heterogeneity showed most pronounced positive effects at intermediate levels of urbanisation. In contrast, foliage-layer richness had weak associations with bird richness across urbanization intensities. Together, these results demonstrate that sustaining urban bird diversity requires urbanisation-intensity-dependent design of green-space heterogeneity. Increasing plant richness is generally recommended across urbanization intensities. Increasing habitat heterogeneity is more effective at intermediate levels of urbanisation and appears less suitable in highly urbanised contexts. Beyond simply expanding green space area or their spatial complexity alone, urban planning should focus on the thoughtful design of different types of environmental heterogeneity. This includes city-wide species-rich planting and structurally diverse habitat mosaics in mid-density areas to sustain urban bird diversity.

ecology↗

bioRxiv2026

Elimination of intramuscular immunoglobulin accumulation alleviates Duchenne Muscular Dystrophy

Duchenne muscular dystrophy (DMD) is a devastating neuromuscular disorder due to loss of dystrophin, a cytoskeletal protein critical for muscle integrity and functionality. Despite recent therapeutic advances, there remains a significant unmet need for more effective and accessible therapeutics. Here, we discovered an early accumulation of immunoglobulin G (IgG) in the sarcolemma, which exacerbates tissue inflammation and disease progression. The IgG accumulation primarily resulted from ectopic localization of Fc{gamma}R1, a high-affinity IgG Fc receptor, on dystrophin-deficient myofibers. In two independent murine models, eliminating IgG accumulation via B cell depletion provided sustained benefit to alleviate DMD progression. Our findings uncover a novel disease accelerator in DMD and demonstrate the potential to target this mechanism as therapeutics for broader population of patients with DMD.

immunology↗

bioRxiv2026

Differential higher-order superassembly of HECT-type UBE3 ligases controlled by calcium signals

The yeast E4 ligase Hul5 transiently associates with the proteasome during heat shock and proteotoxic stress to maintain cytosolic protein quality control. Two of its human orthologs, UBE3B and UBE3C, have specialized to safeguard mitochondria and inherit Hul5 function, respectively. We determined cryo-electron microscopy structures of full-length human UBE3B and UBE3C in complex with calmodulin at 2.9-3.5 [A] in calcium-free and calcium-saturated conditions. Calmodulin acts as an inter-protomer molecular glue clamping UBE3B into ring-shaped anti-parallel homodimers or asymmetric trimers, and remodels UBE3C into a conformation competent for proteasome association. Calcium binding to calmodulin promotes disassembly of these higher-order complexes, toggling UBE3B/C from E4 to E3 activity. These findings reveal how calmodulin regulates higher-order architectures of E3/E4 ligases to rewire the ubiquitin-proteasome system via calcium signaling.

biochemistry↗

bioRxiv2026

Computational modeling of head direction cells in three-dimensional space: directional encoding and visual cue manipulation

Head direction (HD) cells can fire selectively as a function of the animals head azimuth direction and form an internal compass for navigation. They were found in the mammalian limbic system including the dorsal presubiculum and entorhinal cortex. The underlying network updates its directional estimate in a self-organized fashion and can be recalibrated by external sensory cues. Although ring-attractor models were proposed to account for azimuth coding on horizontal planes, they cannot explain conjunctive azimuth-and-pitch tuning observed in HD cells of the presubiculum of flying bats navigating in three-dimensional (3-D) space. Based on the 3-D electrophysiological recordings, we developed a toroidal continuous attractor network that jointly encodes horizontal azimuth and vertical pitch angle of head direction. The model can reproduce the experimentally recorded tuning curves of individual HD cells, and accurately encode the 3-D dynamic head direction of bat by HD cell population. The model also simulate the influence of horizontal visual cue manipulation on the HD system in 3-D space and predicts how horizontal landmark rotation induces a sustained azimuthal offset that persists after the cue is removed, which is comparable to two-dimensional experimental findings. This research clarifies how conjunctive 3-D direction codes are generated and modified by vestibular input, visual information and recurrent connectivity. It also uncovers the computational principles and properties of the brains navigation functions in realistic 3-D environments and offers new theoretical reference for future studies. Author summaryA central function of the brains navigation system is to track head direction, which in terrestrial mammals is largely confined to a horizontal plane. However, for animals like bats that navigate freely in three-dimensional (3-D) space, the neural code for head direction has been found to be high-dimensional. While ring attractor network models elegantly explain horizontal azimuth coding, how the 3-D head direction code is formed and affected by sensory information remains unknown. Here, we develop a toroidal continuous attractor network model with vestibular and visual modules that explains the jointly encoding of azimuth and pitch angles, and the effect of visual cue. We introduce the toroidal topology to the continuous attractor network, and the high-dimensional angular velocity signal from vestibular system and visual input are used to update the population dynamics of the network. Our model is constrained by and reproduces 3-D electrophysiological data from flying bats, captures the unique tuning curves of individual head direction cells, and further achieves the accurate encoding of dynamic 3-D head movements by population activity. Evidences in the rodent have suggested visual cue manipulation recalibrates head direction coding horizontally. Our model further successfully simulates the influence of visual cue rotation in 3-D space, predicting a persistent, global offset in the azimuth encoding--an effect that endures after cue removal and aligns with 2-D rodent experimental phenomena. This work provides a mechanistic, network-level explanation for 3-D head direction encoding and reveals how multimodal cues are integrated to form the internal compass in a volumetric world.

neuroscience↗

bioRxiv2026

Temperature and intrinsic Ca2+ reshape TRPM4 pharmacology

Proteins operate in dynamic environments where ions, lipids, and temperature collectively define their properties, yet most studies rely on simplified conditions that overlook these intrinsic variables. Here, we show two such factors--temperature and Ca2+-- remodel the function and pharmacology of TRPM4, an ion channel implicated in cardiac conduction, immune regulation, cancer, and intestinal fluid homeostasis. At physiological temperature and Ca2+, TPPO--previously considered a selective TRPM5 inhibitor inactive toward TRPM4--potently activates TRPM4, revealing strong synergy among temperature, Ca2+, and ligand binding. In contrast, Necrocide-1, a necroptotic activator targeting the same binding pocket, defies this logic: it opens TRPM4 without Ca2+ but is antagonized by Ca2+. Meanwhile, the inhibitors NBA and CBA engage a nearby pocket, locking the channel in a non-conductive pre-open state. Our findings highlight that even rigid binding pockets can exhibit temperature-dependent ligand recognition, revealing hidden pharmacology and informing selective, environment-aware therapeutic strategies.

biophysics↗

bioRxiv2026

DNA synthesis inside the hepatitis B virus creates a high-energy spool

The Hepatitis B Virus (HBV) capsid assembles around an RNA pregenome which is reverse-transcribed into double-stranded DNA. It remains unclear how this DNA, which is stiff, bulky, and has significant negative charge, is accommodated within the capsid. The organization of the genome will answer this and lend insight into the viral reverse transcription reaction. We determined the structures of mature HBV and Duck HBV, finding that the DNA forms a spool that is coaxial with the capsids fivefold symmetry and interacts with charges on the capsid interior. We calculate that the energy of DNA bending would create a metastable capsid that just awaits a trigger for DNA release. Thus, we see how nature has created a fragile energy minimum that enables genome uncoating.

microbiology↗

bioRxiv2026

Novel Bacillus altitudinis endolysin (ArtE2) targeting both Gram-positive and Gram-negative bacteria

Antibiotic resistance is a major global health concern. The development of new antibiotics and therapeutics is crucial for the future. Bacteriophages produce endolysins that induce bacterial lysis, making them a promising treatment option. Deep sequencing was used to identify and isolate genes encoding endolysins from Bacillus spp.. We characterized the biological activities of these endolysins. Additionally, this study focused on the design of a new chimeric endolysin, ArtE2, which combines endolysin-2 with a polycationic peptide to address the bacterial activity in gram-negative pathogenic bacteria. Using bioinformatic tools, we conducted three-dimensional modeling of the endolysin ArtE2 and its interactions with peptidoglycan fragments. In this study, we tested the activity of chimeric endolysins against both Gram-positive and Gram-negative bacteria. All endolysins share the same catalytic domain and diverse cell-binding domains. Some endolysins are highly specific to certain bacterial species or strains, whereas others have broader specificities. Histidine interactions are an important part of the mechanism by which ArtE2 connects with bacterial peptidoglycan. Additionally, the engineered endolysin ArtE2 was highly effective at killing Staphylococcus aureus and Escherichia coli. In silico analysis showed that the fusion did not negatively affect endolysin folding or activity. These findings suggest that ArtE2 could be used to develop efficient antibacterial controls targeting pathogenic Gram-positive and Gram-negative bacteria.

microbiology↗

bioRxiv2026

Organic Components Modulate the Morphology of Respirable Aerovirology Relevant Aerosols

Airborne transmission of pathogens occurs via aerosol particles, whose morphology provides insights into the microenvironments that pathogens experience. Aerosol morphology includes particle size, shape, phase state, and chemical homogeneity, yet systematic studies remain limited. Here, we characterized model bioaerosol morphologies generated from (1) NaCl-organic two-component mixtures, (2) common cell culture media, and (3) artificial respiratory fluids. Particles were collected using a virtual impactor and Andersen cascade impactor and analyzed by scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDX). Results show that organic components modulate the morphology: dipalmitoylphosphatidylcholine (DPPC) promotes organic-inorganic phase separation while proteins prohibit formation of large crystals and leads to better mixing among components. At 30% RH with a drying period of 10 seconds, most aerosols appeared desiccated, though NaCl-glucose, DMEM-complete-media and artificial saliva with mucin remained semi-solid or gel-like. Among all formulations examined EMEM-complete-media and artificial saliva (non mucin) show a size-dependent morphology. Our study demonstrates how chemical composition and size alters surrogate bioaerosol phase (semi-solid or solid) and morphology and provides new insights into the microenvironment of aerosol particles for aerovirology investigations.

biochemistry↗

bioRxiv2026

A micropeptide component of the OGDH complex modulates ATP production in the TCA cycle

Since its elucidation, the tricarboxylic acid (TCA) cycle has been regarded as a fully defined enzymatic pathway. Here, we report the discovery of a previously unrecognized micropeptide component of this central metabolic system. Through analyzing ribosome profiling data from the mouse sORFs.org database, we discovered APPM (ATP production-promoting micropeptide), a 29-amino acid peptide encoded by a non-canonical small open reading frame within the mouse Ctsb gene. APPM localizes to the mitochondrial matrix and inner membrane, where it directly binds to the E1 subunit (OGDH) of the -ketoglutarate dehydrogenase complex (OGDHc). This interaction modulates OGDHc enzymatic activity, thereby regulating NADH and ATP production. We identified tyrosine-13 as the critical residue mediating the APPM-OGDH interaction and functional activation. Exogenous APPM administration increased ATP levels in vivo and, in a mouse model of heart failure, restored cardiac function, outperforming the reference drug trimetazidine. Collectively, our findings identify APPM as the first micropeptide regulator of the OGDH complex, expanding the known repertoire of the TCA cycle and presenting a potential therapeutic strategy for bioenergetic disorders.

molecular biology↗

bioRxiv2026

Codon Deoptimization of Multispecific Biologics Reduces Mispairing During Transient Mammalian Protein Expression

Codon optimization is utilized in biologics design to maximize protein expression. Selecting the host organisms most frequently used codons for each amino acid can significantly enhance recombinant protein expression yields. However, non-optimal codons in mRNA can be critical for functional protein production through inducing pauses in or attenuating protein translation. In our study, we have investigated the effect of deoptimizing serine codons in biologics by shifting them from the five most frequently used codons to the least (TCG). Rare serine codons were strategically inserted into the coding sequences of the constant regions in a trispecific antibody (Protein 1), a bispecific antibody (Protein 2), and multiple non-proprietary bispecific antibodies. We observed that inserting 1-2 rare serine codons within an open reading frame led to expression changes that reduced the formation of mispaired 2x light chain and half-molecule species. Protein purity was drastically increased by incorporating two deoptimized serine codons into a single chain. Notably, we observed a negative correlation between total protein expression yield and final product purity. Taken together, our work demonstrates that incorporation of deoptimized serine codons into a single chain can significantly influence multispecific biologic pairing and enhance final product purity. Our findings align with existing literature showing that rare codon usage modulates translation kinetics and protein folding. Future investigation is warranted to enable a priori identification of the rate-limiting chain in multispecific biologics, thereby guiding strategic codon deoptimization prior to expression.

bioengineering↗

bioRxiv2025

Kilohertz-rate two-photon voltage imaging of population dynamics in vivo

Understanding how neural circuits compute requires capturing voltage dynamics across large neuronal populations with millisecond resolution in vivo. However, two-photon voltage imaging remains fundamentally limited by a trade-off among imaging speed, field of view, and excitation efficiency. We introduce HS2PM, a hybrid scanning two-photon microscope that overcomes this bottleneck, enabling kilohertz-rate imaging over a 650 x 524 m2 field of view at single-cell resolution while preserving the photon efficiency of single-point excitation. HS2PM stably records deep-layer membrane potentials from over 160 neurons simultaneously, with minimal photobleaching and phototoxicity. It resolves both spikes and subthreshold voltage dynamics in vivo, revealing how these jointly shape sensory adaptation and population coding. Beyond voltage imaging, HS2PM supports high-speed fluorescence lifetime and vascular flow imaging, establishing a multimodal platform for dissecting fast circuit dynamics with precision previously inaccessible to optical methods.

neuroscience↗

bioRxiv2025

Transcriptomic Profiling Reveals Key Molecular Events and Pathways Driving Acquired Chemotherapy Resistance in Relapsed Acute Myeloid Leukemia

BackgroundAcute myeloid leukemia (AML) is a highly heterogeneous hematologic malignancy. Although induction therapy induces remission in many patients, relapse and acquired chemoresistance remain the major causes of treatment failure. Defining the molecular mechanisms underlying relapse is essential for improving therapeutic strategies. MethodsBone marrow samples from nine AML patients were analyzed, including five newly diagnosed cases and four relapsed cases after chemotherapy. Transcriptome sequencing and integrative bioinformatics analyses were performed, including differential expression analysis, GO/KEGG enrichment, GSEA, and protein-protein interaction (PPI) network analysis, to delineate relapse-associated molecular alterations. ResultsPrincipal component analysis demonstrated clear transcriptional segregation between primary and relapsed AML, indicating extensive molecular reprogramming during relapse. A total of 2,025 differentially expressed genes were identified, enriched in pathways related to epithelial-mesenchymal transition-like programs, leukemia stem cell maintenance, apoptosis evasion, and bone marrow microenvironment remodeling. Marked upregulation of FOXC1, HOXA11/HOXA11-AS, and AXL suggests key roles in sustaining stemness and promoting drug resistance. GO/KEGG analysis revealed coordinated activation of small GTPase, Rho/Ras signaling, ion transport, and epigenetic regulatory pathways, reflecting multilayered adaptive responses. GSEA indicated metabolic-epigenetic reprogramming in relapsed AML, while primary AML showed enrichment of energy metabolism and chromatin assembly pathways. PPI network analysis highlighted a central inflammation-metabolism axis involving TP53, IL6, CXCL8, and CCL2, associated with apoptosis resistance and metabolic adaptation. ConclusionsRelapsed AML is characterized by transcriptional reprogramming, metabolic remodeling, and microenvironment-driven adaptive resistance. Targeting small GTPase signaling, AXL, or IL6-related inflammatory pathways, alone or combined with epigenetic modulators, may offer promising therapeutic strategies to overcome chemoresistance in AML.

cell biology↗

bioRxiv2025

Plasma Ficolins Enable Liver Macrophages to Capture Blood-Borne Bacteria by Recognizing Capsular Polysaccharides

Ficolins are evolutionarily conserved glycan-binding lectins in plasma or on cell membranes of immune cells, yet their physiological functions remain to be defined. Here we demonstrate that plasma ficolins drives the capture of diverse encapsulated bacteria in the blood circulation by the liver resident macrophages (Kupffer cells). Ficolin-activated immunity in the liver sinusoids provides swift and sterilizing immunity in mice. Mice lacking ficolin-A (the only plasma ficolin) became hypersusceptible to the blood infections of the ficolin-A-recognizable bacterial serotypes. Mechanistically, plasma ficolins activate complement C3 on bacterial surfaces by pattern recognition of acetylated monosaccharides on polysaccharide capsules, and thereby deliver the opsonized bacteria to C3 receptors on Kupffer cells for phagocytic elimination. These findings reveal that plasma ficolins serve as pattern-recognition receptors that are essential for maintaining the bloodstream sterile.

microbiology↗

bioRxiv2025

Closing the Sim-to-Real Gap: An End-to-End Robotic Ultrasound System Leveraging In Vivo Reinforcement Learning and 3D-Prior Guided Hybrid Control

Abdominal ultrasound is a crucial first-line diagnostic tool, yet its efficacy is inherently constrained by a strong dependency on operator skill, leading to significant inter-operator variability and limiting its widespread adoption. While robotic ultrasound systems with artificial intelligence have emerged to mitigate this, current approaches face critical limitations: they often rely on simulated or phantom data for training, which hampers generalizability, and employ control strategies that lack the flexibility to adapt to complex human anatomy. To address these challenges, this paper introduces a novel, end-to-end robotic system for autonomous abdominal scanning. Our methodology is systematic: it begins with coarse scan planning via RGB and 3D point cloud-based localization of key anatomical landmarks (e.g., xiphoid process). The core of our approach involves training a reinforcement learning scanning policy directly on live human volunteers, enabling the development of a strategy that is robust to anatomical diversity. This high-level policy is executed by a sophisticated hybrid force-position controller, enhanced with real-time normal vector calibration and 3D point cloud-based respiratory phase detection to dynamically adjust contact force, particularly during inspiration. This innovation proves critical for improving scan quality in subjects with higher Body Mass Index (BMI). Extensive validation against expert sonographers demonstrates that our system achieves high precision in standard plane recognition and superior scanning efficiency. Furthermore, to holistically assess performance where standard planes are difficult to acquire, we introduce a 3D reconstruction-based coverage metric. Results confirm that our system delivers strong adaptability and significantly improved consistency, marking a substantial step toward clinically viable, operator-independent ultrasound robotics.

bioengineering↗

bioRxiv2025

A comprehensive evaluation of ultraviolet irradiation at 254 nm and 222 nm in inactivating human noroviruses on surfaces

Human norovirus (hNoV) presents significant public health challenges due to its low infectious dose and environmental persistence. This study compared the inactivation efficacy of ultraviolet C irradiation at 254 nm (UV 254) and far-UVC radiation at 222 nm (UV 222) against four hNoV strains and two surrogate viruses, Tulane virus (TV) and bacteriophage MS2. A symptom scoring assay was developed to assess hNoV infectivity following microinjection into zebrafish embryos, being used in combination with reverse transcriptase quantitative PCR (RT-qPCR), long-range RT-qPCR, and RNase-treated RT-qPCR. With a general laboratory set-up of viruses being suspended in deionized water droplets in Petri dish, UV 222 was demonstrated with comparable, if not superior, performance in reducing hNoV infectivity and RNA integrity, and was significantly more effective than UV 254 in damaging viral capsids. MS2 exhibited inactivation patterns similar to hNoVs, whereas TV was markedly more resistant to UV 222. The performance of UV 222 was consistent in inactivating hydrated viruses on both stainless steel and porcine skin surfaces. However, the efficacy of UV-222 was substantially more reduced when virus inocula were dried or mixed with simulated vomitus containing high levels of organic matter, compared with UV-254. No evidence of viral adaptation or persistent genomic diversification was detected following repeated sublethal UV exposures. Taken together, UV 222 can be regarded as a promising technology in surface disinfection, especially for hNoV control, meantime keeping safe for human exposure. ImportanceHuman norovirus, the main cause of foodborne illness and non-bacterial gastroenteritis, can be transmitted through human-to-human contact. Indirectly, food or food related surfaces are readily contaminated by hNoV, completing the transmission route. So far, no standard cultivation tool is available for detecting viable hNoV, resulting in the challenges of evaluating inactivation effectiveness of various disinfection technologies, including UV 222 treatments. The significance of our study lays in attempts to quantify hNoV infectivity loss of four strains using zebrafish model during UV 222 and 254 treatments, together with the underlying antiviral mechanisms indicated by three different types of reverse transcription qPCR methods. In addition, the concerns over possible emergence of variant were subdued by genome wide sequencing results after consecutive UV exposures and passaging in vivo zebrafish model. SynopsisUV 222 is recommended to be applied after surface cleaning and ideally on moist surfaces.

microbiology↗

bioRxiv2025

ColorSTEM: An easy and convenient approach to Multicolor Electron Microscopy of Labeled Biological Specimens

A new method for Multicolor Electron Microscopy (EM) using scanning transmission EM, ColorSTEM has been developed to increase the sensitivity, instrument availability and ease of use compared to that previously developed using electron energy loss spectroscopy and energy filtered transmission EM. Both methods paint multiple subcellular complexes with different colors, enabled by the localized and targeted deposition of diaminobenzidine (DAB) conjugated to different metals, which provides the differentiating signal from each other. With ColorSTEM, elastic scattering that is dependent upon atomic weight (Z-contrast) has far greater signals. Using deposited DAB with copper or gold to label subcellular components, Z-contrast imaging generates a pseudo-elemental map, resulting from differences in the grayscale of the conventional STEM images.

cell biology↗