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Biology subjects

Qian, R.

Publications and source records attributed to Qian, R..

12 recordsLinked to original sources

Sexually Dimorphic Visual Processing in the Yellow-Fever Mosquito, Aedes aegypti

Flying insects process motion across the visual scene to regulate their ground speed, correct course deviations, and behaviorally relevant stimuli such as avoiding predators or finding hosts. The yellow-fever mosquito Aedes aegypti provides a useful model for studying these visually guided behaviors, as both sexes use vision to track moving features. Approaching a moving target presents mosquitoes with a demanding visual problem: they must extract target motion from the changing visual scene while simultaneously controlling their own flight and responding to potentially dangerous movements. To understand this, we first studied free-flight responses to static and moving vertical targets in a wind tunnel system capable of projecting dynamic visual stimuli, and found that males and females are sexually dimorphic with respect to their responses to target motion. When the feature was static, both males and females advanced toward it during flight; however, when it oscillated laterally at 2 Hz, only females continued to pursue it. In a subsequent yaw-unrestrained magnetic tethering paradigm, we showed that this divergence cannot be simply explained by sex-specific differences in visuomotor tuning dynamics, while micro-CT reconstructions revealed only modest sexual differences in eye morphology and broadly similar patterns of estimated spatial acuity. Together, these results indicate that males retain the biomechanical capacity to track oscillating targets but actively suppress approach behavior during free flight, whereas females pursue salient features independently of target motion. This pattern aligns with sex-divergent visual ecologies because the risk of approaching a large moving feature too closely likely outweighs the benefits for males seeking mates, whereas for host-seeking females the reproductive necessity of blood feeding overrides this avoidance.

neuroscience↗

Superposition eyes of diurnal and nocturnal hawkmoths are imperfect spheres and lack acute zones.

Superposition compound eyes improve sensitivity by pooling light from multiple facets and are widespread among nocturnal insects, including moths and beetles. Optical theory predicts that superposition eyes must be nearly spherical to form coherent images and therefore lack highly pronounced acute zones with high spatial resolution. To examine this, we imaged eyes of six hawkmoths (Sphingidae) spanning diurnal and nocturnal activity with high-resolution microcomputed tomography. Our automated pipeline created detailed eye maps quantifying morphological parameters. We measured local eye curvature (radial distance), interommatidial angle ({Delta}{varphi}), facet size and crystalline cone skewness (tilt of cone axes relative to the local surface normal). All species show more curvature in the dorso-ventral plane with flattening in the antero-posterior plane. However, their eyes still retain near-spherical curvature globally, with diurnal species showing greater distortion. For facet parameters, spatial acuity is generally highest (lowest {Delta}{varphi}) near the eye center and decreases gradually toward the periphery. However, overall variation in spatial acuity is low and these eyes lack distinct acute zones. Facet size gradually changes from center to periphery, increasing in some species and decreasing in the others. Cone skewness is present in all six species (0{degrees}-10{degrees}), but in two diurnal species of hummingbird hawkmoths it increases markedly in the posterior region (15{degrees}-30{degrees}) possibly compensating for regional eye flatness. This paper provides foundational data of ommatidial and eye shape measurements and advances our assumptions about how superposition eyes function.

animal behavior and cognition↗

The Human Hippocampus Is Involved in Auditory Short-Term Memory Trace Formation

The human hippocampus has been claimed to play an important role in long-term memory, or episodic memory, but its contribution to short-term memory remains debated. Here, we demonstrate human hippocampal involvement in auditory short-term memory (ASTM) trace formation. We used a classic oddball paradigm and intracranial recordings across various human brain areas. High frequency activities evoked by deviant stimuli in subjects indicate the generation of ASTM trace. Analysis of auditory response latencies across the hippocampus, insula, and temporal, parietal, and frontal lobes revealed the early processing of ASTM trace at a pre-attention stage. Granger causality analysis further showed that ASTM trace processing engages hierarchical cortical areas and clarified their interactions. Bottom-up signals flow from the insula and auditory temporal regions to the frontal lobe early on, followed by top-down information from the frontal lobe to the hippocampus, inferior temporal lobe, and insula at a later pre-attentive stage. Critically, Bayesian model selection of dynamic causal modeling revealed that deviant stimuli selectively enhanced the effectiveness of top-down connections to the hippocampus, thereby facilitating ASTM trace formation. These results provide compelling evidence that the human hippocampus contributes to auditory short-term memory at a pre-attention stage and suggests a challenge to entrenched beliefs in the classification of memory systems.

neuroscience↗

Resolving Heterogeneity in Major Depression: Overcoupling and Undercoupling Subtypes Exhibit Differential Treatment Response and Molecular Pathways

Major depressive disorder (MDD) exhibits significant heterogeneity whose neurobiological mechanisms remain elusive. Alterations in morphological-functional coupling (MFC) have been observed in MDD. This study aims to investigate MDD subtypes based on MFC alterations and their associations with clinical symptoms and molecular basis. We identified two clinically distinct MDD subtypes in multi-center neuroimaging data (Discovery: 828 MDD/776 healthy controls; Validation: 236 MDD/86 healthy controls) by using a semi-supervised machine learning approach based on MFC changes, which were validated and robustly repeated in the validation dataset. Differences among subtypes were then examined in relation to clinical assessments, gene expression patterns, neurotransmitter and cell density, and treatment response. Subtype I (overcoupling) showed elevated MFC in high-order association cortices, linking to synaptic transmission activity and severe symptoms. Subtype II (undercoupling) demonstrated reduced MFC in primary cortices, associated with cell cycle regulation and treatment resistance. Both subtypes shared molecular signatures (cell types: astrocytes and oligodendrocytes; neurotransmitter systems: serotonergic and GABAergic receptors). Crucially, longitudinal data (33 MDD undergoing Escitalopram monotherapy) revealed that undercoupling subtype exhibited better response, implying a potential mechanism of the drug via increasing the MFC. Our work deciphers MFC-driven MDD phenotypes with distinct molecular profiles and differential treatment outcomes, suggesting potential pathways for personalized diagnosis and treatment strategies in MDD, advancing precision psychiatry.

neuroscience↗

Deciphering DEL Pocket Patterns Through Contrastive Learning

DNA-encoded libraries (DELs) facilitate high-throughput screening of trillions of molecules against protein targets through split-pool synthesis and DNA tagging. Despite their potential, only a few DEL-derived compounds have advanced to clinical trials or reached the market. A better understanding of the defining characteristics of target proteins, particularly those with binding pockets suitable for DEL screening, is critical to improving success rates. However, existing approaches remain limited in assessing pocket flexibility and functional similarity. Here, we present ErePOC, a pocket representation model based on contrastive learning with ESM-2 embeddings to address these challenges. ErePOC captures both structural and functional features of binding pockets, enabling identification of shared characteristics among DEL targets. By integrating analyses of low-dimensional physicochemical properties and high-dimensional ErePOC embeddings, we provide a comprehensive view of DEL target space. With 98% precision in downstream classification tasks, ErePOC demonstrates high performance in pocket representation, which is then applied to predict human proteins suitable for DEL screening, with enrichment uncovered across 18 functional categories. This work establishes a new framework for enhancing DEL-based drug discovery through more effective target selection and pocket similarity analysis.

biophysics↗

Neural correlates differ between crystallized and fluid intelligence in adolescents

Fluid and crystallized intelligence are acknowledged as distinct facets of cognitive ability during brain development, but the specific neural substrates and molecular mechanisms underlying them remain unclear. This study used a sample comprising 7471 young adolescents (mean age 9.87 {+/-} 0.62 years) from the ABCD cohort to elucidate the differential neural correlates of fluid and crystallized intelligence. Our findings indicated that micro-level brain MRI phenotypes such as water diffusivity were closely associated with fluid intelligence, whereas macro-level brain MRI phenotypes such as gray matter cortical thickness were indicative of crystallized intelligence. We further investigated the molecular mechanisms underlying fluid and crystallized intelligence by correlating the characteristic MRI markers with spatial transcriptome profiles and PET imaging. Results showed that fluid intelligence had significant associations with serotonin and glutamate system, while crystallized intelligence was related to serotonin, dopamine and acetylcholine system. Furthermore, we examined the impacts of lifestyle factors on these two forms of intelligence and how the molecular pathways mediated these impacts. Our investigation suggested that physical activities, screen use and sleep duration influenced fluid intelligence mainly through mGlu5 receptors and crystallized intelligence through 5HT1a and D2 receptors. In conclusion, these findings illustrated a distinct neural basis between fluid and crystallized intelligence from the perspectives of neuroimaging, neurotransmitters, and lifestyles in young adolescents.

neuroscience↗

Head Direction Cells and Grid Cells as the Core Components of the Core-periphery Structure

Head direction cells and grid cells are neuron types defined by their regular firing patterns in standard experimental arenas. As technology advances, we can record extensive neuronal firing activity over time using electrophysiological or calcium imaging methods. The covariance matrix is a critical measure of this neural populations discharge activity. We developed a method to identify a core-periphery structure in the covariance matrix, highlighting the central role of grid cells and head direction cells in firing correlations. This method effectively redefines these cell types in terms of firing activity correlations, with core nodes exhibiting a higher mutual information rate for spatial variables. Additionally, we developed a periodic spring network algorithm, which uses the covariance matrix alone to estimate the spatial phases of both head direction cells and grid cells due to their periodic properties. This approach offers a new perspective on utilizing the covariance matrix of the neural population to better understand and identify these specialized cell types, even when traditional firing pattern-based definitions are challenging to apply.

neuroscience↗

Spatial Localization Ability of Planarians Identified Through the Light Maze Paradigm

Spatial localization ability is crucial for free-living animals to fit the environment. As shown by previous studies, planarians can be conditioned to discriminate directions. However, due to their simplicity and primitiveness, they had never been considered to have true spatial localization ability to retrieve locations of objects and places in the environment. Here, we introduce a light maze training paradigm to demonstrate that a planarian worm can navigate to a former recognized place from the start point, even if the worm is transferred into a newly produced maze. This finding identifies the spatial localization ability of planarians for the first time, which provides clues for the evolution of spatial learning. Since the planarians have a primitive brain with simple structures, this paradigm can also provide a simplified model for a detailed investigation of spatial learning.

animal behavior and cognition↗

Diving Behavior Reveals Humidity Sensing Ability of Water Deprived Planarians

Humidity sensing ability is crucial to terrestrial animals for fitting the environment. Researchers made great progress in recent study about humidity sensing mechanisms of terrestrial animals. However, it is poorly understood whether humidity sensing exists in aquatic animals. Here, we demonstrate that the aquatic planarians, one of the primitive forerunners of later animals, has the ability of humidity sensing and is capable of using the ability to perceive the water beneath itself from a drought place to seek survival. The behavior we discovered is described as diving because the worms twist its body to break away from the mucus that make them adhere to the drought place and drop into the water. The behavior is triggered by rapidly increasing humidity. This finding suggests that humidity sensing ability exists in the lower aquatic animals, and the ability might be used to seek for water when aquatic animals are facing desiccation. The finding also suggests that survival-seeking and decision-making behavior have appeared in the primitive planarian worms.

animal behavior and cognition↗

A survey of optimal strategy for signature-based drug repositioning and an application to liver cancer

Pharmacologic perturbation projects, such as Connectivity Map (CMap) and Library of Integrated Network-based Cellular Signatures (LINCS), have produced many perturbed expression data, providing enormous opportunities for computational therapeutic discovery. However, currently there is no consensus on which methodologies and parameters are the most optimal to conduct such analysis. Aiming to fill this gap, we developed new benchmarking standards for quantitatively estimating drug retrieval performance. Investigations of potential factors influencing drug retrieval were conducted based on these standards. As a result, we determined an optimal strategy for LINCS data-based therapeutic discovery. With this approach, we further identified new therapeutics for liver cancer of which the current treatment modalities remain imperfect. Both computational and experimental results demonstrated homoharringtonine (HHT) could be a promising anti-liver cancer agent. In summary, our findings will not only impact the future applications of LINCS data but also offer new opportunities for therapeutic intervention for liver cancer.

bioinformatics↗

Receptor compaction and GTPase movements drive cotranslational protein translocation

Signal recognition particle (SRP) is a universally conserved targeting machine that couples the synthesis of ~30% of the proteome to their proper membrane localization1,2. In eukaryotic cells, SRP recognizes translating ribosomes bearing hydrophobic signal sequences and, through interaction with SRP receptor (SR), delivers them to the Sec61p translocase on the endoplasmic reticulum (ER) membrane1,2. How SRP ensures efficient and productive initiation of protein translocation at the ER is not well understood. Here, single molecule fluorescence spectroscopy demonstrates that cargo-loaded SRP induces a global compaction of SR, driving a >90 [A] movement of the SRP*SR GTPase complex from the vicinity of the ribosome exit, where it initially assembles, to the distal site of SRP. These rearrangements bring translating ribosomes near the membrane, expose conserved Sec61p docking sites on the ribosome and weaken SRPs interaction with the signal sequence on the nascent polypeptide, thus priming the translating ribosome for engaging the translocation machinery. Disruption of these rearrangements severely impairs cotranslational protein translocation and is the cause of failure in an SRP54 mutant linked to severe congenital neutropenia. Our results demonstrate that multiple largescale molecular motions in the SRP*SR complex are required to drive the transition from protein targeting to translocation; these post-targeting rearrangements provide potential new points for biological regulation as well as disease intervention.

biochemistry↗

Circadian gene Clock regulates mitochondrial morphology and functions by posttranscriptional way

Many daily activities are under the control of circadian clock, including nutrition metabolism and energy generation. Mitochondria, as the core factories of oxidizing substrates and producing ATP, undergo changes in quantity and morphology to adapt to the demand for energy. It has been demonstrated that mitochondrial gene expression, dynamics and functions are all affected by circadian clock. Here, we demonstrated that circadian gene Clock affects the number, architecture and function of mitochondria via posttranscriptional regulation of Drp1. Clock{Delta}19 leads to fragmented mitochondria accompanied with the loss of membrane potential, excessive ROS accumulation and decreased mitochondrial respiration and ATP generation. Clock{Delta}19 mice exhibit disordered lipid metabolism and evident nonalcoholic fatty liver disease (NAFLD), which are rescued by treatment with the mitochondrial fission inhibitor Mdivi-1. These results suggest a strong relationship between Clock, mitochondrial dynamics and metabolic diseases and provide a new perspective on disordered circadian clock and related diseases.

cell biology↗