Biology subjects

Qi, A.

Publications and source records attributed to Qi, A..

10 recordsLinked to original sources

bioRxiv2026

Characterisation of gene expression markers and glucosinolates during discrete infection stages of Pyrenopeziza brassicae in Brassica napus

Light leaf spot (LLS), caused by subcuticular hemibiotrophic ascomycete fungus Pyrenopeziza brassicae, is a major constraint on oilseed rape (Brassica napus) production, yet the genetic and biochemical mechanisms of quantitative disease resistance (QDR) remain poorly defined. Here, disease phenotyping, pathogen quantification, microscopy, gene expression profiling and glucosinolate (GSL) analysis were integrated to dissect resistance mechanisms in B. napus. Disease assays of 19 diverse lines revealed clear contrasts between susceptible and resistant genotypes, with the commercial cultivar Ambassador showing a phenotype inconsistent with the UK Recommended List rating. Microscopy demonstrated that resistance within doubled haploid line Cubs Root does not inhibit spore germination or penetration but restricts hyphal branching and subcuticular colonisation from 4 to 8 days post-inoculation. Expression profiling of seven candidate gene expression markers (GEMs) and pathogenesis-related PR1 showed that cinnamate-4-hydroxylase, phospholipase C4, {beta}-adaptin, universal stress protein and the 40S ribosomal subunit protein S24 were strongly pathogen-induced in resistant lines, whereas a BAHD acyltransferase, a putative susceptibility factor, was induced only in susceptible cultivars. GSL profiling identified negative correlations between disease severity and total GSLs, particularly aliphatic and aromatic GSLs, with 2{square}phenylethyl and 7-methylsulfinyl heptyl GSLs showing the strongest associations with resistance. Together, these results highlight coordinated transcriptional and metabolic responses that limit pathogen proliferation and provide targets for breeding durable LLS resistance in B. napus.

plant biology↗

bioRxiv2026

Statistical Atlas-Based Surrogate Model of Biventricular Wall Mechanics

Here we use a statistical atlas of end-diastolic (ED) and end-systolic (ES) biventricular shapes - previously derived from the UK Biobank imaging substudy - to generate meshes for finite element (FE) simulations of ventricular wall mechanics. The models used the Holzapfel-Ogden constitutive law for passive material properties and a time-varying elastance model of systolic tension development. Simulated ED and ES deformations were projected onto the shape atlas and the principal components were used to train a multi-layer perceptron as a surrogate model. The input layer included shape modes of the unloaded ventricular geometry, and material parameters and ventricular pressures at ED and ES. After training with 444 simulations, the surrogate model achieved a mean square error in predicted displacements of < 2 mm and volumetric overlaps with FE-predicted deformed shapes > 97%, demonstrating good fidelity to the simulated ground truth. This approach may enable accurate prediction of ventricular wall mechanics without computationally expensive finite element analysis, offering a more feasible method for rapid, subject-specific cardiac modeling.

bioengineering↗

bioRxiv2025

Genetically encoded assembly recorder temporally resolves cellular histories in cellulo and in vivo

Mapping cellular activity with high spatiotemporal precision in complex tissues is essential for understanding organ physiology, pathology, and regenerative processes. Here, we introduce Granularly Expanding Memory for Intracellular Narrative Integration (GEMINI), an in cellulo recording platform that leverages a computationally designed protein assembly as an intracellular memory device to record individual cells activity histories. GEMINI grows predictably within live cells with minimal interference to cellular functions, capturing cellular activities as tree-ring-like fluorescent patterns in the expanding scaffolds for imaging-based retrospective readout. Absolute chronological information of activity histories was attainable with hour-level accuracy through the integration of fiducial timestamps. GEMINI effectively resolved differential NF{kappa}B-mediated transcriptional changes, distinguishing fast dynamics of 15 minutes, and providing quantifiable signal amplitudes. In a xenograft model, GEMINI recorded inflammation-induced signaling dynamics across tissue with cellular resolution, revealing spatial heterogeneity linked to vascular density. When expressed in the mouse brain, GEMINI exhibited negligible impact on neuronal survival, with animals maintaining normal motor and cognitive behaviors. In physiological contexts, GEMINI successfully resolved both transcriptional changes and activity patterns of neurons in the brain. Together, GEMINI provides a robust and generalizable means for spatiotemporal mapping of cell dynamics underlying physiological and pathological processes in both culture and intact tissues.

bioengineering↗

bioRxiv2025

Cryo-EM structure of DNA-unbound human MCM2-7 complex reveals new disease-relevant regulation

Chromatin loading of the hexameric replicative helicase MCM2-7 complex requires coordinated interactions with the origin recognition complex (ORC), CDC6, and CDT1. MCM2-7 not bound to DNA forms a single hexamer (SH) with an open DNA entry gate. Two MCM2-7 SHs are loaded sequentially to form the double hexamer (DH) that encircles the DNA duplex. Activated MCM2-7 then unwinds DNA and initiates DNA replication. Our cryo-electron microscopy analyses show that a fraction of human MCM2-7 without DNA exists as DH. Unexpectedly, we find that the MCM3 winged helix domain (WHD) docks on MCM2 in both DNA-free DH and SH, creating a safety latch across the DNA entry gate to block DNA entry into the central channel. The safety latch can be opened by ORC-CDC6 binding. Disrupting this latch by designed or human disease-related mutations of MCM3 causes replication defects and DNA damage checkpoint activation. Our findings uncover a new regulated step in MCM2-7 loading with implications for human diseases.

biophysics↗

bioRxiv2025

A cell type-specific mechanism driving the rapid antidepressant effects of transcranial magnetic stimulation

Repetitive transcranial magnetic stimulation (rTMS) is an emerging treatment for brain disorders, but its therapeutic mechanism is unknown. We developed a novel mouse model of rTMS with superior clinical face validity and investigated the neural mechanism by which accelerated intermittent theta burst stimulation (aiTBS) - the first rapid-acting rTMS antidepressant protocol - reversed chronic stress-induced behavioral deficits. Using fiber photometry, we showed that aiTBS drives distinct patterns of neural activity in intratelencephalic (IT) and pyramidal tract (PT) projecting neurons in dorsomedial prefrontal cortex (dmPFC). However, only IT neurons exhibited persistently increased activity during both aiTBS and subsequent depression-related behaviors. Similarly, aiTBS reversed stress-related loss of dendritic spines on IT, but not PT neurons, further demonstrating cell type-specific effects of stimulation. Finally, chemogenetic inhibition of dmPFC IT neurons during rTMS blocked the antidepressant-like behavioral effects of aiTBS. Thus, we demonstrate a prefrontal mechanism linking rapid aiTBS-driven therapeutic effects to cell type-specific circuit plasticity.

neuroscience↗

bioRxiv2025

Microglia regulate nucleus accumbens synaptic development and circuit function underlying threat avoidance behaviors

While CNS microglia have well-established roles in synapse pruning during neurodevelopment, only a few studies have identified roles for microglia in synapse formation. These studies focused on the cortex and primary sensory circuits during restricted developmental time periods, leaving substantial gaps in our understanding of the early developmental functions of microglia. Here we investigated how the absence of microglia impacts synaptic development in the nucleus accumbens (NAc), a region critical for emotional regulation and motivated behaviors and where dysfunction is implicated in psychiatric disorders that arise early in life. Using a genetically modified mouse that lacks microglia (Csf1r {Delta}FIRE/{Delta}FIRE), we found blunted excitatory synapse formation in the NAc. This effect was most prominent during the second and third postnatal weeks, when we previously found microglia to be overproduced, and was accompanied by an increase in presynaptic release probability and alterations in postsynaptic kinetics. Tissue-level NAc proteomics confirmed that microglial absence impacted numerous proteins involved in synapse structure, trans-synaptic signaling, and pre-synaptic function. However, microglial absence did not perturb levels of astrocyte-derived cues and adhesive proteins that promote synaptogenesis, suggesting that reduced synapse number may be caused by absence of a microglial-derived synaptogenic cue. Although observed electrophysiological synaptic changes were largely normalized by adulthood, we identified lasting effects of microglial absence on threat avoidance behavior, and these behavioral effects were directly associated with alterations of NAc neuronal activity. Together, these results indicate a critical role for microglia in regulating the synaptic landscape of the developing NAc and in establishing functional circuits underlying adult behavioral repertoires.

neuroscience↗

bioRxiv2022

Genome-wide investigation of multiplexed CRISPR-Cas12a-mediated editing in rice

We previously reported highly specific genome editing in rice by CRISPR-Cas9 and Cas12a with single DNA double strand break (DSB) (Tang et al., 2018). Two concurrent DSBs by CRISPR-Cas9 could generate defined deletions (Zhou et al., 2014), inversions (Schmidt et al., 2020), and translocations (Beying et al., 2020). Off-target effects of many simultaneous DSBs are unknown in plants. Here, we used whole-genome sequencing (WGS) to investigate off-target effects in rice plants edited by highly multiplexable CRISPR-Cas12a systems (Zhang et al., 2021). Our WGS study revealed highly specific multiplexed genome editing by CRISPR-Cas12a. We found low-frequency large chromosomal deletion and duplication events in plants that endured many (e.g., >50) simultaneous DSBs, but not in plants that endured a lower order DSBs (e.g., <10). While our short reads sequencing may not capture all chromosomal rearrangements, our results nevertheless shed important light on the analysis and regulation of engineered crops derived from multiplexed genome editing.

genomics↗

bioRxiv2022

Larger cerebral cortex is genetically correlated with greater frontal area and dorsal thickness

Human cortical expansion has occurred non-uniformly across the brain. We assessed the genetic architecture of cortical global expansion and regionalization by comparing two sets of genome-wide association studies of 24 cortical regions with and without adjustment for global measures (i.e. total surface area, mean cortical thickness) using a genetically-informed parcellation in 32,488 adults. We found 393 and 756 significant loci with and without adjusting for globals, respectively, among which 8% and 45% loci were associated with more than one region. Results from analyses without adjustment for globals recounted loci associated with global measures. Genetic factors that contribute to total surface area of the cortex particularly expand anterior/frontal regions, whereas those contributing to thicker cortex predominantly increase dorsal/frontal-parietal thickness. Interactome-based analyses revealed significant overlap of global and regional genetic modules, enriched for neurodevelopmental and immune system pathways. Consideration of global measures is important in understanding the genetic variants underlying cortical morphology.

neuroscience↗

bioRxiv2022

Efficient learning in children with rapid GABA boosting after training

It is unclear why and how children learn more efficiently than adults, although inhibitory systems, which play an important role in stabilizing learning, are immature in children. Here, we found that despite a lower baseline concentration of {gamma}-aminobutyric acid (GABA) in early visual cortical areas in children (8 to 11 years old) than adults (18 to 35 years old), children exhibited a rapid boost of GABA immediately after visual training, whereas the concentration of GABA in adults remained unchanged after training. Moreover, behavioral experiments showed that children stabilized visual learning much faster than adults, showing rapid development of resilience to retrograde interference. These results together suggest that inhibitory systems in childrens brains are more dynamic and adapt more quickly to stabilize learning than in adults. One Sentence SummaryChildren learn more efficiently than adults due to faster stabilization of learning with rapid GABA boosting after training.

neuroscience↗

bioRxiv2019

Perceptual learning of lesions in mammograms induced by response feedback during training

Detecting subtle lesions in mammograms indicative of early breast cancer usually requires years of experience. Well-designed training paradigms could be a strong tool for promoting perceptual learning (PL) with rapid and long-lasting improvement in detectability of these subtle mammographic lesions. Given that PL occurs without feedback about the accuracy of subjects responses, the role of feedback has been completely ignored in clinical applications of PL. However, in this study, we found that the contents of the feedback profoundly and differentially influence the formation and retention of PL to detect calcification and architectural distortion lesions, two types of mammographic lesions that are frequently missed in mammographic screenings. We trained subjects to detect one type of lesion in a mammogram and manipulated the content of the response feedback during training for 3 groups (no feedback, correctness only, and both correctness and location of the lesion). We found that PL occurred for both lesions when both correctness and location feedback were provided. PL also occurred for calcifications but not for distortions when only correctness was provided. No learning occurred without feedback for either lesion. A retest conducted six months later showed that PL was retained only in the group with both correctness and location feedback for both types of lesions. In contrast to the general consensus of basic PL studies, our results demonstrate that the content of the response feedback is a determining factor in forming and retaining PL to detect mammographic lesions.

neuroscience↗