Biology subjects

Shim, S.

Publications and source records attributed to Shim, S..

11 recordsLinked to original sources

bioRxiv2026

A novel fracture lattice in spiny mouse skin facilitates tissue autotomy and regeneration

Autotomy is a unique phenotype whereby an animal sheds a body part to escape predation1-3. The timing and location of autotomy are tightly regulated by preformed planes of weakness (aka fracture planes) which facilitate tissue loss. While autotomy is often followed by regeneration, these phenotypes are rarely reported in mammals4-9. A notable exception are spiny mice (Acomys) which exhibit skin autotomy and more remarkably, complete tissue regeneration10-14. Presently, mechanisms underlying autotomy and complete regeneration in Acomys skin remain elusive. Here, we report the discovery of a honeycomb-like fracture lattice in Acomys skin whose design directs tissue destruction but also facilitates regenerative healing. Unlike the single continuous surface of a fracture plane, this fracture lattice consists of a three-dimensional array of hexagonal units whose boundaries guide tissue breakage. Moreover, we identify collagen VI as the main constituent of the fracture lattice and find that it is distinctly arranged to initiate fracturing and propagation of skin tearing. By preconditioning the tissue for autotomy, the fracture lattice dampens the damage-induced inflammatory response but also upregulates a pro-regenerative gene signature, accelerating skin appendage regeneration. Lastly, we discovered the key role of spiny hairs in fracture lattice formation, as inhibiting their development leads to abnormal pattern formation and changes in skin fracture mechanics. Our results present a novel example of a uniquely evolved structural adaptation in mammalian skin that links tissue patterning, autotomy and regeneration. We expect that the application of a modular compartment structure to artificial skin and other organ engineering may enhance resilience to injury and facilitate efficient regeneration.

developmental biology↗

bioRxiv2026

Mapping and Genetic Dissection of a Novel Tar Spot Resistance QTL on Maize Chromosome 1

Tar spot, caused by the obligately biotrophic fungus Phyllachora maydis, significantly threatens maize (Zea mays L.) production across the Americas. Host genetic resistance offers the most viable long-term management strategy. Building on observed differential tar spot susceptibility, we utilized 92 recombinant-inbred lines (RILs) from the Intermated B73 x Mo17 (IBM-94) population to characterize the genetic architecture of resistance. Phenotypic analysis of 92 RILs plus the highly susceptible parent Mo17 and the moderately resistant parent B73 confirmed stable differences in susceptibility, with B73 consistently demonstrating moderate resistance compared to Mo17. Analysis of variance revealed highly significant genetic variation within the population (F = 12.96; p < 0.001). A high Pearson correlation (r = 0.8706, p < 0.0001) and coefficient of determination (R2 = 0.7579) across environments indicated that 76% of the phenotypic variance is attributable to genetic factors. Linkage mapping identified a novel, consistent major QTL cluster on chromosome 1. This cluster comprises five regions (qTAR_1.1 through qTAR_1.5) exceeding the significance threshold (LOD 3.8) in both years. We identified 74 candidate genes including bZIP and RING/U-box proteins at significant SNP peaks. Additionally, gene annotations revealed a high concentration of wall-associated kinases and S-locus lectin protein kinases within the qTAR_1.4 and qTAR_1.5 regions, alongside potential defense-related transcription factors (MYB, bZIP, and C2H2 zinc fingers). These results provide a framework for high-resolution mapping and functional validation to accelerate the development of tar spot-resistant maize cultivars.

plant biology↗

bioRxiv2026

Microfluidic Agarose Microdroplets for DNA-Encoded Chemical Library Screening

DNA-encoded library (DEL) technology enables high-throughput small-molecule discovery but is typically performed using purified proteins under in vitro conditions that do not reflect native intracellular environments. Here, we present a microfluidic agarose -droplet platform for cellular-context DEL screening. The porous hydrogel droplets provide mechanically stable yet permeable microenvironments that protect weak protein-ligand interactions while enabling efficient buffer exchange and ligand diffusion. Importantly, mild cell permeabilization within droplets selectively retained chromatin-associated proteins, allowing screening directly in a cellular context. Using BRD4 as a model target, we validated intracellular ligand engagement by fluorescence imaging and super-resolution microscopy. Small-scale DEL screening selectively enriched JQ1 in both bead-based and cell-based formats, and large-scale DEL screening across millions of encoded compounds successfully identified hit molecules by sequencing. This agarose -droplet-based strategy expands DEL technology toward biologically relevant and chromatin-associated targets under near-native conditions.

bioengineering↗

bioRxiv2025

Frontostriatal salience network expands as executive networks contract in Obsessive-Compulsive Disorder

Obsessive-compulsive disorder (OCD), marked by intrusive thoughts (obsessions) and repetitive behaviours (compulsions), is linked to dysfunction in frontostriatal circuits. However, neural differences potentially contributing to these alterations are often small, and conflicting evidence obscures the directionality and underlying mechanisms of these alterations. Like many psychiatric conditions, OCD follows a fluctuating symptom trajectory, with symptoms shifting dramatically over months--either naturally or due to treatment. Yet, the absence of longitudinal neuroimaging studies limits our understanding of the neural mechanisms driving these changes. Here, we used precision functional mapping in highly sampled individuals with OCD, uncovering a striking imbalance within frontostriatal networks. We identified a twofold expansion of the salience network in these individuals and a concomitant contraction of the frontoparietal network. Notably, salience network expansion was driven by border shifts, encroaching on adjacent executive networks and leading to their contraction. This imbalance within frontostriatal networks may relate to excessive attention to internal stimuli and lack of goal-directed control, which are classically observed in OCD. Longitudinal analyses of neuroimaging data collected over several months revealed frontostriatal connectivity changes tracking symptom severity. Overall, these findings pinpoint network-level features that may confer risk for individuals with OCD and highlight dynamic connectivity shifts tied to severity of OCD symptoms over time. By isolating frontostriatal abnormalities at the individual level in OCD and their relationship to symptom severity for the first time, this work paves the way for more targeted, personalized treatment strategies and identifies precision functional mapping as a model for precision psychiatry.

neuroscience↗

bioRxiv2025

Vesicular glutamate release is necessary for neural tube formation

The brain and spinal cord originate from a neural tube that is preceded by a flat structure known as the neural plate during early embryogenesis. In humans, failure of the neural plate to convert into a tube by the fourth week of pregnancy leads to neural tube defects (NTDs), birth defects with serious neurological consequences. The signaling mechanisms governing the process of neural tube morphogenesis are unclear. Here we show that in Xenopus laevis embryos, neural plate cells release glutamate during neural plate folding in a Ca2+ and vesicular glutamate transporter-1 (VGluT1)-dependent manner. Vesicular release of glutamate elicits Ca2+ transients in neural plate cells that correlate with activation of Erk1/2. Knocking down or out VGluT1 leads to NTDs through increased expression of Sox2, neural stem cell transcription factor, and neural plate cell proliferation. Exposure during early pregnancy to neuroactive drugs that disrupt these signaling mechanisms might increase the risk of NTDs in offspring.

neuroscience↗

bioRxiv2024

Tar Spot Disease Severity Influences Phyllosphere-Associated Bacterial and Fungal Microbiomes

Tar spot, caused by the obligate fungal pathogen Phyllachora maydis, is a foliar disease of corn that has become a major economic concern in the United States. To test the hypothesis that P. maydis can interact with other foliar microorganisms, we investigated phyllosphere microbiomes in relation to corn inbreds with differential tar spot symptoms under natural infestation in the field. Leaf samples from sixteen inbred lines were assessed for tar spot symptoms, and bacterial and fungal microbiomes were characterized by paired-end sequencing on the Illumina MiSeq platform. Comparison of the phyllosphere microbiomes revealed distinct bacterial and fungal communities between resistant and susceptible lines. Bacterial and fungal species richness was significantly higher in resistant compared to susceptible inbred lines in a sample-specific manner. In contrast, there were no clear differences in diversity when including evenness of bacterial communities between the resistant and susceptible lines. Diversity of fungal communities differed significantly, particularly between twelve of the fourteen susceptible lines versus resistant lines. Plant-beneficial bacterial genera such as Methylorubrum and Quadrisphaera were associated with resistant lines, while Pantoea, Deinococcus and Pseudomonas were the least abundant. The second-most commonly detected fungus likely was a Coniothyrium, but whether it is the same species that was identified as a possible mycoparasite of P. maydis in Central and South America is not known. Fungal genera Cladosporium, Papiliotrema, Cryptococcus, Tilletiopsis and Alternaria were associated with resistant lines while Sphaerellopsis was the least-abundant genus. In contrast, Puccinia, Sphaerellopsis and Phyllachora were the dominant fungal genera in susceptible lines. Our findings imply that P. maydis infection may result in a distinct microbiota with lower diversity. Further analyses of these distinct microbiota between resistant and susceptible lines could lead to a better understanding of the potential role of foliar microbiomes in causing or resisting P. maydis infection.

plant biology↗

bioRxiv2023

Cognitive tasks, anatomical MRI, and functional MRI data evaluating the construct of self-regulation

We describe the following shared data from N=103 healthy adults who completed a broad set cognitive tasks, surveys, and neuroimaging measurements to examine the construct of self-regulation. The neuroimaging acquisition involved task-based fMRI, resting fMRI, and structural MRI. Each subject completed the following ten tasks in the scanner across two 90- minute scanning sessions: attention network test (ANT), cued task switching, Columbia card task, dot pattern expectancy (DPX), delay discounting, simple and motor selective stop signal, Stroop, a towers task, and a set of survey questions. Subjects also completed resting state scans. The dataset is shared openly through the OpenNeuro project, and the dataset is formatted according to the Brain Imaging Data Structure (BIDS) standard.

neuroscience↗

bioRxiv2023

Glycoprotein VI is Critical for the Detection and Progression of Abdominal Aortic Aneurysms

A common feature in patients with abdominal aortic aneurysms (AAA) is the formation of a nonocclusive intraluminal thrombus (ILT) in regions of aortic dilation. Platelets are known to maintain hemostasis and propagate thrombosis through several redundant activation mechanisms, yet the role of platelet activation in the pathogenesis of AAA associated ILT is still poorly understood. Thus, we sought to investigate how platelet activation impacts the pathogenesis of AAA. Using RNA-sequencing, we identify that the platelet-associated transcripts are significantly enriched in the ILT compared to the adjacent aneurysm wall and healthy control aortas. We found that the platelet specific receptor glycoprotein VI (GPVI) is among the top enriched genes in AAA ILT and is increased on the platelet surface of AAA patients. Examination of a specific indicator of platelet activity, soluble GPVI (sGPVI), in two independent AAA patient cohorts is highly predictive of a AAA diagnosis and associates more strongly with aneurysm growth rate when compared to D-dimer in humans. Finally, intervention with the anti-GPVI antibody (J) in mice with established aneurysms blunted the progression of AAA in two independent mouse models. In conclusion, we show that levels of sGPVI in humans can predict a diagnosis of AAA and AAA growth rate, which may be critical in the identification of high-risk patients. We also identify GPVI as a novel platelet-specific AAA therapeutic target, with minimal risk of adverse bleeding complications, where none currently exist. KEY POINTSO_LISoluble glycoprotein VI, which is a platelet-derived blood biomarker, predicts a diagnosis of AAA, with high sensitivity and specificity in distinguishing patients with fast from slow-growing AAA. C_LIO_LIBlockade of glycoprotein VI in mice with established aneurysms reduces AAA progression and mortality, indicating therapeutic potential. C_LI

pathology↗

bioRxiv2023

Uncovering the Environmental Conditions Required for Phyllachora maydis Infection and Tar Spot Development on Corn in the United States for Use as Predictive Models for Future Epidemics

Phyllachora maydis is a fungal pathogen causing tar spot of corn (Zea mays L.), a new and emerging, yield-limiting disease in the United States. Since being first reported in Illinois and Indiana in 2015, P. maydis can now be found across much of the corn growing of the United States. Knowledge of the epidemiology of P. maydis is limited but could be useful in developing tar spot prediction tools. The research presented here aims to elucidate the environmental conditions necessary for the development of tar spot in the field and the creation of predictive models to anticipate future tar spot epidemics. Extended periods (30-day windowpanes) of moderate ambient temperature were most significant for explaining the development of tar spot. Shorter periods (14- to 21-day windowpanes) of moisture (relative humidity, dew point, number of hours with predicted leaf wetness) were negatively correlated with tar spot development. These weather variables were used to develop multiple logistic regression models, an ensembled model, and two machine learning models for the prediction of tar spot development. This work has improved the understanding of P. maydis epidemiology and provided the foundation for the development of a predictive tool for anticipating future tar spot epidemics.

plant biology↗

bioRxiv2023

The response time paradox in functional magnetic resonance imaging analyses

The functional MRI (fMRI) signal is a proxy for an unobservable neuronal signal, and differences in fMRI signals on cognitive tasks are generally interpreted as reflecting differences in the intensity of local neuronal activity. However, changes in either intensity or duration of neuronal activity can yield identical differences in fMRI signals. When conditions differ in response times (RTs), it is thus impossible to determine whether condition differences in fMRI signals are due to differences in the intensity of neuronal activity or to potentially spurious differences in the duration of neuronal activity. The most common fMRI analysis approach ignores RTs, making it difficult to interpret condition differences that could be driven by RTs and/or intensity. Because differences in response time are one of the most important signals of interest for cognitive psychology, nearly every task of interest for fMRI exhibits RT differences across conditions of interest. This results in a paradox, wherein the signal of interest for the psychologist is a potential confound for the fMRI researcher. We review this longstanding problem, and demonstrate that the failure to address RTs in the fMRI time series model can also lead to spurious correlations at the group level related to RTs or other variables of interest, potentially impacting the interpretation of brain-behavior correlations. We propose a simple approach that remedies this problem by including RT in the fMRI time series model. This model separates condition differences from RT differences, retaining power for detection of unconfounded condition differences while also allowing the identification of RT-related activation. We conclude by highlighting the need for further theoretical development regarding the interpretation of fMRI signals and their relationship to response times.

neuroscience↗

bioRxiv2020

EAT-UpTF: Enrichment Analysis Tool for Upstream Transcription Factors of a gene group

EAT-UpTF (Enrichment Analysis Tool for Upstream Transcription Factors of a gene group) is an open-source Python script that analyzes the enrichment of upstream transcription factors (TFs) in a group of genes-of-interest (GOIs). EAT-UpTF utilizes genome-wide lists of TF-target genes generated by DNA affinity purification followed by sequencing (DAP-seq) or chromatin immunoprecipitation followed by sequencing (ChIP-seq). Unlike previous methods based on the two-step prediction of cis-motifs and DNA-element-binding TFs, our EAT-UpTF analysis enabled a one-step identification of enriched upstream TFs in a set of GOIs using lists of empirically determined TF-target genes. Contactsangreashim@gmail.com or pjseo1@snu.ac.kr Availabilityhttps://github.com/sangreashim/EAT-UpTF

bioinformatics↗