Biology subjects

Shan, T.

Publications and source records attributed to Shan, T..

12 recordsLinked to original sources

bioRxiv2026

Dual role of RBM3 in PEDV infection: stabilization of viral RNA and upregulation of the entry factor HSPA5

RBM3, a member of the cold-shock protein family, functions as an RNA chaperone that stabilizes target transcripts by binding to their untranslated regions (UTRs). Porcine epidemic diarrhea virus (PEDV) is an enteric coronavirus that poses a serious threat to the swine industry, and its replication heavily depends on its genomic and subgenomic RNAs, making these RNAs potential targets for host RNA-binding proteins. In this study, we show that RBM3 promotes PEDV replication through a dual mechanism. On one hand, RBM3 exhibits a binding preference for the viral 3'UTR, which prolongs the half-life of viral RNA and thereby promotes PEDV proliferation. RBM3 also interacts with the PEDV nucleocapsid (N) protein and replication-associated double-stranded RNA (dsRNA) signals, suggesting that RBM3 may be associated with viral replication complexes, though its contribution to their functional integrity remains to be determined. On the other hand, RBM3 increases HSPA5 promoter activity and HSPA5 mRNA levels, linking RBM3 to HSPA5, a host factor known to facilitate PEDV attachment and internalization. These two mechanisms together provide a mechanistic basis for efficient PEDV infection. Our findings identify RBM3 as a positive host regulator of PEDV and establish, for the first time, a functional link between RBM3 and HSPA5, offering new insights into coronavirus-host interactions and suggesting RBM3 as a potential target for antiviral intervention.

molecular biology↗

bioRxiv2025

The serine protease homolog Skanda modulates Toll-Phenoloxidase-mediated immunity in Drosophila

Extracellular serine protease (SP) cascades are central regulators of insect innate immunity. These cascades are negatively controlled by serine protease inhibitors (serpins) and fine-tuned by serine protease homologs (SPHs), which resemble SPs but lack catalytic activity. In Drosophila, a key SP cascade--the Toll-phenoloxidase (PO) pathway--governs both the melanization response and Toll-dependent antimicrobial peptide production. This cascade is triggered by secreted pattern-recognition receptors or microbial proteases and converges on two clip-domain SPs, Persephone and Hayan, which activate the Toll ligand Spatzle via the Spatzle-Processing Enzyme (SPE) and process prophenoloxidases. Here, we characterize the SPH Skanda and uncover its role in the Toll-PO cascade. skanda is genomically clustered with hayan and persephone and is transcriptionally induced upon infection. Skanda is unusual among SPHs, containing a long serine/threonine-rich region, two clip domains, and atypical disulfide bonds. Skanda is unstable and subject to cleavage by Grass. Functional assays show that Skanda dampens activation of Hayan, and to a lesser extent Persephone, within the Toll-PO cascade. Notably, skanda-deficient flies are highly susceptible to Staphylococcus aureus despite displaying normal Toll signaling and cuticular melanization. Moreover, compound mutants lacking two members of the hayan-psh-skanda cluster reveal a hidden contribution of Skanda to Toll activation in the absence of Persephone. Together, our results identify Skanda as a modulatory SPH that fine-tunes Toll pathway activity in concert with Persephone and Hayan.

immunology↗

bioRxiv2025

Reproducibility of Scientific Claims in Drosophila Immunity: A Retrospective Analysis of 400 Publications

Drosophila immunity has been the focus of intense study and has impacted other research fields including innate immunity and agriculturally or epidemiologically relevant investigations of insect pests and vectors. Unsurprisingly for such a large body of work, some published results were later found to be irreplicable. Although some results have been contradicted in the literature, many have no published follow-up, either due to a lack of research or low motivation to publish negative or contradictory results. We have addressed this by performing a reproducibility project that analyses the conceptual replicability of claims from articles published on Drosophila immunity before 2011. To assess replicability, we extracted claims from 400 articles on the Drosophila immune response to bacteria and fungi and performed preliminary verification by comparing these claims to other published literature in the field. Using alternative approaches, we also experimentally tested some unchallenged claims, with no published follow-up. The intent of this analysis was to centralize evidence on insights and findings to improve clarity for scientists that may base research programs on these data. Although the aim of the ReproSci project is to assess the replicability of claims made in articles published in the field of Drosophila immunity, it is in no way an assessment of the scientific value of the research. All our data are published on a publicly available website associated with this article (https://ReproSci.epfl.ch/) that encourages community participation. This article provides a short summary of claims that were found to have contradictory evidence, which may help the community to assess past findings on Drosophila immunity and improve clarity going forward. Statistical analysis of this reproducibility study and metascience insights obtained from this approach are discussed in a companion article.

genetics↗

bioRxiv2025

Next-Generation saRNA Platforms: Systematic Screening and Engineering Enhances Superior Protein Expression and Organ-Specific Targeting for RNA Therapeutics

Self-amplifying RNA (saRNA), derived from alphaviruses, encodes nonstructural proteins (NSP1-4) that form a replicase complex, enabling prolonged and amplified protein expression at lower doses than conventional mRNA. However, its high immunogenicity and limited replication efficiency require optimization for improved protein expression. Here, we systematically optimized a widely used Venezuelan Equine Encephalitis Virus (VEEV)-based saRNA by refining its capping structure, nucleotide modifications, polyA tail length, and regulatory elements, achieving over 10-fold enhancement in protein expression compared to the wild-type. Additionally, we screened 28 alphavirus-derived saRNA constructs in vitro, selecting the top 3 candidates Everglades virus (EVEV), Mosso das Pedras virus (MDPV), and Rio Negro virus (RNV) for in vivo evaluation using SM102 lipid nanoparticle (LNP) formulations and luciferase reporters. These optimized saRNAs demonstrated sustained expression and distinct extrahepatic tissue-specific biodistribution, notably high spleen targeting compared to conventional mRNA. Such organ-specific expression profiles present novel strategies for targeted RNA therapeutics, and further integration with advanced delivery technologies could enhance the precision, efficacy, and therapeutic potential of mRNA-based treatments. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=149 SRC="FIGDIR/small/644708v1_ufig1.gif" ALT="Figure 1"> View larger version (56K): org.highwire.dtl.DTLVardef@1eed9bdorg.highwire.dtl.DTLVardef@192815org.highwire.dtl.DTLVardef@196a8e9org.highwire.dtl.DTLVardef@2b6e53_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOTOC figureC_FLOATNO C_FIG

molecular biology↗

bioRxiv2024

Chimeric music reveals an interaction of pitch and time in electrophysiological signatures of music encoding

Pitch and time are the essential dimensions defining musical melody. Recent electrophysiological studies have explored the neural encoding of musical pitch and time by leveraging probabilistic models of their sequences, but few have studied how the features might interact. This study examines these interactions by introducing "chimeric music," which pairs two distinct melodies, and exchanges their pitch contours and note onset-times to create two new melodies, thereby distorting musical pattern while maintaining the marginal statistics of the original pieces pitch and temporal sequences. Through this manipulation, we aimed to dissect the music processing and the interaction between pitch and time. Employing the temporal response function (TRF) framework, we analyzed the neural encoding of melodic expectation and musical downbeats in participants with varying levels of musical training. Our findings revealed differences in the encoding of melodic expectation between original and chimeric stimuli in both dimensions, with a significant impact of musical experience. This suggests that the structural violation due to decoupling the pitch and temporal structure affect expectation processing. In our analysis of downbeat encoding, we found an enhanced neural response when participants heard a note that aligned with the downbeat during music listening. In chimeric music, responses to downbeats were larger when the note was also a downbeat in the original music that provided the pitch sequence, indicating an effect of pitch structure on beat perception. This study advances our understanding of the neural underpinnings of music, emphasizing the significance of pitch-time interaction in the neural encoding of music. Significance StatementListening to music is a complex and multidimensional auditory experience. Recent studies have investigated the neural encoding of pitch and timing sequences in musical structure, but they have been studied independently. This study addresses the gap in understanding of how the interaction between pitch and time affects their encoding. By introducing "chimeric music," which decouples these dimensions in melodies, we investigate how this interaction influences the neural activities using EEG. Leveraging and the temporal response function (TRF) framework, we found that structural violations in pitch-time interactions impact musical expectation processing and beat perception. These results advance our knowledge of how the brain processes complex auditory stimuli like music, underscoring the critical role of pitch and time interactions in music perception.

neuroscience↗

bioRxiv2024

Single-nucleus transcriptomics reveal the cytological mechanism of conjugated linoleic acids in regulating intramuscular fat deposition

Conjugated linoleic acids (CLAs) can serve as a nutritional intervention to regulate quality, function and fat infiltration in skeletal muscles but the specific cytological mechanisms are still unknown. Here, we applied single-nucleus RNA-sequencing (snRNA-seq) to characterize the cytological mechanism of CLAs regulates fat infiltration in skeletal muscles based on pig models. We investigated the regulatory effects of CLAs on cell populations and molecular characteristics in pig muscles and found CLAs could promote the transformation of fast glycolytic myofibers into slow oxidative myofibers. We also observed three subpopulations including SCD+/DGAT2+, FABP5+/SIAH1+, and PDE4D+/PDE7B+ subclusters in adipocytes and CLAs could increase the percentage of SCD+/DGAT2+ adipocytes. RNA velocity analysis showed FABP5+/SIAH1+ and PDE4D+/PDE7B+ adipocytes could differentiate into SCD+/DGAT2+ adipocytes. We further verified the differentiated trajectory of mature adipocytes and identified PDE4D+/PDE7B+ adipocytes could differentiate into SCD+/DGAT2+ and FABP5+/SIAH1+ adipocytes by using high IMF content Laiwu pig models. The cell-cell communication analysis identified the interaction network between adipocytes and other subclusters such as fibro/adipogenic progenitors (FAPs). Pseudotemporal trajectory analysis and RNA velocity analysis also showed FAPs could differentiate into PDE4D+/PDE7B+ preadipocytes and we discovered the differentiated trajectory of preadipocytes into mature adipocytes. Besides, we found CLAs could promote FAPs differentiate into SCD+/DGAT2+ adipocytes via inhibiting c-Jun N-terminal kinase (JNK) signalling pathway in vitro. This study provides a foundation for regulating fat infiltration in skeletal muscles by using nutritional strategies and provides potential opportunities to serve pig as an animal model to study human fat infiltrated diseases.

cell biology↗

bioRxiv2024

Comparing Methods for Deriving the Auditory Brainstem Response to Continuous Speech in Human Listeners

Several tools have recently been developed to derive the Auditory Brainstem Response (ABR) from continuous natural speech, facilitating investigation into subcortical encoding of speech. These tools rely on deconvolution, which models the subcortical auditory pathway as a linear system, where a nonlinearly processed stimulus is taken as the input (i.e., regressor), the electroencephalogram (EEG) data as the output, and the ABR as the impulse response deconvolved from the recorded EEG and the regressor. In this study, we analyzed EEG recordings from subjects listening to both unaltered natural speech and synthesized "peaky speech." We compared the derived ABRs using three regressors: the half-wave rectified stimulus (HWR) from Maddox and Lee (2018), the glottal pulse train (GP) from Polonenko and Maddox (2021), and the auditory nerve modeled response (ANM) from Shan et al. (2024). Our evaluation focused on the fidelity, efficiency, and practicality of each method in different scenarios. The results indicate that the ANM regressor for both peaky and unaltered speech and the GP regressor for peaky speech provided the best performance, whereas the HWR regressor demonstrated relatively poorer performance. The findings in this study will guide future research in selecting the most appropriate paradigm for ABR derivation from continuous, naturalistic speech.

neuroscience↗

bioRxiv2023

Evaluation of recombination rate of microhaplotypes based on the 1000 Genomes Project family data

Microhaplotype, a kind of multi-allelic genetic marker that contains two or more SNPs in the range of hundreds of base pairs, has emerged as an important genetic marker in forensic genetics. However, the recombination within the microhaplotype, which has been neglected in most studies, leads to changes in its alleles during inheritance, producing alleles that are not identical to parental alleles and affecting the likelihood ratio calculation of the MH in forensic DNA analysis involving kinship. We constructed a highly dense and extensive MH set in the human genome based on the expanded 1000 Genomes Project (GRCh38). Using the pedigree data contained in 18 populations and a total of 1204 meioses in the GRCh38 dataset, we scanned and confirmed the recombination events that occurred within the above MH loci, to clarify the relationship between recombination and MH polymorphisms. We investigated the average incidence of MH recombinant alleles and the average recombination rate of genome-wide MHs in the hope of providing a reference for the correction of the likelihood ratio in the MH system of future kinship analysis.

genetics↗

bioRxiv2022

Music and Speech Elicit Similar Subcortical Responses in Human Listeners

Music and speech are two sounds that are unique to human beings and encountered in daily life. Both are transformed by the auditory pathway from an initial acoustical encoding to higher level cognition. Most studies of speech and music processing are focused on the cortex, and the subcortical response to natural, polyphonic music is essentially unstudied. This study was aimed to compare the subcortical encoding of music and speech using the auditory brainstem response (ABR). While several methods have recently been developed to derive the ABR to continuous speech, they are either not applicable to music or give poor results. In this study, we explored deriving the ABR through deconvolution using three regressors: 1) the half-wave rectified stimulus waveform, 2) the modeled inner hair cell potential, and 3) the auditory nerve model firing rate (ANM), where the latter two were generated from a computational auditory periphery model. We found the ANM regressor yields robust and interpretable ABR waveforms to diverse genres of music and multiple types of speech. We then used the ANM-derived ABRs to compare the subcortical responses to music and speech and found that they are highly similar in morphology. We further investigated cortical responses using the same deconvolution method, and found the responses there were also quite similar, which was unexpected based on previous studies. We conclude that when using our proposed deconvolution regressor that accounts for acoustical differences nonlinear effects on peripheral encoding, the derived brainstem and cortical responses to music and speech are highly correlated.

neuroscience↗

bioRxiv2022

Speech-In-Noise Comprehension is Improved When Viewing a Deep-Neural-Network-Generated Talking Face

Listening in a noisy environment is challenging, but many previous studies have demonstrated that comprehension of speech can be substantially improved by looking at the talkers face. We recently developed a deep neural network (DNN) based system that generates movies of a talking face from speech audio and a single face image. In this study, we aimed to quantify the benefits that such a system can bring to speech comprehension, especially in noise. The target speech audio was masked with signal to noise ratios of -9, -6, -3, and 0 dB and was presented to subjects in three audio-visual (AV) stimulus conditions: 1) synthesized AV: audio with the synthesized talking face movie; 2) natural AV: audio with the original movie from the corpus; and 3) audio-only: audio with a static image of the talker. Subjects were asked to type the sentences they heard in each trial and keyword recognition was quantified for each condition. Overall, performance in the synthesized AV condition fell approximately halfway between the other two conditions, showing a marked improvement over the audio-only control but still falling short of the natural AV condition. Every subject showed some benefit from the synthetic AV stimulus. The results of this study support the idea that a DNN-based model that generates a talking face from speech audio can meaningfully enhance comprehension in noisy environments, and has the potential to be used as a "visual hearing aid."

neuroscience↗

bioRxiv2020

Identification of novel tetracycline resistance gene tet(X14) and its co-occurrence with tet(X2) in a tigecycline-resistant and colistin-resistant Empedobacter stercoris

Tigecycline is one of the last-resort antibiotics to treat severe infections. Recently, tigecycline resistance has sporadically emerged with an increasing trend, and Tet(X) family represents a new resistance mechanism of tigecycline. In this study, a novel chromosome-encoded tigecycline resistance gene, tet(X14), was identified in a tigecycline-resistant and colistin-resistant Empedobacter stercoris strain ES183 recovered from a pig fecal sample in China. Tet(X14) shows 67.14-96.39% sequence identity to the other variants [Tet(X) to Tet(X13)]. Overexpression of Tet(X14) in Escherichia coli confers 16-fold increase in tigecycline MIC (from 0.125 to 2 mg/L), which is lower than that of Tet(X3), Tet(X4) and Tet(X6). Structural modelling predicted that Tet(X14) shared a high homology with the other 12 variants with RMSD value from 0.003 to 0.055, and Tet(X14) can interact with tetracyclines by a similar pattern as the other Tet(X)s. tet(X14) and two copies of tet(X2) were identified on a genome island with abnormal GC content carried by the chromosome of ES183, and no mobile genetic elements were found surrounding, suggesting that tet(X14) might be heterologously obtained by ES183 via recombination. Blasting in Genbank revealed that Tet(X14) was exclusively detected on the chromosome of Riemerella anatipestifer, mainly encoded on antimicrobial resistance islands. E. stercoris and R. anatipestifer belong to the family Flavobacteriaceae, suggesting that the members of Flavobacteriaceae maybe the major reservoir of tet(X14). Our study reports a novel chromosome-encoded tigecycline resistance gene tet(X14). The expanded members of Tet(X) family warrants the potential large-scale dissemination and the necessity of continuous surveillance for tet(X)-mediated tigecycline resistance.

genetics↗

bioRxiv2020

Silent dissemination of plasmid-borne tigecycline resistance gene tet(X6) in livestock-associated Acinetobacter towneri

A tigecycline-resistance gene, tet(X6), was detected on a 159-kb novel plasmid carried by a tigecycline-susceptible livestock-associated Acinetobacter towneri isolate. The genetic context of tet(X6) ({Delta}ISVsa3-tet(X6)-abh-guaA-ISVsa3) is highly similar with that of the other plasmid-borne tet(X) variants. The 23-Ala residue of the first FAD binding site conferred higher activity to Tet(X6) than the 23-Gly reside conserved in the other plasmid-borne tet(X)s. To our knowledge, this is the first report of tet(X6) carried by the plasmid.

genetics↗