Biology subjects

wang, k.

Publications and source records attributed to wang, k..

3 recordsLinked to original sources

bioRxiv2026

Cerebellar Normative Modeling Identifies Neuroanatomical Biotypes Predicting dTMS Response in Spinocerebellar Ataxia Type 3

BackgroundSpinocerebellar ataxia type 3 (SCA3) presents with significant clinical heterogeneity. Traditional case-control neuroimaging, based on group means, obscures inter-individual anatomical variability, hindering the identification of stratification biomarkers for interventions like Transcranial Magnetic Stimulation (TMS). MethodsTo quantify individual neuroanatomical deviations, we constructed a cerebellar normative model using a multi-center dataset of 2,071 healthy controls with 2,549 MRI scans. Gray matter volume deviations (Z-scores) were mapped across 27 cerebellar lobules in 114 genetically confirmed SCA3 patients, and unsupervised clustering was applied to identify neuroanatomical biotypes. Clinical relevance was assessed by associating biotypes with ataxia severity and deep TMS (dTMS) outcomes in a longitudinal subset . ResultsWe identified two distinct biotypes: Biotype 1 exhibited relative structural preservation (positive deviations) predominantly in the posterior cerebellum (lobules VIIB, VIIIA), whereas Biotype 2 was characterized by extensive atrophy (negative deviations) centered on the anterior motor cerebellum (lobules I-VI). Clinically, Biotype 2 patients presented with significantly more severe baseline ataxia. However, regarding treatment response, an inverse relationship was observed: Biotype 2 patients demonstrated significantly greater symptomatic improvement following dTMS compared to Biotype 1. To further identify the optimal neuromodulatory strategy for each biotype, we compared the therapeutic efficacy of repetitive TMS (rTMS) and dTMS. While both biotypes showed clinical improvement following rTMS, Biotype 1 exhibited a superior therapeutic response to rTMS relative to dTMS. Furthermore, feature weight analysis identified atrophy of the right lobule VIIB as a critical predictor of clinical severity in Biotype 2. ConclusionThis study demonstrates that normative modeling can decode SCA3 heterogeneity. The identification of these biotypes reveals a dissociation between baseline structural integrity and neuromodulatory responsiveness, suggesting that patients with severe anterior cerebellar atrophy may, counterintuitively, derive greater therapeutic benefit from dTMS. Furthermore, by comparing the therapeutic efficacy of rTMS and dTMS, we further clarified biotype-specific treatment responses. These findings support the use of individualized neuroanatomical mapping for patient stratification in precision medicine.

neuroscience↗

bioRxiv2026

Gene transcription and chromatin packing domains form a self-organizing system

The human genome organizes into several thousand chromatin packing domains that couple euchromatin and heterochromatin into unified nanoscale volumes. Prior work suggested these domains form by transcriptionally driven loops that guide packing domain assembly. Here, we study the process of transcriptionally driven domain formation and maintenance. By pairing auxin-inducible degron technology with nanoscopic imaging, transcriptomics, and Hi-C, we show that Pol-II regulates conformationally defined interphase chromatin packing domains. Pol-II facilitates nascent domain generation and maintains mature domain integrity through the process of generating transcriptional loops. Mechanistically, Pol-II maintains the packing of intronic and intergenic chromatin within domains by transcribing exons within gene bodies. Consequently, polymerase loss disrupts genome connectivity, in situ packing domains, and gene expression, genome-wide. Our findings suggest chromatin packing domains and RNA synthesis are tightly coupled to optimize transcriptional responses in human cells.

molecular biology↗

bioRxiv2019

Long noncoding RNA AVAN promotes antiviral innate immunity by interacting with TRIM25 and enhancing the transcription of FOXO3a

Accumulating evidence has shown that long noncoding RNAs (lncRNAs) are involved in several biological processes, including immune responses. However, the role of lncRNAs in antiviral innate immune responses remains largely unexplored. Here, we identify an uncharacterized human lncRNA from influenza A virus (IAV) patients, antivirus and activate neutrophil (AVAN), that is significantly up-regulated upon virus infection. Mechanistically, nuclear lncRNA-AVAN positively regulates the transcription of forkhead box O3A (FOXO3a) by associating with its promoter and inducing chromatin remodeling to promote neutrophil chemotaxis. Furthermore, we also found that cytoplasmic lncRNA-AVAN directly binds tripartite motif containing 25 (TRIM25) and enhances the association of TRIM25 and Retinoic acid inducible gene-1 proteins (RIG-I) and the ubiquitylation of RIG-I, thereby promoting TRIM25- and RIG-I-mediated antiviral innate immune signaling. More importantly, we enforced the expression of AVAN in transgenic mice and found that it significantly alleviated IAV virulence and virus production. Collectively, these findings highlight the potential clinical implications of lncRNA-AVAN as a key positive regulator of the antiviral innate immune response and a promising target for developing broad antiviral therapeutics.

immunology↗