Biology subjects

Yang, X.-F.

Publications and source records attributed to Yang, X.-F..

5 recordsLinked to original sources

bioRxiv2026

Enhancing the Identification of NHS Ester-Mediated Lysine-Cysteine Cross-Linking via Reduced Trypsin Digestion Time

Abstract Chemical cross-linking mass spectrometry (XL-MS) is a powerful technique for elucidating protein structures and interactions, with NHS ester-based cross-linkers being the most widely used. Traditionally, NHS esters are considered highly specific for primary amines; although their reactivity toward cysteine thiols has been reported, it has not been systematically characterized in XL-MS due to the extreme lability of the resulting thioester bonds. Here, we demonstrate that NHS esters efficiently label cysteine residues and form stable lysine-cysteine (K-C) cross-links--species previously deemed labile in XL-MS. To preserve these thioester-based cross-linked sites , we optimized the standard XL-MS workflow and applied it to four model proteins. K-C cross-links constitute 23% to 59% of total detected cross-links, with C-C distances predominantly ranging from 12 to 40 [A], and 60% satisfying theoretical linker constraints -- confirming that K-C cross-links are as reliable as canonical lysine-lysine (K-K) cross-link sites. Cross-software validation and benchmarking against the heterobifunctional K-C cross-linker GMBS further demonstrated that our optimized workflow captures ~ 40% of GMBS-identified K-C cross-linked sites. Collectively, these findings expand the practical utility of NHS esters and enhance protein structural characterization by enabling simultaneous acquisition of K-K and K-C distance constraints.

biochemistry↗

bioRxiv2025

Species-specific genetic routes to a shared phenotype: convergent adaptation of beans to European long days

The loss of photoperiod sensitivity was a key prerequisite for the adaptation of common bean (Phaseolus vulgaris) and scarlet runner bean (P. coccineus) to European environments. While the genetic architecture of this trait has been studied for decades, primarily through QTL mapping in RILs and NILs, its molecular basis remains incompletely resolved. Here, we combine whole-genome resequencing of over 200 P. vulgaris accessions spanning Mesoamerican, Andean, and European origins with 130 P. coccineus cultivars from Mesoamerica and Europe. Phenotyping under controlled long-day conditions revealed distinct distributions of photoperiod sensitivity across species and gene pools. Genome-wide association and haplotype analyses identified single nucleotide variants strongly linked to flowering under long days. Consistent with prior studies, signals of selection reflect independent domestication events in the Americas. Importantly, we detect species-specific selection on core photoperiod regulators, demonstrating that both species achieved similar adaptive outcomes via functionally convergent genetic routes. By explicitly accounting for major loci shaping growth habit in our analyses, we were able to unmask additional genomic regions contributing to flowering responses in European cultivars. Together, these results show that adaptation to long-day environments occurred through stepwise, species-specific genomic innovations, first during domestication in the Americas and later under European cultivation. Our findings highlight the role of pathway-level convergent evolution in shaping complex domestication traits and underscore the potential of parallel genomic strategies for crop adaptation.

plant biology↗

bioRxiv2025

Intersecting effects of social circumstances and transcendent thinking on mid-adolescents' longitudinal functional connectome development

Socially moderated variation in mid-adolescents functional brain network (FBN) development is insufficiently studied, especially within low-SES contexts. Alongside demographic factors, evidence suggests adolescents malleable psychological dispositions may contribute, with possible clinical and educational implications. We applied graph theory to a unique 2-year longitudinal fMRI dataset (N=65) with an ecologically valid 2-hour interview revealing an emergent mid-adolescent psychological disposition, "transcendent thinking" (TT)--adolescents tendency to consider systems-level, ethical, personal implications of social information. Overall, FBNs showed increased segregation and entropy but decreased integration and energy. Modularity increased particularly in somatosensory subnetworks. Classifying participants by two key demographic factors, parents education (PE) and community violence exposure (CVE), FBN changes differed by group, and TT moderated changes in high-CVE/low-PE participants, arguably the most vulnerable group. Machine learning revealed TT and CVE, but not IQ, as principal FBN change predictors across groups. Findings suggest social context and psychological dispositions influence low-SES adolescents FBN development.

neuroscience↗

bioRxiv2024

Unravelling the progression of the zebrafish primary body axis with reconstructed spatiotemporal transcriptomics

Elucidating the spatiotemporal dynamics of gene expression is essential for understanding complex physiological and pathological processes. Traditional technologies like in situ hybridization (ISH) and immunostaining have been restricted to analyzing expression patterns of a limited number of genes. Spatial transcriptomics (ST) has emerged as a robust alternative, enabling the investigation of spatial patterns of thousands of genes simultaneously. However, current ST methods are hindered by low read depths and limited gene detection capabilities. Here, we introduce Palette, a pipeline that infers detailed spatial gene expression patterns from bulk RNA-seq data, utilizing existing ST data as only reference. This method identifies more precise expression patterns by smoothing, imputing and adjusting gene expressions. We applied Palette to construct the Danio rerio SpatioTemporal Expression Profiles (DreSTEP) by integrating 53-slice serial bulk RNA-seq data from three developmental stages with existing ST references and 3D zebrafish embryo images. DreSTEP provides a comprehensive cartographic resource for examining gene expression and spatial cell-cell interactions within zebrafish embryos. Utilizing machine learning-based screening, we identified key morphogens and transcription factors (TFs) essential for anteroposterior (AP) axis development and characterized their dynamic distribution throughout embryogenesis. In addition, among these TFs, Hox family genes were found to be pivotal in AP axis refinement. Their expression was closely correlated with cellular AP identities, and hoxb genes may act as central regulators in this process.

developmental biology↗

bioRxiv2022

PIMT suppresses endothelial activation and vascular inflammation through methylation of TRAF6

As a repair enzyme, protein L-isoaspartyl O-methyltransferase (PIMT) methylates and converts isoaspartyl residues (isoAsp) back to conventional forms to avoid protein damage during aging and stress responses. This study aims to investigate the pathological significance of PIMT in vascular inflammation. Herein, we show that PIMT is highly expressed in lung endothelial cells (ECs), and its reduction significantly exacerbates pulmonary inflammation in a murine model of acute lung injury (ALI). Mechanistically, we identify tumor necrosis factor receptor-associated factor 6 (TRAF6) as a substrate of PIMT. PIMT-mediated methylation of TRAF6 inhibits TRAF6 oligomerization, autoubiquitination, and LPS-induced NF-{kappa}B transactivation in ECs. Importantly, in addition to transcriptionally attenuating expression of adhesion molecules, PIMT post-translationally impedes site specific N-glycosylation of intercellular adhesion molecule-1 (ICAM-1), which leads to an increased protein degradation of ICAM-1 and a subsequent inhibition of EC interaction with immune cells during inflammatory process. Our results for the first time identify PIMT-mediated protein O-methylation as a key post-translational mechanism in controlling vascular inflammation, and suggest that PIMT may represent a novel therapeutic target in inflammatory vascular diseases.

physiology↗