Biology subjects

liu, m.

Publications and source records attributed to liu, m..

3 recordsLinked to original sources

bioRxiv2026

An electron-bifurcating hydrogenase-like activity associated with mitochondrial Complex I under hypoxia in vascular plants

Abstract Molecular hydrogen (H2) evolution by higher plants under oxygen limitation was reported more than six decades ago, yet its origin, biochemical basis and physiological significance have remained unresolved. Here, we localize this activity to a mitochondrial, Complex I-associated electron-transfer system. Mitochondrial fractions from etiolated Vigna radiata hypocotyls accumulated H2 under hypoxia and mildly acidic conditions. H2 accumulation was nearly abolished by rotenone and was sensitive to perturbations of Complex II, quinone-pool turnover, terminal oxidases and protonmotive force. NADH-generating substrates and succinate-fumarate supplementation stimulated H2 accumulation, while metabolic profiling linked H2 production to succinate and NADH accumulation. Cumulative H2 production exceeded the measured NADH pool by approximately two orders of magnitude, requiring sustained NADH regeneration. These findings support a division-of-labour model involving coexisting mature Complex I and CI*, a Complex I assembly or remodeling state. TCA-cycle dehydrogenation and succinate-driven reverse electron transfer (RET) through mature Complex I replenish the matrix NADH pool, whereas CI* consumes NADH through an H2-evolving branch, regenerating NAD. This model identifies a potential conditional redox function for CI* and an electron outlet coupled to continuous NADH cycling. Unlike mammalian RET, which can generate pronounced reactive oxygen species (ROS), diversion of reducing equivalents into H2 could attenuate the corresponding ROS signature, potentially helping explain the elusive physiological evidence for plant RET. The data establish a RET-compatible supply route, not direct reverse electron flux. Structural and computational analyses support an FMN-Fe-S branched mechanism whose catalytic steps remain unverified. More broadly, Complex I assembly may not merely build the respiratory machinery; under specific physiological conditions, its intermediate states may reshape electron fate, exposing latent hydrogenase-related chemistry associated with Complex I's evolutionary ancestry.

biochemistry↗

bioRxiv2026

Sparse mixed codes on shared manifolds for human-like spatial attention in artificial neural networks

Spatial attention is often partitioned into endogenous, exogenous, and social forms, yet it remains unclear whether a single neural circuit can support all three and how their population codes are organized. Here we trained recurrent artificial neural networks (ANNs) with convolutional sensory front-ends on three classic cueing paradigms (central, peripheral, and gaze cues) to reproduce human reaction time (RT) profiles across cue-target onset asynchronies. Despite differences in sensory architecture and visual experience, all ANNs captured the full facilitation-inhibition time course for all three attention types. Model-based targeted dimensionality reduction (mTDR) revealed that cue- and choice-related activity in the advanced cognitive module evolved as rotations within a shared low-dimensional manifold, with angular deflections that mirrored the distinct temporal dynamics of endogenous, exogenous, and social attention. Attentional signals were encoded by highly sparse, distributed population activity: a small subset of recurrent units explained most task-related variance, was sufficient to recover human-like RT patterns after virtual lesioning, and became progressively sparser as training improved performance. At the same time, single unit responses displayed pervasive mixed selectivity, dominated by nonlinear conjunctions of cue type, cue direction, and validity, whose strength and heterogeneity robustly predicted model performance. Together, these results identified low-dimensional geometric rotations, sparse coding, and nonlinear mixed selectivity as core computational principles through which a single recurrent circuit could generate human-like temporal dynamics across endogenous, exogenous, and social orienting, and provided testable predictions for population-level mechanisms of spatial attention in the brain.

neuroscience↗

bioRxiv2020

SETD2 deficiency impairs β-catenin destruction complex to facilitate renal cell carcinoma formation

Clear cell renal cell carcinoma (ccRCC) is a largely incurable disease that is highly relevant to epigenetic regulation including histone modification and DNA methylation. SET domain-containing 2 (SETD2) is a predominant histone methyltransferase catalyzing the trimethylation of histone H3 Lysine 36 (H3K36me3) and its mutations are highly relevant to clear cell renal cell carcinoma (ccRCC). However, its physiology role in ccRCC remains largely unexplored. Here we report that Setd2 deletion impairs the {beta}-catenin destruction complex to facilitate ccRCC formation in a c-MYC-generated polycystic kidney disease (PKD) model, which can be relieved by an inhibitor of {beta}-catenin-responsive transcription. Clinically, SETD2 loss is widely observed in ccRCC samples, and negatively correlated with expression of some members of {beta}-catenin destruction complex, but positively correlated with the activation of Wnt/{beta}-catenin signaling. Our findings thus highlight a previously unrecognized role of SETD2-mediated H3K36me3 modification in regulation of Wnt/{beta}-catenin pathway in ccRCC. SummaryOur findings for the first time reveal a previously unrecognized role of the SETD2-mediated H3K36me3 modification in regulation of the Wnt/{beta}-catenin pathway in ccRCC and shed light on the molecular mechanisms underlying the formation of renal cell carcinoma with epigenetic disorders.

cancer biology↗