Biology subjects

An, N.

Publications and source records attributed to An, N..

5 recordsLinked to original sources

bioRxiv2026

Structural basis for phosphorylation-induced inactivation of the rice ammonium transporter AMT1;1

Ammonium (NH4+) uptake and transport in plants are mediated by ammonium transporters (AMTs), which are tightly regulated by phosphorylation to prevent excess ammonium influx and toxic accumulation. However, the mechanism of phosphorylation-mediated inactivation is unique and remains unclear. Here, we report cryo-EM structures of the rice (Oryza sativa) ammonium transporter OsAMT1;1 in its wild-type and phosphomimetic variant T452D states. OsAMT1;1 forms a stable homotrimer, with conserved motifs affirming a shared transport mechanism within the AMT/MEP/Rh superfamily. Our structural analysis reveals that T452D phosphomimetic stabilizes an intracellular salt-bridge network and maintains the channel in a closed state, in which the ICL5 loop positions the hydrophobic plug residue Leu360 near the cytoplasmic exit to occlude the channel exit and abolish complementation capacity. Our findings elucidate phosphorylation-induced inactivation mechanism for the plant AMT1 subfamily, providing a structural paradigm for the post-translational regulation of nutrient uptake.

biophysics↗

bioRxiv2026

mTORC2 stabilizes HIF-1β to coordinate metabolic adaptation in lung cancer

Despite extensive genetic heterogeneity, lung tumors frequently converge on shared signaling dependencies that remain therapeutically underexploited. Here, we identify mTORC2 signaling as a convergent dependency across genetically distinct lung cancer subtypes and uncover HIF-1{beta} as a selective metabolic effector downstream of mTORC2 that promotes lung tumor progression. Elevated mTORC2 signaling in lung adenocarcinoma was associated with poor overall survival, metastatic dissemination and metabolic rewiring. Using complementary genetically engineered mouse models of Rictor deletion or overexpression in Kras-driven lung tumors, we show that mTORC2 activity is dispensable for normal lung homeostasis but required for tumor progression and metabolic adaptation in vivo. Mechanistically, mTORC2 stabilized HIF-1{beta} by preventing its ubiquitin-independent proteasomal degradation through a non-canonical PKC-CK2 signaling axis, independently of AKT. Integrated multi-omics analyses identified extensive metabolic rewiring downstream of the mTORC2-HIF-1{beta} axis, with sphingolipid metabolism emerging as a prominent and therapeutically exploitable vulnerability. Accordingly, pharmacological targeting of sphingolipid metabolism markedly impaired the growth of mTORC2-driven lung tumors in vivo. Together, our findings establish a non-canonical mTORC2-HIF-1{beta} signaling axis that couples oncogenic signaling to metabolic adaptation and defines therapeutically actionable metabolic vulnerabilities in lung cancer.

cancer biology↗

bioRxiv2024

Genome sequencing of 'Fuji' apple clonal varieties reveals evolutionary history and genetic mechanism of the spur-type morphology

Somatic variations arising during asexual reproduction can lead to the emergence of bud sports exhibiting advantageous traits, forming the basis for bud sport breeding in perennial plants. Here, we report a near-complete, fully phased genome assembly of Fuji apple, enabling comprehensive identification of somatic variants across 74 clonally propagated Fuji varieties. Phylogenetic analysis of Fuji sport varieties indicates that the emergence of spur-type and early maturation traits results from multiple independent formation events. A number of putative functional somatic variants are identified, including one spur-type specific deletion located in the promoter of the TCP transcription factor gene MdTCP11. DNA methylation level of the deletion-associated miniature inverted-repeat transposable element is lower in the spur-type varieties compared to the standard-type varieties, while the expression of MdTCP11 is significantly higher. Overexpression of MdTCP11 in apple decreases the plant height, highlighting its important role in the development of spur-type apple varieties. This study sheds light on the 80-year cloning history of Fuji and provides valuable candidate causative mutations for apple breeding.

plant biology↗

bioRxiv2024

DeepPrep: An accelerated, scalable, and robust pipeline for neuroimaging preprocessing empowered by deep learning

Neuroimaging has entered the era of big data. However, the advancement of preprocessing pipelines falls behind the rapid expansion of data volume, causing significant computational challenges. Here, we present DeepPrep, a pipeline empowered by deep learning and workflow manager. Evaluated on over 55,000 scans, DeepPrep demonstrates a 11-fold acceleration, exceptional scalability, and robustness compared to the current state-of-the-art pipeline, providing a promising solution to meet the scalability requirements of neuroimaging.

neuroscience↗

bioRxiv2023

Modulation of Pain Perception and Tolerance Following Treadmill Running with Different Intensities

ObjectiveThis study aimed to compare the effects of three intensities of treadmill running on pain perceptions in healthy individuals. And investigate the role of endogenous pain modulation in the exercise-induced hypoalgesia (EIH) effects. MethodsSixty-six healthy female individuals were included in this study and were randomly assigned to one of three treadmill running intensities for 35 minutes: 40% of their reserve heart rate (HRR), 55% HRR, or 70% HRR. The EIH effects were assessed by the changes of pressure pain thresholds (PPT) and pressure pain tolerance thresholds (PPTol) at multiple time points. The assessments were conducted prior to the treadmill running session every 5 minutes during the exercise bout, and at 5 minutes, 10 minutes, and 24 hours post-exercise. The conditioned pain modulation (CPM) was also measured to determine the functions of endogenous pain modulation. ResultsCompared with baseline, there was a significant increase of PPT and PPTol at arm and leg in all groups during running and 5-10min follow-ups. The PPT and PPTol changes of moderate and low intensity groups were significantly higher than the high intensity group during running and 24h after running. While the CPM responses of high intensity group were significantly reduced compared with other groups at 24h follow-up. ConclusionModerate and low intensity running may trigger the endogenous descending inhibition and elicit significant EIH effects following running and persisting over 24h. While the high intensity running only induced limited EIH effects for the activation of both descending pain inhibition and facilitation, with reduced CPM responses. Thus, the pain perception changes following exercises may reveal the potential mechanisms of EIH induced via exercises with different intensities. New findingsWhat is the central question of this study? Both the primary analgesia effect (EIH) and secondary pain allodynia (delayed onset muscle soreness) may occur following exercises, possibly due to the interaction between endogenous pain modulation and exercise intensities. What is the difference in the changes of primary and secondary pain perceptions following exercise with different intensities? What is the main finding and its importance? Moderate and low intensity running induced acute and long-lasting EIH effects via the effective activation of descending inhibition, while the high intensity running may trigger the descending facilitation and attenuate both the acute and long-lasting EIH effects. This result preliminarily explained the non-liner effect of exercise intensity on the acute EIH responds.

neuroscience↗