Biology subjects

Pu, H.

Publications and source records attributed to Pu, H..

4 recordsLinked to original sources

bioRxiv2025

Structural basis of Retron-Eco8-mediated anti-phage defense

Retrons represent a novel class of bacterial defense systems that employ reverse transcriptase (RT), non-coding RNA, and effector proteins to counteract phage infections. In this study, we elucidate the molecular mechanism of a retron system, Retron-Eco8. Biochemical experiments reveal that the Retron-Eco8 holocomplex, rather than the effector alone, exhibits double-stranded DNA cleavage activity in an ATP-independent manner, triggering abortive infection and effectively halting phage propagation. Cryo-electron microscopy (cryo-EM) analysis reveals a supramolecular assembly comprising four RT subunits, four msDNA (multicopy single-stranded DNA) molecules, and four OLD (overcoming lysogenization defect) nucleases--a configuration critical for anti-phage defense. Structural comparisons between apo and ATP-Mg2+-bound states demonstrate a local conformational change. Notably, we identify the phage SSB (single-stranded DNA-binding) protein as an activator of Retron-Eco8, and phylogenetic analysis of SSB proteins further elucidates the phage resistance specificity. Collectively, our findings delineate the structural architecture of the Retron-Eco8 defense complex and provide mechanistic insights into retron-mediated bacterial immunity.

biophysics↗

bioRxiv2025

Dynamically Assembling Biological Intelligence to Predict Novel Cellular Phenotypes

In this work, we introduce Bio-AMLM (Biological Adaptive Modular Learning Model), a new framework designed to address out-of-distribution (OOD) generalization challenges in predicting cellular responses. Unlike monolithic deep learning models or simple data retrieval methods, which struggle to predict the effects of novel genetic or chemical perturbations, Bio-AMLM dynamically constructs a bespoke analytical pipeline for each biological query. It leverages a library of pre-trained, functionally specialized biological modules (e.g., for genomic, proteomic, and metabolic analysis). Guided by a biological context encoder, an adaptive inference planner selects, configures, and links these modules to form an optimal analysis chain. In experiments on several challenging bio-simulation benchmarks, including Gene-Edit-Bench, Drug-Response-Bench, and Toxicity-Bench, Bio-AMLM consistently outperformed state-of-the-art approaches, producing more reliable, robust, and interpretable predictions of cellular behavior in complex OOD scenarios.

bioengineering↗

bioRxiv2025

Quantitative Analysis of Meloidogyne incognita Population Density Using Real-Time PCR and Its Correlation with Root-Knot Disease Index in Tabacco (Nicotiana tabacum)

Tobacco root-knot disease represents a significant threat to tobacco production, particularly in the western Henan region, where Meloidogyne incognita is the predominant species. This study collected samples of M. incognita and soil from Luoyang, Henan, and designed specific primers MiF and MiR based on the amplified 735 bp sequence of the ITS1-5.8S-ITS2 region. These primers exhibit mismatches with related species, including M. javanica, M. minor, M. hapla, and M. arenaria, showing 1, 6, 10, and 10 base differences in the forward direction, respectively, 3, 10, and 9 base mismatches in the reverse direction. Although the primers were used to detect corn-wheat soil samples, no amplification was observed. Additionally a real-time quantitative PCR curve for M. incognita in soil was constructed, revealing a negative correlation between the Ct value (Y) and the log-transformed number of nematodes (x) per 20 g of dry soil, represented by the equation y = -0.9757x + 35.565; (R2 = 0.9999, P < 0.01). According to the decomposition efficiency of nematode DNA in soil, the results showed that nematode DNA degrades rapidly in soil, with a degradation rate of approximately 87.3% at 3 days and 99.97% at 14 days. Furthermore, significant differences were observed in the real-time PCR detection efficiency among various nematode forms: the Ct value of J1 was significantly higher than that of J2, while abnormal eggs (empty eggs or internal bubble eggs) exhibited the highest Ct value. The proportion of abnormal eggs in the soil before planting was significantly higher at 64.08% compared to only 15.3% at harvest, indicating that the activity of nematodes in the soil is significantly reduced after harvesting in October and planting in March of the following year. A survey of 126 tobacco plants indicated a significant positive correlation between the root-knot index (RKI) and root-knot nematode density (r = 0.80, p < 0.01). The study identified a minimum disease threshold of 234 individuals / 20 g soil at harvest and revealed a nonlinear relationship between disease severity and nematode density. Specifically, a weak correlation was observed at low density (Low RKI: 0-1; nematode density<2000 individuals/20 g soil, r = 0.49, P<0.05), while a significant correlation was noted at moderate density (High RKI: nematode density>2000 individuals/20 g soil, r = 0.69, P<0.05). This study showed that as the RKI increases, the rate of increase in nematode density in the soil diminishes. These findings provide valuable insights for the development of effective scientific strategies for nematode control.

plant biology↗

bioRxiv2022

ATR-I774Yfs*5 promotes genomic instability through micronuclei formation

Although mismatch repair (MMR) defects are associated with high risk of malignancy, the specific oncogenic drivers pertinent to MMR-affected cancers are poorly characterized. The heterozygous ATR-I774Yfs*5 mutation, the result of strand slippage in a poly-A tract of the Ataxia Telangiectasia and Rad3 related (ATR) gene, is overexpressed in MMR-defective malignancies including colorectal carcinoma (CRC) and is the most common ATR mutation in cancer. Here, we explore the contribution of ATR-I774Yfs*5 to genomic integrity. Using heterozygous ATR-I774Yfs*5 HCT-116 cells to mimic the native mutation, we found this mutation reduced ATR activity as measured by damage-induced Chk1 phosphorylation at S317 and ATR autophosphorylation ATR at T1989. ATR-I774Yfs*5 expression impaired genomic stability as visualized by the appearance of micronuclei in two stable expression models as well as in cell lines transfected with ATR-I774Yfs*5. Micronucleus development was dependent on replication and independent of ATR copy number. ATR-I774Yfs*5 expression did not alter cellular viability, cell cycle progression, or replicative rate, suggesting this mutation is well-tolerated despite its destabilizing effect on the genome. Taken together, these data suggest that the ATR-I774Yfs*5, whose development is favored in the context of MMR deficiency, may represent an important driver of a mutator phenotype by promoting genomic instability.

cancer biology↗