Jiao Li, Zhiliang Long, Gong-Jun Ji, Shaoqiang Han, Yuan Chen, Guanqun Yao, Yong Xu, Kerang Zhang, Yong Zhang, Jingliang Cheng, Kai Wang, Huafu Chen, Wei Liao <<<

Abstract Accurate prediction of enzyme kinetic parameters is crucial for enzyme exploration and modification. Existing models face the problem of either low accuracy or poor generalization ability due to overfitting. In this work, we first developed unbiased datasets to evaluate the actual performance of these methods and proposed a deep learning model, CataPro, based on pre-trained models and molecular fingerprints to predict turnover number (k c a t ), Michaelis constant (K m ), and catalytic efficiency (k c a t /K m ). Compared with previous baseline models, CataPro demonstrates clearly enhanced accuracy and generalization ability on the unbiased datasets. In a representational enzyme mining project, by combining CataPro with traditional methods, we identified an enzyme (SsCSO) with 19.53 times increased activity compared to the initial enzyme (CSO2) and then successfully engineered it to improve its activity by 3.34 times. This reveals the high potential of CataPro as an effective tool for future enzyme discovery and modification. <<<

Zhiyi Chen, Yancheng Tang, Xuerong Liu, Wei Li, Yuanyuan Hu, Bowen Hu, Ting Xu, Rong Zhang, Lei Xia, Jing-Xuan Zhang, Zhibing Xiao, Ji Chen, Zhengzhi Feng, Yuan Zhou, Qinghua He, Jiang Qiu, Xu Lei, Hong Chen, Shaozheng Qin, Tingyong Feng <<<

Jorge Hernández-García, Vanessa Polet Carrillo-Carrasco, Juriaan Rienstra, Keita Tanaka, Martijn de Roij, Melissa Dipp-Álvarez, Alejandra Freire-Ríos, Isidro Crespo, Roeland Boer, Willy A. M. van den Berg, Simon Lindhoud, Dolf Weijers <<<

AbstractThe Auxin Response Factors (ARFs) family of transcription factors are the central mediators of auxin-triggered transcriptional regulation. Functionally different classes of extant ARFs operate as antagonistic auxin-dependent and -independent regulators. While part of the evolutionary trajectory to the present auxin response functions has been reconstructed, it is unclear how ARFs emerged, and how early diversification led to functionally different proteins. Here, we use in silico and in vivo analyses to revisit the molecular events that led to the origin and subsequent evolution of the ARFs. We reveal the shared origin of ARFs from preexisting domains, uncovering a protein fold homologous to the ARF DNA-binding fold in a conserved eukaryotic chromatin regulator. Building on this, we reconstruct the complete evolutionary history of ARFs, including the divergence events leading to the appearance of the ARF classes and defining the main molecular targets for their functional diversification. We derive a complete evolutionary trajectory that led to the emergence of the nuclear auxin signalling pathway. <<<

Simeng Hu, Can Hu, Jingli Xu, Pengfei Yu, Li Yuan, Ziyu Li, Haohong Liang, Yanqiang Zhang, Jiahui Chen, Qing Wei, Shengjie Zhang, Litao Yang, Dan Su, Yian Du, Zhiyuan Xu, Fan Bai, Xiangdong Cheng <<<

Ting Liu, Jianan Rao, Wenting Hu, Bowen Cui, Jiaoyang Cai, Yuhan Liu, Huiying Sun, Xiaoxiao Chen, Yanjing Tang, Jing Chen, Xiang Wang, Han Wang, Wubin Qian, Binchen Mao, Sheng Guo, Ronghua Wang, Yu Liu, Shuhong Shen <<<

AbstractStudies have revealed key genomic aberrations in pediatric acute myeloid leukemia (AML) based on Western populations. It is unknown to what extent the current genomic findings represent populations with different ethnic backgrounds. Here we present the genomic landscape of driver alterations of Chinese pediatric AML and discover previously undescribed genomic aberrations, including the XPO1-TNRC18 fusion. Comprehensively comparing between the Chinese and Western AML cohorts reveal a substantially distinct genomic alteration profile. For example, Chinese AML patients more commonly exhibit mutations in KIT and CSF3R, and less frequently mutated of genes in the RAS signaling pathway. These differences in mutation frequencies lead to the detection of previously uncharacterized co-occurring mutation pairs. Importantly, the distinct driver profile is clinical relevant. We propose a refined prognosis risk classification model which better reflected the adverse event risk for Chinese AML patients. These results emphasize the importance of genetic background in precision medicine. <<<

Xinyuan Liang, Lianglong Sun, Xuhong Liao, Tianyuan Lei, Mingrui Xia, Dingna Duan, Zilong Zeng, Qiongling Li, Zhilei Xu, Weiwei Men, Yanpei Wang, Shuping Tan, Jia-Hong Gao, Shaozheng Qin, Sha Tao, Qi Dong, Tengda Zhao, Yong He <<<

AbstractCortical thinning is an important hallmark of the maturation of brain morphology during childhood and adolescence. However, the connectome-based wiring mechanism that underlies cortical maturation remains unclear. Here, we show cortical thinning patterns primarily located in the lateral frontal and parietal heteromodal nodes during childhood and adolescence, which are structurally constrained by white matter network architecture and are particularly represented using a network-based diffusion model. Furthermore, connectome-based constraints are regionally heterogeneous, with the largest constraints residing in frontoparietal nodes, and are associated with gene expression signatures of microstructural neurodevelopmental events. These results are highly reproducible in another independent dataset. These findings advance our understanding of network-level mechanisms and the associated genetic basis that underlies the maturational process of cortical morphology during childhood and adolescence. <<<

Qiang Ning, Yinan Jian, Yanfang Du, Yunfu Li, Xiaomeng Shen, Haitao Jia, Ran Zhao, Jimin Zhan, Fang Yang, David Jackson, Lei Liu, Zuxin Zhang <<<

AbstractMaize ear size and kernel number differ among lines, however, little is known about the molecular basis of ear length and its impact on kernel number. Here, we characterize a quantitative trait locus, qEL7, to identify a maize gene controlling ear length, flower number and fertility. qEL7 encodes 1-aminocyclopropane-1- carboxylate oxidase2 (ACO2), a gene that functions in the final step of ethylene biosynthesis and is expressed in specific domains in developing inflorescences. Confirmation of qEL7 by gene editing of ZmACO2 leads to a reduction in ethylene production in developing ears, and promotes meristem and flower development, resulting in a ~13.4% increase in grain yield per ear in hybrids lines. Our findings suggest that ethylene serves as a key signal in inflorescence development, affecting spikelet number, floral fertility, ear length and kernel number, and also provide a tool to improve grain productivity by optimizing ethylene levels in maize or in other cereals. <<<