Article
Biochemistry & Molecular Biology
Himanshu Singh, Chandan K. Das, Benjamin C. Buchmuller, Lars Schaefer, Daniel Summerer, Rasmus Linser
Summary: Researchers have discovered that 5-methylcytosine (mC) and its TET-oxidized derivatives exist in CpG dyads of mammalian DNA and regulate cell fate, but how they function as distinct regulatory signals is not well understood. Designing readers that selectively recognize these novel 'CpG duplex marks' presents a challenge due to their unprecedented selectivity requirements. This study demonstrates the importance of precise conformational plasticity for the selectivity of a designer reader for an oxidized CpG duplex mark.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Plant Sciences
Magali Charvin, Thierry Halter, Romain Blanc-Mathieu, Pierre Barraud, Magali Aumont-Nicaise, Francois Parcy, Lionel Navarro
Summary: DNA methylation decreases binding of Arabidopsis WRKY transcription factors to their genomic regions and binding sites in vitro. Methylation of a single cytosine in the W-box motif repels DNA binding of AtWRKY40 in vitro through steric hindrance. This methylation-dependent mechanism could potentially be widespread across different plant species.
Article
Chemistry, Multidisciplinary
Benjamin C. Buchmuller, Jessica Droeden, Himanshu Singh, Shubhendu Palei, Malte Drescher, Rasmus Linser, Daniel Summerer
Summary: This study evolved a mutant protein capable of specific binding to methylated and hydroxymethylated cytosines, allowing for the identification and enrichment of individual CpG dyads.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Multidisciplinary Sciences
Lili Nian, Xuelu Liu, Yingbo Yang, Xiaolin Zhu, Xianfeng Yi, Fasih Ullah Haider
Summary: The LIM gene family in alfalfa plays a vital role in regulating various biological processes. Through comprehensive analysis, it was found that the 21 identified MsLIM genes can be classified into four subfamilies and share similar gene structures and conserved Motifs. Additionally, the distribution of these genes on chromosomes seems to be uneven and is influenced by segmental duplications.
Article
Biochemistry & Molecular Biology
Adil Malik, Dulari K. Jayarathna, Mark Fisher, Tabassum Khair Barbhuiya, Neha S. Gandhi, Jyotsna Batra
Summary: In this study, the researchers investigated the mechanism of IRX4 homeodomain-DNA recognition and the impact of somatic mutations on these interactions using sequence analysis, homology modeling, and molecular dynamics simulations. They also identified the gene expression and protein expression of IRX4 in various tissues and highlighted the importance of conserved residues in DNA binding and the role of somatic mutations in destabilizing the protein-DNA complex. Additionally, they predicted that the C-terminal sequence of the IRX4 homeodomain could act as a potential cell-penetrating peptide.
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
(2023)
Article
Chemistry, Multidisciplinary
Tianshi Yu, Chanin Nantasenamat, Supicha Kachenton, Nuttapat Anuwongcharoen, Theeraphon Piacham
Summary: This study used cheminformatic analysis and machine learning modeling to investigate the chemical space, scaffolds, structure-activity relationship, and landscape of human androgen receptor antagonists. The findings revealed differences in physicochemical properties between potent/active class molecules and intermediate/inactive class molecules. Low scaffold diversity was observed, especially in the potent/active class molecules, indicating the need for developing molecules with novel scaffolds. The study also identified significant activity cliff generators and provided insights and guidelines for the development of novel androgen receptor antagonists.
Review
Pharmacology & Pharmacy
Sawako Shindo, Satoru Kakizaki, Toshiyuki Sakaki, Yuki Kawasaki, Tsutomu Sakuma, Masahiko Negishi, Ryota Shizu
Summary: Nuclear receptors collectively regulate biological functions and have diverse roles beyond transcription activation. While most are activated by ligand binding, some are phosphorylated. The physiological relevance of phosphorylation in nuclear receptor activity has been confirmed, especially within conserved domains. This review focuses on estrogen and androgen receptors and highlights phosphorylation as a potential drug target.
PHARMACOLOGY & THERAPEUTICS
(2023)
Article
Biochemistry & Molecular Biology
Monique J. Rogals, Alexander Eletsky, Chin Huang, Laura C. Morris, Kelley W. Moremen, James H. Prestegard
Summary: Glycans attached to glycoproteins play important roles in stability, protein-protein interactions, and signal transduction. This study focuses on the conformation of glycans and uses NMR resonances to identify preferred glycan conformers. The results show that the preferred conformers have extensive contacts with the protein surface, which are influenced by interactions between specific glycans and hydrophobic pockets on the protein surface.
ACS CHEMICAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Monique J. Rogals, Alexander Eletsky, Chin Huang, Laura C. Morris, Kelley W. Moremen, James H. Prestegard
Summary: Glycans attached to glycoproteins play important roles in stability, protein-protein interactions, and signal transduction. The conformation of these glycans is critical and highly variable, often sampling a multitude of conformations. In this study, long-range pseudo-contact shifts of NMR resonances were used to identify preferred conformations of glycans attached to a model glycoprotein. The analysis revealed that the preferred glycan conformers have extensive contacts with the protein surface, potentially due to interactions between N-acetyl methyls of GlcNAc residues and hydrophobic surface pockets.
ACS CHEMICAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Hephzibah Cathryn R., George Priya Doss C.
Summary: In this study, the effect of mutations on P53 protein was investigated using molecular dynamics simulation. The results showed that the mutations led to loss of hydrogen bonds between DNA binding bases and caused significant movements of the zinc-binding domain.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Chemistry, Multidisciplinary
Rajesh Kumar Reddy Sannapureddi, Manish Kumar Mohanty, Loic Salmon, Bharathwaj Sathyamoorthy
Summary: DNA G-quadruplexes are essential motifs in molecular biology due to their unique and diverse structures. This study focuses on the conformational plasticity of the parallel G-quadruplex topology. Through various methods such as structure survey, NMR spectroscopy, and molecular dynamics simulations, subtle yet essential features of the parallel G-quadruplex are revealed. The conformational plasticity described in this study provides important insights into biomolecular processes.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Microbiology
Yizhao Luan, Zehua Tang, Yao He, Zhi Xie
Summary: In this study, evidence was provided showing that coevolving residues in TF domains contribute to DNA binding specificity. It was demonstrated that the coevolving residues are more likely to coevolve with other TF subclass-determining sites and mutation of these coevolving residues could significantly reduce the stability of the TF-DNA complex. Overall, this study expands our understanding of the interaction among coevolving residues in TFs and their importance in transcriptional regulation.
MICROBIOLOGY SPECTRUM
(2023)
Article
Multidisciplinary Sciences
Julia A. M. Bakx, Andreas S. Biebricher, Graeme A. King, Panagiotis Christodoulis, Kata Sarlos, Anna H. Bizard, Ian D. Hickson, Gijs J. L. Wuite, Erwin J. G. Peterman
Summary: Topoisomerase IIIa is a type 1A topoisomerase that forms a complex with RMI1 and RMI2 called TRR in human cells. In this study, the authors used optical tweezers and fluorescence microscopy to investigate the catalytic steps of TRR. They found that TRR forms an open gate in single-stranded DNA and can bind a second single-stranded or double-stranded DNA molecule, leading to catenation. Interestingly, double-stranded DNA binding increases the gate size and the helicase BLM affects the flexibility of the gate. These findings suggest that TRR-mediated transfer of double-stranded DNA may be more important than previously believed.
NATURE COMMUNICATIONS
(2022)
Article
Chemistry, Analytical
Takamichi Miyata, Hazuki Shimamura, Ryutaro Asano, Wataru Yoshida
Summary: This study establishes a universal design for fusion protein construction using the SnoopTag/SnoopCatcher protein ligation system. Fusion proteins constructed with this system show specific binding activity to methylated and unmethylated CpG sites. By using these fusion proteins in a dual-color bioluminescence resonance energy transfer (BRET) assay, the global DNA methylation level can be quantified in genomic DNA. These results demonstrate that the SnT/SnC protein ligation system can be used to detect target modifications in genomic DNA based on BRET.
ANALYTICAL CHEMISTRY
(2023)
Article
Biophysics
Phuong Thuy Bui, Trinh Xuan Hoang
Summary: Translation of nascent proteins requires them to escape the ribosomal exit tunnel for complete folding, impacting the ribosome's ability to recycle. Energetic interactions between the tunnel and nascent proteins were found to affect the escape process, with attractive interactions slowing it down and repulsive interactions speeding it up. The escape time correlates with the number of hydrophobic residues and net charge of the protein, providing insights into modulating the escape time by altering the total charge.
BIOPHYSICAL JOURNAL
(2021)
Article
Cardiac & Cardiovascular Systems
Yinan Wang, Yiming Jia, Qingyun Xu, Ruirui Wang, Lulu Sun, Daoxia Guo, Mengyao Shi, Pinni Yang, Yu Wang, Fanghua Liu, Yonghong Zhang, Zhengbao Zhu
Summary: This study used a two-sample Mendelian randomization (MR) approach to investigate the potential causal effect of myeloperoxidase (MPO) on ischemic stroke, ischemic stroke subtypes, heart failure (HF), and atrial fibrillation (AF). The results suggest that elevated plasma MPO levels may be associated with increased risks of ischemic stroke, cardioembolic stroke, HF, and AF, highlighting the importance of MPO in the development of cardiovascular disease.
NUTRITION METABOLISM AND CARDIOVASCULAR DISEASES
(2023)
Article
Rheumatology
Xing-Bo Mo, Yang-Hua Sun, Long-Fei Wu, Pei He, Rong-Rong Cao, Xin Lu, Yong-Hong Zhang, Fei-Yan Deng, Shu-Feng Lei
Summary: This study identified a novel lncRNA, lnc-RNU12, that is downregulated and genetically associated with rheumatoid arthritis (RA) risk in patients. The results showed that lnc-RNU12 influences the T cell cycle by targeting the genes c-JUN and CCNL2, suggesting its involvement in the pathogenesis of RA.
Article
Biochemistry & Molecular Biology
Yiming Jia, Rong Wang, Lulu Sun, Daoxia Guo, Mengyao Shi, Kaixin Zhang, Pinni Yang, Yu Wang, Fanghua Liu, Guo-Chong Chen, Yonghong Zhang, Zhengbao Zhu
Summary: By conducting a Mendelian randomization study, we identified three potential causal mediators, including docosahexaenoic acid, arachidonate, and 1-arachidonoyl-GPE, in the development of atopic dermatitis. Docosahexaenoic acid and arachidonate were found to have beneficial or detrimental effects on multiple diseases beyond atopic dermatitis, while no adverse side effects were predicted for 1-arachidonoyl-GPE. These findings provide valuable insights for the prevention and treatment of atopic dermatitis.
HUMAN MOLECULAR GENETICS
(2023)
Article
Peripheral Vascular Disease
Yujia Zhai, Bizhong Che, Yang Liu, Hao Peng, Aili Wang, Yanbo Peng, Jing Chen, Yonghong Zhang, Tan Xu, Chongke Zhong, Jiang He
Summary: This study investigated whether different blood pressure management strategies should be used for acute stroke patients with or without impaired renal function. The results showed that early antihypertensive treatment had no effect on clinical outcomes in ischemic stroke patients with different renal function status.
Article
Immunology
Jun Zhou, Shan Yan, Xu Guo, Yanguo Gao, Shiqi Chen, Xiaohan Li, Yonghong Zhang, Qibin Wang, Tao Zheng, Li Chen
Summary: This study investigated the effects of salidroside (SAL) on pancreatic beta-cell pyroptosis in diabetic mice. The results showed that SAL can protect beta-cells against pyroptosis by activating AMPK and inhibiting NLRP3/GSDMD signaling.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Clinical Neurology
Jigang Du, Yan Wang, Bizhong Che, Mengyuan Miao, Anran Bao, Yanbo Peng, Zhong Ju, Tan Xu, Jiang He, Yonghong Zhang, Chongke Zhong
Summary: This study utilized repeated measures of the National Institutes of Health Stroke Scale (NIHSS) to identify different trajectories of neurological function after stroke and investigated their association with long-term clinical outcomes. The findings revealed that trajectories characterized by persistent severe and moderate neurological impairment were associated with increased risk of cardiovascular events. These results suggest that evaluating the neurological function trajectories of stroke patients through repeated NIHSS measurements can provide additional predictive information and aid in predicting long-term clinical outcomes.
INTERNATIONAL JOURNAL OF STROKE
(2023)
Article
Clinical Neurology
Yinwei Zhu, Lulu Sun, Tiansheng Huang, Yiming Jia, Pinni Yang, Qi Zhang, Chongquan Fang, Mengyao Shi, Daoxia Guo, Yanbo Peng, Anushka Aghi, Jing Chen, Aili Wang, Jiang He, Yonghong Zhang, Tan Xu, Zhengbao Zhu
Summary: A multicenter cohort study found that elevated serum BDNF concentrations were associated with decreased risks of adverse outcomes after ischemic stroke, suggesting that serum BDNF may be a potential biomarker for prognosis after ischemic stroke.
Article
Immunology
Qiongyu Chen, Yan Zhao, Yonghong Zhang, Jianbo Zhang, Wenshu Lu, Chih-Hao Chang, Shisong Jiang
Summary: The human immunodeficiency virus (HIV) is a global pandemic with no cure identified yet. HIV-induced death of lymphocytes involves both necrosis and apoptosis. A pro-apoptotic TNF peptide (P13) inhibits HIV-related cell death and viral transmission, while a pro-necrotic TNF peptide (P16) has little effect. Understanding cell death mechanisms may provide drug targets to reduce CD4(+) cell loss and viral reservoir formation in HIV infection.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Immunology
Yonghong Zhang, Zhaozhao Liu, Haixiang Sun
Summary: A successful human pregnancy requires the maternal immune system to recognize and tolerate the semi-allogeneic fetus. Dysfunctional maternal-fetal interactions might be associated with the development of pregnancy complications. This review elaborates the interactions between trophoblasts and decidual immune cells, and the role of commensal bacteria in promoting pregnancy progression.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Clinical Neurology
Bizhong Che, Chongke Zhong, Jigang Du, Mengyuan Miao, Mengyao Shi, Yanbo Peng, Pinni Yang, Daoxia Guo, Jing Chen, Aili Wang, Tan Xu, Yonghong Zhang, Jiang He
Summary: This study aimed to examine the prognostic values of CCL19 and CCL21 in ischemic stroke. The results showed that both CCL19 and CCL21 levels were independently associated with adverse outcomes within 3 months after ischemic stroke, and could improve risk reclassification and discrimination for adverse outcomes.
EUROPEAN JOURNAL OF NEUROLOGY
(2023)
Article
Oncology
Hao Peng, Helena Palma-Gudiel, Carolina Soriano-Tarraga, Jordi Jimenez-Conde, Mingzhi Zhang, Yonghong Zhang, Jinying Zhao
Summary: Altered DNA methylation of TRIM6, FLRT2, SOX1, SOX17, AGBL4, and FAM84A genes (increased) and TLN2 gene (decreased) were found to be associated with ischemic stroke in Chinese populations. Experimental evidence suggests these genes may be involved in endothelial cell adhesion and atherosclerosis.
CLINICAL EPIGENETICS
(2023)
Article
Cardiac & Cardiovascular Systems
Fanghua Liu, Pinni Yang, Yinan Wang, Mengyao Shi, Ruirui Wang, Qingyun Xu, Yanbo Peng, Jing Chen, Jintao Zhang, Aili Wang, Tan Xu, Yonghong Zhang, Jiang He
Summary: This study investigated the relationship between baseline platelet count and HS-CRP on clinical outcomes in patients with ischemic stroke. The results showed an interaction effect between platelet count and HS-CRP on adverse clinical outcomes. Elevated platelet count was significantly associated with adverse clinical outcomes in patients with high HS-CRP levels. Strategies for anti-inflammatory and antiplatelet therapy should be developed based on platelet and HS-CRP testing results.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2023)
Article
Immunology
Yonghong Zhang, Huiyan Wang, Panpan Qiu, Jingwen Jiang, Xuhong Wu, Jie Mei, Haixiang Sun
Summary: Placental trophoblasts play a role in the regulation of regulatory T cells through the PD-1/PD-L1 pathway, and decreased expression of PD-L1 in trophoblasts is associated with Treg deficiency in pregnancy failure. YY1 modulates the expression of PD-L1 in trophoblasts, and elevated levels of NO from M1 macrophages may lead to reduced YY1 expression in recurrent miscarriage.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Engineering, Aerospace
Yonghong Zhang, Chengmin Wang, Shuangquan Tang, You Jiang, Hong Chen, Wenjie Ge
Summary: This study investigates and designs a novel stacked hinge with low stiffness, large rotation angle, high strength, and length-adaptive functionality. A theoretical model for the stiffness of stacked flexure hinges is established based on the large deformation theory of cantilever beams and relevant theories of leaf springs. The model is further modified considering the frictional force to reduce errors. A stiffness-testing experimental platform is designed to verify the correctness of the theoretical model. The stacked flexure hinge is applied to the trailing-edge mechanism of a variable camber wing, achieving the desired deformation and demonstrating feasibility.
Meeting Abstract
Biochemistry & Molecular Biology
Yonghong Zhang
