摘要：
Significance Statement This study has revealed an important role of OsTIL1 in maintaining the cell membrane integrity by regulating the 18:3‐containing glycerolipids biosynthesis and reducing reactive oxygen species damage under cold stress in rice seedlings. SUMMARY Lipocalins constitute a conserved protein family that binds to and transports a variety of lipids while fatty acid desaturases (FADs) are required for maintaining the cell membrane fluidity under cold stress. Nevertheless, it remains unclear whether plant lipocalins promote FADs for the cell membrane integrity under cold stress. Here, we identified the role of OsTIL1 lipocalin in FADs‐mediated glycerolipid remodeling under cold stress. Overexpression and CRISPR/Cas9 mediated gene edition experiments demonstrated that OsTIL1 positively regulated cold stress tolerance by protecting the cell membrane integrity from reactive oxygen species damage and enhancing the activities of peroxidase and ascorbate peroxidase, which was confirmed by combined cold stress with a membrane rigidifier dimethyl sulfoxide or a H2O2 scavenger dimethyl thiourea. OsTIL1 overexpression induced higher 18:3 content, and higher 18:3/18:2 and (18:2 + 18:3)/18:1 ratios than the wild type under cold stress whereas the gene edition mutant showed the opposite. Furthermore, the lipidomic analysis showed that OsTIL1 overexpression led to higher contents of 18:3‐mediated glycerolipids, including galactolipids (monoglactosyldiacylglycerol and digalactosyldiacylglycerol) and phospholipids (phosphatidyl glycerol, phosphatidyl choline, phosphatidyl ethanolamine, phosphatidyl serine and phosphatidyl inositol) under cold stress. RNA‐seq and enzyme linked immunosorbent assay analyses indicated that OsTIL1 overexpression enhanced the transcription and enzyme abundance of four ω‐3 FADs (OsFAD3‐1/3‐2, 7, and 8) under cold stress. These results reveal an important role of OsTIL1 in maintaining the cell membrane integrity from oxidative damage under cold stress, providing a good candidate gene for improving cold tolerance in rice.
摘要：
Eukaryotic DNA is packaged into chromatin in the nucleus, restricting the binding of transcription factors (TFs) to their target DNA sites. FOXA1 functions as a pioneer TF to bind condensed chromatin and initiate the opening of local chromatin for gene expression. However, the principles of FOXA1 recruitment and how it subsequently unpacks the condensed chromatin remain elusive. Here, we revealed that FOXA1 intrinsically forms submicron-sized condensates through its N- and C-terminal intrinsically disordered regions (IDRs). Notably, both IDRs enable FOXA1 to dissolve the condensed chromatin. In addition, the DNA-binding capacity of FOXA1 contributes to its ability to both form condensates and dissolve condensed chromatin. Further genome-wide investigation showed that IDRs enable FOXA1 to bind and unpack the condensed chromatin to regulate the proliferation and migration of breast cancer cells. This work provides a principle of how pioneer TFs function to initiate competent chromatin states using their IDRs.
期刊：
Journal of Environmental Management,2024年351:119729 ISSN：0301-4797
通讯作者：
Yang, S
作者机构：
[Peng, Kaida; Yang, Shao; Yang, Hongyan; Xu, Min; Cheng, Hu; Liu, Yi; Yang, S; Liu, Pan; Liu, Xiaofeng] Cent China Normal Univ, Sch Life Sci, Wuhan 430079, Peoples R China.
通讯机构：
[Yang, S ] C;Cent China Normal Univ, Sch Life Sci, Wuhan 430079, Peoples R China.
关键词：
Anthropogenic activities;Bloom-forming cyanobacterial genera;Climate change;Driving factors;Sedimentary ancient DNA;Thresholds
摘要：
Cyanobacterial blooms pose a global environmental concern, with various genera contributing to their formation. The harmfulness of cyanobacterial blooms varies depending on the specific genus, yet the factors triggering their formation remain incompletely understood. This study conducted qPCR of sediment DNA in Lake Erhai to reconstruct the historical succession of three common bloom-forming cyanobacterial genera (i.e., Microcystis, Dolichospermum, and Aphanizomenon). The driving factors and their corresponding thresholds were identified, and human activities related to driving factors were evaluated. The results revealed two successions in the past century. The first succession transitioned from Aphanizomenon (1902-1978) to Microcystis and Dolichospermum (1978-1999), driven by TN:TP and TP. The second succession shifted from Microcystis and Dolichospermum (1978-1999) to Microcystis (1999-2010), driven by TP, TN:TP, and temperature. The thresholds of TP and TN:TP for the Microcystis bloom were 0.023mg/L and 17, respectively. TN:TP was significantly influenced by domestic pollution and crop farming in both successions, while TP was significantly impacted by domestic pollution in the first succession and by pollution from crop and dairy farming in the second succession. These results shed light on the underlying mechanism responsible for the blooms of various cyanobacterial genera and could serve as a valuable reference for effectively preventing and controlling nutrient input in the watershed.
期刊：
BRIEFINGS IN BIOINFORMATICS,2024年25(2) ISSN：1467-5463
通讯作者：
Yunjie Zhao<&wdkj&>Yunhui Peng
作者机构：
[Xu, Wang; Peng, Yunhui; Zhang, Houfang; Zhao, Yunjie] Institute of Biophysics and Department of Physics, Central China Normal University, Wuhan 430079, China;[Guo, Wenhan] Computational Science Program, University of Texas at El Paso, El Paso, TX 79902, USA;[Jiang, Lijun] Hubei Key Laboratory of Genetic Regulation & Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan 430079, China
通讯机构：
[Yunjie Zhao; Yunhui Peng] I;Institute of Biophysics and Department of Physics, Central China Normal University , Wuhan 430079 , China
关键词：
epigenetic regulation;histone cancer mutation;histone/nucleosome interaction;interaction network;nucleosome binding mode
摘要：
Nucleosomes represent hubs in chromatin organization and gene regulation and interact with a plethora of chromatin factors through different modes. In addition, alterations in histone proteins such as cancer mutations and post-translational modifications have profound effects on histone/nucleosome interactions. To elucidate the principles of histone interactions and the effects of those alterations, we developed histone interactomes for comprehensive mapping of histone-histone interactions (HHIs), histone-DNA interactions (HDIs), histone-partner interactions (HPIs) and DNA-partner interactions (DPIs) of 37 organisms, which contains a total of 3808 HPIs from 2544 binding proteins and 339 HHIs, 100 HDIs and 142 DPIs across 110 histone variants. With the developed networks, we explored histone interactions at different levels of granularities (protein-, domain- and residue-level) and performed systematic analysis on histone interactions at a large scale. Our analyses have characterized the preferred binding hotspots on both nucleosomal/linker DNA and histone octamer and unraveled diverse binding modes between nucleosome and different classes of binding partners. Last, to understand the impact of histone cancer-associated mutations on histone/nucleosome interactions, we complied one comprehensive cancer mutation dataset including 7940 cancer-associated histone mutations and further mapped those mutations onto 419,125 histone interactions at the residue level. Our quantitative analyses point to histone cancer-associated mutations' strongly disruptive effects on HHIs, HDIs and HPIs. We have further predicted 57 recurrent histone cancer mutations that have large effects on histone/nucleosome interactions and may have driver status in oncogenesis.
期刊：
Trends in Pharmacological Sciences,2024年45(3):193-196 ISSN：0165-6147
通讯作者：
Jinrong Min
作者机构：
[Li, Yanxi; Huang, Yunyuan] Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan, Hubei, China;[Min, Jinrong] Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan, Hubei, China. Electronic address: minjinrong@ccnu.edu.cn
通讯机构：
[Jinrong Min] H;Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan, Hubei, China
摘要：
The PWWP domain binds to both histone and DNA of a nucleosome in a bivalent way. PWWP domain-containing proteins are involved in different biological processes, and their aberrant expression is implicated in various human diseases. Here, we discuss the recent developments and challenges in targeting the PWWP domain for therapeutic intervention.
关键词：
Antibiotic alternatives;Antibiotic resistance genes;Layer feces;Microbiome;Mobile genetic elements
摘要：
Although antibiotic alternatives are widely used in livestock and poultry breeding industry after in-feed antibiotics ban, their intervention effects on antibiotic resistance genes (ARGs) in these food animals' feces remain poorly understood. Here effects of fructooligosaccharide (FOS) and astragalus polysaccharide (APS), as typical antibiotic alternatives in China, on ARGs in layer feces were estimated by performing metagenomic sequencings and fluorescence quantitative PCR. Fructooligosaccharide significantly reduced sum abundance of ARGs and mobile genetic elements (MGEs) by increasing Lactobacillus clones and reducing Escherichia clones which had relatively higher abundances of ARG subtypes and MGE subtypes in layer feces. However, at least parts of core ARGs and MGEs categories were not reduced by FOS, such as aminoglycosides- and tetracyclines-resistant genes, Tn916, Integrase, and so on. MGEs and microbiome, especially Escherichia genus and Lactobacillus genus, were the key factors affecting ARGs' sum abundance. MGEs had a higher correlation coefficient with ARGs' sum abundance than Escherichia genus and Lactobacillus genus. These findings firstly reveal the defects of antibiotic alternatives in controlling bacterial resistance in livestock and poultry breeding after in-feed antibiotics ban, and more strategies are needed to control pollutions and risks of core ARGs and MGEs in food animals' feces under a special environment.
作者机构：
[Wen-Wen Wang; Pei Xiong; Xu-Sheng Liu; Yu-Feng Wang] Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan, 430079, China;[Jia-Lin Wang] Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan, 430079, China. jlwang@ccnu.edu.cn
通讯机构：
[Jia-Lin Wang] H;Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan, China
摘要：
Gut bacteria are beneficial to the host, many of which must be passed on to host offspring. During metamorphosis, the midgut of holometabolous insects undergoes histolysis and remodeling, and thus risks losing gut bacteria. Strategies employed by holometabolous insects to minimize this risk are obscure. How gut bacteria affect host insects after entering the hemocoel and causing opportunistic infections remains largely elusive. We used holometabolous Helicoverpa armigera as a model and found low Lactobacillus load, high level of a C-type lectin (CTL) gene CD209 antigen-like protein 2 (CD209) and its downstream lysozyme 1 (Lys1) in the midgut of the wandering stage. CD209 or Lys1 depletion increased the load of midgut Lactobacillus, which further translocate to the hemocoel. In particular, CD209 or Lys1 depletion, injection of Lactobacillus plantarum, or translocation of midgut L. plantarum into the hemocoel suppressed 20-hydroxyecdysone (20E) signaling and delayed pupariation. Injection of L. plantarum decreased triacylglycerol and cholesterol storage, which may result in insufficient energy and 20E available for pupariation. Further, Lysine-type peptidoglycan, the major component of gram-positive bacterial cell wall, contributed to delayed pupariation and decreased levels of triacylglycerols, cholesterols, and 20E, in both H. armigera and Drosophila melanogaster. A mechanism by which (Lactobacillus-induced) opportunistic infections delay insect metamorphosis was found, namely by disturbing the homeostasis of lipid metabolism and reducing 20E production. Moreover, the immune function of CTL − Lys was characterized for insect metamorphosis by maintaining gut homeostasis and limiting the opportunistic infections.
摘要：
To fully harness the potential of laccase in the efficient decolorization and detoxification of single and mixed dyes with diverse chemical structures, we carried out a systematic study on the decolorization and detoxification of single and mixed dyes using a crude laccase preparation obtained from a white-rot fungus strain, Pleurotus eryngii. The crude laccase preparation showed efficient decolorization of azo, anthraquinone, triphenylmethane, and indigo dyes, and the reaction rate constants followed the order Remazol Brilliant Blue R > Bromophenol blue > Indigo carmine > New Coccine > Reactive Blue 4 > Reactive Black 5 > Acid Orange 7 > Methyl green. This laccase preparation exhibited notable tolerance to SO(4)(2-) salts such as MnSO(4), MgSO(4), ZnSO(4), Na(2)SO(4), K(2)SO(4), and CdSO(4) during the decolorization of various types of dyes, but was significantly inhibited by Cl(-) salts. Additionally, this laccase preparation demonstrated strong tolerance to some organic solvents such as glycerol, ethylene glycol, propanediol, and butanediol. The crude laccase preparation demonstrated the efficient decolorization of dye mixtures, including azo + azo, azo + anthraquinone, azo + triphenylmethane, anthraquinone + indigo, anthraquinone + triphenylmethane, and indigo + triphenylmethane dyes. The decolorization kinetics of mixed dyes provided preliminary insight into the interactions between dyes in the decolorization process of mixed dyes, and the underlying reasons and mechanisms were discussed. Importantly, the crude laccase from Pleurotus eryngii showed efficient repeated-batch decolorization of single-, two-, and four-dye mixtures. This crude laccase demonstrated high stability and reusability in repeated-batch decolorization. Furthermore, this crude laccase was efficient in the detoxification of different types of single dyes and mixed dyes containing different types of dyes, and the phytotoxicity of decolorized dyes (single and mixed dyes) was significantly reduced. The crude laccase efficiently eliminated phytotoxicity associated with single and mixed dyes. Consequently, the crude laccase from Pleurotus eryngii offers significant potential for practical applications in the efficient decolorization and management of single and mixed dye pollutants with different chemical structures.
摘要：
Previous studies have reported the association between particulate matter (PM) and childhood allergic rhinitis (AR). However, it is unclear whether food allergy (FA) modifies the PM-AR association. We aimed at evaluating the effect of the modification of FA on PM-AR association in preschool children. We adopted a cross-sectional study and conducted a questionnaire survey among preschool children aged 3-6 years in 7 cities in China from June 2019 to June 2020 to collect information on AR and FA. We used a combination of multilevel logistic regression and restricted cubic spline functions to quantitatively assess whether FA modifies the associations between size-specific PM exposure (1 × 1 km) and the risk of AR. The adjusted odds ratios (ORs) for AR among the children with FA as per a 10 μg/m(3) increase in early life PM(1), PM(2.5), and PM(10) were significantly higher than the corresponding ORs among the children without FA [e.g., OR: 1.58, 95% CI: (1.32, 1.90) vs 1.29, 95% CI: (1.18, 1.41), per 10 μg/m(3) increase in PM(1)]. The interactions between FA and size-specific PM exposure and their effects on AR were statistically significant (all p-int < 0.001). FA, as an important part of the allergic disease progression, may modify the PM-AR association in preschool children.
作者机构：
[Chen, Xian; Mo, Zhenzhuo; Wang, Jiaoyang; Wang, Kai; Han, Lu; Cheng, Kaiqing; Pan, Jie] Hubei Univ, Coll Hlth Sci & Engn, Wuhan 430062, Peoples R China.;[Jiang, Lijun] Cent China Normal Univ, Coll Life Sci, Wuhan 430079, Peoples R China.;[Xie, Cheng; Liu, GY; Liu, Genyan] Wuhan Inst Technol, Sch Chem Engn & Pharm, Hubei Key Lab Novel Reactor & Green Chem Technol, Wuhan 430205, Peoples R China.
通讯机构：
[Wang, K; Pan, J ] H;[Liu, GY ] W;[Jiang, LJ ] C;Hubei Univ, Coll Hlth Sci & Engn, Wuhan 430062, Peoples R China.;Cent China Normal Univ, Coll Life Sci, Wuhan 430079, Peoples R China.
摘要：
The aggregation of amyloid-beta (A beta) is one of the important pathological markers of Alzheimer's disease. Ruthenium(ii) complexes have good stability, low cytotoxicity, a high fluorescence quantum yield, and a good Stokes shift as fluorescent probes. Based on this, we constructed a fluorescent probe for in vivo real-time imaging and inhibition of A beta-fibril formation using a complex of Ru polypyridine with organic fluorophores (N,N-dimethylaniline) and hydrophobic peptides (KLVFF). DLS and TEM studies have shown that Ru-YH has an inhibitory effect on the fibrotic aggregation of A beta. Both in vivo and in vitro studies have shown that Ru-WJ and Ru-YH can quickly cross the blood-brain barrier and successfully detect A beta in early (2.5-month old) transgenic mouse models. In summary, we have explored the potential of Ru complex based biological probes for early diagnosis and inhibition of AD. Two Ru complexes, Ru-WJ and Ru-YH, were designed and synthesized to detect A beta aggregates at an early AD stage. Ru-WJ and Ru-YH could quickly cross the BBB of young AD mice. Ru-YH can also inhibit the growth of A beta.
摘要：
Colpoda are cosmopolitan unicellular eukaryotes primarily inhabiting soil and benefiting plant growth, but they remain one of the least understood taxa in genetics and genomics within the realm of ciliated protozoa. Here, we investigate the architecture of de novo assembled mitogenomes of six Colpoda species, using long-read sequencing and involving 36 newly isolated natural strains in total. The mitogenome sizes span from 43 to 63 kbp and typically contain 28-33 protein-coding genes. They possess a linear structure with variable telomeres and central repeats, with one Colpoda elliotti strain isolated from Tibet harboring the longest telomeres among all studied ciliates. Phylogenomic analyses reveal that Colpoda species started to diverge more than 326 million years ago, eventually evolving into two distinct groups. Collinearity analyses also reveal significant genomic divergences and a lack of long collinear blocks. One of the most notable features is the exceptionally high level of gene rearrangements between mitochondrial genomes of different Colpoda species, dominated by gene loss events. Population-level mitogenomic analysis on natural strains also demonstrates high sequence divergence, regardless of geographic distance, but the gene order remains highly conserved within species, offering a new species identification criterion for Colpoda species. Furthermore, we identified underlying heteroplasmic sites in the majority of strains of three Colpoda species, albeit without a discernible recombination signal to account for this heteroplasmy. This comprehensive study systematically unveils the mitogenomic structure and evolution of these ancient and ecologically significant Colpoda ciliates, thus laying the groundwork for a deeper understanding of the evolution of unicellular eukaryotes.IMPORTANCEColpoda, one of the most widespread ciliated protozoa in soil, are poorly understood in regard to their genetics and evolution. Our research revealed extreme mitochondrial gene rearrangements dominated by gene loss events, potentially leading to the streamlining of Colpoda mitogenomes. Surprisingly, while interspecific rearrangements abound, our population-level mitogenomic study revealed a conserved gene order within species, offering a potential new identification criterion. Phylogenomic analysis traced their lineage over 326 million years, revealing two distinct groups. Substantial genomic divergence might be associated with the lack of extended collinear blocks and relaxed purifying selection. This study systematically reveals Colpoda ciliate mitogenome structures and evolution, providing insights into the survival and evolution of these vital soil microorganisms.
期刊：
JOURNAL OF EXPERIMENTAL BIOLOGY,2024年227(6):jeb246355 ISSN：0022-0949
通讯作者：
Jinhong Luo
作者机构：
[Xia, Hangjing; Ma, Nina; Wei, Tingting; Luo, Jinhong] Institute of Evolution and Ecology, School of Life Sciences, Central China Normal University, Wuhan 430079, China;[Yin, Kuiying; Yu, Chao] Nanjing Research Institute of Electronics Technology, Nanjing, Jiangsu 210039, China
通讯机构：
[Jinhong Luo] I;Institute of Evolution and Ecology, School of Life Sciences, Central China Normal University , Wuhan 430079 , China
摘要：
Doppler shift compensation (DSC) is a unique feature observed in certain species of echolocating bats and is hypothesized to be an adaptation to detecting fluttering insects. However, current research on DSC has primarily focused on bats that are not engaged in foraging activities. In this study, we investigated the DSC performance of Pratt's roundleaf bat, Hipposideros pratti, which was trained to pursue insects in various motion states within a laboratory setting. Our study yielded three main results. First, H. pratti demonstrated highly precise DSC during insect pursuit, aligning with previous findings of other flutter-detecting foragers during orientation or landing tasks. Second, we found that the motion state of the insect prey had little effect on the DSC performance of H. pratti. Third, we observed variations in the DSC performance of H. pratti throughout the course of insect pursuit. The bats exhibited the highest DSC performance during the phase of maximum flight speed but decreased performance during the phase of insect capture. These findings of high precision overall and the time-dependent performance of DSC during insect pursuit support the hypothesis that DSC is an adaptation to detecting fluttering insects.
期刊：
JOURNAL OF PROTEOME RESEARCH,2024年23(1):368-376 ISSN：1535-3893
通讯作者：
Wan, CH
作者机构：
[Wang, Yi; Wan, Cuihong; Wan, CH; Peng, Mingbo; Yi, Zi; Li, Shenglan; Zhou, Yutian] Cent China Normal Univ, Sch Life Sci, Wuhan 430079, Hubei, Peoples R China.;[Wang, Yi; Wan, Cuihong; Wan, CH; Peng, Mingbo; Yi, Zi; Li, Shenglan; Zhou, Yutian] Cent China Normal Univ, Hubei Key Lab Genet Regulat & Integrat Biol, Wuhan 430079, Hubei, Peoples R China.
通讯机构：
[Wan, CH ] C;Cent China Normal Univ, Sch Life Sci, Wuhan 430079, Hubei, Peoples R China.;Cent China Normal Univ, Hubei Key Lab Genet Regulat & Integrat Biol, Wuhan 430079, Hubei, Peoples R China.
摘要：
The low-molecular-weight proteins (LMWP) in serum and plasma are related to various human diseases and can be valuable biomarkers. A small open reading frame-encoded peptide (SEP) is one kind of LMWP, which has been found to function in many bioprocesses and has also been found in human blood, making it a potential biomarker. The detection of LMWP by a mass spectrometry (MS)-based proteomic assay is often inhibited by the wide dynamic range of serum/plasma protein abundance. Nanoparticle protein coronas are a newly emerging protein enrichment method. To analyze SEPs in human serum, we have developed a protocol integrated with nanoparticle protein coronas and liquid chromatography (LC)/MS/MS. With three nanoparticles, TiO2, Fe3O4@SiO2, and Fe3O4@SiO2@TiO2, we identified 164 new SEPs in the human serum sample. Fe3O4@SiO2 and a nanoparticle mixture obtained the maximum number and the largest proportion of identified SEPs, respectively. Compared with acetonitrile-based extraction, nanoparticle protein coronas can cover more small proteins and SEPs. The magnetic nanoparticle is also fit for high-throughput parallel protein separation before LC/MS. This method is fast, efficient, reproducible, and easy to operate in 96-well plates and centrifuge tubes, which will benefit the research on SEPs and biomarkers.
摘要：
Nuclear respiratory factor 1 (NRF1) regulates the expression of genes that are vital for mitochondrial biogenesis, respiration, and various other cellular processes. While NRF1 has been reported to bind specifically to GC-rich promoters as a homodimer, the precise molecular mechanism governing its recognition of target gene promoters has remained elusive. To unravel the recognition mechanism, we have determined the crystal structure of the NRF1 homodimer bound to an ATGCGCATGCGCAT dsDNA. In this complex, NRF1 utilizes a flexible linker to connect its dimerization domain (DD) and DNA binding domain (DBD). This configuration allows one NRF1 monomer to adopt a U-turn conformation, facilitating the homodimer to specifically bind to the two TGCGC motifs in the GCGCATGCGC consensus sequence from opposite directions. Strikingly, while the NRF1 DBD alone could also bind to the half-site (TGCGC) DNA of the consensus sequence, the cooperativity between DD and DBD is essential for the binding of the intact GCGCATGCGC sequence and the transcriptional activity of NRF1. Taken together, our results elucidate the molecular mechanism by which NRF1 recognizes specific DNA sequences in the promoters to regulate gene expression. Graphical Abstract
作者机构：
[Li, Weifang; Zhang, Jin; Liu, Ke; Min, Jinrong; Xiao, Yuqing; Gan, Linyao] Cent China Normal Univ, Sch Life Sci, Hubei Key Lab Genet Regulat & Integrat Biol, Wuhan 430079, Peoples R China.
通讯机构：
[Liu, K; Min, JR ] C;Cent China Normal Univ, Sch Life Sci, Hubei Key Lab Genet Regulat & Integrat Biol, Wuhan 430079, Peoples R China.
摘要：
The TFAP2 family regulates gene expression during differentiation, development, and organogenesis, and includes five homologs in humans. They all possess a highly conserved DNA binding domain (DBD) followed by a helix-span-helix (HSH) domain. The DBD-HSH tandem domain specifically binds to a GCC(N3)GGC consensus sequence, but the precise recognition mechanisms remain unclear. Here, we found that TFAP2 preferred binding to the GCC(N3)GGC sequence, and the pseudo-palindromic GCC and GGC motifs and the length of the central spacer between the two motifs determined their binding specificity. Structural studies revealed that the two flat amphipathic α-helical HSH domains of TFAP2A stacked with each other to form a dimer via hydrophobic interactions, while the stabilized loops from both DBD domains inserted into two neighboring major grooves of the DNA duplex to form base-specific interactions. This specific DNA binding mechanism controlled the length of the central spacer and determined the DNA sequence specificity of TFAP2. Mutations of the TFAP2 proteins are implicated in various diseases. We illustrated that reduction or disruption of the DNA binding ability of the TFAP2 proteins is the primary cause of TFAP2 mutation-associated diseases. Thus, our findings also offer valuable insights into the pathogenesis of disease-associated mutations in TFAP2 proteins.
期刊：
Journal of Advanced Research,2023年48:105-123 ISSN：2090-1232
通讯作者：
Xie, Na;Huang, CH;Chen, MQ
作者机构：
[Huang, Canhua; Xie, Na; Huang, CH; Duan, Jiufei; Huang, Zhao] West China Hosp, State Key Lab Biotherapy, Chengdu 610041, Peoples R China.;[Huang, Canhua; Xie, Na; Huang, CH; Duan, Jiufei; Huang, Zhao] West China Hosp, Canc Ctr, Chengdu 610041, Peoples R China.;[Huang, Canhua; Xie, Na; Huang, CH; Duan, Jiufei; Huang, Zhao] Sichuan Univ, West China Sch Basic Med Sci & Forens Med, Chengdu 610041, Peoples R China.;[Huang, Canhua; Xie, Na; Huang, CH; Duan, Jiufei; Huang, Zhao] Collaborat Innovat Ctr Biotherapy, Chengdu 610041, Peoples R China.;[Nice, Edouard C.] Monash Univ, Dept Biochem & Mol Biol, Clayton, Vic, Australia.
通讯机构：
[Chen, MQ ] C;[Xie, N; Huang, CH ] W;West China Hosp, State Key Lab Biotherapy, Chengdu 610041, Peoples R China.;West China Hosp, Canc Ctr, Chengdu 610041, Peoples R China.;Sichuan Univ, West China Sch Basic Med Sci & Forens Med, Chengdu 610041, Peoples R China.
关键词：
Long noncoding RNAs;Lipid metabolism;Lipid chaperones;Lipid receptors;Therapeutic target
摘要：
Background: The investigation of lncRNAs has provided a novel perspective for elucidating mechanisms underlying diverse physiological and pathological processes. Compelling evidence has revealed an intrin-sic link between lncRNAs and lipid metabolism, demonstrating that lncRNAs-induced disruption of lipid metabolism and signaling contribute to the development of multiple cancers and some other diseases, including obesity, fatty liver disease, and cardiovascular disease.Aimof Review: The current review summarizes the recent advances in basic research about lipid metabo-lism and lipid signaling-related lncRNAs. Meanwhile, the potential and challenges of targeting lncRNA for the therapy of cancers and other lipid metabolism-related diseases are also discussed.Key Scientific Concept of Review: Compared with the substantial number of lncRNA loci, we still know little about the role of lncRNAs in metabolism. A more comprehensive understanding of the function and mechanism of lncRNAs may provide a new standpoint for the study of lipid metabolism and signaling. Developing lncRNA-based therapeutic approaches is an effective strategy for lipid metabolism-related diseases.(c) 2023 Published by Elsevier B.V. on behalf of Cairo University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
摘要：
As hotspots for the dissemination of antibiotic resistance genes (ARGs), wastewater treatment plants (WWTPs) have attracted global attention. However, there lacks a sufficient metagenomic surveillance of antibiotic resistome in the WWTPs located on the Qinghai-Tibet Plateau. Here, metagenomic approaches were used to comprehensively investigate the occurrence, mobility potential, and bacterial hosts of ARGs in influent and effluent of 18 WWTPs located on the Qinghai-Tibet Plateau. The total ARG relative abundances and diversity were significantly decreased from influent to effluent across the WWTPs. Multidrug, bacitracin, sulfonamide, aminoglycoside, and beta-lactam ARGs generally consisted of the main ARG types in effluent samples, which were distinct from influent samples. A group of 72 core ARGs accounting for 61.8-95.8 % of the total ARG abundances were shared by all samples. Clinically relevant ARGs mainly conferring resistance to beta-lactams were detected in influent (277 ARGs) and effluent (178 ARGs). Metagenomic assembly revealed that the genetic location of an ARG on a plasmid or a chromosome was related to its corresponding ARG type, demonstrating the distinction in the mobility potential of different ARG types. The abundance of plasmid-mediated ARGs accounted for a much higher proportion than that of chromosome-mediated ARGs in both influent and effluent. Moreover, the ARGs co-occurring with diverse mobile genetic elements in the effluent exhibited a comparable mobility potential with the influent. Furthermore, 137 metagenome-assembled genomes (MAGs) assigned to 13 bacterial phyla were identified as the ARG hosts, which could be effectively treated in most WWTPs. Notably, 46 MAGs were found to carry multiple ARG types and the potential pathogens frequently exhibited multi-antibiotic resistance. Some ARG types tended to be carried by certain bacteria, showing a specific host-resistance association pattern. This study highlights the necessity for metagenomic surveillance and will facilitate risk assessment and control of antibiotic resistome in WWTPs located on the vulnerable area.
摘要：
West of Beijing, Chinese white‐bellied rats (Niviventer confucianus, CWR) and Korean field mice (Apodemus peninsulae, KFM) are common and share similar habitat, diet, and activity, but differ in body size (CWR are bigger than KFM), food hoarding habit, and ability to protect caches. Intense asymmetric competition for food exists between the 2 rodent species, in that CWR have distinct advantage than KFM. However, how KFM coexists with CWR is less known. By tracking seed competition of 15 pairs of CWR–KFM over a 10‐day period for each under enclosure conditions, we found KFM could not compete over CWR at the seed source, but in terms of relative number (seed number/2) and relative energy of seeds (seed energy/3), they hoarded more seeds than CWR at the end of the trials. These results may promote their coexistence under the conditions of asymmetric competition. Abstract Asymmetric competition occurs when some species have distinct advantages over their competitors and is common in animals with overlapping habitats and diet. However, the mechanism allowing coexistence between asymmetric competitors is not fully clear. Chinese white‐bellied rats (Niviventer confucianus, CWR) and Korean field mice (Apodemus peninsulae, KFM) are common asymmetric competitors in shrublands and forests west of Beijing city. They share similar diet (e.g. plant seeds) and activity (nocturnal), but differ in body size (CWR are bigger than KFM), food hoarding habit (CWR: mainly larder hoarding; KFM: both larder and scatter hoarding), and ability to protect cached food (CWR are more aggressive than KFM). Here, we tested seed competition in 15 CWR–KFM pairs over a 10‐day period under semi‐natural enclosure conditions to uncover the differences in food hoarding, cache pilferage, and food protection between the 2 rodents, and discuss the implication for coexistence. Prior to pilferage, CWR harvested and ate more seeds than KFM. CWR tended to larder hoard seeds, whereas KFM preferred to scatter hoard seeds. Following pilferage, CWR increased consumption, decreased intensity of hoarding, and pilfered more caches from KFM than they lost, while KFM increased consumption more than they hoarded, and they preferred to hoard seeds in low and medium competition areas. Accordingly, both of the 2 rodent species increased their total energy consumption and hoarding following pilferage. Both rodent species tended to harvest seeds from the source, rather than pilfer caches from each other to compensate for cache loss via pilferage. Compared to CWR, KFM consumed fewer seeds when considering seed number, but hoarded more seeds when considering the seeds’ relative energy (energy of hoarded seeds/rodent body mass2/3) at the end of the trials. These results suggest that asymmetric competition for food exists between CWR and KFM, but differentiation in hoarding behavior could help the subordinate species (i.e. KFM) hoard more energy than the dominant species (i.e. CWR), and may contribute to their coexistence in the field.
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS,2023年1867(1):194952 ISSN：1874-9399
作者机构：
[Wu, Zhibin; Huang, Yunyuan] Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan 430079, PR China;[Liu, Ke] Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan 430079, PR China. Electronic address: keliu2015@ccnu.edu.cn;[Min, Jinrong] Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan 430079, PR China. Electronic address: minjinrong@ccnu.edu.cn
摘要：
Ubiquitination is a fascinating post-translational modification that has received continuous attention since its discovery. In this review, we first provide a concise overview of the E3 ubiquitin ligases, delving into classification, characteristics and mechanisms of ubiquitination. We then specifically examine the ubiquitination pathways mediated by the N/C-degrons, discussing their unique features and substrate recognition mechanisms. Finally, we offer insights into the current state of development pertaining to inhibitors that target the N/C-degron pathways, as well as the promising advances in the field of PROTAC (PROteolysis TArgeting Chimeras). Overall, this review offers a comprehensive understanding of the rapidly-evolving field of ubiquitin biology.
