ATP Binding Activity Research Articles

Genome-Wide Scan for Copy Number Variations in Chinese Merino Sheep Based on Ovine High-Density 600K SNP Arrays

Sheep are a vital species in the global agricultural economy, providing essential resources such as meat, milk, and wool. Merino sheep (Junken type) are a key breed of fine wool sheep in China. However, research on fine wool traits has largely overlooked the role of SNPs and their association with phenotypes. Copy number variations (CNVs) have emerged as one of the most important sources of genetic variation, influencing phenotypic traits by altering gene expression and dosage. To generate a comprehensive CNVR map of the ovine genome, we conducted genome-wide CNV detection using genotyping data from 285 fine wool sheep. This analysis revealed 656 CNVRs, including 628 on autosomes and 28 on the X chromosome, covering a total of 43.9 Mbs of the sheep genome. The proportion of CNVRs varied across chromosomes, from 0.45% on chromosome 26 to 3.72% on chromosome 10. Functional annotation through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses highlighted significantly enriched GO terms, including odorant binding, ATP binding, and sulfuric ester hydrolase activity. The KEGG analysis identified involvement in pathways such as neuroactive ligand–receptor interaction, axon guidance, ECM–receptor interaction, the one-carbon pool by folate, and focal adhesion (p < 0.05). To validate these CNVRs, we performed quantitative real-time PCR experiments to verify copy number predictions made by PennCNV software (v1.0.5). Out of 11 selected CNVRs with predicted gain, loss, or gain–loss statuses, 8 (IDs 68, 156, 201, 284, 307, 352, 411, 601) were successfully confirmed. This study marks a significant step forward in mapping CNVs in the ovine genome and offers a valuable resource for future research on genetic variation in sheep.

The RNA helicase LOS4 regulates pre-mRNA splicing of key genes (EIN2, ERS2, CTR1) in the ethylene signaling pathway.

The Arabidopsis RNA helicase LOS4 plays a key role in regulating pre-mRNA splicing of the genes EIN2, CTR1, and ERS2 in ethylene signaling pathway. The plant hormone ethylene plays diverse roles in plant growth, development, and responses to stress. Ethylene is perceived by the membrane-bound ethylene receptors complex, and then triggers downstream components, such as EIN2, to initiate signal transduction into the nucleus, leading to the activation of ethylene-responsive genes. Over the past decades, substantial information has been accumulated regarding gene cloning, protein-protein interactions, and downstream gene expressions in the ethylene pathway. However, our understanding of mRNA post-transcriptional processing and modification of key genes in the ethylene signaling pathway remains limited. This study aims to provide evidence demonstrating the involvement of the Arabidopsis RNA helicase LOS4 in pre-mRNA splicing of the genes EIN2, CTR1, and ERS2 in ethylene signaling pathway. Various genetic approaches including RNAi gene silencing, CRISPR-Cas9 gene editing, and amino acid mutations were employed in this study. When LOS4 was silenced or knocked down, the ethylene sensitivity of etiolated seedlings was significantly enhanced. Further investigation revealed errors in the EIN2 pre-mRNA splicing when LOS4 was knocked down. In addition, aberrant pre-mRNA splicing was observed in the ERS2 and CTR1 genes in the pathway. Biochemical assays indicated that the los4-2 (E94K) mutant protein exhibited increased ATP binding and enhanced ATP hydrolytic activity. Conversely, the los4-1 (G364R) mutant had reduced substrate RNA binding and lower ATP binding activities. These findings significantly advanced our comprehension of the regulatory functions and molecular mechanisms of RNA helicase in ethylene signaling.

Computational exploration of Ganoderma lucidum metabolites as potential anti-atherosclerotic agents: Insights from molecular docking and dynamics simulations

Ganoderma lucidum is a unique form of fungus utilized in Chinese medicine for various therapies as it exhibits a wide range of pharmacological activity. In this study, the purpose is to evaluate the possible drug-like qualities of the metabolites of G. lucidium as well as the impact that these metabolites have on the pathways involved in atherosclerosis. Throughout our research, a total of 17 compounds were chosen based on their drug-like properties. These compounds were then utilized in the subsequent networking and docking simulations. According to the findings, the compound ganodone has a maximum binding energy of −7.243 Kcal/mol. In terms of the binding energy, it has been discovered that the compound cianidanol has the lowest value. Based on the findings of the molecular docking investigations, it was determined that TNF, AKT1, SRC, and STAT3 exhibited a higher affinity for the complex. To determine this, molecular dynamics simulation was performed for about 100 nanoseconds. Following the completion of the GO functional analysis, it was discovered that the target genes were involved in the processes of protein binding, ATP binding, enzyme binding, and protein tyrosine kinase activity. Overall, the study results provide a view of possible metabolites that may have an impact on disease progression.

The comparative toxicity of biobased, modified biobased, biodegradable, and petrochemical-based microplastics on the brackish water flea Diaphanosoma celebensis

The escalating production and improper disposal of petrochemical-based plastics have led to a global pollution issue with microplastics (MPs), which pose a significant ecological threat. Biobased and biodegradable plastics are believed to mitigate plastic pollution. However, their environmental fate and toxicity remain poorly understood. This study compares the in vivo effects of different types of MPs, poly(butylene adipate-co-terephthalate) as a biodegradable plastic, polylactic acid (PLA) as a biobased plastic, β-cyclodextrin-grafted PLA as a modified biobased plastic, and low density polyethylene as the reference petrochemical-based plastic, on the key aquatic primary consumer Diaphanosoma celebensis. Exposure to MPs resulted in significant reproductive decline, with comparable effects observed irrespective of MP type or concentration. Exposure to MPs induced distinct responses in redox stress, with transcriptional profiling revealing differential gene expression patterns that indicate varied cellular responses to different types of MPs. ATP-binding cassette transporter activity assays demonstrated altered efflux activity, mainly in response to modified biobased and biodegradable MPs. Overall, this study highlights the comparable in vivo and in vitro effects of biobased, biodegradable, and petrochemical-based MPs on aquatic primary consumers, highlighting their potential ecological implications.

Biochemical characterization of the meiosis-essential yet evolutionarily divergent topoisomerase VIB-like protein MTOPVIB from Arabidopsis thaliana.

Formation of programmed DNA double-strand breaks is essential for initiating meiotic recombination. Genetic studies on Arabidopsis thaliana and Mus musculus have revealed that assembly of a type IIB topoisomerase VI (Topo VI)-like complex, composed of SPO11 and MTOPVIB, is a prerequisite for generating DNA breaks. However, it remains enigmatic if MTOPVIB resembles its Topo VI subunit B (VIB) ortholog in possessing robust ATPase activity, ability to undergo ATP-dependent dimerization, and activation of SPO11-mediated DNA cleavage. Here, we successfully prepared highly pure A. thaliana MTOPVIB and MTOPVIB-SPO11 complex. Contrary to expectations, our findings highlight that MTOPVIB differs from orthologous Topo VIB by lacking ATP-binding activity and independently forming dimers without ATP. Most significantly, our study reveals that while MTOPVIB lacks the capability to stimulate SPO11-mediated DNA cleavage, it functions as a bona fide DNA-binding protein and plays a substantial role in facilitating the dsDNA binding capacity of the MOTOVIB-SPO11 complex. Thus, we illustrate mechanistic divergence between the MTOPVIB-SPO11 complex and classical type IIB topoisomerases.

Characterising ATP binding activity of PilB ATPase of Shewanella oneidensis MR-1 using a molecular modeling and simulations approach

Characterising ATP binding activity of PilB ATPase of Shewanella oneidensis MR-1 using a molecular modeling and simulations approach

Proteomic profile of Toxoplasma gondii stress granules by high-resolution mass spectrometry.

Ribonucleoprotein granules are bio-condensates that form a diverse group of dynamic membrane-less organelles implicated in several cellular functions, including stress response and cellular survival. In Toxoplasma gondii, a type of bio-condensates referred to as stress granules (SGs) are formed prior to the parasites' egress from the host cell and are implicated in the survival and invasion competency of extracellular tachyzoites. We used paraformaldehyde to fix and cross-link SG proteins to allow purification by centrifugation and analysis by mass spectrometry. We profiled protein components of SGs at 10 and 30min post-egress when parasite's invasion ability is significantly diminished. Thirty-three proteins were identified from 10min SGs, and additional 43 proteins were identified from 30min SGs. Notably, common SG components such as proteins with intrinsically disordered domains were not identified. Gene ontology analysis of both 10 and 30min SGs shows that overall molecular functions of SGs' proteins are ATP-binding, GTP-binding, and GTPase activity. Discernable differences between 10 and 30min SGs are in the proportions of translation and microtubule-related proteins. Ten-minute SGs have a higher proportion of microtubule-related proteins and a lower proportion of ribosome-related proteins, while a reverse correlation was identified for those of 30min. It remains to be investigated whether this reverse correlation contributes to the ability of extracellular tachyzoites to reinvade host cells.

Betasatellite-encoded βC1 protein regulates helper virus accumulation by interfering with the ATP hydrolysis activity of geminivirus-encoded replication initiator protein.

Geminivirus-betasatellite disease complexes are an epidemic threat to the majority of economically important crops across the world. Plant virus satellites including betasatellites are maintained by their associated helper virus. Geminivirus-betasatellites influence viral pathogenesis by substantially increasing or decreasing their helper virus accumulation. In the present study, we attempted to understand the mechanistic details of the geminivirus-betasatellite interaction. Here, we used tomato leaf curl Gujarat virus (ToLCGV) and tomato leaf curl Patna betasatellite (ToLCPaB) as a model system. This study reveals that ToLCGV can efficiently trans-replicate ToLCPaB in Nicotiana benthamiana plants, but ToLCPaB greatly reduced the accumulation of its helper virus DNA. For the first time, we have identified that the ToLCPaB-encoded βC1 protein is able to interact with ToLCGV-encoded replication initiator protein (Rep). In addition, we demonstrate that the C-terminal region of βC1 interacts with the C-terminus of Rep (RepC) protein. Our previous study had established that βC1 proteins encoded by diverse betasatellites possess a novel ATP hydrolysis activity and the conserved lysine/arginine residues at positions 49 and 91 are necessary for this function. Here, we show that mutating lysine at positions 49 to alanine of βC1 (βC1K49A) protein did not affect its ability to interact with RepC protein. Biochemical studies performed with ATP hydrolysis activity-deficient K49A mutated βC1 (βC1K49A) and RepC proteins revealed that Rep-βC1 interaction interferes with the ATP hydrolysis activity of Rep protein. Further, we demonstrate that βC1 protein is able to interact with D227A and D289A mutated RepC proteins but not with D262A, K272A or D286A mutated RepC proteins, suggesting that the βC1-interacting region of Rep protein encompasses its Walker-B and B' motifs. The results of docking studies supported that the βC1-interacting region of Rep protein encompasses its motifs associated with ATP binding and ATP hydrolysis activities. Docking studies also provided evidence that the Rep-βC1 interaction interferes with the ATP binding activity of Rep protein. Together, our findings suggest that βC1 protein regulates helper virus accumulation by interfering with the ATP hydrolysis activity of helper virus Rep protein.

Genetic mapping of candidate loci for water‐deficit stress‐induced proline accumulation in bread wheat (Triticum aestivum)

AbstractProline is an important metabolite that plays an adaptive role in plants under water‐deficit stress. Understanding the genetic basis of water‐deficit‐induced proline accumulation remains elusive in crop plants, especially in wheat. Here, we investigated proline accumulation under control and water‐deficit conditions using a diversity panel which comprises of 150 bread wheat cultivars. Water‐deficit stress significantly increased proline accumulation than well‐water treated plants. Water‐deficit‐induced proline variability was dissected using genome‐wide association studies that identified significant marker‐trait associations, especially on 1A and 1B chromosomes. Population structure analysis revealed the cultivars originated from Europe were associated with higher proline content. Further, linkage disequilibrium analysis identified minor allele of haplotypes, and single markers were linked with higher proline accumulation under water‐deficit conditions. The identified candidate genes were mostly involved in ATP and ADP binding, protein and oligopeptide transporter activity and also found in defence response, carbohydrate and fatty acid biosynthetic processes. Next, an in silico transcript analysis found higher expression of candidate genes in shoot/leaves under water‐deficit stress conditions. Overall, the key genomic regions controlling water deficit‐induced proline accumulation can be utilized in improving plant adaptation to drought.

Resistance screening and in silico characterization of cloned novel RGA from multi-race resistant lentil germplasm against Fusarium wilt (Fusarium oxysporum f. sp. lentis).

Fusarium wilt caused by Fusarium oxysporum f. sp. lentis (Fol) is the most devastating disease of lentil present worldwide. Identification of multi-race fusarium wilt resistance genes and their incorporation into existing cultivars will help to reduce yield losses. In the present study, 100 lentil germplasms belonging to seven lentil species were screened against seven prevalent races of Fol, and accessions IC201561 (Lens culinaris subsp. culinaris), EC714243 (L. c. subsp. odemensis), and EC718238 (L. nigricans) were identified as resistant. The typical R gene codes for the nucleotide-binding site and leucine-rich repeats (NBS-LRR) at the C terminal are linked to either the Toll/interleukin 1-like receptor (TIR) or coiled coil (CC) at the N terminal. In the present study, degenerate primers, designed from the NBS region amplifying the P-loop to the GLPLA motif, isolated forty-five resistance gene analogues (RGAs) from identified resistant accessions. The sequence alignment identified both classes of RGAs, TIR and non-TIR, based on the presence of aspartate (D) and tryptophan (W) at the end of the kinase motif, respectively. The phylogenetic analysis grouped the RGAs into six classes, from LRGA1 to LRGA6, which determined the diversity of the RGAs present in the host. Grouping of the RGAs identified from Lens nigricans, LnRGA 2, 9, 13 with I2 revealed the structural similarity with the fusarium resistance gene. The similarity index ranged from 27.85% to 86.98% among the RGAs and from 26.83% to 49.41% among the known R genes, I2, Gpa2, M, and L6. The active binding sites present along the conserved motifs grouped the RGAs into 13 groups. ADP/ATP, being the potential ligand, determines the ATP binding and ATP hydrolysis activity of the RGAs. The isolated RGAs can be used to develop markers linked to the functional R gene. Furthermore, expression analysis and full-length gene isolation pave the path to identifying the molecular mechanism involved in resistance.

In-silico structural characterization and phylogenetic analysis of Nucleoside diphosphate kinase: A novel antiapoptotic protein of Porphyromonas gingivalis.

The Nucleoside diphosphate kinase (NDK) protein of Porphyromonas gingivalis (P. gingivalis) plays a crucial role in immune evasion and inhibition of apoptosis in host cells and has the potential to cause cancer. However, its structure has not yet been characterized. We used an in-silico approach to determine the 3D structure of the P. gingivalis NDK. Furthermore, structural characterization and functional annotation were performed using computational approaches. The 3D structure of NDK was predicted through homology modeling. The structural domains predicted for the model protein belong to the NDK family. Structural alignment of prokaryotic and eukaryotic NDKs with the model protein revealed the conservation of the domain region. Structure-based phylogenetic analysis depicted a significant evolutionary relationship between the model protein and the prokaryotic NDK. Functional annotation of the model confirmed structural homology, exhibiting similar enzymatic functions as NDK, including ATP binding and nucleoside diphosphate kinase activity. Furthermore, molecular dynamic (MD) simulation technique stabilized the model structure and provides a thermo-stable protein structure that can be used as a therapeutic target for further studies.

Transcriptome Analysis of Marbled Rockfish Sebastiscus marmoratus under Salinity Stress.

The marbled rockfish, Sebastiscus marmoratus, belongs to the euryhaline fish and is an oviparous scleractinian fish. There are few studies on the adaptation mechanism, functional genes, and related pathways of S. marmoratus and salinity. The results showed that a total of 72.1 GB of clean reads were obtained and all clean reads annotated a total of 25,278 Unigenes, of which 2,160 were novel genes. Compared to 20‱, 479 and 520 differential genes were obtained for 35‱ and 10‱, respectively. Gene ontology (GO) enrichment analysis revealed significant enrichment in protein binding, ion binding, ATP binding, and catalytic activity. Kyoto Encyclopedia of Genes and Genomes (KEGG) showed that differentially expressed genes significantly expressed under salinity stress were mainly involved in the pathways of the cytochrome P450 metabolism of xenobiotics, tryptophan metabolism, cellular senescence, and calcium signaling pathways. Among them, pik3r6b, cPLA2γ-like, and WSB1 were differentially expressed in all three groups, and they were associated with apoptosis, inflammation, DNA damage, immune regulation, and other physiological processes. Six differentially expressed genes were randomly selected for qRT-PCR validation, and the results showed that the transcriptomic data were of high confidence.

PD-L1 expression is regulated by ATP-binding of the ERBB3 pseudokinase domain

How PD-L1 expression is regulated in cancer is poorly understood. Here, we report that the ATP-binding activity of ERBB3 pseudokinase regulates PD-L1 gene expression in colorectal cancers (CRCs). ERBB3 is one of the four members of the EGF receptor family, all with protein tyrosine kinase domains. ERBB3 is a pseudokinase with a high binding affinity to ATP. We showed that ERBB3 ATP-binding inactivation mutant reduces tumorigenicity in genetically engineered mouse models and impairs xenograft tumor growth of CRC cell lines. The ERBB3 ATP-binding mutant cells dramatically reduce IFN-γ-induced PD-L1 expression. Mechanistically, ERBB3 regulates IFN-γ-induced PD-L1 expression through the IRS1-PI3K-PDK1-RSK-CREB signaling axis. CREB is the transcription factor that regulates PD-L1 gene expression in CRC cells. Knockin of a tumor-derived ERBB3 mutation located in the kinase domain sensitizes mouse colon cancers to anti-PD1 antibody therapy, suggesting that ERBB3 mutations could be predictive biomarkers for tumors amenable to immune checkpoint therapy.

GSK-3β phosphorylation of DHX33 leads to its ubiquitination mediated protein degradation

DHX33 is a member of DEAD/H box protein family, and is involved in both RNA and DNA metabolism. It plays diverse roles in multiple cellular activities. DHX33 overexpression has been found to promote the development of many human cancers. However, the underlying mechanism to explain its high expression in cancer cells remains incompletely resolved. In this study, with both human cancer cell lines and normal fibroblasts, we found glycogen synthase kinase 3β (GSK-3β) regulates DHX33 protein stability. This is through its direct phosphorylation of DHX33 on T482, which triggers ubiquitination mediate protein degradation. We further identified one of the major ubiquitination sites of DHX33 to be on its N-terminal K94, a critical residue previously found to be important and highly conserved for ATP binding and helicase activity. Our study for the first time reveals an important upstream regulator, GSK-3β, as a critical kinase to phosphorylate DHX33 at the post-translational level leading to its degradation. Moreover, cancer cells have frequent GSK3β deactivation to disrupt this signaling cascade. Therefore, DHX33 is stabilized in many cancer cells as compared to normal cells. Our study unveils an important post-translational regulation of DHX33 in cells and further unveils a novel mechanism for DHX33 overexpression in cancer cells.

Clinical and biological impact of ATP-binding cassette transporter activity in adult acute myeloid leukemia.

Chemotherapy resistance is the main cause of treatment failure in acute myeloid leukemia (AML) and has been related to ATP-binding cassette (ABC) transporter activity. However, the links between ABC activity, immunophenotype, and molecular AML parameters have been poorly evaluated. Moreover, the prognostic value of ABC activity, when compared to new molecular markers, is unknown. Here we investigated the links between ABC activity, as evaluated by JC-1 +/- cyclosporine A assay, and immunophenotypic, cytogenetic, molecular, and targeted next-generation sequencing features in 361 AML patients. High ABC activity was found in 164 patients and was significantly associated with less proliferating disease, an immature immunophenotype (expression of CD34, HLA-DR, CD117, CD13), and gene mutations defining AML as belonging to secondary-type ontogenic groups. Low ABC activity was associated with more mature myeloid differentiation (CD34-, cyMPO+, CD15+, CD33+) or monocytic commitment (CD64+, CD4+weak, CD14+), with NPM1 mutations, KMT2A rearrangements, and core-binding factor gene fusions, hallmarks of the de novo-type AML ontogeny. ABC activity was one of the major factors we identified using a random forest model for early prediction of AML ontogeny. In the 230 patients evaluated at diagnosis and intensively treated, high ABC activity was a predictive factor for primary resistance, and in multivariate analysis including full molecular data, an independent factor for event-free survival (P=0.0370). JC-1 +/- cyclosporine A assay could be used at diagnosis to predict AML ontogeny and to complete prognosis evaluation in addition to new molecular markers.

Exploration and validation of Taraxacum mongolicum anti-cancer effect

Taraxacum mongolicum gained a lot of concern and was applied in 93 formulas in China due to its fame as a traditional Chinese medicine. The earliest recorded application of Taraxacum mongolicum was traced back to the Han dynasty. Generations of doctors boosted the usage and enriched the pharmacological mechanism. Clinical application of the Taraxacum mongolicum is flourishing as it treats multiple diseases. This study aims to explore the anti-cancer effect, retrieve the active ingredients and screen the key targets of Taraxacum mongolicum in cancer therapy. We collected and evaluated 10 key active compounds to investigate the anti-cancer effect via 69 significant targets and a variety of biological processes and pathways. Gene Ontology (GO) enrichment analysis uncovered targets associated with protein phosphorylation, cell proliferation and apoptotic processes via regulation of kinases, ATP and enzyme binding activities. Half of the top 20 enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were directly involved in cancer. Based on standard selection criteria, seven hub targets were obtained. These targets functioned through distinct patterns and pathways in realizing the anti-cancer effect. Molecular docking was conducted to validate the potential combination between compounds and hub targets to explore the pharmacological mechanism of key compounds in Taraxacum mongolicum against cancer. In summary, our findings indicate that the famous and widely used Chinese herb, Taraxacum mongolicum, shows good anti-cancer effect through its active compounds, targeted genes, and multiple involved biological processes. The results may provide a theoretical basis for subsequent experimental validation and drug development of Taraxacum mongolicum extract against cancer.

Whole-exome sequencing analysis of NSCLC reveals the pathogenic missense variants from cancer-associated genes

BackgroundNon-small-cell lung cancer (NSCLC) is the most common type of lung cancer. NSCLC accounts for 84% of all lung cancer cases. In recent years, advances in pathway understanding, methods for discovering novel genetic biomarkers, and new drugs designed to inhibit the signaling cascades have enabled clinicians to personalize therapy for NSCLC. ObjectivesThe primary aim of this study is to identify the genes associated with NSCLC that harbor pathogenic variants that could be causative for NSCLC. The second aim is to investigate their roles in different pathways that lead to NSCLC. MethodsWe examined exome-sequencing datasets from 54 NSCLC patients to characterize the variants associated with NSCLC. ResultsOur findings revealed that 17 variants in 14 genes were considered highly pathogenic, including CDKN2A, ERBB2, FOXP1, IDH1, JAK3, KMT2D, K-Ras, MSH3, MSH6, POLE, RNF43, TCF7L2, TP53, and TSC1. Gene set enrichment analysis revealed the involvement of transmembrane receptor protein tyrosine kinase activity, protein binding, ATP binding, phosphatidylinositol-4,5-bisphosphate 3-kinase, and Ras guanyl-nucleotide exchange factor activity. Pathway analysis of these genes yielded different cancer-related pathways, including colorectal, prostate, endometrial, pancreatic, PI3K-Akt signaling pathways, and signaling pathways regulating pluripotency of stem cells. Module 1 from protein-protein interactions (PPIs) identified genes that harbor pathogenic SNPs. Three of the most deleterious SNPs are ERBB2 (rs1196929947), K-Ras (rs121913529), and POLE (rs751425952). Interestingly, one patient has a pathogenic K-Ras variant (rs121913529) co-occurred with the missense variant (rs752054698) inTSC1 gene. ConclusionThis study maps highly pathogenic variants associated with NSCLC and investigates their contributions to the pathogenesis of NSCLC. This study sheds light on the potential applications of precision medicine in patients with NSCLC.

Baicalin Targets HSP70/90 to Regulate PKR/PI3K/AKT/eNOS Signaling Pathways.

Baicalin is a major active ingredient of traditional Chinese medicine Scutellaria baicalensis, and has been shown to have antiviral, anti-inflammatory, and antitumor activities. However, the protein targets of baicalin have remained unclear. Herein, a chemical proteomics strategy was developed by combining baicalin-functionalized magnetic nanoparticles (BCL-N3@MNPs) and quantitative mass spectrometry to identify the target proteins of baicalin. Bioinformatics analysis with the use of Gene Ontology, STRING and Ingenuity Pathway Analysis, was performed to annotate the biological functions and the associated signaling pathways of the baicalin targeting proteins. Fourteen proteins in human embryonic kidney cells were identified to interact with baicalin with various binding affinities. Bioinformatics analysis revealed these proteins are mainly ATP-binding and/or ATPase activity proteins, such as CKB, HSP86, HSP70-1, HSP90, ATPSF1β and ACTG1, and highly associated with the regulation of the role of PKR in interferon induction and the antiviral response signaling pathway (P = 10−6), PI3K/AKT signaling pathway (P = 10−5) and eNOS signaling pathway (P = 10−4). The results show that baicalin exerts multiply pharmacological functions, such as antiviral, anti-inflammatory, antitumor, and antioxidant functions, through regulating the PKR and PI3K/AKT/eNOS signaling pathways by targeting ATP-binding and ATPase activity proteins. These findings provide a fundamental insight into further studies on the mechanism of action of baicalin.

Genome-wide superior alleles, haplotypes and candidate genes associated with tolerance on sodic-dispersive soils in wheat (Triticum aestivum L.)

Key messageThe pleiotropic SNPs/haplotypes, overlapping genes (metal ion binding, photosynthesis), and homozygous/biallelic SNPs and transcription factors (HTH myb-type and BHLH) hold great potential for improving wheat yield potential on sodic-dispersive soils.Sodic-dispersive soils have multiple subsoil constraints including poor soil structure, alkaline pH and subsoil toxic elemental ion concentration, affecting growth and development in wheat. Tolerance is required at all developmental stages to enhance wheat yield potential on such soils. An in-depth investigation of genome-wide associations was conducted using a field phenotypic data of 206 diverse Focused Identification of Germplasm Strategy (FIGS) wheat lines for two consecutive years from different sodic and non-sodic plots and the exome targeted genotyping by sequencing (tGBS) assay. A total of 39 quantitative trait SNPs (QTSs), including 18 haplotypes were identified on chromosome 1A, 1B, 1D, 2A, 2B, 2D, 3A, 3B, 5A, 5D, 6B, 7A, 7B, 7D for yield and yield-components tolerance. Among these, three QTSs had common associations for multiple traits, indicating pleiotropism and four QTSs had close associations for multiple traits, within 32.38 Mb. The overlapping metal ion binding (Mn, Ca, Zn and Al) and photosynthesis genes and transcription factors (PHD-, Dof-, HTH myb-, BHLH-, PDZ_6-domain) identified are known to be highly regulated during germination, maximum stem elongation, anthesis, and grain development stages. The homozygous/biallelic SNPs having allele frequency above 30% were identified for yield and crop establishment/plants m−2. These SNPs correspond to HTH myb-type and BHLH transcription factors, brassinosteroid signalling pathway, kinase activity, ATP and chitin binding activity. These resources are valuable in haplotype-based breeding and genome editing to improve yield potential on sodic-dispersive soils.

Computational Identification of Co-Expression Networks, Key Genes and Pathways in Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is characterized by proliferative, poorly differentiated cells of the hematopoietic system. The aim of this study was to identify biomarkers of AML by gene co-expression network analysis. Microarray dataset was retrieved from Gene Expression Omnibus (GEO) database. Weighted Co-expression Network Analysis (WGCNA) method was applied to evaluate key modules. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was performed using Database for Annotation, Visualization and Integrated Discovery (DAVID) web server. Then, hub genes were identified using Cytoscape software. Finally, expression of hub genes was validated using Gene Expression Profiling Interactive Analysis (GEPIA). A total of 1602 co­expressed genes with highest connectivity were identified in dark red and magenta modules. GO analysis suggested that co-expressed genes were mainly enriched in apoptotic process, signal transduction, cytosol, nucleus, protein binding and ATP binding activity. KEGG pathway analysis revealed that co-expressed genes were significantly enriched in MAPK signaling pathway and pathways in cancer. Protein-Protein Interaction network (PPI) demonstrated that the top 10 hub genes were identified. Survival analysis showed that genes downregulation of ITGB1, JUN and upregulation of ATM, MYC, NOTCH1, PTPN11 were associated with poor overall survival.