The two-component system (TCS) gene family is among the most important signal transduction families in plants and is involved in the regulation of various abiotic stresses, cell growth and division. To understand the role of TCS genes in mango (Mangifera indica ), a comprehensive analysis of TCS gene family was carried out in mango leading to identification of 65 MiTCS genes. Phylogenetic analysis divided MiTCSs into three groups (histidine kinases, histidine-containing phosphotransfer proteins, and response regulators) and 11 subgroups. One tandem duplication and 23 pairs of segmental duplicates were found within the MiTCSs . Promoter analysis revealed that MiTCSs contain a large number of cis -elements associated with environmental stresses, hormone response, light signalling, and plant development. Gene ontology analysis showed their involvement in various biological processes and molecular functions, particularly signal transduction. Protein-protein interaction analysis showed that MiTCS proteins interacted with each other. The expression pattern in various tissues and under many stresses (drought, cold, and disease) showed that expression levels varied among various genes in different conditions. MiTCSs 3D structure predictions showed structural conservation among members of the same groups. This information can be further used to develop improved cultivars and will serve as a foundation for gaining more functional insights into the TCS gene family.
Gene Expression Regulation, Plant , Mangifera , Multigene Family , Phylogeny , Plant Proteins , Stress, Physiological , Mangifera/genetics , Mangifera/metabolism , Stress, Physiological/genetics , Plant Proteins/genetics , Plant Proteins/metabolism , Plant Proteins/chemistry , Gene Expression Profiling , Computational Biology , Promoter Regions, Genetic , Signal Transduction
In the genomics of plants and the phytoecosystem, Pyrus (pear) is among the most nutritious fruits and contains fiber that has great health benefits to humans. It is mostly cultivated in temperate regions and is one of the most cultivated pome fruits globally. Pears are highly subjected to biotic and abiotic stresses that affect their yield. TIR1/AFB proteins act as auxin co-receptors during the signaling of nuclear auxins and play a primary role in development-related regulatory processes and responses to biotic and abiotic stresses. However, this gene family and its members have not been explored in Pyrus genomes, and understanding these genes will help obtain useful insights into stress tolerance and ultimately help maintain a high yield of pears. This study reports a pangenome-wide investigation of TIR1/AFB genes from eight Pyrus genomes: Cuiguan (Pyrus pyrifolia), Shanxi Duli (P. betulifolia), Zhongai 1 [(P. ussuriensis × communis) × spp.], Nijisseiki (P. pyrifolia), Yunhong No.1 (P. pyrifolia), d'Anjou (P. communis), Bartlett v2.0 (P. communis), and Dangshansuli v.1.1 (P. bretschneideri). These genes were randomly distributed on 17 chromosomes in each genome. Based on phylogenetics, the identified TIR1/AFB genes were divided into six groups. Their gene structure and motif pattern showed the intraspecific structural conservation as well as evolutionary patterns of Pyrus TIR1/AFBs. The expansion of this gene family in Pyrus is mainly caused by segmental duplication; however, a few genes showed tandem duplication. Moreover, positive and negative selection pressure equally directed the gene's duplication process. The GO and PPI analysis showed that Pyrus TIR1/AFB genes are associated with abiotic stress- and development-related signaling pathways. The promoter regions of Pyrus TIR1/AFB genes were enriched in hormone-, light-, development-, and stress-related cis elements. Furthermore, publicly available RNA-seq data analysis showed that DaTIR1/AFBs have varied levels of expression in various tissues and developmental stages, fruit hardening disease conditions, and drought stress conditions. This indicated that DaTIR1/AFB genes might play critical roles in response to biotic and abiotic stresses. The DaTIR1/AFBs have similar protein structures, which show that they are involved in the same function. Hence, this study will broaden our knowledge of the TIR1/AFB gene family in Pyrus, elucidating their contribution to conferring resistance against various environmental stresses, and will also provide valuable insights for future researchers.
Passion fruit is widely cultivated in tropical, subtropical regions of the world. The attack of bacterial and fungal diseases, and environmental factors heavily affect the yield and productivity of the passion fruit. The CC-NBS-LRR (CNL) gene family being a subclass of R-genes protects the plant against the attack of pathogens and plays a major role in effector-triggered immunity (ETI). However, no information is available regarding this gene family in passion fruit. To address the underlying problem a total of 25 and 21 CNL genes have been identified in the genome of purple (Passiflora edulis Sims.) and yellow (Passiflora edulis f. flavicarpa) passion fruit respectively. Phylogenetic tree was divided into four groups with PeCNLs present in 3 groups only. Gene structure analysis revealed that number of exons ranged from 1 to 9 with 1 being most common. Most of the PeCNL genes were clustered at the chromosome 3 and underwent strong purifying selection, expanded through segmental (17 gene pairs) and tandem duplications (17 gene pairs). PeCNL genes contained cis-elements involved in plant growth, hormones, and stress response. Transcriptome data indicated that PeCNL3, PeCNL13, and PeCNL14 were found to be differentially expressed under Cucumber mosaic virus and cold stress. Three genes were validated to be multi-stress responsive by applying Random Forest model of machine learning. To comprehend the biological functions of PeCNL proteins, their 3D structure and gene ontology (GO) enrichment analysis were done. Our research analyzed the CNL gene family in passion fruit to understand stress regulation and improve resilience. This study lays the groundwork for future investigations aimed at enhancing the genetic composition of passion fruit to ensure robust growth and productivity in challenging environments.
The nucleotide-binding site-leucine-rich repeat (NBS-LRR) gene family is the largest group of disease resistance (R) genes in plants and is active in response to viruses, bacteria, and fungi usually involved in effector-triggered immunity (ETI). Pangenome-wide studies allow researchers to analyze the genetic diversity of multiple species or their members simultaneously, providing a comprehensive understanding of the evolutionary relationships and diversity present among them. The draft pan-genome of three Mangifera indica cultivars (Alphonso, Hong Xiang Ya, and Tommy atkins) was constructed and Presence/absence variants (PAVs) were filtered through the ppsPCP pipeline. As a result, 2823 genes and 5907 PAVs from H. Xiang Ya, and 1266 genes and 2098 PAVs from T. atkins were added to the reference genome. For the identification of CC-NBS-LRR (CNL) genes in these mango cultivars, this draft pan-genome study has successfully identified 47, 27, and 36 members in Alphonso, H. Xiang Ya, and T. atkins respectively. The phylogenetic analysis divided MiCNL proteins into four distinct subgroups. All MiCNL genes are unevenly distributed on chromosomes. Both tandem and segmental duplication events played a significant role in the expansion of the CNL gene family. These genes contain cis-elements related to light, stress, hormone, and development. The analysis of protein-protein interactions (PPI) revealed that MiCNL proteins interacted with other defense-responsive proteins. Gene Ontology (GO) analysis indicated that MiCNL genes play a role in defense mechanisms within the organism. The expression level of the identified genes in fruit peel was observed under disease and cold stress which showed that Mi_A_CNL13 and 14 were up-regulated while Mi_A_CNL15, 25, 30, 31, and 40 were down-regulated in disease stress. On the other hand, Mi_A_CNL2, 14, 41, and 45 were up-regulated and Mi_A_CNL47 is down-regulated in cold stress. Subsequently, the Random Forest (RF) classifier was used to assess the multi-stress response of MiCNLs. It was found that Mi_A_CNL14 is a gene that responds to multiple stress conditions. The CNLs have similar protein structures which show that they are involved in the same function. The above findings provide a foundation for a deeper understanding of the functional characteristics of the mango CNL gene family.
Arachis hypogaea (peanut) is a leading oil and protein-providing crop with a major food source in many countries. It is mostly grown in tropical regions and is largely affected by abiotic and biotic stresses. Cysteine-rich receptor-like kinases (CRKs) is a family of transmembrane proteins that play important roles in regulating stress-signaling and defense mechanisms, enabling plants to tolerate stress conditions. However, almost no information is available regarding this gene family in Arachis hypogaea and its progenitors. This study conducts a pangenome-wide investigation of A. hypogaea and its two progenitors, A. duranensis and A. ipaensis CRK genes (AhCRKs, AdCRKs, and AiCRKs). The gene structure, conserved motif patterns, phylogenetic history, chromosomal distribution, and duplication were studied in detail, showing the intraspecies structural conservation and evolutionary patterns. Promoter cis-elements, protein-protein interactions, GO enrichment, and miRNA targets were also predicted, showing their potential functional conservation. Their expression in salt and drought stresses was also comprehensively studied. The CRKs identified were divided into three groups, phylogenetically. The expansion of this gene family in peanuts was caused by both types of duplication: tandem and segmental. Furthermore, positive as well as negative selection pressure directed the duplication process. The peanut CRK genes were also enriched in hormones, light, development, and stress-related elements. MicroRNA (miRNA) also targeted the AhCRK genes, which suggests the regulatory association of miRNAs in the expression of these genes. Transcriptome datasets showed that AhCRKs have varying expression levels under different abiotic stress conditions. Furthermore, the multi-stress responsiveness of the AhCRK genes was evaluated using a machine learning-based method, Random Forest (RF) classifier. The 3D structures of AhCRKs were also predicted. Our study can be utilized in developing a detailed understanding of the stress regulatory mechanisms of the CRK gene family in peanuts and its further studies to improve the genetic makeup of peanuts to thrive better under stress conditions.
The Two-component system (TCS) consists of Histidine kinases (HKs), Phosphotransfers (HPs), and response regulator (RR) proteins. It has an important role in signal transduction to respond to a wide variety of abiotic stresses and hence in plant development. Brassica oleracea (cabbage) is a leafy vegetable, which is used for food and medicinal purposes. Although this system was identified in several plants, it had not been identified in Brassica oleracea yet. This genome-wide study identified 80 BoTCS genes consisting of 21 HKs, 8 HPs, 39 RRs, and 12 PRRs. This classification was done based on conserved domains and motif structure. Phylogenetic relationships of BoTCS genes with Arabidopsis thaliana, Oryza sativa, Glycine max, and Cicer arietinum showed conservation in TCS genes. Gene structure analysis revealed that each subfamily had conserved introns and exons. Both tandem and segmental duplication led to the expansion of this gene family. Almost all of the HPs and RRs were expanded through segmental duplication. Chromosomal analysis showed that BoTCS genes were dispersed across all nine chromosomes. The promoter regions of these genes were found to contain a variety of cis-regulatory elements. The 3D structure prediction of proteins also confirmed the conservation of structure within subfamilies. MicroRNAs (miRNAs) involved in the regulation of BoTCSs were also predicted and their regulatory roles were also evaluated. Moreover, BoTCSs were docked with abscisic acid to evaluate their binding. RNA-seq-based expression analysis and validation by qRT-PCR showed significant variation of expression for BoPHYs, BoERS1.1, BoERS2.1, BoERS2.2, BoRR10.2, and BoRR7.1 suggesting their importance in stress response. These genes showing unique expression can be further used in manipulating the plant's genome to make the plant more resistant the environmental stresses which will ultimately help in the increase of plant's yield. More specifically, these genes have altered expression in shade stress which clearly indicates their importance in biological functions. These findings are important for future functional characterization of TCS genes in generating stress-responsive cultivars.
Liver cancer is a malignant tumor that grows on the surface or inside the liver. The leading cause is a viral infection with hepatitis B or C virus. Natural products and their structural analogues have historically made a major contribution to pharmacotherapy, especially for cancer. A list of studies evidences the therapeutic efficacy of Bacopa monnieri against liver cancer, but the precise molecular mechanism is yet to be discovered. This study combines data mining, network pharmacology, and molecular docking analysis to potentially revolutionize liver cancer treatment by identifying effective phytochemicals. Initially, the information on active constituents of B. monnieri and target genes of both liver cancer and B. monnieri were retrieved from literature as well as from publicly available databases. Based on the matching results between B. monnieri potential targets and liver cancer targets, the protein-protein interaction (PPI) network was constructed using the STRING database and imported into Cytoscape for screening of hub genes based on their degree of connectivity. Later, the interactions network between compounds and overlapping genes was constructed using Cytoscape software to analyze the network pharmacological prospective effects of B. monnieri on liver cancer. Gene Ontology (GO) and KEGG pathway analysis of hub genes revealed that these genes are involved in the cancer-related pathway. Lastly, the expression level of core targets was analyzed using microarray data (GSE39791, GSE76427, GSE22058, GSE87630, and GSE112790). Further, the GEPIA server and PyRx software were used for survival and molecular docking analysis, respectively. In summary, we proposed that quercetin, luteolin, apigenin, catechin, epicatechin, stigmasterol, beta-sitosterol, celastrol, and betulic acid inhibit tumor growth by affecting tumor protein 53 (TP53), interleukin 6 (IL6), RAC-alpha serine/threonine protein kinases 1 (AKT1), caspase-3 (CASP3), tumor necrosis factor (TNF), jun proto-oncogene (JUN), heat shot protein 90 AA1 (HSP90AA1), vascular endothelial growth factor A (VEGFA), epidermal growth factor receptor (EGFR), and SRC proto-oncogene (SRC). Through, microarray data analysis, the expression level of JUN and IL6 were found to be upregulated while the expression level of HSP90AA1 was found to be downregulated. Kaplan-Meier survival analysis indicated that HSP90AA1 and JUN are promising candidate genes that can serve as diagnostic and prognostic biomarkers for liver cancer. Moreover, the molecular docking and molecular dynamic simulation of 60ns well complemented the binding affinity of the compound and revealed strong stability of predicted compounds at the docked site. Calculation of binding free energies using MMPBSA and MMGBSA validated the strong binding affinity between the compound and binding pockets of HSP90AA1 and JUN. Despite that, in vivo and in vitro studies are mandatory to unveil pharmacokinetics and biosafety profiles to completely track the candidature status of B. monnieri in liver cancer.
Bacopa , Drugs, Chinese Herbal , Liver Neoplasms , Vascular Endothelial Growth Factor A , Molecular Docking Simulation , Interleukin-6 , Network Pharmacology , Liver Neoplasms/drug therapy , Liver Neoplasms/genetics , Data Mining
Introduction: The prevalence of appendiceal mucinous neoplasms (AMN) is about 0.2%-0.3% in the specimens of the appendix. The LAMN may appear unremarkable or can present as mucin-filled, crystally dilated tissues. The diagnosis of early-stage AMN is mostly incidental. It is of vital importance to know the features of LAMN for a timely diagnosis. Case presentation: A 46-year-old male came with the complaint of right iliac fossa swelling along with severe intensity pain and a single episode of vomiting. A 4 × 4cm tender, soft, cystic, mobile swelling was found upon the examination. Contrast-enhanced Computerized tomography (CT) scan of the abdomen revealed the appendix diameter of 10mm well-circumscribed cystic measuring 2.1 × 2 cm. Therefore, an open resection surgery was performed. The histopathological report revealed an intraepithelial lesion composed of flat mucinous epithelial cells having eosinophilic cytoplasm and low-grade nuclear atypia. Case discussion: The AMNs are very rare neoplasms. The imaging modalities that can be diagnostic methods are abdominal and transvaginal ultrasonography (US), and abdominal computed tomography (CT). The low-grade features of the appendiceal mucinous neoplasms have the possibility of recurrence. The CT-scan findings of appendiceal lump>1.3cm along with cystic dilation and the calcification of the wall are the suggestive features of AMN. There is a high chance of dissemination and port site seeding in case of pneumoperitoneum. Conclusion: This rare case suggests the significance of adding AMNs as a differential diagnosis in patients with abdominal pain and choosing the right approach to treat such patients to avoid complications.
Cyclic nucleotide-gated channels (CNGC) gene family has been found to be involved in physiological processes including signaling pathways, environmental stresses, plant growth, and development. This gene family of non-selective cation channels is known to regulate the uptake of calcium and is reported in several plant species. The pangenome-wide studies enable researchers to understand the genetic diversity comprehensively; as a comparative analysis of multiple plant species or member of a species at once helps to better understand the evolutionary relationships and diversity present among them. In the current study, pangenome-wide analysis of the CNGC gene family has been performed on five Citrus species. As a result, a total of 32 genes in Citrus sinensis, 27 genes in Citrus recticulata, 30 genes in Citrus grandis, 31 genes in Atalantia buxfolia, and 30 genes in Poncirus trifoliata were identified. In addition, two unique genes CNGC13 and CNGC14 were identified, which may have potential roles. All the identified CNGC genes were unevenly distributed on 9 chromosomes except P. trifoliata had genes distributed on 7 chromosomes and were classified into four major groups and two sub-groups namely I, II, III, IV-A, and IV-B. Cyclic nucleotide binding (CNB) motif, calmodulin-binding motif (CaMB), and motif for IQ-domain were conserved in Citrus Spp. Intron exon structures of citrus species were not exactly as same as the gene structures of Arabidopsis. The majority of cis-regulatory elements (CREs) were light responsive and others include growth, development, and stress-related indicating potential roles of the CNGC gene family in these functions. Both segmental and tandem duplication were involved in the expansion of the CNGC gene family in Citrus Spp. The miRNAs are involved in the response of CsCNGC genes towards drought stress along with having regulatory association in the expression of these genes. Protein- Protein interaction (PPI) analysis also showed the interaction of CNGC proteins with other CNGCs which suggested their potential role in pathways regulating different biological processes. GO enrichment revealed that CNGC genes were involved in the transport of ions across membranes. Furthermore, tissue-specific expression patterns of leaves sample of C. sinensis were studied under drought stress. Out of 32 genes of C. sinensis 3 genes i.e., CsCNGC1.4, CsCNGC2.1, and CsCNGC4.2 were highly up-regulated, and only CsCNGC4.6 was highly down-regulated. The qRT-PCR analysis also showed that CNGC genes were highly expressed after treatment with drought stress, while gene expression was lower under controlled conditions. This work includes findings based on multiple genomes instead of one, therefore, this will provide more genomic information rather than single genome-based studies. These findings will serve as a basis for further functional insights into the CNGC gene family.
Superoxide dismutase (SOD) proteins are important antioxidant enzymes that help plants to grow, develop, and respond to a variety of abiotic stressors. SOD gene family has been identified in a number of plant species but not yet in Daucus carota. A total of 9 DcSOD genes, comprising 2 FeSODs, 2 MnSODs, and 5 Cu/ZnSODs, are identified in the complete genome of D. carota, which are dispersed in five out of nine chromosomes. Based on phylogenetic analysis, SOD proteins from D. carota were categorized into two main classes (Cu/ZnSODs and MnFeSODs). It was predicted that members of the same subgroups have the same subcellular location. The phylogenetic analysis was further validated by sequence motifs, exon-intron structure, and 3D protein structures, with each subgroup having a similar gene and protein structure. Cis-regulatory elements responsive to abiotic stresses were identified in the promoter region, which may contribute to their differential expression. Based on RNA-seq data, tissue-specific expression revealed that DcCSD2 had higher expression in both xylem and phloem. Moreover, DcCSD2 was differentially expressed in dark stress. All SOD genes were subjected to qPCR analysis after cold, heat, salt, or drought stress imposition. SODs are antioxidants and play a critical role in removing reactive oxygen species (ROS), including hydrogen peroxide (H2O2). DcSODs were docked with H2O2 to evaluate their binding. The findings of this study will serve as a basis for further functional insights into the DcSOD gene family.
Neurological disorders (NDs) are recognized as one of the major health concerns globally. According to the World Health Organization (WHO), neurological disorders are one of the main causes of mortality worldwide. Neurological disorders include Alzheimer's disease, Parkinson's disease, Huntington's disease, Amyotrophic lateral sclerosis, Frontotemporal dementia, Prion disease, Brain tumor, Spinal cord injury, and Stroke. These diseases are considered incurable diseases because no specific therapies are available to cross the blood-brain barrier (BBB) and reach the brain in a significant amount for the pharmacological effect in the brain. There is a need for the development of strategies that can improve the efficacy of drugs and circumvent BBB. One of the promising approaches is the use of different types of nano-scale materials. These nano-based drugs have the ability to increase the therapeutic effect, reduce toxicity, exhibit good stability, targeted delivery, and drug loading capacity. Different types and shapes of nanomaterials have been widely used for the treatment of neurological disorders, including quantum dots, dendrimers, metallic nanoparticles, polymeric nanoparticles, carbon nanotubes, liposomes, and micelles. These nanoparticles have unique characteristics, including sensitivity, selectivity, and the ability to cross the BBB when used in nano-sized particles, and are widely used for imaging studies and treatment of NDs. In this review, we briefly summarized the recent literature on the use of various nanomaterials and their mechanism of action for the treatment of various types of neurological disorders.
The two-component signal transduction system (TCS) acts in a variety of physiological processes in lower organisms and has emerged as a key signaling system in both prokaryotes and eukaryotes, including plants. TCS genes assist plants in processes such as stress resistance, cell division, nutrition signaling, leaf senescence, and chloroplast division. In plants, this system is composed of three types of proteins: response regulators (RRs), histidine kinases (HKs), and histidine phosphotransfer proteins (HPs). We aimed to study the Sorghum bicolor genome and identified 37 SbTCS genes consisting of 13 HKs, 5 HPs, and 19 RRs (3 type-A RRs, 7 type-B RRs, 2 type-C RRs, and 7 pseudo-RRs). The structural and phylogenetic comparison of the SbTCS members with their counterparts in Arabidopsis thaliana, Oryza sativa, Cicer arietinum, and Glycine max showed group-specific conservations and variations. Expansion of the gene family members is mostly a result of gene duplication, of both the tandem and segmental types. HKs and RRs were observed to be originated from segmental duplication, while some HPs originated from tandem duplication. The nuclear genome of S. bicolor contain 10 chromosomes and these SbTCS genes are randomly distributed on all the chromosomes. The promoter sequences of the SbTCS genes contain several abiotic stress-related cis-elements. RNA-seq and qRT-PCR-based expression analysis demonstrated most of the TCS genes were responsive to drought and salt stresses in leaves, which suggest their role in leaf development. This study lays a foundation for further functional study of TCS genes for stress tolerance and developmental improvement in S. bicolor.
