In-Cheol Baek, Soo Yeun Sim, Byung-Kyu Suh, Tai-Gyu Kim, Won Kyoung Cho
{"title":"Assessment of XCI skewing and demonstration of XCI escape region based on single-cell RNA sequencing: comparison between female Grave's disease and control.","authors":"In-Cheol Baek, Soo Yeun Sim, Byung-Kyu Suh, Tai-Gyu Kim, Won Kyoung Cho","doi":"10.1186/s12860-025-00533-z","DOIUrl":"10.1186/s12860-025-00533-z","url":null,"abstract":"<p><strong>Background: </strong>The reactivation and loss of mosaicism hypothesis due to X chromosome inactivation (XCI) skewing and escape could influence gender differences in autoimmune diseases. XCI selectively inactivates one of the two X chromosomes in females.</p><p><strong>Methods: </strong>To estimate XCI skewing and the occurrence of XCI escape, we conducted a normal female (NF) without a history of autoimmune thyroid disease (AITD) and a patient with Grave's disease (GD) based on a thyroid diagnosis. After single-cell RNA sequencing, heterozygous variants were converted and transformed. XCI skewing was calculated using the formula and the skewing degree was defined. NF/GD genes were compared using correction methods. Positions are heterozygous within a single cell as indicated by a unique barcode.</p><p><strong>Results: </strong>XCI skewing showed 45.8%/48.9% relatively random, 29.4%/27.0% skewing, 24.6%/23.7% severe skewing, and 0.2%/0.4% extreme severe skewing. 24.8%/24.1% in NF/GD exhibited severe skewing or higher. A total of 13 genes were significantly associated with XCI skewing ratios in NF/GD cells. In total, 371/250 nucleotide positions with only one barcode (representing a unique cell) were identified for XCI escape. A total of 143/52 nucleotide positions spanned 20/6 genes, and 12/1 genes were identified as XCI escapes.</p><p><strong>Conclusions: </strong>These results could aid in understanding the immunogenetics of gender differences in various autoimmune disease pathophysiologies.</p>","PeriodicalId":9099,"journal":{"name":"BMC Molecular and Cell Biology","volume":"26 1","pages":"8"},"PeriodicalIF":2.4,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11786500/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143073833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dmitry Lifanov, Dulamsuren Zorigt, Evgenya Shabalina, Abdullah Khalil, Konstantin Gorbunov, Elena Petersen
{"title":"Method for determining of cytotoxicity based on the release of fluorescent proteins.","authors":"Dmitry Lifanov, Dulamsuren Zorigt, Evgenya Shabalina, Abdullah Khalil, Konstantin Gorbunov, Elena Petersen","doi":"10.1186/s12860-025-00532-0","DOIUrl":"10.1186/s12860-025-00532-0","url":null,"abstract":"<p><p>This paper describes a method for determining the cytotoxicity of chemical compounds based on the detection of fluorescent proteins-in this case, green fluorescent protein (GFP) and red fluorescent protein (RFP), which are released into the medium from dead cells. This method is similar in principle to the lactate dehydrogenase test (LDH test), but it does not require a reaction with a chromogenic substrate. This method also makes it possible to independently determine the viability of different lines when used in cocultures. Experiments were performed on a classical monolayer, spheroids and 3D cultures in alginate hydrogel. Capecitabine was used as a model cytotoxic agent. We included liver cells (Huh7) in a coculture model and determined changes in the cytotoxicity levels of capecitabine against NCI-H1299 cells. The experimental part also found that there were differences in sensitivity to capecitabine depending on the type of 3D cultures used.</p>","PeriodicalId":9099,"journal":{"name":"BMC Molecular and Cell Biology","volume":"26 1","pages":"7"},"PeriodicalIF":2.4,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11776130/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143057914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chuang Li, Xiaojuan Zhao, Jingge Zhao, Jing Zhao, Lemei An, Gang Wu
{"title":"BRAF regulates circPSD3/miR-526b/RAP2A axis to hinder papillary thyroid carcinoma progression.","authors":"Chuang Li, Xiaojuan Zhao, Jingge Zhao, Jing Zhao, Lemei An, Gang Wu","doi":"10.1186/s12860-024-00528-2","DOIUrl":"10.1186/s12860-024-00528-2","url":null,"abstract":"<p><strong>Background: </strong>Papillary thyroid carcinoma (PTC) is a common malignant tumor. BRAF<sup>V600E</sup> mutation has become a common molecular event in PTC pathogenesis. Circular RNA PSD3 (circPSD3) is known to be highly expressed in PTC. However, the bio-functional role of circPSD3 and its possible relationship with the BRAF in PTC is not clear. This study aims to probe the biofunction and molecular mechanism of circPSD3 in PTC pathogenesis.</p><p><strong>Methods: </strong>RT-qPCR was utilized to measure the expression of circPSD3 and BRAF in PTC tissues and cells. The CCK-8 and EdU assays were employed to assess cell viability and proliferation. Cell apoptosis was quantified using flow cytometry. The migratory and invasive capabilities of the cells were evaluated via wound healing and transwell assays. The interaction between RNAs was investigated using luciferase reporter assay. Additionally, xenograft tumor experiments were conducted to validate our findings in vivo.</p><p><strong>Results: </strong>Data showed that circPSD3 was highly expressed in PTC patients and cell lines. CircPSD3 was found to promote cell growth and migration and inhibit apoptosis in PTC cells. Results also revealed that circPSD3 upregulated RAP2A expression by specifically sponging miR-526b. Interestingly, inhibiting miR-526b reversed the tumorigenic properties of circPSD3 in PTC. Additionally, BRAF expression was low in PTC patients, and overexpression of BRAF hampered PTC development by downregulating circPSD3 and RAP2A while upregulating miR-526b expressions.</p><p><strong>Conclusions: </strong>Our study reveals that circPSD3 is a key regulator promoting PTC progression via the circPSD3/miR-526b/RAP2A pathway. Furthermore, we found that overexpressing BRAF, which inhibits circPSD3, significantly hampers the progression of PTC.</p>","PeriodicalId":9099,"journal":{"name":"BMC Molecular and Cell Biology","volume":"26 1","pages":"6"},"PeriodicalIF":2.4,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11753155/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143000029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Camila Sabatini, Huey-Jiun Lin, Galib Ovik, Richard Hall, Techung Lee
{"title":"The proneural transcription factor Atoh1 promotes odontogenic differentiation in human dental pulp stem cells (DPSCs).","authors":"Camila Sabatini, Huey-Jiun Lin, Galib Ovik, Richard Hall, Techung Lee","doi":"10.1186/s12860-025-00530-2","DOIUrl":"10.1186/s12860-025-00530-2","url":null,"abstract":"<p><strong>Background: </strong>Bioengineering of human teeth for replacement is an appealing regenerative approach in the era of gene therapy. Developmentally regulated transcription factors hold promise in the quest because these transcriptional regulators constitute the gene regulatory networks driving cell fate determination. Atonal homolog 1 (Atoh1) is a transcription factor of the basic helix-loop-helix (bHLH) family essential for neurogenesis in the cerebellum, auditory hair cell differentiation, and intestinal stem cell specification. The functional versatility of Atoh1 prompted us to test the possibility that Atoh1 may intersect the dental pulp stem cell (DPSC) gene regulatory network governing odontogenic differentiation.</p><p><strong>Methods: </strong>We isolated DPSCs from human dental pulps and treated the cells with a replication-deficient adenoviral vector to achieve robust ectopic expression of Atoh1, following which the growth and odontogenic differentiation profiles of DPSCs were characterized.</p><p><strong>Results: </strong>DPSCs harboring the Atoh1 expression vector exhibited an approximately 3,000-fold increase in the expression of Atoh1 compared to the negative control, leading to increased DPSC proliferation in the growth medium (P < 0.05). In the odontogenic medium, Atoh1 caused an early induction of BMP2 (P < 0.001) followed by a late induction of BMP7 (P < 0.01) and increased Wnt signaling (P < 0.01). The increased BMP/Wnt signaling led to up to 8-fold increased expression of the master osteogenic transcription factor Osterix (P < 0.005) while exhibiting no significant effect on Runx2 or Dlx5, which are abundantly expressed in DPSCs. Atoh1 stimulated expression of type I collagen (P < 0.005) and small integrin-binding ligand, N-linked glycoproteins (SIBLINGs) such as bone sialoprotein (P < 0.001), dentin matrix protein 1 (P < 0.05), dentin sialophosphoprotein (P < 0.005), and osteopontin (P < 0.001), resulting in increased dentin matrix mineralization (P < 0.05). The odontogenic phenotype is associated with metabolic remodeling marked by enhanced glycolytic flux and attenuated mitochondrial metabolic enzyme activities.</p><p><strong>Conclusions: </strong>Atoh1, despite being a proneural transcription factor in development, possesses a novel odontogenic function upon ectopic expression in DPSCs. This in vitro study demonstrates a novel odontogenic mechanism mediated by ectopic expression of the transcription factor Atoh1 in human DPSCs. The finding may offer an innovative strategy for gene-based regeneration of the pulp-dentin complex.</p>","PeriodicalId":9099,"journal":{"name":"BMC Molecular and Cell Biology","volume":"26 1","pages":"5"},"PeriodicalIF":2.4,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11744864/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143000031","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hoyeon Lee, Sang Woo Cho, Hyo Sun Cha, Kun Tae, Cheol Yong Choi
{"title":"Transient activation of YAP/TAZ confers resistance to morusin-induced apoptosis.","authors":"Hoyeon Lee, Sang Woo Cho, Hyo Sun Cha, Kun Tae, Cheol Yong Choi","doi":"10.1186/s12860-025-00531-1","DOIUrl":"10.1186/s12860-025-00531-1","url":null,"abstract":"<p><strong>Background: </strong>The Hippo signaling pathway involves a kinase cascade that controls phosphorylation of the effector proteins YAP and TAZ, leading to regulation of cell growth, tissue homeostasis, and apoptosis. Morusin, a compound extracted from Morus alba, has shown potential in cancer therapy by targeting multiple signaling pathways, including the PI3K/Akt/mTOR, JAK/STAT, MAPK/ERK, and apoptosis pathways. This study explores the effects of morusin on YAP activation and its implications for apoptosis resistance.</p><p><strong>Results: </strong>Our investigation revealed that morusin induces transient YAP activation, characterized by the dephosphorylation of YAP at S127 and nuclear localization, followed by gradual rephosphorylation in multiple cancer cells. Notably, this activation occurs independently of the canonical Hippo pathway and involves the LATS1/2, MINK1, and MAPK pathways during the YAP inactivation stage. Furthermore, morusin-induced stress granule formation was significantly impaired in YAP/TAZ-depleted cells, suggesting a role in apoptosis resistance. Additionally, the expression of constitutively active MINK1 maintained YAP activation and reduced apoptosis, indicating that prolonged YAP activation can enhance resistance to cell death.</p><p><strong>Conclusions: </strong>These findings suggest that YAP/TAZ are crucial in resistance to morusin-induced apoptosis, and targeting YAP/TAZ could enhance the anti-cancer efficacy of morusin. Our study provides new insights into the molecular mechanisms of morusin, highlighting potential therapeutic strategies against cancer by disrupting apoptosis resistance.</p>","PeriodicalId":9099,"journal":{"name":"BMC Molecular and Cell Biology","volume":"26 1","pages":"4"},"PeriodicalIF":2.4,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11744988/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143000035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Functional significance of some common oxytocin receptor SNPs involved in complex human traits.","authors":"Suk Ling Ma, Michael Thomas Bowen, Mark R Dadds","doi":"10.1186/s12860-024-00529-1","DOIUrl":"https://doi.org/10.1186/s12860-024-00529-1","url":null,"abstract":"<p><strong>Background: </strong>Oxytocin function is associated with a range of human traits and is often indexed by common polymorphisms of the receptor gene OXTR. Little is known however about the functional significance of these polymorphisms.</p><p><strong>Objectives: </strong>To examine the effects of common polymorphisms of OXTR on transcription expression in human neural cells.</p><p><strong>Method: </strong>The impact of four common OXTR SNPs (rs1042778, rs4686302, rs2254298 and rs237887) on OXTR gene expression were tested in human neuroblastoma cell line, SH-SY5Y, a commonly used cell line for neurological disease. SNPs were chosen as having robust evidence for associations with complex human traits after consideration of linkage patterns across OXTR.</p><p><strong>Results: </strong>The expression level of GG genotype of rs1042778 was significantly lower than TT genotypes. None of the other SNPs were related to functional transcription.</p><p><strong>Conclusions: </strong>OXTR polymorphisms showing robust associations with complex human traits are not reliably associated with changes in transcription of OXTR. Increasing cooperation between behavioral and biological scientists is needed to bridge the gap between human trait and functional biological studies to improve our understanding of oxytocin and other important mammalian neuroendocrine processes.</p>","PeriodicalId":9099,"journal":{"name":"BMC Molecular and Cell Biology","volume":"26 1","pages":"3"},"PeriodicalIF":2.4,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11705901/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142944633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hannah Demond, Soumen Khan, Juan Castillo-Fernandez, Courtney W Hanna, Gavin Kelsey
{"title":"Transcriptome and DNA methylation profiling during the NSN to SN transition in mouse oocytes.","authors":"Hannah Demond, Soumen Khan, Juan Castillo-Fernandez, Courtney W Hanna, Gavin Kelsey","doi":"10.1186/s12860-024-00527-3","DOIUrl":"https://doi.org/10.1186/s12860-024-00527-3","url":null,"abstract":"<p><strong>Background: </strong>During the latter stages of their development, mammalian oocytes under dramatic chromatin reconfiguration, transitioning from a non-surrounded nucleolus (NSN) to a surrounded nucleolus (SN) stage, and concomitant transcriptional silencing. Although the NSN-SN transition is known to be essential for developmental competence of the oocyte, less is known about the accompanying molecular changes. Here we examine the changes in the transcriptome and DNA methylation during the NSN to SN transition in mouse oocytes.</p><p><strong>Results: </strong>To study the transcriptome and DNA methylation dynamics during the NSN to SN transition, we used single-cell (sc)M&T-seq to generate scRNA-seq and sc-bisulphite-seq (scBS-seq) data from GV oocytes classified as NSN or SN by Hoechst staining of their nuclei. Transcriptome analysis showed a lower number of detected transcripts in SN compared with NSN oocytes as well as downregulation of 576 genes, which were enriched for processes related to mRNA processing. We used the transcriptome data to generate a classifier that can infer chromatin stage in scRNA-seq datasets. The classifier was successfully tested in multiple published datasets of mouse models with a known skew in NSN: SN ratios. Analysis of the scBS-seq data showed increased DNA methylation in SN compared to NSN oocytes, which was most pronounced in regions with intermediate levels of methylation. Overlap with chromatin immunoprecipitation and sequencing (ChIP-seq) data for the histone modifications H3K36me3, H3K4me3 and H3K27me3 showed that regions gaining methylation in SN oocytes are enriched for overlapping H3K36me3 and H3K27me3, which is an unusual combination, as these marks do not typically coincide.</p><p><strong>Conclusions: </strong>We characterise the transcriptome and DNA methylation changes accompanying the NSN-SN transition in mouse oocytes. We develop a classifier that can be used to infer chromatin status in single-cell or bulk RNA-seq data, enabling identification of altered chromatin transition in genetic knock-outs, and a quality control to identify skewed NSN-SN proportions that could otherwise confound differential gene expression analysis. We identify late-methylating regions in SN oocytes that are associated with an unusual combination of chromatin modifications, which may be regions with high chromatin plasticity and transitioning between H3K27me3 and H3K36me3, or reflect heterogeneity on a single-cell level.</p>","PeriodicalId":9099,"journal":{"name":"BMC Molecular and Cell Biology","volume":"26 1","pages":"2"},"PeriodicalIF":2.4,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11697814/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142926658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mengnan Chen, Dongmei Sun, Siu-Pok Yee, Zhaoyang Yuan, Li Lin, Bing Cui, Yi Wang, Chao Liu, Peihong Liu
{"title":"Mutant Fam20c knock-in mice recapitulate both lethal and non-lethal human Raine Syndrome.","authors":"Mengnan Chen, Dongmei Sun, Siu-Pok Yee, Zhaoyang Yuan, Li Lin, Bing Cui, Yi Wang, Chao Liu, Peihong Liu","doi":"10.1186/s12860-024-00526-4","DOIUrl":"10.1186/s12860-024-00526-4","url":null,"abstract":"<p><strong>Background: </strong>Inactivation or mutations of FAM20C causes human Raine Syndrome, which manifests as lethal osteosclerosis bone dysplasia or non-lethal hypophosphatemia rickets. However, it is only hypophosphatemia rickets that was reported in the mice with Fam20c deletion or mutations. To further investigate the local and global impacts of Fam20c mutation, we constructed a knock-in allele carrying Fam20c mutation (D446N) found in the non-lethal Raine Syndrome. The Fam20c<sup>D446N</sup> allele replaced the WT Fam20c by 3.6Kb Col1a1-Cre to get the conditional knock-in mice, and by Hprt-cre to get conventional knock-in mice, respectively.</p><p><strong>Results: </strong>The radiology, serum biochemistry and immunohistochemistry indicated that all conditional and most conventional Fam20c<sup>D446N</sup> knock-in mice displayed hypophosphatemic rickets with the increased Fgf23 and deceased Dmp1 expression, which survived to adulthood. However, a few conventional Fam20c<sup>D446N</sup> knock-in mice died before weaning with the osteosclerotic X-ray radiography, though micro-CT assay displayed a reduced mineral density and increased porosity in the osteosclerotic tibia. Our results suggested that hypophosphatemia rickets was the predominant phenotype in both conditional and conventional Fam20c deficient mice, while the lethal osteosclerotic phenotype occasionally took place in the conventional Fam20c mutant mice.</p><p><strong>Conclusion: </strong>This finding also implicated that the osteosclerotic features resulting from Fam20c deficiency could be a semblance on the basis of rickets, which is most likely triggered by the alterations in the systems other than skeleton.</p>","PeriodicalId":9099,"journal":{"name":"BMC Molecular and Cell Biology","volume":"26 1","pages":"1"},"PeriodicalIF":2.4,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11697891/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142920705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jadoon Khan, Asma Sadiq, May M Alrashed, Nosheen Basharat, Syed Nadeem Ul Hassan Mohani, Tawaf Ali Shah, Kotb A Attia, Aamer Ali Shah, Hayat Khan, Ijaz Ali, Arif Ahmed Mohammed
{"title":"Designing multi-epitope vaccines against Echinococcus granulosus: an in-silico study using immuno-informatics.","authors":"Jadoon Khan, Asma Sadiq, May M Alrashed, Nosheen Basharat, Syed Nadeem Ul Hassan Mohani, Tawaf Ali Shah, Kotb A Attia, Aamer Ali Shah, Hayat Khan, Ijaz Ali, Arif Ahmed Mohammed","doi":"10.1186/s12860-024-00524-6","DOIUrl":"10.1186/s12860-024-00524-6","url":null,"abstract":"<p><p>Cystic echinococcosis (CE) is a worldwide zoonotic public health issue. The reasons for this include a lack of specific therapy options, increasing antiparasitic drug resistance, a lack of control strategies, and the absence of an approved vaccine. The aim of the current study is to develop a multiepitope vaccine against CE by in-silico identification and using different Antigen B subunits. The five Echinococcus granulosus antigen B (EgAgB) subunits were examined for eminent antigenic epitopes, and then the best B-cell and Major Histocompatibility Complex MHC-binding epitopes were predicted. Most significant epitopes were combined to create an effective multi-epitope vaccine, which was then validated by testing its secondary and tertiary structures, physicochemical properties, and molecular dynamics (MD) modelling. A multi-epitope vaccine construct of 483 amino acid sequences was designed. It contains B-cell, Helper T Lymphocyte (HTL), and Cytotoxic T Lymphocyte (CTL) epitopes as well as the appropriate adjuvant and linker molecules. The resultant vaccinal construct had a GDT-HA value of 0.9725, RMSD of 0.299, MolProbity of 1.891, Clash score of 13.1, Poor rotamers of 0.9, and qualifying features with Rama favoured of 89.9. It was also highly immunogenic and less allergic. The majority of the amino acids were positioned in the Ramachandran plot's favourable area, and during the molecular dynamic simulation at 100 ns, no notable structural abnormalities were noticed. The resultant construct was significantly expressed and received good endorsement in the pIB2-SEC13-mEGFP expressional vector. In conclusion, the current in-silico multi-epitope vaccine may be evaluated in-vitro, in-vivo, and in clinical trials as an immunogenic vaccine model. It can also play a vital role in preventing this zoonotic parasite infection.</p>","PeriodicalId":9099,"journal":{"name":"BMC Molecular and Cell Biology","volume":"25 1","pages":"29"},"PeriodicalIF":2.4,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11686936/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142906576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Convergent evolution of type I antifreeze proteins from four different progenitors in response to global cooling.","authors":"Laurie A Graham, Peter L Davies","doi":"10.1186/s12860-024-00525-5","DOIUrl":"10.1186/s12860-024-00525-5","url":null,"abstract":"<p><p>Alanine-rich, alpha-helical type I antifreeze proteins (AFPs) in fishes are thought to have arisen independently in the last 30 Ma on at least four occasions. This hypothesis has recently been proven for flounder and sculpin AFPs, which both originated by gene duplication and divergence followed by substantial gene copy number expansion. Here, we examined the origins of the cunner (wrasse) and snailfish (liparid) AFPs. The cunner AFP has arisen by a similar route from the duplication and divergence of a GIMAP gene. The coding region for this AFP stems from an alanine-rich region flanking the GTPase domain of GIMAPa. The AFP gene has remained in the GIMAP gene locus and has undergone amplification there along with the GIMAPa gene. The AFP gene originated after the cunner diverged from its common ancestor with the closely related spotty and ballan wrasses, which exhibit similar gene synteny but lack AFP genes. Snailfish AFPs have also recently evolved because they are confined to a single genus of this family. In these AFP-producing species, the AFP locus does not share any similarity to functional genes. Instead, it is replete with repetitive DNAs and transposons, several stretches of which could encode alanine tracts with a dominant codon (GCC) that matches the bias observed in the AFP genes. All four known instances of type I AFPs occurring in fishes are independent evolutionary events that occurred soon after the onset of Northern Hemisphere Cenozoic glaciation events. Collectively, these results provide a remarkable example of convergent evolution to one AFP type.</p>","PeriodicalId":9099,"journal":{"name":"BMC Molecular and Cell Biology","volume":"25 1","pages":"27"},"PeriodicalIF":2.4,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11687183/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142906575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}