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2021 ◽  
Author(s):  
Chengzhi Xu ◽  
Yupeng Shen ◽  
Yong Shi ◽  
Ming Zhang ◽  
Liang Zhou

Abstract Background: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer type worldwide. Deregulation of mRNA translation is a frequent feature of cancer. Eukaryotic Translation Initiation Factor 3 Subunit B (EIF3B) has reported as oncogenes in cancer. However, the role of EIF3B in HNSCC remains unclear. Methods: In this study, the clinical significance of EIF3B expression in TCGA was analyzed. Then the expression of EIF3B was knockdown, and its role in HNSC was revealed. To explore the molecular mechanism of EIF3B, we applied RNA sequencing and proteomics, and deregulated pathways were acquired. RNA immunoprecipitation (RIP) sequencing was conducted to uncover the targeting mRNAs of EIF3B. Potential targets of EIF3B were validated with TCGA datasets.Results: EIF3B serves a hazardous prognostic marker in HNSCC. Besides, EIF3B promotes HNSCC proliferation and progression in vitro and in vivo. EIF3B promotes CEBPB translation and activate MAPK pathway. IL6R and CCNG2 is a target of EIF3B regulated CEBPB translation. Conclusion: In sum, this study reveals EIF3B as a novel oncogene in HNSCC, by promoting CEBPB translation and IL6R expression.


2021 ◽  
Author(s):  
◽  
Joanna Eveline Grace Elliott

<p>The Hautawa Shellbed, Whanganui Basin is described in detail to uncover lateral variations in depositional paleoenvironment. This was achieved through the in situ documentation of the macrofaunal assemblage and its taphonomic attributes at three localities. The sites from west to east are: Ridge Road, Old Hautawa Road, and the type section on West Road. They are all exposures on farm tracks and cover a 20-km range across the central Whanganui Basin. The descriptions were collected at 15-cm intervals and analysed using k-means clustering and Principal Component Analysis (PCA) to uncover trends within the data set. Combining the assemblage data with the taphonomic has allowed six major biofacies to be recognised. In turn, the arrangement of the biofacies in the sections suggest three subunits: A, B, and C. Subunits A and C are laterally continuous between all of the sections and always relate to the lowermost and upper-most portions of the Hautawa Shellbed. In contrast, subunit B is only observed to occur at West Road overlying subunit A. These subunits have can also be equated to sequence stratigraphic terminology. Subunits A and B form an onlap shellbed and subunit C a backlap shellbed. Hence, the Hautawa Shellbed represents deposition during the transgressive systems tract of a single cyclothem. This study is unique compared to other Whanganui Basin stratigraphic research in its statistically robust approach for comparing data gathered at various sites along outcrop strike to better understand the preserved paleoenvironment. To support the macro-faunal investigation, census counts of foraminifera were conducted for samples collected from the fine-grained sediments encompassing the Hautawa Shellbed at each of the three sites. Together, the macrofaunal and foraminiferal studies reveal temporal and spatial paleoenvironmental changes within the Hautawa Shellbed. The presence of biostratigraphically important fauna within the Hautawa Shellbed has been used to link the unit to other similar formations in both the Whanganui and East Coast Basins. This key assemblage which highlights the Nukumaruan-Mangapanian Stage boundary at 2.40 Ma includes: Zygochlamys delicatula, Crassostrea ingens, Phialopecten thomsoni, Phialopecten triphooki, and Mesopeplum convexum. The paleoenvironmental variations observed and presented here for the Hautawa Shellbed have been combined with published work on other parallel formations to produce a paleogeographic map of the Whanganui Basin for 2.40 Ma.</p>


2021 ◽  
Author(s):  
◽  
Joanna Eveline Grace Elliott

<p>The Hautawa Shellbed, Whanganui Basin is described in detail to uncover lateral variations in depositional paleoenvironment. This was achieved through the in situ documentation of the macrofaunal assemblage and its taphonomic attributes at three localities. The sites from west to east are: Ridge Road, Old Hautawa Road, and the type section on West Road. They are all exposures on farm tracks and cover a 20-km range across the central Whanganui Basin. The descriptions were collected at 15-cm intervals and analysed using k-means clustering and Principal Component Analysis (PCA) to uncover trends within the data set. Combining the assemblage data with the taphonomic has allowed six major biofacies to be recognised. In turn, the arrangement of the biofacies in the sections suggest three subunits: A, B, and C. Subunits A and C are laterally continuous between all of the sections and always relate to the lowermost and upper-most portions of the Hautawa Shellbed. In contrast, subunit B is only observed to occur at West Road overlying subunit A. These subunits have can also be equated to sequence stratigraphic terminology. Subunits A and B form an onlap shellbed and subunit C a backlap shellbed. Hence, the Hautawa Shellbed represents deposition during the transgressive systems tract of a single cyclothem. This study is unique compared to other Whanganui Basin stratigraphic research in its statistically robust approach for comparing data gathered at various sites along outcrop strike to better understand the preserved paleoenvironment. To support the macro-faunal investigation, census counts of foraminifera were conducted for samples collected from the fine-grained sediments encompassing the Hautawa Shellbed at each of the three sites. Together, the macrofaunal and foraminiferal studies reveal temporal and spatial paleoenvironmental changes within the Hautawa Shellbed. The presence of biostratigraphically important fauna within the Hautawa Shellbed has been used to link the unit to other similar formations in both the Whanganui and East Coast Basins. This key assemblage which highlights the Nukumaruan-Mangapanian Stage boundary at 2.40 Ma includes: Zygochlamys delicatula, Crassostrea ingens, Phialopecten thomsoni, Phialopecten triphooki, and Mesopeplum convexum. The paleoenvironmental variations observed and presented here for the Hautawa Shellbed have been combined with published work on other parallel formations to produce a paleogeographic map of the Whanganui Basin for 2.40 Ma.</p>


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shingo Mitaki ◽  
Yasuko Wada ◽  
Abdullah Md. Sheikh ◽  
Shuhei Yamaguchi ◽  
Atsushi Nagai

AbstractIdentifying new biomarkers beyond the established risk factors that make it possible to predict and prevent ischemic stroke has great significance. Extracellular vesicles are powerful cell‒cell messengers, containing disease-specific biomolecules, which makes them powerful diagnostic candidates. Therefore, this study aimed to identify proteins derived from extracellular vesicles enriched serum related to future ischemic stroke events, using a proteomic method. Of Japanese subjects who voluntarily participated in health checkups at our institute a number of times, 10 subjects (6 males and 4 females, age: 64.2 ± 3.9 years) who developed symptomatic ischemic stroke (7.3 ± 4.4 years’ follow-up) and 10 age‒sex matched controls without brain lesions (6.7 ± 2.8 years’ follow-up) were investigated. Extracellular vesicles enriched fractions were derived from serum collected at the baseline visit. Differentially expressed proteins were evaluated using isobaric tagging for relative and absolute protein quantification (iTRAQ)-based proteomic analysis. Of the 29 proteins identified, alpha-2-macroglobulin, complement C1q subcomponent subunit B, complement C1r subcomponent, and histidine-rich glycoprotein were significantly upregulated (2.21-, 2.15-, 2.24-, and 2.16-fold, respectively) in subjects with future ischemic stroke, as compared with controls. Our study supports the concept of serum-derived extracellular vesicles enriched fractions as biomarkers for new-onset stroke. These proteins may be useful for prediction or for targeted therapy.


2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Yuehong Ma ◽  
Ling Fang ◽  
Rui Zhang ◽  
Peng Zhao ◽  
Yafeng Li ◽  
...  

Objectives. Most patients with systemic lupus erythematosus (SLE) develop lupus nephritis (LN) with severe kidney manifestations. Renal fibrosis can be primarily attributed to overproliferation of mesangial cells (MCs), which are subject to drug treatment. Nevertheless, the detailed mechanisms remain elusive. We sought to identify the effect of cyclophosphamide (CTX), a drug commonly used for LN treatment, on MC proliferation and explore its underlying mechanisms. Material/Methods. Cell proliferation and fibrosis in mouse kidney tissues were determined by histopathology staining techniques. Flow cytometry was used for cell cycle analysis. Cell cycle regulators were examined in vitro following treatment of immortalized human MCs with platelet-derived growth factor subunit B (PDGF-B). Quantitative real-time PCR and western blot analyses were used to measure the mRNA and protein levels of candidate cell cycle regulators, respectively. Results. CTX inhibited cell overproliferation induced by platelet-derived growth factor subunit B in vitro and in vivo. CTX (40 mg/l) was sufficient to induce G0/G1 phase cell cycle arrest. CTX treatment downregulated many critical cell cycle regulators including cyclins and cyclin-dependent kinases but upregulated cyclin-dependent kinase inhibitors. Additionally, CTX-treated samples showed significantly reduced fibrosis, as indicated by lower expression of interleukin-1β and α-smooth muscle actin. Conclusion. CTX inhibits proliferation of MCs by modulating cell cycle regulator and therefore arresting them at G1 phase. CTX treatment significantly alleviates the severity of renal fibrosis. These findings provide novel insights into the mechanisms by which CTX affects LN.


Author(s):  
C. Pratheebha ◽  
Jayaseelan Vijayshree Priyadharsini ◽  
A. S. Smiline Girija ◽  
P. Sankar Ganesh ◽  
Nidhi Poddar

Introduction: Hypericin is the anthraquinone derivative and has many properties like antiviral, antifungal and antibacterial. The red complex pathogens which include Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia in association with other microbes found in the periodontal pockets, cause severe inflammation resulting in periodontitis. Novel bioactive agents from several sources have been tested against the microbial pathogens to deduce antimicrobial activity.  Aim: The aim of the study is to virtually screen and identify the protein network interaction of hypericin in red complex pathogens. Methodology: The STITCH v5.0 pipeline was primarily used to identify the drug-protein interactions. The VirulentPred and VICMPred software were used for elucidating the functional class of the proteins and virulence property. The sub cellular localization of virulent proteins was analysed with pSORTb v3.0 software. Further, the epitopes in virulent proteins were identified using BepiPred v1.0 linear epitope prediction tool. Results: Heat shock protein 90 of Porphyromonas gingivalis were found to involve in the cellular process and DNA topoisomerase IV subunit B, heat shock protein 90, DNA gyrase subunit A and DNA gyrase subunit B of Treponema denticola were found to be the virulent factors. The virulent proteins were located in the cytoplasm, which would further increase the potential effect of the drug to serve as antimicrobial agents. Finally, epitopes were predicted on the virulent proteins which can be specifically docked to further ascertain their interactions with the phytocompound. Conclusion: Hypericin with all its potential and biological benefits can be addressed, can be used as an antimicrobial agent to eradicate dental pathogens which are recalcitrant to treatment. The mode of action of hypericin is, it is targeting crucial proteins in red complex pathogens. Further in vitro studies should be performed on a wide range of pathogens to substantiate the true interactions between the drugs and the protein repertoire of pathogens.


2021 ◽  
Author(s):  
Caroline E. Dewar ◽  
Silke Oeljeklaus ◽  
Bettina Warscheid ◽  
André Schneider

The mitochondrial F1Fo ATP synthase of Trypanosoma brucei has been studied in detail. Whereas its F1 moiety is relatively highly conserved in structure and composition, the same is not the case for the Fo part and the peripheral stalk. A core subunit of the latter, the normally conserved subunit b, could not be identified in trypanosomes suggesting that it might be absent. Here we have identified a 17 kDa mitochondrial protein of the inner membrane that is essential for normal growth, efficient oxidative phosphorylation and membrane potential maintenance. Pulldown experiments and native PAGE analysis indicate that the protein is associated with the F1Fo ATP synthase. Its ablation reduces the levels of Fo subunits, but not those of F1, and disturbs the cell cycle. HHpred analysis showed that the protein has structural similarities to subunit b of other species, indicating that the Fo part of the trypanosomal ATP synthase does contain a highly diverged subunit b. Thus, the Fo part of the trypanosomal ATPase synthase may be more widely conserved than initially thought.


Author(s):  
Patil Tejaswini D. ◽  
Amrutkar Sunil V.

Background: DNA gyrase subunit B (1KZN) is an attractive target for antibacterial drug development because of its role in DNA replication. The fast development of antimicrobial medication resistance necessitates the quick discovery of new antimicrobial medicines. Objective: The goal of this research is to design, synthesize, and discover benzo-fused five-membered nitrogen-containing heterocycles that bind to DNA gyrase subunit B via molecular docking (1KZN). Methods: Based on literature research, 2-(1H-1,2,3-Benzotriazol-1-yl)-N-substituted acetamide was synthesized using an efficient method. All synthesized compounds were evaluated for antibacterial activity against three distinct organisms: E. coli, Pseudomonas aeruginosa, Staphylococcus aureus. In a docking investigation, the chemical interacts with the active site of DNA gyrase subunit B (1KZN), indicating that it might have antibacterial action. Conclusion: According to the findings of this research, the compounds 3d and 3f show antibacterial properties. For Staphylococcus aureus, 3c has the potential to be an antibacterial agent.


2021 ◽  
Author(s):  
Janet R Keast ◽  
Peregrine B Osborne ◽  
John-Paul Fuller-Jackson

This protocol is used to visualise sensory and autonomic neurons innervating organs of the lower urinary tract in an experimental adult male or female rat. The protocol is performed under anesthesia and should incorporate all local requirements for standards of animal experimentation, including methods of anesthesia, surgical environment, and post-operative monitoring and care.


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