Frontiers in Molecular Biosciences最新文献

{"title":"Autophagy-lysosomal pathway impairment and cathepsin dysregulation in Alzheimer's disease.","authors":"Alquiandra Stefani Ferreira Mançano, Juliana Guanaes Pina, Bruna Rojas Froes, Juliana Mozer Sciani","doi":"10.3389/fmolb.2024.1490275","DOIUrl":"10.3389/fmolb.2024.1490275","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is characterized by neuronal loss, attributed to amyloid-beta (Aβ) aggregation and accumulation. The autophagy-lysosomal pathway, including cathepsins B and D, is crucial for protein degradation and clearance, but it is impaired in some diseases. This review summarizes current knowledge on the dysregulation of this pathway in AD. Accumulating evidence suggests that Aβ overload impairs autophagy-lysosomal function and cathepsin activity, exacerbating Aβ accumulation and neurodegeneration. However, the precise mechanisms underlying these interactions remain elusive. Despite these challenges, targeting the lysosomal pathway emerges as a promising therapeutic strategy, and a comprehensive understanding of the autophagy-lysosomal system is essential to develop effective interventions for AD.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1490275"},"PeriodicalIF":3.9,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11560772/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142635845","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":"A matrix-centered view of mass spectrometry platform innovation for volatilome research.","authors":"Andras Szeitz, Annika G Sutton, Steven J Hallam","doi":"10.3389/fmolb.2024.1421330","DOIUrl":"10.3389/fmolb.2024.1421330","url":null,"abstract":"<p><p>Volatile organic compounds (VOCs) are carbon-containing molecules with high vapor pressure and low water solubility that are released from biotic and abiotic matrices. Because they are in the gaseous phase, these compounds tend to remain undetected when using conventional metabolomic profiling methods. Despite this omission, efforts to profile VOCs can provide useful information related to metabolic status and identify potential signaling pathways or toxicological impacts in natural or engineered environments. Over the past several decades mass spectrometry (MS) platform innovation has instigated new opportunities for VOC detection from previously intractable matrices. In parallel, volatilome research linking VOC profiles to other forms of multi-omic information (DNA, RNA, protein, and other metabolites) has gained prominence in resolving genotype/phenotype relationships at different levels of biological organization. This review explores both on-line and off-line methods used in VOC profiling with MS from different matrices. On-line methods involve direct sample injection into the MS platform without any prior compound separation, while off-line methods involve chromatographic separation prior to sample injection and analyte detection. Attention is given to the technical evolution of platforms needed for increasingly resolved VOC profiles, tracing technical progress over time with particular emphasis on emerging microbiome and diagnostic applications.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1421330"},"PeriodicalIF":3.9,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11557394/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142618022","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":"Genome-wide identification and analysis of the HD-Zip transcription factor family in oats.","authors":"Yiqun Xu, Changlai Liu","doi":"10.3389/fmolb.2024.1475276","DOIUrl":"10.3389/fmolb.2024.1475276","url":null,"abstract":"<p><strong>Introduction: </strong>HD-Zip transcription factors are an important class of plant transcription factors involved in regulating plant growth and development as well as various stress responses. In order to explore the characteristics of oat HD-Zip transcription factors and their transcriptomic expression patterns under abiotic stress, this study identified members of the HD-Zip gene family in the oat genome through bioinformatics methods and analyzed their basic physicochemical properties, evolutionary relationships, conserved structural domains, gene duplication relationships, and expression profiles.</p><p><strong>Results: </strong>74 HD-Zip gene sequences were identified in the oat genome, unevenly distributed in all chromosomes except the 4D chromosome. The 74 HD-Zip genes can be divided into four subfamilies (HD-Zip Ⅰ-Ⅳ), containing 30 (HD-Zip Ⅰ), 38 (HD-Zip Ⅱ), 4 (HD-Zip III), and 2 (HD-Zip IV) genes, respectively. The grouping of this study is completely consistent with the clustering results of family members in the oat HD-Zip gene phylogenetic tree, further supporting the reliability of the sequence grouping. In addition, there are significant differences in conserved motifs and gene lengths between subfamilies, but they are conserved within the same subfamily. Under drought and salt stress, the expression levels of a large number of oat HD-Zip genes were significantly induced or suppressed, indicating that these HD-Zip genes are likely to be involved in regulating the oat's response to adversity.</p><p><strong>Conclusions: </strong>The results of this study provide excellent candidate HD-Zip genes for the study of oat resistance, and provide a reference for oat gene improvement and genetic breeding.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1475276"},"PeriodicalIF":3.9,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11557432/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142618024","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":"Spectral cluster supertree: fast and statistically robust merging of rooted phylogenetic trees.","authors":"Robert N McArthur, Ahad N Zehmakan, Michael A Charleston, Yu Lin, Gavin Huttley","doi":"10.3389/fmolb.2024.1432495","DOIUrl":"10.3389/fmolb.2024.1432495","url":null,"abstract":"<p><p>The algorithms for phylogenetic reconstruction are central to computational molecular evolution. The relentless pace of data acquisition has exposed their poor scalability and the conclusion that the conventional application of these methods is impractical and not justifiable from an energy usage perspective. Furthermore, the drive to improve the statistical performance of phylogenetic methods produces increasingly parameter-rich models of sequence evolution, which worsens the computational performance. Established theoretical and algorithmic results identify supertree methods as critical to divide-and-conquer strategies for improving scalability of phylogenetic reconstruction. Of particular importance is the ability to explicitly accommodate rooted topologies. These can arise from the more biologically plausible non-stationary models of sequence evolution. We make a contribution to addressing this challenge with Spectral Cluster Supertree, a novel supertree method for merging a set of overlapping rooted phylogenetic trees. It offers significant improvements over Min-Cut supertree and previous state-of-the-art methods in terms of both time complexity and overall topological accuracy, particularly for problems of large size. We perform comparisons against Min-Cut supertree and Bad Clade Deletion. Leveraging two tree topology distance metrics, we demonstrate that while Bad Clade Deletion generates more correct clades in its resulting supertree, Spectral Cluster Supertree's generated tree is generally more topologically close to the true model tree. Over large datasets containing 10,000 taxa and <math><mrow><mo>∼</mo></mrow> </math> 500 source trees, where Bad Clade Deletion usually takes <math><mrow><mo>∼</mo></mrow> </math> 2 h to run, our method generates a supertree in on average 20 s. Spectral Cluster Supertree is released under an open source license and is available on the python package index as sc-supertree.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1432495"},"PeriodicalIF":3.9,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11561713/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142618026","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":"Corrigendum: Cellular heterogeneity and plasticity during NAFLD progression.","authors":"Hyun-Ju Park, Juyong Choi, Hyunmi Kim, Da-Yeon Yang, Tae Hyeon An, Eun-Woo Lee, Baek-Soo Han, Sang Chul Lee, Won Kon Kim, Kwang-Hee Bae, Kyoung-Jin Oh","doi":"10.3389/fmolb.2024.1511947","DOIUrl":"https://doi.org/10.3389/fmolb.2024.1511947","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.3389/fmolb.2023.1221669.].</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1511947"},"PeriodicalIF":3.9,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11551535/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142635861","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":"Novel cuproptosis metabolism-related molecular clusters and diagnostic signature for Alzheimer's disease.","authors":"Fang Jia, Wanhong Han, Shuangqi Gao, Jianwei Huang, Wujie Zhao, Zhenwei Lu, Wenpeng Zhao, Zhangyu Li, Zhanxiang Wang, Ying Guo","doi":"10.3389/fmolb.2024.1478611","DOIUrl":"https://doi.org/10.3389/fmolb.2024.1478611","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD) is a progressive neurodegenerative disorder with no effective treatments available. There is growing evidence that cuproptosis contributes to the pathogenesis of this disease. This study developed a novel molecular clustering based on cuproptosis-related genes and constructed a signature for AD patients.</p><p><strong>Methods: </strong>The differentially expressed cuproptosis-related genes (DECRGs) were identified using the DESeq2 R package. The GSEA, PPI network, GO, KEGG, and correlation analysis were conducted to explore the biological functions of DECRGs. Molecular clusters were performed using unsupervised cluster analysis. Differences in biological processes between clusters were evaluated by GSVA and immune infiltration analysis. The optimal model was constructed by WGCNA and machine learning techniques. Decision curve analysis, calibration curves, receiver operating characteristic (ROC) curves, and two additional datasets were employed to confirm the prediction results. Finally, immunofluorescence (IF) staining in AD mice models was used to verify the expression levels of risk genes.</p><p><strong>Results: </strong>GSEA and CIBERSORT showed higher levels of resting NK cells, M2 macrophages, naïve CD4⁺ T cells, neutrophils, monocytes, and plasma cells in AD samples compared to controls. We classified 310 AD patients into two molecular clusters with distinct expression profiles and different immunological characteristics. The C1 subtype showed higher abundance of cuproptosis-related genes, with higher proportions of regulatory T cells, CD8⁺T cells, and resting dendritic cells. We subsequently constructed a diagnostic model which was confirmed by nomogram, calibration, and decision curve analysis. The values of area under the curves (AUC) were 0.738 and 0.931 for the external datasets, respectively. The expression levels of risk genes were further validated in mouse brain samples.</p><p><strong>Conclusion: </strong>Our study provided potential targets for AD treatment, developed a promising gene signature, and offered novel insights for exploring the pathogenesis of AD.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1478611"},"PeriodicalIF":3.9,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11540791/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603509","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":"The function of nicotinamide phosphoribosyl transferase (NAMPT) and its role in diseases.","authors":"Aihong Peng, Junqin Li, Jianxiao Xing, Yuanjun Yao, Xuping Niu, Kaiming Zhang","doi":"10.3389/fmolb.2024.1480617","DOIUrl":"https://doi.org/10.3389/fmolb.2024.1480617","url":null,"abstract":"<p><p>Nicotinamide phosphoribosyl transferase (NAMPT) is a rate-limiting enzyme in the mammalian nicotinamide adenine dinucleotide (NAD) salvage pathway, and plays a vital role in the regulation of cell metabolic activity, reprogramming, aging and apoptosis. NAMPT synthesizes nicotinamide mononucleotide (NMN) through enzymatic action, which is a key protein involved in host defense mechanism and plays an important role in metabolic homeostasis and cell survival. NAMPT is involved in NAD metabolism and maintains intracellular NAD levels. Sirtuins (SIRTs) are a family of nicotinamide adenine dinucleotide (NAD)-dependent histone deacetylases (HDACs), the members are capable of sensing cellular NAD+ levels. NAMPT-NAD and SIRT constitute a powerful anti-stress defense system. In this paper, the structure, biological function and correlation with diseases of NAMPT are introduced, aiming to provide new ideas for the targeted therapy of related diseases.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1480617"},"PeriodicalIF":3.9,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11540786/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603514","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":"Corrigendum: Exosomes released by environmental pollutant-stimulated Keratinocytes/PBMCs can trigger psoriatic inflammation in recipient cells via the AhR signaling pathway.","authors":"Hye Ran Kim, So Yeon Lee, Ga Eun You, Chun Wook Park, Hye One Kim, Bo Young Chung","doi":"10.3389/fmolb.2024.1494968","DOIUrl":"10.3389/fmolb.2024.1494968","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.3389/fmolb.2023.1324692.].</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1494968"},"PeriodicalIF":3.9,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11537886/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590491","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":"Prognosis prediction of head and neck squamous cell carcinoma through the basement membrane-related lncRNA risk model.","authors":"Wenchao Bu, Mingguo Cao, Xinru Wu, Qiancheng Gao","doi":"10.3389/fmolb.2024.1421335","DOIUrl":"10.3389/fmolb.2024.1421335","url":null,"abstract":"<p><strong>Background: </strong>Head and neck squamous cell carcinoma (HNSCC) ranks among the most widespread and significantly heterogeneous malignant tumors globally. Increasing evidence suggests that the basement membrane (BM) and associated long non-coding RNAs (lncRNA) are correlated with the onset of HNSCC and its prognosis. Our study aims to construct a basement membrane-associated lncRNAs (BMlncRNAs) marker to accurately predict the prognosis of HNSCC patients and find novel immunotherapy targets.</p><p><strong>Methods: </strong>The Cancer Genome Atlas (TCGA) database was accessed to acquire the transcriptome expression matrices, somatic mutation data, and clinical follow-up data of HNSCC patients. Utilizing co-expression analysis, the BMlncRNAs were identified and the differentially expressed lncRNAs (DEBMlncRNA) were then filtered, The filtering thresholds are FDR<0.05 and |log2FC|≥1. Furthermore, univariate analysis, least absolute shrinkage and selection operator (LASSO), and multivariable Cox regression were utilized to develop the risk model. The model then underwent thorough evaluation across diverse perspectives, encompassing tumor immune infiltration, tumor mutation burden (TMB), functional enrichment, and chemotherapy sensitivity.</p><p><strong>Results: </strong>The risk assessment model consists of 14 BMlncRNA pairs. The acquired data is indicative of the reliability of the risk score in its capacity as a prognostic factor. Individuals at high risk exhibited a poorer prognosis, and a statistically significant variance was noted in TMB and tumor immune infiltration compared to the low-risk group. Additionally, heightened sensitivity to paclitaxel and docetaxel was evident in the patients at high risk.</p><p><strong>Conclusion: </strong>We have established a BMLncRNA-based prognostic model that can provide clinical guidance for future laboratory and clinical studies of HNSCC.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1421335"},"PeriodicalIF":3.9,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11538083/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590492","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":"Soft-sensor model development for CHO growth/production, intracellular metabolite, and glycan predictions.","authors":"George Liang, Sha Sha, Zhao Wang, Huolong Liu, Seongkyu Yoon","doi":"10.3389/fmolb.2024.1441885","DOIUrl":"10.3389/fmolb.2024.1441885","url":null,"abstract":"<p><p>Efficaciously assessing product quality remains time- and resource-intensive. Online Process Analytical Technologies (PATs), encompassing real-time monitoring tools and soft-sensor models, are indispensable for understanding process effects and real-time product quality. This research study evaluated three modeling approaches for predicting CHO cell growth and production, metabolites (extracellular, nucleotide sugar donors (NSD) and glycan profiles): Mechanistic based on first principle Michaelis-Menten kinetics (MMK), data-driven orthogonal partial least square (OPLS) and neural network machine learning (NN). Our experimental design involved galactose-fed batch cultures. MMK excelled in predicting growth and production, demonstrating its reliability in these aspects and reducing the data burden by requiring fewer inputs. However, it was less precise in simulating glycan profiles and intracellular metabolite trends. In contrast, NN and OPLS performed better for predicting precise glycan compositions but displayed shortcomings in accurately predicting growth and production. We utilized time in the training set to address NN and OPLS extrapolation challenges. OPLS and NN models demanded more extensive inputs with similar intracellular metabolite trend prediction. However, there was a significant reduction in time required to develop these two models. The guidance presented here can provide valuable insight into rapid development and application of soft-sensor models with PATs for ipurposes. Therefore, we examined three model typesmproving real-time product CHO therapeutic product quality. Coupled with emerging -omics technologies, NN and OPLS will benefit from massive data availability, and we foresee more robust prediction models that can be advantageous to kinetic or partial-kinetic (hybrid) models.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1441885"},"PeriodicalIF":3.9,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11535473/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582563","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}