BBA Advances最新文献

{"title":"Plant acetyl-CoA carboxylase: The homomeric form and the heteromeric form","authors":"Dilawar Niazi,&nbsp;Greg B.G. Moorhead","doi":"10.1016/j.bbadva.2025.100148","DOIUrl":"10.1016/j.bbadva.2025.100148","url":null,"abstract":"<div><div>Across the domains of life, the enzyme acetyl-CoA carboxylase (ACC) converts HCO₃⁻, ATP, and acetyl-CoA to malonyl-CoA, ADP, and P_i. Malonyl-CoA is the building block for all de novo fatty acid biosynthesis. ACC is found in two forms, (1) as a heteromeric enzyme, and (2) as a homomeric enzyme. Whether a single polypeptide, or various subunit combinations, they all catalyze the ATP-dependent carboxylation of acetyl-CoA to form malonyl-CoA. Here, we explore five burning questions pertaining to this fascinatingly intricate and complicated molecular machine, and the prospect of increasing oil production in plant vegetative tissues through its manipulation. We ask: 1. Can we manipulate the interplay of starch-lipid biosynthesis to increase the total TAG content in the vegetative tissues of plants? 2. Why is ACC such a complex enzyme? 3. How is ACC regulated? 4. Why is the plant plastid ACC recruited to the chloroplast membrane? 5. Will structural biology provide insights into the regulation of plant ACC?</div></div>","PeriodicalId":34672,"journal":{"name":"BBA Advances","volume":"7 ","pages":"Article 100148"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143453117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MALDI O-antigen glycotyping of Y. pseudotuberculosis using DAN/DHB/K matrix","authors":"Shogo Urakami ,&nbsp;Hiroshi Hinou","doi":"10.1016/j.bbadva.2024.100131","DOIUrl":"10.1016/j.bbadva.2024.100131","url":null,"abstract":"<div><div><em>Yersinia pseudotuberculosis</em> is a zoonotic gram-negative bacterium with a wide range of hosts. Twenty-one classifications of O-antigens of <em>Y. pseudotuberculosis</em>, including their glyco-subtypes, have been reported and used as epidemiological indicators of health damage caused by this bacterium. In this study, we performed rapid identification of <em>Y. pseudotuberculosis</em> O-antigens using a modified MALDI O-antigen glycotyping method. By employing a DAN/DHB/K matrix, the O-antigen repeating units were detected as potassium adduct ions, facilitating the discrimination between hexoses, deoxyhexoses, and dideoxyhexoses, compared to the conventional matrix system with sodium ions. The branched dideoxyhexose of <em>Y. pseudotuberculosis</em> O-antigens was eliminated by the pretreatment or ionization process of MALDI glycotyping, and the repeating unit pattern reflecting the main-chain glycan sequence was given as the main spectrum. Of the four strains investigated, O2b and O3 polysaccharides with the same main-chain glycan sequence gave characteristic repeating unit pattern peaks, reflecting the difference in the position and stereochemistry of the branching dideoxyhexose. This study will accelerate the implementation of intraspecies classification targeting O-antigens in microbial identification techniques using MALDI-TOF MS.</div></div>","PeriodicalId":34672,"journal":{"name":"BBA Advances","volume":"7 ","pages":"Article 100131"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143170586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracellular vesicles display distinct glycosignatures in high-grade serous ovarian carcinoma","authors":"Kristina Mae Bienes ,&nbsp;Akira Yokoi ,&nbsp;Masami Kitagawa ,&nbsp;Hiroaki Kajiyama ,&nbsp;Morten-Thaysen Andersen ,&nbsp;Rebeca Kawahara","doi":"10.1016/j.bbadva.2025.100140","DOIUrl":"10.1016/j.bbadva.2025.100140","url":null,"abstract":"<div><div>High-grade serous ovarian carcinoma (HGSOC) is a deadly subtype of ovarian cancer (OC), often diagnosed at late stages due to nonspecific symptoms and lack of effective markers for early detection. Aberrant protein N-linked glycosylation has been reported in HGSOC, holding a potential for improving the diagnosis and prognosis of affected patients. Building on our recent observation documenting that HGSOC-derived extracellular vesicles (EVs) exhibit aberrant protein expression patterns, we here explore the protein N-glycosylation displayed by EVs isolated from HGSOC cell lines and patient ascites relative to those from matching controls to unveil candidate markers for HGSOC. Comparative glycoproteomics of small EVs (sEVs, &lt;200 nm) and medium/large EVs (m/lEVs, &gt;200 nm) isolated from HGSOC and non-cancerous cell lines revealed lower overall N-glycosylation of EV proteins and a decreased protein expression of oligosaccharyltransferase (OST) subunits from HGSOC compared to non-cancerous cell lines. Increased α2,6-sialylation was also observed in m/lEVs from HGSOC cell lines and patient ascites by lectin blotting, which correlated with increased gene expression of <em>ST6GAL1</em> and decreased gene expression of <em>ST3GAL3/4</em> in HGSOC compared to normal ovary tissues. Our study provides insights into the EV glycoproteome of HGSOC and the underlying changes in the glycosylation machinery in HGSOC tissues, opening new avenues for the discovery of novel markers against HGSOC.</div></div>","PeriodicalId":34672,"journal":{"name":"BBA Advances","volume":"7 ","pages":"Article 100140"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143170979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New insights into the N-glycomes of Dictyostelium species","authors":"Alba Hykollari ,&nbsp;Daniel Malzl ,&nbsp;Chunsheng Jin (金春生) ,&nbsp;Carina Eschenbach ,&nbsp;Kristína Kianičková ,&nbsp;Iain B.H. Wilson ,&nbsp;Katharina Paschinger","doi":"10.1016/j.bbadva.2025.100142","DOIUrl":"10.1016/j.bbadva.2025.100142","url":null,"abstract":"<div><div>Dictyostelia are cellular slime molds, a group of Amoebozoa, that form multicellular fruiting bodies out of aggregating cells able of differentiating into resistant spore forms. In previous studies on <em>Dictyostelium discoideum</em>, it was demonstrated that their N-glycans, as in most eukaryotes, derive from the Glc₃Man₉GlcNAc₂-PP-Dol precursor; however, unique glyco-epitopes, including intersecting GlcNAc, core α1,3-fucosylation, sulphation and methylphosphorylation, were detected. In the present study, we have examined the N-glycans of two other <em>Dictyostelium</em> species, <em>D. purpureum,</em> whose genome is also sequenced, and <em>D. giganteum</em>. The detailed glycomic analysis of their fruiting bodies was based on isomeric separation of the glycan structures by HPLC, followed by mass spectrometry in combination with enzymatic digests and chemical treatments. Two features absent from the 'model' dictyostelid <em>D. discoideum</em> were found: especially in <em>D. purpureum,</em> a long linear galactose arm β1,4-linked to the β1,4-<em>N</em>-acetylglucosamine on the 'lower' A-branch of its oligo-mannosylated structures could be identified. In contrast, neutral N-glycans with multiple fucose residues attached to terminal mannoses were found in <em>D. giganteum</em>. All three species have common modifications on their anionic N-glycans: while (methyl)phosphorylated residues are always associated with terminal mannose residues, the sulphation position differs. While <em>D. discoideum</em> has 6-sulphation of subterminal mannose residues, <em>D. giganteum</em> and <em>D. purpureum</em> may rather have 2-sulphation of core α1,6-mannose. Overall, we have discovered species-specific glycan variations and our data will contribute to future comparative and functional studies on these three species within the same genus.</div></div>","PeriodicalId":34672,"journal":{"name":"BBA Advances","volume":"7 ","pages":"Article 100142"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143170981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Best evidence linking the extracellular factor TGF-β to cancer-associated alternative splicing programs","authors":"Opeoluwa Alli-Oke ,&nbsp;Jean-Philippe Brosseau","doi":"10.1016/j.bbadva.2024.100132","DOIUrl":"10.1016/j.bbadva.2024.100132","url":null,"abstract":"<div><div>Alternative splicing is a mechanism by which several RNA transcripts can be created from one gene. Splicing factors are RNA binding proteins recognizing cis-acting sequences that positively or negatively influence the splicing decision based on their relative position to the splice site and identity. However, few studies have focused on the regulation of splicing factors, and even less on the regulation of alternative splicing from extracellular factors. Transforming growth factor beta 1 (TGF-β) is a well study extracellular factors regulating multiple cancer-associated cell phenotype (apoptosis, epithelial to mesenchymal transition, angiogenesis, differentiation into cancer-associated fibroblasts) in a cell type-dependent manner. Intriguingly, there is examples of alternative splicing variants and/or their regulatory splicing factors influencing each of these hallmarks in vitro. Here, we provide the best evidence suggesting that TGF-β may drive cancer-associated alternative splicing programs.</div></div>","PeriodicalId":34672,"journal":{"name":"BBA Advances","volume":"7 ","pages":"Article 100132"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143170985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Valosin-containing protein (VCP), a component of tumor-derived extracellular vesicles, impairs the barrier integrity of brain microvascular endothelial cells","authors":"Ramon Handerson Gomes Teles ,&nbsp;Nicolas Jones Villarinho ,&nbsp;Ana Sayuri Yamagata ,&nbsp;Camila Tamy Hiroki ,&nbsp;Murilo Camargo de Oliveira ,&nbsp;Gisela Ramos Terçarioli ,&nbsp;Ruy Gastaldoni Jaeger ,&nbsp;Patrick Meybohm ,&nbsp;Malgorzata Burek ,&nbsp;Vanessa Morais Freitas","doi":"10.1016/j.bbadva.2024.100130","DOIUrl":"10.1016/j.bbadva.2024.100130","url":null,"abstract":"<div><div>Metastases are the leading cause of cancer-related deaths, and their origin is not fully elucidated. Recently, studies have shown that extracellular vesicles (EVs), particularly small extracellular vesicles (sEV), can disrupt the homeostasis of organs, promoting the development of a secondary tumor. However, the role of sEV in brain endothelium and their association with metastasis related to breast cancer is unknown. Thus, this study aimed to investigate sEV-triggered changes in the phosphorylation state of proteins on the surface of brain endothelial cells, as they form the first barrier in contact with circulating tumor cells and EVs, and once identified, to modulate its interactors and effects from this through different functional assays. We used the most aggressive breast cancer cell line, MDA-MB-231, and its brain-seeking variant, MDA-MB-231-br. From these cells, small and large extracellular vesicles were harvested to treat hCMEC/D3 cells, an immortalized cell line from the human brain microvasculature. Higher levels of phosphorylation of VEGFR1 and VEGFR2 were found in hCMEC/D3 cells treated with MDA-MB-231-br sEV. By computational analysis, the Valosin-Containing Protein (VCP) was predicted to be an important sEV cargo affecting the VEGFR2 intracellular trafficking, validated by western blotting analysis. Then, VCP was modulated by cell transfection or chemical inhibition in hCMEC/D3 cells and assessed in different functional in vitro assays evidencing a significant effect on the functionality of these cells. Thus, this study demonstrates that the VCP-containing sEVs induce modifications at different phosphor sites of VEGFR2 and effectively modulate the state of brain microvascular endothelial cells.</div></div>","PeriodicalId":34672,"journal":{"name":"BBA Advances","volume":"7 ","pages":"Article 100130"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11722580/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142972345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"\"Netrin-slaying nanoparticles: A new frontier in cancer therapy\"","authors":"Vishakha Sherawat,&nbsp;Deepika Sharma","doi":"10.1016/j.bbadva.2025.100163","DOIUrl":"10.1016/j.bbadva.2025.100163","url":null,"abstract":"<div><div>Netrin-1, a secreted laminin-related protein, was first characterized for its pivotal role in guiding axonal growth during nervous system development. However, recent research has revealed its involvement in cancer progression and metastasis. Understanding the signaling pathways through which Netrin-1 operates in cancer is crucial for elucidating its mechanisms and exploring therapeutic interventions. Netrin-1 protein controls the biological processes of cancer cells, guiding axon pathfinding and transmitting signals that are essential for migration, differentiation and cell survival via UNC5 and DCC-family receptors. To elaborate further, Netrin1 controls YAP signalling through its neogenin receptor, which affects the EMT process in gastric cancer. Researchers have also utilized the Netrin-1 protein with different nanoparticles to explore its way to prevent cancer progression. Moreover, Researchers evaluated the use of nanoparticles as an immunosensor, therapeutic and imaging tools targetting the Netrin-1 protein, which open several ways to combat cancer. This review explores how Netrin-1 influences the AKT signaling cascade impacting hippo signaling, YAP pathways and EMT process with DCC receptor. It also discusses the involvement of UNC5B and Netrin-1 in regulating ERK/MAPK signaling pathways and induction of apoptosis when Netrin-1 is absent. Moreover, it underscores the therapeutic potential of UNC5B-induced cell cycle arrest in specific cancer. Also, it delves into the diverse forms of netrin and its potential role in cancer and the glims of nanoparticles use with it. Underlining the necessity for more research to comprehend their functions in signaling cascades using the nanomaterials.</div></div>","PeriodicalId":34672,"journal":{"name":"BBA Advances","volume":"8 ","pages":"Article 100163"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144289208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent advances in the science of human milk oligosaccharides","authors":"Tadasu Urashima ,&nbsp;Katsumi Ajisaka ,&nbsp;Tetsuro Ujihara ,&nbsp;Eri Nakazaki","doi":"10.1016/j.bbadva.2024.100136","DOIUrl":"10.1016/j.bbadva.2024.100136","url":null,"abstract":"<div><div>Human colostrum and mature milk contain oligosaccharides (Os), designated as human milk oligosaccharides (HMOs). Approximately 200 varieties of HMOs have been characterized.</div><div>Although HMOs are not utilized as an energy source by infants, they have important protective functions, including pathogenic bacteria and viral infection inhibitors and immune modulators, among other functions, and HMOs stimulate brain-nerve development. The Os concentration is average 11 g/L in human milk but &gt;100 mg/L in mature bovine milk, which is used to manufacture infant formula, suggesting that human-identical milk oligosaccharides (HiMOs) should be incorporated into milk substitutes. Some infant formulas incorporating 2′-fucosyllactose and lacto-N<em>-</em>neotetraose are now commercially available, and intervention trials have been concluded.</div><div>We review basic HMO information, including their chemical structures and concentrations, attempts to synthesize HMOs at small and plant scale, studies that clarified HMO biological functions, and interventions with milk substitutes incorporating HiMOs in formula-fed infants.</div></div>","PeriodicalId":34672,"journal":{"name":"BBA Advances","volume":"7 ","pages":"Article 100136"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143170980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The second wave of formose research","authors":"Akihito Hashidzume","doi":"10.1016/j.bbadva.2025.100141","DOIUrl":"10.1016/j.bbadva.2025.100141","url":null,"abstract":"<div><div>This review article highlights key developments in the second wave of formose research (from approximately 2000), summarizing approximately 100 relevant studies. Section 1 introduces the basics of formose reaction and its historical context. Section 2 provides a brief overview of the pioneering works from the first wave of formose research (from 1970 to 1990). Section 3 then overviews the second wave of formose research, in which formose reactions under various conditions, mechanistic studies of the formose reaction, formose reactions and the origin of life, and applications of formose reactions are described. Finally, Section 4 offers summary and outlook.</div></div>","PeriodicalId":34672,"journal":{"name":"BBA Advances","volume":"7 ","pages":"Article 100141"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143170983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current issues of tandem mass spectrum (MS2)-based glycoproteomics and efforts to complement them","authors":"Hiroyuki Kaji","doi":"10.1016/j.bbadva.2025.100158","DOIUrl":"10.1016/j.bbadva.2025.100158","url":null,"abstract":"<div><div>With the development of liquid chromatography/mass spectrometers that support proteomics and the associated development of analytical methods and data analysis software, the number of proteins that can be identified and quantified in a single analysis is approaching the level of transcriptomics. However, many problems remain to be solved in protein glycosylation analysis. This mini-review discusses the technical issues of MS2-based glycoprotein identification and efforts to complement them by the Human Glycome Atlas (HGA) Project in Japan.</div></div>","PeriodicalId":34672,"journal":{"name":"BBA Advances","volume":"7 ","pages":"Article 100158"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143679821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}