{"title":"The enigmatic world of tear extracellular vesicles (EVs)-exploring their role in ocular health and beyond.","authors":"Azima Fatima, Shalini Sanyal, Gaurab Kumar Jha, Swathi Kaliki, Rani Pallavi","doi":"10.1002/1873-3468.70004","DOIUrl":"https://doi.org/10.1002/1873-3468.70004","url":null,"abstract":"<p><p>Extracellular vesicles (EVs) are released by all kind of cells into the extracellular space, where they shuttle parental cell-derived molecular cargoes (DNA, RNA, proteins) to both adjacent and distant cells, influencing the physiology of target cells. Their specific cargo content and abundance in liquid biopsies make them excellent candidates for biomarker studies. Indeed, EVs isolated from various body fluids, including blood, pleural fluid, urine, cerebrospinal fluid, saliva, milk, ascites, and tears, have been recognized for their potential as biomarkers in diagnosis, monitoring treatment, and predicting outcomes for various diseases. Increasing studies suggest that tears have great promise as a noninvasive liquid biopsy source for EVs. Our aim here is to provide a comprehensive review of the exploration of tears as a noninvasive reservoir of EVs and their contents, evaluating their accessibility and potential utility as a liquid biopsy method. Additionally, the potential of tear EVs in various cancers, including ocular cancer, is discussed. Finally, the advantages and challenges of employing tear-based liquid biopsy for EVs for the disease's biomarker studies are evaluated.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143440349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
FEBS LettersPub Date : 2025-02-17DOI: 10.1002/1873-3468.70009
Yi Zhang, Xingle Xia, Qian Jin, Guixiang Yang, Manzhu Cao, Xingxing Zong, Jingjing Shi, Chen Wang, Liqin Li
{"title":"Brain lipidomic profiles of sleep enhancement through co-administration of alprazolam and CGS21680.","authors":"Yi Zhang, Xingle Xia, Qian Jin, Guixiang Yang, Manzhu Cao, Xingxing Zong, Jingjing Shi, Chen Wang, Liqin Li","doi":"10.1002/1873-3468.70009","DOIUrl":"https://doi.org/10.1002/1873-3468.70009","url":null,"abstract":"<p><p>Alprazolam and CGS21680 are both drugs known for their sleep and sedation effects. The study aimed to utilize mass spectrometry imaging to assess the regulatory changes in brain lipids of mice by the sleep-enhancing effects of the co-administration of alprazolam and CGS21680. A seven-day continuous administration mouse model was established using alprazolam and CGS21680. Glycerophosphoinositols were elevated in nine regions, glycerophosphoglycerols rising in six brain regions, and glycerophosphoserines increasing in six regions. Other lipid classes exhibited reductions, with fatty acids decreasing in 10 regions, carnitines in seven regions, ceramides in nine regions, and diacylglycerols in 10 regions. The research provides valuable insights into sleep-related regulation pathways by delineating the regulation of various lipid biomarkers in multiple brain regions.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143440348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
FEBS LettersPub Date : 2025-02-14DOI: 10.1002/1873-3468.70003
{"title":"Correction to: Gemin5 plays a role in unassembled-U1 snRNA disposal in SMN-deficient cells.","authors":"","doi":"10.1002/1873-3468.70003","DOIUrl":"https://doi.org/10.1002/1873-3468.70003","url":null,"abstract":"","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143413918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
FEBS LettersPub Date : 2025-02-11DOI: 10.1002/1873-3468.70008
Victor Zegarra, Paul Weiland, Pauline Anka Plitzko, Julia Thiery, Laura Czech, Felix Willmund, Patricia Bedrunka, Gert Bange
{"title":"Structural and mechanistic basis for the regulation of the chloroplast signal recognition particle by (p)ppGpp.","authors":"Victor Zegarra, Paul Weiland, Pauline Anka Plitzko, Julia Thiery, Laura Czech, Felix Willmund, Patricia Bedrunka, Gert Bange","doi":"10.1002/1873-3468.70008","DOIUrl":"https://doi.org/10.1002/1873-3468.70008","url":null,"abstract":"<p><p>The alarmones (p)ppGpp play a critical role in chloroplasts by acting as signalling molecules that regulate gene expression, protein synthesis and chloroplast (cp) development, particularly in response to stress and nutrient availability. However, the underlying molecular mechanisms are still poorly understood. Here, we show that (p)ppGpp binds to the GTPase-containing NG domains of the chloroplast signal recognition particle (SRP) and its receptor, preventing their GTP-dependent association through a competitive mechanism. The structure of (cp)FtsY bound to ppGpp reveals that the alarmone employs the same binding mode as its GDP counterpart and hinders chloroplast SRP:FtsY complex formation via its pyrophosphate moiety. Consequently, (p)ppGpp also inhibits the mutual stimulation of the two GTPases present in the (cp)SRP54:FtsY complex. Taken together, our findings provide the first description of how the alarmones (p)ppGpp may regulate the SRP-dependent protein trafficking pathway in plants.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143398863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
FEBS LettersPub Date : 2025-02-11DOI: 10.1002/1873-3468.15104
{"title":"Correction to: Umbilical cord mesenchymal stem cell-derived exosomes alleviate collagen-induced arthritis by balancing the population of Th17 and regulatory T cells.","authors":"","doi":"10.1002/1873-3468.15104","DOIUrl":"https://doi.org/10.1002/1873-3468.15104","url":null,"abstract":"","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143398861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
FEBS LettersPub Date : 2025-02-10DOI: 10.1002/1873-3468.70007
Sofia Appelgren, Pia Ädelroth
{"title":"Insertion of the Fe<sub>B</sub> cofactor in cNORs lacking metal inserting chaperones.","authors":"Sofia Appelgren, Pia Ädelroth","doi":"10.1002/1873-3468.70007","DOIUrl":"https://doi.org/10.1002/1873-3468.70007","url":null,"abstract":"<p><p>Cytochrome c-dependent nitric oxide reductase (cNOR) catalyzes the reduction of NO into nitrous oxide (N<sub>2</sub>O), a strong greenhouse gas released from denitrifying microorganisms. The cNOR active site holds an essential non-heme iron, Fe<sub>B</sub>, inserted using the chaperone complex NorQD. However, in Thermus thermophilus, the cNOR (TtcNOR) cluster lacks the norQD genes. Here we investigated Fe<sub>B</sub> insertion into TtcNOR and characterized and compared TtcNOR expressed in Escherichia coli to that natively produced. We show that Fe<sub>B</sub> is present in the natively produced TtcNOR only. Analysis of cNOR operon sequences suggests that a hydrophilic K-pathway analogue is present in cNORs that do not rely on NorQD for iron insertion. We discuss the implications of our data for the evolution of the NOR family.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143382043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
FEBS LettersPub Date : 2025-02-10DOI: 10.1002/1873-3468.70006
Qi-Tong Lin, Danielle M Colussi, Peter B Stathopulos
{"title":"The apo LETM1 F-EF-hand adopts a closed conformation that underlies a multi-modal sensory role in mitochondria.","authors":"Qi-Tong Lin, Danielle M Colussi, Peter B Stathopulos","doi":"10.1002/1873-3468.70006","DOIUrl":"https://doi.org/10.1002/1873-3468.70006","url":null,"abstract":"<p><p>Leucine zipper EF-hand containing transmembrane protein-1 (LETM1) plays a critical role in mitochondrial function, with haploinsufficiency linked to Wolf-Hirschhorn syndrome. Here, we present the solution NMR structure of the calcium (Ca<sup>2+</sup>)-depleted LETM1 EF-hand domain, revealing a closed conformation facilitated by a distinct F<sub>1</sub>-helix pivot rather than decreased interhelical angle. Further, we observe regiospecific unfolding in response to hot and cold denaturation and show H662 has a pKa in-line with physiological pH fluctuations. Finally, we demonstrate Ca<sup>2+</sup>-dependent transient interactions between the EF-hand and other LETM1 or GHITM protein domains. Collectively, our data reveal the apo-to-holo structural dynamics and mechanisms underlying the multi-modal sensing by the LETM1 EF-hand domain, highlighting its role as an adaptable regulatory element within the mitochondrial matrix.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143382046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
FEBS LettersPub Date : 2025-02-06DOI: 10.1002/1873-3468.70002
Thiago Giove Mitsugi, Matt Sherwood, Elisa Helena Farias Jandrey, Amanda Faria Assoni, Joseph Bell, Brandon Coke, Paul Skipp, Rob Ewing, Oswaldo Keith Okamoto
{"title":"Integrated interactome, proteomic and functional analyses reveal molecular pathways driving L1TD1-induced aggressiveness in CNS embryonal tumor cells.","authors":"Thiago Giove Mitsugi, Matt Sherwood, Elisa Helena Farias Jandrey, Amanda Faria Assoni, Joseph Bell, Brandon Coke, Paul Skipp, Rob Ewing, Oswaldo Keith Okamoto","doi":"10.1002/1873-3468.70002","DOIUrl":"https://doi.org/10.1002/1873-3468.70002","url":null,"abstract":"<p><p>L1TD1 is a pluripotency factor required for embryonic stem cell self-renewal; its expression has also been detected in solid tumors, including embryonal tumors of the central nervous system (CNS). Previously, we showed that L1TD1 expression correlates with metastasis formation and shorter overall survival of medulloblastoma patients. Here, we used affinity purification coupled to mass spectrometry to map the L1TD1 interactome, and global proteomics to assess proteins differentially regulated by L1TD1 expression in patient-derived embryonal CNS tumor cell lines. We identified novel L1TD1 interactors and differentially expressed proteins related to cell proliferation, death and motility. Finally, we demonstrated that L1TD1-overexpressing tumor cells have distinct cell morphology with enhanced filopodial formation, higher cell motility, greater proliferation capability, and reduced sensitivity to cisplatin treatment.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
FEBS LettersPub Date : 2025-02-06DOI: 10.1002/1873-3468.15105
Ole Golten, Lorenz Schwaiger, Zarah Forsberg, Kelsi R Hall, Anton A Stepnov, Tom Z Emrich-Mills, Iván Ayuso-Fernández, Morten Sørlie, Roland Ludwig, Åsmund Kjendseth Røhr, Vincent G H Eijsink
{"title":"Functional variation among LPMOs revealed by the inhibitory effects of cyanide and buffer ions.","authors":"Ole Golten, Lorenz Schwaiger, Zarah Forsberg, Kelsi R Hall, Anton A Stepnov, Tom Z Emrich-Mills, Iván Ayuso-Fernández, Morten Sørlie, Roland Ludwig, Åsmund Kjendseth Røhr, Vincent G H Eijsink","doi":"10.1002/1873-3468.15105","DOIUrl":"https://doi.org/10.1002/1873-3468.15105","url":null,"abstract":"<p><p>Enzymes known as lytic polysaccharide monooxygenases (LPMOs) are mono-copper polysaccharide-degrading peroxygenases that engage in several on- and off-pathway redox reactions involving O<sub>2</sub> and H<sub>2</sub>O<sub>2</sub>. Herein, we show that the known metalloenzyme inhibitor cyanide inhibits reductive activation of LPMOs by binding to the LPMO-Cu(II) state and that the degree of inhibition depends on the concentrations of the polysaccharide substrate, the reductant and H<sub>2</sub>O<sub>2</sub>. Importantly, this analysis revealed differences between fungal NcAA9C and bacterial SmAA10A, which have different secondary copper coordination spheres. These differences were also highlighted by the observation that phosphate, a commonly used buffer ion, strongly inhibits NcAA9C while not affecting reactions with SmAA10A. The results provide insight into LPMO inhibition and catalysis and highlight pitfalls in the analysis thereof.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
FEBS LettersPub Date : 2025-02-06DOI: 10.1002/1873-3468.15107
Liz Curtis, Maria E O'Hanlon, Katie Waller, Duncan E Wright
{"title":"The Lily Foundation: supporting patients, raising awareness and funding research into mitochondrial diseases.","authors":"Liz Curtis, Maria E O'Hanlon, Katie Waller, Duncan E Wright","doi":"10.1002/1873-3468.15107","DOIUrl":"https://doi.org/10.1002/1873-3468.15107","url":null,"abstract":"<p><p>Primary mitochondrial diseases ('mito') are a group of genetically and phenotypically diverse disorders caused by defects in mitochondrial structure or function. Although they are individually rare, they collectively have an incidence of around 1 : 4300. Mitochondrial diseases can arise from mutations in either mitochondrial or nuclear genes, complicating genetic diagnosis. The Lily Foundation was founded by Liz Curtis in the UK in 2007 in order to raise awareness of mitochondrial diseases and to fund research into diagnosis and treatment. In this first of a new series on patient advocacy, FEBS Letters interviews Founder and CEO Liz Curtis MBE, Head of Patient Programmes Katie Waller and Research Manager Dr. Maria O'Hanlon on the aims, achievements and activities of the Lily Foundation.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}