Open BiologyPub Date : 2024-01-01Epub Date: 2024-01-10DOI: 10.1098/rsob.230262
Shradha Maharjan, Ruth S Kirk, Scott P Lawton, Anthony J Walker
{"title":"Human growth factor-mediated signalling through lipid rafts regulates stem cell proliferation, development and survival of <i>Schistosoma mansoni</i>.","authors":"Shradha Maharjan, Ruth S Kirk, Scott P Lawton, Anthony J Walker","doi":"10.1098/rsob.230262","DOIUrl":"10.1098/rsob.230262","url":null,"abstract":"<p><p>Although the mechanisms by which schistosomes grow and develop in humans are poorly defined, their unique outer tegument layer, which interfaces with host blood, is considered vital to homeostasis of the parasite. Here, we investigated the importance of tegument lipid rafts to the biology of <i>Schistosoma mansoni</i> in the context of host-parasite interactions. We demonstrate the temporal clustering of lipid rafts in response to human epidermal growth factor (EGF) during early somule development, concomitant with the localization of anteriorly orientated EGF receptors (EGFRs) and insulin receptors, mapped using fluorescent EGF/insulin ligand. Methyl-<i>β</i>-cyclodextrin (M<i>β</i>CD)-mediated depletion of cholesterol from lipid rafts abrogated the EGFR/IR binding at the parasite surface and led to modulation of protein kinase C, extracellular signal-regulated kinase, p38 mitogen-activated protein kinase and Akt signalling pathways within the parasite. Furthermore, M<i>β</i>CD-mediated lipid raft disruption, and blockade of EGFRs using canertinib, profoundly reduced somule motility and survival, and attenuated stem cell proliferation and somule growth and development particularly to the fast-growing liver stage. These findings provide a novel paradigm for schistosome development and vitality in the host, driven through host-parasite interactions at the tegument, that might be exploitable for developing innovative therapeutic approaches to combat human schistosomiasis.</p>","PeriodicalId":19629,"journal":{"name":"Open Biology","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10776228/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139403923","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}
Open BiologyPub Date : 2024-01-01Epub Date: 2024-01-24DOI: 10.1098/rsob.230407
Megan M Schmit, Ryan M Baxley, Liangjun Wang, Peter Hinderlie, Marissa Kaufman, Emily Simon, Anjali Raju, Jeffrey S Miller, Anja-Katrin Bielinsky
{"title":"A critical threshold of MCM10 is required to maintain genome stability during differentiation of induced pluripotent stem cells into natural killer cells.","authors":"Megan M Schmit, Ryan M Baxley, Liangjun Wang, Peter Hinderlie, Marissa Kaufman, Emily Simon, Anjali Raju, Jeffrey S Miller, Anja-Katrin Bielinsky","doi":"10.1098/rsob.230407","DOIUrl":"10.1098/rsob.230407","url":null,"abstract":"<p><p>Natural killer (NK) cell deficiency (NKD) is a rare disease in which NK cell function is reduced, leaving affected individuals susceptible to repeated viral infections and cancer. Recently, a patient with NKD was identified carrying compound heterozygous variants of <i>MCM10</i> (<i>minichromosome maintenance protein 10</i>), an essential gene required for DNA replication, that caused a significant decrease in the amount of functional MCM10. NKD in this patient presented as loss of functionally mature late-stage NK cells. To understand how MCM10 deficiency affects NK cell development, we generated <i>MCM10</i> heterozygous (<i>MCM10<sup>+/-</sup></i>) induced pluripotent stem cell (iPSC) lines. Analyses of these cell lines demonstrated that <i>MCM10</i> was haploinsufficient, similar to results in other human cell lines. Reduced levels of MCM10 in mutant iPSCs was associated with impaired clonogenic survival and increased genomic instability, including micronuclei formation and telomere erosion. The severity of these phenotypes correlated with the extent of MCM10 depletion. Significantly, <i>MCM10<sup>+/-</sup></i> iPSCs displayed defects in NK cell differentiation, exhibiting reduced yields of hematopoietic stem cells (HSCs). Although <i>MCM10<sup>+/-</sup></i> HSCs were able to give rise to lymphoid progenitors, these did not generate mature NK cells. The lack of mature NK cells coincided with telomere erosion, suggesting that NKD caused by these <i>MCM10</i> variants arose from the accumulation of genomic instability including degradation of chromosome ends.</p>","PeriodicalId":19629,"journal":{"name":"Open Biology","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10805602/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139542632","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}
Open BiologyPub Date : 2024-01-01Epub Date: 2024-01-31DOI: 10.1098/rsob.230366
Yueming Tian, Elena S Babaylova, Alexander V Gopanenko, Alexey E Tupikin, Marsel R Kabilov, Alexey A Malygin
{"title":"Deficiency of the ribosomal protein uS10 (RPS20) reorganizes human cells translatome according to the abundance, CDS length and GC content of mRNAs.","authors":"Yueming Tian, Elena S Babaylova, Alexander V Gopanenko, Alexey E Tupikin, Marsel R Kabilov, Alexey A Malygin","doi":"10.1098/rsob.230366","DOIUrl":"10.1098/rsob.230366","url":null,"abstract":"<p><p>Ribosomal protein uS10, a product of the <i>RPS20</i> gene, is an essential constituent of the small (40S) subunit of the human ribosome. Disruptive mutations in its gene are associated with a predisposition to hereditary colorectal carcinoma. Here, using HEK293T cells, we show that a deficiency of this protein leads to a decrease in the level of ribosomes (ribosomal shortage). RNA sequencing of the total and polysome-associated mRNA samples reveals hundreds of genes differentially expressed in the transcriptome (t)DEGs and translatome (p)DEGs under conditions of uS10 deficiency. We demonstrate that the (t)DEG and (p)DEG sets partially overlap, determine genes with altered translational efficiency (TE) and identify cellular processes affected by uS10 deficiency-induced ribosomal shortage. We reveal that translated mRNAs of upregulated (p)DEGs and genes with altered TE in uS10-deficient cells are generally more abundant and that their GC contents are significantly lower than those of the respective downregulated sets. We also observed that upregulated (p)DEGs have longer coding sequences. Based on our findings, we propose a combinatorial model describing the process of reorganization of mRNA translation under conditions of ribosomal shortage. Our results reveal rules according to which ribosomal shortage reorganizes the transcriptome and translatome repertoires of actively proliferating cells.</p>","PeriodicalId":19629,"journal":{"name":"Open Biology","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10827436/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139642721","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}
Open BiologyPub Date : 2023-12-01Epub Date: 2023-12-06DOI: 10.1098/rsob.230253
Ping K Yip, Zhou-Hao Liu, Shumaila Hasan, Mark B Pepys, Christopher E G Uff
{"title":"Serum amyloid P component accumulates and persists in neurones following traumatic brain injury.","authors":"Ping K Yip, Zhou-Hao Liu, Shumaila Hasan, Mark B Pepys, Christopher E G Uff","doi":"10.1098/rsob.230253","DOIUrl":"10.1098/rsob.230253","url":null,"abstract":"<p><p>The mechanisms underlying neurodegenerative sequelae of traumatic brain injury (TBI) are poorly understood. The normal plasma protein, serum amyloid P component (SAP), which is normally rigorously excluded from the brain, is directly neurocytotoxic for cerebral neurones and also binds to A<i>β</i> amyloid fibrils and neurofibrillary tangles, promoting formation and persistence of A<i>β</i> fibrils. Increased brain exposure to SAP is common to many risk factors for dementia, including TBI, and dementia at death in the elderly is significantly associated with neocortical SAP content. Here, in 18 of 30 severe TBI cases, we report immunohistochemical staining for SAP in contused brain tissue with blood-brain barrier disruption. The SAP was localized to neurofilaments in a subset of neurones and their processes, particularly damaged axons and cell bodies, and was present regardless of the time after injury. No SAP was detected on astrocytes, microglia, cerebral capillaries or serotoninergic neurones and was absent from undamaged brain. C-reactive protein, the control plasma protein most closely similar to SAP, was only detected within capillary lumina. The appearance of neurocytotoxic SAP in the brain after TBI, and its persistent, selective deposition in cerebral neurones, are consistent with a potential contribution to subsequent neurodegeneration.</p>","PeriodicalId":19629,"journal":{"name":"Open Biology","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10697800/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138488215","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}
Open BiologyPub Date : 2023-12-01DOI: 10.1098/rsob.230327
M. D. Molina, Dema Abduljabbar, Anna Guixeras, S. Fraguas, F. Cebrià
{"title":"LIM-HD transcription factors control axial patterning and specify distinct neuronal and intestinal cell identities in planarians","authors":"M. D. Molina, Dema Abduljabbar, Anna Guixeras, S. Fraguas, F. Cebrià","doi":"10.1098/rsob.230327","DOIUrl":"https://doi.org/10.1098/rsob.230327","url":null,"abstract":"Adult planarians can regenerate the gut, eyes and even a functional brain. Proper identity and patterning of the newly formed structures require signals that guide and commit their adult stem cells. During embryogenesis, LIM-homeodomain (LIM-HD) transcription factors act in a combinatorial ‘LIM code’ to control cell fate determination and differentiation. However, our understanding about the role these genes play during regeneration and homeostasis is limited. Here, we report the full repertoire of LIM-HD genes in Schmidtea mediterranea. We found that lim homeobox (lhx) genes appear expressed in complementary patterns along the cephalic ganglia and digestive system of the planarian, with some of them being co-expressed in the same cell types. We have identified that Smed-islet1, -lhx1/5-1, -lhx2/9-3, -lhx6/8, -lmx1a/b-2 and -lmx1a/b-3 are essential to pattern and size the planarian brain as well as for correct regeneration of specific subpopulations of dopaminergic, serotonergic, GABAergic and cholinergic neurons, while Smed-lhx1/5.2 and -lhx2/9.2 are required for the proper expression of intestinal cell type markers, specifically the goblet subtype. LIM-HD are also involved in controlling axonal pathfinding (lhx6/8), axial patterning (islet1, lhx1/5-1, lmx1a/b-3), head/body proportions (islet2) and stem cell proliferation (lhx3/4, lhx2/9-3, lmx1a/b-2, lmx1a/b-3). Altogether, our results suggest that planarians might present a combinatorial LIM code that controls axial patterning and axonal growing and specifies distinct neuronal and intestinal cell identities.","PeriodicalId":19629,"journal":{"name":"Open Biology","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138610360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Open BiologyPub Date : 2023-12-01Epub Date: 2023-12-13DOI: 10.1098/rsob.230228
Junjun Liu, Haibo Xie, Mengfan Wu, Yidan Hu, Yunsi Kang
{"title":"The role of cilia during organogenesis in zebrafish.","authors":"Junjun Liu, Haibo Xie, Mengfan Wu, Yidan Hu, Yunsi Kang","doi":"10.1098/rsob.230228","DOIUrl":"https://doi.org/10.1098/rsob.230228","url":null,"abstract":"<p><p>Cilia are hair-like organelles that protrude from the surface of eukaryotic cells and are present on the surface of nearly all human cells. Cilia play a crucial role in signal transduction, organ development and tissue homeostasis. Abnormalities in the structure and function of cilia can lead to a group of human diseases known as ciliopathies. Currently, zebrafish serves as an ideal model for studying ciliary function and ciliopathies due to its relatively conserved structure and function of cilia compared to humans. In this review, we will summarize the different types of cilia that present in embryonic and adult zebrafish, and provide an overview of the advantages of using zebrafish as a vertebrate model for cilia research. We will specifically focus on the roles of cilia during zebrafish organogenesis based on recent studies. Additionally, we will highlight future prospects for ciliary research in zebrafish.</p>","PeriodicalId":19629,"journal":{"name":"Open Biology","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10715920/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138807556","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}
Open BiologyPub Date : 2023-12-01Epub Date: 2023-12-20DOI: 10.1098/rsob.230181
André Gomes-Dos-Santos, Nair Vilas-Arrondo, André M Machado, Esther Román-Marcote, Jose Luís Del Río Iglesias, Francisco Baldó, Montse Pérez, Miguel M Fonseca, L Filipe C Castro, Elsa Froufe
{"title":"Mitochondrial replication's role in vertebrate mtDNA strand asymmetry.","authors":"André Gomes-Dos-Santos, Nair Vilas-Arrondo, André M Machado, Esther Román-Marcote, Jose Luís Del Río Iglesias, Francisco Baldó, Montse Pérez, Miguel M Fonseca, L Filipe C Castro, Elsa Froufe","doi":"10.1098/rsob.230181","DOIUrl":"10.1098/rsob.230181","url":null,"abstract":"<p><p>Mitogenomes are defined as compact and structurally stable over aeons. This perception results from a vertebrate-centric vision, where few types of mtDNA rearrangements are described. Here, we bring a new light to the involvement of mitochondrial replication in the strand asymmetry of the vertebrate mtDNA. Using several species of deep-sea hatchetfish (Sternoptychidae) displaying distinct mtDNA structural arrangements, we unravel the inversion of the coding direction of protein-coding genes (PCGs). This unexpected change is coupled with a strand asymmetry nucleotide composition reversal and is shown to be directly related to the strand location of the Control Region (CR). An analysis of the fourfold redundant sites of the PCGs (greater than 6000 vertebrates), revealed the rarity of this phenomenon, found in nine fish species (five deep-sea hatchetfish). Curiously, in Antarctic notothenioid fishes (Trematominae), where a single PCG inversion (the only other record in fish) is coupled with the inversion of the CR, the standard asymmetry is disrupted for the remaining PCGs but not yet reversed, suggesting a transitory state. Our results hint that a relaxation of the classic vertebrate mitochondrial structural <i>stasis</i> promotes disruption of the natural balance of asymmetry of the mtDNA. These findings support the long-lasting hypothesis that replication is the main molecular mechanism promoting the strand-specific compositional bias of this unique and indispensable molecule.</p>","PeriodicalId":19629,"journal":{"name":"Open Biology","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10730292/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138807554","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}
Open BiologyPub Date : 2023-11-01Epub Date: 2023-11-03DOI: 10.1098/rsob.230404
{"title":"Retraction: 'MALAT1 promotes gastric adenocarcinoma through the MALAT1/miR-181a-5p/AKT3 axis' (2019), by Lu <i>et al.</i>","authors":"","doi":"10.1098/rsob.230404","DOIUrl":"10.1098/rsob.230404","url":null,"abstract":"","PeriodicalId":19629,"journal":{"name":"Open Biology","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10624246/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71434438","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}
Open BiologyPub Date : 2023-11-01Epub Date: 2023-11-29DOI: 10.1098/rsob.230257
Bethan Clark, Muktai Kuwalekar, Bettina Fischer, Joost Woltering, Jakob Biran, Scott Juntti, Claudius F Kratochwil, M Emília Santos, Miguel Vasconcelos Almeida
{"title":"Genome editing in East African cichlids and tilapias: state-of-the-art and future directions.","authors":"Bethan Clark, Muktai Kuwalekar, Bettina Fischer, Joost Woltering, Jakob Biran, Scott Juntti, Claudius F Kratochwil, M Emília Santos, Miguel Vasconcelos Almeida","doi":"10.1098/rsob.230257","DOIUrl":"10.1098/rsob.230257","url":null,"abstract":"<p><p>African cichlid fishes of the Cichlidae family are a group of teleosts important for aquaculture and research. A thriving research community is particularly interested in the cichlid radiations of the East African Great Lakes. One key goal is to pinpoint genetic variation underlying phenotypic diversification, but the lack of genetic tools has precluded thorough dissection of the genetic basis of relevant traits in cichlids. Genome editing technologies are well established in teleost models like zebrafish and medaka. However, this is not the case for emerging model organisms, such as East African cichlids, where these technologies remain inaccessible to most laboratories, due in part to limited exchange of knowledge and expertise. The Cichlid Science 2022 meeting (Cambridge, UK) hosted for the first time a Genome Editing Workshop, where the community discussed recent advances in genome editing, with an emphasis on CRISPR/Cas9 technologies. Based on the workshop findings and discussions, in this review we define the state-of-the-art of cichlid genome editing, share resources and protocols, and propose new possible avenues to further expand the cichlid genome editing toolkit.</p>","PeriodicalId":19629,"journal":{"name":"Open Biology","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10685126/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138452009","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}