Biology Open最新文献_第5页

A subpopulation of cortical neurons altered by mutations in the autism risk gene DDX3X.

IF 1.8 4区生物学

Biology Open Pub Date : 2025-01-15 Epub Date: 2025-01-29 DOI: 10.1242/bio.061854

Michael A Flores, Marta Garcia-Forn, Alexa von Mueffling, Praise Ola, Yeaji Park, Andrea Boitnott, Silvia De Rubeis

{"title":"A subpopulation of cortical neurons altered by mutations in the autism risk gene DDX3X.","authors":"Michael A Flores, Marta Garcia-Forn, Alexa von Mueffling, Praise Ola, Yeaji Park, Andrea Boitnott, Silvia De Rubeis","doi":"10.1242/bio.061854","DOIUrl":"10.1242/bio.061854","url":null,"abstract":"Cell fate decisions during cortical development sculpt the identity of long-range connections that subserve complex behaviors. These decisions are largely dictated by mutually exclusive transcription factors, including CTIP2/Bcl11b for subcerebral projection neurons and BRN1/Pou3f3 for intra-telencephalic projection neurons. We have recently reported that the balance of cortical CTIP2-expressing neurons is altered in a mouse model of DDX3X syndrome, a female-biased neurodevelopmental disorder associated with intellectual disability, autism spectrum disorder, and significant motor challenges. Here, we studied the developmental dynamics of a subpopulation of cortical neurons co-expressing CTIP2 and BRN1. We found that CTIP2+BRN1+ neurons are born during early phases of neurogenesis like other CTIP2+ neurons, peak in expression during perinatal life, and persist in adult brains. We also found that CTIP2+BRN1+ neurons are excessive in number in prenatal and mature cortical motor areas of Ddx3x mutant mice, translating into altered laminar distribution of subcerebral projection neurons extending axons to the brainstem. These findings underscore the critical role of molecular specification during cortical development in health and disease.","PeriodicalId":9216,"journal":{"name":"Biology Open","volume":"14 1","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11815569/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

α-catenin phosphorylation is elevated during mitosis to resist apical rounding and epithelial barrier leak. α-连环蛋白磷酸化在有丝分裂过程中升高，以抵抗顶圆和上皮屏障泄漏。

IF 1.8 4区生物学

Biology Open Pub Date : 2025-01-15 Epub Date: 2025-01-08 DOI: 10.1242/bio.061726

Phuong M Le, Jeanne M Quinn, Annette S Flozak, Adam W T Steffeck, Che-Fan Huang, Cara J Gottardi

{"title":"α-catenin phosphorylation is elevated during mitosis to resist apical rounding and epithelial barrier leak.","authors":"Phuong M Le, Jeanne M Quinn, Annette S Flozak, Adam W T Steffeck, Che-Fan Huang, Cara J Gottardi","doi":"10.1242/bio.061726","DOIUrl":"10.1242/bio.061726","url":null,"abstract":"Epithelial cell cohesion and barrier function critically depend on α-catenin, an actin-binding protein and essential constituent of cadherin-catenin-based adherens junctions. α-catenin undergoes actomyosin force-dependent unfolding of both actin-binding and middle domains to strongly engage actin filaments and its various effectors; this mechanosensitivity is critical for adherens junction function. We previously showed that α-catenin is highly phosphorylated in an unstructured region that links the mechanosensitive middle and actin-binding domains (known as the P-linker region), but the cellular processes that promote α-catenin phosphorylation have remained elusive. Here, we leverage a previously published phospho-proteomic data set to show that the α-catenin P-linker region is maximally phosphorylated during mitosis. By reconstituting α-catenin CRISPR knockout MDCK cells with wild-type, phospho-mutant and phospho-mimic forms of α-catenin, we show that full phosphorylation restrains mitotic cell rounding in the apical direction, strengthening the interactions between dividing and non-dividing neighbors to limit epithelial barrier leak. As the major scaffold components of adherens junctions, tight junctions and desmosomes are also differentially phosphorylated during mitosis, we reason that epithelial cell division may be a tractable system to understand how junction complexes are coordinately regulated to sustain barrier function under tension-generating morphogenetic processes.","PeriodicalId":9216,"journal":{"name":"Biology Open","volume":"14 1","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11744050/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142944871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Retraction: Overexpression of long non-coding RNA SBF2-AS1 promotes cell progression in esophageal squamous cell carcinoma (ESCC) by repressing miR-494 to up-regulate PFN2 expression.

IF 1.8 4区生物学

Biology Open Pub Date : 2025-01-15 Epub Date: 2025-01-24 DOI: 10.1242/bio.048793retraction

Qiu Zhang, Xixiang Pan, Dongyang You

引用次数: 0

Retraction: Overexpression of long non-coding RNA SBF2-AS1 promotes cell progression in esophageal squamous cell carcinoma (ESCC) by repressing miR-494 to up-regulate PFN2 expression. 长非编码 RNA SBF2-AS1 的过表达会抑制 miR-494 上调 PFN2 的表达，从而促进食管鳞状细胞癌（ESCC）的细胞进展。

IF 1.8 4区生物学

Biology Open Pub Date : 2025-01-15 Epub Date: 2025-01-24 DOI: 10.1242/bio.048793

Qiu Zhang, Xixiang Pan, Dongyang You

引用次数: 0

Cellular signalling protrusions enable dynamic distant contacts in spinal cord neurogenesis.

IF 1.8 4区生物学

Biology Open Pub Date : 2025-01-15 Epub Date: 2025-01-21 DOI: 10.1242/bio.061765

Joshua Hawley, Robert Lea, Veronica Biga, Nancy Papalopulu, Cerys Manning

{"title":"Cellular signalling protrusions enable dynamic distant contacts in spinal cord neurogenesis.","authors":"Joshua Hawley, Robert Lea, Veronica Biga, Nancy Papalopulu, Cerys Manning","doi":"10.1242/bio.061765","DOIUrl":"10.1242/bio.061765","url":null,"abstract":"In the developing mouse ventral spinal cord, HES5, a transcription factor downstream of Notch signalling, is expressed as evenly spaced clusters of high HES5-expressing neural progenitor cells along the dorsoventral axis. While Notch signalling requires direct membrane contact for its activation, we have previously shown mathematically that contact needs to extend beyond neighbouring cells for the HES5 pattern to emerge. However, the presence of cellular structures that could enable such long-distance signalling was unclear. Here, we report that cellular protrusions are present all along the apicobasal axis of individual neural progenitor cells. Through live imaging, we show that these protrusions dynamically extend and retract reaching lengths of up to ∼20 µm, enough to extend membrane contact beyond adjacent cells. The Notch ligand DLL1 was found to colocalise with protrusions, further supporting the idea that Notch signalling can be transduced at a distance. The effect of protrusions on the HES5 pattern was tested by reducing the density of protrusions using the CDC42 inhibitor ML141, leading to a tendency to decrease the distance between high HES5 cell clusters. However, this tendency was not significant and leaves an open question about their role in the fine-grained organisation of neurogenesis.","PeriodicalId":9216,"journal":{"name":"Biology Open","volume":"14 1","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11789279/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Microbiome transplants may not improve health and longevity in Drosophila melanogaster. 微生物组移植可能不会改善黑腹果蝇的健康和寿命。

IF 1.8 4区生物学

Biology Open Pub Date : 2025-01-15 Epub Date: 2025-01-21 DOI: 10.1242/bio.061745

Benjamin H Levine, Jessica M Hoffman

{"title":"Microbiome transplants may not improve health and longevity in Drosophila melanogaster.","authors":"Benjamin H Levine, Jessica M Hoffman","doi":"10.1242/bio.061745","DOIUrl":"10.1242/bio.061745","url":null,"abstract":"The gut microbiome, which is composed of bacteria, viruses, and fungi, and is involved in multiple essential physiological processes, changes measurably as a person ages, and can be associated with negative health outcomes. Microbiome transplants have been proposed as a method to improve gut function and reduce or reverse multiple disorders, including age-related diseases. Here, we take advantage of the laboratory model organism, Drosophila melanogaster, to test the effects of transplanting the microbiome of a young fly into middle-aged flies, across multiple genetic backgrounds and both sexes, to test whether age-related lifespan could be increased, and late-life physical health declines mitigated. Our results suggest that, overall, microbiome transplants do not improve longevity and may even be detrimental in flies, and the health effects of microbiome transplants were minor, but sex- and genotype-dependent. This discovery supports previous evidence that axenic flies, those with no gut microbiome, live healthier and longer lives than their non-axenic counterparts. The results of this study suggest that, at least for fruit flies, microbiome transplants may not be a viable intervention to improve health and longevity, though more research is still warranted.","PeriodicalId":9216,"journal":{"name":"Biology Open","volume":"14 1","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11789278/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143000469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Chromosome number alterations cause apoptosis and cellular hypertrophy in induced pluripotent stem cell models of embryonic epiblast cells.

IF 1.8 4区生物学

Biology Open Pub Date : 2025-01-15 Epub Date: 2025-01-24 DOI: 10.1242/bio.061814

Althea Stella Anil Martis, Loshini Soundararajan, Pallavi Shetty, Syed Moin, Tejashree Vanje, Yogeshwaran Jai Sankar, Shagufta Parveen

{"title":"Chromosome number alterations cause apoptosis and cellular hypertrophy in induced pluripotent stem cell models of embryonic epiblast cells.","authors":"Althea Stella Anil Martis, Loshini Soundararajan, Pallavi Shetty, Syed Moin, Tejashree Vanje, Yogeshwaran Jai Sankar, Shagufta Parveen","doi":"10.1242/bio.061814","DOIUrl":"10.1242/bio.061814","url":null,"abstract":"Chromosomal aneuploidies are a major cause of developmental failure and pregnancy loss. To investigate the possible consequences of aneuploidy on early embryonic development in vitro, we focused on primed pluripotent stem cells that are relatable to the epiblast of post-implantation embryos in vivo. We used human induced pluripotent stem cells (iPSCs) as an epiblast model and altered chromosome numbers by treating with reversine, a small-molecule inhibitor of monopolar spindle 1 kinase (MSP1) that inactivates the spindle assembly checkpoint, which has been strongly implicated in chromosome mis-segregation and aneuploidy generation. Upon reversine treatment, we obtained cells with varied chromosomal content that retained pluripotency and potential to differentiate into cells of three germ lineages. However, these cells displayed lagging chromosomes, increased micronuclei content, high p53 expression and excessive apoptotic activity. Cell proliferation was not affected. Prolonged in vitro culture of these cells resulted in a selective pool of cells with supernumerary chromosomes, which exhibited cellular hypertrophy, enlarged nuclei, and overproduction of total RNAs and proteins. We conclude that increased DNA damage responses, apoptosis, and improper cellular mass and functions are possible mechanisms that contribute to abnormal epiblast development.","PeriodicalId":9216,"journal":{"name":"Biology Open","volume":"14 1","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11789280/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143032280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Emerging models of human and non-human primate placental development - Centre for Trophoblast Research 17th annual meeting 2024. 人类和非人灵长类胎盘发育的新兴模型 - 滋养细胞研究中心第 17 届年会 2024。

IF 1.8 4区生物学

Biology Open Pub Date : 2024-12-15 Epub Date: 2024-11-28 DOI: 10.1242/bio.061774

Irving L M H Aye

引用次数: 0

The fission yeast SUMO-targeted ubiquitin ligase Slx8 functionally associates with clustered centromeres and the silent mating-type region at the nuclear periphery. 裂变酵母sumo靶向的泛素连接酶Slx8与聚集的着丝粒和核周围的沉默交配型区域有功能关联。

IF 1.8 4区生物学

Biology Open Pub Date : 2024-12-15 Epub Date: 2024-12-30 DOI: 10.1242/bio.061746

Shrena Chakraborty, Joanna Strachan, Kamila Schirmeisen, Laetitia Besse, Eve Mercier, Karine Fréon, Haidao Zhang, Ning Zhao, Elizabeth H Bayne, Sarah A E Lambert

{"title":"The fission yeast SUMO-targeted ubiquitin ligase Slx8 functionally associates with clustered centromeres and the silent mating-type region at the nuclear periphery.","authors":"Shrena Chakraborty, Joanna Strachan, Kamila Schirmeisen, Laetitia Besse, Eve Mercier, Karine Fréon, Haidao Zhang, Ning Zhao, Elizabeth H Bayne, Sarah A E Lambert","doi":"10.1242/bio.061746","DOIUrl":"10.1242/bio.061746","url":null,"abstract":"The SUMO-targeted ubiquitin ligase (STUbL) family is involved in multiple cellular processes via a wide range of mechanisms to maintain genome stability. One of the evolutionarily conserved functions of STUbL is to promote changes in the nuclear positioning of DNA lesions, targeting them to the nuclear periphery. In Schizossacharomyces pombe, the STUbL Slx8 is a regulator of SUMOylated proteins and promotes replication stress tolerance by counteracting the toxicity of SUMO conjugates. In order to study the dynamic dialectic between ubiquitinylation and SUMOylation in the nuclear space of the S. pombe genome, we analyzed Slx8 localization. Unexpectedly, we did not detect replication stress-induced Slx8 foci. However, we discovered that Slx8 forms a single nuclear focus, enriched at the nuclear periphery, which marks both clustered centromeres at the spindle pole body and the silent mating-type region. The formation of this single Slx8 focus requires the E3 SUMO ligase Pli1, poly-SUMOylation and the histone methyl transferase Clr4 that is responsible for the heterochromatin histone mark H3-K9 methylation. Finally, we established that Slx8 promotes centromere clustering and gene silencing at heterochromatin domains. Altogether, our data highlight evolutionarily conserved and functional relationships between STUbL and heterochromatin domains to promote gene silencing and nuclear organization.","PeriodicalId":9216,"journal":{"name":"Biology Open","volume":"13 12","pages":""},"PeriodicalIF":1.8,"publicationDate":"2024-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11708773/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142944836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Knee position affects medial gastrocnemius and soleus activation during dynamic plantarflexion: no evidence for an inter-muscle compensation in healthy young adults. 在动态跖屈时，膝关节位置影响内侧腓骨肌和比目鱼肌的激活：在健康年轻人中没有肌间代偿的证据。

IF 1.8 4区生物学

Biology Open Pub Date : 2024-12-15 Epub Date: 2024-12-30 DOI: 10.1242/bio.061810

Bálint Kovács, Dániel Csala, Song Yang, József Tihanyi, Yaodong Gu, Tibor Hortobágyi

{"title":"Knee position affects medial gastrocnemius and soleus activation during dynamic plantarflexion: no evidence for an inter-muscle compensation in healthy young adults.","authors":"Bálint Kovács, Dániel Csala, Song Yang, József Tihanyi, Yaodong Gu, Tibor Hortobágyi","doi":"10.1242/bio.061810","DOIUrl":"10.1242/bio.061810","url":null,"abstract":"Knee joint position influences ankle torque, but it is unclear whether the soleus compensates to counteract the reductions in gastrocnemius output during knee-flexed versus knee-extended plantarflexions. Therefore, the purpose of this study was to determine the effects of knee joint position and plantarflexion contraction velocity on ankle plantarflexion torque and electromyography activity of the medial gastrocnemius and soleus in healthy young adults. Healthy male participants (n=30) performed concentric plantar flexions in a custom-built dynamometer from 15° dorsiflexion to 30° plantarflexion at gradually increasing velocities during each contraction at 30, 60, 120, 180, and 210° s-1 in a supine position with the knee fully extended and while kneeling with the knee fixed in 90° flexion. Two 16-channel linear electromyographic (EMG) arrays were placed over the medial gastrocnemius and soleus muscles. Plantarflexion torque during flexed-knee versus extended-knee plantarflexions was 31% lower (P=0.002) averaged across the five contraction velocities. The overall EMG activity of the medial gastrocnemius was 35% lower (P=0.002) during knee-flexed versus knee-extended plantarflexions. In the first half of plantarflexions at slower contractions, soleus EMG activity was 15% and 28% higher (both P=0.002) in knee-flexed versus knee-extended plantarflexion, respectively. We conclude that knee position affects medial gastrocnemius and soleus activation during dynamic plantarflexion, with plantarflexion torque being smaller in the knee-flexed versus knee-extended position. However, we found no evidence that changes in soleus activation would compensate for the decrease in medial gastrocnemius activation.","PeriodicalId":9216,"journal":{"name":"Biology Open","volume":"13 12","pages":""},"PeriodicalIF":1.8,"publicationDate":"2024-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11708772/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142944822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0