Biology Open最新文献_第4页

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

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

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

Disrupting the interaction between AMBRA1 and DLC1 prevents apoptosis while enhancing autophagy and mitophagy. 破坏 AMBRA1 和 DLC1 之间的相互作用可防止细胞凋亡，同时增强自噬和有丝分裂。

IF 1.8 4区生物学

Biology Open Pub Date : 2024-12-15 Epub Date: 2024-11-26 DOI: 10.1242/bio.060380

Kate Hawkins, Meg Watt, Sébastien Gillotin, Maya Hanspal, Martin Helley, Jill Richardson, Nicola Corbett, Janet Brownlees

{"title":"Disrupting the interaction between AMBRA1 and DLC1 prevents apoptosis while enhancing autophagy and mitophagy.","authors":"Kate Hawkins, Meg Watt, Sébastien Gillotin, Maya Hanspal, Martin Helley, Jill Richardson, Nicola Corbett, Janet Brownlees","doi":"10.1242/bio.060380","DOIUrl":"10.1242/bio.060380","url":null,"abstract":"AMBRA1 has critical roles in autophagy, mitophagy, cell cycle regulation, neurogenesis and apoptosis. Dysregulation of these processes are hallmarks of various neurodegenerative diseases and therefore AMBRA1 represents a potential therapeutic target. The flexibility of its intrinsically disordered regions allows AMBRA1 to undergo conformational changes and thus to perform its function as an adaptor protein for various different complexes. Understanding the relevance of these multiple protein-protein interactions will allow us to gain information about which to target pharmacologically. To compare potential AMBRA1 activation strategies, we have designed and validated several previously described mutant constructs in addition to characterising their effects on proliferation, apoptosis, autophagy and mitophagy in SHSY5Y cells. AMBRA1TAT, which is a mutant form of AMBRA1 that cannot interact with DLC1 at the microtubules, produced the most promising results. Overexpression of this mutant protected cells against apoptosis and induced autophagy/mitophagy in SHSY5Y cells in addition to enhancing the switch from quiescence to proliferation in mouse neural stem cells. Future studies should focus on designing compounds that inhibit the protein-protein interaction between AMBRA1/DLC1 and thus have potential to be used as a drug strategy for neurodegeneration.","PeriodicalId":9216,"journal":{"name":"Biology Open","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2024-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11625884/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142520984","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

Effect of cigarette smoke on the proliferation, viability, gene expression, and cellular functions of adipose-derived mesenchymal stem cells from smoking and non-smoking donors. 吸烟对吸烟和不吸烟供体脂肪源性间充质干细胞增殖、活力、基因表达和细胞功能的影响

IF 1.8 4区生物学

Biology Open Pub Date : 2024-12-15 Epub Date: 2024-12-03 DOI: 10.1242/bio.061665

Bareqa Salah, Diana Shahin, Momen Sarhan, Joud Al-Karmi, Ban Al-Kurdi, Renata Al-Atoom, Mohammad A Ismail, Nouran Hammad, Hanan Jafar, Abdalla Awidi, Nidaa A Ababneh

{"title":"Effect of cigarette smoke on the proliferation, viability, gene expression, and cellular functions of adipose-derived mesenchymal stem cells from smoking and non-smoking donors.","authors":"Bareqa Salah, Diana Shahin, Momen Sarhan, Joud Al-Karmi, Ban Al-Kurdi, Renata Al-Atoom, Mohammad A Ismail, Nouran Hammad, Hanan Jafar, Abdalla Awidi, Nidaa A Ababneh","doi":"10.1242/bio.061665","DOIUrl":"10.1242/bio.061665","url":null,"abstract":"Cigarette smoking negatively impacts mesenchymal stem cell functionality, including proliferation, viability, and differentiation potential. Adipose-derived mesenchymal stem cells (ADMSCs) are increasingly used for therapeutic purposes, but the specific effects of smoking in vivo on these cells are poorly understood. This study investigates the effects of cigarette smoke on the proliferation, viability, gene expression, and cellular functions of ADMSCs from smoking and non-smoking donors. In this study, ADMSCs were isolated from healthy smokers and non-smokers, and cell proliferation was assessed using the MTT assay, viability with apoptosis assays, mitochondrial membrane potential (MMP), and gene expression related to oxidative stress and cellular functions. Cell cycle analysis was also conducted. Our findings reveal a significant decrease in the proliferation of ADMSCs from smokers. Apoptosis assays showed reduced viable cells in smokers without a significant change in MMP, suggesting alternative pathways contributing to decreased viability. Gene expression analysis indicated the upregulation of genes associated with oxidative stress response and cellular defense mechanisms and the downregulation of genes related to inflammatory signaling, detoxification, and cellular metabolism. Cell cycle analysis indicates cycle arrest or delay in smokers, possibly due to stress and potential DNA damage. Smoking negatively affects ADMSCs' proliferation, viability, and function through oxidative stress and gene expression alterations. These findings highlight the importance of considering smoking status in ADMSC therapies and the need for further research to mitigate the effect of smoking on stem cells.","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/PMC11646114/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142766418","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

Patient-matched tumours, plasma, and cell lines reveal tumour microenvironment- and cell culture-specific microRNAs. 患者匹配的肿瘤、血浆和细胞系显示肿瘤微环境和细胞培养特异性microrna。

IF 1.8 4区生物学

Biology Open Pub Date : 2024-12-15 Epub Date: 2024-12-23 DOI: 10.1242/bio.060483

Latasha Ludwig, Emma N Vanderboon, Heather Treleaven, R Darren Wood, Courtney R Schott, Geoffrey A Wood

{"title":"Patient-matched tumours, plasma, and cell lines reveal tumour microenvironment- and cell culture-specific microRNAs.","authors":"Latasha Ludwig, Emma N Vanderboon, Heather Treleaven, R Darren Wood, Courtney R Schott, Geoffrey A Wood","doi":"10.1242/bio.060483","DOIUrl":"10.1242/bio.060483","url":null,"abstract":"MicroRNAs (miRNAs) are small non-coding RNA molecules that are present in all cell types and bodily fluids and are commonly dysregulated in cancer. miRNAs in cancer have been studied by measuring levels in cell lines, tumour tissues, and in circulation; however, no study has specifically investigated miRNA expression in patient-matched samples across all three sample types. Canine osteosarcoma is a well-established spontaneously occurring model of human osteosarcoma for which matched samples are available. We analysed a panel of miRNAs by real-time quantitative PCR and compared across patients and sample types. While some miRNAs are highly expressed in all three sample types, tumour tissue and cell lines had the most in common. There were several miRNAs that were highly expressed in plasma and tumour tissue but not in cell lines and likely represent miRNAs produced in the tumour microenvironment. Two highly expressed miRNAs were exclusive to plasma and are known to be expressed in circulating cells. This study highlights the importance of considering sample type when studying miRNAs in cancer and demonstrates the power of using patient-matched samples.","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/PMC11695573/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876126","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

Early-life challenge enhances cortisol regulation in zebrafish larvae. 生命早期的挑战会增强斑马鱼幼体的皮质醇调节能力。

IF 1.8 4区生物学

Biology Open Pub Date : 2024-12-15 Epub Date: 2024-11-28 DOI: 10.1242/bio.061684

Luis A Castillo-Ramírez, Ulrich Herget, Soojin Ryu, Rodrigo J De Marco

{"title":"Early-life challenge enhances cortisol regulation in zebrafish larvae.","authors":"Luis A Castillo-Ramírez, Ulrich Herget, Soojin Ryu, Rodrigo J De Marco","doi":"10.1242/bio.061684","DOIUrl":"10.1242/bio.061684","url":null,"abstract":"The hypothalamic-pituitary-adrenal (HPA) axis in mammals and the hypothalamic-pituitary-interrenal (HPI) axis in fish are open systems that adapt to the environment during development. Little is known about how this adaptation begins and regulates early stress responses. We used larval zebrafish to examine the impact of prolonged forced swimming at 5 days post-fertilization (dpf), termed early-life challenge (ELC), on cortisol responses, neuropeptide expression in the nucleus preopticus (NPO), and gene transcript levels. At 6 dpf, ELC-exposed larvae showed normal baseline cortisol but reduced reactivity to an initial stressor. Conversely, they showed increased reactivity to a second stressor within the 30-min refractory period, when cortisol responses are typically suppressed. ELC larvae had fewer corticotropin-releasing hormone (crh), arginine vasopressin (avp), and oxytocin (oxt)-positive cells in the NPO, with reduced crh and avp co-expression. Gene expression analysis revealed upregulation of genes related to cortisol metabolism (hsd11b2, cyp11c1), steroidogenesis (star), and stress modulation (crh, avp, oxt). These results suggest that early environmental challenge initiates adaptive plasticity in the HPI axis, tuning cortisol regulation to balance responsiveness and protection during repeated stress. Future studies should explore the broader physiological effects of prolonged forced swimming and its long-term impact on cortisol regulation and stress-related circuits.","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/PMC11625891/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142738408","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

EFEMP1 contributes to light-dependent ocular growth in zebrafish. EFEMP1有助于斑马鱼依赖光的眼球生长。

IF 1.8 4区生物学

Biology Open Pub Date : 2024-12-15 Epub Date: 2024-11-28 DOI: 10.1242/bio.061741

Jiaheng Xie, Bang V Bui, Patrick T Goodbourn, Patricia R Jusuf

{"title":"EFEMP1 contributes to light-dependent ocular growth in zebrafish.","authors":"Jiaheng Xie, Bang V Bui, Patrick T Goodbourn, Patricia R Jusuf","doi":"10.1242/bio.061741","DOIUrl":"10.1242/bio.061741","url":null,"abstract":"Myopia (short-sightedness) is the most common ocular disorder. It generally develops after over-exposure to aberrant visual environments, disrupting emmetropization mechanisms that should match eye growth with optical power. A pre-screening of strongly associated myopia-risk genes identified through human genome-wide association studies implicates efemp1 in myopia development, but how this gene impacts ocular growth remains unclear. Here, we modify efemp1 expression specifically in the retina of zebrafish. We found that under normal lighting, efemp1 mutants developed axial myopia, enlarged eyes, reduced spatial vision and altered retinal function. However, under myopia-inducing dark-rearing, compared to control fish, mutants remained emmetropic and showed changes in retinal function. Efemp1 modification changed the expression of efemp1, egr1, tgfb1a, vegfab and rbp3 genes in the eye, and changed the inner retinal distributions of myopia-associated EFEMP1, TIMP2 and MMP2 proteins. Efemp1 modification also impacted dark-rearing-induced responses of vegfab and wnt2b genes and above-mentioned myopia-associated proteins. Together, we provided robust evidence that light-dependent ocular growth is regulated by efemp1.","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/PMC11625888/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142738409","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

Age- and oxidative stress-induced centrosome amplification and renal stones in Drosophila Malpighian tubules. 年龄和氧化应激诱导的果蝇马氏小管中心体扩增和肾结石。

IF 1.8 4区生物学

Biology Open Pub Date : 2024-12-15 Epub Date: 2024-12-16 DOI: 10.1242/bio.061743

Hyun-Jin Na, Mi-Jeong Sung, Joung-Sun Park

引用次数: 0