Biology OpenPub Date : 2024-12-15Epub Date: 2024-11-26DOI: 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":"<p><p>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.</p>","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}
Biology OpenPub Date : 2024-12-15Epub Date: 2024-12-03DOI: 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":"<p><p>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.</p>","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}
Biology OpenPub Date : 2024-12-15Epub Date: 2024-12-23DOI: 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":"<p><p>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.</p>","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}
Biology OpenPub Date : 2024-12-15Epub Date: 2024-12-30DOI: 10.1242/bio.060597
Sarah C Chalmer, Seth M Rudman, Mads K Andersen, Paul Schmidt, Heath A MacMillan
{"title":"Elemental stoichiometry and insect chill tolerance: evolved and plastic changes in organismal Na+ and K+ content in Drosophila.","authors":"Sarah C Chalmer, Seth M Rudman, Mads K Andersen, Paul Schmidt, Heath A MacMillan","doi":"10.1242/bio.060597","DOIUrl":"10.1242/bio.060597","url":null,"abstract":"<p><p>Acclimation and evolutionary adaptation can produce phenotypic changes that allow organisms to cope with challenges. Determining the relative contributions and the underlying mechanisms driving phenotypic shifts from acclimation and adaptation is of central importance to understanding animal responses to change. Rates of evolution have traditionally been considered slow relative to ecological processes that shape biodiversity. Many organisms nonetheless show patterns of genetic variation that suggest that adaptation may act sufficiently fast to allow continuous change in phenotypes in response to environmental change (called 'adaptive tracking'). In Drosophila, both plastic and evolved differences in chill tolerance are associated with ionoregulation. Here, we combine an acclimation experiment, field collections along a well-characterized latitudinal cline, and a replicated field experiment to assess the concordance in the direction, magnitude, and potential mechanisms of acclimation and adaptation on chill coma recovery and elemental (Na and K) stoichiometry in both sexes of Drosophila melanogaster. Acclimation strongly shaped chill coma recovery, spatial adaptation produced comparatively modest effects, and temporal adaptation had no significant effect. Leveraging knowledge on the mechanisms underlying variation in chill tolerance traits, we find that relationships between elemental stoichiometry and chill coma recovery in the context of acclimation may differ from those that are associated with spatial adaptive change.</p>","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/PMC11708776/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142784206","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}
Biology OpenPub Date : 2024-12-15Epub Date: 2024-12-30DOI: 10.1242/bio.060613
Heino J Hulsey-Vincent, Elizabeth A Cameron, Caroline L Dahlberg, Domenico F Galati
{"title":"Spectral scanning and fluorescence lifetime imaging microscopy (FLIM) enable separation and characterization of C. elegans autofluorescence in the cuticle and gut.","authors":"Heino J Hulsey-Vincent, Elizabeth A Cameron, Caroline L Dahlberg, Domenico F Galati","doi":"10.1242/bio.060613","DOIUrl":"10.1242/bio.060613","url":null,"abstract":"<p><p>Caenorhabditis elegans gut and cuticle produce a disruptive amount of autofluorescence during imaging. Although C. elegans autofluorescence has been characterized, it has not been characterized at high resolution using both spectral and fluorescence lifetime-based approaches. We performed high resolution spectral scans of whole, living animals to characterize autofluorescence of adult C. elegans. By scanning animals at 405 nm, 473 nm, 561 nm, and 647 nm excitations, we produced spectral profiles that confirm the brightest autofluorescence has a clear spectral overlap with the emission of green fluorescent protein (GFP). We then used fluorescence lifetime imaging microscopy (FLIM) to further characterize autofluorescence in the cuticle and the gut. Using FLIM, we were able to isolate and quantify dim GFP signal within the sensory cilia of a single pair of neurons that is often obscured by cuticle autofluorescence. In the gut, we found distinct spectral populations of autofluorescence that could be excited by 405 nm and 473 nm lasers. Further, we found lifetime differences between subregions of this autofluorescence when stimulated at 473 nm. Our results suggest that FLIM can be used to differentiate biochemically unique populations of gut autofluorescence without labeling. Further studies involving C. elegans may benefit from combining high resolution spectral and lifetime imaging to isolate fluorescent protein signal that is mixed with background autofluorescence and to perform useful characterization of subcellular structures in a label-free manner.</p>","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/PMC11708769/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876123","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}
Biology OpenPub Date : 2024-12-15Epub Date: 2024-12-16DOI: 10.1242/bio.061743
Hyun-Jin Na, Mi-Jeong Sung, Joung-Sun Park
{"title":"Age- and oxidative stress-induced centrosome amplification and renal stones in Drosophila Malpighian tubules.","authors":"Hyun-Jin Na, Mi-Jeong Sung, Joung-Sun Park","doi":"10.1242/bio.061743","DOIUrl":"10.1242/bio.061743","url":null,"abstract":"<p><p>Renal diseases, including cancer, are rapidly increasing worldwide, driven by rising temperatures and changing diets, especially among younger people. Renal stones, a major risk for chronic renal disease, are increasingly common due to various health issues. Research on the underlying mechanisms, drug discovery, and the effects of aging and stress is limited. We used Drosophila, due to its similarity to the human renal system and ease of use, to identify cancer hallmarks and renal stone formation related to aging and oxidative stress. Our results indicate that centrosome amplification and stone formation increase with age and oxidative stress, and high sucrose feeding also heightens stone formation in the renal system. Our results show a close relationship between these diseases and aging, reactive oxygen species (ROS) stress, and chronic diseases. We suggest that the Drosophila renal model could be a powerful tool to study the relationship between age and age-related diseases and to discovering new agents for nephropathy.</p>","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/PMC11683567/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833850","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}
Biology OpenPub Date : 2024-12-15Epub Date: 2024-11-28DOI: 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":"<p><p>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.</p>","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}
Biology OpenPub Date : 2024-12-15Epub Date: 2024-11-28DOI: 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":"<p><p>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.</p>","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}
Biology OpenPub Date : 2024-12-15Epub Date: 2024-12-30DOI: 10.1242/bio.061817
Michael A Q Martinez, David Q Matus
{"title":"Response to Correspondence: Hajnal et al. 'The role of lin-12 notch in C. elegans anchor cell proliferation'.","authors":"Michael A Q Martinez, David Q Matus","doi":"10.1242/bio.061817","DOIUrl":"10.1242/bio.061817","url":null,"abstract":"","PeriodicalId":9216,"journal":{"name":"Biology Open","volume":"13 12","pages":"1-3"},"PeriodicalIF":1.8,"publicationDate":"2024-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11708766/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142944823","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}
Biology OpenPub Date : 2024-12-15Epub Date: 2024-12-23DOI: 10.1242/bio.061830
Alexandria Borges, Naoki Irie
{"title":"Maternal immune activation does not affect maternal microchimeric cells.","authors":"Alexandria Borges, Naoki Irie","doi":"10.1242/bio.061830","DOIUrl":"10.1242/bio.061830","url":null,"abstract":"<p><p>We are naturally chimeras. Apart from our own cells originating from the fertilized egg, placental mammals receive small numbers of maternal cells called maternal microchimerism (MMc) that persist throughout one's whole life. Not only are varying frequencies of MMc cells reported in seemingly contradicting phenomena, including immune tolerance and possible contribution to autoimmune-like disease, but frequencies are observable even among healthy littermates showing varying MMc frequencies and cell type repertoire. These varying differences in MMc frequencies or cell types could be contributing to the diverse phenomena related to MMc. However, factors biasing these MMc differences remain largely unknown. Here, we tested whether immunological activation leads to differing MMc frequencies, based on our recent study that suggests that most maternal cells are immune-related. Unexpectedly, fluorescence-activated cell sorting analysis on the murine spleen, thymus, and liver following maternal immune activation by mid-gestational lipopolysaccharide intraperitoneal injections detected no significant difference in the number, or ratio of, immune-related maternal cells in the tested embryonic organs of healthy offspring. These findings suggest that MMc frequencies remain stable even under immune-activated conditions, implying a possible control system of MMc migration against changes in the immunological conditions.</p>","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/PMC11695574/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876124","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}