Biology OpenPub Date : 2025-03-15Epub Date: 2025-03-17DOI: 10.1242/bio.061677
Helen M Bellchambers, Maria B Padua, Stephanie M Ware
{"title":"A CRISPR mis-insertion in the Zic3 5'UTR inhibits in vivo translation and is predicted to result in formation of an mRNA stem-loop hairpin.","authors":"Helen M Bellchambers, Maria B Padua, Stephanie M Ware","doi":"10.1242/bio.061677","DOIUrl":"10.1242/bio.061677","url":null,"abstract":"<p><p>Zic3 loss of function is associated with a range of congenital defects, including heterotaxy and isolated heart defects in humans, as well as neural tube defects, situs anomalies, and tail kinks in model organisms. Here, we describe a novel Zic3ins5V mouse line generated due to a mis-insertion during the CRISPR genome editing process, which altered the Zic3 5'UTR structure. Mice with this insertion developed similar phenotypes to Zic3LacZ null mice, including heterotaxy, isolated heart defects, neural tube defects and tail kinks. Surprisingly, gene expression analysis revealed that the novel Zic3ins5V line displays higher levels of Zic3 mRNA, but western blot analysis confirmed that levels of ZIC3 were greatly reduced in vivo. RNAfold, an RNA secondary structure prediction tool, showed that this mis-insertion may cause the formation of a large stem-loop hairpin incorporating some of the 5'UTR and first exon of Zic3, and the insertion of similar hairpins in a cell-based assay caused the loss of ZIC3 expression. Thus, this mouse line displays a loss of ZIC3 protein consistent with the inhibitory effects of 5'UTR stem-loop hairpin structures.</p>","PeriodicalId":9216,"journal":{"name":"Biology Open","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11957448/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254749","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}
{"title":"Effects of vessel noise on beluga (Delphinapterus leucas) call type use: ultrasonic communication as an adaptation to noisy environments?","authors":"Valeria Vergara, Marie-Ana Mikus, Clément Chion, Dominic Lagrois, Marianne Marcoux, Robert Michaud","doi":"10.1242/bio.061783","DOIUrl":"10.1242/bio.061783","url":null,"abstract":"<p><p>Animal vocalizations can evolve structural features as long-term adaptations to noisy environments. Using such signals, cetaceans could mitigate masking from vessel noise. This study investigates whether beluga whales (Delphinapterus leucas) use ultrasonic high-frequency burst pulse (HFBP) calls to communicate in noisy conditions. We identified HFBP calls in three populations: St Lawrence Estuary, Eastern High Arctic-Baffin Bay, and Western Hudson Bay. Focusing on the industrialized St Lawrence, we investigated the effects of vessel noise on HFBP call rates compared to other call types. Ultrasonic calls, spanning a bandwidth of 36.4±6.5 to 144 kHz (Nyquist frequency), comprised 13% of the St Lawrence beluga repertoire (n=25,435). Noise events (n=21) were defined as periods when at least one vessel was visible within 2 km of the hydrophone while belugas were within 500 m. Sound pressure levels were measured before, during, and after exposure. Generalized linear mixed models revealed consistent HFBP call rates before, during, and after vessel noise exposure, while contact calls and other call types declined during exposure (n=4528). These findings suggest that ultrasonic signals that evolved in the Arctic - where ice-associated noise may have created a need for high-frequency communication - remain a viable communication channel in vessel noise, allowing belugas to exploit these signals to maintain communication. Understanding how belugas use signals in noisy environments can inform conservation strategies for noise-impacted marine mammals.</p>","PeriodicalId":9216,"journal":{"name":"Biology Open","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11957452/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490681","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 : 2025-02-17DOI: 10.1242/bio.061789
Debadas Sahoo, Sibakalyani Acharya
{"title":"Metabolic depression and non-specific immune response during hibernation of common Asian toad, Duttaphrynus melanostictus.","authors":"Debadas Sahoo, Sibakalyani Acharya","doi":"10.1242/bio.061789","DOIUrl":"https://doi.org/10.1242/bio.061789","url":null,"abstract":"<p><p>To assess metabolic depression and non-specific immune response during hibernation in the common Asian toad, Duttaphrynus melanostictus, we measured activities of different enzymes of both aerobic (Oxygen-dependent) and anaerobic (Oxygen-independent) metabolic pathways in liver tissue and some non-specific immune responses in blood and liver tissue by obtaining hibernating toads directly from their hibernaculum in nature. Though decreased activities of enzymes and suppressions of non-specific immune responses were hypothesised, some contrasting results were found. Activities of citrate synthase (CS) and isocitrate dehydrogenase (ICDH) enzymes of aerobic metabolic pathways showed a significant decrease in their activities during hibernation up to 29% and 61% respectively of their active period value. Contrary to our hypothesis enzymes of oxygen-independent metabolic pathways i.e. pyruvate kinase (PK) and lactate dehydrogenase (LDH) showed no significant changes in their activities during hibernation compared to the active period. This shows aerobic metabolic depression during normoxic hibernation in common Asian toads and maintenance of vital activities at a minimum level with utilisation of energy (ATP) generated from the oxygen-independent metabolic pathway. Likewise, the non-specific immune response comprising total leucocyte count, individual leucocytes like neutrophil, eosinophil, basophil, lymphocyte and monocytes showed a significant decrease in their count during hibernation along with a reduction in complement proteins indicated by serum bacteria-killing ability, compared to active period. In contrast, the levels of reactive oxygen species (ROS) in liver tissue resulting in oxidative stress in terms of TBARS formed and GSSG/GSH ratio were significantly higher during hibernation, suggesting some components of non-specific immunity remain elevated. So, we conclude that, though there is suppression of non-specific immune response during hibernation to a maximum extent to conserve energy, some components of it in terms of oxidative stress are still in an active state to provide the signal to adaptive immunity for a quick response that is expected during post hibernation phase. Further, it indicates that non-specific immune response during hibernation is variable and tissue-specific.</p>","PeriodicalId":9216,"journal":{"name":"Biology Open","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143432425","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}
{"title":"Glycogen synthase is required for heat shock-mediated autophagy induction in neuronal cells.","authors":"Pratibha Bhadauriya, Akanksha Onkar, Kamali Nagarajan, Kavikumar Angamuthu Karuppusamy, Subramaniam Ganesh, Saloni Agarwal","doi":"10.1242/bio.061605","DOIUrl":"10.1242/bio.061605","url":null,"abstract":"<p><p>Autophagy is an essential cellular process that facilitates the degradation of aggregated proteins and damaged organelles to maintain cellular homeostasis and promote cell survival. Recent studies have indicated a direct role for glycogen synthase (GS) in activating neuronal autophagy and in conferring protection against cytotoxic misfolded proteins. Since heat shock induces protein misfolding and autophagy is an essential component of the heat shock response that clears the misfolded proteins, we looked at the possible role of GS in heat shock response pathways in neuronal cells. We demonstrate an increase in the activity and level of GS and a concomitant increase in the glycogen level during the heat shock and post-heat shock recovery period. These changes had a direct correlation with autophagy induction. We further demonstrate that heat shock transcription factor 1 regulates the level and activation of GS during heat shock and that GS is essential for the induction of autophagy during heat stress in neuronal cells. Intriguingly, the partial knock-down of GS led to increased death due to heat shock in neuronal cells and Drosophila. Our study offers a novel insight into the role of GS and glycogen metabolic pathways in heat shock response in neuronal cells.</p>","PeriodicalId":9216,"journal":{"name":"Biology Open","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11876841/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254767","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 : 2025-02-15Epub Date: 2025-02-24DOI: 10.1242/bio.061825
Cameron T Dixon, Pamela Yang, Kimberly McCall
{"title":"Traumatic injury leads to ovarian cell death and reproductive disturbances in Drosophila melanogaster.","authors":"Cameron T Dixon, Pamela Yang, Kimberly McCall","doi":"10.1242/bio.061825","DOIUrl":"10.1242/bio.061825","url":null,"abstract":"<p><p>Traumatic injury (TI), or global blunt force trauma, can arise from many sources such as car crashes, sports and intimate partner violence. Effects from these injuries impact the whole organism and can lead to many different pathologies, such as inflammation, neurodegeneration, gut dysbiosis, and female reproductive detriments. Drosophila melanogaster has recently emerged as a powerful model to study traumatic injuries due to their high conservation of physiological effects post-trauma and the genetic toolset that they leverage. Previously, we reported female-specific reproductive deficits post mild TI in Drosophila. Here we investigate the effects of more severe trauma on females and found an increased retention of mature eggs and decrease in egg laying. Additionally, severe trauma led to an increase of midstage egg chamber death and formation of melanization, a known marker of immune activation. These studies provide a valuable invertebrate model to understand disturbances to female reproduction post-trauma.</p>","PeriodicalId":9216,"journal":{"name":"Biology Open","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11892359/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143432407","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 : 2025-02-15Epub Date: 2025-02-12DOI: 10.1242/bio.061840
María Nazareth González Alvarado, Jessica Aprato
{"title":"Sox8: a multifaceted transcription factor in development and disease.","authors":"María Nazareth González Alvarado, Jessica Aprato","doi":"10.1242/bio.061840","DOIUrl":"10.1242/bio.061840","url":null,"abstract":"<p><p>Sox8 is a transcription factor that belongs to the Sox family of high-mobility-group domain containing proteins and is closely related to Sox9 and Sox10. During prenatal development, Sox8 is expressed in several ectoderm-, endoderm- and mesoderm-derived tissues and has been implicated in processes of organogenesis and differentiation. Sox8 expression is found in several important cells such as Sertoli cells in the male gonad, glial cells, satellite cells, and chondrocytes. However, Sox8 is not essential for the proper development of any of the involved systems, as it functions redundantly with Sox9 or Sox10 and no major developmental disturbances have been noticed in its absence. Despite its perceived limited importance as a developmental regulator, Sox8 exhibits a more significant role in late development and adult tissues. Several studies highlight the importance of Sox8 for the homeostasis of adipose tissue, Sertoli cells and the blood-testis-barrier functioning, and the maintenance of myelin in the central nervous system. Emerging evidence points to SOX8 as a promising candidate for a disease-causing gene in humans and suggests that changes in SOX8 function or expression could contribute to pathological states. For instance, genetic variants of SOX8 have been linked to multiple sclerosis and familial essential tremor, while SOX8 alterations have been related to poor cancer prognosis and infertility. This Review provides an overview of Sox8's versatile role in development and adult tissues as well as its lesser-known contributions to various diseases, and its potential as a therapeutic target.</p>","PeriodicalId":9216,"journal":{"name":"Biology Open","volume":"14 2","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11849977/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143398127","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}
{"title":"The story of Biology Open: a conversation with past and present Editors-in-Chief.","authors":"Saanjbati Adhikari, Alejandra Clark, Rachel Hackett","doi":"10.1242/bio.061897","DOIUrl":"10.1242/bio.061897","url":null,"abstract":"","PeriodicalId":9216,"journal":{"name":"Biology Open","volume":"14 2","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11892354/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143499298","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 : 2025-02-15Epub Date: 2025-02-06DOI: 10.1242/bio.061828
Ariadna Carol Illa, Henning Hvid, Torben Elm, Christa Andsbjerg Frederiksen, Lonnie Frimodt Bangshof, Dennis Funch Danielsen, Søren Skov, Carsten Dan Ley
{"title":"From early development to maturity: a phenotypic analysis of the Townes sickle cell disease mice.","authors":"Ariadna Carol Illa, Henning Hvid, Torben Elm, Christa Andsbjerg Frederiksen, Lonnie Frimodt Bangshof, Dennis Funch Danielsen, Søren Skov, Carsten Dan Ley","doi":"10.1242/bio.061828","DOIUrl":"10.1242/bio.061828","url":null,"abstract":"<p><p>Well-characterised mouse models of disease may provide valuable insights into pathophysiology. This study characterises the Townes mouse model of sickle cell disease (SCD) and establishes a time window in which the disease is present but does not progress significantly in terms of severity. We examined Townes mice with the HbAA, HbAS, and HbSS genotypes from young (4 weeks) to mature (5 months) stages of life to assess the disease state at different ages and any progression. We conducted blood tests, histological organ damage evaluations, and metabolic assessments to identify a suitable time frame for study based on welfare considerations. Townes HbSS mice displayed key SCD features such as anaemia, haemolysis, thromboinflammation and organ pathology. Notably, these manifestations remained relatively stable over the study period, indicating a stable phase suitable for conducting intervention studies. Mice with HbAS and HbAA genotypes served as comparative controls, showing minimal to no pathology throughout. These findings are valuable for future research on SCD and may ultimately lead to the development of more effective treatments for this debilitating disease.</p>","PeriodicalId":9216,"journal":{"name":"Biology Open","volume":"14 2","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11832121/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254703","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 : 2025-02-15Epub Date: 2025-01-30DOI: 10.1242/bio.061811
Wangsun Choi, Dennis Goldfarb, Feng Yan, Michael B Major, Alan S Fanning, Mark Peifer
{"title":"Proximity proteomics provides a new resource for exploring the function of Afadin and the complexity of cell-cell adherens junctions.","authors":"Wangsun Choi, Dennis Goldfarb, Feng Yan, Michael B Major, Alan S Fanning, Mark Peifer","doi":"10.1242/bio.061811","DOIUrl":"10.1242/bio.061811","url":null,"abstract":"<p><p>The network of proteins at the interface between cell-cell adherens junctions and the actomyosin cytoskeleton provides robust yet dynamic connections that facilitate cell shape change and motility. While this was initially thought to be a simple linear connection via classic cadherins and their associated catenins, we now have come to appreciate that many more proteins are involved, providing robustness and mechanosensitivity. Defining the full set of proteins in this network remains a key objective in our field. Proximity proteomics provides a means to define these networks. Mammalian Afadin and its Drosophila homolog Canoe are key parts of this protein network, facilitating diverse cell shape changes during gastrulation and other events of embryonic morphogenesis. Here we report results of several proximity proteomics screens, defining proteins in the neighborhood of both the N- and C-termini of mammalian Afadin in the premier epithelial model, MDCK cells. We compare our results with previous screens done in other cell types, and with proximity proteomics efforts with other junctional proteins. These reveal the value of multiple screens in defining the full network of neighbors and offer interesting insights into the overlap in protein composition between different epithelial cell junctions.</p>","PeriodicalId":9216,"journal":{"name":"Biology Open","volume":"14 2","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11810119/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063974","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}