Biology OpenPub Date : 2025-07-15Epub Date: 2025-07-18DOI: 10.1242/bio.061941
Rashmi Sivasengh, Andrew Scott, Brendan M Gabriel
{"title":"Live-cell GLUT4 translocation assay reveals Per3 as a novel regulator of circadian insulin sensitivity in skeletal muscle cells.","authors":"Rashmi Sivasengh, Andrew Scott, Brendan M Gabriel","doi":"10.1242/bio.061941","DOIUrl":"10.1242/bio.061941","url":null,"abstract":"<p><p>Type 2 diabetes (T2D) is a growing global health concern, with skeletal muscle playing a central role due to its contribution to postprandial glucose disposal. Insulin resistance in skeletal muscle often precedes the clinical onset of T2D and is characterised by impaired GLUT4 trafficking. Circadian disruption is increasingly recognised as a contributor to metabolic dysfunction, yet its impact on skeletal muscle insulin sensitivity remains poorly defined. We hypothesised that circadian regulators influence GLUT4 translocation and glucose uptake, contributing to the metabolic impairments observed in T2D. To investigate this, we developed a high-throughput, live-cell GLUT4 translocation assay capable of capturing circadian dynamics in skeletal muscle cells. Using publicly available transcriptomic data from primary human myotubes derived from individuals with and without T2D, our re-analysis identified altered rhythmic expression of several genes, including PER3, ARNTL, HOXB5, and TSSK6. Publicly available phenome-wide association study (PheWAS) data further supported associations between these genes and T2D-related traits. Functional validation using siRNA knockdown revealed that PER3 silencing significantly impaired GLUT4 translocation and glucose uptake in human skeletal muscle cells, while also abolishing rhythmic insulin responsiveness. ARNTL knockdown caused a moderate reduction in GLUT4 translocation, suggesting complementary roles in metabolic regulation. Our findings identify PER3 as a novel circadian regulator of GLUT4 translocation and insulin sensitivity in skeletal muscle. This work also introduces a sensitive, live-cell assay suitable for real-time assessment of GLUT4 dynamics and circadian regulation, offering a powerful platform for discovering new therapeutic targets in T2D.</p>","PeriodicalId":9216,"journal":{"name":"Biology Open","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12309902/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144265275","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 : 2025-07-15Epub Date: 2025-07-25DOI: 10.1242/bio.062105
Katherine H Fisher, Sen-Lin Lai, Chris Q Doe
{"title":"Imp and Chinmo are required for embryonic motor neuron axon and dendrite targeting.","authors":"Katherine H Fisher, Sen-Lin Lai, Chris Q Doe","doi":"10.1242/bio.062105","DOIUrl":"10.1242/bio.062105","url":null,"abstract":"<p><p>Neural progenitors generate distinct neuronal populations over time. Drosophila larval neural progenitors, neuroblasts (NBs), generate neuronal diversity by expressing temporal gradients of transcription factors and RNA-binding proteins, including early factors Imp and Chinmo and late factors Syp, Mamo, and Broad. These factors have been well characterized in the larval central nervous system (CNS), yet nothing is known about their expression or function in the embryonic CNS. We show that embryonic Imp is expressed in a low-to-high temporal gradient, the opposite of the larval Imp gradient. Embryonic Chinmo is expressed in all post-mitotic neurons, but not in a gradient, while the late larval factors Mamo, E93, Syp, and Broad show little embryonic expression. We show that Imp is required for Chinmo expression in postmitotic neurons, and loss of Chinmo - but not Imp - derepresses Syp. Finally, we tested whether Imp and Chinmo are required for motor neuron molecular identity or morphology. Although neither is required to specify temporal or molecular neuronal identity, both are required for axon targeting to the correct body wall muscle, and downregulating dendrite outgrowth. We conclude that temporal factors are regulated differently in embryos and larvae, and that Imp and Chinmo are required for proper neuronal axon and dendrite projections.</p>","PeriodicalId":9216,"journal":{"name":"Biology Open","volume":"14 7","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12352280/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144728049","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":"Genetic perturbation of cellular homeostasis regulates integrated stress response signaling to control Drosophila hematopoiesis.","authors":"Kishalay Ghosh, Rohit Krishnan Iyer, Saloni Sood, Mohamed Sabeelil Islam, Jyotsana G Labad, Rohan Jayant Khadilkar","doi":"10.1242/bio.062046","DOIUrl":"10.1242/bio.062046","url":null,"abstract":"<p><p>Aging results in a decline in cellular and molecular functions. One of the hallmarks of aging is stem cell exhaustion, which impacts self-renewal and differentiation. We employ the Drosophila larval lymph gland (LG) to investigate the impact of genetic perturbation of cellular homeostasis on hematopoiesis. The LG consists of a posterior signaling center (PSC) - a stem cell niche that maintains medullary zone (MZ) prohemocytes, whereas the cortical zone (CZ) consists of differentiated hemocytes. We employed over-activation of Toll or Imd pathway to disrupt cellular homeostasis, whereas we over-expressed Foxo or Atg8 to balance it. Genetic perturbation of cellular homeostasis displays hallmarks of aging. Induction of Toll or Imd pathway locally and systemically leads to a decreased niche size and increased differentiation, whereas Foxo or Atg8 over-expression shows an opposite trend. We showed that the integrated stress response (ISR) pathway is induced upon Toll or Imd over-activation and LGs with ISR perturbation show increased hemocyte differentiation. Genetic epistasis shows that ectopic over-expression of ISR components upon Imd activation can rescue hematopoietic defects. Overall, our study explores how genetic perturbation of cellular homeostasis can impact hematopoiesis. Our research has implications in understanding how abrogation of cellular homeostatic mechanisms may lead to onset of malignancies.</p>","PeriodicalId":9216,"journal":{"name":"Biology Open","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144483153","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":"Caspar modulates primordial germ cell fate both in an Oskar-dependent and Oskar-independent manner.","authors":"Subhradip Das, Adheena Elsa Roy, Kanika, Girish Deshpande, Girish S Ratnaparkhi","doi":"10.1242/bio.062119","DOIUrl":"10.1242/bio.062119","url":null,"abstract":"<p><p>Primordial germ cell (PGC) formation and specification is a fundamental conserved process as PGCs are the progenitors of germline stem cells (GSCs). In Drosophila melanogaster, maternally deposited Oskar (Osk) and centrosome dynamics are two independent determinants of PGC fate. Caspar, Drosophila homolog of Fas-associated factor 1 (FAF1), promotes PGC formation/specification and maintains the PGC count by modulating both the Osk levels and centrosome function. Consistently, casplof PGCs display reduction and inefficient release/transmission of germ plasm. Defective centrosome migration and behavior are evident even prior to PGC formation engineered by Osk and its targets. Taken together with the inability of Osk to regulate nuclear and centrosome migration, our data demonstrate that Casp encodes a novel bi-modal regulator of PGC fate as it controls Osk levels likely by downregulating translational repressor, Smaug (Smg) and also influences nuclear/centrosome migration during early mitotic nuclear division cycles (NCs 6-9), which are Osk-independent. We discuss dual functionality of Casp vis-à-vis germline/soma segregation as it helps acquire both the PGCs and the surrounding soma their individual identities.</p>","PeriodicalId":9216,"journal":{"name":"Biology Open","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12352277/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144564585","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 : 2025-07-15DOI: 10.1242/bio.062010
Angela H S Fan, Yoldas Yildiz, Amanda A Hartoun, Mikayla L Newby, Rujuta Durwas, Yan Ngai, Sarah Flury, Toni R Pak
{"title":"Ethanol induces subcellular trafficking of the RNA-binding protein, hnRNP A1, in neuronal cells in vitro, but not in the peripubertal rat brain.","authors":"Angela H S Fan, Yoldas Yildiz, Amanda A Hartoun, Mikayla L Newby, Rujuta Durwas, Yan Ngai, Sarah Flury, Toni R Pak","doi":"10.1242/bio.062010","DOIUrl":"10.1242/bio.062010","url":null,"abstract":"<p><p>The RNA-binding protein, heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1), plays a critical role in RNA metabolism, including splicing, stabilization, and transport. hnRNP A1 predominantly resides in the cell nucleus; however, it can be dynamically trafficked to the cytoplasm in response to cellular stressors, such as osmotic or oxidative stress. Although the cytoplasmic functions of hnRNP A1 are not well understood, our previous work demonstrated that hnRNP A1 associates with mature microRNAs in the cytoplasm, including those that are regulated by adolescent binge-pattern alcohol use. Therefore, this study tested the effects of repeated binge-pattern ethanol (EtOH) exposure during adolescence on hnRNP A1 subcellular localization in the rat brain and in neuronal-derived cell lines. Our results showed that EtOH exposure induced hnRNP A1 re-localization from the nucleus to the cytoplasm in neuronal cell lines, but not in the rat brain. Moreover, the primary end metabolite of EtOH, acetate, failed to induce hnRNP A1 re-localization in neuronal cell lines, suggesting that EtOH metabolism in vivo abrogated hnRNP A1 subcellular trafficking. We also observed that EtOH-induced hnRNP A1 re-localization to the cytoplasm was correlated with increased neuronal cell volume, suggesting that osmotic stress could be a cellular stressor driving subcellular trafficking in neurons. Notably, our study also revealed that there are brain region- and sex-specific differences in hnRNP A1 expression levels in the adolescent rat brain.</p>","PeriodicalId":9216,"journal":{"name":"Biology Open","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12309889/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144483152","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 : 2025-06-15Epub Date: 2025-06-02DOI: 10.1242/bio.061883
Steven G Lautzenheiser, Patricia Ann Kramer
{"title":"Muscle forces and the demands of turning while walking.","authors":"Steven G Lautzenheiser, Patricia Ann Kramer","doi":"10.1242/bio.061883","DOIUrl":"10.1242/bio.061883","url":null,"abstract":"<p><p>Turning is a ubiquitous feature of human locomotion and like straight path walking, requires muscular force both to propel the individual forward and to stabilize the trunk over the stance limb. The purpose of this study is to identify muscle force patterns while making a turn and compare them to those of straight path walking. Kinematic and kinetic data were collected from 10 adults who walked unshod at their self-selected normal velocity in four conditions: straight line, 45° and 90° turns with a sidestep, and a 45° crossover event. A musculoskeletal model was used to calculate muscle forces in the pelvis and lower limb. Statistical parameter mapping (SPM) was used to determine whether the muscle force patterns of the three turning conditions were different from walking in a straight path. We find that, overall, the muscles that stabilize the hip and ankle during walking demonstrate differences in timing and magnitude of their force patterns across all turning conditions.</p>","PeriodicalId":9216,"journal":{"name":"Biology Open","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12182865/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143979203","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 : 2025-06-15Epub Date: 2025-06-10DOI: 10.1242/bio.061963
Mary A Gannon, Thanushri Srikantha, Rudradip Pattanayak, Navya Kapa, Aneesh Pathak, A Claire Roberts, William J Stone, Kasandra Scholz, Roschongporn Ekkatine, Talene A Yacoubian
{"title":"A novel 14-3-3θ phosphomimetic mouse model demonstrates social dominance defects.","authors":"Mary A Gannon, Thanushri Srikantha, Rudradip Pattanayak, Navya Kapa, Aneesh Pathak, A Claire Roberts, William J Stone, Kasandra Scholz, Roschongporn Ekkatine, Talene A Yacoubian","doi":"10.1242/bio.061963","DOIUrl":"10.1242/bio.061963","url":null,"abstract":"<p><p>14-3-3 proteins, particularly the 14-3-3θ isoform, are neuroprotective in several models of Parkinson's disease (PD). Evidence for increased 14-3-3θ phosphorylation observed in PD and other neurodegenerative diseases points to a possible pathogenic role for 14-3-3θ phosphorylation in neurodegenerative disease. We recently created a novel conditional knock-in mouse to express the 14-3-3θ S232D phosphomimetic mutation. After crossing this conditional knock-in mouse with the Emx1-Cre mouse in order to induce expression of the S232D mutation in the cortex and hippocampus, we evaluated the effect of 14-3-3θ phosphorylation on behavior and pathology. These mice demonstrated mild motor deficits and reduced social dominance behavior but showed normal cognition and anxiety levels compared to Cre control mice. S232D mice did not show any α-synuclein or phospho-tau pathology at baseline, and dendritic arborization was normal in primary hippocampal cultures from S232D mice. Overall, this mouse model is a novel tool that can be used to look at the effect of 14-3-3θ phosphorylation at S232 in the context of neurodegenerative disease models.</p>","PeriodicalId":9216,"journal":{"name":"Biology Open","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12182864/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144109751","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 : 2025-06-15Epub Date: 2025-06-27DOI: 10.1242/bio.062111
Reinier Prosée, Katherine Brown
{"title":"Staying ahead of the curve: a decade of preprints in biology.","authors":"Reinier Prosée, Katherine Brown","doi":"10.1242/bio.062111","DOIUrl":"10.1242/bio.062111","url":null,"abstract":"","PeriodicalId":9216,"journal":{"name":"Biology Open","volume":"14 6","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12264737/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144511594","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 : 2025-06-15Epub Date: 2025-06-23DOI: 10.1242/bio.061962
Huy Tran, Nathalie Dostatni, Ariane Ramaekers
{"title":"EyeHex toolbox for complete segmentation of ommatidia in fruit fly eyes.","authors":"Huy Tran, Nathalie Dostatni, Ariane Ramaekers","doi":"10.1242/bio.061962","DOIUrl":"10.1242/bio.061962","url":null,"abstract":"<p><p>Variation in Drosophila compound eye size is studied across research fields, from evolutionary biology to biomedical studies, requiring the collection of large datasets to ensure robust statistical analyses. To address this, we present EyeHex, a Matlab-based tool for automatic segmentation of fruit fly compound eyes from brightfield and scanning electron microscopy (SEM) images. EyeHex features two integrated modules: the first uses machine learning to generate probability maps of the eye and ommatidia locations, while the second, a hard-coded module, leverages the hexagonal organization of the compound eye to map individual ommatidia. This iterative segmentation process, which adds one ommatidium at a time based on registered neighbors, ensures robustness to local perturbations. EyeHex also includes an analysis tool that calculates key metrics of the eye, such as ommatidia count and diameter distribution across the eye. With minimal user input for training and application, EyeHex achieves exceptional accuracy (>99.6% compared to manual counts on SEM images) and adapts to different fly strains, species, and image types. EyeHex offers a cost-effective, rapid, and flexible pipeline for extracting detailed statistical data on Drosophila compound eye variation, making it a valuable resource for high-throughput studies.</p>","PeriodicalId":9216,"journal":{"name":"Biology Open","volume":"14 6","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12233063/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144473964","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 : 2025-06-15Epub Date: 2025-06-10DOI: 10.1242/bio.062002
Gonzalo Germán Guendulain, Ana Lis Moyano, Vanesa Mattera, Melisa Carolina Monteleone
{"title":"2024 Argentine Group for Extracellular Vesicles (GAVE) Workshop: promoting science in challenging times.","authors":"Gonzalo Germán Guendulain, Ana Lis Moyano, Vanesa Mattera, Melisa Carolina Monteleone","doi":"10.1242/bio.062002","DOIUrl":"10.1242/bio.062002","url":null,"abstract":"<p><p>The Argentine Group for Extracellular Vesicles (GAVE) was established in 2022 with the objective of bringing together researchers working in Argentina dedicated to extracellular vesicle (EV) studies. Following its successful inaugural meeting in 2023, the II GAVE Workshop was held on 12-13 September 2024, at the University of Buenos Aires, Argentina. This event brought together over 140 participants from diverse disciplines, fostering collaboration and strengthening the national EV research field. Moreover, international speakers and renowned experts in their fields shared valuable insights and experiences with the audience. Despite the challenges posed by the national government's funding cuts, the 2024 GAVE workshop showcased the Argentine scientists' strong commitment to high-quality research and the growth of local science in the field of EVs. Supported by international organizations and local companies, the II GAVE Workshop prioritized inclusivity and provided valuable networking opportunities, particularly for students and early-career researchers. This financial support was fundamental to broadening the impact of the event by promoting the assistance of underrepresented groups. This Meeting Review highlights the outcomes of our workshop and shows the advances of the Argentinian scientific community involved in EV research.</p>","PeriodicalId":9216,"journal":{"name":"Biology Open","volume":"14 6","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12182863/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144257408","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}