{"title":"The zinc contraceptive effect: targets, timing, and quantitative thresholds.","authors":"Kirsten Shankie-Williams, Margot Day, Samson Dowland","doi":"10.1242/bio.062546","DOIUrl":"10.1242/bio.062546","url":null,"abstract":"<p><p>There is a critical need for novel non-hormonal contraceptives. Zinc-based intrauterine devices (IUDs) demonstrate 100% efficacy in rats, yet the mechanism remains unclear. We investigated whether zinc targets sperm, embryos, or the endometrium. Rats with zinc, copper, or nylon IUDs were mated. All retrieved embryos were fertilised, indicating no primary spermicidal effect. However, embryos from rats with a zinc IUD failed to reach the blastocyst stage, unlike those from rats with a copper IUD. In vitro embryo culture confirmed that zinc significantly inhibited mouse embryo development in a dose-dependent manner, with 5 μg/ml zinc causing a 97% decrease in blastocyst formation, whilst copper caused a 61% decrease. Surviving zinc-treated embryos also had significantly reduced attachment to human endometrial cells, unlike copper-treated embryos. There was also no reduced attachment of untreated mouse embryos to zinc- and copper-treated endometrial cells. These findings suggest that zinc's primary contraceptive mechanism is the potent inhibition of pre-implantation embryo development.</p>","PeriodicalId":9216,"journal":{"name":"Biology Open","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13383112/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148223184","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 : 2026-07-15Epub Date: 2026-08-04DOI: 10.1242/bio.062386
Yuka Morikawa, Ann Bromley, Jeffrey D Steimle, James F Martin
{"title":"Fucci-G1 insertion partially disrupts Shh expression.","authors":"Yuka Morikawa, Ann Bromley, Jeffrey D Steimle, James F Martin","doi":"10.1242/bio.062386","DOIUrl":"10.1242/bio.062386","url":null,"abstract":"<p><p>The Fucci mouse lines are valuable tools for tracing cell cycle stages during development and in postnatal tissues; however, the insertion loci for the transgenes remain unidentified. Here, we report the genomic insertion sites of both the Fucci-G1 and -S/G2/M transgenes, identified through whole-genome sequencing. Interestingly, the Fucci-G1 transgene is located proximal to the Shh lung gut enhancer (SLGE) on chromosome 5. Homozygous Fucci-G1 embryos are perinatal lethal but survive until embryonic day (E)18.5, exhibiting craniofacial and foregut-related defects. Expression of Shh and canonical targets are downregulated in the pharyngeal arches of E11.5 homozygous Fucci-G1 embryos. Furthermore, in situ hybridization analysis showed diminished Shh expression in the pharyngeal and foregut endoderm, consistent with disruptions to SLGE activity. Our results indicate that heterozygous Fucci-G1 mice are suitable for cell cycle studies; however, we caution potential genetic interference when investigating SHH-related pathways.</p>","PeriodicalId":9216,"journal":{"name":"Biology Open","volume":"15 7","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13488407/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148668346","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":"Conserved skeletal muscle transcriptomic responses to pacing strategies in Thoroughbred horses.","authors":"Kenya Takahashi, Kazutaka Mukai, Takanaga Shirai, Yusaku Ebisuda, Fumi Sugiyama, Toshinobu Yoshida, Hideo Hatta, Yu Kitaoka","doi":"10.1242/bio.062724","DOIUrl":"10.1242/bio.062724","url":null,"abstract":"<p><p>This study investigated whether different pacing patterns during high-intensity exercise elicit distinct transcriptional responses in equine skeletal muscle. Eight Thoroughbred horses completed two treadmill exercise sessions in a randomized crossover design. In the positive-pacing condition, horses exercised at 110% maximal O2 uptake (V̇O2max) for 1 min followed by 90% V̇O2max for 1 min, whereas in the negative-pacing condition, the order was reversed. At 4 h after exercise, the positive-pacing protocol resulted in upregulation of 1989 genes and downregulation of 840 genes, whereas the negative-pacing protocol resulted in upregulation of 1710 genes and downregulation of 593 genes (false discovery rate <0.05; fold change ≥1.5). Despite these differences, most exercise-responsive genes and pathways related to hypoxia signaling, extracellular matrix remodeling, and metabolic regulation were shared between protocols. A direct comparison of gene expression between the two protocols identified four genes with higher expression after positive pacing, including RP1, MORN5, and two unannotated equine transcripts (ENSECAG00000060378 and ENSECAG00000057614), whereas five genes (OLFML2B, POSTN, ANGPTL1, MAP1A, and ZNF554) showed higher expression after negative pacing. These findings indicate that the skeletal muscle transcriptomic response to workload-matched high-intensity exercise is largely conserved between pacing strategies in Thoroughbred horses, with only limited pacing-dependent differences.</p>","PeriodicalId":9216,"journal":{"name":"Biology Open","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13446558/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148374580","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 : 2026-07-15Epub Date: 2026-07-09DOI: 10.1242/bio.062429
Katharina Gritsch, Kiara Skrobar, Kristian Bredies, Heimo Wolinski
{"title":"Lipid droplet size profiling in yeast.","authors":"Katharina Gritsch, Kiara Skrobar, Kristian Bredies, Heimo Wolinski","doi":"10.1242/bio.062429","DOIUrl":"10.1242/bio.062429","url":null,"abstract":"<p><p>Lipid droplets are central hubs of cellular lipid metabolism and play crucial roles in health and disease. The yeast Saccharomyces cerevisiae serves as a powerful model for studying lipid droplet biology at the cellular level. Estimation of the number and size distribution of lipid droplets in a cell population is critical for functional studies. However, accurate segmentation and quantification of lipid droplets through image-based methods present significant challenges. Organelle motion, point-spread function (PSF) overlap of closely associated organelles and heterogeneous fluorescence labeling often compromise histogram-, shape- or machine-learning-based methods. Here, we present an alternative, seeding-based radial raytracing approach that is independent of image histograms and considers the PSF-blurred nature of imaged organelles. To improve lipid droplet resolution and contrast, we applied custom 3D deconvolution and integrated a supervised machine-learning step that corrected typical deconvolution artifacts. An integrated, extensible toolset including deep-learning-based cell registration enables detailed lipid droplet statistics, including user-defined size classes. As a proof of principle, we applied our approach to analyze lipid droplets in wild-type and mutant cells lacking the Sei1-Ldb16 seipin complex required for regular lipid droplet biogenesis.</p>","PeriodicalId":9216,"journal":{"name":"Biology Open","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13383019/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148270466","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 : 2026-07-15Epub Date: 2026-07-16DOI: 10.1242/bio.062675
Daniela Lopes Cardoso, Marilena Loizou, Danai D Fourla, Charles Woodman, Matthew J Guille, Colin Sharpe
{"title":"Signalling through RXRβ and its agonist, bexarotene, promotes neuron formation in Xenopus laevis embryos.","authors":"Daniela Lopes Cardoso, Marilena Loizou, Danai D Fourla, Charles Woodman, Matthew J Guille, Colin Sharpe","doi":"10.1242/bio.062675","DOIUrl":"10.1242/bio.062675","url":null,"abstract":"<p><p>Retinoic acid, acting through RAR/RXR nuclear receptors, is required for neuronal differentiation in Xenopus laevis. Bexarotene, characterised as a pan-RXR agonist, reduces the symptoms of Alzheimer's disease in mouse models by clearing amyloid plaque and by promoting neurogenesis. In this paper, we show that RXR-initiated bexarotene signalling generates additional neurons both during normal X. laevis development and in ectodermal explants in which bone morphogenetic protein (BMP) signalling is inhibited. Differential gene expression analysis between ectodermal explants taken from uninjected embryos and from embryos co-injected with mRNA that expresses Noggin, a BMP antagonist, and RXRβ identifies genes mediating the transition from an epidermal to a neural fate. The explants express genes associated with an anterior neural fate, but not a neuronal fate. The addition of bexarotene to equivalent co-injected explants activates genes that promote neuronal differentiation and posterior character, including genes of the canonical Wnt signalling pathway. Xenopus ectodermal explants therefore provide a simple and efficient tool to identify novel retinoid agonists that promote neuronal differentiation. The genes expressed in response to bexarotene are consistent with a pathway to neuronal differentiation allied to standard retinoid signalling.</p>","PeriodicalId":9216,"journal":{"name":"Biology Open","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13446568/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148307166","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 : 2026-07-15Epub Date: 2026-07-28DOI: 10.1242/bio.062644
Yelena Ivanova, Miguel Ramirez-Moreno, Jie Liu, Leila Abtahi, Baidong Wu, Amber S Cooper, Zengbo Wang, Douglas W Allan, Amritpal Mudher, Aaron A Comeault, Lovesha Sivanatharajah
{"title":"Context-dependent toxicity of human tau isoforms in a Drosophila tauopathy model.","authors":"Yelena Ivanova, Miguel Ramirez-Moreno, Jie Liu, Leila Abtahi, Baidong Wu, Amber S Cooper, Zengbo Wang, Douglas W Allan, Amritpal Mudher, Aaron A Comeault, Lovesha Sivanatharajah","doi":"10.1242/bio.062644","DOIUrl":"10.1242/bio.062644","url":null,"abstract":"<p><p>Tauopathies are characterised by progressive deterioration of brain regions due to abnormal accumulation of microtubule-associated protein tau (MAPT). Alternative splicing of MAPT pre-mRNA produces six isoforms, classified as 3R or 4R depending on whether they contain three or four microtubule-binding repeats. Although many tauopathies are 3R or 4R specific, individual isoform contributions to neurotoxicity remain unclear. To investigate isoform-specific toxicity, we generated Drosophila lines with transgenes encoding each human tau (hTau) isoform inserted at the same locus. In young adults, hTau abundance did not differ significantly among lines, yet expression levels were sufficient to induce visible, isoform-specific phenotypes. Across assays, hTau toxicity depended on expression window, tissue type, and neuronal identity; 4R isoforms were generally more toxic than 3R isoforms, but individual isoform effects differed by context. In selected neuronal populations, neurons classed as vulnerable showed early degeneration and continued decline, whereas resilient neurons degenerated only at the later time point. This suggests that, in some neurons, resilience may reflect early resistance to disease processes that is lost with age and exposure to age-related stressors. These phenotypes were not readily explained by hTau abundance or AT8-positive hTau. Together, we show that tau toxicity emerges from interactions between isoform-specific properties and cellular environment.</p>","PeriodicalId":9216,"journal":{"name":"Biology Open","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13474566/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148403745","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 : 2026-07-15Epub Date: 2026-07-08DOI: 10.1242/bio.062691
Erik Rollwitz, Martin Jastroch
{"title":"Retention and tissue-specific expression of uncoupling protein homoeologs in Xenopus laevis.","authors":"Erik Rollwitz, Martin Jastroch","doi":"10.1242/bio.062691","DOIUrl":"10.1242/bio.062691","url":null,"abstract":"<p><p>Mitochondrial uncoupling proteins (UCPs) play central roles in vertebrate energy metabolism, with UCP1 specializing as a thermogenic effector in placental mammals. Comparative genomics demonstrated that UCP1, UCP2, and UCP3 originated prior to the emergence of endothermy, suggesting that their ancestral functions evolved in ectothermic vertebrates. Here, we investigated the genomic organization, conserved synteny, and mRNA expression of all three UCP paralogs and homoeologs in the allotetraploid amphibian Xenopus laevis. Comparative genome analyses revealed that all three UCP paralogs and their long (L) and short (S) homoeologs were retained following polyploidization, although local rearrangements were evident for neighboring genes at the UCP2/UCP3 locus. Quantitative expression analyses across adult frog tissues revealed pronounced tissue specificity, with predominant expression of UCP1 and UCP2 in kidney, UCP3 in muscle, and differences in UCP2 homoeolog expression levels. Together, these findings establish a framework for UCPs in an amphibian model organism, primarily linking them to energetically demanding tissues.</p>","PeriodicalId":9216,"journal":{"name":"Biology Open","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13382700/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148249203","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 : 2026-07-09DOI: 10.1242/bio.062482
Bhavika Gambhava, Janvi Patel, Niyati Buch
{"title":"A Python-based automated pipeline for phylogenetic tree construction, visualization, and comparative statistical evaluation.","authors":"Bhavika Gambhava, Janvi Patel, Niyati Buch","doi":"10.1242/bio.062482","DOIUrl":"https://doi.org/10.1242/bio.062482","url":null,"abstract":"<p><p>Phylogenetic analysis is a fundamental concept in computational biology, which helps in understanding evolutionary relationships, species divergence, and functional conservation based on biological sequence data. In general, phylogenetic analysis involves a number of sequential steps, such as sequence collection, multiple sequence alignment, model selection, phylogenetic tree construction, and statistical validation, which are usually carried out using different software tools with heterogeneous workflows. In this work, we propose a Python-based phylogenetic analysis pipeline, which integrates a number of important steps in phylogenetic analysis into a unified framework. The proposed system incorporates a number of popular sequence alignment algorithms, such as Multiple Alignment using Fast Fourier Transform (MAFFT), Multiple Sequence Comparison by Log-Expectation (MUSCLE), and ClustalW, as well as different phylogenetic tree reconstruction approaches, such as Neighbor-Joining (NJ), Unweighted Pair Group Method with Arithmetic Mean (UPGMA), Maximum Likelihood (ML), and Maximum Parsimony (MP). In addition, tree visualization, as well as comparative assessment using topological distance measures and statistical hypothesis tests, is performed in the proposed system, which includes Robinson-Foulds (RF), Approximately Unbiased (AU), Kishino-Hasegawa (KH), and Shimodaira-Hasegawa (SH). The results obtained from the analysis of the datasets demonstrate that the combination of the MAFFT-based alignment methods with the Maximum Likelihood tree reconstruction strategy results in the generation of trees with high statistical support according to the tests used for the analysis.</p>","PeriodicalId":9216,"journal":{"name":"Biology Open","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148410439","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":"Preparation of soluble and functional recombinant HTLV-1 Tax protein using bacterial chaperones.","authors":"Michi Miura, Kazutaka Murayama, Satoshi Uemura, Hiroshi Kitamura, Mineki Saito, Teru Kanda","doi":"10.1242/bio.062659","DOIUrl":"10.1242/bio.062659","url":null,"abstract":"<p><p>HTLV-1 viral protein Tax physically interacts with multiple host proteins to disrupt their normal functions, causing debilitating haematological malignancy and inflammatory disorders. The recombinant Tax protein, like other intrinsically disordered proteins, is insoluble when expressed in Escherichia coli due to the inclusion body formation, hampering structural studies of this important viral protein. We report that the bacterial chaperone Trigger Factor significantly enhances the solubility of HTLV-1 Tax fused to maltose-binding protein (MBP) as a solubility tag. Using a hexahistidine tag in addition to MBP enabled a two-step purification to isolate Tax from the MBP moiety after cleaving the fusion protein with HRV 3C protease. The purified recombinant protein activated NF-κB, indicating that the recombinant protein, solubilised by Trigger Factor, was functional. A molecular thermodynamics simulation, using a 3D model generated by AlphaFold2 as the initial state, suggested two putative domains within the Tax protein. These predicted domains could also be expressed and purified in the presence of exogenous Trigger Factor. By enabling the production of full-length and predicted domains of HTLV-1 Tax in the soluble form, this study takes the first step towards structural studies to understand how HTLV-1 Tax mechanistically interacts with various host factors.</p>","PeriodicalId":9216,"journal":{"name":"Biology Open","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13382831/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148027363","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 : 2026-06-15Epub Date: 2026-06-10DOI: 10.1242/bio.062651
Miyuki Suzuki, Yosuke Kato, Rima Mizuno, Hiroshi Yajima, Shinichirou Miura, Tetsuya Endo, Makoto Mochii, Ken-Ichi T Suzuki
{"title":"Visualization of peripheral nerves in developing and regenerating limbs using a novel peripherin reporter line of Xenopus laevis.","authors":"Miyuki Suzuki, Yosuke Kato, Rima Mizuno, Hiroshi Yajima, Shinichirou Miura, Tetsuya Endo, Makoto Mochii, Ken-Ichi T Suzuki","doi":"10.1242/bio.062651","DOIUrl":"10.1242/bio.062651","url":null,"abstract":"<p><p>Peripherin (PRPH) is a class III intermediate filament protein expressed in peripheral nerves and upregulated during axon outgrowth and regeneration. In this study, we developed a transgenic Xenopus laevis line for long-term in vivo visualization of the peripheral nervous system. Deletion and motif analyses identified cis-regulatory regions within the promoter and intron 1, which are important for the neuronal expression of the X. laevis prph gene. Stable lines exhibited robust enhanced GFP reporter activity in developing neural primordia in embryos and in the peripheral nerves of tadpoles. Transgenic tadpoles enabled in vivo imaging of peripheral nerves throughout limb development. During larval limb regeneration, we observed modest early nerve entry into the blastema, recapitulating that seen in early limb development. In contrast, post-metamorphic limb blastemas displayed extensive innervation from the early phase of regeneration. Moreover, increased reporter activity in the nerves of the regenerating adult forelimb suggests regeneration-associated regulation of peripheral innervation and its potential role in blastema formation. This transgenic line will serve as a versatile tool for analyzing such large-scale neural remodeling across development, metamorphosis, and regeneration.</p>","PeriodicalId":9216,"journal":{"name":"Biology Open","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13312924/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147962300","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}