{"title":"O-GlcNAc transferase promotes synaptic assembly independent of catalytic activity in <i>C. elegans</i>.","authors":"Mengting Wu, Huihui Jiang, Qian Li, Yunhe Liu, Hongjun Zhang, Zhiyong Shao","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Synapses are specialized intercellular connections where neurons transfer information, and they are funda mental for complex brain functions. Synaptic assembly is precisely regulated, and its dysfunction often leads to neurodevelopmental disorders. Previously, we demonstrated that O-GlcNAc transferase (OGT-1) is required for synaptic development in <i>C. elegans</i>. However, the underlying molecular mechanisms remain largely unknown. In this study, we found that OGT-1, the <i>C. elegans</i> homolog of mammalian OGT, regulates presynaptic assembly in AIY interneurons in a catalysis-independent manner. Mechanistically, OGT-1 acts upstream of a specific isoform of the transcription factor DAF-16/FOXO in the insulin signaling pathway. Finally, we found that OGT-1 regulates presynaptic assembly in a subset of neurons and is required for associative learning. Our findings provide insights into the role of OGT-1 in synaptic assembly.</p>","PeriodicalId":15171,"journal":{"name":"Journal of Biosciences","volume":"50 ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143709858","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":"Analysis of downstream targets of PAX6 and LHX2, fundamental regulators of the developing mammalian neocortex.","authors":"Mansi Srivastava, Varun Suresh, Shubha Tole","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The transcription factors PAX6 and LHX2 play fundamental roles in mammalian cerebral cortical development. Loss of either factor causes depletion of the cortical progenitor pool and reduction of neurogenesis of later-born cortical neurons. We compared the chromatin occupancy of PAX6 and LHX2 and transcriptional dysregulation upon loss of each factor to analyze whether they function via common gene regulatory networks. We identified common direct and indirect targets that were dysregulated either concordantly or discordantly, based on whether their expression showed similar up- or downregulation upon loss of either factor. Finally, we examined single-cell RNA-seq datasets from neocortical progenitors to identify the cell types within which each common direct/indirect and concordantly/discordantly regulated target gene is expressed as cortical progenitors undergo neurogenesis. Our analysis shows that PAX6 and LHX2 have several common targets that suggest similar pathways for progenitor maintenance, but the regulation of neurogenesis may occur via at least partially non-overlapping pathways. Furthermore, each factor functions to suppress the expression of a set of common Cajal-Retzius cell-specific and interneuron-specific genes which are not normally expressed by cortical progenitors. Together, our analysis offers experimentally testable hypotheses for how PAX6 and LHX2 may execute their critical roles.</p>","PeriodicalId":15171,"journal":{"name":"Journal of Biosciences","volume":"50 ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255552","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":"A jack of all trades: Hermaphrodite-specific serotonergic neuron in <i>C. elegans</i>.","authors":"Patrick Laurent","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>How does a single neuron type shape both short- and long-term behavior? A study reveals how co-transmission by two hermaphrodite-specific neurons (HSNs) of <i>Caenorhabditis elegans</i> produces both transient and long-lasting effects on its egg-laying behavior. A key question in neuroscience is how neurons and circuits integrate information to drive behavior. In the nematode <i>C. elegans</i>, locomotion, feeding, defecation and egg-laying motor programs are all generated by a simple nervous system consisting of 302 neurons whose connectivity patterns are fully described (White <i>et al</i>. 1986). Egg-laying behavior allows dispersal of eggs in the most appropriate locations. The egg-laying circuit consists of two hermaphrodite-specific serotonergic neurons (HSNs) and six ventral cholinergic C-neurons (VCs) connected to the vulval muscle. In addition, <i>uv1</i> neuroendocrine cells mechanically respond to egg laying by the release of tyramine and neuropeptides. Together, they produce a rhythmic behavior modulated by environmental cues that alternates between egg-laying phases and resting periods (Hardaker <i>et al</i>. 2001; Ringstad and Horvitz 2008; Fenk and de Bono 2015). How can such a simple circuit generate rhythmic and regulated behavior?</p>","PeriodicalId":15171,"journal":{"name":"Journal of Biosciences","volume":"50 ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144000971","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":"<i>Caenorhabditis elegans</i> as a model for studying intercellular communication via extracellular vesicles.","authors":"Tingting Li, Yunpeng Zhao, Yan Zou, Yue Wang","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Intercellular communication embodies an evolutionarily conserved mechanism facilitated through the release of extracellular vesicles (EVs). These EVs, membranous structures secreted by cells, serve as carriers for a variety of biological molecules, including proteins, lipids, and nucleic acids, facilitating intercellular information exchange and material transfer. Studies in classical genetic model organisms represented by <i>Caenorhabditis elegans</i> revealed the developmental and behavioral roles of EVs. In this review, we discuss the effect of EV-mediated intercellular communication on neuronal activity and aging. Notably, we summarize the roles of EVs released from ciliary sensory neurons and a class of evolutionarily conserved large EVs known as exophers, shedding light on their contributions to the regulation of multicellular organismal development and function.</p>","PeriodicalId":15171,"journal":{"name":"Journal of Biosciences","volume":"50 ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143648612","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}
Hye Jin Hwang, Francis R G Amrit, Brandon J Berry, Claudette St Croix, Andrew P Wojtovich, Sruti Shiva, Arjumand Ghazi
{"title":"Germline loss diminishes somatic mitochondria but confers preservation of respiratory function during aging and hypothermia.","authors":"Hye Jin Hwang, Francis R G Amrit, Brandon J Berry, Claudette St Croix, Andrew P Wojtovich, Sruti Shiva, Arjumand Ghazi","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Reproductive status influences metabolism and health across the lifespan in diverse ways, and mitochondrial function plays a critical role in mediating this relationship. Using the <i>Caenorhabditis elegans</i> germline ablation model, we investigated the impact of germline stem cell (GSC) loss on mitochondrial dynamics and respiratory function. Our results show that GSC loss reduces mitochondrial volume and respiratory function in young adulthood but preserves mitochondrial activity during aging and upon exposure to hypothermic stress, correlating with enhanced survival. We found that the transcription factor NHR-49/PPARα, but not DAF-16/ FOXO3A, was essential for preserving mitochondrial function and hypothermia resistance in these long-lived mutants. Together, these findings reveal the impact of germline signals on somatic mitochondrial health and underscore the intricate relationship between reproductive fitness and organismal health.</p>","PeriodicalId":15171,"journal":{"name":"Journal of Biosciences","volume":"50 ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144018114","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":"Role of EhLINE1_ORF1p outside retrotransposition: Downregulation causes growth defects in <i>Entamoeba histolytica</i>.","authors":"Devinder Kaur, Shashi Shekhar Singh, Shraddha Sharma, Sudha Bhattacharya","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The constitutive expression of EhLINE1_ORF1p in <i>Entamoeba histolytica</i> cells in the absence of retrotransposition suggests that this protein may serve roles beyond retrotransposition. To delve into this possibility, we generated and analyzed transcriptomic data of EhLINE1_ORF1p partial-knockdown cell lines. This analysis unveiled the significance of EhLINE1_ORF1p in the growth of <i>E. histolytica</i> cells. Our investigation of the consequences of EhLINE1_ORF1p partial-knockdown highlighted its impact on the genes involved in ribosome biogenesis, pre-rRNA processing, RNA helicase, and oxidoreductase activity, particularly those associated with amoebiasis. These affected genes are categorized as having high expression and are essential for optimal cell growth. Validation through western blotting confirmed a substantial and pronounced decline in EhLINE1_ORF1p level, and growth kinetics confirmed decline in cell growth. These findings provide compelling evidence supporting the plausible role of EhLINE1_ORF1p in regulating the growth of <i>E. histolytica</i>.</p>","PeriodicalId":15171,"journal":{"name":"Journal of Biosciences","volume":"50 ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143648621","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":"Independent control of functional rewiring after axon injury by <i>let-7</i> miRNA and insulin/insulin-like growth factor signaling pathways.","authors":"Sruthy Ravivarma, Sibaram Behera, Dipanjan Roy, Anindya Ghosh-Roy","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The capability of neurons to regenerate after injury becomes poor in adulthood. Previous studies indicated that loss of either <i>let-7</i> miRNA or components of insulin/insulin-like growth factor signaling (IIS) can overcome age-related decline in axon regeneration in <i>Caenorhabditis elegans</i>. In this study, we wanted to understand the relationship between these two pathways in axon regeneration. We found that the simultaneous removal of <i>let-7</i> and the gene for insulin receptor <i>daf-2</i> in parallel increased functional recovery involving posterior touch sensation following axotomy of posterior lateral microtubule (PLM) neurons in adulthood. Conversely, the loss of <i>let-7</i> could bypass the regeneration block due to the loss of DAF-16, a transcriptional mediator of DAF-2. Similarly, the loss of <i>daf-2</i> could bypass the requirement of LIN-41, a transcriptional co-factor of the <i>let-7</i> pathway. Our analysis revealed that these two pathways independently control the targeting of the regenerating axon to the ventral nerve cord (VNC), which leads to functional recovery. The computational analysis of the gene expression data revealed that a large number of genes, their interacting modules, and hub genes under the <i>let-7</i> and IIS pathways are exclusive in nature. Our study highlights a potential to promote neurite regeneration by harnessing the independent gene expression program involving the <i>let-7</i> and IIS pathways.</p>","PeriodicalId":15171,"journal":{"name":"Journal of Biosciences","volume":"50 ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143811363","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}
Priya Dharshini Veeraragavan, M Karunanithi, Sathya Albert
{"title":"Discovery of potent inhibitors from traditional rice varieties targeting α-amylase: A computational approach and <i>in vitro</i> validation.","authors":"Priya Dharshini Veeraragavan, M Karunanithi, Sathya Albert","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Diabetes involves complex metabolic dysregulation and necessitates approaches such as α-amylase inhibition to moderate postprandial glucose spikes and hyperglycemia. Thus, this study scrutinizes the α-amylase inhibitory potential of selected traditional rice varieties (Athur Kichili Samba, Poonkar, Karuppu Kavuni) as well as a modern variety (CO 43) in the cooked condition, using computational approaches alongside <i>in vitro</i> validation. The 156 metabolites obtained from gas chromatography-mass spectrometry analysis, docked with human pancreatic α-amylase (HPA), and based on the binding energies top-five-ranked metabolites were shortlisted (PubChem IDs: 91714169, 13821354, 167795, 2756016, and 3075922). In addition, molecular dynamics simulation was carried out for a timescale of 200 ns to assess protein-ligand complex stability, with parameters such as root mean square deviation, root mean square fluctuation, radius of gyration, solventaccessible surface area, H-bond, and interaction energy. Furthermore, molecular mechanics Poisson- Boltzmann surface area (MM/PBSA) and molecular mechanics generalized Born surface area (MM/GBSA) analyses were performed to validate the selected inhibitors. <i>In vitro</i> studies corroborated inhibitory effectiveness, with Athur Kichili Samba having the highest potency (IC50=4.48 mg/mL), followed by CO 43, Poonkar, and Karuppu Kavuni (IC50=5.12, 6.29, and 11.35 mg/mL). The consistent ranking of antidiabetic functionality observed across both computational and experimental approaches highlights the potential of these traditional rice varieties, suggesting additional clinical investigations to endorse their global consumption.</p>","PeriodicalId":15171,"journal":{"name":"Journal of Biosciences","volume":"50 ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143811168","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":"Glutamate metabolism disruption in Johanson-Blizzard syndrome: Insights from <i>C. elegans ubr-1</i> model.","authors":"Yi Li, Shangbang Gao","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The Johanson-Blizzard syndrome (JBS) is a complex autosomal recessive disorder that manifests through a spectrum of symptoms, with deficiencies in the ubiquitin-protein ligase E3 component N-recognin 1 (UBR-1) at its genetic core. Despite its clinical significance, the molecular intricacies of UBR-1's role in JBS remain largely elusive, presenting a formidable challenge in devising targeted treatments. The nematode <i>Caenorhabditis elegans</i>, with its genetic tractability and conservation of fundamental biological mechanisms, emerges as an invaluable model for unravelling the molecular underpinnings of JBS. This review integrates the latest discoveries from <i>C. elegans</i> studies, shedding light on UBR-1's multiple functions: its regulatory impact on cellular pathways and, particularly, its crucial involvement in glutamate metabolism. By assessing the contributions of these studies to our understanding of JBS, this review highlights the potential significance of glutamate metabolic dysfunction in JBS pathogenesis.</p>","PeriodicalId":15171,"journal":{"name":"Journal of Biosciences","volume":"50 ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255560","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":"Evolution of body size and selfhood: Size-scaling from selfless reproduction to enhanced self-preservation.","authors":"Douglas S Glazier","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Our knowledge of how and why various biological and ecological traits relate (scale) to body size has grown at a rapid pace. In this exploratory analysis, I aim to further advance our knowledge of biological scaling by arguing that individuality and selfhood increase along a size spectrum from tiny microbes to huge trees and whales, as driven by a gradient of decreasing mortality. According to a proposed size-self spectrum (SSS) model, tiny short-lived organisms are continuously engaged in relatively rapid, all-consuming, selfless reproduction, whereas large long-lived organisms have evolved relatively high levels of individuality and selfpreservation. Grades of individuality in organisms along the SSS are recognized by their levels of development of (a) protective boundaries between their inner and outer environments, (b) autonomy and identity preservation, and (c) self-awareness and regulation. Paradoxically, as increasingly large organisms have evolved increased independence from their external environments, they have also exerted greater per-capita impacts on them. With increasing body size, the prevailing direction of influence of an individual organism's internal versus external environments switches from inward in small 'exocentric' species to outward in large 'endocentric' species. Implications of the SSS model for understanding the nature and environmental impact of humans, who are relatively large organisms, as well as various other controversial biological, ecological, and philosophical issues are discussed.</p>","PeriodicalId":15171,"journal":{"name":"Journal of Biosciences","volume":"50 ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143972557","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}