Open Biology[JOURNAL]
Sun
200 papers
Pattern recognition in living cells through the lens of machine learning.
Britto Bisso F, Aguilar R, Shree D … +4 more , Zhu Y, Espinoza M, Diaz B, Cuba Samaniego C
Open Biol · 2025 Jul · PMID 40664239 · Full text
At a coarse level, pattern recognition within cells involves sensing of environmental signals by surface receptors, and activating downstream signalling pathways that ultimately drive a transcriptome response, enabling b...
At a coarse level, pattern recognition within cells involves sensing of environmental signals by surface receptors, and activating downstream signalling pathways that ultimately drive a transcriptome response, enabling biological functions such as differentiation, migration, proliferation, apoptosis or cell-type specification. This kind of decision-making process resembles a classification task that, inspired by machine learning concepts, can be understood in terms of a decision boundary: the combination of inputs relative to the classification region defined by this boundary defines context-specific responses. In this report, we contextualize machine learning concepts within a biological framework to explore the structural and functional similarities (and differences) between artificial neural networks, signalling pathways and gene regulatory networks. We take a preliminary look at neural network architectures that may better suit biological classification tasks, explore how learning fits into this paradigm, and address the role of competitive binding in cellular computation. Altogether, we envision a new research direction at the intersection of systems and synthetic biology, advancing our understanding of the inherent computational capacities of signalling pathways and gene regulatory networks.
Biochemistry and physiology of voltage-gated calcium channel trafficking: a target for gabapentinoid drugs.
Dolphin AC
Open Biol · 2025 Jul · PMID 40664238 · Full text
Voltage-gated calcium channels are multi-pass transmembrane proteins that have key features that are essential for their correct function. For example, the concerted movement of the voltage sensor domains in response to...
Voltage-gated calcium channels are multi-pass transmembrane proteins that have key features that are essential for their correct function. For example, the concerted movement of the voltage sensor domains in response to depolarization is required to ensure the channels open over a particular range of voltages, essential for the physiological function of each of the 10 different mammalian calcium channels. Furthermore, their selectivity filter is required to maintain the Ca selectivity of these channels. The auxiliary subunits, αδ and β, play important roles in aiding the channels to fold, traffic and function correctly. Of therapeutic importance, the αδ subunits are a drug target of the gabapentinoid αδ ligands, whose mechanism of action is now better understood. However, much is still unknown about how these calcium channels reach and are retained in specific locations, and how these processes are modified by various forms of modulation and synaptic plasticity.
Identification of novel components of the retinal determination gene network in cell lines.
Drewell RA, Dresch JM
Open Biol · 2025 Jul · PMID 40664237 · Full text
The retinal determination genetic network controls the development of the visual system in all seeing animals through the molecular regulation of cells to adopt an eye tissue fate. The compound eye of the fruit fly, , is...
The retinal determination genetic network controls the development of the visual system in all seeing animals through the molecular regulation of cells to adopt an eye tissue fate. The compound eye of the fruit fly, , is an excellent model system to study the complex mechanisms within the network that regulate specification of cellular identity during embryogenesis. In , the two paralogues, and , sit at the very pinnacle of the network and their expression early in development activates critical downstream components of the retinal determination pathway. In this study, we investigate the expression of 21 known components of the network in two established embryonic cell lines, Kc167 and S2 cells, that show reciprocal expression patterns for the two paralogues. Network mapping reveals that many of the components of the network demonstrate extensive interactions with additional factors. Integrating the transcriptional profile of the cell lines, interaction maps and embryonic expression patterns enables us to identify 16 potential novel components of the genetic network, 11 of which are transcription factors. We confirm the regulatory potential for a subset of the novel transcription factors through the identification of predicted binding sites in previously characterized enhancers for the core genes in the network.
Establish a simple and quantitative deep learning-based method to analyse complicated intra- and inter-species social interaction behaviour for four stag beetle species.
Suryanto ME, Siregar P, Ger TR … +1 more , Hsiao CD
Open Biol · 2025 Jul · PMID 40628294 · Full text
Stag beetles (Lucanidae) exhibit diverse social behaviours, yet quantifying these interactions remains challenging. Understanding social interactions within and between species is crucial for comprehending their behaviou...
Stag beetles (Lucanidae) exhibit diverse social behaviours, yet quantifying these interactions remains challenging. Understanding social interactions within and between species is crucial for comprehending their behaviour, ecology and evolution. Stag beetles exhibit diverse social behaviours, including intraspecific competition, courtship and interspecific interactions, often involving complex physical displays and subtle cues. Traditional ethological methods for analysing these behaviours are time-consuming, subjective and limited in their ability to capture the nuances of dynamic interactions. This project aims to develop a simple and quantitative deep learning-based method to analyse complicated intra- and inter-species social interaction behaviour in four stag beetle species. This study utilizes DeepLabCut™ (DLC), a state-of-the-art deep learning-based pose estimation tool, to analyse and compare intra- and inter-species social interactions in four stag beetle species: , , and . High-resolution videos of staged encounters were collected, and DLC was trained to accurately track key body parts of individual beetles. Behavioural parameters such as distance between individuals, orientation angles and movement trajectories were extracted from the pose data. Statistical analyses were conducted to identify species-specific differences in social behaviour, including aggression levels, courtship displays and dominance hierarchies. This study demonstrates the effectiveness of DLC in objectively quantifying complex social interactions in insects, providing valuable insights into the social ecology and evolutionary divergence of stag beetles.
The Slit-Robo signalling pathway in nervous system development: a comparative perspective from vertebrates and invertebrates.
Sanhueza N, Avilés EC, Oliva C
Open Biol · 2025 Jul · PMID 40628293 · Full text
During nervous system development, growing axons find their targets with the help of guidance cues. These cues, which can be secreted molecules provided by neighbouring cells or transmembrane proteins mediating cell-cell...
During nervous system development, growing axons find their targets with the help of guidance cues. These cues, which can be secreted molecules provided by neighbouring cells or transmembrane proteins mediating cell-cell contacts with the growing axons, act as either chemoattractants or chemorepellents. Over the last decades, several axon guidance molecules have been identified. One of the classical guidance cues is the Slit protein. Slit is a secreted protein, initially identified in a genetic screen in the fruit fly but later shown to be present in other organisms including vertebrates. Slit was originally classified as a repellent guidance cue, but nowadays it is recognized as a promoter of axonal growth in some contexts. Slit action is mediated mainly by the Roundabout (Robo) family of single pass transmembrane proteins, although it has been shown more recently that other proteins can also function as Slit receptors. In this review, we describe the main aspects of Slit-Robo signalling during development of the nervous system. We start with a historical view of the discovery of these proteins, followed by a description of their main molecular characteristics. We then explore specific examples that describe the functions and signal transduction mechanisms of this signalling pathway.
Store-operated calcium entry facilitates LPS-induced superoxide anion-dependent macrophage extracellular traps.
Nguyen TN, Lin TC, Chimphlee W … +5 more , Siew KX, Vongmanee N, Hsiao SC, Visitsattapongse S, Chiu WT
Open Biol · 2025 Jul · PMID 40628292 · Full text
Macrophage extracellular traps (METs) represent a recently discovered complex defence mechanism that is distinct from phagocytosis and involves the release of DNA and antibacterial proteins. They play an important role i...
Macrophage extracellular traps (METs) represent a recently discovered complex defence mechanism that is distinct from phagocytosis and involves the release of DNA and antibacterial proteins. They play an important role in pathogen removal, and calcium ions (Ca) have also been reported to be involved. In the present study, we identified METotic cells using digitonin as an alternative to Triton X-100, coupled with immunofluorescence staining using lamin antibodies. The limited permeability of digitonin ensures exclusive intranuclear antibody labelling of MET cells, therefore providing a straightforward and intuitive differentiation method. We found that under lipopolysaccharide stimulation, macrophages undergo store-operated Ca entry (SOCE) to facilitate Ca influx. Elevation of cytoplasmic Ca levels by SOCE promotes the generation of superoxide anions by NADPH oxidase (NOX), ultimately leading to METosis. In summary, our study strengthens the role of Ca in NOX-dependent METosis, which differs from previous studies focusing on Ca in the NOX-independent pathway. Our research reveals that Ca-mediated regulation of NOX plays a crucial role in METosis, especially in SOCE, and provides novel ideas for future research.
variant implications for biological understanding and human health.
Cheng CW, Earle SL, Povstyan OV … +15 more , Randall C, Smith KA, Debant M, Macrae FL, Beech DG, McGrane A, Bartoli F, Chuntharpursat-Bon E, Cubbon RM, Griffin KJ, Bailey MA, Kalli AC, Morley LC, Witte KK, Beech DJ
Open Biol · 2025 Jul · PMID 40628291 · Full text
The large membrane protein PIEZO1 assembles as trimers to form exceptional mechanical force-sensing ion channels of eukaryotes. When these channels are activated by force, cell membrane permeability to calcium ions and o...
The large membrane protein PIEZO1 assembles as trimers to form exceptional mechanical force-sensing ion channels of eukaryotes. When these channels are activated by force, cell membrane permeability to calcium ions and other ions increases rapidly, coupling force to cell function through ionic control. In humans and other species, PIEZO1 is both widely expressed and functional across major systems that include the cardiovascular, haematological and musculoskeletal systems, thereby serving diverse needs. In this narrative review of the scientific literature, we address what has been learned about PIEZO1 from associations of its gene variation with human characteristics. A particular physiological importance of PIEZO1 is emerging in lymphatics and thus in the control of tissue fluid homeostasis with relevance to the disease conditions of non-immune fetal hydrops and generalized lymphatic dysplasia. Other vascular relevance is seen in lower limb venous varicosities. PIEZO1 may be non-essential in red blood cells but the amplification of its function by gene variation quite selectively alters these cells, leading to haemolytic anaemia and other related disturbances that may be only mildly adverse and confer survival advantage. We speculate on what else might be learned in humans, guided by knowledge from PIEZO1 studies in mice, and describe how knowledge accumulated to date highlights new opportunities for PIEZO1 understanding and pathways to patient benefit.
GLP-1/GLP-1R axis: from metabolism (obesity and T2DM) to immunity.
Kumar V
Open Biol · 2025 Jan · PMID 40592472 · Full text
The discovery of glucagon-like peptide-1 (GLP-1) has revolutionized metabolism research in the context of obesity and type 2 diabetes mellitus (T2DM). For example, worldwide, more than 537 million adults are affected wit...
The discovery of glucagon-like peptide-1 (GLP-1) has revolutionized metabolism research in the context of obesity and type 2 diabetes mellitus (T2DM). For example, worldwide, more than 537 million adults are affected with T2DM, and more than 30.3 million people in the USA alone are suffering from T2DM. Obesity is one independent risk factor for T2DM; therefore, targeting obesity may lower the T2DM development risk. Hence, pharmaceutical companies have developed different GLP-1R agonists (GLP-1RAs) to target obesity and T2DM, which comprised multibillion-dollar businesses. However, metabolism and immune response are well-correlated processes that affect each other. For example, recent advances in metabolic processes governing the immune response have led to the evolution of , which can be divided into cellular, tissue and systemic immunometabolism. The current open-question article is intended to explore the impact of the GLP-1/GLP-1R axis on the immune response governed by the functioning of various immune cells and their interaction with the nervous system and microbiota axis that further depends on the gender and circadian clock of the host. Along with food/sugar ingestion, several other factors controlling the GLP-1 secretion and its immunomodulatory functions have been discussed to highlight the importance of the GLP-1/GLP-1R axis in immunoregulation. Therefore, understanding the GLP-1/GLP-1R axis/interaction at the immunological level will help to understand the adverse events associated with GLP-1RAs and their use as an immunomodulatory agent in acute and chronic inflammatory conditions depending on the gender and metabolic status of the host.
Frizzled1 and Frizzled2 are not redundant for competitive survival under low-Wingless levels in the developing wing epithelium.
Hingole S, Verma K, Chaudhary V
Open Biol · 2025 Jan · PMID 40592471 · Full text
In the wing epithelium, canonical Wnt signalling is activated by the gradient of secreted Wingless protein (Wnt1 homolog), which interacts redundantly with the Frizzled1 and Frizzled2 receptors. While sharing overlappin...
In the wing epithelium, canonical Wnt signalling is activated by the gradient of secreted Wingless protein (Wnt1 homolog), which interacts redundantly with the Frizzled1 and Frizzled2 receptors. While sharing overlapping functions, these receptors also have distinct non-canonical roles and exhibit differential expression patterns along the Wingless gradient. Moreover, Frizzled2, unlike Frizzled1, is thought to be essential for sustaining low-level Wingless signalling and promoting cell survival in the absence of the ligand. This raises the possibility of the two receptors acting differently along the Wingless gradient. In this study, we investigated the role of these receptors in cell survival across varying Wingless levels. We find that the loss of Frizzled2 in cells at a distance from the Wingless-producing cells-where Wingless levels are low-leads to competitive elimination of cells. In contrast, Frizzled1 is dispensable for cell survival, regardless of distance from the Wingless source. Our findings show that Frizzled2 is essential for competitive cell survival under low-Wingless conditions, and the two receptors are not equally redundant across the Wingless concentration gradient, providing insight into a mechanism for spatial and temporal precision in developmental signalling.
Recent advances in understanding of enterobacterial common antigen synthesis and regulation.
Bennett HC, Mitchell AM
Open Biol · 2025 Jan · PMID 40592470 · Full text
Antibiotic resistance has become one of the most significant global health threats, with nearly three million antibiotic-resistant infections occurring per year in the United States alone. This problem is especially acut...
Antibiotic resistance has become one of the most significant global health threats, with nearly three million antibiotic-resistant infections occurring per year in the United States alone. This problem is especially acute in Gram-negative bacteria, which possess an outer membrane (OM) that surrounds the aqueous periplasm and cytoplasmic membrane and acts as a permeability barrier capable of excluding many antibiotics. The OM of Enterobacterales also contains a highly conserved, invariant carbohydrate-derived moiety known as enterobacterial common antigen (ECA), which has been shown to play a significant role in this membrane permeability barrier. Although ECA was first discovered in the 1960s, its precise function and regulation remain largely mysterious. Here, we highlight recent studies that have advanced our understanding of the structure, biosynthesis, regulation and potential functions of ECA. We also review new insights into the complex interactions of the cell envelope biosynthesis pathways which may also play a role in surface antigen biosynthesis.
O-GlcNAcylation of the intellectual disability protein DDX3X exerts proteostatic cell cycle control.
Mitchell CW, Yuan H, Sønderstrup-Jensen M … +2 more , Ferenbach AT, van Aalten DMF
Open Biol · 2025 Jan · PMID 40592469 · Full text
O-GlcNAcylation of intracellular proteins is a key regulator of diverse cellular and developmental processes. Previous studies have demonstrated the acute sensitivity of cell cycle progression to chemical and genetic man...
O-GlcNAcylation of intracellular proteins is a key regulator of diverse cellular and developmental processes. Previous studies have demonstrated the acute sensitivity of cell cycle progression to chemical and genetic manipulation of O-GlcNAc homeostasis. However, the mechanisms by which O-GlcNAc regulates the cell cycle remain poorly understood. Here, we report Ser584 O-GlcNAcylation of the RNA helicase DDX3X, a microcephaly associated protein, as a proteostatic mechanism regulating S-phase entry. Loss of Ser584 O-GlcNAcylation promoted degradation of DDX3X by the proteasome, resulting in reduced expression of the DDX3X target gene and impaired cell cycle progression from G1 to S phase. These findings display how a single O-GlcNAc site affects DDX3X stability and thereby the cell cycle.
Unravelling the pathological roles of anastasis in cancer recurrence.
Tang HM, Tang HL
Open Biol · 2025 Jun · PMID 40555379 · Full text
Can anastasis contribute to cancer recurrence? Anastasis is a cell recovery mechanism to spare dying cells after the initiation of the cell death process. Emerging studies interrogate anastasis as an unexpected escape ta...
Can anastasis contribute to cancer recurrence? Anastasis is a cell recovery mechanism to spare dying cells after the initiation of the cell death process. Emerging studies interrogate anastasis as an unexpected escape tactic for cancer cells to evade cell death-inducing anti-cancer therapy, leading to recurrence. After anastasis, cancer cells display increased invasiveness and genomic instability, which could be associated with the common and fatal features of metastasis and drug resistance at the cancer recurrence. These studies open an encouraging new conceptual avenue for arresting cancer recurrence by targeting anastasis in cancer cells after conventional anti-cancer therapy. Here, we highlight recent findings towards unravelling pathological roles of anastasis in cancer recurrence, for the purpose of stimulating ideas and promoting the development of this new field of cancer research.
Reinventing the spermatheca: unveiling a novel sperm storage organ in Epilachninae ladybirds.
Rezende PH, Dias G, Paulo MDS … +3 more , Ayala-Costa D, Teixeira ACP, Lino-Neto J
Open Biol · 2025 Jun · PMID 40555378 · Full text
This study investigates the reproductive apparatus of , focusing on its secondary spermatheca, first described as a 'seminal node' by Katakura . for the Asian Epilachninae. We corroborate their previous findings that hig...
This study investigates the reproductive apparatus of , focusing on its secondary spermatheca, first described as a 'seminal node' by Katakura . for the Asian Epilachninae. We corroborate their previous findings that highlight this organ as the primary sperm storage site, contrasting with a vestigial typical spermatheca that lacks significant functionality. The functional spermatheca is a dilated, secretory region of the common oviduct filled with sperm. It features a specialized epithelium containing class 3 secretory cells and is lined by a thin chitinous cuticle, indicating that it qualifies as a true spermatheca. This organ seems to optimize sperm storage and maintenance when compared to the vestigial spermatheca. Additionally, we emphasize the close association between sperm and epithelial structures as mechanisms for efficient sperm retention and dosage, which could quantitatively and qualitatively improve reproductive success. Our findings may contribute to a greater understanding of the evolutionary adaptations of reproductive structures in Epilachninae and raise questions regarding the evolutionary history of these organs within ladybirds.
The challenge of measuring mosquito flight performance: going beyond sterile insect technique and into transgenic and gene drive-based approaches.
Najera P, Ogaugwu CE, Chan TF … +2 more , Kushwah RBS, Adelman Z
Open Biol · 2025 Jun · PMID 40555377 · Full text
Invasive insects inflict global costs of more than 70 billion USD annually by destroying crops and spreading disease-causing pathogens. Sterile insect technique (SIT), an insect population control method, involves the ir...
Invasive insects inflict global costs of more than 70 billion USD annually by destroying crops and spreading disease-causing pathogens. Sterile insect technique (SIT), an insect population control method, involves the irradiation or chemical sterilization of insects to produce sterile males that are mass-released. SIT has proven effective in reducing populations of the Mediterranean fruit fly, Mexican fruit fly and screwworm fly. In the past decade, efforts to improve SIT with transgenic approaches have increased, including the development of potentially highly invasive gene drive transgenes. Determining flight capability is vital to the success of any insect control programme, and various flight assays can be used to analyse insect dispersal, flight behaviour and the mechanics behind flight. However, traditional flight assays such as mark-release-recapture become more challenging with transgenic or gene drive arthropods due to ecological concerns, while assays such as wind tunnels or flight mills/arenas may not capture the full range of flight abilities. This review seeks to cover current flight assays and their limitations as well as the requirements for flight assays to establish comparative flight ability for genetically modified insects to better prioritize strains prior to any potential field-based releases.
Cell fate acquisition and reprogramming by the proneural transcription factor ASCL1.
Lundie-Brown J, Puletti F, Philpott A … +1 more , Azzarelli R
Open Biol · 2025 Jun · PMID 40527452 · Full text
ASCL1 is a key member of the proneural basic helix-loop-helix (bHLH) transcription factor (TF) family and it plays diverse roles in nervous system development and maintenance. ASCL1 is also one of the most studied bHLH T...
ASCL1 is a key member of the proneural basic helix-loop-helix (bHLH) transcription factor (TF) family and it plays diverse roles in nervous system development and maintenance. ASCL1 is also one of the most studied bHLH TFs in the field of somatic cell reprogramming, as it can reconfigure the chromatin of the cell of origin to impose a neuronal identity. However, the ability of ASCL1 to drive neuronal fate does not come without exceptions, as there are cell types that are refractory to ASCL1-mediated reprogramming, and there are developmental contexts where ASCL1 does not drive neurogenesis but supports the generation of other lineages. ASCL1 has also emerged as an important player in cancers like neuroblastoma and glioblastoma, underscoring the clinical need for a robust understanding of how ASCL1 controls cell identity. In this review, we revisit the foundational studies that established ASCL1 as a critical regulator of neuronal differentiation and incorporate recent advances in our understanding of ASCL1 post-translational regulation and transcriptional control. By integrating these perspectives, this review provides a comprehensive overview of the diverse roles of ASCL1 in development, reprogramming and cancer, offering insights into its molecular functions and therapeutic potential.
Enterohaemorrhagic AdhE spirosome length correlates with enzymatic directionality and is perturbed by salicylidene acylhydrazides.
Serrano E, Zhao T, Mark DR … +8 more , Soroor M, Floria I, Terrill NJ, Kapur N, Tyler AII, Horrocks MH, Roe AJ, Byron O
Open Biol · 2025 Jun · PMID 40527451 · Full text
Enterohaemorrhagic causes sporadic, and sometimes large-scale, food poisoning outbreaks, for which antibiotic treatment in humans is contraindicated. As an alternative form of therapy, previous studies developed the fam...
Enterohaemorrhagic causes sporadic, and sometimes large-scale, food poisoning outbreaks, for which antibiotic treatment in humans is contraindicated. As an alternative form of therapy, previous studies developed the family of salicylidene acylhydrazide (SA) anti-virulence compounds. One target of the SA compounds is AdhE, an enzyme that converts acetyl-CoA to ethanol and vice versa. AdhE oligomerizes, forming helicoidal filaments, heterogeneous in length, called spirosomes. We show it is possible to only partially fractionate AdhE spirosomes because they oligomerize in the absence of stimuli, and that spirosome formation is necessary to regulate the direction of AdhE enzymatic reactions. We also show that the SA compound ME0054 binds and perturbs AdhE spirosomes, enhancing the conversion of ethanol to acetyl-CoA. This mechanistic understanding of how ME0054 impacts AdhE function will help in the development of SA compounds as novel anti-virulence inhibitors.
The role of endothelial-derived factors in neural tube development: implications for organoid models.
van der Hoven A, Goolam M
Open Biol · 2025 Jun · PMID 40495809 · Full text
The study of the neural tube (NT), the antecedent structure of the central nervous system, is challenging due to the inaccessibility of the embryo. Thus, our understanding of this crucial timepoint in development is limi...
The study of the neural tube (NT), the antecedent structure of the central nervous system, is challenging due to the inaccessibility of the embryo. Thus, our understanding of this crucial timepoint in development is limited. The use of organoid models in recent years has proven immensely beneficial in the field of embryology, allowing the direct study of models of early neural development. As organoids advance in complexity, the vascularization of brain organoids has become a point of interest due to its significant role in neural development. This raises the question of whether the vascularization of NT organoids is necessary to improve their accuracy. This review summarizes the role of vascularization both during and before NT formation and explores the effects of endothelial-derived factors on this process. While the data indicate that vascularization is essential for proper NT formation, this review also highlights a significant gap in our knowledge and the need to clarify these interactions in order to generate more accurate organoid models.
Unravelling axonal transcriptional landscapes: insights from induced pluripotent stem cell-derived cortical neurons and implications for motor neuron degeneration.
Xu J, Hörner M, Nagel M … +8 more , Perhat P, Korneck M, Noß M, Hauser S, Schoels L, Admard J, Casadei N, Schuele R
Open Biol · 2025 Jun · PMID 40495808 · Full text
Neuronal function and pathology are deeply influenced by the distinct molecular profiles of the axon and soma. Traditional studies have often overlooked these differences due to the technical challenges of compartment-sp...
Neuronal function and pathology are deeply influenced by the distinct molecular profiles of the axon and soma. Traditional studies have often overlooked these differences due to the technical challenges of compartment-specific analysis. In this study, we employ a robust RNA-sequencing approach, using microfluidic devices, to generate high-quality axonal transcriptomes from induced pluripotent stem cells-derived cortical neurons (CNs). We achieve high specificity of axonal fractions, ensuring sample purity without contamination. Comparative analysis revealed a unique and specific transcriptional landscape in axonal compartments, characterized by diverse transcript types, including protein-coding mRNAs, RNAs encoding ribosomal proteins, mitochondrial-encoded RNAs and long non-coding RNAs. Previous works have reported the existence of transcription factors (TFs) in the axon. Here, we detect a set of TFs specific to the axon and indicative of their active participation in transcriptional regulation. To investigate transcripts and pathways essential for central motor neuron (MN) degeneration and maintenance we analysed kinesin family member 1C ()knockout ) CNs, modelling hereditary spastic paraplegia, a disorder associated with prominent length-dependent degeneration of central MN axons. We found that several key factors crucial for survival and health were absent in axons, highlighting a possible role of these also in other neurodegenerative diseases. Taken together, this study underscores the utility of microfluidic devices in studying compartment-specific transcriptomics in human neuronal models and reveals complex molecular dynamics of axonal biology. The impact of on the axonal transcriptome not only deepens our understanding of MN diseases but also presents a promising avenue for exploration of compartment-specific disease mechanisms.
Kaiso mediates transcription and RNA splicing in colorectal carcinoma: role of BRCA1 in the Kaiso enhanceosome.
Luo W, Tripathi MK, Liu Q … +6 more , Chen L, Cowan RW, Daniel JM, Yan C, Richmond A, Reynolds AB
Open Biol · 2025 Jun · PMID 40460875 · Full text
Kaiso (ZBTB33) is a transcription factor involved in mitotic clonal expansion and tumorigenesis in association with Adenomatous Polyposis Coli (APC) loss of heterozygosity. ENCODE data show strong overlap of the Kaiso pr...
Kaiso (ZBTB33) is a transcription factor involved in mitotic clonal expansion and tumorigenesis in association with Adenomatous Polyposis Coli (APC) loss of heterozygosity. ENCODE data show strong overlap of the Kaiso promoter-binding site-encode-derived Kaiso-binding site (eKBS) and many other transcription factors, including BRCA1. Here we sought to determine whether BRCA1 is a component of the Kaiso enhanceosome that regulates gene transcription. Using proximal ligation assays, immunoprecipitation followed by mass spectrometry, luciferase assays and ChIP-seq experiments, we evaluated the association between BRCA1 and Kaiso. Kaiso nuclear extract immunoprecipitation experiments revealed that Kaiso associates strongly with genes involved in RNA splicing and processing. When Kaiso was not crosslinked to DNA, BRCA1 was not detected among Kaiso-binding proteins. However, overexpression of BRCA1 increased Kaiso-mediated gene transcription in luciferase assays in a Kaiso-dependent manner. Comparison of BRCA1 ChIP-seq and Kaiso ChIP-seq data from HCT116 cells revealed both BRCA1 and Kaiso commonly bind to the promoters of 379 genes. The most enriched term associated with these genes where BRCA1 and Kaiso bind their promoters is metabolism of RNA. Disease processes associated with these BRCA1/Kaiso gene promoters indicate that BRCA1 is functionally linked to a Kaiso-directed programme of RNAP2-mediated gene transcription and likely associated with colorectal cancer development and maintenance.
Functional characterization of the store-operated calcium entry pathway in naked mole-rat cells.
Drugachenok P, Urriola-Muñoz P, Qiu L … +3 more , Han ZZ, Smith ESJ, Rahman T
Open Biol · 2025 Jun · PMID 40460874 · Full text
Naked mole-rats (NMRs, ) are highly unusual rodents exhibiting remarkable adaptations to their subterranean habitat and resistance to developing various age-related diseases such as those related to abnormal cell prolife...
Naked mole-rats (NMRs, ) are highly unusual rodents exhibiting remarkable adaptations to their subterranean habitat and resistance to developing various age-related diseases such as those related to abnormal cell proliferation or cancer, neurodegeneration and inflammation. In other rodents, as well as humans, a ubiquitous Ca influx pathway, namely the store-operated Ca entry (SOCE), has been implicated in all these diseases. SOCE is triggered by intracellular Ca store depletion resulting in interaction of Stim proteins with Orai proteins, the putative homologues of which appear to be present in the NMR genome, but no functional characterization of SOCE in NMRs has yet been conducted. In this study, we provide the first functional and pharmacological characterization of SOCE in NMR using both excitable and non-excitable cells.
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