Open Biology[JOURNAL]
Sun
200 papers
A distinct phase of cyclin B (Cdc13) nuclear export at mitotic entry in .
Chethan SG, Rogers JM, Vijayakumari D … +4 more , Williams W, Gligorovski V, Rahi SJ, Hauf S
Open Biol · 2025 Sep · PMID 40957559 · Full text
In eukaryotes, cell division requires coordination between the nucleus and cytoplasm. Entry into cell division is driven by cyclin-dependent kinases (CDKs), which need a cyclin binding partner for their activity. In (fi...
In eukaryotes, cell division requires coordination between the nucleus and cytoplasm. Entry into cell division is driven by cyclin-dependent kinases (CDKs), which need a cyclin binding partner for their activity. In (fission yeast), the B-type cyclin Cdc13 is essential and sufficient for cell cycle progression and is strongly enriched in the nucleus. Here, we show that a fraction of Cdc13 is exported from the nucleus to the cytoplasm just prior to mitosis. This export could be critical to propagate CDK activity throughout the cell. Mutating three Cdc13 nuclear localization signals (NLSs) led to precocious enrichment of Cdc13 in the cytoplasm but did not accelerate mitotic entry, indicating that the export is not sufficient to trigger entry into mitosis. The export coincides with spindle pole body integration into the nuclear envelope and may be required to coordinate nuclear and cytoplasmic signalling required for this integration. The onset and stop of Cdc13 nuclear export are remarkably abrupt, underscoring that mitotic entry consists of several switch-like transitions over the course of minutes. Our findings add another instance to the various cyclin nuclear transport events known to occur at critical cell cycle transitions throughout eukaryotes.
The E3 ligase MEX3B forms a tripartite complex with and to determine the proliferative capacity of neural progenitor cells.
Garg K, Sharma G, Samaddar S … +1 more , Banerjee S
Open Biol · 2025 Sep · PMID 40925537 · Full text
E3 ubiquitin ligases regulate the cellular proteome proteasome-dependent protein degradation; however, there exist limited studies outlining their non-canonical functions. RNA-binding ubiquitin ligases (RBULs) represent...
E3 ubiquitin ligases regulate the cellular proteome proteasome-dependent protein degradation; however, there exist limited studies outlining their non-canonical functions. RNA-binding ubiquitin ligases (RBULs) represent a subset of E3 ligases that harbour RNA-binding domains, making them uniquely positioned to function as both RNA-binding proteins and E3 ligases. Our initial microarray screen for E3 ligases from mouse cortical neural progenitor cells identified MEX3B, a known RNA-binding ubiquitin ligase, to be differentially expressed. Here, we characterize the non-canonical role of MEX3B in the context of neural proliferation. We find that MEX3B is significantly reduced following the differentiation of neural progenitor cells (NPCs). The knockdown of MEX3B blocks the proliferative state of NPCs and leads to the enhancement of neurite length and dendrite branching. We observed that MEX3B regulates the stability of mRNA in proliferative NPCs. Mechanistically, MEX3B interacts with mRNA and the lncRNA to form a tripartite complex in the presence of basic fibroblast growth factor (bFGF). Loss of disrupts this complex; conversely, MEX3B RNAi significantly reduces abundance. mRNA levels remain unaffected by knockdown, suggesting that the latter acts as a scaffold to facilitate bFGF-dependent MEX3B interaction in the MEX3B tripartite axis. Our study demonstrates an RNA-driven post-transcriptional mechanism underlying NPC proliferation.
Freshwater-adapted polychaetes exhibit a complete enzymatic machinery for synthesizing long-chain polyunsaturated fatty acids.
Bainour K, Zulkifli N, Sam KK … +5 more , Navarro JC, Castro LFC, Glasby CJ, Shu-Chien AC, Monroig Ó
Open Biol · 2025 Sep · PMID 40898956 · Full text
The sustainability of aquaculture is challenged by limited fishmeal and fish oil supplies, key sources of long-chain polyunsaturated fatty acids (LC-PUFA) such as eicosapentaenoic acid (EPA, 20:5 n-3), docosahexaenoic ac...
The sustainability of aquaculture is challenged by limited fishmeal and fish oil supplies, key sources of long-chain polyunsaturated fatty acids (LC-PUFA) such as eicosapentaenoic acid (EPA, 20:5 n-3), docosahexaenoic acid (DHA, 22:6 n-3) and arachidonic acid (ARA, 20:4 n-6), essential for fish health and product quality. Polychaetes represent a promising alternative. While marine polychaetes show complete LC-PUFA biosynthetic pathways involving elongases (Elovl), front-end desaturases (Fed), and methyl-end desaturases (ω des), freshwater species remain poorly studied. We hypothesize that freshwater-adapted polychaetes exhibit enhanced LC-PUFA biosynthesis to compensate for limited dietary sources in freshwater environments. This study focuses on , a freshwater nereid polychaete found in Southeast Asia. We isolated and characterized elongase and desaturase genes from using a yeast-based heterologous expression system. Our results revealed three Elovl (Elovl2/5, Elovl4, Elovl1/7) that elongate PUFA substrates from C to C, two Fed (Fed1 with Δ5 and Fed2 with dual Δ6/Δ8 activities), and two ω des: a Δ12 desaturase enabling linoleic acid (18:2 n-6) synthesis, and an ω3 desaturase converting n-6 into n-3 PUFA. These findings indicate that has the enzymatic capacity to synthesize LC-PUFA like ARA and EPA, supporting its potential for sustainable biomass production using low-nutrient substrates.
The curious family of cytochrome P450 4F fatty acid ω-hydroxylases: recent developments in their function and relevance for human health.
Alves Chagas BC, Jia H, Brixius B … +1 more , Brixius-Anderko S
Open Biol · 2025 Aug · PMID 40858268 · Full text
Cytochrome P450 enzymes (CYP, P450) are indispensable for human health and catalyse a plethora of reactions contributing to the clearance of xenobiotics, steroid and bile acid biosynthesis, and the functionalization of v...
Cytochrome P450 enzymes (CYP, P450) are indispensable for human health and catalyse a plethora of reactions contributing to the clearance of xenobiotics, steroid and bile acid biosynthesis, and the functionalization of vitamins in the human body. The family of CYP4F fatty acid ω-hydroxylases consists of five isoforms, CYP4F2, CYP4F3A, CYP4F3B, CYP4F11 and CYP4F22, which share a high amino acid sequence similarity but assume different physiological functions in humans. While CYP4F2 and CYP4F3B are the major enzymes producing a lipid mediator from arachidonic acid, CYP4F3A inactivates leukotriene B4 as anti-inflammatory response, CYP4F11 is capable of effectively metabolizing drugs, and CYP4F22 contributes to a healthy skin barrier. In this review, we provide an overview of recent developments in CYP4F function and discuss potential future directions underlining their growing relevance in human health and disease.
Functional disruption of oxytocin projections participates atypical social and anxiety-like behaviours in BTBR mouse model of autism.
Higuchi Y, Ozawa A, Kobayashi R … +2 more , Konno T, Arakawa H
Open Biol · 2025 Aug · PMID 40858267 · Full text
Oxytocin (OXT) neurons in the paraventricular nucleus of the hypothalamus (PVN), which send projections to the medial amygdala (MeA) and the bed nucleus of the stria terminalis (BnST), are implicated in regulation of pro...
Oxytocin (OXT) neurons in the paraventricular nucleus of the hypothalamus (PVN), which send projections to the medial amygdala (MeA) and the bed nucleus of the stria terminalis (BnST), are implicated in regulation of prosocial-emotional behaviours and abnormalities resembling autism spectrum disorders (ASD). Compared with standard C57BL6J (B6) mice, BTBR mice, a behaviour-based ASD model, exhibited decreased densities of OXT neurons and attenuated OXT neuronal responses to a social encounter. OXT receptor mRNA expressions in the MeA and BnST as a response to a social encounter were blunted in BTBR mice. OXT promoter retrograde viral tracing revealed that the OXT projections were defective in those BTBR mice. Thus, chemogenetic excitation of OXT neurons using OXT promoter adeno-associated viruses (AAV) enhanced anxiety-like behaviour and facilitated social investigation in both strains, while excitation of OXT neurons attenuated anxiety-like behaviour along with social investigation in B6 mice and failed to induce a change in their socio-emotional behaviours in BTBR mice. Altogether, OXT circuits serve as a key regulator for socio-emotional behaviour; MeA-OXT projection facilitates social investigation and anxiety-like behaviour, while BnST-OXT projection conversely attenuates these behaviours; hence a defect of the OXT circuits contributes to the development of ASD-like social phenotypes in BTBR mice.
Using diapause as a platform to understand the biology of dormancy.
Sweet NA, Hu CK
Open Biol · 2025 Aug · PMID 40829645 · Full text
Diapause is a fascinating form of biological dormancy that is employed by a broad array of animals as a survival strategy to endure adverse environmental conditions. This unique dormant state can suspend organismal devel...
Diapause is a fascinating form of biological dormancy that is employed by a broad array of animals as a survival strategy to endure adverse environmental conditions. This unique dormant state can suspend organismal development until a more favourable condition arises, giving the species the greatest chance to survive as a whole. Remarkably, while following the same principle of suspending development, diapause exists in different forms and can occur at various stages before reaching the adult form. Functionally, with multiple evolutionary origins across the animal kingdom, diapause demonstrates the ability to respond to diverse environmental challenges while converging to maintain the same core function of suspending development. At the physiological level, these different diapause states share a similar metabolic adaptation to conserve resources and energy throughout dormancy. Underneath, the same genes have been repeatedly identified as regulators and effectors of diapause at different developmental stages in both invertebrates and vertebrates. This suggests the presence of a conserved molecular programme comprised of the same set of key genes repeatedly reprogrammed and utilized at the core of diapause. The knowledge of diapause from the organismal to molecular levels, together, should serve as a useful window to better understand the biology of dormancy.
Systemic analyses show that the biosynthesis and spatial distribution of fatty acids, triglycerides and lipids differed in male and female mice and humans.
Furse S, Virtue S, Huang-Doran I … +5 more , Vidal-Puig A, Chiarugi D, Stevenson PC, Snowden SG, Koulman A
Open Biol · 2025 Aug · PMID 40829644 · Full text
Recent work has shown that the prevalence and character of metabolic diseases differs between male and female mammals. This strongly suggests that the control mechanisms that govern, for example lipid metabolism, differ...
Recent work has shown that the prevalence and character of metabolic diseases differs between male and female mammals. This strongly suggests that the control mechanisms that govern, for example lipid metabolism, differ between the sexes. If true, a one-size-fits-all approach to treating metabolic disease will not be effective in all patients. We tested three hypotheses to understand how the lipid metabolism of male and female mammals may differ. First, whether endogenous fatty acid biosynthesis differed between tissues in the same male and female mice. Second, whether the system-level control of lipid pathways differed between the sexes. Third, whether lipid composition differs between males and females at a population level. We found that fatty acid biosynthesis was distinct in male and female mice across tissues. Systemic control of phospholipid and triglyceride metabolism also differed between the sexes. A human population showed that both phospholipid and triglyceride metabolism differed between males and females.
Developmental remodelling of flight muscle sarcomeres: a scaled myofilament lattice model based on multiscale morphometrics.
Görög P, Novák T, Polgár TF … +9 more , Bíró P, Gutheil A, Kozma C, Gajdos T, Tóth K, Tóth A, Erdélyi M, Mihály J, Szikora S
Open Biol · 2025 Aug · PMID 40795996 · Full text
The indirect flight muscle is a widely used model for studying sarcomere structure and muscle development due to its extremely regular architecture. Nevertheless, precise measurement of the basic sarcomeric parameters re...
The indirect flight muscle is a widely used model for studying sarcomere structure and muscle development due to its extremely regular architecture. Nevertheless, precise measurement of the basic sarcomeric parameters remains a challenge even in this greatly ordered tissue. In this study, we identified several factors affecting measurement reliability and developed a software tool for precise, high-throughput measurement of sarcomere length and myofibril width. The accuracy of this new tool was validated against simulated images and blinded manual measurements. To extend the scope of this morphometric analysis to the sub-sarcomeric scale, we used electron and super-resolution microscopy to quantify myofilament number and filament length during myofibrillogenesis. Our findings revealed the dynamics of thin and thick filament elongation, as well as the addition of myofilaments at the sarcomere periphery during myofibrillogenesis. We precisely measured the dimensions of the Z-disc, I-band and H-zone during development, enabling us to construct refined models of sarcomere growth at the level of individual myofilaments, providing a spatial framework for interpreting nanoscopic localization data. These models deepen our understanding of sarcomere growth and lay the groundwork for future studies on the molecular mechanisms driving myofilament elongation and assembly.
Mitochondrial-derived gene expression in hibernation: tissue-specific responses in the thirteen-lined ground squirrel.
Emser SV, Millesi E
Open Biol · 2025 Aug · PMID 40795995 · Full text
Hibernation is a remarkable physiological adaptation in many mammals, characterized by prolonged torpor and profound metabolic suppression. Despite its importance, the molecular mechanisms regulating mitochondrial-derive...
Hibernation is a remarkable physiological adaptation in many mammals, characterized by prolonged torpor and profound metabolic suppression. Despite its importance, the molecular mechanisms regulating mitochondrial-derived gene expression during hibernation remain poorly understood. In this study, we analysed mitochondrial gene expression across multiple tissues of the hibernating thirteen-lined ground squirrel () using publicly available RNA sequencing (RNA-seq) data. We assessed all known mitochondrial DNA-derived transcripts-including mitochondrial mRNAs, mitochondrial-derived peptides and proteins (MDPs), rRNAs, and long non-coding RNAs (lncRNAs)-in the liver, adrenal gland, three brain regions, and brown adipose tissue (BAT) across different hibernation states. Our findings reveal distinct tissue-specific expression patterns of mitochondrial transcripts. Differential expression was observed in three of the six tissues analysed (liver, adrenal gland, and BAT) while no significant changes were detected in the three brain regions. In tissues exhibiting differential expression, a consistent pattern emerged: lncRNAs such as Mdl1, Mdl1as, and lncCyb were generally upregulated, whereas mRNAs, including a novel transcript encoding the putative mitochondrial protein Rudel, were predominantly downregulated. These results provide new insights into mitochondrial gene regulation during hibernation and highlight tissue-specific adaptations at the level of mitochondrial gene expression.
Selective loss of ATP carriers in favour of SLC25A43 orthologues in metamonad mitochondria adapted to anaerobiosis.
Janowicz N, Dohnálek V, Zítek J … +9 more , Peña-Diaz P, Pyrihová E, King MS, Husová M, Žárský V, Kunji E, Zikova A, Hampl V, Dolezal P
Open Biol · 2025 Aug · PMID 40795994 · Full text
Metamonada is a eukaryotic supergroup of free-living and parasitic anaerobic protists. Their characteristic feature is the presence of highly reduced mitochondria that have lost the ability to produce ATP by oxidative ph...
Metamonada is a eukaryotic supergroup of free-living and parasitic anaerobic protists. Their characteristic feature is the presence of highly reduced mitochondria that have lost the ability to produce ATP by oxidative phosphorylation and in some cases even by substrate phosphorylation, with all ATP being imported from the cytosol. Given this striking difference in cellular ATP metabolism when compared to aerobic mitochondria, we studied the presence of mitochondrial carrier proteins (MCPs) mediating the transport of ATP across the inner mitochondrial membrane. Our bioinformatic analyses revealed remarkable reduction of MCP repertoire in Metamonada with striking loss of the major ADP/ATP carrier (AAC). Instead, nearly all species retained carriers orthologous to human SLC25A43 protein, a little-characterized MCP. Heterologous expression of metamonad SLC25A43 carriers confirmed their mitochondrial localization, and functional analysis revealed that SLC25A43 orthologues represent a distinct group of ATP transporters, which we designate as ATP-importing carriers (AIC). Together, our findings suggest that AIC facilitate the ATP import into highly reduced anaerobic mitochondria, compensating for their diminished or absent energy metabolism.
Transcriptional regulation as a dose-dependent process: insights from transcription factor tuning.
Noviello G
Open Biol · 2025 Aug · PMID 40763802 · Full text
Several biological processes, including transcriptional regulation by transcription factors (TFs), are dose-dependent. At the mathematical level, dose-dependent processes can be modelled by fitting dose-response curves,...
Several biological processes, including transcriptional regulation by transcription factors (TFs), are dose-dependent. At the mathematical level, dose-dependent processes can be modelled by fitting dose-response curves, for istance, employing Hill-type equations. At the experimental level, however, quantitatively regulating, or tuning, endogenous gene expression to characterize dose-dependent processes is challenging. Here, existing methods to fine-tune endogenous gene expression are compared and contrasted. Relatively small TF dosage variations have been shown to underpin cell fate decisions. Nonetheless, the current understanding of the molecular mechanisms by which TFs quantitatively regulate gene expression is limited, due to the paucity of genome-wide studies in endogenous and physiological conditions. Recent works combining quantitative perturbations of TFs and genome-wide response analyses are untangling an underexplored layer of transcriptional control. At the same time, new questions are emerging in the field, which will require further technological advancements in order to be addressed.
Brain amino acid sensing for organismal amino acid homeostasis.
Tsang AH, Samson L, Blouet C
Open Biol · 2025 Aug · PMID 40763801 · Full text
Amino acids are essential for normal physiological functions, and disruptions in their circulating concentrations are implicated in the pathophysiology of various diseases. Therefore, understanding the mechanisms that re...
Amino acids are essential for normal physiological functions, and disruptions in their circulating concentrations are implicated in the pathophysiology of various diseases. Therefore, understanding the mechanisms that regulate circulating amino acid levels in normal physiology is of critical importance. Evidence indicates that in healthy mammals, post-absorptive circulating levels of essential amino acids are maintained within a range that varies little from day to day or following bidirectional changes in dietary protein intake. This suggests the presence of homeostatic control mechanisms. Here, we propose a conceptual framework for the homeostatic regulation of essential amino acid availability, emphasizing the role of the brain in generating feedback controls to restore baseline levels acutely after a meal and during chronic changes in dietary protein intake. We review current evidence supporting brain amino acid sensing as a component of this regulatory system, integrating peripheral and central signals to modulate dietary protein intake and peripheral amino acid metabolism. We highlight major knowledge gaps regarding the specific neural circuits, molecular mechanisms and physiological outcomes of brain amino acid sensing. Future inquiry using the proposed framework and addressing these gaps will significantly enhance our understanding of the pathways involved in the maintenance of circulating amino acid availability and the regulation of lean mass in health, disease states or in response to therapeutic strategies for metabolic diseases.
Double trouble: cytosolic and nuclear IKKα in cancer.
Tinto K, Cunningham M, Plevin R
Open Biol · 2025 Aug · PMID 40763800 · Full text
IκB kinase alpha (IKKα) is a serine/threonine kinase originally known for its role in nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signalling, which integrates inflammatory processes and cancer....
IκB kinase alpha (IKKα) is a serine/threonine kinase originally known for its role in nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signalling, which integrates inflammatory processes and cancer. IKKα can function within the IKK complex in canonical NF-κB signalling, alongside its homologous family member, IKKβ, and regulatory subunit IKKγ (NEMO). However, a key role for IKKα is its ability to promote non-canonical NF-κB signalling. Additionally, the dynamic ability of IKKα to shuttle between the cytosol and nucleus, mediates NF-κB-independent effects which further its role in inflammation and tumour progression. More recently, an endosomal-generated, nuclear-active IKKα isoform, p45-IKKα has been discovered and implicated in cancer and chemoresistance. This review focuses on current knowledge of the complex and intricate roles of nuclear and cytosolic IKKα in promoting tumour progression. By highlighting the molecular roles of IKKα in several cancer subtypes, and its integral roles in many of the hallmarks of cancer throughout this review, we highlight the therapeutic potential of IKKα as a future anti-cancer drug target.
Discovery of unique mitotic mechanisms in .
Akiyoshi B, Faktorová D, Lukeš J
Open Biol · 2025 Aug · PMID 40763799 · Full text
Diplonemids are highly diverse and abundant marine plankton with significant ecological importance. However, little is known about their biology, even in the model diplonemid whose genome sequence is available. Examinin...
Diplonemids are highly diverse and abundant marine plankton with significant ecological importance. However, little is known about their biology, even in the model diplonemid whose genome sequence is available. Examining the subcellular localization of proteins using fluorescence microscopy is a powerful approach to infer their putative function. Here, we report a plasmid-based method that enables YFP-tagging of a gene at the endogenous locus. By examining the localization of proteins whose homologs are involved in chromosome organization or segregation in other eukaryotes, we discovered several notable features in mitotically dividing cells. Cohesin is enriched on condensed interphase chromatin. During mitosis, chromosomes organize into two rings (termed mitotic rings herein) that surround the elongating nucleolus and align on a bipolar spindle. Homologs of chromosomal passenger complex components (INCENP, two Aurora kinases and KIN-A), a CLK1 kinase, meiotic chromosome axis protein SYCP2L1, spindle checkpoint protein Mad1 and microtubule regulator XMAP215 localize in between the two mitotic rings. In contrast, a Mad2 homolog localizes near basal bodies as in trypanosomes. By representing the first molecular characterization of mitotic mechanisms in and raising many questions, this study forms the foundation for dissecting mitotic mechanisms in diplonemids.
Long-read RNA-sequencing reveals transcript-specific regulation in human-derived cortical neurons.
Xu J, Hörner M, Atienza EB … +7 more , Manibarathi K, Nagel M, Hauser S, Admard J, Casadei N, Ossowski S, Schuele R
Open Biol · 2025 Jul · PMID 40735840 · Full text
Long-read RNA sequencing has transformed transcriptome analysis by enabling comprehensive mapping of full-length transcripts, providing an unprecedented resolution of transcript diversity, alternative splicing and transc...
Long-read RNA sequencing has transformed transcriptome analysis by enabling comprehensive mapping of full-length transcripts, providing an unprecedented resolution of transcript diversity, alternative splicing and transcript-specific regulation. In this study, we employed nanopore long-read RNA sequencing to profile the transcriptomes of three cell types commonly used to model brain disorders, human fibroblasts, induced pluripotent stem cells and stem cell-derived cortical neurons, identifying extensive transcript diversity with 15 072 transcripts in stem cell-derived cortical neurons, 13 048 in fibroblasts and 12 759 in induced pluripotent stem cells. Our analyses uncovered 35 519 differential transcript expression events and 5135 differential transcript usage events, underscoring the complexity of transcriptomic regulation across these cell types. Importantly, by integrating differential transcript expression and usage analyses, we gained deeper insights into transcript dynamics that are not captured by gene-level expression analysis alone. Differential transcript usage analysis highlighted transcript-specific changes in disease-relevant genes such as , and , associated with Alzheimer's disease, neuronal migration disorders and degenerative axonopathies, respectively. This added resolution emphasizes the significance of transcript-level variations that often remain hidden in traditional differential gene expression analyses. Overall, our work provides a framework for understanding transcript diversity in both pluripotent and specialized cell types, which can be used to investigate transcriptomic changes in disease states in future work. Additionally, this study underscores the utility of differential transcript usage analysis in advancing our understanding of neurodevelopmental and neurodegenerative diseases, paving the way for identifying transcript-specific therapeutic targets.
Oxidized phospholipid damage signals as modulators of immunity.
Choi JH, Kagan JC
Open Biol · 2025 Jul · PMID 40730233 · Full text
Damage-associated molecular patterns (DAMPs) are self-derived molecules released during tissue damage that influence immune responses. Phospholipids, essential to cell membranes and lung surfactants, become oxidized unde...
Damage-associated molecular patterns (DAMPs) are self-derived molecules released during tissue damage that influence immune responses. Phospholipids, essential to cell membranes and lung surfactants, become oxidized under conditions of cellular stress, forming oxidized phospholipids. Unlike their unoxidized counterparts, oxidized phospholipids function as DAMPs and engage pattern recognition receptors (PRRs) on innate immune cells, activating signalling pathways that regulate immune responses. This activity alters innate immune cells, which in turn modulate the adaptive immune response, ultimately contributing to the pathogenesis of disease. Traditionally considered pro-inflammatory, recent studies reveal a more nuanced role for these lipids, with their effects on immune cells being context dependent. This review examines the mechanisms behind the generation of oxidized phospholipids and their induction in disease. We focus on recent studies that clarify how these lipids affect innate immune cells, leading to downstream effects on adaptive immunity, as well as their direct influence on adaptive immune cells. Finally, we explore therapeutic strategies targeting oxidized phospholipids to regulate immunity, offering insights into their broader role in immune regulation and potential applications in disease prevention.
How many plasmids can bacteria carry? A synthetic biology perspective.
Kiattisewee C
Open Biol · 2025 Jul · PMID 40730232 · Full text
Plasmids are pinnacle tools in synthetic biology and other biotechnological applications. They serve as the simplest approach to introduce recombinant DNA, which is then transcribed into RNA that functions as is or is tr...
Plasmids are pinnacle tools in synthetic biology and other biotechnological applications. They serve as the simplest approach to introduce recombinant DNA, which is then transcribed into RNA that functions as is or is translated into a protein of interest. Despite their widespread utility, the question 'how many plasmids can be used in this bacterium?' remains underexplored in the existing literature. In this article, I discuss the maintenance of multiple unique plasmids in bacteria through a microbial synthetic biology perspective, both in theoretical and practical aspects. I delve into the existing evidence of multi-plasmid systems, aiming to pinpoint the possible maximum number of unique plasmids a single microbe can carry. Finally, I highlight how the existing applications of multi-plasmid systems drive novel discovery and development in metabolic engineering, synthetic biology and other relevant areas in comparison to other non-plasmid strategies.
Hypoxia impedes differentiation of cranial neural crest cells into derivatives relevant for craniofacial development.
Schmid T, Rodrian G, Bachmann E … +4 more , Kohler A, Wegner M, Gölz L, Weider M
Open Biol · 2025 Jul · PMID 40695323 · Publisher ↗
Orofacial clefts are the second-most prevalent congenital malformation. Risk factors are multifactorial and include genetic components, but also environmental factors. One environmental factor is hypoxia during pregnancy...
Orofacial clefts are the second-most prevalent congenital malformation. Risk factors are multifactorial and include genetic components, but also environmental factors. One environmental factor is hypoxia during pregnancy, caused for instance by tobacco smoking, medication or living at high altitudes. We here show that hypoxia has only modest effects on proliferating cranial neural crest cells (CNCC), but dramatically influences their differentiation potential. We detected massive perturbations in their differentiation to chondrocytes, osteoblasts and smooth muscle cells. The transcriptional induction of the majority of regulated genes during each of these processes was grossly impaired by hypoxic conditions, as evidenced by genome-wide transcriptomic analyses. These hypoxia-attenuated genes include several orofacial cleft risk genes. Among these, we bioinformatically identified the hedgehog co-receptor and the cysteine dioxygenase as two central genes that display hypoxia-attenuated induction during all three differentiation pathways and that are relevant during craniofacial development. Moreover, several components of signalling pathways between undifferentiated CNCC and their derivatives, as well as components of signalling pathways from CNCC to epithelial cells, were affected by hypoxia. Our analyses reveal a drastic influence of hypoxia on the differentiation potential of CNCC as a possible cause for the occurrence of orofacial clefts.
Interplay between circadian rhythm, ageing and neurodegenerative disorder.
Nagayach A, Bhaskar R, Ghosh S … +10 more , M D, Abomughaid MM, Han SS, Singh KK, Almutary AG, Chaudhary K, Atteri S, Chauhan AS, Jha NK, Sinha JK
Open Biol · 2025 Jul · PMID 40695322 · Publisher ↗
Circadian rhythm, as a homeostatic tool of biological life, plays a vital role in regulating human physiology, metabolism, endocrinology, and emotional and cognitive behaviour. A disrupted circadian rhythm, marked by age...
Circadian rhythm, as a homeostatic tool of biological life, plays a vital role in regulating human physiology, metabolism, endocrinology, and emotional and cognitive behaviour. A disrupted circadian rhythm, marked by age-related alterations such as decreased variation in sleep-wake patterns and instability in the timing of these patterns, can worsen age-related problems such as increased oxidative stress and inflammation. Advancing age is associated with anomalies in the redox balance, gradual alterations in physiological functions and deregulation of various metabolic pathways. The mutual interaction between circadian rhythm and ageing may potentially contribute to the development of neurodegenerative disorders. Consistent alterations in circadian rhythms could lead to various degenerative disorders and aggravate age-related ailments. Therefore, understanding and unravelling the intricate interplay between circadian rhythm and ageing holds immense potential for developing therapeutic interventions and promoting healthy ageing strategies. In this review article, we discuss the role of circadian rhythms in physiology and their age-related changes that impact health. We focus on how disruptions in circadian rhythms, common with ageing, may increase risks for neurodegenerative disorders. Understanding this interaction holds promise for developing therapeutic approaches to support healthy ageing.
CRISPR-Cas9 genome editing in ,a key species for understanding animal origins.
Ara PS, Casacuberta E, Scazzocchio C … +2 more , Ruiz-Trillo I, Najle SR
Open Biol · 2025 Jul · PMID 40695321 · Publisher ↗
Microbial holozoans are the closest unicellular relatives of animals. They share a substantial gene repertoire with animals and exhibit complex life cycles. Studying these organisms is crucial for understanding the evolu...
Microbial holozoans are the closest unicellular relatives of animals. They share a substantial gene repertoire with animals and exhibit complex life cycles. Studying these organisms is crucial for understanding the evolution of multicellularity, and significant progress has been made in uncovering key aspects of the biology of the four microbial holozoans lineages: choanoflagellates, filastereans, ichthyosporeans and corallochytreans. However, reverse genetic tools are still lacking in corallochytreans, one of the earliest-branching holozoan lineages and the only known group with both coenocytic and binary fission development. Here, we present CRISPR-Cas9-mediated gene inactivation and point mutation methodologies in the corallochytrean . As a proof of concept, we inactivated the gene, a component of the mTOR pathway, conferring rapamycin resistance, and introduced a point mutation in , encoding a subunit of succinate dehydrogenase, conferring carboxin resistance. Our results demonstrate the presence of both non-homologous end-joining and homology-directed repair pathways in and shows an editing efficiency of approximately 2%. Furthermore, simultaneous gene targeting revealed a co-editing frequency of approximately 20%. Finally, this study establishes unequivocally that is haploid, making it an ideal model for genetic studies and gene editing applications to unravel the molecular mechanisms involved in animal origins.
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