Open Biology最新文献

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.

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 (Ca²⁺) 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 Ca²⁺ entry (SOCE) to facilitate Ca²⁺ influx. Elevation of cytoplasmic Ca²⁺ 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 Ca²⁺ in NOX-dependent METosis, which differs from previous studies focusing on Ca²⁺ in the NOX-independent pathway. Our research reveals that Ca²⁺-mediated regulation of NOX plays a crucial role in METosis, especially in SOCE, and provides novel ideas for future research.

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 Ca²⁺ selectivity of these channels. The auxiliary subunits, α₂δ and β, play important roles in aiding the channels to fold, traffic and function correctly. Of therapeutic importance, the α₂δ subunits are a drug target of the gabapentinoid α₂δ 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.

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.

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.

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: Phalacrognathus muelleri, Prosopocoilus astacoides, Dorcus titanus and Prosopocoilus inclinatus. 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.

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.

Culturing protists offers a powerful approach to exploring eukaryotic diversity, especially for deep-branching lineages. In this study, we cultured and described a novel protist species, named Glissandra oviformis n sp. within the poorly studied and unclassified genus Glissandra. While an SSU rDNA gene phylogeny failed to resolve its phylogenetic placement in the eukaryotic tree, a phylogenomic analysis of 340 proteins indicated G. oviformis as a member of the CRuMs clade. Prior to this study, this clade consisted of diverse heterotrophic amoeba and flagellates, and lacked clear synapomorphies. Ultrastructural observations revealed that G. oviformis shares the characteristics with some CRuMs members, including the pellicle underlying the plasma membrane and an internal sleeve surrounding the central pair of the axoneme at the flagellar transitional region. Our findings suggest potential shared characteristics and synapomorphies for CRuMs and contribute to a deeper understanding of the character evolution within this clade.

Naked mole-rats (NMRs, Heterocephalus glaber) 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 Ca²⁺ influx pathway, namely the store-operated Ca²⁺ entry (SOCE), has been implicated in all these diseases. SOCE is triggered by intracellular Ca²⁺ 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.

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 (KIF1C)-knockout (KO) 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 KIF1C-KO 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 KIF1C 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.