Open Biology最新文献

Typically, unchecked pancreatic cell proliferation results in the development of pancreatic cancer, which has the potential to spread to other bodily organs. About 90% of instances of pancreatic cancer are pancreatic adenocarcinomas. About 10-20% of pancreatic carcinomas are resectable and potentially curable, and the 5-year survival rate is only 4%; as a result, the majority of pancreatic cancer treatments are palliative in nature. Surgical resection is the only curative treatment; however, because of late diagnosis, the majority of patients appear at an advanced stage, and only a small percentage (10-20%) of them are candidates for surgery. Due to pancreatic cancer's strong resistance to practically all chemotherapeutic drugs and conventional radiotherapies, conventional radiation and chemotherapies have little effectiveness in extending patients' overall life. A lot of scientific studies, however, frequently use the metaphorical term 'double-edged sword' to indicate how autophagy plays a different function in cancer. The use of autophagy inhibitors is thought to be advantageous in combining antineoplastic drugs to improve the sensitivity of cancer cells to therapeutic compounds that activate autophagy. In this review, we aim to look into autophagy along with searching for the most effective strategy in order to treat pancreatic adenocarcinoma with the least drug resistance.

Many marine invertebrates have a biphasic life cycle with a free-swimming larva and a bottom-dwelling adult. The transition from a planktonic to a benthic lifestyle is a significant step in the animal's life history, highly regulated and influenced by external and internal factors. Since the readiness to settle and the presence of a suitable seafloor habitat do not always coincide, larvae sometimes need to extend their planktonic phase. Little is currently known regarding how larvae partition their energy for coordinating development and growth according to food type and availability in their settlement habitat. Here, I investigate the effect of food availability and type on development in Platynereis dumerilii larvae. I assessed cell proliferation, growth and feeding onset over six days using two different food sources. The results indicate that food availability and type affect larval growth, with starved larvae slowing development and conserving resources, whereas fed larvae allocate resources to brain development and posterior growth. Overall, this work contributes to our understanding of how competent marine larvae regulate the duration of their planktonic phase and how nutritional status affects development.

Locomotion is essential for executing most behaviours. In Caenorhabditis elegans, efficient locomotion is exhibited as a result of the coordination of excitatory and inhibitory signals from the nervous system onto the body-wall muscles. Although neurotransmitters play a vital role in maintaining and executing coordinated movements, neuropeptides have emerged as important players in the regulation and sustenance of locomotory states. In this study we show that mutants in the neuropeptide flp-15 show a large increase in the mean amplitude of body-bends, indicating defects in the locomotory state of these animals. Our data suggest that FLP-15 partially functions through the G-protein coupled receptor (GPCR) NPR-3 to regulate the amplitude of body-bends. Finally, we show that loss of flp-15 leads to an increase in the expression of another neuropeptide, NLP-12, whose over-expression has been implicated in causing increased amplitude of body-bends, allowing us to speculate that the regulation of NLP-12 by FLP-15 may allow for the observed locomotory defects in flp-15 mutant animals.

Ageing is an intricate and progressive decline across all biological systems, marked by various molecular and cellular processes termed as the hallmarks of ageing. One of the hallmarks is mitochondrial dysfunction, which is brought about through several pathways: mutations in mitochondrial DNA, elevated reactive oxygen species production, disrupted mitochondrial dynamics and impaired mitophagy. Here, we explore the role of high mobility group box 1 (HMGB1) as a potential contributor to mitochondrial dysfunction, examining how it may influence these pathways through its dual roles as both a protector of mitochondrial integrity and a promoter of inflammatory damage. Furthermore, we consider how mitochondrial dysfunction, possibly mediated by HMGB1, could link to other hallmarks of ageing, positioning HMGB1 as a possible central regulator in the ageing process.

Fetal skin has an intrinsic regenerative capability to restore an injured site's architecture and functionality. This is preserved until the third trimester, when wound healing transitions to a scarring reparative response. This change coincides with the dynamic remodelling of dermal extracellular matrix (ECM). Here, we used primary human fetal or adult dermal fibroblast (fHDF and aHDF)-derived ECMs to demonstrate that different extrinsic signals from these ECMs dramatically altered gene expression in a primary human keratinocyte population grown on these matrices. Gene array data revealed keratinocytes grown on fHDF ECM markedly upregulated expression of cell-cycle genes, whereas on aHDF ECM expression of differentiation genes was favoured. Detailed proteomic analyses indicated compositionally distinct ECMs were deposited by aHDFs and fHDFs. Moreover, aHDFs and fHDFs contained subpopulation(s) that differentially expressed CD90, CD146 and CD26. On fHDFs the extracellular domain of CD26 was shed whereas on aHDFs full-length CD26 dominated. The proteomic and gene array data supported the fine-tuning of BMP/TGFβ/SMAD signalling pathways being a mechanism by which fetal matrices promote keratinocyte self-renewal. Collectively, these findings revealed that a fundamental aspect of skin development is dictated by the ECM of the dermis, specifically extrinsic signals from dermal fibroblast ECM direct keratinocyte self-renewal or differentiation.

Candida albicans, a commensal fungal pathogen, is a leading cause of opportunistic infections in immunocompromised individuals. High-resolution imaging of its cellular architecture is essential for uncovering pathogenic mechanisms and identifying antifungal targets. Here, we applied live-cell stimulated emission depletion (STED) microscopy to visualize subcellular structures in C. albicans with nanoscale precision. We found that fluorophores commonly used for STED imaging in mammalian cells were ineffective in C. albicans. In contrast, Nile Red enabled robust labelling of dynamic lipid-rich structures, including lipid droplets and intracellular membranes, with sufficient signal for long-term imaging. Using Nile Red with STED microscopy, we achieved over threefold improvement in lateral resolution (approx. 85 nm) compared to confocal microscopy, with minimal photobleaching even during continuous time-lapse acquisition over 8 h. Notably, dynamic tracking of lipid droplets revealed heterogeneous mobility patterns across individual cells, suggesting functional compartmentalization. Our findings establish STED microscopy with Nile Red staining as a powerful approach for visualizing dynamic ultrastructure in live fungal cells, expanding the toolkit for high-resolution fungal cell biology and offering new avenues for studying fungal pathogenesis and antifungal action at the nanoscale.

Histones are the fundamental building blocks of chromatin and serve as pivotal regulators of gene expression. Differential expression and mutations of H3.1 and H3.3 genes have been implicated in the pathogenesis of various cancer types. Mutations in H3.3, especially lysine to methionine substitutions (K27M/K36M), are particularly prevalent. Moreover, genetic alterations such as G34R/W/V/L, as well as variations in H3F3A and H3F3B genes, have also been identified. Despite high similarity in amino acid sequences, H3.1 and H3.3 have discrete functions in cancer. In this review, we delve into the recent advances in elucidating the implications of canonical histone H3.1 and its variant H3.3 on chromatin structure and function. Additionally, we explore how potential enhancing factors such as PTEN, MLL5, GPR87 and histone chaperones influence H3.1/H3.3 function.

Neuropeptides play a critical role in neurotransmission and organismal development. Members of the phylum Cnidaria, with a diffused nervous system, are one of the earliest divergent animals and might provide insights into the fundamentals of the emergence of neuronal communications. The neuropeptide diversity in Hydra (a cnidarian model) has been extensively studied using various strategies, each with certain limitations. Here, we have developed an in silico pipeline which identified both reported peptides and many new potential candidates. A comparative analysis within Cnidaria suggests a rapid divergence of neuropeptides which might be involved in complex behaviours. We identified new Hydra neuropeptides that belong to the RFamide and PRXamide families and a novel class of peptides lacking amidation (LW-peptides). A detailed expression and functional analysis of a new LW-peptide indicates its role in the longitudinal contraction of Hydra polyps. This study provides compelling evidence for the existence of intricate peptidergic communication in early neuronal circuits. The extensive diversity of neuropeptides within this phylum underscores their rapid evolutionary adaptability. This current pipeline also proves to be simple and adaptable to perform neuropeptide identification in other multicellular organisms.

Embryos are among the most temperature-sensitive life stages. To survive and produce juvenile stages, embryos must be robust to changes in temperature that also change development time profoundly. Yet, how robustness is achieved during embryogenesis, and which developmental events are most prone to perturbation by temperature, is only known for a handful of species. Such insights are especially lacking for marine ectotherms, which often develop in direct contact with the external environment. We address these gaps using the tubeworm, Galeolaria caespitosa, a typical marine ectotherm with external development. We fluorescently labelled F-actin and nuclear DNA in embryos sampled hourly throughout embryogenesis at the minimum temperature of the coldest month (11°C), annual mean temperature (17°C) and maximum temperature of the warmest month (22°C) in nature. Based on confocal imaging, we identified key developmental stages (milestones) in embryogenesis and compared their progression across temperatures. We found that developmental progression is similar across temperatures when normalized to development time, but earlier milestones are less robust to warming than later ones. Our results suggest that embryos achieve robustness by tightly coordinating the relative timing of embryonic events, offering clues to how embryos may withstand contemporary climate change in marine systems.

E3 ubiquitin ligases regulate the cellular proteome via 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 Rest mRNA in proliferative NPCs. Mechanistically, MEX3B interacts with Rest mRNA and the lncRNA Hotair to form a tripartite complex in the presence of basic fibroblast growth factor (bFGF). Loss of Hotair disrupts this complex; conversely, MEX3B RNAi significantly reduces Hotair abundance. Rest mRNA levels remain unaffected by Hotair knockdown, suggesting that the latter acts as a scaffold to facilitate bFGF-dependent MEX3B-Rest interaction in the MEX3B-Rest-Hotair tripartite axis. Our study demonstrates an RNA-driven post-transcriptional mechanism underlying NPC proliferation.