A nanoscale visual exploration of the pathogenic effects of bacterial extracellular vesicles on host cells.

Background: Bacterial extracellular vesicles (EVs) are pivotal mediators of intercellular communication and influence host cell biology, thereby contributing to the pathogenesis of infections. Despite their significance, the precise effects of bacterial EVs on the host cells remain poorly understood. This study aimed to elucidate ultrastructural changes in host cells upon infection with EVs derived from a pathogenic bacterium, Staphylococcus aureus (S.

Changes of synaptic vesicles in three-dimensional synapse models by treatment with umbelliferone in scopolamine-induced hippocampal injury model.

The neuroprotective effects of umbelliferone (UMB) were visualized in three-dimensional (3D) images on vesicle density changes of organotypic hippocampal slice tissues (OHSCs) induced by scopolamine by high voltage electron microscopy. Observations revealed that the number of vesicles decreased in OHSCs induced by scopolamine, and UMB was found to inhibit scopolamine-induced reduction in vesicles, resulting in an increase in vesicle count. These 3D models provide valuable insight for understanding the increase of synapse vesicles in hippocampal tissues treated with UMB.

Orthodenticle homeobox 2 is transported to lysosomes by nuclear budding vesicles.

Transcription factors (TFs) are transported from the cytoplasm to the nucleus and disappear from the nucleus after they regulate gene expression. Here, we discover an unconventional nuclear export of the TF, orthodenticle homeobox 2 (OTX2), in nuclear budding vesicles, which transport OTX2 to the lysosome. We further find that torsin1a (Tor1a) is responsible for scission of the inner nuclear vesicle, which captures OTX2 using the LINC complex.

Mitochondrial fragmentation and donut formation enhance mitochondrial secretion to promote osteogenesis.

Mitochondrial components have been abundantly detected in bone matrix, implying that they are somehow transported extracellularly to regulate osteogenesis. Here, we demonstrate that mitochondria and mitochondrial-derived vesicles (MDVs) are secreted from mature osteoblasts to promote differentiation of osteoprogenitors. We show that osteogenic induction stimulates mitochondrial fragmentation, donut formation, and secretion of mitochondria through CD38/cADPR signaling.

Suppression of Lung Cancer Malignancy by Micellized siRNA through Cell Cycle Arrest.

UBA6-specific E2 conjugation enzyme 1 (USE1) is frequently overexpressed in lung cancer patients. Moreover, the critical role of USE1 in the progression of human lung cancer is also indicated. As the next step, the authors aim to develop USE1-targeted therapeutic agents based on RNA interference (RNAi).

Ultrastructure of selected life history stages of the parasitic dinoflagellate Euduboscquella cachoni.

Euduboscquella species differ from most other syndinean dinoflagellates by having mononucleate trophonts, but resemble species of Amoebophrya and Sphaeripara by episome-hyposome differentiation and cortical complexity. Cytology and development of Euduboscquella species are well characterized, but their ultrastructure remains essentially unexplored. Transmission electron microscopy of Euduboscquella cachoni trophonts, tomont, and sporocytes revealed previously unrecognized structures.

A novel role of CRTC2 in promoting nonalcoholic fatty liver disease.

Objective: Diet-induced obesity is often associated with nonalcoholic fatty liver disease (NAFLD), which instigates severe metabolic disorders, including cirrhosis, hepatocellular carcinoma, and type 2 diabetes. We have shown that hepatic depletion of CREB regulated transcription co-activator (CRTC) 2 protects mice from the progression of diet-induced fatty liver phenotype, although the exact mechanism by which CRTC2 modulates this process is elusive to date. Here, we investigated the role of hepatic CRTC2 in the instigation of NAFLD in mammals.

Carrier-free micellar CpG interacting with cell membrane for enhanced immunological treatment of HIV-1.

Unmethylated CpG motifs activate toll-like receptor 9 (TLR9), leading to sequence- and species-specific immune stimulation. Here, we engineered a CpG oligodeoxyribonucleotide (ODN) with multiple hydrophobic moieties, so-called lipid-modified uracil, which resulted in a facile micelle formation of the stimulant. The self-assembled CpG nanostructure (U4CpG) containing the ODN 2216 sequence was characterized by various spectroscopic and microscopic methods together with molecular dynamics simulations.

Super-resolution imaging reveals cytoskeleton-dependent organelle rearrangement within platelets at intermediate stages of maturation.

A steady supply of platelets maintains their levels in the blood, and this is achieved by the generation of progeny from platelet intermediates. Using systematic super-resolution microscopy, we examine the ultrastructural organization of various organelles in different platelet intermediates to understand the mechanism of organelle redistribution and sorting in platelet intermediate maturation as the early step of platelet progeny production. We observe the dynamic interconversion between the intermediates and find that microtubules are responsible for controlling the overall shape of platelet intermediates.

Super-resolution imaging of platelet-activation process and its quantitative analysis.

Understanding the platelet activation molecular pathways by characterizing specific protein clusters within platelets is essential to identify the platelet activation state and improve the existing therapies for hemostatic disorders. Here, we employed various state-of-the-art super-resolution imaging and quantification methods to characterize the platelet spatiotemporal ultrastructural change during the activation process due to phorbol 12-myristate 13-acetate (PMA) stimuli by observing the cytoskeletal elements and various organelles at nanoscale, which cannot be done using conventional microscopy. Platelets could be spread out with the guidance of actin and microtubules, and most organelles were centralized probably due to the limited space of the peripheral thin regions or the close association with the open canalicular system (OCS).

Targeting YAP-p62 signaling axis suppresses the EGFR-TKI-resistant lung adenocarcinoma.

Background: Despite the progress of advanced target therapeutic agents and immune checkpoint inhibitors, EGFR-TKI resistance is still one of the biggest obstacles in treating lung cancer. Clinical studies with autophagy inhibitors are actively underway to overcome drug resistance.

Methods: We used PC9, PC9/GR, and HCC827/GR cell lines to evaluate the activation of autophagy and EGFR-TKI resistance.

Biocompatible liquid-type carbon nanodots (C-paints) as light delivery materials for cell growth and astaxanthin induction of Haematococcus pluvialis.

In this study, we aimed to demonstrate the feasibility of the application of biocompatible liquid type fluorescent carbon nanodots (C-paints) to microalgae by improving microalgae productivity. C-paints were prepared by a simple process of ultrasound irradiation using polyethylene glycol (PEG) as a passivation agent. The resulting C-paints exhibited a carbonyl-rich surface with good uniformity of particle size, excellent water solubility, photo-stability, fluorescence efficiency, and good biocompatibility (<10.

Diverse Structural Conversion and Aggregation Pathways of Alzheimer's Amyloid-β (1-40).

Complex amyloid aggregation of amyloid-β (1-40) (Aβ) in terms of monomer structures has not been fully understood. Herein, we report the microscopic mechanism and pathways of Aβ aggregation with macroscopic viewpoints through tuning its initial structure and solubility. Partial helical structures of Aβ induced by low solvent polarity accelerated cytotoxic Aβ amyloid fibrillation, while predominantly helical folds did not aggregate.

The role of the p38-activated protein kinase signaling pathway-mediated autophagy in cadmium-exposed monogonont rotifer Brachious koreanus.

Autophagy is a 'self-eating' system that regulates the degradation of cellular components and is involved in various biological processes including survival and development. However, despite its crucial role in organisms, the regulatory mechanism of autophagy remains largely unclear, particularly in invertebrates. In this study, conserved autophagy in the rotifer Brachionus koreanus in response to cadmium (Cd) exposure was verified by measuring acidic vesicle organelles using acridine orange (AO) and neutral red (NR) staining, and by detecting LC3 I/II on Western blot and immunofluorescence.

Halomonas aestuarii sp. nov., a moderately halophilic bacterium isolated from a tidal flat.

Strain Hb3 was isolated from a tidal flat in Jeollabuk-do Gunsan, Republic of Korea. Cells were Gram-stain-negative, oxidase- and catalase-positive, rod-shaped and motile. The strain grew optimally at 25-35 °C, at pH 6.

Do All Dinoflagellates have an Extranuclear Spindle?

The syndinean dinoflagellates are a diverse assemblage of alveolate endoparasites that branch basal to the core dinoflagellates. Because of their phylogenetic position, the syndineans are considered key model microorganisms in understanding early evolution in the dinoflagellates. Closed mitosis with an extranuclear spindle that traverses the nucleus in cytoplasmic grooves or tunnels is viewed as one of the morphological features shared by syndinean and core dinoflagellates.

Optimized reduction of uncertainty in bursty human dynamics.

Human dynamics is known to be inhomogeneous and bursty but the detailed understanding of the role of human factors in bursty dynamics is still lacking. In order to investigate their role we devise an agent-based model, where an agent in an uncertain situation tries to reduce the uncertainty by communicating with information providers while having to wait time for responses. Here the waiting time can be considered as cost.