Adhesion-driven vesicle translocation through membrane-covered pores.

Translocation across barriers and through constrictions is a mechanism that is often used in vivo for transporting material between compartments. A specific example is apicomplexan parasites invading host cells through the tight junction that acts as a pore, and a similar barrier crossing is involved in drug delivery using lipid vesicles penetrating intact skin. Here, we use triangulated membranes and energy minimization to study the translocation of vesicles through pores with fixed radii.

Ferroptosis triggers mitochondrial fragmentation via Drp1 activation.

Constitutive mitochondrial dynamics ensure quality control and metabolic fitness of cells, and their dysregulation has been implicated in various human diseases. The large GTPase Dynamin-related protein 1 (Drp1) is intimately involved in mediating constitutive mitochondrial fission and has been implicated in mitochondrial cell death pathways. During ferroptosis, a recently identified type of regulated necrosis driven by excessive lipid peroxidation, mitochondrial fragmentation has been observed.

Recombinant Antibodies Inhibit Enzymatic Activity of the E3 Ubiquitin Ligase CHIP via Multiple Mechanisms.

Carboxyl-terminus of Hsp70-Interacting Protein (CHIP) is an E3 ubiquitin ligase that marks misfolded substrates for degradation. Hyper-activation of CHIP has been implicated in multiple diseases, including cystic fibrosis and cancer, suggesting that it may be a potential drug target. However, there are few tools available for exploring this possibility.

Event-related theta synchronization over sensorimotor areas differs between younger and older adults and is related to bimanual motor control.

When engaged in dynamic or continuous movements, action initiation involves modifying an ongoing motor program rather than initiating it from rest. Event-related theta synchronization over sensorimotor areas is a neurophysiological marker for modifying motor programs. We used electroencephalography (EEG) to examine how task complexity and age affect event-related synchronization (ERS) in the theta band during a dynamic bimanual, visuomotor pinch force task.

Ligand interaction landscape of transcription factors and essential enzymes in E. coli.

Knowledge of protein-metabolite interactions can enhance mechanistic understanding and chemical probing of biochemical processes, but the discovery of endogenous ligands remains challenging. Here, we combined rapid affinity purification with precision mass spectrometry and high-resolution molecular docking to precisely map the physical associations of 296 chemically diverse small-molecule metabolite ligands with 69 distinct essential enzymes and 45 transcription factors in the gram-negative bacterium Escherichia coli. We then conducted systematic metabolic pathway integration, pan-microbial evolutionary projections, and independent in-depth biophysical characterization experiments to define the functional significance of ligand interfaces.

Dual-mode, regenerated DNA motor for simultaneous detection of viral gene fragments and diagnosis of infectious disease.

This study presents a dual-mode and regenerated DNA motor powered by exonuclease III (Exo III) for the simultaneous detection of viral gene fragments. The detection methodology is categorized into two distinct operational modes. The first mode emphasizes the simultaneous detection of two viral gene fragments from a specific virus.

Task activation results in regional C-lactate signal increase in the human brain.

Hyperpolarized-C magnetic resonance imaging (HP-C MRI) was used to image changes in C-lactate signal during a visual stimulus condition in comparison to an eyes-closed control condition. Whole-brain C-pyruvate, C-lactate and C-bicarbonate production was imaged in healthy volunteers (N = 6, ages 24-33) for the two conditions using two separate hyperpolarized C-pyruvate injections. BOLD-fMRI scans were used to delineate regions of functional activation.

Targeting Brain Drug Delivery with Macromolecules Through Receptor-Mediated Transcytosis.

Brain diseases pose significant treatment challenges due to the restrictive nature of the blood-brain barrier (BBB). Recent advances in targeting macromolecules offer promising avenues for overcoming these obstacles through receptor-mediated transcytosis (RMT). We summarize the current progress in targeting brain drug delivery with macromolecules for brain diseases.

Advancing the Taxonomy of the Diatom Through an Integrative Study Conducted in the Central and Southeastern Adriatic Sea.

The marine diatom genus comprises cosmopolitan phytoplankton species commonly present in the Adriatic Sea. Species within the genus have been of significant concern because they produce domoic acid (DA), which can cause amnesic shellfish poisoning (ASP). In this study, we identified species along the Central and Southeastern Adriatic Sea, where monthly sampling carried out from February 2022 to February 2024 allowed for comprehensive species documentation.

Brassinosteroids Render Cell Walls Softer but Less Extensible in Growing Arabidopsis Hypocotyls.

Cell wall extensibility is a key biophysical characteristic that defines the rate of plant cell growth. It depends on the wall structure and is controlled by numerous proteins that cut and/or (re)form links between the wall constituents. Cell wall extensibility is currently estimated by different in vitro biomechanical tests.

Prescribed Hospital Diet Influence on Dietary Intake of Hospitalised Patients: A Cross-Sectional Study.

Background: The dietary intake of hospitalised patients is often compromised during hospitalisation, which can be a causal factor for hospital malnutrition. This is considered a public health problem worldwide and is associated with an increased risk of other complications.

Objectives: Our objective was to determine the dietary intake of hospitalised individuals and if the prescribed diet influences it.

The General Principle of the Warburg Effect as a Possible Approach for Cancer Immunotherapy: The Regulatory Effect of Plant Extracts Could Change the Game.

The interpretation of the biochemistry of immune metabolism could be considered an attractive scientific field of biomedicine research. In this review, the role of glycolysis in macrophage polarization is discussed together with mitochondrial metabolism in cancer cells. In the first part, the focus is on the Warburg effect and redox metabolism during macrophage polarization, cancer development, and management of the immune response by the cancer cells.

Navigating the Collective: Nanoparticle-Assisted Identification of Leader Cancer Cells During Migration.

Cancer-related deaths primarily occur due to metastasis, a process involving the migration and invasion of cancer cells. In most solid tumors, metastasis occurs through collective cell migration (CCM), guided by "cellular leaders". These leader cells generate forces through actomyosin-mediated protrusion and contractility.

Advances and Mechanisms of RNA-Ligand Interaction Predictions.

The diversity and complexity of RNA include sequence, secondary structure, and tertiary structure characteristics. These elements are crucial for RNA's specific recognition of other molecules. With advancements in biotechnology, RNA-ligand structures allow researchers to utilize experimental data to uncover the mechanisms of complex interactions.

Black Chokeberry () Juice Supplementation Affects Age-Related Myocardial Remodeling in Rats.

Background: Cardiac aging is associated with myocardial remodeling and reduced angiogenesis. Counteracting these changes with natural products is a preventive strategy with great potential. The aim of this study was to evaluate the effect of fruit juice (AMJ) supplementation on age-related myocardial remodeling in aged rat hearts.

MK-8776 and Olaparib Combination Acts Synergistically in Hepatocellular Carcinoma Cells, Demonstrating Lack of Adverse Effects on Liver Tissues in Ovarian Cancer PDX Model.

Hepatocellular carcinoma (HCC) cells critically depend on PARP1 and CHK1 activation for survival. Combining the PARP inhibitor (PARPi) olaparib with a CHK1 inhibitor (MK-8776, CHK1i) produced a synergistic effect, reducing cell viability and inducing marked oxidative stress and DNA damage, particularly in the HepG2 cells. This dual treatment significantly increased apoptosis markers, including γH2AX and caspase-3/7 activity.

HERC1 E3 Ubiquitin Ligase Is Necessary for Autophagy Processes and for the Maintenance and Homeostasis of Vesicles in Motor Nerve Terminals, but Not for Proteasomal Activity.

The ubiquitin proteasome system (UPS) is implicated in protein homeostasis. One of the proteins involved in this system is HERC1 E3 ubiquitin ligase, which was associated with several processes including the normal development and neurotransmission at the neuromuscular junction (NMJ), autophagy in projection neurons, myelination of the peripheral nervous system, among others. The tambaleante (tbl) mouse model carries the spontaneous mutation Gly483Glu substitution in the HERC1 E3 protein.

A Fresh Look at Celery Collenchyma and Parenchyma Cell Walls Through a Combination of Biochemical, Histochemical, and Transcriptomic Analyses.

Celery () can be considered as a model plant for studying pectin-enriched primary cell walls. In addition to parenchyma cells with xyloglucan-deficient walls, celery petioles contain collenchyma, a mechanical tissue with thickened cell walls of similar composition. This study presents a comprehensive analysis of these tissues at both early and late developmental stages, integrating data on polysaccharide yield, composition, localization, and transcriptome analysis.

Charge Reversal of the Uppermost Arginine in Sliding Helix S4-I Affects Gating of Cardiac Sodium Channel.

Several mutations of the uppermost arginine, R219, in the voltage-sensing sliding helix S4 of cardiac sodium channel Nav1.5 are reported in the ClinVar databases, but the clinical significance of the respective variants is unknown (VUSs). AlphaFold 3 models predicted a significant downshift of S4 in the R219C VUS.

Olaparib Combined with DDR Inhibitors Effectively Prevents EMT and Affects miRNA Regulation in -Mutated Epithelial Ovarian Cancer Cell Lines.

Epithelial ovarian cancer (EOC) remains a leading cause of gynecologic cancer mortality. Despite advances in treatment, metastatic progression and resistance to standard therapies significantly worsen patient outcomes. Epithelial-mesenchymal transition (EMT) is a critical process in metastasis, enabling cancer cells to gain invasive and migratory capabilities, often driven by changing miRNA expression involved in the regulation of pathological processes like drug resistance.

SARS-CoV-2 FP1 Destabilizes Lipid Membranes and Facilitates Pore Formation.

SARS-CoV-2 viral entry requires membrane fusion, which is facilitated by the fusion peptides within its spike protein. These predominantly hydrophobic peptides insert into target membranes; however, their precise mechanistic role in membrane fusion remains incompletely understood. Here, we investigate how FP1 (SFIEDLLFNKVTLADAGFIK), the N-terminal fusion peptide, modulates membrane stability and barrier function across various model membrane systems.

Molecular Mechanisms of Dietary Compounds in Cancer Stem Cells from Solid Tumors: Insights into Colorectal, Breast, and Prostate Cancer.

Cancer stem cells (CSC) are known to be the main source of tumor relapse, metastasis, or multidrug resistance and the mechanisms to counteract or eradicate them and their activity remain elusive. There are different hypotheses that claim that the origin of CSC might be in regular stem cells (SC) and, due to accumulation of mutations, these normal cells become malignant, or the source of CSC might be in any malignant cell that, under certain environmental circumstances, acquires all the qualities to become CSC. Multiple studies indicate that lifestyle and diet might represent a source of wellbeing that can prevent and ameliorate the malignant phenotype of CSC.

Probing Spatiotemporal Effects of Intertrack Recombination with a New Implementation of Simultaneous Multiple Tracks in TRAX-CHEM.

Among the most investigated hypotheses for a radiobiological explanation of the mechanism behind the FLASH effect in ultra-high dose rate radiotherapy, intertrack recombination between particle tracks arriving at a close spatiotemporal distance has been suggested. In the present work, we examine these conditions for different beam qualities and energies, defining the limits of both space and time where a non-negligible chemical effect is expected. To this purpose the TRAX-CHEM chemical track structure Monte Carlo code has been extended to handle several particle tracks at the same time, separated by pre-defined spatial and temporal distances.

Enhancing Radiation Therapy Response in Prostate Cancer Through Metabolic Modulation by Mito-Lonidamine: A H and P Magnetic Resonance Spectroscopy Study.

Radiation therapy (RT) is the cornerstone treatment for prostate cancer; however, it frequently induces gastrointestinal and genitourinary toxicities that substantially diminish the patients' quality of life. While many individuals experience transient side effects, a subset endures persistent, long-term complications. A promising strategy to mitigate these toxicities involves enhancing tumor radiosensitivity, potentially allowing for lower radiation doses.

The Structural, Biophysical, and Antigenic Characterization of the Goose Parvovirus Capsid.

Goose parvovirus (GPV) is an etiological agent of Derzsy's disease, afflicting geese and Muscovy ducks worldwide. Its high mortality rate among goslings and ducklings causes large losses to the waterfowl industry. Toward molecular and structural characterization, virus-like particles (VLPs) of GPV were produced, and the capsid structure was determined by cryogenic electron microscopy (cryo-EM) at a resolution of 2.