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Cell biologists, including those seeking molecular mechanistic explanations of cellular phenomena, frequently rely on experimental strategies focused on identifying the cellular context relevant to their investigations. We suggest that such practices can be understood as a guided decomposition strategy, where molecular explanations of phenomena are defined in relation to natural contextual (cell) boundaries. This "top-down" strategy contrasts with "bottom-up" reductionist approaches where well-defined molecular structures and activities are orphaned by their displacement from actual biological functions. We focus on the central role of microscopic imaging in cell biology to uncover possible constraints on the system. We show how identified constraints are used heuristically to limit possible mechanistic explanations to those that are biologically meaningful. Historical examples of this process described here include discovery of the mechanism of oxidative phosphorylation in mitochondria, molecular explanation of the first steps in protein secretion, and identification of molecular motors. We suggest that these instances are examples of a form of downward causation or, more specifically, constraining relations, where higher-level structures and variables delimit and enable lower-level system states. The guided decomposition strategy in our historical cases illustrates the irreducibility of experimentally identified constraints in explaining biological activities of cells. Rather than viewing decomposition and recomposition as separate epistemic activities, we contend that they need to be iteratively integrated to account for the ontological complexity of multi-level systems., (© 2024. Springer Nature Switzerland AG.)

How plants sense their orientation in relation to gravity and steer their root and shoot growth accordingly is not fully understood. The discovery of key steps needed for this process fills in some of the gaps in our knowledge.LAZY proteins hitchhike when roots reorient relative to gravity. [ABSTRACT FROM AUTHOR]

A new wave of research is unpicking the relationship between cancer and neurons — and looking for ways to stop the crosstalk. [ABSTRACT FROM AUTHOR]

Trove of health data from space tourists and astronauts reveals the effects of microgravity, radiation and more. [ABSTRACT FROM AUTHOR]

Scientists are beginning to crack the fiendishly complex code that helps us to sense odours. [ABSTRACT FROM AUTHOR]

The discovery that an evolutionarily conserved molecule used to make cholesterol also acts as a defence against a cell-death mechanism called ferroptosis might lead to new ways to treat cancer and other clinical conditions.Molecule used to make cholesterol also protects against cell death. [ABSTRACT FROM AUTHOR]

Background: Petasites japonicus (PJ), also known as Butterbur, has a rich history as a traditional healing remedy across numerous countries. Objectives: This study was designed to evaluate the potential anti-cancer properties of the methanol extract derived from PJ (PJE). Materials and Methods: Cell viability was measured with 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide. Cell cycle analysis, caspase activity assays, western blotting, and reactive oxygen species (ROS) assays were also used to investigate the anticancer effects of PJE on cancer cells. Results: It was shown that PJE inhibited the cell viability of the colon carcinoma cell line Caco-2 (half-maximal inhibitory concentration [IC50]: 268.4 µg/mL), of the hepatocellular carcinoma cell line Hep3B (IC50: 420.2 µg/mL), and of the bladder carcinoma cell line 5637 (IC50: 99.43 µg/mL). Analysis of DNA content indicated an increase in the sub-G1 population of 5637 cells as a result of PJE treatment. Furthermore, PJE caused a reduction in mitochondrial membrane potential and the ratio of Bcl-2 to Bax. Moreover, PJE enhanced the levels of various components involved in the proapoptotic cascade, such as caspase-3, caspase-9, and poly-adenosine diphosphate-ribose polymerase. Moreover, it was observed that PJE modulated mitogen-activated protein kinases (MAPKs) activation and induced an elevation in intracellular production of ROS. Conclusion: These combined results strongly suggest that PJE possesses significant proapoptotic properties as an herbal medicine, acting through ROS-dependent MAPK signaling pathways in bladder cancer cells. [ABSTRACT FROM AUTHOR]

Background: This study aimed to evaluate dentin wear and biological performance of desensitizing materials. Methods: Seventy bovine root dentin blocks were sectioned. Half of the surface of each specimen was untreated (control) and the other half was immersed in EDTA and treated with the following desensitizing materials: placebo varnish (PLA), fluoride varnish (FLU), sodium fluoride (NaF) varnish + sodium trimetaphosphate (TMP), universal adhesive (SBU), S-PRG varnish (SPRG), biosilicate (BIOS), and amelotin solution (AMTN). After application, the specimens were submitted to an erosive-abrasive challenge and the wear analyzed by optical profilometer. Serial dilutions of extracts obtained from the culture medium containing discs impregnated with those desensitizers were applied on fibroblasts and odontoblasts-like cells cultures. Cytotoxicity and production of total protein (TP) by colorimetric assays were determined after 24 h. Data were statistically analyzed using Kruskal-Wallis, Dunn's, One-way ANOVA and Tukey tests (p ≤ 0.05). Results: No dentin wear was observed only for SBU. The lowest dentin wear was observed for AMTN and TMP. Cell viability was significantly reduced after treatment with undiluted extracts of PLA, FLU, TMP and SBU in fibroblasts and TMP and SBU in odontoblast-like cells. SPRG, BIOS and AMTN were cytocompatible at all dilutions tested. Considering TP results, no statistical difference was observed among the groups and high levels for TP were observed after TMP and FLU treatments. Conclusions: Universal adhesive system may protect dentin with opened tubules from wear after challenge. Extracts of adhesive and fluoride varnishes presented cytotoxic mainly on fibroblasts. The enamel protein may be a future alternative to treat dentin with opened tubules because it may cause low wear under erosive-abrasive challenge with low cytotoxic effects. [ABSTRACT FROM AUTHOR]

Adjacent plant cells are connected by specialized cell wall regions, called middle lamellae, which influence critical agricultural characteristics, including fruit ripening and organ abscission. Middle lamellae are enriched in pectin polysaccharides, specifically homogalacturonan (HG). Here, we identify a plant-specific Arabidopsis DUF1068 protein, called NKS1/ELMO4, that is required for middle lamellae integrity and cell adhesion. NKS1 localizes to the Golgi apparatus and loss of NKS1 results in changes to Golgi structure and function. The nks1 mutants also display HG deficient phenotypes, including reduced seedling growth, changes to cell wall composition, and tissue integrity defects. These phenotypes are comparable to qua1 and qua2 mutants, which are defective in HG biosynthesis. Notably, genetic interactions indicate that NKS1 and the QUAs work in a common pathway. Protein interaction analyses and modeling corroborate that they work together in a stable protein complex with other pectin-related proteins. We propose that NKS1 is an integral part of a large pectin synthesis protein complex and that proper function of this complex is important to support Golgi structure and function. [ABSTRACT FROM AUTHOR]

Flow cytometry is a mainstay technique in cell biology research, where it is used for phenotypic analysis of mixed cell populations. Quantitative approaches have unlocked a deeper value of flow cytometry in drug discovery research. As the number of drug modalities and druggable mechanisms increases, there is an increasing drive to identify meaningful biomarkers, evaluate the relationship between pharmacokinetics and pharmacodynamics (PK/PD), and translate these insights into the evaluation of patients enrolled in early clinical trials. In this review, we discuss emerging roles for flow cytometry in the translational setting that supports the transition and evaluation of novel compounds in the clinic. [ABSTRACT FROM AUTHOR]

An unusual form of cell death called ferroptosis can sweep over embryonic tissues in a wave-like manner to ensure proper muscle development — evidence that ferroptosis has a role in normal physiology.Iron-dependent cell death sweeps across tissue to shape embryonic muscle. [ABSTRACT FROM AUTHOR]

Researcher who established the role of cellular senescence in cancer and ageing. [ABSTRACT FROM AUTHOR]

Virtual laboratory simulations (VLs), particularly in Biology education, are gaining popularity. This study focused on assessing students' and teachers' perceptions of VLs, developed by Labster, in a first-year undergraduate cell biology course. The evaluation involved surveys and interviews with 352 respondents. Findings indicate that over 90% of students found VLs user-friendly and visually engaging. However, around 60% noted the need for significant technical resources, which could limit accessibility. Over 80% of students reported that VLs increased their motivation, autonomy, interest, and confidence. While only 72% viewed them as potential replacements for traditional labs, more than 90% preferred using VLs as preparatory material for practical sessions. Teachers generally agreed with these perceptions, emphasizing the need for technical support for effective use. They suggested that VLs are better as pre-lab activities rather than full replacements. Both students and teachers recognized VLs as beneficial for academic performance and learning attitude but noted limitations in technical support for home use. The consensus was that VLs are most effective as complementary material before in-person lab sessions. [ABSTRACT FROM AUTHOR]

Methylene blue is a versatile substance used for various medical purposes for years. It has shown promise as a diagnostic tool and a potential treatment option for illnesses such as methemoglobinemia, cyanide poisoning, and malaria, but primarily neurodegenerative diseases like Alzheimer's. The present study aimed to investigate the hypothesis that hydrogen peroxide-induced neuronal cell death debris could activate inflammation, leading to endothelial cell death. To test this hypothesis, we employed two innovative transwell models, the distant and adjacent models, to replicate intercellular interactions between endothelial and neuronal cells at varying brain ranges. We also analyzed the expression levels of pro-apoptotic genes BAX and BIK in three conditions. Our findings suggest that the proximity between endothelial and neuron cells is crucial in inducing endothelial cell death. We further found that the methylene blue treatment significantly decreased the percentage of cell death in both distant and adjacent models. Moreover, our analysis of IL-2, IL-8, and TNF-alpha expression levels using RT-PCR suggests that MBS may protect endothelial cells by blocking the inflammation pathway, which is critical in regulating inflammation and cell death pathways. Dysregulation of these cytokines and their downstream signaling pathways can lead to cell death and brain damage, contributing to the pathogenesis of inflammatory diseases. Therefore, methylene blue has potential therapeutic benefits as a treatment option for diseases involving neuronal and endothelial cell death. [ABSTRACT FROM AUTHOR]

Rhabdomyosarcoma (RMS) is the most common type of soft tissue sarcoma in children and adolescents. Fusion-negative RMS (FN-RMS) accounts for more than 80% of all RMS cases. The long-term event-free survival rate for patients with high-grade FN-RMS is below 30%, highlighting the need for improved therapeutic strategies. CD73 is a 5' ectonucleotidase that hydrolyzes AMP to adenosine and regulates the purinergic signaling pathway. We found that CD73 is elevated in FN-RMS tumors that express high levels of TWIST2. While high expression of CD73 contributes to the pathogenesis of multiple cancers, its role in FN-RMS has not been investigated. We found that CD73 knockdown decreased FN-RMS cell growth while up-regulating the myogenic differentiation program. Moreover, mutation of the catalytic residues of CD73 rendered the protein enzymatically inactive and abolished its ability to stimulate FN-RMS growth. Overexpression of wildtype CD73, but not the catalytically inactive mutant, in CD73 knockdown FN-RMS cells restored their growth capacity. Likewise, treatment with an adenosine receptor A2A-B agonist partially rescued FN-RMS cell proliferation and bypassed the CD73 knockdown defective growth phenotype. These results demonstrate that the catalytic activity of CD73 contributes to the pathogenic growth of FN-RMS through the activation of the purinergic signaling pathway. Therefore, targeting CD73 and the purinergic signaling pathway represents a potential therapeutic approach for FN-RMS patients. [ABSTRACT FROM AUTHOR]

Summary: Cells’ structure is key to understanding cellular function, diagnostics, and therapy development. Soft X-ray tomography (SXT) is a unique tool to image cellular structure without fixation or labeling at high spatial resolution and throughput. Fast acquisition times increase demand for accelerated image analysis, like segmentation. Currently, segmenting cellular structures is done manually and is a major bottleneck in the SXT data analysis. This paper introduces ACSeg, an automated 3D cytoplasm segmentation model. ACSeg is generated using semi-automated labels and 3D U-Net and is trained on 43 SXT tomograms of immune T cells, rapidly converging to high-accuracy segmentation, therefore reducing time and labor. Furthermore, adding only 6 SXT tomograms of other cell types diversifies the model, showing potential for optimal experimental design. ACSeg successfully segmented unseen tomograms and is published on Biomedisa, enabling high-throughput analysis of cell volume and structure of cytoplasm in diverse cell types.

Fluorescent labels that have greater resistance to bleaching could help researchers to get more from biological imaging. [ABSTRACT FROM AUTHOR]

When chromosomes are lost or gained, massive changes in gene expression disrupt the delicate balance of proteins in a cell. Yeasts with incorrect chromosome numbers counteract this by degrading excess proteins.Aneuploid cells boost protein degradation to rebalance proteome. [ABSTRACT FROM AUTHOR]

Organelles called mitochondria are transferred to blood-vessel-forming cells by support cells. Unexpectedly, these mitochondria are degraded, kick-starting the production of new ones and boosting vessel formation.Mitochondrial transfer enhances endothelial-cell grafts. [ABSTRACT FROM AUTHOR]

Summary: Non-immune cells, like innate immune cells, can develop a memory-like phenotype in response to priming with microbial compounds or certain metabolites, which enables an enhanced response to a secondary unspecific stimulus. This paper describes a step-by-step protocol for the induction and analysis of trained immunity in human endothelial and smooth muscle cells. We then describe steps for cell culture with cryopreserved vascular cells, subcultivation, and induction of trained immunity. We then provide detailed procedures for downstream analysis using ELISA and qPCR.For complete details on the use and execution of this protocol, please refer to Sohrabi et al. (2020)1 and Shcnack et al.2 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

A burgeoning technique called time-resolved cryo-EM is granting insights into the tiny motors and devices that power life. [ABSTRACT FROM AUTHOR]

Direct interactions between cells in tissue are incompletely understood because the advanced technologies required to examine them are still in their infancy. A new method can decipher cell–cell interactions on a large scale.Tagging method offers versatile way to track interactions between cells. [ABSTRACT FROM AUTHOR]

How do mitochondrial organelles remove damaged parts of inner membrane for recycling in the cytoplasm? The discovery of an exit route that flips inner membrane outside the organelle provides some answers. Pathway selectively removes inner membrane from mitochondrial organelles. [ABSTRACT FROM AUTHOR]

Cells that form tissue barriers rely on cell–cell contacts called tight junctions. These structures assemble from protein condensates that spread along the cell membrane like a water droplet spreading over glass.Step-by-step formation of tight junctions between epithelial cells. [ABSTRACT FROM AUTHOR]

The enzyme angiogenin functions in stress responses and aids the formation of blood vessels. It emerges that the ribosome takes a break from its usual role of making proteins to activate angiogenin and position it to cleave transfer RNA.The ribosome activates an enzyme that cleaves transfer RNA. [ABSTRACT FROM AUTHOR]

Once a plant recognizes a pathogen, part of its defence strategy is to withhold iron. The mechanism involves suppression of root acquisition of iron by degrading a molecule that activates the iron-uptake pathway. Plants attacked by bacteria degrade a protein needed for iron uptake. [ABSTRACT FROM AUTHOR]

DNA in the cytoplasm can be a sign of abnormalities such as viral infections or cancer. A protein with a role in DNA-damage response was unexpectedly found to activate defences against the threats indicated by cytoplasmic DNA. The MRN protein complex helps to activate the enzyme cGAS. [ABSTRACT FROM AUTHOR]

A suppressive type of immune cell called a regulatory T cell has a key role in helping muscles to adapt to exercise — guarding muscle mitochondrial organelles against damage mediated by proinflammatory factors generated during physical activity. Regulatory T cells protect mitochondria from damage caused by interferon. [ABSTRACT FROM AUTHOR]

Modified components of messenger RNA can cause the protein-production machinery to stall during the process of translation. This might change the protein being made, a finding with implications for vaccines or therapies. Modified mRNA component affects the fidelity of protein production. [ABSTRACT FROM AUTHOR]