Search Results (630)

The unicellular ciliate Paramecium caudatum undergoes a developmental transition from asexual binary fission to sexual reproduction during its mature stage. This transition is triggered by mating interactions between cells of complementary mating types, leading to aggregate formation, mating pairs, and the meiotic division of micronuclei. Although calcium-driven EF-hand kinases have been implicated as mating type proteins, the spatiotemporal dynamics of calcium signaling during conjugation have not been comprehensively characterized. In this study, we established a behavioral assay to isolate committed cells from aggregates immediately after mating onset, and developed an experimental system to monitor intracellular calcium fluctuations specifically expressed in these cells. By combining Ca²⁺/EGTA buffering and microinjection approaches, we manipulated extracellular and intracellular calcium levels and confirmed the continuous requirement of calcium ions for conjugation-specific functions. Two significant findings emerged. First, we identified, for the first time, a calcium atlas covering the entire cell, with ascending centers localized in the anterior, oral apparatus, and posterior regions. The calcium/Indo-1-AM fluorescence peaked at 6 h after mating initiation and declined gradually, but persisted until conjugation was completed at ~48 h. Second, we demonstrated that distinct intracellular calcium thresholds are required for each stage of mating, including maintenance of mating activity, commitment of micronuclei to meiosis, and two-stepwise formation of mating pairs. These thresholds function as regulatory checkpoints that coordinate subcellular localization and stage synchronization. Collectively, our findings highlight calcium ions as pivotal regulators of conjugation in Paramecium and propose a novel framework, the Paramecium calcium atlas, for understanding the cellular and molecular mechanisms underlying sexual reproduction in ciliates. Full article

Gibberellin (GA)-based seedless cultivation is widely used in the skin-edible interspecific table grape (Vitis labruscana × Vitis vinifera) ‘Shine Muscat’, yet when and how GA treatment reshapes fracture-type texture during berry development remains unclear. This study aimed to identify developmental stages and tissue/cell-wall features associated with GA-dependent differences in berry fracture behavior. We integrated intact-berry fracture testing at harvest (DAFB105), quantitative histology of pericarp/mesocarp tissues just before veraison (DAFB39) and at harvest, sequential cell-wall fractionation assays targeting pectin-rich (uronic acid) and hemicellulose/cellulose-related pools at cell division period, cell expansion period and harvest, and stage-resolved RNA-Seq across the same three developmental stages. GA-treated berries had a larger diameter and showed a higher fracture load and a lower fracture strain than non-treated berries at harvest, while toughness did not differ significantly. Histology revealed thicker pericarp tissues and lower mesocarp cell density in GA-treated berries, together with increased cell-size heterogeneity and enhanced radial cell expansion. Cell wall analyses showed stage-dependent decreases in uronic acid contents in water-, EDTA-, and Na₂CO₃-soluble fractions in GA-treated berries. Transcriptome profiling indicated GA-responsive expression of putative cell expansion/primary-wall remodeling genes, EXORDIUM and xyloglucan endotransglucosylase/hydrolases, at DAFB24 and suggested relatively enhanced ethylene-/senescence-associated transcriptional programs together with pectin-modifying related genes, Polygaracturonase/pectate lyase and pectin methylesterase, in non-treated mature berries. Collectively, GA treatment modifies mesocarp cellular architecture and pectin-centered wall status in a stage-dependent manner, providing a tissue- and cell wall–based framework for interpreting fracture-related texture differences under GA-based seedless cultivation in ‘Shine Muscat’. Full article

Biophotons are non-thermal and non-bioluminescent ultraweak photon emissions, first hypothesised by Gurwitsch as a regulatory mechanism in cell division, and then experimentally observed in living organisms. Today, two main hypotheses explain their origin: stochastic decay of excited molecules and coherent electromagnetic fields produced in biochemical processes. Recent interest focuses on the role of biophotons in cellular communication and disease monitoring. This study presents the first campaign of biophoton emission measurements from cultured astrocytes and glioblastoma cells, conducted at Fondazione Pisana per la Scienza (FPS) using two ultra-sensitive setups developed in collaboration between the National Laboratories of Frascati (LNF-INFN) and the University of Rome II Tor Vergata. The statistical analyses of the collected data revealed a clear separation between cellular signals and dark noise, confirming the high sensitivity of the apparatus. The Diffusion Entropy Analysis (DEA) was applied to the data to uncover dynamic patterns, revealing anomalous diffusion and long-range memory effects that may be related to intercellular signaling and cellular communication. These findings support the hypothesis that biophoton emissions encode rich information beyond intensity, reflecting metabolic and pathological states. The differences revealed by applying the Diffusion Entropy Analysis to the biophotonic signals of Astrocytes and Glioblastoma are highlighted and discussed in the paper. This work lays the groundwork for future studies on neuronal cultures and proposes biophoton dynamics as a promising tool for non-invasive diagnostics and the study of cellular communication. Full article

The progression of neoplastic diseases is driven by a complex interplay of biological processes, including uncontrolled proliferation, enhanced invasion, metastasis, and profound metabolic reprogramming. Among the hallmarks of cancer, as revised by Hanahan and Weinberg, the reprogramming of energy metabolism has emerged as a critical feature that enables cancer cells to meet their heightened bioenergetic and biosynthetic demands. One significant aspect of this metabolic adaptation is the accumulation of lipid droplets (LDs) dynamic, cytoplasmic organelles primarily involved in lipid storage and metabolic regulation. LDs serve as reservoirs of neutral lipids and play a multifaceted role in cancer cell physiology. Their accumulation is increasingly recognized as a marker of tumor aggressiveness and poor prognosis. By storing lipids, LDs provide a readily accessible source of energy and essential building blocks for membrane synthesis, supporting rapid cell division and growth. Moreover, LDs contribute to cellular homeostasis by modulating oxidative stress, maintaining redox balance, and regulating autophagy, particularly under nutrient-deprived or hypoxic conditions commonly found in the tumor microenvironment. Importantly, LDs have been implicated in the development of resistance to cancer therapies. They protect cancer cells from the cytotoxic effects of chemotherapeutic agents by buffering endoplasmic reticulum (ER) stress, inhibiting apoptosis, and facilitating survival pathways. The presence of LDs has been shown to correlate with increased resistance to a variety of chemotherapeutic drugs, although the precise molecular mechanisms underlying this phenomenon remain incompletely understood. Emerging evidence suggests that chemotherapy itself can induce changes in LD accumulation, further complicating treatment outcomes. Given their central role in cancer metabolism and therapy resistance, LDs represent a promising target for therapeutic intervention. Strategies aimed at disrupting lipid metabolism or inhibiting LD biogenesis have shown potential in sensitizing cancer cells to chemotherapy and overcoming drug resistance. In this review, we comprehensively examine the current understanding of LD biology in cancer, highlight studies that elucidate the link between LDs and drug resistance, and discuss emerging approaches to target lipid metabolic pathways to enhance therapeutic efficacy across diverse cancer types. Full article

Platelet-rich fibrin (PRF) is widely used in regenerative dentistry and oral surgery for its ability to promote tissue healing and modulate cellular responses. However, PRF contains not only platelets but also leukocytes and plasma components, complicating efforts to define the specific contribution of platelets to its biological activity. To address this, we used washed, leukocyte-depleted platelets activated with thrombin to generate platelet-released supernatant (PRS), which was applied to gingival fibroblasts. RNA sequencing identified 147 upregulated and 39 downregulated genes (|log₂ fold change| ≥ 2, FDR < 0.001), including cytokines IL11 and CXCL8 previously associated with PRF, as well as mitosis-related genes such as centromere-associated proteins, cell division cycle proteins, kinesin-like proteins, and shugoshins, consistent with gene ontology analyses. Validation by RT-PCR and immunoassays confirmed robust upregulation of IL11 and CXCL8. Functionally, PRS activated TGF-β signaling, indicated by Smad2/3 nuclear translocation, but did not induce NF-κB signaling. These findings demonstrate that platelets are major contributors to PRF’s biological effects, independent of leukocytes and plasma, and elicit a pronounced mitogenic and TGF-β-dominant response in gingival fibroblasts. They also provide insight into the cellular mechanisms underlying PRF-mediated tissue regeneration. Full article

This study was conducted to elucidate the molecular and metabolic differences in ileal development according to birth weight in neonatal piglets. A total of 126 neonatal piglets born from Yorkshire × Landrace × Duroc crossbred sows were used, and the top 5% (H group, 1.77 ± 0.02 kg) and bottom 5% (L group, 0.72 ± 0.03 kg) of birth weights were selected for analysis. Ileal tissues were collected for transcriptomic (RNA-seq) and targeted metabolomic (GC–MS) analyses, and selected genes were validated using RT-qPCR. A total of 112 differentially expressed genes (DEGs) were identified, among which RFC3, PCNA, MCM3, MCM10, AURKA, AURKB, CCNB2, CCNA2, CCNF, and SI were significantly upregulated in the H group (p < 0.05). These genes were mainly involved in pathways related to DNA replication, cell division, and nutrient digestion and absorption. In addition, metabolomic analysis revealed that pyruvic acid concentrations were significantly higher in the H group (p < 0.05), indicating the activation of energy metabolic pathways. These results indicate that high-birth-weight piglets possess a genetic foundation for enhanced cellular proliferation and energy metabolism, and they further highlight potential molecular targets for improving growth performance and intestinal development in low-birth-weight piglets. Full article

The anti-aging gene/protein Klotho (Kl), most present in kidneys, has been well studied in mice (mKl), but not in rats (rKl). This study investigated the renal rKl expression in male and female rats. Sex-related measurement of rKl-controlled electrolytes was performed in plasma/urine samples, as were tests on species differences in renal Kl expression (rats vs. mice). rKl mRNA/protein expression was studied by qRT-PCR/Western-blotting in renal total RNA/cell membranes and its localization by immunofluorescence microscopy. Urine/plasma ions (phosphate/total calcium) and macroelements (phosphorus/calcium) were measured biochemically and by ICP-MS, respectively. In rat kidneys, the rKl mRNA/protein was detected in the cortex, outer and inner stripe but not in the papilla, and was immunolocalized in the basolateral membrane of proximal tubules in the cortex and outer stripe, but not in the intercalating cells of the cortical distal tubules, whereas mKl was observed in the mouse kidney cortex but not the outer stripe. Female-dominant expression of renal rKl, affected by androgen’s inhibitory effect, may have contributed to the sex-related level of urine electrolytes, particularly phosphates. Renal mKl expression was male-dominant. Sex- and species-related differences in renal Kl expression may be relevant for the selection of the sex and/or the model organism in studies addressing aging/mineral homeostasis. Full article

To date, there is extensive scientific evidence affirming that physical exercise plays a fundamental role in both the prevention and treatment of various pathological conditions in humans as well as in animals. It is understood that the advantages of movement and exercise have a multifactorial origin and they depend on a category of bioactive molecules vehicolated by extracellular microvesicles known as exosomes. The exosomes act as potential delivery systems for messages within the organism. These findings have drawn significant attention, leading researchers to further investigate the role of exosomes, delving into the study of microRNAs (miRNAs). In particular, these molecules are found inside exosomes and play a key role in cellular communication, with an impact on numerous physiological functions of the organism. It has been suggested that during physical exercise, the expression levels of miRNAs increase in parallel with those of exosomes, and their release enables intercellular communication in multicellular organisms, thereby regulating both cell growth and division. Studies have not only been carried out in humans, but also in laboratory animals and in mammals following exercise. Specifically, a change in exosome expression has been found in athletic horses following physical exercise. The aim of the current review was to highlight what is known about the role played by exosomes and miRNAs during physical exercise in equine species by considering, on a broad scale, the published data on this topic, including comparative data from humans and rodent models. Full article

Head and neck cancer (HNC) affects nearly 1 million people every year. The main risk factors include tobacco, alcohol, or human papilloma virus (HPV) viral infections, which contribute to HNC development through various, mostly unknown, mechanisms. One of these postulated mechanisms is cellular senescence. This biological aging-associated process is responsible not only for the arrest of cellular growth and division but also mediates the modulation of cell metabolism and secretory phenotype. Consequently, it may play a crucial role in carcinogenesis, which makes it an interesting topic in the context of cancer development, prognosis, prevention, and therapy. This review focuses on the current state of knowledge regarding all aspects of the association between cellular senescence and head and neck cancer. Full article

Cellular memory, or epigenetic memory, represents the capacity for cells to retain information beyond the underlying DNA sequence. This heritable characteristic is primarily governed by epigenetic mechanisms which enable cells to maintain specialized characteristics across divisions. This persistent cellular state is essential for fundamental biological processes, such as maintaining tissue identity and facilitating cell differentiation, especially embryonic cells. Early-stage perturbations such as assisted reproductive technologies (ART) and nutritional stress links embryonic exposures to adult health and disease within the Developmental Origins of Health and Disease (DOHaD) framework. Crucially, memory established during early embryogenesis links these epigenetic modifications to adult long-term phenotypes related to metabolic disorders. These modifications—including DNA methylation, histone modifications, and non-coding RNAs—support cellular memory transmission across cell divisions, and in certain organisms, can be transmitted across generations without alterations to the DNA sequence. This review synthesizes recent advances in epigenetic pathways that mediate cellular memory, highlights critical preimplantation windows of vulnerability and outlines gaps necessary for mammalian developing interventions that safeguard future generations. Full article

Microgravity during space travel induces significant regulatory changes in the body, posing health risks for astronauts, including alterations in cell morphology and cytoskeletal integrity. The Small Ubiquitin-like Modifier (SUMO) is crucial for cellular adaptation, regulating DNA repair, cytoskeletal dynamics, cell division, and protein turnover—all processes affected by microgravity. To determine the extent to which SUMO mediates the cellular response to microgravity stress, Saccharomyces cerevisiae cells were cultured under normal gravity and simulated microgravity (SMG) in rotating wall vessels. After 12 h of culture, we investigated changes in SUMO modified proteins and protein expression. We identified 347 SUMOylated proteins, 18 of which demonstrated a 50% change in abundance under SMG. Of 3773 proteins identified, protein expression for 34 proteins decreased and 8 increased by over 50% in SMG (p < 0.05). Differentially expressed proteins represented changes in cellular processes for DNA repair, cell division, histone modification, and cytoskeleton regulation. These findings underscore the pivotal role of SUMOylation in orchestrating cellular adaptation to the unique stress of microgravity, revealing potential targets for mitigating spaceflight-induced health risks. Full article

This paper presents an advanced signal processing framework for multi-channel forward-scatter radar (MC-FSR) systems based on the Multiple Signal Classification (MUSIC) algorithm. The proposed framework addresses the inherent limitations of FFT-based space-domain processing, such as limited angular resolution and the poor detectability of weak or closely spaced targets, which become particularly severe in low-cost FSR systems, which are typically operated with small antenna arrays. The MUSIC algorithm is adapted to operate on real-valued data obtained from the non-coherent, amplitude-based MC-FSR approach by reformulating the steering vectors and adjusting the degrees of freedom (DoFs). While compatible with arbitrary transmitting waveforms, particular emphasis is placed on Orthogonal Frequency Division Multiplexing (OFDM) signals, which are widely used in modern communication systems such as Wi-Fi and cellular networks. An analysis of the OFDM waveform’s autocorrelation properties is provided to assess their impact on target detection, including strategies to mitigate rapid target signature decay using a sub-band approach and to manage signal correlation through spatial smoothing. Simulation results, including multi-target scenarios under constrained array configurations, demonstrate that the proposed MUSIC-based approach significantly enhances angular resolution and enables reliable discrimination of closely spaced targets even with a limited number of receiving channels. Experimental validation using an S-band MC-FSR prototype implemented with software-defined radios (SDRs) and commercial Wi-Fi antennas, involving cooperative targets like people and drones, further confirms the effectiveness and practicality of the proposed method for real-world applications. Overall, the proposed MUSIC-based MC-FSR framework exhibits strong potential for implementation in low-cost, hardware-constrained environments and is particularly suited for emerging Integrated Sensing and Communication (ISAC) systems. Full article

Thraustochytrium aureum ssp. strugatskii, a marine protist belonging to the class Labyrinthulea, exhibits a complex life cycle characterized by alternating motile and vegetative phases. Using an integrative multimodal microscopy approach, we reconstructed its full developmental cycle and analyzed the coordination between cellular morphology, subcellular architecture, and population-level behavior. Transmission and scanning electron microscopy, combined with fluorescence and time-lapse imaging, revealed the dynamics of nuclear division, organelle rearrangement, and zoospore formation. Morphometric analysis of serial ultrathin sections demonstrated distinct changes in mitochondrial distribution, Golgi apparatus, and lipid droplet abundance during transitions between stages. We have shown that vegetative cells undergo synchronized karyokinesis coupled with stable nuclear-to-cytoplasmic ratios, leading to the emergence of multinucleate stages prior to zoospore formation. The integration of ultrastructural and dynamic data enabled us to propose a systems-level model linking metabolic state, morphogenesis, and population structure. This model highlights feedback regulation between nutrient availability, biomass accumulation, and developmental synchronization. Our results establish that T. aureum ssp. strugatskii has good potential to serve as a tractable model organism for systems-level studies of protists and provide an initial framework for predictive modeling of its life cycle under controlled conditions. Full article

The RCC1 gene is active in ensuring many cellular functions related to cell division in Drosophila melanogaster and Homo sapiens. A detailed comparison of the structure and functions of the RCC1 gene in Drosophila melanogaster and Homo sapiens was carried out using different analytical techniques (bioinformatics, immunofluorescence and confocal microscopy, FISH, and molecular genetic methods). The Drosophila RCC1 gene belongs to the family of housekeeping genes, since it resides in the interbands and gray bands of polytene chromosomes within aquamarine/lazurite chromatin in D. melanogaster. Furthermore, the databases demonstrate that RCC1 in D. melanogaster is expressed in all the tissues at all the developmental stages. According to The Human Protein Atlas, RCC1 in humans also exhibits low tissue specificity for 29 tissues. Immunostaining of polytene chromosomes with RCC1 antibodies revealed approximately 260 sites of RCC1 protein localization exclusively in black bands (sites of developmental genes) and in heterochromatin. The size of the coding gene portions is almost identical for D. melanogaster and H. sapiens, being ~2 kb. The group of Drosophila proteins related to condensed chromatin, RCC1 being a member of this group, has homologs forming similar interaction networks in humans. The conserved nature of the RCC1 gene has been confirmed by cell cycle studies in both species. It was found that expression of the RCC1 gene is upregulated in glioblastoma; the RCC1 protein predominantly resides on centrioles during metaphase. Full article

Mutations in the gene encoding the p150 subunit of the dynactin complex (DCTN1) are linked to amyotrophic lateral sclerosis, spinal and bulbar muscular atrophy, and Perry syndrome. These neurodegenerative diseases can cause muscle weakness and atrophy, parkinsonian-like symptoms, and paralysis. To examine the evolution of neuropathology caused by a mutation in DCTN1 and cellular mechanisms of disease for therapeutic discovery, we characterized mice expressing either human wildtype or mutant (G59S) DCTN1. Neuron-specific expression of mutant, but not wildtype, DCTN1 caused fatal age-related paralytic disease and motor neuron (MN) degeneration in the spinal cord with axonopathy and chromatolysis without apoptotic morphology. MNs became positive for cleaved caspase-3, cleaved caspase-8, and nitrated Hsp90. Mitochondria accumulated and appeared fragmented and dysmorphic and then were lost. This pathology was accompanied by invasion of CD95- and CD8-positive mononuclear T cells into the ventral horn and accumulation of TNFα and IL9. Administration of the mitochondrial division inhibitor-1 (Mdivi-1) protected MNs and extended the lifespan of G59S-DCTN1 mice. A mitochondrial permeability transition pore inhibitor also extended lifespan. Thus, mutant DCTN1 causes degeneration of MNs associated with axonopathy, mitochondriopathy, nitrative stress, and caspase activation. It appears as retrograde neurodegeneration and inflammatory T-cell-like cytolysis. Mitochondria are possible therapeutic targets in DCTN1-linked neurodegenerative disorders. Full article