Search Results (2,524)

Goat reproductive performance is a key determinant of the productivity and economic value of goat farming, especially in meat and milk production. In a previous study, to investigate the genetic basis of prolificacy, we divided goats into groups according to their consistent reproductive performance (producing either single kids or twins) over five consecutive kidding cycles, and performed whole-genome resequencing and RNA-seq analysis on their ovarian tissues. Through integrated analysis, we identified three candidate genes—IGF2BP1 (insulin-like growth factor 2 mRNA-binding protein 1), CDC25A (cell division cycle 25A), and RXFP2 (relaxin family peptide receptor 2)—as potential key regulators of reproductive capacity. Using goat ovarian granulosa cells, we systematically assessed the impact of each gene through gain- and loss-of-function experiments. Overexpression of IGF2BP1 promoted cell proliferation and suppressed apoptosis, underscoring its role in maintaining cellular viability. Conversely, its knockdown significantly impeded growth and induced cell death. Similarly, CDC25A enhanced granulosa cell proliferation, whereas its knockdown led to marked growth impairment and increased apoptosis. Proliferation was also enhanced by RXFP2 overexpression but impaired upon its knockdown, suggesting that RXFP2 is functionally important for follicular development. Collectively, these findings establish IGF2BP1, CDC25A, and RXFP2 as fundamental regulators of granulosa cell dynamics and ovarian follicular development, providing crucial functional insights and promising targets for genetic selection to enhance reproductive efficiency in goats. Full article

Retromer is an evolutionarily conserved protein complex first identified in budding yeast. It was originally described for its essential role in endosome-to-Golgi retrieval of lysosomal hydrolase receptors. Retromer is now known to mediate trafficking of many endosomal cargoes. The mammalian retromer is constituted by a core heterotrimer encoded by the vacuolar protein sorting (VPS) gene products VPS26, VPS35, and VPS29. To mediate cargo recognition and endosomal sorting into various pathways, this trimer can cooperate with phosphoinositide-binding sorting nexin family members. Defective retromer functioning has been associated with alterations in cellular homeostasis, leading to disease. To gain insights into how it may mediate these broad processes, a proteomic strategy in polarized Madin-Darby canine kidney cells was devised to identify retromer-interacting proteins. Subsequent validation of one of the candidates, i.e., cytokeratin 19, led to the unexpected finding that retromer localizes to the pericentriolar region in dividing cells and subsequently translocates to the midbody during cytokinesis. Retromer was found interacting with CK19, and its antisense depletion led to delocalization from CK19. Subcellular fractionation and live cell monitoring of depleted cells provided evidence of a role by retromer in post-metaphase progression and in epithelial cell migration, thereby connecting retromer with key processes of cellular dynamics. Full article

Syspastoxyelidae is an extinct basal hymenopteran lineage currently known only from mid-Cretaceous Burmese amber. Here, we describe a new genus and species, Cilioxyela setosa gen. et sp. nov., based on a well-preserved female specimen from the Hukawng Valley, northern Myanmar. The new taxon is assigned to Syspastoxyelidae based on diagnostic characters, including strongly proximally condensed forewing venation, a composite first flagellomere formed by fused ancestral segments, tibiae bearing dense robust spines, and segmented cerci. Cilioxyela gen. nov. differs from all previously described genera by a unique character combination, most notably, a distal forewing veinless membrane lacking longitudinal corrugation and conspicuously elongated marginal setae, together with a narrowed forewing, elongate pterostigma and anal cell, and distinctive antennal segmentation. These features support the establishment of a new genus. Comparative analysis indicates that distal forewing morphology in Syspastoxyelidae is more variable than previously recognized. The presence or absence of longitudinal corrugation in the distal forewing membrane likely reflects genus-level differentiation rather than a stable family-level synapomorphy. The new genus also supports a tentative division of Syspastoxyelidae into at least two morphologically cohesive groups, pending testing through additional fossil discoveries and quantitative phylogenetic analyses. The discovery of Cilioxyela setosa expands the known morphological disparity of Syspastoxyelidae and highlights evolutionary plasticity in distal forewing architecture among early Hymenoptera, contributing to a better understanding of morphological diversification in mid-Cretaceous forest ecosystems. Full article

Background/Objectives: Nitrogen, as an indispensable macroelement for plants, is essential for tuber development. The objective of the present study was to ascertain the key factors underlying nitrogen regulation of potato tuber formation. Methods: The potato variety Kexin 37 was used as the material, and nitrogen deficiency, normal nitrogen level and excessive nitrogen level were employed as treatments, respectively. The response of potato tuber formation to nitrogen was systematically analyzed from the perspective of physiology and transcriptomics. Results: Nitrogen deficiency led to the thickening of the cell wall and plasma membrane, an increase in intercellular space and a decrease in mitochondria in the stolon. The plant height, chlorophyll content, dry matter quality and nitrogen accumulation were significantly reduced, and the number of tubers per plant, tuber weight per plant and commodity rate were significantly reduced. Excessive nitrogen application resulted in late maturity of plants and excessive formation of small potatoes. Transcriptome analysis revealed that differentially expressed genes related to nitrogen stress were mainly enriched in pathways associated with material transport, cell division and carbohydrate metabolism. In addition, there are a series of hub genes in response to nitrogen stress, including polyubiquitin-like, auxin response factor 7-like and protein RRP6-like 2. By constructing a co-expression network, transcription factors (TFs) such as C2H2, WRKY and ARF are involved in regulating tuber formation. Conclusions: The present study constitutes an investigation into the identification of hub genes and potential pathways associated with the formation of potato tubers under varying nitrogen conditions. It provides new insights for further study on enhancing nitrogen use efficiency in potato. Full article

The design and optimization of microalgae processes are usually focused on maximizing biomass productivity, neglecting the impact of cell-to-cell heterogeneity. Flow cytometry (FCM) represents a powerful and high-throughput tool for analyzing and examining microalgae intrinsic characteristics, such as their physiology, metabolism and response at the single-cell level. The aim of this work is to develop a novel FCM sensor-based single-cell analysis method to monitor and study the effect of several process conditions, mainly variations of light spectral composition (blue, red and green), nitrogen depletion and moderate osmotic stress conditions (0.2 M NaCl), on the subpopulation structure and dynamics of the green microalgae Chromochloris zofingiensis, a natural source for lipids, proteins and carotenoids. The FCM procedures developed in this study proved to be effective for monitoring the population dynamics of microalgae, demonstrating how the process conditions have a direct and significant impact on population heterogeneity of C. zofingiensis on a single-cell level. Cell division was found to be adversely affected by the moderate osmotic stress (N⁺S⁺), nitrogen depletion (N⁻), and their combined occurrence (N⁻S⁺), independent of the light spectral composition used for culture illumination. In terms of cell-to-cell heterogeneity, a higher proportion of large cells (~20 µm) was observed under green light across all conditions with 21%, 29%, 35% and 52% under N⁻, N⁻S⁺, N⁺S⁺ and N⁺ conditions, respectively, followed by red light combined with osmotic stress (46%), whereas blue light consistently led to a predominance of smaller cells (≤4 µm) with 30%, 47%, 50% and 55% under N⁺S⁺, N⁺, N⁻S⁺ and N⁻ conditions, respectively. Full article

Cell division is a highly regulated process that actively involves dynamic changes to the genetic material within the nucleus. DNA is faithfully replicated in the S-Phase of the cell cycle, being converted from loose, relaxed chromatin into tight, condensed chromosomes to be segregated in mitosis. In addition to scaffolding proteins that shape these mitotic chromosomes, post-translational modifications of histones within nucleosomes modulate chromosome dynamics throughout the cell cycle. In this review, we use a comparative approach to highlight some of the major epigenetic marks affected by the cell cycle during embryogenesis of Caenorhabditis elegans: H4K20me1, H3S10ph, H4S1ph, H2AS1ph, and H3T118ph. These five histone post-translational modifications will be specifically highlighted in the context of the mitotic cell cycle, as they are well documented in the C. elegans literature. Full article

The vascular cambium serves as the fundamental meristem for wood formation. It determines wood biomass and structural properties by balancing self-renewal with the bidirectional production of xylem and phloem. This process is controlled by a complex network of peptides, transcription factors, and phytohormones. These regulatory networks coordinate cambial stem cell activity, balancing cell division and differentiation. Additionally, layers of regulation such as chromatin state, protein stability, and non-coding RNAs add significant complexity to these networks. Emerging single-cell and spatial transcriptomics, together with quantitative modeling, now resolve cambial heterogeneity, predicting the dynamic characteristics of wood formation. This review synthesizes current knowledge of cambial regulation, highlighting how feedback loops, spatial gradients, and dynamic signaling networks collectively orchestrate the predictive potential for improving cambial activity and wood formation. Full article

DENSE AND ERECT PANICLE 2 (DEP2) is a key pleiotropic gene regulating panicle architecture and grain shape in rice. To explore its favorable allelic variations, a stably inherited mutant with short, round and thick grains (srt) was identified in this study using the Japonica rice variety ‘Zhonghua 11’ (ZH11) as the genetic background. Compared with ZH11, srt exhibited reduced plant height and a shorter panicle length but significantly increased numbers of primary branches, secondary branches, and grains per panicle. The mutant grains showed decreased length, increased width, and thickness, ultimately leading to reductions in both thousand-grain weight and grain yield per plant. Cytological analysis revealed that both the longitudinal and transverse dimensions of hull cells in srt were significantly enlarged, while the number of longitudinal cells per unit length decreased. This suggests that srt remodels grain shape by altering the balance between cell division and expansion. Genetic analysis indicated that the phenotype is controlled by a single recessive gene. Map-based cloning and whole-genome resequencing localized the target gene to chromosome 7 and confirmed that srt is the DEP2 gene. Sequence analysis revealed the presence of a large fragment insertion of approximately 87 kb entirely within the seventh exon region of the DEP2 gene in srt. However, unlike most reported DEP2 mutants, in which the numbers of primary branches, secondary branches, and grains per panicle showed no significant difference from the wild type, the srt mutant exhibited a significant increase in all these traits. This unique phenotypic combination expands the understanding of the functional diversity of this gene. This study provides new genetic material for further elucidating the molecular mechanisms by which DEP2 regulates panicle development and for molecular design breeding of rice grain shape. Full article

Protein Kinase N1 (PKN1) is a PKC-related serine/threonine kinase of the AGC group within the eukaryotic protein kinase superfamily (ePK) that orchestrates oncogenic, metabolic, and cytoskeletal signaling. Despite these critical roles, the phosphorylation-dependent regulatory network of PKN1 remains largely undefined. We performed a large-scale phosphoproteomic data integration of publicly available human datasets (892 profiling datasets and 191 differential datasets) to identify recurrent PKN1 phosphorylation sites. This analysis identified two predominant PKN1 phosphosites, S562 and S916, that were frequently observed and differentially regulated across studies. The S916 maps to a turn motif (TM) in the AGC group of kinases, which is evolutionarily conserved among PKN paralogs, while S562 is non-conserved and appears to be PKN1-specific. Co-regulation and enrichment analyses suggest that S916 is associated with insulin/AMPK signaling and metabolic pathways, whereas S562 co-occurs with phosphosites involved in cell division, cytoskeletal regulation, and microtubule cytoskeleton organization. Integrating predicted and experimentally validated kinases, substrates, and interactors, we reconstructed a phospho-regulatory network that positions PKN1 at the crossroads of cytoskeleton organization and metabolic signaling. To assess the disease relevance of these phosphorylation events, we integrated transcriptomic and phosphoproteomic data from the hepatocellular carcinoma database (HCCDB). PKN1 was markedly up-regulated in HCC, and its phosphorylation at S916 was positively co-regulated with multiple oncogenic and proliferation-associated protein phosphosites. These results predict S562 and S916 as potential sites for targeted biochemical validation and functional experiments. The identification of S562 and S916 as key regulatory sites provides new mechanistic insight into PKN1 activation and highlights potential avenues for therapeutic targeting. Full article

This article presents a comprehensive and analytically explicit study of optimal discrete quantization on spherical geometries equipped with the geodesic metric. Focusing on highly symmetric configurations on the unit sphere ${\mathbb{S}}^2$, we investigate three explicit models of discrete uniform distributions and derive closed-form expressions for their optimal quantizers and corresponding mean square quantization errors. (I) For N equally spaced points on the equator, we obtain exact error formulas for both divisible and non-divisible cases $n\nmid N$, demonstrating that optimal Voronoi cells form contiguous arcs with midpoint representatives. (II) For two antipodally symmetric small circles at latitudes $\pm {\varphi }_0$, each with M longitudes, we prove a no-cross-circle Voronoi phenomenon, establish symmetry-preserving optimality, and derive finite-sum error formulas together with sharp curvature-dependent bounds and asymptotics. (III) For a single small circle at latitude ${\varphi }_0$, we obtain analogous exact error formulas and show that curvature reduces distortion by a factor of ${cos}^2{\varphi }_0$, while preserving the $n^{-2}$ decay rate. Across all models, we rigorously establish the “block midpoint principle”: optimal Voronoi cells on a circle are contiguous azimuthal blocks, and their optimal representatives are the corresponding azimuthal midpoints. Numerical tables and illustrative figures highlight curvature effects and compare divisible and non-divisible cases. An algorithmic appendix provides pseudocode and a small, commented Python implementation to facilitate reproducibility. Written with didactic clarity while maintaining full mathematical rigor, this work bridges geometric intuition and analytic precision, providing explicit benchmark models that illuminate curvature effects and support further developments in quantization on curved manifolds. Full article

Background: Osteosarcoma is the most common primary malignant bone tumor in children and adolescents. At present, multi-agent chemotherapy and surgery provide only limited effects and the prognosis for patients with recurrent or metastatic disease remains poor, with 5-year survival rates below 30%. These challenges highlight the need for innovative therapeutic approaches targeting osteosarcoma more effectively. Fenretinide, a synthetic derivative of all-trans retinoic acid, has shown significant antitumor activity in various cancers. In a recent high-throughput drug screening study, fenretinide emerged as the most active molecule against diffuse midline glioma over more than 3500 compounds. Fenretinide also demonstrated cytotoxic activity against osteosarcoma cell lines in vitro and in preclinical models and is endowed with a favorable safety and toxicity profile. However, its poor water solubility and limited bioavailability have hindered its clinical translation. To improve fenretinide bioavailability and enhance tumor exposure, different nanotechnology-based drug delivery systems have been proposed. Here we propose a tertiary complex made of fenretinide, bovine serum albumin, and hydroxypropyl-betacyclodextrin, indicated as BSAF. Methods: BSAF was evaluated for the main physico-chemical parameters such as hydrodynamic size, zeta potential, stability to drug leakage, and the biological effect on the osteosarcoma cell line MG63. Results: BSAF showed hydrodynamic size at the nanoscale, enhanced drug solubilization, high drug loading and size stability to dilution, characteristics that make this complex useful for targeted therapy. When tested on the MG63 osteosarcoma cell line, BSAF demonstrated significantly enhanced cytotoxicity, with half-maximal inhibitory concentration (IC₅₀) values ~50% lower than free fenretinide. The complex was more efficient than free fenretinide in inhibiting cell migration as demonstrated by wound healing assay. Live-cell imaging analyses revealed a cytostatic effect at sub-cytotoxic concentrations. Specifically, treatment with concentrations below the IC₅₀ resulted in significantly prolonged cell doubling time, decreased cell divisions, increased cellular sphericity and thickness, and decreased cell area. These morphological changes are more consistent with cell cycle arrest rather than apoptosis. These findings were corroborated by stable dry mass measurements, an indication of a cytostatic state rather than progressive cell death. In addition, cell motility parameters (e.g., instantaneous velocity, track speed, and displacement) at the single-cell and population level were markedly reduced at sub-IC₅₀ concentrations, further supporting a cytostatic phenotype. Conclusions: Collectively, the new BSAF complex showed promise as a potential therapeutic agent for treating osteosarcoma cancer, due to the favorable physico-chemical characteristics and the cytotoxic/cytostatic effects on MG63 cells. BSAF effects may be therapeutically valuable, particularly in preventing tumor recurrence by suppressing the proliferative and migratory potential of residual drug-resistant clones. Unlike conventional anticancer agents that mainly rely on cell death, fenretinide, when complexed, demonstrates a dual capacity to induce both cytotoxic and cytostatic responses, depending on concentrations, potentially overcoming multiple resistance mechanisms that are generally associated with tumor exposure to drug sub-cytotoxic concentrations. Full article

Background: Tubulin plays a pivotal role in cell division and other essential cellular processes, making it a key pharmacological target for cancer therapy, antiparasitic treatments, and neurodegenerative diseases. Numerous compounds have been developed to regulate microtubule polymerization through tubulin binding; however, most have shown significant limitations, including adverse side effects, poor bioavailability and limited specificity. In recent years, peptide-based therapies have gained considerable attention, particularly for their ability to modulate protein–protein interaction while offering improved selectivity and safety profiles. Methods: In this study, we employed an integrated computational–experimental approach combining molecular docking, molecular dynamics simulations, and MM-GBSA free energy calculations to design and evaluate 14 peptides derived from the αβ-tubulin dimer interface. Results: The peptide NH₂-P14-COOH emerged as the most promising candidate, displaying the stronger inhibition of tubulin polymerization activity (IC₅₀ = 11.24 ± 3.82 μM), selective cytotoxicity against NCI-H1299 lung carcinoma cells (IC₅₀ = 45.64 ± 3.20 μM), and no significant toxicity toward non-cancerous EA.hy926 endothelial cells (IC₅₀ > 100 μM). Flow cytometry analysis confirmed that NH₂-P14-COOH induces apoptosis, supporting a mechanism of action based on microtubule disruption. Conclusions: These findings highlight NH₂-P14-COOH as a selective antimitotic peptide with a favorable therapeutic index and demonstrate the potential of structure-guided peptide design for the development of novel microtubule-targeting agents with reduced off-target toxicity. Full article

Nanobubbles (NBs) (<1 µm) exhibit unique physicochemical properties and high stability, which have potential applications in biological systems, including microbial metabolism enhancement, fibroblast proliferation, and tumor inhibition. However, the influence of different gaseous components on cell viability remains unclear. This study examined the effects of nitrogen, oxygen, and hydrogen NBs on human lung fibroblast cell (MRC-5) viability. NBs were generated in a Dulbecco’s modified Eagle’s medium using a gas–liquid mixing method and characterized by a nanoparticle tracking analysis. After 48 h of culture, cell viability increased 1.34-, 1.30-, and 1.29-fold for nitrogen, oxygen, and hydrogen NBs, respectively, with only nitrogen NBs showing a significant increase (p < 0.05). Flow cytometry with carboxyfluorescein succinimidyl ester analysis showed no difference in proliferation among groups, indicating that enhanced viability might result from gas-specific effects rather than direct stimulation of cell division. These findings highlight the potential biomedical applications of nanobubbles and their constituent gases. Full article

Background: Chromosome 3p (chr3p) is frequently deleted in multiple cancers, indicating the presence of shared tumor suppressors. In aggressive uveal melanomas (UVM), this deletion often co-occurs with chr8q amplification (8q+), suggesting strong selection pressure during UVM evolution. Methods: To understand the pattern of genomic alterations mediated by chr3p deletion, we have developed an algorithm for detecting isochromosomes in 10,632 TCGA cancer patients. We further perform integrative genomics analysis to investigate how chr3p deletion could affect subsequent cancer genome evolution and synthetic lethality in UVM. Results: Analysis of genomic alterations in 33 different cancer types implicates the deletion or deleterious mutations of SET-domain-containing 2 (SETD2) at chr3p21 in significantly facilitating the formation of isochromosomes, thereby promoting genomic instability conducive to rapid cancer genome evolution. Fracturing of dicentric isochromosomes during cell division is pervasive and follows the dynamic fragmentation pattern of solids under impulse. In the most aggressive UVM subtype, chr3 deletion includes MITF, a master regulator of melanocyte survival and differentiation, and co-occurs with 8q+. We demonstrate that MITF is a master transcriptional regulator of GNAQ/GNA11 and associated synthetic-lethal genes in UVM. MITF maintains MAPK and calcium homeostasis in UVM, and its hemizygous deletion is thus accidental, likely creating an early crisis during oncogenesis. We further show that MITF, MYC, and GNAQ/GNA11 form coupled regulatory feedback loops in the melanocyte lineage, and MITF deletion in UVM creates acute dependency on MYC-mediated rescue via 8q+. The discovered feedback loops predict both overall and relapse-free patient survival within the most aggressive UVM subtype, explain sensitivity to therapeutic gene perturbations, and inform effective combinatorial therapies. Conclusions: SETD2 deletion potentiates isochromosome formation across diverse cancers. Combinatorial targeting of MITF together with a previously identified synthetic lethal gene may benefit UVM patients harboring both chr3 deletion and 8q+. Full article

In mitotic cell division, cytokinesis is followed by abscission, the final separation of the cytoplasmic canal, to release the two genetically identical daughter cells; however, sometimes chromatin bridges connecting the daughter nuclei appear. Preserving intact chromatin bridges is crucial because their breakage can cause DNA damage, aneuploidy, and cancer predisposition. For this purpose, cells use two main mechanisms: first, they activate the abscission checkpoint, a mechanism that delays the final cut of the cytoplasmic canal to prevent chromatin bridge breakage and secondly, they form accumulations of actin (“actin patches”) at the base of the intercellular canal to stabilize chromatin bridges. Here, we highlight new findings from our laboratory on how human cells “sense” chromatin bridges and remodel the actin cytoskeleton to generate actin patches in cytokinesis. More specifically, we discuss findings showing that the nuclear membrane Sun1/2-Nesprin-2-LINC (linker of nucleoskeleton and cytoskeleton) complex promotes the generation of mechanical tension on daughter nuclei with chromatin bridges. This tension leads to accumulation of Sun1/2 and Nesprin-2, and cytoplasmic accumulation of PDZ RhoGEF (PDZ domain-containing Rho guanine nucleotide exchange factor) at the base of the intercellular canal. In turn, PDZ RhoGEF activates downstream RhoA-ROCK-LIMK-Cofilin and RhoA-mDia1 signaling pathways to promote actin patches and prevent chromatin bridge breakage in cytokinesis. Full article