Search Results (306)

Flammulina velutipes is a widely cultivated edible mushroom in East Asia, recognized for its nutritional benefits and distinct morphology characterized by a long stipe and a compact, hemispherical pileus. The pileus not only plays a critical biological role in reproduction through spore formation but also serves as a key commercial trait influencing consumer preference and market value. Despite its economic importance, pileus development in F. velutipes is highly sensitive to environmental factors, among which carbon dioxide (CO₂) concentration is particularly influential under indoor cultivation conditions. While previous studies have reported that elevated CO₂ levels can inhibit pileus expansion in other mushroom species, the molecular mechanisms by which CO₂ affects pileus growth in F. velutipes remain poorly understood. In this study, we investigated the impact of CO₂ concentration on pileus morphology and gene expression in F. velutipes by cultivating fruiting bodies under two controlled atmospheric conditions: low (1000 ppm) and high (10,000 ppm) CO₂. Morphometric analysis revealed that elevated CO₂ levels significantly suppressed pileus expansion, reducing the average diameter by more than 50% compared to the low CO₂ condition. To elucidate the underlying genetic response, we conducted RNA sequencing and identified 102 differentially expressed genes (DEGs), with 78 being downregulated under elevated CO₂. Functional enrichment analysis highlighted the involvement of cyclin-dependent protein kinase regulatory pathways in this response. Two cyclin genes were found to be significantly downregulated under elevated CO₂ conditions, and their suppression was validated through quantitative real-time PCR. These genes, possessing conserved cyclin_N domains, are implicated in the regulation of the eukaryotic cell cycle, particularly in mitotic growth. These results indicate that CO₂-induced downregulation of cyclin genes may underlie cell cycle arrest, contributing to inhibited pileus development. This study is the first to provide transcriptomic evidence that elevated CO₂ concentrations specifically repress PHO80-like cyclin genes in F. velutipes, revealing a molecular mechanism by which CO₂ stress inhibits pileus development. These findings suggest that elevated CO₂ triggers a morphogenetic checkpoint by repressing PHO80-like cyclins, thereby modulating cell cycle progression during fruiting body development. This study provides the first evidence of such a transcriptional response in edible mushrooms and offers promising molecular targets for breeding CO₂-resilient strains and optimizing commercial cultivation conditions. Full article

Eukaryotic cells double their mass and divide at the same rate, allowing cells to maintain a uniform cell size over many cell divisions. We hypothesize that aneuploid cancer cells are more sensitive to forced overgrowth, more than doubling their mass during a single longer-duration cell division cycle, relative to healthy diploid cells. This hypothesis stems from the observation that cancer cells are under proteotoxic stress, during which heat-shock proteins become rate-limiting and the unfolded-protein response network has a growth-suppressive phenotype. Forced overgrowth will lead to the production of more individual proteins per cell division cycle and increase the duration of time during which any mis-folded or aggregated proteins might disrupt the function of properly folded proteins. To induce these potential forced overgrowth effects, we suggest targeting the cell division cycle regulatory enzyme, the anaphase-promoting complex/cyclosome (APC/C), to suppress—but not inhibit—its activity. We conclude by proposing experiments to test this hypothesis in which an APC/C inhibitor, such as a low level of proTAME, is combined with the clinically approved heat-shock protein 90 (HSP90)-inhibitor pimitespib (TAS-116) or the pre-clinical molecule tanespimycin, which, to the best of our knowledge, are combinations that have not been investigated before. Full article

Excess selenium (Se) can cause a variety of toxic effects in aquatic animals. However, there is currently a lack of comprehensive studies about the toxicity effects of Se in culture water on shrimp. Based on the 96 h acute toxicity test, which confirmed the 96 h LC₅₀ of Se (Na₂SeO₃) for Litopenaeus vannamei as 2.69 mg/L, L. vannamei (7.25 ± 0.05 g) were divided into three groups (named CON, S1 and S2) and exposed to Se at concentrations of 0, 0.0269 (0.01 × 96 h LC₅₀), and 0.269 (0.1 × 96 h LC₅₀) mg/L in the water for 72 h, respectively. The toxic effects of Se exposure on L. vannamei were evaluated based on histopathology, oxidative stress, immunity, apoptosis, transcriptional responses, and intestinal microbiota. Results demonstrated that Se exposure induced structural damage to the hepatopancreas of L. vannamei, including hepatocyte vacuolation and necrosis. Compared to the CON group, serum Caspase-3 activity significantly increased, while Bcl-2 activity markedly decreased in the S1 and S2 groups (p < 0.05). No significant differences in Bax activity were observed among groups (p > 0.05). ROS content, as well as activities of SOD, PO, GSH-PX, LYS, AKP, and ACP, exhibited an upward trend under Se exposure (p < 0.05). However, MDA levels showed no significant intergroup differences (p > 0.05). Hemocyte transcriptomic analysis revealed 2103 differentially expressed genes (DEGs) (1294 upregulated, 809 downregulated) in the S2 group compared to CON. GO enrichment indicated significant enrichment of DEGs in cellular processes, binding, and cell components. KEGG pathway analysis highlighted prominent enrichment in ribosome biogenesis in eukaryotes, lysosome, cell cycle, and pancreatic secretion pathways. Intestinal microbiota analysis showed that the Shannon, Simpson, and Pielou indices in the S2 group were significantly lower than those in the CON group (p < 0.05). The relative abundance of Vibrio and Acinetobacter increased significantly in the S2 group, while Enterococcus and Pseudomonas decreased markedly (p < 0.05). In conclusion, Se exposure triggered elevated immune enzyme activities, induced oxidative damage and apoptosis, transcriptional level metabolic disorders, and disrupted intestinal microbiota structure in L. vannamei. Full article

The ubiquitin-proteasome pathway performs a strictly controlled degradation of specific protein substrates within the eukaryotic cell. This catabolic mechanism allows the rapid removal of proteins damaged in any way, and therefore potentially capable of compromising cellular homeostasis, as well as the constant turnover of all cellular proteins, in order to balance their synthesis and thus maintain the correct levels of proteins required by the cell at any given time. Consequently, the ubiquitin-proteasome system plays a fundamental role in regulating essential cellular processes, such as the cell cycle, apoptosis, immune responses, and inflammation, whose dysregulation or malfunction can lead to neoplastic transformation. Not surprisingly, therefore, alterations in the activity and regulatory mechanisms of the proteasome are common not only in various types of tumors, but often represent a contributing cause of oncogenesis itself. Among proteasome modulators, PA28γ, due to its function in promoting cell growth and proliferation, while inhibiting apoptosis and cell-mediated immune responses, has received great attention in recent years for its well established pro-tumoral activity. Conversely, the role played in oncogenesis by the second paralogue of the PA28 family of proteasome activators, namely PA28αβ, is less clearly defined, which is also related to the lower level of general understanding of its cellular activities and biological functions. However, increasing experimental evidence has demonstrated that PA28αβ also plays a non-secondary role in the process of neoplastic transformation and tumor growth, both by virtue of its regulatory function on class I cell-mediated immune responses and through activity promoting cell duplication and growth. This review aims to summarize the current knowledge and evidence on the molecular mechanisms and cellular functions through which PA28αβ may support development and growth of cancer. Full article

NAA10 (N-alpha-acetyltransferase 10) is a pivotal enzyme in eukaryotic cells, serving as the catalytic subunit of the NatA complex, which is responsible for the N-terminal acetylation of approximately 40–50% of the human proteome. Beyond its canonical role in co-translational N-terminal acetylation, NAA10 also acetylates internal lysine residues of various proteins and exerts non-catalytic regulatory functions through diverse protein–protein interactions. Pathogenic variants in NAA10 are linked to a spectrum of developmental disorders, most notably Ogden syndrome, which is characterized by neurodevelopmental delay, cardiac defects, and craniofacial anomalies. In cancer, NAA10 is frequently overexpressed or genomically amplified, where its dysregulation correlates with tumor aggressiveness and poor prognosis. Functional studies implicate NAA10 in regulating cell cycle progression, apoptosis, migration, and other hallmarks of cancer. In this review, we summarize the structure, molecular mechanisms, and physiological functions of NAA10, as well as its roles in human diseases and cancer. We present in silico pan-cancer analyses that highlight its clinical significance and potential downstream pathways. Furthermore, we discuss the therapeutic potential and challenges of targeting NAA10 in cancer, and propose future research directions to better understand its multifaceted roles in health and disease. Full article

Protein phosphatases are crucial enzymes that regulate key cellular processes such as the cell cycle, gene transcription, and translation in eukaryotes. Seven PP2C protein phosphatases have been identified in Magnaporthe oryzae. However, their synergistic roles in the pathology and physiology of M. oryzae remain poorly investigated. By qRT-PCR analysis, we found that PTC1 and PTC2 are significantly upregulated in the PTC5 deletion mutant. The double deletion of the MoPTC5/MoPTC1 and MoPTC5/MoPTC2 genes significantly reduced hyphal growth, conidiophore formation, sporulation, and virulence in M. oryzae. In addition, the double-knockout mutants were increasingly sensitive to different osmotic, oxidative, and cell wall stresses. Western blot analysis revealed that MoPtc5 plays a synergistic function with MoPtc1 and MoPtc2 in the regulation of MoMps1 and MoOsm1 phosphorylation levels. Lastly, appressorium formation and turgor generation were remarkably affected in the ΔMoptc5ΔMoptc1 and ΔMoptc5ΔMoptc2 double-deletion mutants. These findings demonstrate the overlapping roles of PP2c protein phosphatase in the fungal development and pathogenesis of M. oryzae. Full article

The increasing prevalence of overweight and obesity not only in adults but also among children and adolescents has become one of the most alarming health problems worldwide. Metabolic disorders accompanying fat accumulation during pathological weight gain induce chronic low-grade inflammation, which, in a vicious cycle, increases the immune response through pro-inflammatory changes in the cytokine (adipokine) profile. Obesity decreases life expectancy, largely because obese individuals are at an increased risk of many medical complications, often referred to as metabolic syndrome, which refers to the co-occurrence of insulin resistance (IR), impaired glucose tolerance, type 2 diabetes (T2D), atherogenic dyslipidemia, hypertension, and premature ischemic heart disease. Metabotropic G protein-coupled receptors (GPCRs) constitute the most numerous and diverse group of cell surface transmembrane receptors in eukaryotes. Among the GPCRs, researchers are focusing on the connection of G protein-coupled receptor 120 (GPR120), also known as free fatty acid receptor 4 (FFAR4), with signaling pathways regulating the inflammatory response and insulin sensitivity. This review presents the current state of knowledge concerning the involvement of GPR120 in anti-inflammatory and metabolic signaling. Since both inflammation in adipose tissue and insulin resistance are key problems in obesity, there is a rationale for the development of novel, GPR120-based therapies for overweight and obese individuals. The main problems associated with introducing this type of treatment into clinical practice are also discussed. Full article

Recent discoveries revealed mechanistic insights into the control of adipogenesis by the Constitutive Photomorphogenesis 9 Signalosome (CSN) and its variants, CSN^CSN7A and CSN^CSN7B, which differ in the paralog subunits, CSN7A and CSN7B. CSN^CSN7A and CSN^CSN7B variants form permanent complexes with cullin-RING-ubiquitin ligases 3 and 4A (CRL3 and CRL4A), respectively. These complexes can be found in most eukaryotic cells and represent a critical reservoir for cellular functions. In an early stage of adipogenesis, mitotic clonal expansion (MCE), CSN-CRL1, and CSN^CSN7B-CRL4A are blocked to ubiquitinate the cell cycle inhibitor p27^KIP, leading to cell cycle arrest. In addition, in MCE CSN-CRL complexes rearrange the cytoskeleton for adipogenic differentiation and CRL3^KEAP1 ubiquitylates the inhibitor of adipogenesis C/EBP homologous protein (CHOP) for degradation by the 26S proteasome, an adipogenesis-specific proteolysis. During terminal adipocyte differentiation, the CSN^CSN7A-CRL3 complex is recruited to a lipid droplet (LD) membrane by RAB18. Currently, the configuration of the substrate receptors of CSN^CSN7A-CRL3 on LDs is unclear. CSN^CSN7A-CRL3 is activated by neddylation on the LD membrane, an essential adipogenic step. Damage to CSN/CUL3/CUL4A genes is associated with diverse diseases, including obesity. Due to the tremendous impact of CSN-CRLs on adipogenesis, we need strategies for adequate treatment in the event of malfunctions. Full article

Protein glutathionylation is defined as a reversible, ubiquitous post-translational modification, resulting in the formation of mixed disulfides between glutathione and proteins’ cysteine residues. Glutathionylation has been implicated in several cellular mechanisms ranging from protection from oxidative stress to the control of cellular homeostasis and the cell cycle. A significant body of research has examined the multifaceted effects of this post-translational modification under physiological conditions in eukaryotes, with a particular focus on its impact on the development of various diseases in humans. In contrast, the role of glutathionylation in prokaryotic organisms remains to be extensively investigated. However, there has been a recent increase in the number of studies investigating this issue, providing details about the role of glutathione and other related thiols as post-translational modifiers of selected bacterial proteins. It can be concluded that in addition to the classical role of such thiols in protecting against cysteine oxidation and consequent protein inactivation, many more specialized roles of glutathionylation in bacterial pathogenicity, virulence, interspecies competition and survival, and control of gene expression are emerging, and new ones may emerge in the future. In this short review, we aim to summarize the current state-of-the-art in this field of research. Full article

Microalgae are photosynthetic microorganisms that have a rapid growth cycle and carbon fixation ability. They have diverse cellular structures, ranging from prokaryotic cyanobacteria to more complex eukaryotic forms, which enable them to thrive in a variety of environments and support biomass production. They utilize both photosynthesis and heterotrophic pathways, indicating their ecological importance and potential for biotechnological applications. Reproducing primarily through asexual means, microalgae have complex cell cycles that are crucial for their growth and ability to adapt to changing conditions. Additionally, microalgae possess bioactive compounds that make them both nutritious and functional. Thanks to their content of proteins, lipids, carbohydrates, vitamins, and minerals, they play an important role in the development of functional food products, particularly by enhancing nutritional content and product quality. Furthermore, studies have demonstrated that algae and algal bioactive compounds support cardiovascular health, immune function, and gut health, especially in relation to obesity and other metabolic diseases. They also contribute to skin health and cognitive functions, including memory. This review article explores the biological, nutritional, and functional properties of microalgae based on the studies conducted. Full article

RNA metabolism is focused on RNA molecules and encompasses all the crucial processes an RNA molecule may or will undergo throughout its life cycle. It is an essential cellular process that allows all cells to function effectively. The transcriptomic landscape of a cell is shaped by the processes such as RNA biosynthesis, maturation (RNA processing, folding, and modification), intra- and inter-cellular transport, transcriptional and post-transcriptional regulation, modification, catabolic decay, and retrograde signaling, all of which are interconnected and are essential for cellular RNA homeostasis. In eukaryotes, sRNAs, typically 20–31 nucleotides in length, are a class of ncRNAs found to function as nodes in various gene regulatory networks. sRNAs are known to play significant roles in regulating RNA population at the transcriptional, post-transcriptional, and translational levels. Along with sRNAs, such as miRNAs, siRNAs, and piRNAs, new categories of ncRNAs, i.e., lncRNAs and circRNAs, also contribute to RNA metabolism regulation in eukaryotes. In plants, various genetic screens have demonstrated that sRNA biogenesis mutants, as well as RNA metabolism pathway mutants, exhibit similar growth and development defects, misregulated primary and secondary metabolism, as well as impaired stress response. In addition, sRNAs are both the “products” and the “regulators” in broad RNA metabolism networks; gene regulatory networks involving sRNAs form autoregulatory loops that affect the expression of both sRNA and the respective target. This review examines the interconnected aspects of RNA metabolism with sRNA regulatory pathways in plants. It also explores the potential conservation of these pathways across different kingdoms, particularly in plants and animals. Additionally, the review highlights how cellular RNA homeostasis directly impacts adaptive responses to environmental changes as well as different developmental aspects in plants. Full article

The eukaryotic ribosome is a large ribonucleoprotein complex consisting of four types of ribosomal RNA (rRNA) and approximately 80 ribosomal proteins (RPs), forming the 40S and 60S subunits. In all living cells, its primary function is to produce proteins by converting messenger RNA (mRNA) into polypeptides. In addition to their canonical role in protein synthesis, RPs are crucial in controlling vital cellular processes such as cell cycle progression, cellular proliferation, differentiation, DNA damage repair, genome structure maintenance, and the cellular stress response. Viruses, as obligate intracellular parasites, depend completely on the machinery of the host cell for their replication and survival. During viral infection, RPs have been demonstrated to perform a variety of extra-ribosomal activities, which are especially important in viral disease processes. These functions cover a wide range of activities, ranging from controlling inflammatory responses and antiviral immunity to promoting viral replication and increasing viral pathogenicity. Deciphering the regulatory mechanisms used by RPs in response to viral infections has greatly expanded our understanding of their functions outside of the ribosome. Furthermore, these findings highlight the promising role of RPs as targets for the advancement of antiviral therapies and the development of novel antiviral approaches. This review comprehensively examines the many functions of RPs outside of the ribosome during viral infections and provides a foundation for future research on the host–virus interaction. Full article

Cell division cycle 6 (CDC6) is essential for the initiation of DNA replication in eukaryotic cells and contributes to the development of various human tumors. Polycystic ovarian syndrome (PCOS) is a reproductive endocrine disease in women of childbearing age, with a significant risk of endometrial cancer (EC). However, the role of CDC6 in the progression of PCOS to EC is unclear. Therefore, we examined CDC6 expression in patients with PCOS and EC. We evaluated the relationship between CDC6 expression and its prognostic value, potential biological functions, and immune infiltrates in patients with EC. In vitro analyses were performed to investigate the effects of CDC6 knockdown on EC proliferation, migration, invasion, and apoptosis. CDC6 expression was significantly upregulated in patients with PCOS and EC. Moreover, this protein caused EC by promoting the aberrant infiltration of macrophages into the immune microenvironment in patients with PCOS. A functional enrichment analysis revealed that CDC6 exerted its pro-cancer and pro-immune cell infiltration functions via the PI3K-AKT pathway. Moreover, it promoted EC proliferation, migration, and invasion but inhibited apoptosis. This protein significantly reduced EC survival when mutated. These findings demonstrate that CDC6 regulates the progression of PCOS to EC and promotes immune infiltration. Full article

The Chlamydiaceae are a family of obligate intracellular bacteria known for their unique biphasic developmental cycle. Chlamydial are associated with various host organisms, including humans, and have been proposed as emerging pathogens. Genomic studies have significantly enhanced our understanding of chlamydial biology, host adaptation, and evolutionary processes. In this study, we conducted a complete pangenome association analysis (pan-GWAS) using 101 genomes from the Chlamydiaceae family to identify differentially represented genes in Chlamydia and Chlamydophila, revealing their distinct evolutionary strategies for interacting with eukaryotic hosts. Our analysis identified 289 genes with differential abundance between the two clades: 129 showed a strong association with Chlamydia and 160 with Chlamydophila. Most genes in Chlamydia were related to the type III secretion system, while Chlamydophila genes corresponded to various functional categories, including translation, replication, transport, and metabolism. These findings suggest that Chlamydia has developed a high dependence on mammalian cells for replication, facilitated by a complex T3SS for intracellular manipulation. In contrast, the metabolic and functional diversity in Chlamydophila allows it to colonize a broad range of hosts, such as birds, reptiles, amphibians, and mammals, making it a less specialized clade. Full article

N6-methyladenosine (m⁶A) is the most common modification in eukaryotic RNAs. Growing research indicates that m⁶A methylation is crucial for a multitude of biological processes. However, research on the m⁶A modifications in the regulation of porcine muscle growth is lacking. In this study, we identified differentially expressed genes in the neonatal period of muscle development between Large White (LW) and NingXiang (NX) pigs and further reported m⁶A methylation patterns via MeRIP-seq. We found that m⁶A modification regulates muscle cell development, myofibrils, cell cycle, and phosphatase regulator activity during the neonatal phase of muscle development. Interestingly, differentially expressed genes in LW and NX pigs were mainly enriched in pathways involved in protein synthesis. Furthermore, we performed a conjoint analysis of MeRIP-seq and RNA-seq data and identified 27 differentially expressed and m⁶A-modified genes. Notably, a typical muscle-specific envelope transmembrane protein, WFS1, was differentially regulated by m⁶A modifications in LW and NX pigs. We further revealed that the m⁶A modification accelerated the degradation of WFS1 in a YTHDF2-dependent manner. Noteworthy, we identified a single nucleotide polymorphism (C21551T) within the last exon of WFS1 that resulted in variable m⁶A methylation, contributing to the differing WFS1 expression levels observed in LW and NX pigs. Our study conducted a comprehensive analysis of the m⁶A modification on NX and LW pigs during the neonatal period of muscle development, and elucidated the mechanism by which m⁶A regulates the differential expression of WFS1 in the two breeds. Full article