International Journal of Molecular Sciences最新文献

The starch metabolic network was investigated in relation to other metabolic processes by examining a mutant with altered single-gene expression of ATP citrate lyase (ACL), an enzyme responsible for generating cytosolic acetyl-CoA pool from citrate. Previous research has shown that transgenic antisense plants with reduced ACL activity accumulate abnormally enlarged starch granules. In this study, we explored the underlying molecular mechanisms linking cytosolic acetyl-CoA generation and starch metabolism under short-day photoperiods. We performed transcriptome and quantification of starch accumulation in the leaves of wild-type and antisense seedlings with reduced ACL activity. The antisense-ACLA mutant accumulated more starch than the wild type under short-day conditions. Zymogram analyses were conducted to compare the activities of starch-metabolizing enzymes with transcriptomic changes in the seedling. Differential expression between wild-type and antisense-ACLA plants was detected in genes implicated in starch and acetyl-CoA metabolism, and cell wall metabolism. These analyses revealed a strong correlation between the transcript levels of genes responsible for starch synthesis and degradation, reflecting coordinated regulation at the transcriptomic level. Furthermore, our data provide novel insights into the regulatory links between cytosolic acetyl-CoA metabolism and starch metabolic pathways.

Experimental methods of single-molecule enzymology allow scientists to determine physicochemical properties of distinct single molecules of various enzymes and to perform direct monitoring of functioning of enzymes at different steps of their catalytic cycle. The approach based on the use of solid-state nanopores is a promising tool for studying the functioning of single-enzyme molecules. Herein, this approach is employed for monitoring the functioning of cytochrome P450 BM3, which represents a very convenient model of cytochrome P450-containing monooxygenase systems. A nanopore of ~5 nm in diameter has been formed in a 40 nm-thick silicon nitride chip by electron beam drilling (EBD), and a single molecule of the BM3 enzyme has been entrapped in the pore. The functioning of the enzyme molecule has been monitored by recording the time dependence of the ion current through the nanopore during the reaction of laurate hydroxylation. In our experiments, the enzyme molecule has been found to be active for 1500 s. The results of our research can be further used in the development of highly sensitive detectors for single-molecule studies in enzymology.

The loss of one of the two copies of the 9 bp tandem repeat sequence (CCCCCTCTA) located in the small non-coding region between the cytochrome oxidase II (COII) and the lysine tRNA genes in human mtDNA has been reported to be polymorphic in Asian, Oceanian and Sub-Saharan African populations, but it has rarely been observed in Europe. In this study, we will evaluate the possible association between the MIC9D polymorphism and cognitive disorders. A genetic analysis of unrelated Sicilian patients with cognitive deficits was performed to identify the 9 bp deletion MIC9D polymorphism. The MIC9D polymorphism was found in six patients, whereas this variant was absent in control individuals without cognitive deficits. The patients with the MIC9D polymorphism exhibited more complex clinical presentations; in particular, all had neuromuscular disorders and five also presented with behavioral disorders. The present study suggests a potential association between the MIC9D polymorphism and cognitive impairment with concurrent neuromuscular and behavioral involvement.

Eukaryotic protein translation has slowly gained the scientific community's attention for its advanced and powerful therapeutic potential. However, recent technical developments in studying ribosomes and global translation have revolutionized our understanding of this complex multistep process. These developments have improved and deepened the current knowledge of mRNA translation, sparking excitement and new possibilities in this field. Translation factors are crucial for maintaining protein synthesis homeostasis. Since actively proliferating cancer cells depend on protein synthesis, dysregulated protein translation is central to tumorigenesis. Translation factors and their abnormal expressions directly affect multiple oncogenes and tumor suppressors. Recently, small molecules have been used to target translation factors, resulting in translation inhibition in a gene-specific manner, opening the door for developing translation inhibitors that can lead to novel chemotherapeutic drugs for treating multiple cancer types caused by dysregulated translation machinery. This review comprehensively summarizes the involvement of translation factors in tumor progression and oncogenesis. Also, it sheds light on the evolution of translation factors as novel drug targets for developing future therapeutic drugs for treating cancer.

Fungi are diverse organisms with various characteristics and functions. Some play a role in recycling essential elements, such as nitrogen and carbon, while others are utilized in the food and drink production industry. Some others are known to cause diseases in various organisms, including humans. Fungal pathogens cause superficial, subcutaneous, and systemic infections. Consequently, many scientists have focused on studying the factors contributing to the development of human diseases. Therefore, multiple approaches have been assessed to examine the biology of these intriguing organisms. The genome-scale metabolic models (GEMs) have demonstrated many advantages to microbial metabolism studies and the ability to propose novel therapeutic alternatives. Despite significant advancements, much remains to be elucidated regarding the use of this tool for investigating fungal metabolism. This review aims to compile the data provided by the published GEMs of human fungal pathogens. It gives specific examples of the most significant contributions made by these models, examines the advantages and difficulties associated with using such models, and explores the novel approaches suggested to enhance and refine their development.

The basic helix-loop-helix (bHLH) gene family is a crucial regulator in plants, orchestrating various developmental processes, particularly flower formation, and mediating responses to hormonal signals. The molecular mechanism of bamboo flowering regulation remains unresolved, limiting bamboo breeding efforts. In this study, we identified 309 bHLH genes and divided them into 23 subfamilies. Structural analysis revealed that proteins in specific DlbHLH subfamilies are highly conserved. Collinearity analysis indicates that the amplification of the DlbHLH gene family primarily occurs through segmental duplications. The structural diversity of these duplicated genes may account for their functional variability. Many DlbHLHs are expressed during flower development, indicating the bHLH gene's significant role in this process. In the promoter region of DlbHLHs, different homeopathic elements involved in light response and hormone response co-exist, indicating that DlbHLHs are related to the regulation of the flower development of D. latiflorus.

Apples are consumed lavishly worldwide, while demand is increasing for the management of the huge apple-waste amounts that lead to significant disposal costs and ecological issues. Additionally, apples represent fruits with several bioactive constituents, which are key factors in a healthy, balanced diet. In the present study, an extensive review is presented regarding the bioactive compounds of an apple processing by-product, namely apple pomace, mentioning their significance as viable ingredients/substances in foods and cosmetics aiming at chronic disease prevention and health promotion. Apple pomace contains several constituents, such as polar lipids, phenolics, vitamins and dietary fibers, with potential antioxidant, anti-inflammatory, anti-thrombotic, anti-aging and skin-protecting properties, and thus, they may contribute to minimizing the risk of various health conditions. Additionally, the mechanisms of action of such functional bioactives from apple pomace exert health benefits that will be examined, while the potential synergistic effects will also be investigated. Moreover, we will present the methods and techniques needed for the utilization of apple pomace in the appropriate form, such as powder, extracts, essential oil and so on, and their several applications in the food and cosmeceutical industry sectors, which summarize that apple pomace represents an ideal alternative to synthetic bioactive compounds.

Cyclin-dependent kinase 1 (Cdk1) is a master regulator of the G2-M transition between DNA replication and cell division. This study investigates the regulation of cardiomyocyte (CM) proliferation during the early neonatal period and following ischemic injury in adult mice. We analyzed cell cycle dynamics with the assessment of DNA synthesis, and cytokinesis in murine hearts during the first 15 days after birth. A distinct proliferative block was observed at 1 day, followed by a second wave of DNA synthesis at 4 days, leading to CM binucleation (CMBN) by day 5. Genome-wide mRNA profiling revealed the differential expression of cell cycle regulatory genes during this period, with a downregulation of factors involved in cell division and mitosis. The loss of Cdk1 impaired CMBN but extended the neonatal CM proliferation window until day 10 post-birth. In adult hearts, the cardiac-specific ablation of Cdk1 triggered CM proliferation post-myocardial-infarction (MI) in specific zones, driven by the activation of EGFR1 signaling and suppression of the anti-proliferative p38 and p53 signaling. This was accompanied by restoration of fractional shortening, mitochondrial function, and decreased reactive oxygen species. Additionally, cardiac hypertrophy was mitigated, and survival rates post-MI were increased in Cdk1-knockout mice. These findings reveal a novel role of Cdk1 in regulating cell cycle exit and re-entry in differentiated CMs and offer insights into potential strategies for cardiac repair.

Phage φ29 and related bacteriophages are currently the smallest known tailed viruses infecting various representatives of both Gram-positive and Gram-negative bacteria. They are characterised by genomic content features and distinctive properties that are unique among known tailed phages; their characteristics include protein primer-driven replication and a packaging process characteristic of this group. Searches conducted using public genomic databases revealed in excess of 2000 entries, including bacteriophages, phage plasmids and sequences identified as being archaeal that share the characteristic features of phage φ29. An analysis of predicted proteins, however, indicated that the metagenomic sequences attributed as archaeal appear to be misclassified and belong to bacteriophages. An analysis of the translated polypeptides of major capsid proteins (MCPs) of φ29-related phages indicated the dissimilarity of MCP sequences to those of almost all other known Caudoviricetes groups and a possible distant relationship to MCPs of T7-like (Autographiviridae) phages. Sequence searches conducted using HMM revealed the relatedness between the main structural proteins of φ29-like phages and an unusual lactococcal phage, KSY1 (Chopinvirus KSY1), whose genome contains two genes of RNA polymerase that are similar to the RNA polymerases of phages of the Autographiviridae and Schitoviridae (N4-like) families. An analysis of the tail tube proteins of φ29-like phages indicated their dissimilarity of the lower collar protein to tail proteins of all other viral groups, but revealed its possible distant relatedness with proteins of toxin translocation complexes. The combination of the unique features and distinctive origin of φ29-related phages suggests the categorisation of this vast group in a new order or as a new taxon of a higher rank.

Osteoarthritis (OA) is a chronic, progressive, degenerative joint disease characterized by joint pain, stiffness, and limited movement. It presents significant intra- and inter-individual variability-in particular, between genders. Recent research has increasingly focused on the role of adipokines-especially leptin, adiponectin, and resistin-in the development of OA. Adipokines, peptide hormones primarily secreted by adipose tissue, are involved in crucial physiological processes related to metabolism and immunity. They can also impact bone and cartilage turnover by interacting with joint cells such as osteoblasts, osteoclasts, chondrocytes, and mesenchymal stem cells, thereby linking inflammation with bone cartilage homeostasis. This review aims to elucidate the structure and functions of various adipokines, their serum and synovial levels, and their association with clinical presentation and radiographic progression in OA patients, with a focus on differences between sexes. A narrative literature review was conducted using three databases specifically analyzing sex differences. OA patients generally show elevated serum and synovial levels of leptin, chemerin, and visfatin, as well as high plasma levels of resistin and visfatin. In contrast, synovial levels of adiponectin and omentin are reduced in OA patients compared to healthy individuals, with an inverse relationship to disease severity, suggesting a potential protective role. Resistin and leptin were positively correlated with pain severity and radiographic progression, while adiponectin's role in OA remains controversial. Regarding sex differences, male OA patients exhibited higher serum levels of leptin, chemerin, and omentin compared to healthy controls, with a positive correlation to the BMI and estrogen levels, potentially explaining the sexual dimorphism observed in this condition. Studies on visfatin and lipocalin did not reveal significant differences in synovial or serum levels between the sexes. The role of resistin remains controversial. Adipokines influence the joint microenvironment and contribute to the progression of osteoarthritis (OA). However, the precise biological mechanisms are not yet fully understood due to the complex interactions between the metabolic, mechanical, and immune systems. Further research is needed to clarify their roles in OA and to identify targeted therapies for managing this degenerative disease.