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Regulatory mechanism in arterial smooth muscle contraction.

The regulatory mechanism in the aortic actomyosin system was studied. Superprecipitation of desensitized aortic myosin B was not exhibited even in the presence of Ca2+, but was observable only in the presence of native tropomyosin and Ca2+. Reconstituted actomyosin composed of pure aortic myosin and pure skeletal actin did not show superprecipitation. Addition of aortic native tropomyosin and Ca2+ caused a marked superprecipitation. The ATPase of reconstituted actomyosin was enhanced three- or fourfold by aortic native tropomyosin and Ca2+. The extent of superprecipitation of aortic myosin B did not show a biphasic type of response to Mg-ATP concentration. Thus, aortic native tropomyosin induces a real activation of the myosin, actin, and ATP system in the presence of Ca2+, in contrast with the case of skeletal native tropomyosin, which induces the depression of skeletal myosin-actin-ATP interaction in the absence of Ca2+.

Actomyosin

Genomic analysis of regulatory mechanisms governing EPS66A biosynthesis in Streptomyces changanensis HL-66.

Streptomyces changanensis HL-66 produces the α-(1,4)/(1,6)-glucan exopolysaccharide EPS66A, a potent plant immune elicitor with promising applications in plant protection. However, its low native fermentation yield limits large-scale application. To investigate the biosynthetic potential and regulatory mechanisms underlying EPS66A production, the whole genome of HL-66 was sequenced and analyzed. The HL-66 genome is 6.82 Mb in size, with a GC content of 74%, and encodes 6081 predicted functional genes. Among these, 1390 genes were annotated to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, 4187 were assigned to Gene Ontology (GO) terms, and 143 were classified into Clusters of Orthologous Groups (COG) categories. antiSMASH analysis identified 22 secondary metabolite biosynthetic gene clusters, including multiple polyketide synthase (PKS) and nonribosomal peptide synthetase (NRPS) clusters. Functional analyses revealed that the glycosyltransferase gene (GTy) and the global regulatory gene (bldD) are involved in EPS66A biosynthesis. bldD is involved in morphological development and EPS66A production, whereas GTy specifically regulates EPS66A production without affecting growth or development. In both in vivo and potted-plant experiments, EPS66A (200 μg/mL) significantly reduced the severity of tobacco mosaic virus, apple anthracnose leaf spot, walnut bacterial leaf spot, and jujube anthracnose, achieving control efficacies of 90.21%, 87.95%, 77.41%, and 68.55%, respectively, and outperforming a commercial chitosan oligosaccharide control. These findings provide new insights into the genetic architecture and regulatory mechanisms of EPS66A biosynthesis and support its development as a polysaccharide-based green pesticide.

Streptomyces

Interaction analysis of miRNA and mRNA reveals the regulatory mechanism of immune response in golden pompano (Trachinotus ovatus) spleen to Streptococcus iniae infection.

Streptococcus iniae is a major warm-water pathogen that cause high mortality and severe economic losses in golden pompano industry. In the present study, we performed the mRNA-miRNA integrated transcriptomic analysis of spleen of golden pompano challenged with S. iniae to explore the possible regulatory mechanism to bacterial infection. In total, we excavated 5072 DEGs, of which 2765 up-regulated and 2307 down-regulated genes. KEGG enrichment analysis indicated that the DEGs were primarily enriched in immune-related pathways, such as proteasome, cytokine-cytokine receptor interaction, p53 signaling pathway, lysosome, phagosome, Herpes simplex virus 1 infection. Additionally, a protein-protein interaction (PPI) network was constructed to extract hub genes. And the result showed that 4 hub genes, comprising cd4, il10, tnfsf2, myd88, may play vital roles in response to S. iniae infection. Furthermore, a total of 46 differentially expressed miRNAs (DEMs) were identified, containing 23 known and 23 novel DEMs. By integrating mRNA and miRNA joint analysis, we established a miRNA-mRNA regulatory network, including 12 miRNAs and 14 genes. Among them, novel-miR-357 were identified as a multi-target hub miRNA. These results provide important insights into the molecular regulatory mechanisms of immune response and inflammation processes in the defense of golden pompano against S. iniae infection.

Integrative interaction

Biosynthesis and regulatory mechanism of tanshinones and phenolic acids in Salvia miltiorrhiza.

Salvia miltiorrhiza, a perennial plant of the genus Salvia in the family Lamiaceae, is one of the most important traditional Chinese medicinal herbs, renowned for its significant economic and medicinal value. Its application in China dates back to 200 BC, where it has been utilized clinically either as a monotherapy or in combination with other herbal medicines for treating cardiovascular and cerebrovascular diseases, as well as various other ailments. The bioactive constituents of S. miltiorrhiza primarily include lipophilic tanshinones and hydrophilic phenolic acids. Over the past decades, the biosynthetic pathways of tanshinones and phenolic acids have been elucidated. Coupled with the sequencing of its genome, substantial progress has been made in deciphering the biosynthesis and regulatory mechanisms of bioactive compounds in S. miltiorrhiza, including tanshinones, phenolic acids, flavonoids, and prenylated quinones. This review summarizes recent advances in the regulatory mechanisms underlying the biosynthesis of phenolic acids and tanshinones in S. miltiorrhiza, focusing on transcriptional regulation, post-translational modifications, and epigenetic regulation. These insights provide a foundation for enhancing the production of bioactive compounds through biotechnological approaches and advancing pharmacological applications.

Salvia miltiorrhiza

The NagY antiterminator in Enterococcus faecalis: a novel regulatory mechanism and its impact on cell metabolism.

The Enterococcus genus is the most controversial group of lactic acid bacteria. While some strains are used as probiotics, other species, including Enterococcus faecalis, are responsible for health-related pathologies. Under conditions of infection, the N-acetylglucosamine metabolism of E. faecalis undergoes significant changes in expression, even more important than those of virulence factors. This metabolism is mediated by the nagY-nagE operon, which is regulated by the transcriptional antiterminator NagY. In this report, we focus on the regulatory mechanism of NagY and its impact on bacterial metabolism. We showed that NagY requires the interaction with the RNase III to achieve optimal induction of its own expression by cleaving the 5' untranslated region of the nagY mRNA. The NagY regulon was identified and the central role of the antiterminator in the E. faecalis metabolism was demonstrated, highlighting its importance in the opportunistic nature of the bacterium. This study provides a valuable advance in the understanding of regulation and the importance of post-transcriptional actors in E. faecalis adaptation.IMPORTANCEAs a commensal, Enterococcus faecalis colonizes the gastrointestinal tract of 31 to 80% of the intestinal microbiota in adults and is considered ubiquitous, due to its strong environmental stress resistance capabilities. However, in immunocompromised patients, the poorly understood transition from commensal to opportunistic pathogen occurs, and many studies suggest that the metabolism plays a central role in this process. In this study, we focus on the regulator NagY, which is involved in the metabolism of N-acetylglucosamine, an important carbon source for bacterial pathogens in the human host. We characterized a novel regulatory mechanism involving the NagY antiterminator and the ribonuclease RNase III. In addition, we identified the target genes of the regulator, through which we were able to demonstrate that NagY has a strong impact on the metabolism of β-glucosides. Overall, this work highlights the importance of regulation of the bacterial metabolic adaptation in the host.

Enterococcus faecalis

Concerted repression of the synthesis of the arginine biosynthetic enzymes by aminoacids: a comparison between the regulatory mechanisms controlling aminoacid biosyntheses in bacteria and in yeast.

It has been shown that in bacteria, besides specific regulatory mechanisms, the synthesis of aminoacid biosynthetic enzymes is also controlled by the endogenous aminoacid pool. The latter regulates the intracellular level of ppGpp, a positive effector of RNA messenger transcription. A similar regulatory control exists in yeast but does not appear to involve the same general effector. This was established by the observation that derepression of the enzymes belonging to several aminoacid biosynthetic pathways follows aminoacid starvation or tRNA discharging. We now report the repression of the arginine pathway by the total aminoacid pool. New mutations affecting the repressibility of the arginine enzymes as well as enzymes belonging to other aminoacid biosyntheses, when cells are grown in the presence of an excess of aminoacids, were identified.

Amino Acids

L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT): A probe for regulatory mechanisms in antibody responses.

The synthetic random terpolymer of L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT) has been used as a probe to investigate regulatory mechanisms in antibody responses in tissue culture systems. In this brief review, the mechanisms of H-2 linked Ir gene control of antibody responses to GAT and genetic restrictions governing Mphi-immune T cell interactions in antibody responses to GAT are summarized.

Alanine

Phosphorylation as a regulatory mechanism of HP1 protein multifunctionality.

The Heterochromatin Protein 1 (HP1) family proteins are key regulators of chromatin structure and genome function, acting as "reader" proteins that recognize and bind to histone H3 lysine 9 methylation (H3K9me). Beyond their canonical role in heterochromatin formation and transcriptional repression, HP1 proteins exhibit functional versatility, participating in transcriptional activation, RNA processing, DNA repair, and chromosome segregation. This multifunctionality is mediated partially by post-translational modifications (PTMs), with phosphorylation emerging as a central regulatory mechanism. This review explores the diverse effects of HP1 phosphorylation on protein function and chromatin interactions, focusing on Drosophila melanogaster HP1a and its orthologs, mammalian HP1α and S. pombe Swi6. Phosphorylation in the N-terminal tail enhances HP1's affinity for H3K9me, promoting transcriptional silencing. Mitotic phosphorylation of serine residues in the hinge region, regulated by kinases such as AURKB and NDR1/2, leads to chromatin release and relocalization to the kinetochore, enabling proper chromosome segregation. Additionally, phosphorylation modulates HP1 phase separation dynamics, influencing nuclear compartmentalization and chromatin condensation. These findings highlight phosphorylation as a versatile molecular switch that enables HP1 proteins to transition between structural and regulatory roles, contributing to their evolutionary conserved multifunctionality in genome regulation and cell division. Further investigation into HP1 phosphorylation across species and contexts is essential to fully understand its contributions to chromatin biology.

Phosphorylation

[The acid-base balance in the CSF of normal subjects regulatory mechanisms (author's transl)].

1. The acid-base balance (pH, pCO2 and HCO-3) of 23 normal subjects was determined both in arterialized capillary blood and in the CSF. 2. Statistically significant correlations (determined by means of Spearman's rank correlation) were found between: pCO2 in arterialized blood and CSF pH (Rs=--0.372, p is less than 0.05), pCO2 in the CSF and CSF pH (Rs=--0.421, p is less than 0.05), HCO-3 in the CSF and in arterialized blood (Rs=0.623, p is less than 0.05), blood pH and CSF pH (Rs=0.485, p is less than 0.025), pCO2 in the CSF and HCO-3 in the CSF (Rs=0.559, p is less than 0.005). 3. The regulatory mechanisms of the CSF acid-base balance in normal subjects and also in patients with extra-neural or CNS disturbances are discussed.

Acid-Base Equilibrium

Analysis of the regulatory mechanisms controlling the synthesis of the hexitol transport systems in Escherichia coli K12.

The synthesis of the transport systems (enzymeII-complexes) coded for in the mtl and in the gut (srl) operon was found to be induced by unphosphorylated D-mannitol and D-glucitol respectively. Induction from the outside however is only possible if these polyols are taken up into the cells. Induction of the D-mannitol system is immediate, resistant against catabolite repression, relatively insensitive towards transient repression and starts from a high uninduced level (5--30%). By contrast, the induction of the D-glucitol system starts at a low basal level (0.5--2.5%), does show a pronounced lag from 25 to 90 min, and is hypersensitive towards catabolite and transient repression. These differences apparently reflect primarely differences in the corresponding operator-promotor genes mtl (P,O) and gut (P,O) as well as differences in the uptake of the first, inducing hexitol molecules. For each operon additional regulatory genes exist, called mtlR and gutR respectively, in which transrecessive, temperature sensitive mutations leading to a constitutive expression of the corresponding operon can be found. The influence of these regulatory mechanisms in diauxie experiments and their importance for the differentiation of the three operons during evolution from apparently one common ancestor operon will be discussed.

Biological Transport

Possible regulatory mechanisms of the cornea. I. Epithelial-stromal interaction in vitro.

Electron microscopic studies of pure epithelial and stromal cultures and of combined cultures demonstrated that keratocytes activity was inhibited by the presence of epithelial cells in culture. The degradation of collagen and the formation of clear zones around the keratocytes within the explants of pure stroma is interpreted as an indication for the production of a collagenolytic substance by the active keratocytes. The collagenolytic activity of the keratocytes was not observed within the stroma of combined cultures and was probably inhibited by the activity of epithelial cells in these cultures. Furthermore, using a microculture method for the assessment of the metabolic activity of corneal cells in vitro, supernatants of epithelial cell cultures were shown to have a marked inhibitory effect on the capacity of keratocytes to synthesize DNA. No effect of stromal cell supernatant on epithelial cell activity could be detected by the same methods. It is suggested that this "one way" influence as observed in vitro might, in certain conditions, play a role as a regulatory mechanism in vivo.

Animals

Activation of the alternative complement pathway due to resistance of zymosan-bound amplification convertase to endogenous regulatory mechanisms.

The surface of zymosan (Zy), by affording a protected microenvironment for C3b and the amplification convertase stabilized by properdin, P,C3b,Bb, shifts the alternative complement pathway from slow fluid phase turnover to the amplification phase of its expression. This mode of activation is in contradistinction to that of the classical pathway, which follows conversion of a proenzyme, Cl, to its active form, C1. Under conditions in which the control proteins, C3b inactivator (C3bINA) and beta1H, completely, inactivated C3b on the sheep erythrocyte intermediate, EAC4b,3b, the activity of C3b bound to Zy,ZyC3b, was diminished by only one-third. Further, when ZyC3b was converted to ZyC3b,Bb,P there was an additional point of deregulation in that the convertase was resistant to beta1H-mediated decay-dissociation while P,C3b,Bb on the sheep erythrocyte exhibited the usual susceptibility to beta1H. That Zy alone could indeed promote rapid C3 cleavage by the alternative pathway through assembly and protection of the amplification convertase on its surface was demonstrated with a mixture of alternative pathway proteins, C3,B,D,P, C3bINA, and beta1H, that had each been purified to homogeneity. Interaction of these proteins at one-tenth their relative serum concentrations with Zy permitted low-grade inactivation of C3 and B to advance to the level of amplification after a 15 min lag period. Because the reaction of the purified proteins proceeded spontaneously when either regulatory protein was deleted, the effect of Zy was attributed to deregulation rather than to conversion of one of the proteins to a specific initiating state. The alternative pathway, through the normal presence of D, interacts with a microbial surface, such as Zy, to amplify deposition of C3b by circumvention of endogenous regulatory mechanisms, thereby augmenting host defense.

Animals

Multi-omics reveals cross-tissue regulatory mechanisms of autism risk loci via gut microbiota-immunity-brain axis.

Autism Spectrum Disorder (ASD) involves a multi-system interaction mechanism among genetics, immunity, and gut microbiota, yet its regulatory network remains undefined. This study conducted a meta-analysis on Genome-Wide Association Study data from four independent ASD cohorts to identify potential genetic loci. By integrating Polygenic Priority Score, brain region, and brain cell eQTL enrichment analyses, and combining summary-data-based Mendelian Randomisation (SMR) analyses of brain cis-eQTL and mQTL, bidirectional Mendelian Randomisation analyses of 473 gut microbiota, and SMR analysis of blood eQTL, SNPs such as rs2735307 and rs989134 with significant multi-dimensional associations were identified. These loci exert cross-tissue regulatory effects by participating in gut microbiota regulation, involving immune pathways such as T cell receptor signal activation and neutrophil extracellular trap formation, as well as cis-regulating neurodevelopmental genes (HMGN1 and H3C9P), or synergistically influencing epigenetic methylation modifications to regulate the expression of BRWD1 and ABT1. The cross-scale evidence chain constructed in this study provides a theoretical foundation for precision medicine research in ASD, holding promise to advance the development of innovative therapeutic strategies.

Autism spectrum disorder

Regulatory mechanisms of maternal imprinting at the murine Dlk1-Dio3 domain.

Genomic imprinting is an epigenetic process causing parent-of-origin specific gene expression. The Dlk1-Dio3 domain is one of the largest imprinted clusters. While DNA methylation at an intergenic CpG-island (IG-CGI) within the imprinting control region (ICR) controls expression from the paternal chromosome, mechanisms regulating the unmethylated maternal chromosome remain unknown. Within the transcriptional regulatory element (IG-TRE) of the ICR, deletions identified a minimal region in vitro exhibiting both silencing and enhancing activity, with SOX2 and ZFP281 contributing to enhancer function on the maternal chromosome. In vivo, however, this deletion did not affect maternal expression in mouse embryos; instead it activated Dlk1 on both parental chromosomes. Combining deletion of this IG-TRE with the lethal IG-CGI deletion rescued lethality in mice by balancing Dlk1 expression, despite persistent maternal gene upregulation. These results demonstrate that loss of expression at this domain is more detrimental than gain, highlighting the importance of in vivo analysis. Identification of active regulatory factors on the unmethylated maternal chromosome challenges the prevailing view that imprinting is primarily a methylation-driven phenomenon, further revealing the sophisticated hierarchical mechanisms governing imprinting control.

Animals

Research progress on the regulatory mechanisms of the PSY promoter.

Carotenoids are essential pigments in the plant photosynthetic apparatus, functioning in light harvesting, photoprotection, and signal transduction, and serving as precursors of vital nutrients such as vitamin A. Phytoene synthase (PSY) is the first rate-limiting enzyme in the plant carotenoid biosynthetic pathway, and its transcriptional regulation primarily depends on cis-acting promoter elements, associated transcription factors, and epigenetic status. The PSY promoter region contains core cis-elements as well as multiple light-, hormone-, and stress-responsive elements, which collectively function as key regulatory sites governing spatiotemporal expression. This review systematically summarizes recent advances in PSY promoter regulation by plant hormones (e.g., abscisic acid, ethylene, jasmonic acid), environmental factors (light signaling, temperature, salinity, and drought), and epigenetic mechanisms (DNA methylation, histone modifications, and chromatin remodeling). In addition, the application of transgenic and biotechnological approaches to PSY promoter regulation is further summarized. Including promoter sequence engineering with precise editing of cis-elements and promoter-targeted CRISPR activation/interference (CRISPRa/i) for tunable transcriptional control. Emphasis is placed on how these signals are integrated at the promoter level. Deeper insights into these mechanisms will provide both theoretical foundations and practical strategies for enhancing carotenoid accumulation and stress tolerance in crops through molecular design.

Promoter Regions, Genetic

Integrated transcriptomic, transcriptional factors, and protein interaction reveal the regulatory mechanisms of flowering time in rice (Oryza sativa L.).

Appropriate flowering time is important for rice regional adaptation and optimum rice production, but little is known about the omics of heading date in rice. Here, we studied omics including transcriptome, proteome and transcriptional factors to identify regulatory genes related to flowering time. A total of 1402 differentially expressed genes (DEGs, 721 up-regulated and 681 down-regulated) were detected in wild and mutant. These transcripts are classified according to biological processes, cellular components, and molecular functions. Among these differentially expressed genes, many transcription factor genes demonstrated multiple regulatory pathways involved in flowering time. Gene expression analysis showed that Os03g0122600 (OsMADS50), Os08g0105000 (Ehd3), Os06g0275000 (Hd1) were expressed higher and Os06g0199500 (OsHAL3), Os06g0498800 (OsMFT1), Os08g0105000 (Ehd3), Os06g0157700 (Hd3a), and Os02g0731700 (Ghd2), were expressed lower in wild compared to mutant, which are the key genes that regulate the flowering in rice. In addition, Ghd7 interacted with Os10g30860 and Os12g08260 using yeast two-hybrid assay. We identified 28 potential Ghd7 transcriptional regulators using the transcription factor-centered yeast one hybrid (TF-Centered Y1H) assay. Taken together, this study developed a new set of genomic resources to identify and characterize genes, proteins, and motifs associated with flowering time.

Oryza

Teleost lincRNAs: Functional roles, regulatory mechanisms, and future applications in aquaculture.

Long intergenic non-coding RNAs (lincRNAs) regulate gene expression across vertebrate physiological systems, yet their functional roles in teleost fish remain incompletely synthesized. This review systematically integrates current evidence through PRISMA-guided searches across PubMed, Web of Science, and Scopus, identifying ten lincRNA-focused functional studies with genetic, mechanistic, or developmental validation, complemented by twenty two supplementary contextual references. Findings span development, immunity, environmental adaptation, reproduction, regeneration, and toxicology, with each association graded as experimentally validated, bioinformatically predicted, correlational, or speculative. This synthesis offers three core contributions. First, it shows that cis-acting regulation on neighboring genes, mediated through Wnt, NF-κB, and AHR signaling, is the dominant validated lincRNA mechanism across teleost physiological domains. Second, it demonstrates that direct experimental validation, primarily via CRISPR-Cas9 and chromatin-capture assays, remains concentrated in zebrafish, whereas aquaculture-species associations remain largely correlational. Third, it identifies two findings that challenge current lincRNA classification: unexpected regulatory directionality at the slincR-sox9b locus, and micropeptide-encoding potential within annotated lincRNAs. Together, these contributions establish an evidence-graded foundation for future mechanistic studies and translational aquaculture applications.

Aquaculture