Mode Of Regulation Research Articles

Neurogranin modulates the rate of association between calmodulin and target peptides

The best-known mode of action of calmodulin (CaM) is binding of Ca2+ to its N- and C-domains, followed by binding to target proteins. An underappreciated facet of this process is that CaM is typically bound to proteins at basal levels of free Ca2+, including the small, intrinsically disordered, neuronal IQ-motif proteins called PEP-19 and neurogranin (Ng). PEP-19 and Ng would not be effective competitive inhibitors of high-affinity Ca2+-dependent CaM targets at equilibrium because they bind to CaM with relatively low affinity, but they could influence the time course of CaM signaling by affecting the rate of association of CaM with high-affinity Ca2+-dependent targets. This mode of regulation may be domain specific because PEP-19 binds to the C-domain of CaM, whereas Ng binds to both N- and C-domains. In this report, we used a model CaM binding peptide (CKIIp) to characterize the preferred pathway of complex formation with Ca2+-CaM at low levels of free Ca2+ (0.25–1.5 μM), and how PEP-19 and Ng affect this process. We show that the dominant encounter complex involves association of CKIIp with the N-domain of CaM, even though the C-domain has a greater affinity for Ca2+. We also show that Ng greatly decreases the rate of association of Ca2+-CaM with CKIIp due to the relatively slow dissociation of Ng from CaM, and to interactions between the Gly-rich C-terminal region of Ng with the N-domain of CaM, which inhibits formation of the preferred encounter complex with CKIIp. These results provide the general mechanistic paradigms that binding CaM to targets can be driven by its N-domain, and that low-affinity regulators of CaM signaling have the potential to influence the rate of activation of high-affinity CaM targets and potentially affect the distribution of limited CaM among multiple targets during Ca2+ oscillations.

Proclaimed and Real Purposes of Policies for Regulation of Access to Higher Education in Brazil (1997-2017)

The article aimed to analyze the purposes of educational policies that reformed the last stage of basic education (high school) and higher education in Brazil, between 1997 and 2017, considering the mode of state regulation established in its relationship with access to education Brazilian public superior. Starting from a Marxian theoretical perspective, we undertook descriptive and explanatory research taking as sources the legal provisions enacted in the period that reformed secondary education and higher education in the period established in the study. The analysis of the proclaimed and real purposes of the devices showed that although there are specific regulations for higher education, access to this level is also impacted by policies relating to basic education, especially secondary education, which is why we infer that the regulation of basic and higher education produced in the period calibrates processes of state regulation of access to higher education. To the extent that they are reforming policies that directly (higher education) and indirectly (secondary education), due to their purposes analyzed here, have an impact on expanding or slowing access to higher education, highlighting societal and educational projects in dispute that, for a certain period, they maintain hegemony by implementing their policies. expanding or slowing down access to higher education, highlighting societal and educational projects in dispute that, for a certain period, hold hegemony by implementing their policies.

The power to transform structures: power complexes and the challenges for realising a wellbeing economy

This article draws on different strands of existing scholarship to provide an analytical framework for understanding the barriers to achieving a well-being economy. It explores the interplay between agential and structural power, where some actor-coalitions can reproduce or transform pre-existing structures. Conversely, these structures are strategically selective, favouring some actors, interests, and strategies over others. Making sense of this interplay between agential and structural power, the article introduces the notion of power complexes—time-space-specific actor-coalitions with common industry-related interests and the power to reproduce or transform structures in a given conjuncture. To understand the historical “becoming” of today’s political-economic terrain, the article provides a regulationist-inspired history of the rise, fall, and re-emergence of four power complexes: the financial, fossil, livestock-agribusiness, and digital. They pose significant threats to pillars of a wellbeing economy such as ecological sustainability, equ(al)ity, and democracy. Subsequently, today’s structural context is scrutinised in more detail to understand why certain actors dominate strategic calculations in contemporary power complexes. This reveals strategic selectivities that favour multi- and transnational corporate actors over civil society, labour movements, and public bureaucracies. The article then examines firm-to-state lobbying as a strategy employed by corporate actors within today’s structural context to assert their interests. It presents illustrative cases of Blackstone, BP, Bayer, and Alphabet. Finally, it explores implications and challenges for realising a wellbeing economy based on post-/degrowth visions. It emphasises the double challenge faced by such a wellbeing-economy actor-coalition. On one hand, it has to navigate within contemporary modes of regulation that favour corporate strategies of capital accumulation while, on the other, it must confront the self-expanding and extractive logic of capital. In this context, three key challenges are outlined: the need to form unconventional strategic alliances, operate on various spatial dimensions simultaneously, and institutionalise alternatives to firm-to-state lobbying to influence policymaking.

China’s development path, 1949–2022

China’s path is conceived as a transition from an economically underdeveloped and semi-colonised country of the Global South into a modern socialist country in a multipolar world where successive steps (modes of regulation) were shaped by China’s external environment (uneven and combined development) and a succession of contradictions and crises encountered along the way. Three phases are examined: a turbulent phase of socialist construction in a context of capital shortage and US embargoes; a phase of reform and opening up in an era of neoliberal globalisation, whose early roots lay in the early 1970s’ rapprochement with the US; and a New Era dating from 2017. In each phase, crises and contradictions saw waves of reform, involving successive joint transformations of economic structures and institutions, while each phase was anticipated in the years that preceded it, so opening up started in the early 1970s with the rapprochement with the US, and aspects of the New Era concern with innovation, green development, common prosperity and an equitable global order started to emerge earlier.

Abstract 162: Post-transcriptional Regulation Of FGF21 In Obesity And Metabolism

Imbalances in energy intake and expenditure are the leading cause of the dramatic surge in obesity and cardiovascular disease affecting >60% of Americans. Increasing fat content in the average diet alters metabolism and contributes to disease. FGF21, a secreted hepatokine, modulates feeding behavior and energy expenditure (EE) primarily through signaling in brain and adipose tissue. FGF21 analogues are actively in clinical trials for several metabolic diseases, and it is therefore important to understand the various pathways that control FGF21. FGF21 is regulated by well-defined transcriptional programs, but its post-transcriptional regulation is less understood. Post-transcriptional regulation is mediated by RNA binding proteins (RBPs) that control mRNA stability. One family of such RBPs is the ZFP36 family proteins (ZFP36, ZFP36L1, ZFP36L2) that bind to AU-rich regions in the 3’UTR, leading to mRNA degradation. All 3 ZFP36 family proteins are redundant, therefore we knocked out Zfp36 , Zfp36l1 and Zfp36l2 in livers of adult mice. Fgf21 was the most upregulated gene following loss of ZFP36 family proteins in the liver. Consistent with elevated FGF21, these mice rapidly lost weight and fat mass while remaining metabolically healthy. Using metabolic cages, we observed that mice lacking hepatic ZFP36 family proteins had increased food intake and EE and decreased respiratory exchange ratio, indicating preferential fat burning. We then generated mice lacking the ZFP36 family proteins and Fgf21 which partially restored the metabolic phenotypes observed, leading to the hypothesis that ZFP36 family proteins post-transcriptionally regulate Fgf21 in controlling food intake and energy homeostasis. To determine if loss of ZFP36 family proteins protects against diet-induced obesity, we fed mice lacking the ZFP36 family proteins a high fat diet, however, they were entirely protected from diet induced obesity. The protection was partially reversed by additional deletion of Fgf21 . These findings demonstrate that FGF21 is regulated post-transcriptionally by the ZFP36 family proteins and loss of this mode of regulation has significant metabolic implications in diet-induced obesity and could lead to new therapeutic approaches to treat metabolic disease.

A novel bivalent interaction mode underlies a non-catalytic mechanism for Pin1-mediated protein kinase C regulation.

Regulated hydrolysis of the phosphoinositide phosphatidylinositol(4,5)-bis-phosphate to diacylglycerol and inositol-1,4,5-P3 defines a major eukaryotic pathway for translation of extracellular cues to intracellular signaling circuits. Members of the lipid-activated protein kinase C isoenzyme family (PKCs) play central roles in this signaling circuit. One of the regulatory mechanisms employed to downregulate stimulated PKC activity is via a proteasome-dependent degradation pathway that is potentiated by peptidyl-prolyl isomerase Pin1. Here, we show that contrary to prevailing models, Pin1 does not regulate conventional PKC isoforms α and βII via a canonical cis-trans isomerization of the peptidyl-prolyl bond. Rather, Pin1 acts as a PKC binding partner that controls PKC activity via sequestration of the C-terminal tail of the kinase. The high-resolution structure of full-length Pin1 complexed to the C-terminal tail of PKCβII reveals that a novel bivalent interaction mode underlies the non-catalytic mode of Pin1 action. Specifically, Pin1 adopts a conformation in which it uses the WW and PPIase domains to engage two conserved phosphorylated PKC motifs, the turn motif and hydrophobic motif, respectively. Hydrophobic motif is a non-canonical Pin1-interacting element. The structural information combined with the results of extensive binding studies and experiments in cultured cells suggest that non-catalytic mechanisms represent unappreciated modes of Pin1-mediated regulation of AGC kinases and other key enzymes/substrates.

Persistent ∆FosB expression limits recurrent seizure activity and provides neuroprotection in the dentate gyrus of APP mice

Recurrent seizures lead to accumulation of the activity-dependent transcription factor ∆FosB in hippocampal dentate granule cells in both mouse models of epilepsy and mouse models of Alzheimer’s disease (AD), which is also associated with increased incidence of seizures. In patients with AD and related mouse models, the degree of ∆FosB accumulation corresponds with increasing severity of cognitive deficits. We previously found that ∆FosB impairs spatial memory in mice by epigenetically regulating expression of target genes such as calbindin that are involved in synaptic plasticity. However, the suppression of calbindin in conditions of neuronal hyperexcitability has been demonstrated to provide neuroprotection to dentate granule cells, indicating that ∆FosB may act over long timescales to coordinate neuroprotective pathways. To test this hypothesis, we used viral-mediated expression of ∆JunD to interfere with ∆FosB signaling over the course of several months in transgenic mice expressing mutant human amyloid precursor protein (APP), which exhibit spontaneous seizures and develop AD-related neuropathology and cognitive deficits. Our results demonstrate that persistent ∆FosB activity acts through discrete modes of hippocampal target gene regulation to modulate neuronal excitability, limit recurrent seizure activity, and provide neuroprotection to hippocampal dentate granule cells in APP mice.

Sm-like protein Rof inhibits transcription termination factor ρ by binding site obstruction and conformational insulation.

Transcription termination factor ρ is a hexameric, RNA-dependent NTPase that can adopt active closed-ring and inactive open-ring conformations. The Sm-like protein Rof, a homolog of the RNA chaperone Hfq, inhibits ρ-dependent termination in vivo but recapitulation of this activity in vitro has proven difficult and the precise mode of Rof action is presently unknown. Here, our cryo-EM structures of ρ-Rof and ρ-RNA complexes show that Rof undergoes pronounced conformational changes to bind ρ at the protomer interfaces, undercutting ρ conformational dynamics associated with ring closure and occluding extended primary RNA-binding sites that are also part of interfaces between ρ and RNA polymerase. Consistently, Rof impedes ρ ring closure, ρ-RNA interactions and ρ association with transcription elongation complexes. Structure-guided mutagenesis coupled with functional assays confirms that the observed ρ-Rof interface is required for Rof-mediated inhibition of cell growth and ρ-termination in vitro. Bioinformatic analyses reveal that Rof is restricted to Pseudomonadota and that the ρ-Rof interface is conserved. Genomic contexts of rof differ between Enterobacteriaceae and Vibrionaceae, suggesting distinct modes of Rof regulation. We hypothesize that Rof and other cellular anti-terminators silence ρ under diverse, but yet to be identified, stress conditions when unrestrained transcription termination by ρ may be detrimental.

RUNX1 regulates promoter activity in the absence of cognate DNA binding motifs.

Runt-related transcription factor 1 (RUNX1) plays an important role in normal haematopoietic cell development and function, and its function is frequently disrupted in leukaemia. RUNX1 is widely recognised as a sequence-specific DNA binding factor that recognises the motif 5'-TG(T/C)GGT-3' in promoter and enhancer regions of its target genes. Moreover, RUNX1 fusion proteins, such as RUNX1-ETO formed by the t(8;21) translocation, retain the ability to recognise and bind to this sequence to elicit atypical gene regulatory effects on bona fide RUNX1 targets. However, our analysis of publicly available RUNX1 chromatin immunoprecipitation sequencing (ChIP-Seq) data has provided evidence challenging this dogma, revealing that this motif-specific model of RUNX1 recruitment and function is incomplete. Our analyses revealed that the majority of RUNX1 genomic localisation occurs outside of promoters, that 20% of RUNX1 binding sites lack consensus RUNX motifs, and that binding in the absence of a cognate binding site is more common in promoter regions compared to distal sites. Reporter assays demonstrate that RUNX1 can drive promoter activity in the absence of a recognised DNA binding motif, in contrast to RUNX1-ETO. RUNX1-ETO supresses activity when it is recruited to promoters containing a sequence specific motif, while interestingly, it binds but does not repress promoters devoid of a RUNX1 recognition site. These data suggest that RUNX1 regulation of target genes occurs through multiple mechanisms depending on genomic location, the type of regulatory element and mode of recruitment.

Gene expression regulation by modulating Hfq expression in coordination with tailor-made sRNA-based knockdown in Escherichia coli

The tailor-made synthetic sRNA-based gene expression knockdown system has demonstrated its efficacy in achieving pathway balancing in microbes, facilitating precise target gene repression and fine-tuned control of gene expression. This system operates under a competitive mode of gene regulation, wherein the tailor-made synthetic sRNA shares the intrinsic intracellular Hfq protein with other RNAs. The limited intracellular Hfq amount has the potential to become a constraining factor in the post-transcription regulation of sRNAs. To enhance the efficiency of the tailor-made sRNA gene expression regulation platform, we introduced an Hfq expression level modulation-coordinated sRNA-based gene knockdown system. This system comprises tailor-made sRNA expression cassettes that produce varying Hfq expression levels using different strength promoters. Modulating the expression levels of Hfq significantly improved the repressing capacity of sRNA, as evidenced by evaluations with four fluorescence proteins. In order to validate the practical application of this system, we applied the Hfq-modulated sRNA-based gene knockdown cassette to Escherichia coli strains producing 5-aminolevulinic acid and L-tyrosine. Diversifying the expression levels of metabolic enzymes through this cassette resulted in substantial increases of 74.6% in 5-aminolevulinic acid and 144% in L-tyrosine production. Tailor-made synthetic sRNA-based gene expression knockdown system, coupled with Hfq copy modulation, exhibits potential for optimizing metabolic fluxes through biosynthetic pathways, thereby enhancing the production yields of bioproducts.

Deciphering cell types by integrating scATAC-seq data with genome sequences.

The single-cell assay for transposase-accessible chromatin using sequencing (scATAC-seq) technology provides insight into gene regulation and epigenetic heterogeneity at single-cell resolution, but cell annotation from scATAC-seq remains challenging due to high dimensionality and extreme sparsity within the data. Existing cell annotation methods mostly focus on the cell peak matrix without fully utilizing the underlying genomic sequence. Here we propose a method, SANGO, for accurate single-cell annotation by integrating genome sequences around the accessibility peaks within scATAC data. The genome sequences of peaks are encoded into low-dimensional embeddings, and then iteratively used to reconstruct the peak statistics of cells through a fully connected network. The learned weights are considered as regulatory modes to represent cells, and utilized to align the query cells and the annotated cells in the reference data through a graph transformer network for cell annotations. SANGO was demonstrated to consistently outperform competing methods on 55 paired scATAC-seq datasets across samples, platforms and tissues. SANGO was also shown to be able to detect unknown tumor cells through attention edge weights learned by the graph transformer. Moreover, from the annotated cells, we found cell-type-specific peaks that provide functional insights/biological signals through expression enrichment analysis, cis-regulatory chromatin interaction analysis and motif enrichment analysis.

Effects of plant extracts and derivatives on cardiac K+, Nav, and Cav channels: a review.

Natural products (NPs) are endless sources of compounds for fighting against several pathologies. Many dysfunctions, including cardiovascular disorders, such as cardiac arrhythmias have their modes of action regulation of the concentration of electrolytes inside and outside the cell targeting ion channels. Here, we highlight plant extracts and secondary metabolites' effects on the treatment of related cardiac pathologies on hERG, Nav, and Cav of cardiomyocytes. The natural product's pharmacology of expressed receptors like alpha-adrenergic receptors causes an influx of Ca2+ ions through receptor-operated Ca2+ ion channels. We also examine the NPs associated with cardiac contractions such as myocardial contractility by reducing the L-type calcium current and decreasing the intracellular calcium transient, inhibiting the K+ induced contractions, decreasing amplitude of myocyte shortening and showed negative ionotropic and chronotropic effects due to decreasing cytosolic Ca2+. We examine whether the NPs block potassium channels, particular the hERG channel and regulatory effects on Nav1.7.

Tourism e-commerce marketing following live-streaming: consumer behavior and verification psychology

Purpose Based on social cognitive theory, this study aims to explore the psychological mechanism behind consumer verification behavior following tourism e-commerce live-streaming. Design/methodology/approach Based on grounded theory, data were collected through 20 semi-structured in-depth interviews and analyzed. Findings This study identified that companies commonly use reminder messages and secondary promotions to facilitate the verification of tourism live-streaming products. Throughout this process, consumers undergo various psychologies related to verification. Specifically, they experience four positive verification psychologies: fear of missing out, anticipated emotions, status self-esteem and promotional perception. They also encounter two negative verification psychologies: psychological reactance and invasiveness. In addition, environmental factors such as the type of tourism live-streaming products and tourism destinations, along with individual trait factors like cognitive miserliness, tourism experience, autonomy, regulatory mode and impulsiveness, play significant roles in shaping verification behavior. These factors collectively influence the formation of verification behavior. Originality/value This study can provide recommendations for tourism companies to conduct marketing events following live-streaming. It is one of the earlier comprehensive studies discussing how to promote verification behavior following tourism e-commerce live-streaming. It helps to understand the psychological mechanism underlying the formation of verification behavior.

Unveiling the intricacies of allosteric regulation in aspartate kinase from the Wolbachia endosymbiont of Brugia Malayi: Mechanistic and therapeutic insights

Aspartate kinase (AK), an enzyme from the Wolbachia endosymbiont of Brugia malayi (WBm), plays a pivotal role in the bacterial cell wall and amino acid biosynthesis, rendering it an attractive candidate for therapeutic intervention. Allosteric inhibition of aspartate kinase is a prevalent mode of regulation across microorganisms and plants, often modulated by end products such as lysine, threonine, methionine, or meso-diaminopimelate. The intricate and diverse nature of microbial allosteric regulation underscores the need for rigorous investigation. This study employs a combined experimental and computational approach to decipher the allosteric regulation of WBmAK. Molecular Dynamics (MD) simulations elucidate that ATP (cofactor) and ASP (substrate) binding induce a closed conformation, promoting enzymatic activity. In contrast, the binding of lysine (allosteric inhibitor) leads to enzyme inactivation and an open conformation. The enzymatic assay demonstrates the optimal activity of WBmAK at 28 °C and a pH of 8.0. Notably, the allosteric inhibition study highlights lysine as a more potent inhibitor compared to threonine. Importantly, this investigation sheds light on the allosteric mechanism governing WBmAK and imparts novel insights into structure-based drug discovery, paving the way for the development of effective inhibitors against filarial pathogens.

On the relation between oral contraceptive use and self-control.

In two studies we examined the relation between oral contraceptive (OC) use and self-reported levels of self-control in undergraduate women using OCs (Study 1: OC group N = 399, Study 2: OC group N = 288) and naturally cycling women not using any form of hormonal contraceptives (Study 1: Non-OC group N = 964, Study 2: Non-OC group N = 997). We assessed the self-overriding aspect of self-control using the Brief Self-Control Scale (BSCS) and strategies for self-regulation using the Regulatory Mode Scale (RMS), which separately measures the tendency to assess one's progress towards a goal (assessment), and the tendency to engage in activities that move one towards an end goal (locomotion). In Study 1, we found no significant differences between OC and non-OC groups in their levels of self-overriding or self-regulatory assessment. However, we found that those in the OC group reported significantly greater levels of self-regulatory locomotion compared to those in the non-OC group, even after controlling for depression symptoms and the semester of data collection. The findings from Study 2 replicated the findings from Study 1 in a different sample of participants, with the exception that OC use was also related to higher levels of assessment in Study 2. These results indicate that OC use is related to increases in self-regulatory actions in service of goal pursuit and perhaps the tendency to evaluate progress towards goals.

With whom do people compare at work? The role of regulatory mode and social comparison motives

AbstractWe investigate whether people's regulatory mode (assessment and locomotion) and social comparison motives (self‐evaluation vs. self‐enhancement) jointly influence with whom—either a peer or their leader—individuals prefer to compare. In three preregistered studies (N = 839), we measured participants' chronic regulatory mode and assessed their comparison target preference separately for different social comparison motives. For each motive, participants indicated with whom they would prefer to compare, using choice (Study 1) and rating (Studies 2 and 3) measures. Supporting our predictions, assessment interacted with social comparison motives such that assessment was positively associated with preferring to compare to peers for self‐enhancement motives, but unrelated to comparison target preference regarding self‐evaluation motives. In addition, and as predicted, locomotion was consistently positively associated with preferring leaders as comparison target, independently of social comparison motives. These results contribute to emerging research highlighting the key role of individuals' regulatory mode in understanding interpersonal dynamics at work.

Energy Performance of Higher Education Institutions Buildings Operating During Quarantine Restrictions and/or Martial Law in Ukraine

Abstract During the pandemic and periods of martial law, educational institutions in Ukraine implemented various forms of organising the educational process, combining in-person and remote classes. As a result, there has been a decrease in the level of use of building premises. The analysis of the characteristics of energy consumption in these conditions requires additional attention. In this study, a dynamic energy model of the building was created using the educational building of Igor Sikorsky Kyiv Polytechnic Institute as an example. Energy consumption for heating needs was determined for normal operating conditions and quarantine conditions in Ukraine (only a specific part of the premises is being operated, ensuring that the standard temperature value is maintained while people are present). Based on the results of the study, the features of the energy consumption of the building during quarantine/martial law restrictions, subject to the partial use of the building, were analysed, and the main disadvantages of such a mode were identified. For the educational building of the university, the total energy consumption for heating needs depends on the number of rooms that are actively used, and the modes of regulation of heating and ventilation; the consumption can decrease depending on the chosen scenario by 61 %, 56 %, and 34 % in quarantine mode. The findings indicate that the efficiency of regulation modes can decrease by more than four times when compared to normal mode due to internal heat exchange with unoccupied rooms.

The impact of advice uncertainty and individual regulatory modes on advice taking

AbstractIn previous research on advice taking, researchers have mainly focused on certain types of advice. However, in practice, when people give advice to others, there is often a degree of uncertainty (e.g. I think that the distance between Beijing and Shanghai is between 800 and 1200 km). To date, only a few studies have examined the impact of uncertain advice on advice taking. Through two studies, the present research explores the influence of advice uncertainty and individuals’ regulatory mode predominance on advice taking and the mediating mechanism. In Study 1, the participants' chronic regulatory mode was measured by a questionnaire, and in Study 2, we induced the predominance of the participants’ situational regulatory mode using a recall task. We found that people are more likely to adopt advice with low uncertainty. The moderating effect of participants' regulatory mode on the impact of advice uncertainty on advice taking occurs only when the regulatory mode is induced by the situation. For the assessment‐predominant group, there was a significant difference between the no‐uncertainty group and the high‐uncertainty group, while for the locomotion‐predominant group, this difference was not significant. Additionally, our study revealed the mediating role of advice reliability, which existed only when the participants were able to compare low‐ and no‐uncertainty advice in a within‐participant design. That is, when decision makers adopt uncertainty advice within ranges, they not only consider reliability but also weigh multiple factors. Our findings contribute to understanding the mechanisms underlying individuals' preferences for uncertain advice and reasoning about individual differences.

Genome-wide identification analysis of the 4-Coumarate: CoA ligase (4CL) gene family expression profiles in Juglans regia and its wild relatives J. Mandshurica resistance and salt stress

Persian walnut (Juglans regia) and Manchurian walnut (Juglans mandshurica) belong to Juglandaceae, which are vulnerable, temperate deciduous perennial trees with high economical, ecological, and industrial values. 4-Coumarate: CoA ligase (4CL) plays an essential function in plant development, growth, and stress. Walnut production is challenged by diverse stresses, such as salinity, drought, and diseases. However, the characteristics and expression levels of 4CL gene family in Juglans species resistance and under salt stress are unknown. Here, we identified 36 Jr4CL genes and 31 Jm4CL genes, respectively. Based on phylogenetic relationship analysis, all 4CL genes were divided into three branches. WGD was the major duplication mode for 4CLs in two Juglans species. The phylogenic and collinearity analyses showed that the 4CLs were relatively conserved during evolution, but the gene structures varied widely. 4CLs promoter region contained multiply cis-acting elements related to phytohormones and stress responses. We found that Jr4CLs may be participated in the regulation of resistance to anthracnose. The expression level and some physiological of 4CLs were changed significantly after salt treatment. According to qRT-PCR results, positive regulation was found to be the main mode of regulation of 4CL genes after salt stress. Overall, J. mandshurica outperformed J. regia. Therefore, J. mandshurica can be used as a walnut rootstock to improve salt tolerance. Our results provide new understanding the potential functions of 4CL genes in stress tolerance, offer the theoretical genetic basis of walnut varieties adapted to salt stress, and provide an important reference for breeding cultivated walnuts for stress tolerance.

Roles of Histone Deacetylase 4 in the Inflammatory and Metabolic Processes.

Histone deacetylase 4 (HDAC4), a class IIa HDAC, has gained attention as a potential therapeutic target in treating inflammatory and metabolic processes based on its essential role in various biological pathways by deacetylating non-histone proteins, including transcription factors. The activity of HDAC4 is regulated at the transcriptional, post-transcriptional, and post-translational levels. The functions of HDAC4 are tissue-dependent in response to endogenous and exogenous factors and their substrates. In particular, the association of HDAC4 with non-histone targets, including transcription factors, such as myocyte enhancer factor 2, hypoxia-inducible factor, signal transducer and activator of transcription 1, and forkhead box proteins, play a crucial role in regulating inflammatory and metabolic processes. This review summarizes the regulatory modes of HDAC4 activity and its functions in inflammation, insulin signaling and glucose metabolism, and cardiac muscle development.