Co-regulatory Mechanisms Research Articles

Co-Regulation Mechanism of Host p53 and Fos in Transcriptional Activation of ILTV Immediate-Early Gene ICP4.

Infectious laryngotracheitis virus (ILTV) exhibits a cascade expression pattern of encoded genes, and ICP4 is the only immediate-early gene of ILTV, which plays a crucial role in initiating the subsequent viral genes. Therefore, studying the transcriptional regulation mechanism of ICP4 holds promise for effectively blocking ILTV infection and spread. Host transcriptional factors p53 and Fos are proven to regulate a variety of viral infections, and our previous studies have demonstrated their synergistic effects in regulating ILTV infection. In this study, we constructed eukaryotic expression vectors for p53 and Fos as well as their specific siRNAs and transfected them into a chicken hepatoma cell line. The results showed that knocking down p53 or Fos significantly inhibited ICP4 transcription, while overexpressing p53 or Fos had an opposite effect. A further CoIP and ChIP-qPCR assay suggested p53 and Fos physically interacted with each other, and jointly bound to the upstream transcriptional regulatory region of ICP4. To elucidate the specific mechanisms of p53 and Fos in regulating ICP4 transcription, we designed p53 and Fos protein mutants by mutating their DNA binding domains, which significantly reduced their binding ability to DNA without affecting their interaction. The results showed that Fos directly bound to the promoter region of ICP4 as a binding target of p53, and the p53-Fos protein complex acted as a transcriptional co-regulator of ICP4. Studying the transcriptional process and regulatory pattern of ICP4 is of great significance for understanding the molecular mechanism of ILTV infection, and thus for finding effective methods to control and prevent it.

Co-regulatory mechanisms and potential markers of oxidative stress-related genes in vitiligo and alopecia areata.

The specific role of oxidative stress (OS) in vitiligo and alopecia areata (AA) remains unclear. The aim of this study was to analyze and identify the key markers of OS in vitiligo and AA by bioinformatics. We obtained vitiligo and AA datasets from gene expression omnibus (GEO) database. The difference-expressed genes of vitiligo and AA were identified by differential analysis, and the functions of difference-expressed genes were identified by gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) enrichment analysis. Subsequently, Veen package was used to obtain the intersection genes of OS-related genes with vitiligo and AA. Finally, we used CIBERSORT to assess the infiltration of immune cells in vitiligo and AA. Through enrichment analysis, we found that vitiligo and AA were mainly enriched in cell cycle and cell adhesion molecular channels. We identified KLB and EIF3C as key genes in OS regulation of vitiligo and AA, and found that KLB and EIF3C participate in disease progression by regulating T cells and neutrophils. According to our findings, KLB and EIF3C play a crucial role in the progression and development of vitiligo and AA, which have been identified as biomarkers and target for early diagnosis of patients.

A “trapezoidal” relationship between solar radiation and chlorophyll concentrations at the center of the South Pacific Gyre

Understanding the driving mechanism of phytoplankton dynamics is key to forecasting future changes in the ocean. Here, we report an apparent “trapezoidal” relationship between chlorophyll concentrations (Chl) and surface photosynthetically available radiation (PAR(0)) at the center of the South Pacific Gyre (cSPG) based on 18 years of MODIS Aqua measurements. A comparison of Chl with a photoacclimation model revealed that photoacclimation alone could not explain the temporal dynamics of Chl. Instead, the Chl dynamics were explained by a combination of photoacclimation, nutrient limitation, and the grazing pressure of zooplankton at different times throughout the year. An annual “trapezoidal” spiral relationship between Chl and PAR(0) suggested that the steady state of phytoplankton populations at the cSPG could be influenced by the alternation of co-regulation mechanisms during a year. Because this same pattern occurs in other subtropical gyres, this understanding of the underlying mechanisms not only facilitates simulating and forecasting phytoplankton dynamics but also provides a new perspective on how multiple stressors may impact phytoplankton communities in a warmer climate.

Spatial distribution and environmental/biological co-regulation mechanism of dimethyl sulfur compounds in the eastern Indian Ocean

Dimethyl sulfur compounds including dimethylsulfoniopropionate (DMSP), dimethyl sulfide (DMS), and dimethyl sulfoxide (DMSO), play a crucial part in global sulfur cycling. The eastern Indian Ocean (EIO), characterized by its remarkable diversity of biomes and climate dynamics, is integral to global climate regulation. However, the regulation mechanism of DMS (P, O) in the EIO remains to be elucidated in detail. This paper presented a field survey aimed at investigating the spatial distribution of DMS (P, O) and their relationships with environmental and biological factors in the EIO. The surface concentrations of DMS, DMSPt, and DMSOt varied from 0.07 to 7.37 nmol/L, 0.14 to 9.17 nmol/L, and 0.15 to 3.32 nmol/L, respectively, and their distributions are attributed to high Chl-a concentration near Sri Lanka and the influence of ocean currents (Wyrtki jets, Bay of Bengal runoff). Higher concentrations of DMS (P) and DMSOt were predominantly observed in water columns shallower than 75m and deeper than 75m deep, respectively. The monthly DMS fluxes in the study area peaked in August. Temperature and Dissolved Silica Index (DSI) were the key environmental determinants for DMS distribution, while nitrate (NO3-) was the primary factor for both DMSPt and DMSOt. In terms of biological factors, Prochlorococcus and Synechococcus were significant contributors to DMS (P, O) dynamics. Synechococcus was the dominant influence on the DMS source and DMSPt sink, whereas Prochlorococcus primarily consumed DMSOt. Furthermore, the structural equation modeling (SEM) revealed the relationship between DMS, DMSPt, DMSOt, and the key environmental/biological factors, as well as among them, and together they formed a co-regulatory network in the EIO. This contributes significantly to the advancement of global ecosystem models for DMS (P, O).

Coregulatory effects of multiple histone modifications in key ferroptosis-related genes for lung adenocarcinoma.

Aim: The present study was designed to investigate the coregulatory effects ofmultiple histone modifications (HMs) on gene expression in lung adenocarcinoma (LUAD). Materials & methods: Ten histones forLUAD were analyzed usingChIP-seq and RNA-seq data. An innovative computational method is proposed to quantify the coregulatory effects of multiple HMs on gene expressionto identify strong coregulatory genes and regions. This method was appliedto explore the coregulatory mechanisms of key ferroptosis-related genes in LUAD. Results: Nine strong coregulatory regions were identified for six ferroptosis-related genes with diverse coregulatory patterns (CA9, PGD, CDKN2A, PML, OTUB1 and NFE2L2). Conclusion: This quantitative method could be usedto identify important HMcoregulatory genes and regions that may be epigenetic regulatory targets in cancers.

The relational change mechanisms of child‐centered play therapy with children exposed to adverse childhood experiences

AbstractThe researchers examined the relational mechanisms and coregulatory change mechanisms of child‐centered play therapy (CCPT) with children (ages 5–8) who endured multiple adverse childhood experiences (ACEs). The researchers computed surrogate synchrony analyses to measure heart rate synchrony between counselor and child participants during CCPT treatment. Child participants received between 10 and 14 CCPT sessions in the elementary school setting. Participants and counselor wore Empatica© E4 wristbands during sessions to collect heart rate data continuously during play therapy sessions. The researchers found consistent, large child‐counselor heart rate synchrony levels across play therapy sessions. The researchers discuss the implications of this research for counselors and play therapists working with children impacted by ACEs.

Effectiveness of a gamified learning analytics dashboard with coregulation mechanism for self-regulated learning in college ethics courses

ABSTRACT It is known that teachers commonly utilize learning platforms equipped with Learning Analytics Dashboards (LAD) to support students in their Self-Regulated Learning (SRL) endeavors. However, students may struggle to effectively employ LAD due to a lack of sufficient metacognitive skills. Co-regulation of learning (CoRL) has been proven to facilitate metacognitive knowledge sharing. However, the implementation of LAD with CoRL mechanisms in self-paced, asynchronous learning environments, aimed at enhancing students' SRL, remains unclear. Investigating how students utilize a LAD with CoRL and how such a system can promote SRL in selfpaced, asynchronous courses is an important topic. This study designed a gamified LAD utilizing a futures trading market interactive interface as the CoRL mechanism. A quasi-experimental design was adopted to assess the effects of the gamified LAD with CoRL on SRL, learning engagement, and academic achievement among 60 students from two Business Ethics classes over the course of a semester. The gamified LAD with CoRL had positive effects on the SRL and learning engagement of the asynchronous learners in the experimental group. Significant differences were observed in the academic achievement of the experimental and control groups. The gamified LAD with CoRL had positive effects on learners in self-paced, asynchronous courses.

Prevalence of different virulence factors and their association with antimicrobial resistance among Pseudomonas aeruginosa clinical isolates from Egypt

BackgroundEmergence of multi-drug resistant Pseudomonas aeruginosa, coupled with the pathogen’s versatile virulence factors, lead to high morbidity and mortality rates. The current study investigated the potential association between the antibiotic resistance and the production of virulence factors among P. aeruginosa clinical isolates collected from Alexandria Main University Hospital in Egypt. We also evaluated the potential of the phenotypic detection of virulence factors to reflect virulence as detected by virulence genes presence. The role of alginate in the formation of biofilms and the effect of ambroxol, a mucolytic agent, on the inhibition of biofilm formation were investigated.ResultsA multi-drug resistant phenotype was detected among 79.8% of the isolates. The most predominant virulence factor was biofilm formation (89.4%), while DNase was least detected (10.6%). Pigment production was significantly associated with ceftazidime susceptibility, phospholipase C production was significantly linked to sensitivity to cefepime, and DNase production was significantly associated with intermediate resistance to meropenem. Among the tested virulence genes, lasB and algD showed the highest prevalence rates (93.3% and 91.3%, respectively), while toxA and plcN were the least detected ones (46.2% and 53.8%, respectively). Significant association of toxA with ceftazidime susceptibility, exoS with ceftazidime and aztreonam susceptibility, and plcH with piperacillin-tazobactam susceptibility was observed. There was a significant correlation between alkaline protease production and the detection of algD, lasB, exoS, plcH and plcN; pigment production and the presence of algD, lasB, toxA and exoS; and gelatinase production and the existence of lasB, exoS and plcH. Ambroxol showed a high anti-biofilm activity (5% to 92%). Quantitative reverse transcriptase polymerase chain reaction showed that alginate was not an essential matrix component in P. aeruginosa biofilms.ConclusionsHigh virulence coupled with the isolates’ multi-drug resistance to commonly used antimicrobials would increase morbidity and mortality rates among P. aeruginosa infections. Ambroxol that displayed anti-biofilm action could be suggested as an alternative treatment option, yet in vivo studies are required to confirm these findings. We recommend active surveillance of antimicrobial resistance and virulence determinant prevalence for better understanding of coregulatory mechanisms.

Exploration of the Shared Hub Genes and Biological Mechanism in Osteoporosis and Type 2 Diabetes Mellitus based on Machine Learning.

A substantial amount of evidence suggests a close relationship between osteoporosis (OP) and Type 2 Diabetes Mellitus (T2DM), but the mechanisms involved remain unknown. Therefore, we conducted this study with the aim of screening for hub genes common to both diseases and conducting a preliminary exploration of common regulatory mechanisms. In the present study, we first screened genes significantly associated with OP and T2DM by the univariate logistic regression algorithm. And then, based on cross-analysis and random forest algorithm, we obtained three hub genes (ACAA2, GATAD2A, and VPS35) and validated the critical roles and predictive performance of the three genes in both diseases by differential expression analysis, receiver operating characteristic (ROC) curves, and genome wide association study (GWAS) analysis. Finally, based on gene set enrichment analysis (GSEA) and the construction of the miRNA-mRNA regulatory network, we conducted a preliminary exploration of the co-regulatory mechanisms of three hub genes in two diseases. In conclusion, this study provides promising biomarkers for predicting and treating both diseases and offers novel directions for exploring the common regulatory mechanisms of both diseases.

Genome-wide scan for oil quality reveals a coregulation mechanism of tocopherols and fatty acids in soybean seeds

Tocopherols (vitamin E) play essential roles in human health because of their antioxidant activity, and plant-derived oils are the richest sources of tocopherols in the human diet. Although soybean (Glycine max) is one of the main sources of plant-derived oil and tocopherol in the world, the relationship between tocopherol and oil in soybean seeds remains unclear. Here, we focus on dissecting tocopherol metabolism with the long-term goal of increasing α-tocopherol content and soybean oil quality. We first collected tocopherol and fatty acid profiles in a soybean population (>800 soybean accessions) and found that tocopherol content increased during soybean domestication. A strong positive correlation between tocopherol and oil content was also detected. Five tocopherol pathway–related loci were identified using a metabolite genome-wide association study strategy. Genetic variations in three tocopherol pathway genes were responsible for total tocopherol content and composition in the soybean population through effects on enzyme activity, mainly caused by non-conserved amino acid substitution or changes in gene transcription level. Moreover, the fatty acid regulatory transcription factor GmZF351 directly activated tocopherol pathway gene expression, increasing both fatty acid and tocopherol contents in soybean seeds. Our study reveals the functional differentiation of tocopherol pathway genes in soybean populations and provides a framework for development of new soybean varieties with high α-tocopherol content and oil quality in seeds.

Human Milk Oligosaccharides Are Associated with Lactation Stage and Lewis Phenotype in a Chinese Population.

Human milk oligosaccharides (HMOs) are the third most abundant component of human milk. Various factors may affect the concentration of HMOs, such as the lactation period, Lewis blood type, and the maternal secretor gene status. The purpose of this study is to investigate factors associated with HMO concentrations in Chinese populations. A sub-sample of 481 was randomly selected from a large cross-sectional study in China (n = 6481) conducted in eight provinces (Beijing, Heilongjiang, Shanghai, Yunnan, Gansu, Guangdong, Zhejiang, and Shandong) between 2011 and 2013. HMO concentrations were determined by a high-throughput UPLC-MRM method. Various factors were collected through face-to-face interviews. Anthropometric measurement was conducted by trained staff. Median total HMO concentration was 13.6 g/L, 10.7 g/L, and 6.0 g/L for colostrum, transitional milk, and mature milk, respectively. HMO concentration decreased significantly as the lactation period increased (p < 0.0001). There were significant differences of average total HMO concentration between secretor mothers and non-secretor mothers (secretor 11.3 g/L vs. non-secretor 5.8 g/L, p < 0.0001). There were significant differences of average total HMO concentrations among three Lewis blood types (p = 0.003). Comparing with the concentration of total oligosaccharides of Le+ (a-b+), average of total oligosaccharides concentrations increased by 3.9 (Le+ (a+b-), p = 0.004) and 1.1 g/L (Le- (a-b-), p = 0.049). The volume of breast milk expressed and the province the mother came from affected the concentration of total oligosaccharides (all p < 0.0001). Maternal BMI (p = 0.151), age (p = 0.630), prematurity (p = 0.850), mode of delivery (p = 0.486), infants' gender (p = 0.685), maternal education level (p = 0.989), maternal occupation (p = 0.568), maternal allergic history (p = 0.370), maternal anemia (p = 0.625), pregnancy-induced hypertension (p = 0.739), gestational diabetes (p = 0.514), and parity (p = 0.098) were not significantly correlated with the concentration of milk oligosaccharides. The concentrations of 2'-fucosyllactose (2'-FL), lacto-N-neotetraose (LNnT), sialyllacto-N-tetraose c (LSTc), lacto-N-fucopentaose I (LNFP-I), disialylated lacto-N-tetraose (DSLNT), difucosyl-para-lacto-N-neohexaose (DFpLNnH), difucosyl-lacto-N-hexaose (DFLNH[a]), and 3-sialyllactose (3'-SL) showed a gradual downward trend, while the concentration of 3-fucosyllactose (3-FL) showed a gradual upward trend among three lactation stages (p < 0.05). The concentration of HMOs changes throughout lactation, and it varies between different HMOs. HMO concentrations differed between lactation stage, maternal secretor gene status, Lewis blood type, volume of breast milk expressed, and the province the mother came from. Prematurity, mode of delivery, parity, infants' gender, and maternal characteristics did not affect the HMO concentration. Geographical region may be not associated with HMOs concentration in human milk. There may be a mechanism for co-regulation of the secretion of some of the oligosaccharides such as 2'FL vs. 3FL, 2'FL vs. LNnT, and lacto-N-tetraose (LNT).

MicroRNAs Markedly Expressed in Apical Periodontitis Cooperatively Regulate Cytokines and Growth Factors Promoting an Anti-inflammatory Response

IntroductionMicroRNAs have been shown to play a role in the pathogenesis of apical periodontitis. Upregulation of miR-10a-5p and downregulation of miR-891a-5p were previously reported in apical periodontitis samples. This study aims to perform a functional characterization of miR-10a-5p, investigating its capacity to regulate the expression of inflammatory cytokines and growth factors, as well as a possible co-regulation mechanism with miR-891a-5p in the development of apical periodontitis. MethodsmiR-10a-5p mimics/controls and miR-891a-5p inhibitors/controls were introduced to human K-562 cells in the presence or absence of lipopolysaccharide. Total RNA was extracted from cell lysates, and target genes were examined via quantitative reverse transcription-polymerase chain reaction. Cell lysates were also subjected to proteomics analysis. Furthermore, mimics of miR-10a-5p and inhibitors of miR-891a-5p were co-transfected into K-562 cells. RNA sequencing and quantitative reverse transcription-polymerase chain reaction were carried out to examine their target genes. ResultsOverexpression of miR-10a-5p led to downregulation of tumor necrosis factor-alpha and interleukin-1 beta mRNA and upregulation of transforming growth factor-beta 1 (TGFB1) mRNA expression, whereas interleukin 3 and TGF-β1 proteins were upregulated. Simultaneous overexpression of miR-10a-5p and inhibition of miR-891a-5p further increased TGFB1 mRNA transcript levels. RNA sequencing revealed that genes co-regulated by miR-10a-5p and miR-891a-5p may be involved in apical periodontitis-related pathways such as tumor necrosis factor, transient receptor potential, and vascular endothelial growth factor signaling pathways. ConclusionsmiR-10a-5p may modulate the expression of multiple inflammatory cytokines and growth factors such as tumor necrosis factor-alpha, IL-1β, interleukin 3, and TGF-β1. In addition, miR-10a-5p and miR-891a-5p cooperatively regulate TGFB1 gene expression, and the gene network of this co-regulation is integrated with many pathways in apical periodontitis.

A Multi-Level Iterative Bi-Clustering Method for Discovering miRNA Co-regulation Network of Abiotic Stress Tolerance in Soybeans.

Although growing evidence shows that microRNA (miRNA) regulates plant growth and development, miRNA regulatory networks in plants are not well understood. Current experimental studies cannot characterize miRNA regulatory networks on a large scale. This information gap provides an excellent opportunity to employ computational methods for global analysis and generate valuable models and hypotheses. To address this opportunity, we collected miRNA–target interactions (MTIs) and used MTIs from Arabidopsis thaliana and Medicago truncatula to predict homologous MTIs in soybeans, resulting in 80,235 soybean MTIs in total. A multi-level iterative bi-clustering method was developed to identify 483 soybean miRNA–target regulatory modules (MTRMs). Furthermore, we collected soybean miRNA expression data and corresponding gene expression data in response to abiotic stresses. By clustering these data, 37 MTRMs related to abiotic stresses were identified, including stress-specific MTRMs and shared MTRMs. These MTRMs have gene ontology (GO) enrichment in resistance response, iron transport, positive growth regulation, etc. Our study predicts soybean MTRMs and miRNA-GO networks under different stresses, and provides miRNA targeting hypotheses for experimental analyses. The method can be applied to other biological processes and other plants to elucidate miRNA co-regulation mechanisms.

FMR1 is identified as an immune-related novel prognostic biomarker for renal clear cell carcinoma: A bioinformatics analysis of TAZ/YAP.

WW domain-containing transcription regulator 1 (TAZ, or WWTR1) and Yes-associated protein 1 (YAP) are both important effectors of the Hippo pathway and exhibit different functions. However, few studies have explored their co-regulatory mechanisms in kidney renal clear cell carcinoma (KIRC). Here, we used bioinformatics approaches to evaluate the co-regulatory roles of TAZ/YAP and screen novel biomarkers in KIRC. GSE121689 and GSE146354 were downloaded from the GEO. The limma was applied to identify the differential expression genes (DEGs) and the Venn diagram was utilized to screen co-expressed DEGs. Co-expressed DEGs obtained the corresponding pathways through GO and KEGG analysis. The protein-protein interaction (PPI) network was constructed using STRING. The hub genes were selected applying MCODE and CytoHubba. GSEA was further applied to identify the hub gene-related signaling pathways. The expression, survival, receiver operating character (ROC), and immune infiltration of the hub genes were analyzed by HPA, UALCAN, GEPIA, pROC, and TIMER. A total of 51 DEGs were co-expressed in the two datasets. The KEGG results showed that the enriched pathways were concentrated in the TGF-β signaling pathway and endocytosis. In the PPI network, the hub genes (STAU2, AGO2, FMR1) were identified by the MCODE and CytoHubba. The GSEA results revealed that the hub genes were correlated with the signaling pathways of metabolism and immunomodulation. We found that STAU2 and FMR1 were weakly expressed in tumors and were negatively associated with the tumor stages. The overall survival (OS) and disease-free survival (DFS) rate of the high-expressed group of FMR1 was greater than that of the low-expressed group. The ROC result exhibited that FMR1 had certainly a predictive ability. The TIMER results indicated that FMR1 was positively correlated to immune cell infiltration. The abovementioned results indicated that TAZ/YAP was involved in the TGF-β signaling pathway and endocytosis. FMR1 possibly served as an immune-related novel prognostic gene in KIRC.

Voluntary safety commitments provide an escape from over-regulation in AI development

With the introduction of Artificial Intelligence (AI) and related technologies in our daily lives, fear and anxiety about their misuse as well as their inherent biases, incorporated during their creation, have led to a demand for governance and associated regulation. Yet regulating an innovation process that is not well understood may stifle this process and reduce benefits that society may gain from the generated technology, even under the best intentions. Instruments to shed light on such processes are thus needed as they can ensure that imposed policies achieve the ambitions for which they were designed. Starting from a game-theoretical model that captures the fundamental dynamics of a race for domain supremacy using AI technology, we show how socially unwanted outcomes may be produced when sanctioning is applied unconditionally to risk-taking, i.e. potentially unsafe, behaviours. We demonstrate here the potential of a regulatory approach that combines a voluntary commitment approach reminiscent of soft law, wherein technologists have the freedom of choice between independently pursuing their course of actions or establishing binding agreements to act safely, with either a peer or governmental sanctioning system of those that do not abide by what they pledged. As commitments are binding and sanctioned, they go beyond the classic view of soft law, akin more closely to actual law-enforced regulation. Overall, this work reveals how voluntary but sanctionable commitments generate socially beneficial outcomes in all scenarios envisageable in a short-term race towards domain supremacy through AI technology. These results provide an original dynamic systems perspective of the governance potential of enforceable soft law techniques or co-regulatory mechanisms, showing how they may impact the ambitions of developers in the context of the AI-based applications.

An Emergence Model of Team Burnout

Because we work in teams more than ever, we should craft them fostering team members’ motivation, wellbeing, and performance. To that aim, we propose a multi-level model explaining the emergence of team burnout, articulating the interplay between individual and team level mechanisms around ten empirically testable research propositions. Drawing from the JD-R theory, we formulated an emergence model of team burnout by combining team effectiveness and occupational health literatures. Our model explains how cycles of attention, information integration, and information-affect sharing on burnout cues foster the emergence of team burnout. It also explains how team burnout moderates the relationship between team structural variables and team members’ burnout and how team burnout impairs team effectiveness through co-regulatory mechanisms. This model is timely because it addresses the importance of team burnout through a systematic effort connecting individual and team levels in explaining its emergence and the mechanisms through which it impairs team effectiveness.

INTS7-ABCD3 Interaction Stimulates the Proliferation and Osteoblastic Differentiation of Mouse Bone Marrow Mesenchymal Stem Cells by Suppressing Oxidative Stress.

Increased adipocyte and decreased osteoblast differentiation, combined with the ectopic proliferation of bone marrow mesenchymal stem cells (BM-MSCs), represent the primary causes of osteoporosis. The dysregulation of numerous intracellular bioactive factors is responsible for the aberrant differentiation and growth of BM-MSCs. In this study, we focused on a new stimulative factor, integrator complex subunit 7 (INTS7), and its cooperative protein ATP-binding cassette subfamily D member 3 (ABCD3)/high-density lipoprotein-binding protein (HDLBP) in mouse BM-MSCs. We aimed to uncover the effects of the INTS7–ABCD3/HDLBP interaction on BM-MSC biological behaviors and the potential mechanism underlying these effects. Functional in vitro experiments showed that the suppression of the INTS7–ABCD3 interaction rather than HDLBP could impair BM-MSC proliferation and induce cell apoptosis. Moreover, Alizarin Red S and Oil Red O staining, respectively, revealed that INTS7 and ABCD3 knockdown but not HDLBP knockdown could decrease osteoblastic differentiation and accelerate the adipogenic differentiation of BM-MSCs. Mechanistically, reactive oxygen species (ROS) and histone γ-H2AX quantities significantly increased, whereas the levels of antioxidants declined due to INTS7 and ABCD3 inhibition in BM-MSCs. These findings indicated that the suppression of oxidative stress could be involved in the INTS7/ABCD3 co-regulatory mechanisms for BM-MSC proliferation and differentiation, identifying new potential candidates for osteoporosis therapy.

Genotype-Dependent Effect of Silencing of TaCKX1 and TaCKX2 on Phytohormone Crosstalk and Yield-Related Traits in Wheat.

The influence of silenced TaCKX1 and TaCKX2 on coexpression of other TaCKX gene family members (GFMs), phytohormone regulation and yield-related traits was tested in awned-spike cultivar. We documented a strong feedback mechanism of regulation of TaCKX GFM expression in which silencing of TaCKX1 upregulated expression of TaCKX2 genes and vice versa. Additionally, downregulation of TaCKX2 highly upregulated the expression of TaCKX5 and TaNAC2-5A. In contrast, expression of these genes in silenced TaCKX1 was downregulated. Silenced TaCKX1 T2 lines with expression decreased by 47% had significantly higher thousand grain weight (TGW) and seedling root mass. Silenced TaCKX2 T2 lines with expression of TaCKX2.2.1 and TaCKX2.2.2 decreased by 33% and 30%, respectively, had significantly higher chlorophyll content in flag leaves. TaCKX GFM expression, phytohormone metabolism and phenotype were additionally modified by Agrobacterium-mediated transformation. Two novel phytohormones, phenylacetic acid (PAA) and topolins, lack of gibberellic acid (GA) and changed phytohormone contents in the 7 days after pollination (DAP) spikes of the awned-spike cultivar compared to a previously tested, awnless one, were detected. We documented that major mechanisms of coregulation of the expression of TaCKX GFMs were similar in different spring wheat cultivars, but, depending on content and composition of phytohormones, regulation of yield-related traits was variously impacted.

FliW and CsrA Govern Flagellin (FliC) Synthesis and Play Pleiotropic Roles in Virulence and Physiology of Clostridioides difficile R20291.

Clostridioides difficile flagellin FliC is associated with toxin gene expression, bacterial colonization, and virulence, and is also involved in pleiotropic gene regulation during in vivo infection. However, how fliC expression is regulated in C. difficile remains unclear. In Bacillus subtilis, flagellin homeostasis and motility are coregulated by flagellar assembly factor (FliW), flagellin Hag (FliC homolog), and Carbon storage regulator A (CsrA), which is referred to as partner-switching mechanism “FliW-CsrA-Hag.” In this study, we characterized FliW and CsrA functions by deleting or overexpressing fliW, csrA, and fliW-csrA in C. difficile R20291. We showed that fliW deletion, csrA overexpression in R20291, and csrA complementation in R20291ΔWA (fliW-csrA codeletion mutant) dramatically decreased FliC production, but not fliC gene transcription. Suppression of fliC translation by csrA overexpression can be relieved mostly when fliW was coexpressed, and no significant difference in FliC production was detected when only fliW was complemented in R20291ΔWA. Further, loss of fliW led to increased biofilm formation, cell adhesion, toxin production, and pathogenicity in a mouse model of C. difficile infection (CDI), while fliW-csrA codeletion decreased toxin production and mortality in vivo. Our data suggest that CsrA negatively modulates fliC expression and FliW indirectly affects fliC expression through inhibition of CsrA post-transcriptional regulation. In light of “FliW-CsrA-Hag” switch coregulation mechanism reported in B. subtilis, our data also suggest that “FliW-CsrA-fliC/FliC” can regulate many facets of C. difficile R20291 pathogenicity. These findings further aid us in understanding the virulence regulation in C. difficile.

Co-Regulatory Network of Transcription Factor and MicroRNA

Transcription factor (TF) and microRNA (miRNA) interaction plays a vital role in the regulation of biological networks. TFs and miRNAs control the gene expression: TF at transcriptional level by affecting the messenger RNA (mRNA) transcription and miRNA at posttranscriptional level by affecting the transcription and translation. Furthermore, sometimes, both miRNAs and TFs regulate one another's expressions; as a consequence, this may influence the expression of the target gene. In order to understand the main co-regulatory mechanisms underlying, it is important to identify biologically relevant network motifs involving TFs, miRNAs and their targets. The present study focuses on TF, miRNA and target gene interactions.