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With an emphasis on the mediating role of relational psychological contracts, this study sets out to investigate the structural connection between perceived organizational support (POS), service quality (SERVQ), and customer satisfaction (CS). Using descriptive and inferential statistics, we tested the heuristic model for the relationship using data from 394 clients at selected banks in Nigeria. It was found that both perceived organizational support and service quality significantly affected customer satisfaction, with the former serving as a predictor of the latter. In addition, a positive and statistically significant influence of the relational psychological contract was found in the connection between “POS” and CS, and perceived organizational support and SERVQ. In addition, it was determined that banks must maintain all required standards in gaining customers by continually providing a higher degree of service to keep clients satisfied. The structural nexus between the identified variables stood out as a novel idea with a heuristic model depicted for business practitioners and society’s opportunities.

To study the effects of the crosslinking of IGF1 and/or the human thyroid-stimulating monoclonal autoantibody (TSmAb), M22 on mouse adipocytes, two- and three-dimensional (2D or 3D) cultures of 3T3-L1 cells were prepared. Each sample was then subjected to the following analyses: (1) lipid staining, (2) a real-time cellular metabolic analysis, (3) analysis of the mRNA expression of adipogenesis-related genes and extracellular matrix (ECM) molecules including collagen (Col) 1, 4 and 6, and fibronectin (Fn), and (4) measurement of the size and physical properties of the 3D spheroids with a micro-squeezer. Upon adipogenic differentiation (DIF+), lipid staining and the mRNA expression of adipogenesis-related genes in the 2D- or 3D-cultured 3T3-L1 cells substantially increased. On adding IGF1 but not M22 to DIF+ cells, a significant enhancement in lipid staining and gene expressions of adipogenesis-related genes was detected in the 2D-cultured 3T3-L1 cells, although some simultaneous suppression or enhancement effects by IGF1 and M22 against lipid staining or Fabp4 expression, respectively, were detected in the 3D 3T3-L1 spheroids. Real-time metabolic analyses indicated that monotherapy with IGF1 or M22 shifted cellular metabolism toward energetic states in the 2D 3T3-L1 cells upon DIF+, although no significant metabolic changes were induced by DIF+ alone in 2D cultures. In addition, some synergistical effects on cellular metabolism by IGF1 and M22 were also observed in the 2D 3T3-L1 cells as well as in cultured non-Graves' orbitopathy-related human orbital fibroblasts (n-HOFs), but not in Graves' orbitopathy-related HOFs (GHOFs). In terms of the physical properties of the 3D 3T3-L1 spheroids, (1) their sizes significantly increased upon DIF+, and this increase was significantly enhanced by the presence of both IGF1 and M22 despite downsizing by monotreatment, and (2) their stiffness increased substantially, and no significant effects by IGF-1 and/or M22 were observed. Regarding the expression of ECM molecules, (1) upon DIF+, significant downregulation or upregulation of Col1 and Fn (3D), or Col4 and 6 (2D and 3D) were observed, and (2) in the presence of IGF-1 and/or M22, the mRNA expression of Col4 was significantly downregulated by M22 (2D and 3D), but the expression of Col1 was modulated in different manners by monotreatment (upregulation) or the combined treatment (downregulation) (3D). These collective data suggest that the human-specific TSmAb M22 induced some unexpected simultaneous crosslinking effects with IGF-1 with respect to the adipogenesis of 2D-cultured 3T3-L1 cells and the physical properties of 3D 3T3-L1 spheroids. [ABSTRACT FROM AUTHOR]

DP6, VS55 and M22 are the most commonly used cryoprotective agent (CPA) cocktails for vitrification experiments in tissues and organs. However, complete phase diagrams for the three CPAs are often unavailable or incomplete (only available for full strength CPAs) thereby hampering optimization of vitrification and rewarming procedures. In this paper, we used differential scanning calorimetry (DSC) to measure the transition temperatures including heterogeneous nucleation temperatures (T het), glass transition temperatures (T g), rewarming phase crystallization (devitrification and/or recrystallization) temperatures (T d) and melting temperatures (T m) while cooling or warming the CPA sample at 5 °C/min and plotted the obtained transition temperatures for different concentrations of CPAs into the phase diagrams. We also used cryomicroscopy cooling or warming the sample at the same rate to record the ice crystallization during the whole process, and we presented the cryomicroscopic images at the transition temperatures, which agreed with the DSC presented phenomena. [ABSTRACT FROM AUTHOR]

Abstract Background Human T-cell leukemia virus type 1 (HTLV-1) infects primarily CD4+ T-lymphocytes and evoques severe diseases, predominantly Adult T-Cell Leukemia/ Lymphoma (ATL/L) and HTLV-1-associated Myelopathy/ Tropical Spastic Paraparesis (HAM/TSP). The viral transactivator of the pX region (Tax) is important for initiating malignant transformation, and deregulation of the major signaling pathway nuclear factor of kappa B (NF-κB) by Tax represents a hallmark of HTLV-1 driven cancer. Results Here we found that Tax mutants which are defective in NF-κB signaling showed diminished protein expression levels compared to Tax wildtype in T-cells, whereas Tax transcript levels were comparable. Strikingly, constant activation of NF-κB signaling by the constitutive active mutant of inhibitor of kappa B kinase (IKK2, IKK-β), IKK2-EE, rescued protein expression of the NF-κB defective Tax mutants M22 and K1-10R and even increased protein levels of Tax wildtype in various T-cell lines while Tax transcript levels were only slightly affected. Using several Tax expression constructs, an increase of Tax protein occurred independent of Tax transcripts and independent of the promoter used. Further, Tax and M22 protein expression were strongly enhanced by 12-O-Tetradecanoylphorbol-13-Acetate [TPA; Phorbol 12-myristate 13-acetate (PMA)]/ ionomycin, inducers of NF-κB and cytokine signaling, but not by tumor necrosis factor alpha (TNF-α). On the other hand, co-expression of Tax with a dominant negative inhibitor of κB, IκBα-DN, or specific inhibition of IKK2 by the compound ACHP, led to a vast decrease in Tax protein levels to some extent independent of Tax transcripts in transiently transfected and Tax-transformed T-cells. Cycloheximide chase experiments revealed that co-expression of IKK2-EE prolongs the half-life of M22, and constant repression of NF-κB signaling by IκBα-DN strongly reduces protein stability of Tax wildtype suggesting that NF-κB activity is required for Tax protein stability. Finally, protein expression of Tax and M22 could be recovered by NH4Cl and PYR-41, inhibitors of the lysosome and the ubiquitin-activating enzyme E1, respectively. Conclusions Together, these findings suggest that Tax’s capability to induce NF-κB is critical for protein expression and stabilization of Tax itself. Overall, identification of this novel positive feedback loop between Tax and NF-κB in T-cells improves our understanding of Tax-driven transformation.

To study the effects of the crosslinking of IGF1 and/or the human thyroid-stimulating monoclonal autoantibody (TSmAb), M22 on mouse adipocytes, two- and three-dimensional (2D or 3D) cultures of 3T3-L1 cells were prepared. Each sample was then subjected to the following analyses: (1) lipid staining, (2) a real-time cellular metabolic analysis, (3) analysis of the mRNA expression of adipogenesis-related genes and extracellular matrix (ECM) molecules including collagen (Col) 1, 4 and 6, and fibronectin (Fn), and (4) measurement of the size and physical properties of the 3D spheroids with a micro-squeezer. Upon adipogenic differentiation (DIF+), lipid staining and the mRNA expression of adipogenesis-related genes in the 2D- or 3D-cultured 3T3-L1 cells substantially increased. On adding IGF1 but not M22 to DIF+ cells, a significant enhancement in lipid staining and gene expressions of adipogenesis-related genes was detected in the 2D-cultured 3T3-L1 cells, although some simultaneous suppression or enhancement effects by IGF1 and M22 against lipid staining or Fabp4 expression, respectively, were detected in the 3D 3T3-L1 spheroids. Real-time metabolic analyses indicated that monotherapy with IGF1 or M22 shifted cellular metabolism toward energetic states in the 2D 3T3-L1 cells upon DIF+, although no significant metabolic changes were induced by DIF+ alone in 2D cultures. In addition, some synergistical effects on cellular metabolism by IGF1 and M22 were also observed in the 2D 3T3-L1 cells as well as in cultured non-Graves’ orbitopathy-related human orbital fibroblasts (n-HOFs), but not in Graves’ orbitopathy-related HOFs (GHOFs). In terms of the physical properties of the 3D 3T3-L1 spheroids, (1) their sizes significantly increased upon DIF+, and this increase was significantly enhanced by the presence of both IGF1 and M22 despite downsizing by monotreatment, and (2) their stiffness increased substantially, and no significant effects by IGF-1 and/or M22 were observed. Regarding the expression of ECM molecules, (1) upon DIF+, significant downregulation or upregulation of Col1 and Fn (3D), or Col4 and 6 (2D and 3D) were observed, and (2) in the presence of IGF-1 and/or M22, the mRNA expression of Col4 was significantly downregulated by M22 (2D and 3D), but the expression of Col1 was modulated in different manners by monotreatment (upregulation) or the combined treatment (downregulation) (3D). These collective data suggest that the human-specific TSmAb M22 induced some unexpected simultaneous crosslinking effects with IGF-1 with respect to the adipogenesis of 2D-cultured 3T3-L1 cells and the physical properties of 3D 3T3-L1 spheroids.

Context: Thyroid-associated ophthalmopathy (TAO) is an organ-specific autoimmune disease closely associated with Graves' disease. IL-38, a novel cytokine in the IL-1 superfamily, has been reported to be involved in the pathogenesis of various autoimmune diseases.Objective: We aimed to evaluate the relationship between IL-38 and TAO disease activity and its role in inflammation and fibrosis in TAO.Methods: Blood samples and orbital connective tissues were collected from TAO patients and controls. Orbital fibroblasts were isolated from patients with TAO. Enzyme-linked immunosorbent assay, immunohistochemistry, flow cytometry, immunofluorescence, quantitative real-time PCR and Western blot analysis were performed.Results: Here, we demonstrated that IL-38 levels decreased in the circulation and orbital connective tissues of patients with TAO compared with the controls, and levels were negatively correlated with the clinical activity score. In vitro, potent anti-inflammatory and antifibrotic effects of IL-38 were observed. Furthermore, we revealed that IL-38 can counteract the phosphorylation of star molecules in multiple classical pathways.Conclusion: IL-38 plays a protective role in TAO and is associated with its pathogenesis. Our data suggest that IL-38 may be a promising marker of TAO disease activity and a potential target for TAO therapy. [ABSTRACT FROM AUTHOR]

To identify the anticancer effect of gallic acid fraction from alcoholic extract of Calvatia craniiformis mushroom in white mice with mammary gland tumor (M-22) as a model for treatment of mammary gland tumor in human. Sixty albino mice were injectedwith M22 cells. Tumor growth was appear after 7-10 days in 50 mice. Tumor size was measured twice a week to after administration of gallic acid of C. craniiformis in 0.2mg/kg, 0.4mg/kg, 0.8 mg/kg to M22 tumor-bearing mice to determine relative tumor volume and growth inhibition (GI%). Administration of gallic acid of C. craniiformis in 0.2mg/kg, 0.4mg/kg, 0.8 mg/kg to M22 tumor-bearing mice show significant differences (P≤0.05) in tumor size compared with control group. Tumor size development was significantly slower in all treated group compared with control (P<0.05). The most effective dose for last days was 0.8mg/kg treated group compared with control, the tumor size was 35.12mm³ compared to 240.15 mm³ and 91.24 mm³ for second and third dose and 3855.80 mm³ for control group. Gallic acid (0.2 mg/kg, 0.4 mg/kg) leads to gradual increase in tumor size until 27 days after inoculation, when the size was reduced significantly after 10 doses, in the last day of experiment the size was 109.00 mm³ ; 41.34 mm³ compared with 1734.23 mm³ in control group. Gallic acid (0.8 mg/kg) leads toslow growth in tumor until 27 days after inoculation, when the size was reduced significantly after 10 doses, in the last day of experiment the size was 15.88 mm³ compared with control group. Significant difference between gallic acid treated group and control group (P>0.05). Tumor inhibition (GI%) increase significantly for all doses with time (P>0.05). The most effective doses was (0.4mg/kg, 0.8 mg/kg) in which GI% was 87.06 and 83.91%, respectively, while in 0.2mg/kg, GI% was 71.91%. There was significant difference in body weight (BW) among treated groups with 0.2 mg/kg; 0.4 mg/kg and 0.8 mg/kg (P < 0.05) compared with control. Gallic acid fraction of C. craniiformis was highly efficient in tumor growth inhibition, causing reduction in the tumor size clinically. Antitumor activity of C. craniiformis alcoholic extract was dose and duration dependent. [ABSTRACT FROM AUTHOR]

Abstract We have looked at the effects of the cryoprotectant M22 upon viability in the model organism C. elegans. M22 is a well-known vitrification solution which has been successfully used in the laboratory to preserve organs destined for transplantation. M22 reduces survival of C. elegans in a concentration-dependent manner. M22 at concentrations of 10% (v/v) or higher inhibits progeny production and development. A few mutants in the ILS (insulin-like signaling) pathway of C. elegans are more resistant to the toxic effect of M22 compared to wild-type worms. Afatinib, an anti-cancer drug, protects against M22 toxicity. Afatinib by itself does not increase longevity. [ABSTRACT FROM AUTHOR]

Thyrotropin (TSH) receptor antibodies (TRAb) mediate the hyperthyroidism of Graves’ disease (GD). The aim of the study was to compare the diagnostic performance and assay agreement between three immunoassays for the measurement of TRAb in patients with newly diagnosed GD. TRAb was measured with three different assays [H-TRAb (BRAHMS Diagnostica), M22-Man (RSR Limited) and M22-Aut (Roche Diagnostics)] in 387 participants who were recruited from two Danish population-based studies and diagnosed with GD (n = 101), multinodular toxic goitre (n = 88), primary autoimmune hypothyroidism (n = 100) or included as controls (n = 98). Coefficient of variation for duplicate measurements with each of the three assays were H-TRAb: 3.6%, M22-Man: 9.4%, M22-Aut: 7.7%. Frequency of TRAb positivity in patients with GD were H-TRAb: 95%, M22-Man: 94%, M22-Aut: 96%. Receiver operating characteristic analysis revealed a high sensitivity (H-TRAb: 95%, M22-Man: 93%, M22-Aut: 95%) and specificity (H-TRAb: 99%, M22-Man: 99%, M22-Aut: 97%) for the diagnosis of GD with all assays. Comparison of TRAb levels showed inter-assay variability and values were considerably lower with the M22-Man assay. All TRAb assays showed a high diagnostic performance for GD, but a high inter-assay variability was observed limiting the use of different assays in clinical monitoring of patients with GD. [ABSTRACT FROM PUBLISHER]

Abstract: Commercial assays to measure thyroid stimulating hormone (TSH) receptor (TSHR) autoantibodies (TRAb) have been available for the serological diagnosis of autoimmune thyroid diseases (AITD) for several years. The widespread assessment of this parameter has identified Graves'' disease (GD) as a common organ-specific autoimmune disease. Within the present article we aim to review immunobiological and epidemiological aspects as well as diagnostic methods available for the detection of TRAb. Over the last decade, TRAb detection in GD became more sensitive since TRAb assays were being largely improved by named research groups. Therefore, functional assay (fas) and diagnostic sensitivity of current TRAb assays will be discussed. Within the second part of this review we will focus on clinical applications of TRAb measurement for outcome prediction of GD as well as the importance of this method to distinguish GD from other AITD. [Copyright &y& Elsevier]

Abstract: The core promoter of eukaryotic genes is the minimal DNA region that recruits the basal transcription machinery to direct efficient and accurate transcription initiation. The fraction of human and yeast genes that contain specific core promoter elements such as the TATA box and the initiator (INR) remains unclear and core promoter motifs specific for TATA-less genes remain to be identified. Here, we present genome-scale computational analyses indicating that ∼76% of human core promoters lack TATA-like elements, have a high GC content, and are enriched in Sp1-binding sites. We further identify two motifs – M3 (SCGGAAGY) and M22 (TGCGCANK) – that occur preferentially in human TATA-less core promoters. About 24% of human genes have a TATA-like element and their promoters are generally AT-rich; however, only ∼10% of these TATA-containing promoters have the canonical TATA box (TATAWAWR). In contrast, ∼46% of human core promoters contain the consensus INR (YYANWYY) and ∼30% are INR-containing TATA-less genes. Significantly, ∼46% of human promoters lack both TATA-like and consensus INR elements. Surprisingly, mammalian-type INR sequences are present – and tend to cluster – in the transcription start site (TSS) region of ∼40% of yeast core promoters and the frequency of specific core promoter types appears to be conserved in yeast and human genomes. Gene Ontology analyses reveal that TATA-less genes in humans, as in yeast, are frequently involved in basic “housekeeping” processes, while TATA-containing genes are more often highly regulated, such as by biotic or stress stimuli. These results reveal unexpected similarities in the occurrence of specific core promoter types and in their associated biological processes in yeast and humans and point to novel vertebrate-specific DNA motifs that might play a selective role in TATA-independent transcription. [Copyright &y& Elsevier]

Background Epidemiological studies indicate environmental pollutants to be involved in the increase in the prevalence of allergic diseases. In human exposure studies, volatile organic compounds (VOCs) have been shown to cause exacerbations of allergic asthma whereas, no data concerning atopic eczema (AE) are available. Objective We investigated the effect of airborne VOCs on the skin of patients with AE and controls in the presence or absence of house dust mite allergen, Der p 1. Methods In a double-blind crossover study, 12 adults with AE and 12 matched healthy volunteers were exposed on their forearms to Der p 1 and subsequently to a mixture of 22 VOCs (M22, 5 mg/m3) in a total body exposure chamber for 4 h. Transepidermal water loss (TEWL) and skin blood flow were measured in all subjects before, during and after exposure. Additionally, an atopy patch test (APT) with Der p 1 was applied to the skin after exposure. Results A significant increase in transepidermal water loss was observed 48 h after exposure to VOCs as compared with exposure with filtered air in all individuals (mean difference: +34%; 95% Confidence Interval: 7–69%). Prior Der p 1 exposure resulted in a significant rise of dermal blood flow after 48 h in patients with AE but not in controls. Six out of seven patients showed enhanced atopy patch test (APT) reactions to HDM allergen after previous exposure to VOCs. Conclusion Our results show that exposure to VOCs – at concentrations commonly found in indoor environments – can damage the epidermal barrier and enhance the adverse effect of Der p 1 on sensitized subjects with AE. These findings may contribute to a better understanding of the mechanisms underlying the increase in prevalence and exacerbation of AE. [ABSTRACT FROM AUTHOR]

Context: Thyroid-associated ophthalmopathy (TAO) is an organ-specific autoimmune disease closely associated with Graves' disease. IL-38, a novel cytokine in the IL-1 superfamily, has been reported to be involved in the pathogenesis of various autoimmune diseases., Objective: We aimed to evaluate the relationship between IL-38 and TAO disease activity and its role in inflammation and fibrosis in TAO., Methods: Blood samples and orbital connective tissues were collected from TAO patients and controls. Orbital fibroblasts were isolated from patients with TAO. Enzyme-linked immunosorbent assay, immunohistochemistry, flow cytometry, immunofluorescence, quantitative real-time PCR and Western blot analysis were performed., Results: Here, we demonstrated that IL-38 levels decreased in the circulation and orbital connective tissues of patients with TAO compared with the controls, and levels were negatively correlated with the clinical activity score. In vitro, potent anti-inflammatory and antifibrotic effects of IL-38 were observed. Furthermore, we revealed that IL-38 can counteract the phosphorylation of star molecules in multiple classical pathways., Conclusion: IL-38 plays a protective role in TAO and is associated with its pathogenesis. Our data suggest that IL-38 may be a promising marker of TAO disease activity and a potential target for TAO therapy., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)