JAZF1, A Novel p400/TIP60/NuA4 Complex Member, Regulates H2A.Z Acetylation at Regulatory Regions

Histone variants differ in amino acid sequence, expression timing and genomic localization sites from canonical histones and convey unique functions to eukaryotic cells. Their tightly controlled spatial and temporal deposition into specific chromatin regions is accomplished by dedicated chaperone and/or remodeling complexes. While quantitatively identifying the chaperone complexes of many human H2A variants by using mass spectrometry, we also found additional members of the known H2A.Z chaperone complexes p400/TIP60/NuA4 and SRCAP. We discovered JAZF1, a nuclear/nucleolar protein, as a member of a p400 sub-complex containing MBTD1 but excluding ANP32E. Depletion of JAZF1 results in transcriptome changes that affect, among other pathways, ribosome biogenesis. To identify the underlying molecular mechanism contributing to JAZF1's function in gene regulation, we performed genome-wide ChIP-seq analyses. Interestingly, depletion of JAZF1 leads to reduced H2A.Z acetylation levels at > 1000 regulatory sites without affecting H2A.Z nucleosome positioning. Since JAZF1 associates with the histone acetyltransferase TIP60, whose depletion causes a correlated H2A.Z deacetylation of several JAZF1-targeted enhancer regions, we speculate that JAZF1 acts as chromatin modulator by recruiting TIP60's enzymatic activity. Altogether, this study uncovers JAZF1 as a member of a TIP60-containing p400 chaperone complex orchestrating H2A.Z acetylation at regulatory regions controlling the expression of genes, many of which are involved in ribosome biogenesis

Inter-domain Communication Mechanisms in an ABC Importer: A Molecular Dynamics Study of the MalFGK2E Complex

ATP-Binding Cassette transporters are ubiquitous membrane proteins that convert the energy from ATP-binding and hydrolysis into conformational changes of the transmembrane region to allow the translocation of substrates against their concentration gradient. Despite the large amount of structural and biochemical data available for this family, it is still not clear how the energy obtained from ATP hydrolysis in the ATPase domains is “transmitted” to the transmembrane domains. In this work, we focus our attention on the consequences of hydrolysis and inorganic phosphate exit in the maltose uptake system (MalFGK2E) from Escherichia coli. The prime goal is to identify and map the structural changes occurring during an ATP-hydrolytic cycle. For that, we use extensive molecular dynamics simulations to study three potential intermediate states (with 10 replicates each): an ATP-bound, an ADP plus inorganic phosphate-bound and an ADP-bound state. Our results show that the residues presenting major rearrangements are located in the A-loop, in the helical sub-domain, and in the “EAA motif” (especially in the “coupling helices” region). Additionally, in one of the simulations with ADP we were able to observe the opening of the NBD dimer accompanied by the dissociation of ADP from the ABC signature motif, but not from its corresponding P-loop motif. This work, together with several other MD studies, suggests a common communication mechanism both for importers and exporters, in which ATP-hydrolysis induces conformational changes in the helical sub-domain region, in turn transferred to the transmembrane domains via the “coupling helices”

Varicellovirus UL49.5 Proteins Differentially Affect the Function of the Transporter Associated with Antigen Processing, TAP

Cytotoxic T-lymphocytes play an important role in the protection against viral infections, which they detect through the recognition of virus-derived peptides, presented in the context of MHC class I molecules at the surface of the infected cell. The transporter associated with antigen processing (TAP) plays an essential role in MHC class I–restricted antigen presentation, as TAP imports peptides into the ER, where peptide loading of MHC class I molecules takes place. In this study, the UL49.5 proteins of the varicelloviruses bovine herpesvirus 1 (BHV-1), pseudorabies virus (PRV), and equine herpesvirus 1 and 4 (EHV-1 and EHV-4) are characterized as members of a novel class of viral immune evasion proteins. These UL49.5 proteins interfere with MHC class I antigen presentation by blocking the supply of antigenic peptides through inhibition of TAP. BHV-1, PRV, and EHV-1 recombinant viruses lacking UL49.5 no longer interfere with peptide transport. Combined with the observation that the individually expressed UL49.5 proteins block TAP as well, these data indicate that UL49.5 is the viral factor that is both necessary and sufficient to abolish TAP function during productive infection by these viruses. The mechanisms through which the UL49.5 proteins of BHV-1, PRV, EHV-1, and EHV-4 block TAP exhibit surprising diversity. BHV-1 UL49.5 targets TAP for proteasomal degradation, whereas EHV-1 and EHV-4 UL49.5 interfere with the binding of ATP to TAP. In contrast, TAP stability and ATP recruitment are not affected by PRV UL49.5, although it has the capacity to arrest the peptide transporter in a translocation-incompetent state, a property shared with the BHV-1 and EHV-1 UL49.5. Taken together, these results classify the UL49.5 gene products of BHV-1, PRV, EHV-1, and EHV-4 as members of a novel family of viral immune evasion proteins, inhibiting TAP through a variety of mechanisms

Customer emotions in service failure and recovery encounters

Emotions play a significant role in the workplace, and considerable attention has been given to the study of employee emotions. Customers also play a central function in organizations, but much less is known about customer emotions. This chapter reviews the growing literature on customer emotions in employee–customer interfaces with a focus on service failure and recovery encounters, where emotions are heightened. It highlights emerging themes and key findings, addresses the measurement, modeling, and management of customer emotions, and identifies future research streams. Attention is given to emotional contagion, relationships between affective and cognitive processes, customer anger, customer rage, and individual differences

Protein-like oligomerisation of carbohydrates

Sugar can, too: Many proteins form noncovalent and thermodynamically reversible oligomers, which can dictate a protein's functionality. For the first time, the presence of multiple oligomeric forms is shown in a whole class of polymeric carbohydrates, the 6-deoxy-6-aminocelluloses, using analytical ultracentrifugation as a probe

Gain-Tunable Complementary Common-Source Amplifier Based on a Flexible Hybrid Thin-Film Transistor Technology

In this letter, we report a flexible complementary common-source (CS) amplifier comprising one p-type spray-coated singlewalled carbon nanotube and one n-type sputtered InGaZnO4 thin-film transistor (TFT). Bottom-gate TFTs were realized on a free-standing flexible polyimide foil using amaximumprocess temperature of 150 degrees C. The resulting CS amplifier operates at 10 V supply voltage and exhibits a gain bandwidth product of 60 kHz. Thanks to the use of a p-type TFT acting as a tunable current source load, the amplifier gain can be programmed from3.5 up to 27.2V/V (28.7 dB). To the best of our knowledge, this is the highest gain ever obtained for a flexible single-stage CS amplifier

Development and initial testing of the self-care of chronic illness inventory

Aim: The aim was to develop and psychometrically test the self-care of chronic illness Inventory, a generic measure of self-care. Background: Existing measures of self-care are disease-specific or behaviour-specific; no generic measure of self-care exists. Design: Cross-sectional survey. Methods: We developed a 20-item self-report instrument based on the Middle Range Theory of Self-Care of Chronic Illness, with three separate scales measuring Self-Care Maintenance, Self-Care Monitoring, and Self-Care Management. Each of the three scales is scored separately and standardized 0–100 with higher scores indicating better self-care. After demonstrating content validity, psychometric testing was conducted in a convenience sample of 407 adults (enrolled from inpatient and outpatient settings at five sites in the United States and ResearchMatch.org). Dimensionality testing with confirmatory factor analysis preceded reliability testing. Results: The Self-Care Maintenance scale (eight items, two dimensions: illness-related and health-promoting behaviour) fit well when tested with a two-factor confirmatory model. The Self-Care Monitoring scale (five items, single factor) fitted well. The Self-Care Management scale (seven items, two factors: autonomous and consulting behaviour), when tested with a two-factor confirmatory model, fitted adequately. A simultaneous confirmatory factor analysis on the combined set of items supported the more general model. Conclusion: The self-care of chronic illness inventory is adequate in reliability and validity. We suggest further testing in diverse populations of patients with chronic illnesses

Cross-cultural assessment of the Self-Care of Chronic Illness Inventory: A psychometric evaluation

Background: Self-care refers to behaviors that individuals adopt to prevent or maintain the stability of an illness (self-care maintenance), to monitor signs and symptoms (self-care monitoring), and to respond to signs and symptoms of an illness exacerbation (self-care management). A generic measure of self-care, the Self-Care of Chronic Illness Inventory, based on the Theory of Self-Care of Chronic Illness, was developed for use in individuals with any number and type of chronic conditions. Objective: The current study investigated the measurement equivalence of the Self-Care of Chronic Illness Inventory in individuals from three different cultural groups. We were interested in determining if Italians, Swedes, and Americans interpret the measure in a conceptually similar way. Methods: This cross-sectional study enrolled 1629 patients, 784 recruited in Italy, 438 in Sweden and 407 in the United States. Self-care (self-care maintenance, self-care monitoring and self-care management) was measured with the Self-Care of Chronic Illness Inventory. A multi-group confirmatory factor analytic approach was used to assess the equivalence of the measures across the three countries. Configural, metric, scalar and strict invariance were tested through a series of nested models where increasingly stringent equality constraints were posited. Results: Participants were mostly males (56.3%), older adults (69.8%) and had at least two chronic conditions. Results indicated that three out of four measurement equivalence levels were partially or totally supported in all three of the Self-Care of Chronic Illness Inventory scales. The partial scalar invariance level was reached for self-care maintenance [χ2(50) = 63.495, p = 0.095; RMSEA = 0.022, p = 0.999, 90% CI = 0.000 0.038; CFI = 0.981; TLI = 0.977; SRMR = 0.036], self-care monitoring [χ2(22) = 28.770, p = 0.095; RMSEA = 0.024, p = 0.978, 90% CI = 0.000 0.046; CFI = 0.996; TLI = 0.995; SRMR = 0.054], and self-care management [χ2(51) = 91.334, p = 0.001; RMSEA = 0.048, p = 0.576, 90% CI = 0.031 0.063; CFI = 0.949; TLI = 0.937; SRMR = 0.047] scales. Conclusions: These findings suggest that patients in the three countries used an identical cognitive framework or mental model when responding and used the 1-5 Likert response scale in an almost identical way, almost without bias. In spite of sociocultural differences, patients in these countries seem to share the same fundamental view of self-care. The results of the Self-Care of Chronic Illness Inventory will be comparable in these countries

Cross-cultural assessment of the self-care of chronic illness inventory: a psychometric evaluation

Background: Self-care refers to behaviors that individuals adopt to prevent or maintain the stability of an illness (self-care maintenance), to monitor signs and symptoms (self-care monitoring), and to respond to signs and symptoms of an illness exacerbation (self-care management). A generic measure of self-care, the Self-Care of Chronic Illness Inventory, based on the Theory of Self-Care of Chronic Illness, was developed for use in individuals with any number and type of chronic conditions. Objective: The current study investigated the measurement equivalence of the Self-Care of Chronic Illness Inventory in individuals from three different cultural groups. We were interested in determining if Italians, Swedes, and Americans interpret the measure in a conceptually similar way. Methods: This cross-sectional study enrolled 1629 patients, 784 recruited in Italy, 438 in Sweden and 407 in the United States. Self-care (self-care maintenance, self-care monitoring and self-care management) was measured with the Self-Care of Chronic Illness Inventory. A multi-group confirmatory factor analytic approach was used to assess the equivalence of the measures across the three countries. Configural, metric, scalar and strict invariance were tested through a series of nested models where increasingly stringent equality constraints were posited. Results: Participants were mostly males (56.3%), older adults (69.8%) and had at least two chronic conditions. Results indicated that three out of four measurement equivalence levels were partially or totally supported in all three of the Self-Care of Chronic Illness Inventory scales. The partial scalar invariance level was reached for self-care maintenance [χ2(50) = 63.495, p = 0.095; RMSEA = 0.022, p = 0.999, 90% CI = 0.000 0.038; CFI = 0.981; TLI = 0.977; SRMR = 0.036], self-care monitoring [χ2(22) = 28.770, p = 0.095; RMSEA = 0.024, p = 0.978, 90% CI = 0.000 0.046; CFI = 0.996; TLI = 0.995; SRMR = 0.054], and self-care management [χ2(51) = 91.334, p = 0.001; RMSEA = 0.048, p = 0.576, 90% CI = 0.031 0.063; CFI = 0.949; TLI = 0.937; SRMR = 0.047] scales. Conclusions: These findings suggest that patients in the three countries used an identical cognitive framework or mental model when responding and used the 1–5 Likert response scale in an almost identical way, almost without bias. In spite of sociocultural differences, patients in these countries seem to share the same fundamental view of self-care. The results of the Self-Care of Chronic Illness Inventory will be comparable in these countries