The Resentful Embittered Personality, Adjustment and Depression in Student and Marital Relationships

Hostility and anger have long been shown to be predictive of negative psychological, interpersonal and physical outcomes. Much of the literature, has focused on hostility as a state rather than a personality trait and has not attempted to explicate the link between embittered personality and depression. To achieve these goals, a newly created measure called the Resentful Embittered Personality Scale (REPS) was evaluated in detail. First, the literature examining the construct of embitterment and hostility was reviewed, its links with depression was explained, and unpublished pilot data were reviewed. Next, the psychometric properties, convergent and divergent validity, and reliability of the REPS were evaluated in the first study by exploring correlations with the NEO-FFI and other specific personality constructs and measures of hostility and distress. The second study evaluated the REPS with the larger measure of general personality, the NEO-PI-R, to further understand the nuances of these relationships between the REPS and the specific facets from the Big Five measure of personality. The focus of the third study was to examine the REPS with respect to both well-being and distress along with measures of stress. Finally, the fourth study examined the predictive validity of the REPS with respect to dyadic adjustment and depression six months later, after the birth of their first child. Results showed that the REPS was a valid and reliable measure and that the construct’s associations with certain factors of the NEO-PI R suggested that it reflected a highly ego-defensive and interpersonally sensitive personality style that likely functioned to set up a self-fulfilling prophecy of expected and elicited interpersonally conflictual exchanges. Multiple hierarchical regression analyses found that the REPS predicted both main and interactive effects of psychological distress and well-being over and above other personality and stress measures. Finally, embittered personality predicted poorer dyadic adjustment and depression for both male and female heterosexual couples three months after the birth of their first child. Together these results lent support to the interpersonal and negative affectivity theories of depression and have shown the REPS to be a valid, reliable and useful personality measure for personality, interpersonal and clinical purposes

Recognition of Chiral Carboxylic Anions by Artificial Receptors

Many carboxylic molecules, ranging from drugs to flavors and fragrances, contain chiral centers. As a consequence, research has been carried out in order to design and synthesize artificial receptors for carboxylic anions. Many problems have to be solved for binding anions. The results obtained in the binding of carboxylic anions by guanidine, secondary ammonium and metal-center have been selected. The last part of this review focuses on chiral recognition of carboxylic anions by organic and metal-based chiral receptors

Perturbation-Response Scanning Reveals Ligand Entry-Exit Mechanisms of Ferric Binding Protein

We study apo and holo forms of the bacterial ferric binding protein (FBP) which exhibits the so-called ferric transport dilemma: it uptakes iron from the host with remarkable affinity, yet releases it with ease in the cytoplasm for subsequent use. The observations fit the “conformational selection” model whereby the existence of a weakly populated, higher energy conformation that is stabilized in the presence of the ligand is proposed. We introduce a new tool that we term perturbation-response scanning (PRS) for the analysis of remote control strategies utilized. The approach relies on the systematic use of computational perturbation/response techniques based on linear response theory, by sequentially applying directed forces on single-residues along the chain and recording the resulting relative changes in the residue coordinates. We further obtain closed-form expressions for the magnitude and the directionality of the response. Using PRS, we study the ligand release mechanisms of FBP and support the findings by molecular dynamics simulations. We find that the residue-by-residue displacements between the apo and the holo forms, as determined from the X-ray structures, are faithfully reproduced by perturbations applied on the majority of the residues of the apo form. However, once the stabilizing ligand (Fe) is integrated to the system in holo FBP, perturbing only a few select residues successfully reproduces the experimental displacements. Thus, iron uptake by FBP is a favored process in the fluctuating environment of the protein, whereas iron release is controlled by mechanisms including chelation and allostery. The directional analysis that we implement in the PRS methodology implicates the latter mechanism by leading to a few distant, charged, and exposed loop residues. Upon perturbing these, irrespective of the direction of the operating forces, we find that the cap residues involved in iron release are made to operate coherently, facilitating release of the ion

Studying protein–protein affinity and immobilized ligand–protein affinity interactions using MS-based methods

This review discusses the most important current methods employing mass spectrometry (MS) analysis for the study of protein affinity interactions. The methods are discussed in depth with particular reference to MS-based approaches for analyzing protein–protein and protein–immobilized ligand interactions, analyzed either directly or indirectly. First, we introduce MS methods for the study of intact protein complexes in the gas phase. Next, pull-down methods for affinity-based analysis of protein–protein and protein–immobilized ligand interactions are discussed. Presently, this field of research is often called interactomics or interaction proteomics. A slightly different approach that will be discussed, chemical proteomics, allows one to analyze selectivity profiles of ligands for multiple drug targets and off-targets. Additionally, of particular interest is the use of surface plasmon resonance technologies coupled with MS for the study of protein interactions. The review addresses the principle of each of the methods with a focus on recent developments and the applicability to lead compound generation in drug discovery as well as the elucidation of protein interactions involved in cellular processes. The review focuses on the analysis of bioaffinity interactions of proteins with other proteins and with ligands, where the proteins are considered as the bioactives analyzed by MS

Methyl group assignment using pseudocontact shifts with PARAssign

Macromolecular Biochemistr

Bipolar disorder with comorbid anxiety disorders: impact of comorbidity on treatment outcome in cognitive-behavioral therapy and psychoeducation

Abstract Background: Comorbid anxiety disorders are extremely prevalent in bipolar disorder (BD) and have substantial impact on the course of illness. Limited evidence regarding treatment factors has led to a renewal of research efforts examining both the impact of treatments on comorbid anxiety and the impact of comorbid anxiety on treatments. The current study examines the impact of comorbid anxiety disorders on response to two psychosocial interventions for BD. Methods: A sample of 204 patients with BD took part in the study. Of them, 41.7% had a comorbid anxiety disorder. All participants received either individual cognitive-behavioral therapy or group psychoeducation for BD. Evaluations included complete pretreatment and 18-month follow-up assessments of mood and anxiety symptoms, functioning, medication compliance, dysfunctional attitudes, and coping style. Outcome was compared based on the presence or absence of a comorbid anxiety disorder. Results and discussion: The participants with comorbid anxiety disorders ranked more severe than those without on several measures. Despite more severe illness characteristics, the magnitude of their treatment gains was equivalent or superior to that of the participants without anxiety disorders on a variety of outcome measures. Although the treatments did not specifically target the anxiety disorder, the participants made significant improvements in anxiety symptoms. Despite greater illness severity, patients with comorbid anxiety disorders can make substantial gains from psychosocial interventions targeting BD. Even in the presence of an anxiety disorder, they are able to attend to the content of the psychosocial treatments and apply it to better manage their condition. The presence of a comorbid anxiety disorder should not be considered a deterrent to offering BDfocused psychosocial treatments

Measurement of Active Site Ionization Equilibria in the 670 kDa Proteasome Core Particle Using Methyl-TROSY NMR

The 20S proteasome core particle is a molecular machine that plays a central role in the regulation of cellular function through proteolysis, and it has emerged as a valuable drug target for certain classes of cancers. Central to the development of new and potent pharmaceuticals is an understanding of the mechanism by which the proteasome cleaves substrates. A number of high-resolution structures of the 20S proteasome with and without inhibitors have emerged that provide insight into the chemistry of peptide bond cleavage and establish the role of Thr1 Oγ1 as the catalytic nucleophile. The source of the base that accepts the Thr1 Hγ1 is less clear. Using a highly deuterated sample of the proteasome labeled with ¹³CH₃ at the Thr-γ positions, the p<i>K</i>_A of the Thr1 amino group has been measured to be 6.3 and hence deprotonated in the range of maximal enzyme activity. This provides strong evidence that the terminal amino group of Thr1 serves as the base in the first step of the peptide bond cleavage reaction

Bipolar disorder with comorbid anxiety disorders: impact of comorbidity on treatment outcome in cognitive-behavioral therapy and psychoeducation

Abstract Background Comorbid anxiety disorders are extremely prevalent in bipolar disorder (BD) and have substantial impact on the course of illness. Limited evidence regarding treatment factors has led to a renewal of research efforts examining both the impact of treatments on comorbid anxiety and the impact of comorbid anxiety on treatments. The current study examines the impact of comorbid anxiety disorders on response to two psychosocial interventions for BD. Methods A sample of 204 patients with BD took part in the study. Of them, 41.7% had a comorbid anxiety disorder. All participants received either individual cognitive-behavioral therapy or group psychoeducation for BD. Evaluations included complete pretreatment and 18-month follow-up assessments of mood and anxiety symptoms, functioning, medication compliance, dysfunctional attitudes, and coping style. Outcome was compared based on the presence or absence of a comorbid anxiety disorder. Results and discussion The participants with comorbid anxiety disorders ranked more severe than those without on several measures. Despite more severe illness characteristics, the magnitude of their treatment gains was equivalent or superior to that of the participants without anxiety disorders on a variety of outcome measures. Although the treatments did not specifically target the anxiety disorder, the participants made significant improvements in anxiety symptoms. Despite greater illness severity, patients with comorbid anxiety disorders can make substantial gains from psychosocial interventions targeting BD. Even in the presence of an anxiety disorder, they are able to attend to the content of the psychosocial treatments and apply it to better manage their condition. The presence of a comorbid anxiety disorder should not be considered a deterrent to offering BD-focused psychosocial treatments

Fluorinated Ethylamines as Electrospray-Compatible Neutral pH Buffers for Native Mass Spectrometry

Native electrospray ionization mass spectrometry (ESI-MS) has emerged as a potent tool for examining the native-like structures of macromolecular complexes. Despite its utility, the predominant “buffer” used, ammonium acetate (AmAc) with pKa values of 4.75 for acetic acid and 9.25 for ammonium, provides very little buffering capacity within the physiological pH range of 7.0–7.4. ESI-induced redox reactions alter the pH of the liquid within the ESI capillary. This can result in protein unfolding or weakening of pH-sensitive interactions. Consequently, the discovery of volatile, ESI-compatible buffers, capable of effectively maintaining pH within a physiological range, is of high importance. Here, we demonstrate that 2,2-difluoroethylamine (DFEA) and 2,2,2-trifluoroethylamine (TFEA) offer buffering capacity at physiological pH where AmAc falls short, with pKa values of 7.2 and 5.5 for the conjugate acids of DFEA and TFEA, respectively. Native ESI-MS experiments on model proteins cytochrome c and myoglobin electrosprayed with DFEA and TFEA demonstrated the preservation of noncovalent protein–ligand complexes in the gas phase. Protein stability assays and collision-induced unfolding experiments further showed that neither DFEA nor TFEA destabilized model proteins in solution or in the gas phase. Finally, we demonstrate that multisubunit protein complexes such as alcohol dehydrogenase and concanavalin A can be studied in the presence of DFEA or TFEA using native ESI-MS. Our findings establish DFEA and TFEA as new ESI-compatible neutral pH buffers that promise to bolster the use of native ESI-MS for the analysis of macromolecular complexes, particularly those sensitive to pH fluctuations

Fluorinated Ethylamines as Electrospray-Compatible Neutral pH Buffers for Native Mass Spectrometry

Native electrospray ionization mass spectrometry (ESI-MS) has emerged as a potent tool for examining the native-like structures of macromolecular complexes. Despite its utility, the predominant “buffer” used, ammonium acetate (AmAc) with pKa values of 4.75 for acetic acid and 9.25 for ammonium, provides very little buffering capacity within the physiological pH range of 7.0–7.4. ESI-induced redox reactions alter the pH of the liquid within the ESI capillary. This can result in protein unfolding or weakening of pH-sensitive interactions. Consequently, the discovery of volatile, ESI-compatible buffers, capable of effectively maintaining pH within a physiological range, is of high importance. Here, we demonstrate that 2,2-difluoroethylamine (DFEA) and 2,2,2-trifluoroethylamine (TFEA) offer buffering capacity at physiological pH where AmAc falls short, with pKa values of 7.2 and 5.5 for the conjugate acids of DFEA and TFEA, respectively. Native ESI-MS experiments on model proteins cytochrome c and myoglobin electrosprayed with DFEA and TFEA demonstrated the preservation of noncovalent protein–ligand complexes in the gas phase. Protein stability assays and collision-induced unfolding experiments further showed that neither DFEA nor TFEA destabilized model proteins in solution or in the gas phase. Finally, we demonstrate that multisubunit protein complexes such as alcohol dehydrogenase and concanavalin A can be studied in the presence of DFEA or TFEA using native ESI-MS. Our findings establish DFEA and TFEA as new ESI-compatible neutral pH buffers that promise to bolster the use of native ESI-MS for the analysis of macromolecular complexes, particularly those sensitive to pH fluctuations