Biting the hand that feeds: A status-based model of when and why receiving help motivates social undermining.

Social exchange theory suggests that after receiving help, people reciprocate by helping the original help giver. However, we propose that help recipients may respond negatively and harm the help giver when they perceive helping as a status threat and experience envy. Integrating the helping as status relations framework and the social functional perspective of envy, we examine when and why receiving help may prompt help recipients to undermine help givers. Across four studies, we find progressive support for our results, which show that when individuals receive task-related help from help givers who are perceived to be more, rather than less, competent than them, they experience greater status threat and envy. As help recipients experience envy toward help givers, they are likely to undermine help givers, and this positive relationship becomes stronger for help recipients who have higher status striving motivation. Our findings underscore the status dynamics implicated in helping interactions by highlighting that help recipients, especially those with higher status striving motivation, may paradoxically undermine help givers when they perceive status threat from and feel envious of help givers, as a result of receiving help from more competent help givers. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

The mutual constitution of culture and psyche: The bidirectional relationship between individuals' perceived control and cultural tightness-looseness.

According to the theory of mutual constitution of culture and psyche, just as culture shapes people, individuals' psychological states can influence culture. We build on compensatory control theory, which suggests that low personal control can lead people to prefer societal systems that impose order, to examine the mutual constitution of personal control and cultural tightness. Specifically, we tested whether individuals' lack of personal control increases their preference for tighter cultures as a means of restoring order and predictability, and whether tighter cultures in turn reduce people's feelings of personal control. Seven studies (five preregistered) with participants from the United States, Singapore, and China examine this cycle of mutual constitution. Specifically, documenting the correlational link between person and culture, we found that Americans lower on personal control preferred to live in tighter states (Study 1). Chinese employees lower on personal control also desired more structure and preferred a tighter organizational culture (Study 2). Employing an experimental causal chain design, Studies 3-5 provided causal evidence for our claim that lack of control increases desire for tighter cultures via the need for structure. Finally, tracing the link back from culture to person, Studies 6a and 6b found that whereas tighter cultures decreased perceptions of individual personal control, they increased people's sense of collective control. Overall, the findings document the process of mutual constitution of culture and psyche: lack of personal control leads people to seek more structured, tighter cultures, and that tighter cultures, in turn, decrease people's sense of personal control but increase their sense of collective control. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Gender, bottom-line mentality, and workplace mistreatment: The roles of gender norm violation and team gender composition.

Although gender has been identified as an important antecedent in workplace mistreatment research, empirical research has shown mixed results. Drawing on role congruity theory, we propose an interactive effect of gender and bottom-line mentality on being the target of mistreatment. Across two field studies, our results showed that whereas women experienced more mistreatment when they had higher levels of bottom-line mentality, men experienced more mistreatment when they had lower levels of bottom-line mentality. In another field study, using round-robin survey data, we found that team gender composition influenced the degree to which the adoption of a bottom-line mentality by female team members was perceived to be a gender norm violation, which subsequently predicted their likelihood of being mistreated. Specifically, women who had higher (vs. lower) levels of bottom-line mentality were more likely to be perceived to violate gender norms in teams with a lower proportion of women, and in turn, perceived gender norm violation was positively associated with being mistreated. We discuss theoretical and practical implications of our findings and directions for future research. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Fit to be good: Physical fitness is negatively associated with deviance.

While modern organizations generate economic value, they also produce negative externalities in terms of human physical fitness, such that workers globally are becoming physically unfit. In the current research, we focus on a significant but overlooked indirect cost that lack of physical fitness entails-deviance. In contrast to early (and methodologically limited) research in criminology, which suggests that physically fit people are more likely to behave in a deviant manner, we draw on self-control theory to suggest the opposite: That physically fit people are less likely to engage in deviance. In Study 1, we assembled a dataset on 50 metropolitan areas in the U.S. spanning a 9-year period, and found that physical fitness index of a metropolitan area is negatively related to deviance in that area in a concurrent as well as time-lagged fashion. We complemented this aggregate-level theory test with two studies testing the theory at the individual level. In Study 2, we collected multi-source data from 3,925 military recruits who underwent physical training and found that those who score higher on physical fitness test are less likely to engage in deviance. Study 3 conceptually replicated the effect with both concurrent and time-lagged models using a five-wave longitudinal design in a sample of employees working in service roles, and also found that ego depletion mediates the effect of physical activity on workplace deviance. We speculate on economic implications of the observed relationship between physical fitness and deviance and discuss its relevance for organizations and public policy. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Microbicidal effects of α- and θ-defensins against antibiotic-resistant Staphylococcus aureus and Pseudomonas aeruginosa.

Antibiotic-resistant bacterial pathogens threaten public health. Because many antibiotics target specific bacterial enzymes or reactions, corresponding genes may mutate under selection and lead to antibiotic resistance. Accordingly, antimicrobials that selectively target overall microbial cell integrity may offer alternative approaches to therapeutic design. Naturally occurring mammalian α- and θ-defensins are potent, non-toxic microbicides that may be useful for treating infections by antibiotic-resistant pathogens because certain defensin peptides disrupt bacterial, but not mammalian, cell membranes. To test this concept, clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA), including vancomycin heteroresistant strains, and ciprofloxacin-resistant Pseudomonas aeruginosa (Cip(R)-PA) were tested for sensitivity to α-defensins Crp-4, RMAD-4 and HNPs 1-3, and to RTD-1, macaque θ-defensin-1. In vitro, 3 µM Crp-4, RMAD-4 and RTD-1 reduced MRSA cell survival by 99%, regardless of vancomycin susceptibility. For PA clinical isolates that differ in fluoroquinolone resistance and virulence phenotype, peptide efficacy was independent of strain ciprofloxacin resistance, site of isolation or virulence factor expression. Thus, Crp-4, RMAD-4 and RTD-1 are effective in vitro antimicrobials against clinical isolates of MRSA and Cip(R)-PA, perhaps providing templates for development of α- and θ-defensin-based microbicides against antibiotic resistant or virulent infectious agents.

Hydrophobic determinants of α-defensin bactericidal activity.

Mammalian α-defensins are approximately 4- to 5-kDa broad-spectrum antimicrobial peptides and abundant granule constituents of neutrophils and small intestinal Paneth cells. The bactericidal activities of amphipathic α-defensins depend in part on electropositive charge and on hydrophobic amino acids that enable membrane disruption by interactions with phospholipid acyl chains. Alignment of α-defensin primary structures identified conserved hydrophobic residues in the loop formed by the Cys(III)-Cys(V) disulfide bond, and we have studied their role by testing the effects of mutagenesis on bactericidal activities. Mouse α-defensin 4 (Crp-4) and rhesus myeloid α-defensin 4 (RMAD-4) were selected for these studies, because they are highly bactericidal in vitro and have the same overall electropositive charge. Elimination of hydrophobicity by site-directed mutagenesis at those positions in Crp-4 attenuated bactericidal activity markedly. In contrast to native Crp-4, the (I23/F25/L26/G)-Crp-4 variant lacked bactericidal activity against Salmonella enterica serovar Typhimurium and did not permeabilize Escherichia coli ML35 cells as a result of removing aliphatic side chains by Gly substitutions. Ala replacements in (I23/F25/L26/A)-Crp-4 restored activity, evidence that hydrophobicity contributed by Ala methyl R-groups was sufficient for activity. In macaques, neutrophil α-defensin RMAD-6 is identical to RMAD-4, except for a F28S difference, and (F28S)-RMAD-4 mutagenesis attenuated RMAD-4 bactericidal activity and E. coli permeabilization. Interestingly, (R31/32D)-Crp-4 lacks activity in these assays despite the presence of the Ile23, Phe25, and Leu26 hydrophobic patch. We infer that electrostatic interactions between cationic α-defensin residues and negative charge on bacteria precede interactions between critical hydrophobic residue positions that mediate membrane disruption and bacterial cell killing.

Family incivility and job performance: a moderated mediation model of psychological distress and core self-evaluation.

This study extends the stress literature by exploring the relationship between family incivility and job performance. We examine whether psychological distress mediates the link between family incivility and job performance. We also investigate how core self-evaluation might moderate this mediated relationship. Data from a 2-wave study indicate that psychological distress mediates the relationship between family incivility and job performance. In addition, core self-evaluation moderates the relationship between family incivility and psychological distress but not the relationship between psychological distress and job performance. The results hold while controlling for general job stress, family-to-work conflict, and work-to-family conflict. The findings suggest that family incivility is linked to poor performance at work, and psychological distress and core self-evaluation are key mechanisms in the relationship.

CXCL17 is a mucosal chemokine elevated in idiopathic pulmonary fibrosis that exhibits broad antimicrobial activity.

The mucosal immune network is a crucial barrier preventing pathogens from entering the body. The network of immune cells that mediates the defensive mechanisms in the mucosa is likely shaped by chemokines, which attract a wide range of immune cells to specific sites of the body. Chemokines have been divided into homeostatic or inflammatory depending upon their expression patterns. Additionally, several chemokines mediate direct killing of invading pathogens, as exemplified by CCL28, a mucosa-associated chemokine that exhibits antimicrobial activity against a range of pathogens. CXCL17 was the last chemokine ligand to be described and is the 17th member of the CXC chemokine family. Its expression pattern in 105 human tissues and cells indicates that CXCL17 is a homeostatic, mucosa-associated chemokine. Its strategic expression in mucosal tissues suggests that it is involved in innate immunity and/or sterility of the mucosa. To test the latter hypothesis, we tested CXCL17 for possible antibacterial activity against a panel of pathogenic and opportunistic bacteria. Our results indicate that CXCL17 has potent antimicrobial activities and that its mechanism of antimicrobial action involves peptide-mediated bacterial membrane disruption. Because CXCL17 is strongly expressed in bronchi, we measured it in bronchoalveolar lavage fluids and observed that it is strongly upregulated in idiopathic pulmonary fibrosis. We conclude that CXCL17 is an antimicrobial mucosal chemokine that may play a role in the pathogenesis of interstitial lung diseases.

Arginine in α-defensins: differential effects on bactericidal activity correspond to geometry of membrane curvature generation and peptide-lipid phase behavior.

The conserved tridisulfide array of the α-defensin family imposes a common triple-stranded ß-sheet topology on peptides that may have highly diverse primary structures, resulting in differential outcomes after targeted mutagenesis. In mouse cryptdin-4 (Crp4) and rhesus myeloid α-defensin-4 (RMAD4), complete substitutions of Arg with Lys affect bactericidal peptide activity very differently. Lys-for-Arg mutagenesis attenuates Crp4, but RMAD4 activity remains mostly unchanged. Here, we show that the differential biological effect of Lys-for-Arg replacements can be understood by the distinct phase behavior of the experimental peptide-lipid system. In Crp4, small-angle x-ray scattering analyses showed that Arg-to-Lys replacements shifted the induced nanoporous phases to a different range of lipid compositions compared with the Arg-rich native peptide, consistent with the attenuation of bactericidal activity by Lys-for-Arg mutations. In contrast, such phases generated by RMAD4 were largely unchanged. The concordance between small-angle x-ray scattering measurements and biological activity provides evidence that specific types of α-defensin-induced membrane curvature-generating tendencies correspond directly to bactericidal activity via membrane destabilization.

Biosynthesis and antimicrobial evaluation of backbone-cyclized α-defensins.

Defensins are antimicrobial peptides that are important in the innate immune defense of mammals. Upon stimulation by bacterial antigens, enteric α-defensins are secreted into the intestinal lumen where they have potent microbicidal activities. Cryptdin-4 (Crp4) is an α-defensin expressed in Paneth cells of the mouse small intestine and the most bactericidal of the known cryptdin isoforms. The structure of Crp4 consists of a triple-stranded antiparallel ß-sheet but lacks three amino acids between the fourth and fifth cysteine residues, making them distinct from other α-defensins. The structure also reveals that the α-amino and C-terminal carboxylic groups are in the proximity of each other (d ≈ 3 Å) in the folded structure. We present here the biosynthesis of backbone-cyclized Crp4 using a modified protein splicing unit or intein. Our data show that cyclized Crp4 can be biosynthesized by using this approach both in vitro and in vivo, although the expression yield was significantly lower when the protein was produced inside the cell. The resulting cyclic defensins retained the native α-defensin fold and showed equivalent or better microbicidal activities against several Gram-positive and Gram-negative bacteria when compared to native Crp4. No detectable hemolytic activity against human red blood cells was observed for either native Crp4 or its cyclized variants. Moreover, both forms of Crp4 also showed high stability to degradation when incubated with human serum. Altogether, these results indicate the potential for backbone-cyclized defensins in the development of novel peptide-based antimicrobial compounds.

Criterion for amino acid composition of defensins and antimicrobial peptides based on geometry of membrane destabilization.

Defensins comprise a potent class of membrane disruptive antimicrobial peptides (AMPs) with well-characterized broad spectrum and selective microbicidal effects. By using high-resolution synchrotron small-angle X-ray scattering to investigate interactions between heterogeneous membranes and members of the defensin subfamilies, α-defensins (Crp-4), ß-defensins (HBD-2, HBD-3), and θ-defensins (RTD-1, BTD-7), we show how these peptides all permeabilize model bacterial membranes but not model eukaryotic membranes: defensins selectively generate saddle-splay ("negative Gaussian") membrane curvature in model membranes rich in negative curvature lipids such as those with phosphoethanolamine (PE) headgroups. These results are shown to be consistent with vesicle leakage assays. A mechanism of action based on saddle-splay membrane curvature generation is broadly enabling, because it is a necessary condition for processes such as pore formation, blebbing, budding, and vesicularization, all of which destabilize the barrier function of cell membranes. Importantly, saddle-splay membrane curvature generation places constraints on the amino acid composition of membrane disruptive peptides. For example, we show that the requirement for generating saddle-splay curvature implies that a decrease in arginine content in an AMP can be offset by an increase in both lysine and hydrophobic content. This "design rule" is consistent with the amino acid compositions of 1080 known cationic AMPs.

Small-angle X-ray scattering studies of peptide-lipid interactions using the mouse paneth cell α-defensin cryptdin-4.

In the presence of specialized proteins or peptides, a biological membrane can spontaneously restructure itself to allow communication between the intracellular and the extracellular sides. Examples of these proteins include cell-penetrating peptides and antimicrobial peptides (AMPs), which interact with cell membranes in complex ways. We briefly review cell-penetrating peptides and AMPs, and describe in detail how recombinant AMPs are made and their activity evaluated, using α-defensins as a specific example. We also review X-ray scattering methods used in studying peptide-membrane interactions, focusing on the procedures for small-angle X-ray scattering experiments on peptide-membrane interactions at realistic solution conditions, using both laboratory and synchrotron sources.

Expression and purification of recombinant alpha-defensins and alpha-defensin precursors in Escherichia coli.

Recombinant expression of alpha-defensins can be obtained at efficient levels in Escherichia coli. Amplified alpha-defensin or pro-alpha-defensin coding cDNA sequences are cloned directionally between EcoRI and SalI sites of the pET-28a expression vector and expressed in E. coli BL21 RIS cells. Cells growing exponentially in nutrient-rich liquid medium are induced to express the recombinant protein by addition of 50 mM isopropyl beta-D-1-thiogalactopyranoside for 3-6 h. After bacterial cells collected by centrifugation are lysed in 6 M guanidine-HCl under non-reducing conditions, the expressed defensin fused to its 6xHis-34 amino acid N-terminal fusion partner is purified by affinity chromatography on nickel-NTA columns. A Met codon introduced at the N terminus of expressed Met-free peptides provides a unique CNBr cleavage site, enabling release of the alpha-defensin free of ancillary residues by sequential C18 RP-HPLC. Molecular masses of C18 RP-HPLC purified peptides are confirmed by MALDI-TOF mass spectrometry, and peptide homogeneity is assessed using analytical RP-HPLC and acid-urea polyacrylamide gel electrophoresis. alpha-Defensins prepared in this manner are biochemically equivalent to the natural molecules.

Synthesis, structure, and activities of an oral mucosal alpha-defensin from rhesus macaque.

The oral cavity is an environment challenged by a large variety of pathogens. Consequently, the antimicrobial peptides expressed in that environment are interesting as they evolved to defend against a broad spectrum of bacteria and fungi. Here we report the discovery of new alpha-defensins from rhesus macaque oral mucosa and determine the first alpha-defensin structure from that species. The new peptides were identified by sequencing of reverse transcriptase-PCR products obtained from oral mucosal tissues, disclosing three mucosal alpha-defensins, termed rhesus macaque oral alpha-defensins (ROADs). The peptide corresponding to fully processed ROAD-1 was synthesized, subjected to folding/oxidation conditions, and purified. ROAD-1 was active against Staphylococcus aureus, Escherichia coli, and Candida albicans in a concentration-dependent manner. We determined the structure of ROAD-1 using NMR spectroscopy and find that the synthetic peptide adopts the canonical disulfide pairing and alpha-defensin fold. The antimicrobial mechanism of defensins has been correlated with their ability to disrupt and permeabilize the cell envelope, activities that depend on the surface features of the folded peptide. Although ROAD-1 maintains the defensin fold, the oral defensin displays distinct surface features when compared with other alpha-defensin structures.

Hypoalbuminemia in critically ill children.

OBJECTIVE: To evaluate whether hypoalbuminemia on admission is a predictor of adverse outcome in critically ill children. DESIGN: Retrospective medical record review. SETTING: A 14-bed medical and surgical pediatric intensive care unit (PICU). PARTICIPANTS: All patients admitted to the PICU from January 1, 1998, through December 31, 2000, under the care of the PICU team or trauma service and whose albumin level was measured were potential subjects. One hundred fifty-five patients were divided into 4 groups on the basis of age and appropriate albumin level for that age group. The groups of hypoalbuminemic patients were combined (hypoalbuminemia group) and compared with the combined group of patients with albumin levels above the reference cutoff (normal albumin level group). EXPOSURE: Serum albumin level. MAIN OUTCOME MEASURES: Length of PICU and hospital stays, receipt and length of ventilatory support, survival, pediatric risk of mortality score, mortality risk, and number of organ failures. RESULTS: Controlling for mortality risk, the hypoalbuminemia group had a longer average stay in the PICU (8.08 vs 4.41 days; 95% confidence interval [CI] for difference, 1.02-6.32) and the hospital (11.36 vs 6.63 days; 95% CI for difference, 1.31-8.16) than did the normal albumin level group. The hypoalbuminemia group had a lower survival rate (odds ratio, 0.10; 95% CI, 0.02-0.46) and a higher number of organ failures (1.38 vs 0.65; 95% CI for difference, 0.40-1.04). CONCLUSION: Admission hypoalbuminemia is a significant marker of morbidity and mortality in critically ill children.