Structural basis of TMPRSS2 zymogen activation and recognition by the HKU1 seasonal coronavirus.

The human seasonal coronavirus HKU1-CoV, which causes common colds worldwide, relies on the sequential binding to surface glycans and transmembrane serine protease 2 (TMPRSS2) for entry into target cells. TMPRSS2 is synthesized as a zymogen that undergoes autolytic activation to process its substrates. Several respiratory viruses, in particular coronaviruses, use TMPRSS2 for proteolytic priming of their surface spike protein to drive membrane fusion upon receptor binding. We describe the crystal structure of the HKU1-CoV receptor binding domain in complex with TMPRSS2, showing that it recognizes residues lining the catalytic groove. Combined mutagenesis of interface residues and comparison across species highlight positions 417 and 469 as determinants of HKU1-CoV host tropism. The structure of a receptor-blocking nanobody in complex with zymogen or activated TMPRSS2 further provides the structural basis of TMPRSS2 activating conformational change, which alters loops recognized by HKU1-CoV and dramatically increases binding affinity.

The origin of esterase activity of Parkinson's disease causative factor DJ-1 implied by evolutionary trace analysis of its prokaryotic homolog HchA.

DJ-1, a causative gene for hereditary recessive Parkinsonism, is evolutionarily conserved across eukaryotes and prokaryotes. Structural analyses of DJ-1 and its homologs suggested the 106th Cys is a nucleophilic cysteine functioning as the catalytic center of hydratase or hydrolase activity. Indeed, DJ-1 and its homologs can convert highly electrophilic α-oxoaldehydes such as methylglyoxal into α-hydroxy acids as hydratase in vitro, and oxidation-dependent ester hydrolase (esterase) activity has also been reported for DJ-1. The mechanism underlying such plural activities, however, has not been fully characterized. To address this knowledge gap, we conducted a series of biochemical assays assessing the enzymatic activity of DJ-1 and its homologs. We found no evidence for esterase activity in any of the Escherichia coli DJ-1 homologs. Furthermore, contrary to previous reports, we found that oxidation inactivated rather than facilitated DJ-1 esterase activity. The E. coli DJ-1 homolog HchA possesses phenylglyoxalase and methylglyoxalase activities but lacks esterase activity. Since evolutionary trace analysis identified the 186th H as a candidate residue involved in functional differentiation between HchA and DJ-1, we focused on H186 of HchA and found that an esterase activity was acquired by H186A mutation. Introduction of reverse mutations into the equivalent position in DJ-1 (A107H) selectively eliminated its esterase activity without compromising α-oxoaldehyde hydratase activity. The obtained results suggest that differences in the amino acid sequences near the active site contributed to acquisition of esterase activity in vitro and provide an important clue to the origin and significance of DJ-1 esterase activity.

Elucidating the molecular properties and anti-mycobacterial activity of cysteine peptidase domain of D29 mycobacteriophage endolysin.

Emergence of antibiotic resistance in pathogenic Mycobacterium tuberculosis (Mtb) has elevated tuberculosis to a serious global threat, necessitating alternate solutions for its eradication. D29 mycobacteriophage can infect and kill several mycobacterial species including Mtb. It encodes an endolysin LysA to hydrolyze host bacteria peptidoglycan for progeny release. We previously showed that out of the two catalytically active domains of LysA [N-terminal domain (NTD) and lysozyme-like domain], NTD, when ectopically expressed in Mycobacterium smegmatis (Msm), is able to kill the bacterium nearly as efficiently as full-length LysA. Here, we dissected the functioning of NTD to develop it as a phage-derived small molecule anti-mycobacterial therapeutic. We performed a large-scale site-directed mutagenesis of the conserved residues in NTD and examined its structure, stability, and function using molecular dynamic simulations coupled with biophysical and biochemical experiments. Our data show that NTD functions as a putative cysteine peptidase with a catalytic triad composed of Cys41, His112, and Glu137, acting as nucleophile, base, and acid, respectively, and showing characteristics similar to the NlpC/P60 family of cysteine peptidases. Additionally, our peptidoglycan hydrolysis assays suggested that NTD hydrolyzes only mycobacterial peptidoglycan and does not act on Gram-positive and Gram-negative bacterial peptidoglycans. More importantly, the combined activity of exogenously added NTD and sub-lethal doses of anti-mycobacterial drugs kills Msm in vitro and exhibits disruption of pre-formed mycobacterial biofilm. We additionally show that NTD treatment increases the permeability of antibiotics in Msm, which reduces the minimum inhibitory concentration of the antibiotics. Collectively, we present NTD as a promising phage-derived therapeutic against mycobacteria.IMPORTANCEMycobacteriophages are the viruses that use mycobacteria as host for their progeny production and, in the process, kill them. Mycobacteriophages are, therefore, considered as promising alternatives to antibiotics for killing pathogenic Mycobacterium tuberculosis. The endolysin LysA produced by mycobacteriophage D29 plays an important role in host cell lysis and virion release. Our work presented here highlights the functioning of LysA's N-terminal catalytic domain (NTD) in order to develop it as phage-derived small molecule therapeutics. We show that combined treatment of exogenously added NTD and sub-lethal doses of anti-mycobacterial drugs kills M. smegmatis, shows synergism by reducing the minimum inhibitory concentration of these antibiotics, and exhibits disruption of pre-formed mature biofilm. These outcomes and our detailed biochemical and biophysical dissection of the protein further pave the way toward engineering and development of NTD as a promising therapeutic against mycobacterial infections such as tuberculosis.

Circulating immune complexes and G6PD deficiency predict readmissions for blackwater fever and severe anemia in children with severe malaria in Eastern Uganda.

BACKGROUND: Recently, there has been an unexplained increase in the incidence of blackwater fever (BWF) in Eastern Uganda. In this study, we evaluate the association between immune complexes, glucose-6-phosphate dehydrogenase (G6PD) deficiency, and the occurrence and recurrence of BWF in children with severe malaria (SM). METHODS: Between 2014 and 2017, children aged six months to <4 years hospitalized with SM and community children (CC) were recruited at two hospitals in Central and Eastern Uganda. We measured serum circulating immune complexes (cIC) and their relationship to SM complications and post-discharge outcomes and evaluated effect mediation through G6PD deficiency. RESULTS: 557 children with SM and 101 CC were enrolled. The mean age of children was 2.1 years. Children with SM had higher cIC levels than CC, p<0.001. After controlling for age, sex, and site, cIC were associated with severe anemia, jaundice, and BWF (adjusted odds ratio, 95% confidence interval: 7.33 (3.45, 15.58), p<0.0001; 4.31 (1.68, 11.08), p=0.002; and 5.21 (2.06, 13.18), p<0.0001), respectively. cIC predicted readmissions for SM, severe anemia, and BWF (adjusted incidence rate ratios (95% confidence interval): 2.11 (1.33, 3.34), p=0.001; 8.62 (2.80, 26.59), p<0.0001; and 7.66 (2.62, 22.45), p<0.0001), respectively. The relationship was most evident in males where the frequency of the G6PD African allele (A-) was 16.8%. G6PD deficiency was associated with increases in cIC in males (p=0.01) and mediation analysis suggested G6PD deficiency contributes to recurrent severe anemia and BWF via increased cIC. CONCLUSIONS: Immune complexes are associated with hemolytic complications and predict recurrences in SM survivors.

Recent Advances in Pristine Iron Triad Metal-Organic Framework Cathodes for Alkali Metal-Ion Batteries.

Pristine iron triad metal-organic frameworks (MOFs), i.e., Fe-MOFs, Co-MOFs, Ni-MOFs, and heterometallic iron triad MOFs, are utilized as versatile and promising cathodes for alkali metal-ion batteries, owing to their distinctive structure characteristics, including modifiable and designable composition, multi-electron redox-active sites, exceptional porosity, and stable construction facilitating rapid ion diffusion. Notably, pristine iron triad MOFs cathodes have recently achieved significant milestones in electrochemical energy storage due to their exceptional electrochemical properties. Here, the recent advances in pristine iron triad MOFs cathodes for alkali metal-ion batteries are summarized. The redox reaction mechanisms and essential strategies to boost the electrochemical behaviors in associated electrochemical energy storage devices are also explored. Furthermore, insights into the future prospects related to pristine iron triad MOFs cathodes for lithium-ion, sodium-ion, and potassium-ion batteries are also delivered.

Characteristics of bone mineral density in patients with functional hypothalamic amenorrhoea and its association with reproductive hormones and body composition.

OBJECTIVE: Bone mineral density (BMD) is typically reduced in patients with female athlete triad (FAT) and anorexia nervosa (AN). However, bone health in most patients with functional hypothalamic amenorrhoea (FHA), who may not suffer from severe energy deficiency, has not received adequate attention in clinical practice. This study aimed to investigate BMD and its association with clinical and endocrine features in individuals with FHA and to provide clinical evidence for improving bone loss and preventing osteoporosis in FHA. DESIGN: To assess the bone status of patients with FHA and investigate its association with various clinical and endocrinological characteristics. PATIENTS: We retrospectively analysed 80 patients with FHA who attended the Obstetrics and Gynecology Hospital of Fudan University from January 2022 to March 2023. MEASUREMENTS: The levels of reproductive hormones, including luteinising hormone (LH), follicle-stimulating hormone, oestradiol (E2 ) and total testosterone (TT), were examined at the time of initial diagnosis, and a body composition analyser was used to measure body fat percentage (BF%), lean body mass (LBM) and segmental muscle/fat. Dual-emission X-ray absorptiometry was used to measure lumbar spine BMD and femoral neck BMD in patients with FHA, and the Z score was calculated. RESULTS: The study cohort consisted of 80 female patients with FHA. The average age of the patients was 24.64 ± 6.02 years, and their body mass index (BMI) was 19.47 ± 2.86 kg/m2 . The duration of weight loss was 12 (6, 24) months, while the duration of oligo/amenorrhoea was 12 (4.5, 24) months. The mean degree of weight loss was 18.39 ± 9.53%. Low BMD were present in 15% of patients with FHA at the lumbar spine and/or femoral neck; 12.5% and 10% had low bone mass at the lumbar spine and femoral neck, respectively. The low bone mass group experienced a longer period of weight loss than the normal group [24 (16.5, 60) vs. 12 (4.5, 24) months, p = .037]. In addition, the abnormal group had a lower BMR (basal metabolic rate, BMR) [1158 ± 85 vs. 1231 ± 91 kcal/day, p = .011] and lower bone mineral content [2.15 ± 0.26 vs. 2.43 ± 0.31 kg, p = .009] than the normal group. Both LBMD and femoral neck BMD (Fn BMD) were positively correlated with BMI, BF%, LBM, and regional muscle/fat mass (all p < .05). There was also a positive correlation between LBMD and basal LH levels (p = .009) and waist-to-hip ratio (p = .034), whereas Fn BMD was positively correlated with TT levels (p = .029). Multiple linear regression analysis showed that LBM was positively associated with LBMD (ß = .007, 95% confidence interval [CI] = 0.004-0.009, p < .001), while trunk muscle mass was positively associated with Fn BMD (ß = .046, 95% CI = 0.013-0.080, p = .008). CONCLUSION: Fifteen percent of the patients with FHA exhibited low bone mass, a condition associated with prolonged weight loss. The basal LH and TT levels showed positive correlations with LBMD and Fn BMD, respectively. Meanwhile, BMR levels, BMI, BF%, and muscle mass were all positively correlated with LBMD and Fn BMD. Clinically, we should be attentive to suboptimal bone health in patients with FHA and take early screening, diagnosis and intervention measures, especially appropriate muscle mass gain, to prevent the onset of osteoporosis and fragility fractures in the long term.

Synthesis, Structure and Reactivity of a Mononuclear N,N,O-Bound Fe(II) α-Keto-Acid Complex.

A bulky, tridentate phenolate ligand (ImPh2 NNOtBu ) was used to synthesise the first example of a mononuclear, facial, N,N,O-bound iron(II) benzoylformate complex, [Fe(ImPh2 NNOtBu )(BF)] (2). The X-ray crystal structure of 2 reveals that the iron centre is pentacoordinate (τ=0.5), with a vacant site located cis to the bidentate BF ligand. The Mössbauer parameters of 2 are consistent with high-spin iron(II), and are very close to those reported for α-ketoglutarate-bound non-heme iron enzyme active sites. According to NMR and UV-vis spectroscopies, the structural integrity of 2 is retained in both coordinating and non-coordinating solvents. Cyclic voltammetry studies show that the iron centre has a very low oxidation potential and is more prone to electrochemical oxidation than the redox-active phenolate ligand. Complex 2 reacts with NO to form a S=3 /2 {FeNO}7 adduct in which NO binds directly to the iron centre, according to EPR, UV-vis, IR spectroscopies and DFT analysis. Upon O2 exposure, 2 undergoes oxidative decarboxylation to form a diiron(III) benzoate complex, [Fe2 (ImPh2 NNOtBu )2 (µ2 -OBz)(µ2 -OH)2 ]+ (3). A small amount of hydroxylated ligand was also observed by ESI-MS, hinting at the formation of a high-valent iron(IV)-oxo intermediate. Initial reactivity studies show that 2 is capable of oxygen atom transfer reactivity with O2 , converting methyl(p-tolyl)sulfide to sulfoxide.

Atomistic Simulations Reveal Crucial Role of Metal Ions for Ligand Binding in Guanidine-I Riboswitch.

Riboswitches are structured ribonucleic acid (RNA) segments that act as specific sensors for small molecules in bacterial metabolism. Due to the flexible nature of these highly charged macromolecules, molecular dynamics simulations are instrumental to investigating the mechanistic details of their regulatory function. In the present study, the guanidine-I riboswitch serves as an example of how atomistic simulations can shed light on the effect of ions on the structure and dynamics of RNA and on ligand binding. Relying on two orthologous crystal structures from different bacterial species, it is demonstrated how the ion setup crucially determines whether the simulation yields meaningful insights into the conformational stability of the RNA, functionally relevant residues and RNA-ligand interactions. The ion setup in this context includes diffuse ions in solution and bound ions associated directly with the RNA, in particular a triad of 2 Mg2+ ions and a K+ ion in close proximity to the guanidinium binding site. A detailed investigation of the binding pocket reveals that the K+ from the ion triad plays a decisive role in stabilizing the ligand binding by stabilizing important localized interactions, which in turn contribute to the overall shape of the folded state of the RNA.

Acute cholecystitis, obesity, and steatohepatitis constitute the lethal triad for bile duct injury (BDI) during laparoscopic cholecystectomy.

OBJECTIVE: The most feared complication during laparoscopic cholecystectomy remains a bile duct injury (BDI). Accurately risk-stratifying patients for a BDI remains difficult and imprecise. This study evaluated if the lethal triad of acute cholecystitis, obesity, and steatohepatitis is a prognostic measure for BDI. METHODS: A retrospective review of the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) registry was performed. All laparoscopic cholecystectomy cases within the main NSQIP database for 2012-2019 were queried. Two study cohorts were constructed. One with the lethal triad of acute cholecystitis, BMI ≥ 30, and steatohepatitis. The other cohort did not have the full triad present. Multivariate analysis was performed via logistic regression modeling with calculation of odds ratios (OR) to identify independent factors for BDI. An uncontrolled and controlled propensity score match analysis was performed. RESULTS: A total of 387,501 cases were analyzed. 36,887 cases contained the lethal triad, the remaining 350,614 cases did not have the full triad. 860 BDIs were identified resulting in an overall incidence rate 0.22%. There were 541 BDIs within the lethal triad group with 319 BDIs in the other cohort and an incidence rate of 1.49% vs 0.09% (P < 0.001). Multivariate analysis identified the lethal triad as an independent risk factor for a BDI by over 15-fold (OR 16.35, 95%CI 14.28-18.78, P < 0.0001) on the uncontrolled analysis. For the controlled propensity score match there were 29,803 equivalent pairs identified between the cohorts. The BDI incidence rate remained significantly higher with lethal triad cases at 1.65% vs 0.04% (P < 0.001). The lethal triad was an even more significant independent risk factor for BDI on the controlled analysis (OR 40.13, 95%CI 7.05-356.59, P < 0.0001). CONCLUSIONS: The lethal triad of acute cholecystitis, obesity, and steatohepatitis significantly increases the risk of a BDI. This prognostic measure can help better counsel patients and potentially alter management.

Makeup Usage in Women Is Positively Associated to Narcissism and Extraversion but Negatively to Psychopathy.

Appearance modification practices are ubiquitous, serving to enhance physical attractiveness and accrue social advantages, including increased desirability as a potential mate. Facial cosmetics are frequently used for appearance modification, yet individual differences in makeup usage remain understudied. While makeup usage in women has been linked to traits like narcissism and extraversion, the broader association with Dark Triad traits and how personality influences makeup application across diverse social contexts were less explored. Here we examined these relationships in 1,410 Brazilian women (Mage = 29.9, SD = 10.35), who completed online Big Five and Dark Triad personality measures, reported their usual makeup usage habits, and detailed their makeup usage across different social scenarios. Results revealed makeup usage was positively associated with narcissism and extraversion, and negatively with psychopathy. Additionally, women used less makeup when alone (at home, exercises) and more in social settings, particularly for the first date. However, women with higher narcissism and neuroticism showed larger differences among low and high makeup usage situations, while individuals with higher psychopathy used makeup in similar frequencies among different situations. Further, (1) overall greater users of makeup scored higher on narcissism, conscientiousness, and agreeableness; (2) average users displayed lower psychopathy; and (3) lesser users reported lower narcissism and higher psychopathy. These findings underscore the nuanced relationship between makeup usage and personality, particularly highlighting the influence of narcissism. These findings contribute to the interplay between personality traits and makeup usage, considering interindividual differences and intraindividual variation in understanding cosmetic behaviors among women.

Sex and Sexual Orientation Differences in Dark Triad Traits, Sexual Excitation/Inhibition, and Sociosexuality.

The present study sought to investigate sex and sexual orientation differences in several traits related to sexuality and sexual behavior. Examining sexual orientation differences alongside basic sex differences to help identify correlates of sexual orientation diversity, and whether individuals with varying degrees of same-sex attraction show concurrent sex-atypical shifts in other domains. Males tend to score higher than females in the Dark Triad (DT) traits of sub-clinical narcissism, psychopathy, and Machiavellianism. Similarly, females tend to be more cautious than males in their attitudes and desires toward casual sex activity (i.e., sociosexuality). These sex differences may be related to the propensity for individuals to become easily sexually excited, which is higher in males, or to instead inhibit sexual arousal, which is higher in females. In a large undergraduate sample (N = 2047), we replicated expected sex differences in DT traits, sociosexuality, and sexual excitation/inhibition. We found that non-heterosexual females were "male-shifted" in some of these traits, but these shifts tended to be strongest among mostly heterosexual and bisexual individuals. Furthermore, we found that within-sex variation in sociosexuality, sexual excitation, and sexual inhibition was not related to sexual orientation in a linear fashion. Instead, sociosexuality and sexual excitation were related to sexual orientation in a curvilinear (inverted-U) fashion, especially among females. The fact that traits correlated with bisexuality and homosexuality were somewhat distinct is consistent with the idea that different developmental pathways may lead to these discrete sexual attraction patterns.

Towards agreement amongst parents, teachers and children on perceived psychopathology in children in a Kenyan socio-cultural context: a cross-sectional study.

BACKGROUND: Our objective was to determine levels of agreement between parents, teachers and children on mental symptoms in the children. Teachers, children and parents constitute the TRIAD in the perception of psychopathology in children. Analyzing the perceptions of psychopathology from the perspectives of parents, teachers, and children is essential for a comprehensive understanding of a child's mental health. METHODS: We identified 195 participants across ten randomly sampled primary schools in South East Kenya. Potential participants were randomly selected and a sampling interval calculated to determine the study participants. The children (Class 5-8; aged 11-14) completed the Youth Self-Report (YSR) scale, the parents the Child Behavior Check List (CBCL) on their children and the teachers completed the Teachers Rating Form (TRF) on the children. Only parents and teachers who gave consent as well as children who gave assent were included in the study. Analysis was conducted using Stata 14.1 and Pearson correlation coefficients used to calculate the correlations between CBCL, YSR and TRF. RESULTS: The children agreed least with the parents and more with the teachers. There was a greater agreement between the children and their teachers in 5 (2 internalizing disorders and 3 externalizing disorders) out of the 8 conditions. Children and parents agreed only on somatic disorders and conduct disorders. YSR mean scores were significantly lower than those for CBCL for all problem scales. Mean scores of TRF and YSR were comparable in the majority of the problems measured. CONCLUSION: We suggest broad-based psychoeducation to include children, parents/guardians and teachers to enhance shared awareness of psychopathology and uptake of treatment and for the consideration of an integrated mental health system.

Acetylcholine promotes chronic stress-induced lung adenocarcinoma progression via α5-nAChR/FHIT pathway.

Chronic stress significantly elevates the expression levels of various neurotransmitters in the tumour microenvironment, thereby promoting the cell growth and metastasis of lung adenocarcinoma (LUAD). However, the role of chronic stress in the progression of LUAD remains unclear. In this study, we found that chronic restraint stress increases the levels of the neurotransmitter acetylcholine (ACh), and the α5-nicotinic acetylcholine receptor (α5-nAChR) and decreased fragile histidine triad (FHIT) expression in vivo. Crucially, the increased ACh levels promoted LUAD cell migration and invasion via modulation of the α5-nAChR/DNA methyltransferase 1 (DNMT1)/FHIT axis. In a chronic unpredictable stress (CUMS) mouse model, chronic stress promotes tumour development, accompanied by changes in α5-nAChR, DNMT1, FHIT, and vimentin. Together, these findings reveal a novel chronic stress-mediated LUAD signalling pathway: chronic stress enforces lung adenocarcinoma cell invasion and migration via the ACh/α5-nAChR/FHIT axis, which could be a potential therapeutic target for chronic stress-related LUAD.

Different views on collaboration between older persons, informal caregivers and care professionals.

BACKGROUND: Informal care features high on the policy agenda of many countries to deal with workforce shortages. As a consequence, care provision increasingly takes place in the care triad of care recipients, informal caregivers and care professionals. How collaboration between care partners takes shape depends on how the different partners perceive this collaboration. This paper aims to investigate the relative importance of the different aspects of collaboration from the perspectives of care recipients, informal caregivers and care professionals in the context of the care for older persons in The Netherlands. METHODS: Using Q-methodology, 32 participants ranked 28 statements that reflect different aspects of collaboration in the care triad and explained their ranking during a follow-up interview. Participants comprised 9 older persons, 10 informal caregivers and 13 care professionals. Data were analysed using by-person factor analysis to identify common patterns in the rankings of the statements. Emerging patterns were interpreted and described as views on collaboration using aggregated rankings and qualitative data from the interviews. RESULTS: Five distinct views on collaboration were found: (1) Emphasizing warm collaboration, (2) trusting care professional's expertise, (3) open and compassionate care professionals, (4) responsive decision-making by autonomous care professionals and (5) prioritizing care recipient's and informal caregiver's interests. Care recipients and/or informal caregivers were associated with views 1, 3 and, 5, whereas care professionals were associated with all five views. CONCLUSIONS: Our study highlights the importance of recognizing the potential diversity of views between and within different partner groups in care triads. Governmental and organizational policy makers, as well as healthcare professionals who aim to increase or support the involvement of informal caregivers, should take this heterogeneity into consideration. PATIENT OR PUBLIC CONTRIBUTION: An advisory board of older persons (care recipients and informal caregivers) was involved in the recruitment of the participants, the formulation of the statements and the reflection on the findings of the study and potential implications.

The links of subjective and psychological well-being with the Dark Triad traits: A meta-analysis.

OBJECTIVE: The aim of this study is to investigate the specific links that the Dark Triad traits have with subjective and psychological well-being through a meta-analysis of the existing literature. BACKGROUND: Over the past few years, associations between the Dark Triad traits and well-being have been a stimulating but understudied topic in personality research. METHOD: Cross-sectional, correlational studies examining these relationships were searched in the PsycINFO, PubMed, and Web of Science databases. Meta-analyses were performed at the dimension- and facet-level to account for the multidimensional structure of the Dark Triad traits. RESULTS: A total of 55 studies were included (n = 26,252). In general, grandiose narcissism and boldness/dominance related to higher well-being, while vulnerable narcissism, antagonism, disinhibition, and Machiavellianism related to lower levels of well-being. Age and gender moderated few of these associations. CONCLUSIONS: We recommend including multidimensional measures of the Dark Triad traits as an essential step to move the field forward.

The Connection Between Dark Traits and Emotional Intelligence: A Multistudy Person-Centered Approach.

OBJECTIVE: Several studies have analyzed the relationship between Emotional Intelligence (EI) and dark personality, but the results are inconclusive. One study tested correlations between traits that may underlie a person-centered profile of "dark EI." Our study aimed to replicate and extend that research, identifying profiles in Spaniards and examining the differences between the profiles based on different variables of interest. METHOD: Two studies were designed, the first one (N = 1241) focused on trait EI and the Dark Triad, and the second one expanding the previous (N = 392) focusing on ability EI and the Dark Tetrad. RESULTS: Three profiles were obtained in both studies: nondark and non-EI profile, dark profile, and average narcissistic and high EI profile. The latter showed the highest self-esteem, strengths, well-being, and civic engagement, and the lowest psychological difficulties and personal distress. CONCLUSIONS: Our results reinforced the findings of the study we replicated, not supporting the presence of dark EI, but also not supporting the presence of high EI with very low levels of dark traits. These results have implications when designing preventive actions to improve emotional education.

Will the Dark Triad Engender Psychopathological Symptoms or Vice Versa? A Three-Wave Random Intercept Cross-Lagged Panel Analysis.

INTRODUCTION: The Dark Triad (DT), including narcissism, Machiavellianism, and psychopathy, represents the dark side of human nature and has been related to psychopathological symptoms (e.g., depression, anxiety, and stress). However, little is known about how the two constructs are related longitudinally. To fill this gap and to clarify the directionality between them, we conducted a longitudinal study. METHODS: We measured DT traits and psychopathological symptoms in a large sample of university students (NT1 = 1815) annually for 3 years. We implemented random intercept cross-lagged panel models in analysis. RESULTS: Narcissism and psychopathological symptoms showed a reciprocal relationship at the within-person level: greater narcissism preceded a decline in psychopathological symptoms, while more severe symptoms preceded a decrease in narcissism. Within the same individual, increases in the DT, particularly psychopathy and Machiavellianism, were linked to concurrent escalations in the symptoms. Additionally, all DT traits were positively correlated with psychopathological symptoms as stable differences between individuals. CONCLUSIONS: This study constitutes an important step in clarifying the directionality between the DT and psychopathological symptoms, and advances our understanding of the interplay between these two constructs at both the between-person and within-person levels.

Clinical Presentation of Atopic Dermatitis.

Atopic dermatitis, commonly known as eczema, is a chronic inflammatory dermatosis that can affect individuals from infancy to adulthood. Also referred to as "the itch that rashes," atopic dermatitis is classically associated with significant pruritus that is accompanied by characteristic cutaneous and other clinical findings. The diagnosis of atopic dermatitis can be challenging due to the wide range of clinical presentations based on patient factors such as age, skin type, ethnicity, and other comorbid conditions. This chapter reviews the classical findings as well as the less common manifestations of atopic dermatitis.

Attachment anxiety and the dark triad increase stalking after breakups of romantic relationships through psychological maltreatment of romantic partners and reactions to breakups.

This study examined whether two personality traits, attachment anxiety, and the Dark Triad, longitudinally promote stalking behaviors after romantic breakups through psychological maltreatment of partners during relationships and maladjusted reactions to breakups. We conducted a prospective longitudinal study across four waves of assessment for 1 year of individuals in romantic relationships in Japan. They completed measures of attachment anxiety, the Dark Triad, need for control, and psychological intimate partner violence (IPV) perpetration at Wave 1, and measures of maladjusted reactions to breakups (i.e., anger and rumination) and stalking behaviors at a wave after breakups. The final sample consisted of 356 participants who were involved in romantic relationships at Wave 1 and left by their partners during the survey period. Correlational analysis showed that the Dark Triad at Wave 1 was significantly positively associated with future stalking behaviors, but attachment anxiety was not. Structural equation modeling showed that attachment anxiety and the Dark Triad increased future stalking behaviors after breakups through psychological IPV perpetration during relationships. Additionally, attachment anxiety increased future stalking behaviors through higher levels of postbreakup anger and rumination. Conversely, we did not find any indirect effects of the Dark Triad on stalking behaviors through these reactions toward breakups. Overall, these results suggest that it is necessary to consider personality traits that could damage intimate relationships and to focus on the quality of romantic relationships to prevent stalking after romantic breakups. These results also indicate that emotion regulation may be useful in preventing stalking caused by attachment anxiety.

The foundation of excitation-contraction coupling in skeletal muscle: communication between the transverse tubules and sarcoplasmic reticulum.

The expression excitation-contraction (EC) coupling in skeletal muscle was coined in 1952 (Sandow A. Yale J Biol Med 25: 176-201, 1952). The term evolved narrowly to include only the processes at the triad that intervene between depolarization of the transverse tubular (T-tubular) membrane and Ca2+ release from the sarcoplasmic reticulum (SR). From 1970 to 1988, the foundation of EC coupling was elucidated. The channel through which Ca2+ was released during activation was located in the SR by its specific binding to the plant insecticide ryanodine. This channel was called the ryanodine receptor (RyR). The RyR contained four subunits that together constituted the "SR foot" structure that traversed the gap between the SR and the T-tubular membrane. Ca2+ channels, also called dihydropyridine receptors (DHPRs), were located in the T-tubular membrane at the triadic junction and shown to be essential for EC coupling. There was a precise relationship between the two channels. Four DHPRs, organized as tetrads, were superimposed on alternate RyRs. This structure was consistent with the proposal that EC coupling was mediated via a movement of intramembrane charge in the T-tubular system. The speculation was that the DHPR acted as a voltage sensor transferring information to the RyRs of the SR by protein-protein interaction causing the release of Ca2+ from the SR. A great deal of progress was made by 1988 toward understanding EC coupling. However, the ultimate question of how voltage sensing is coupled to the opening of the SR Ca2+ release channel remains unresolved.NEW & NOTEWORTHY The least understood part of the series of events in excitation-contraction coupling in skeletal muscle was how information was transmitted from the transverse tubules to the sarcoplasmic (SR) and how Ca2+ was released from the SR. Through an explosion of technical approaches including physiological, biochemical, structural, pharmacological, and molecular genetics, much was discovered between 1970 and 1988. By the end of 1988, the foundation of EC coupling in skeletal muscle was established.