E. coli monothiol glutaredoxin GrxD replenishes Fe-S clusters to the essential ErpA A-type carrier under low iron stress.

Iron-sulfur (Fe-S) clusters are required for essential biological pathways, including respiration and isoprenoid biosynthesis. Complex Fe-S cluster biogenesis systems have evolved to maintain an adequate supply of this critical protein cofactor. In Escherichia coli, two Fe-S biosynthetic systems, the "housekeeping" Isc and "stress responsive" Suf pathways, interface with a network of cluster trafficking proteins, such as ErpA, IscA, SufA, and NfuA. GrxD, a Fe-S cluster-binding monothiol glutaredoxin, also participates in Fe-S protein biogenesis in both prokaryotes and eukaryotes. Previous studies in E. coli showed that the ΔgrxD mutation causes sensitivity to iron depletion, spotlighting a critical role for GrxD under conditions that disrupt Fe-S homeostasis. Here, we utilized a global chemoproteomic mass spectrometry (MS) approach to analyse the contribution of GrxD to the Fe-S proteome. Our results demonstrate that 1) GrxD is required for biogenesis of a specific subset of Fe-S proteins under iron-depleted conditions, 2) GrxD is required for cluster delivery to ErpA under iron limitation, 3) GrxD is functionally distinct from other Fe-S trafficking proteins and, 4) GrxD Fe-S cluster binding is responsive to iron limitation. All these results lead to the proposal that GrxD is required to maintain Fe-S cluster delivery to the essential trafficking protein ErpA during iron limitation conditions.

Facial amphiphilic naphthoic acid-derived antimicrobial polymers against multi-drug resistant gram-negative bacteria and biofilms.

Inspired by the facial amphiphilic nature and antimicrobial efficacy of many antimicrobial peptides, this work reported facial amphiphilic bicyclic naphthoic acid derivatives with different ratios of charges to rings that were installed onto side chains of poly(glycidyl methacrylate). Six quaternary ammonium-charged (QAC) polymers were prepared to investigate the structure-activity relationship. These QAC polymers displayed potent antibacterial activity against various multi-drug resistant (MDR) gram-negative pathogens such as Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Acinetobacter baumannii. Polymers demonstrated low hemolysis and high antimicrobial selectivity. Additionally, they were able to eradicate established biofilms and kill metabolically inactive dormant cells. The membrane permeabilization and depolarization results indicated a mechanism of action through membrane disruption. Two lead polymers showed no resistance from MDR-P. aeruginosa and MDR-K. pneumoniae. These facial amphiphiles are potentially a new class of potent antimicrobial agents to tackle the antimicrobial resistance for both planktonic and biofilm-related infections.

Guselkumab, a Novel Monoclonal Antibody Inhibitor of the p19 Subunit of IL-23, for Psoriatic Arthritis and Plaque Psoriasis: A Review of Its Mechanism, Use, and Clinical Effectiveness.

Psoriatic arthritis and plaque psoriasis are autoimmune conditions affecting multiple organs, including the skin. The pathophysiology and etiology of these conditions are not fully understood; however, numerous factors are believed to play a critical role, including genetics and environmental risk factors. Furthermore, research suggests the IL-23/IL-17 pathway partially mediates these diseases. Once the IL-23 receptor is bound and activated, two subunits, p19, and p40, act through different signaling pathways. Ultimately, inflammation is produced through the effector molecule, IL-17, other cytokines, and tumor necrosis factor (TNF). Traditionally, these chronic conditions have been treated with TNF-α inhibitors and methotrexate, a dihydrofolate reductase inhibitor. Although successful in inhibiting the immune system, these drugs can have many adverse effects due to their broad targets. In recent years, more targeted therapy has become popular. Guselkumab is a monoclonal antibody that inhibits the p19 subunit of IL-23. It has been FDA-approved to treat both plaque psoriasis and psoriatic arthritis. Clinical trials showing guselkumab's efficacy have been promising, even showing improvement in symptoms of plaque psoriasis patients resistant to adalimumab, a TNF-α inhibitor. Guselkumab has also been shown to be well tolerated with a similar safety profile as other biologics inhibiting the immune system. In addition to its efficacy in treating plaque psoriasis and psoriatic arthritis, the mechanism of action offers a targeted approach that may minimize the broad immunosuppressive effects often associated with traditional therapies, providing a potential advantage in the long-term management of these autoimmune conditions.

The global assessment of OCD.

Obsessive Compulsive Disorder (OCD) is a common mental disorder that often causes great sufferance, with substantial impairment in social functioning and quality of life and affects family and significant relationships. Notwithstanding its severity, OCD is often not adequately diagnosed, or it is diagnosed with delay, leading often to a long latency between onset of the OCD symptoms and the start of adequate treatments. Several factors contribute to the complexity of OCD's clinical picture: early age of onset, chronic course, heterogeneity of symptoms, high rate of comorbidity with other psychiatric disorders, slow or partial response to therapy. Therefore, it is of primary importance for clinicians involved in diagnosing OCD, to assess all aspects of the disorder. This narrative review focuses on the global assessment of OCD, highlighting crucial areas to explore, pointing out the clinical features which are relevant for the treatment of the disorder, and giving an overview of the psychometric tools that can be useful during the screening procedure.

Evidence that loneliness can be reduced by a whole-of-community intervention to increase neighbourhood identification.

RATIONALE: Social identification with the people in one's neighbourhood has a wide variety of benefits for individual and community health and wellbeing. In particular, previous research shows that residents' social identification with their neighbourhood is protective of mental health. However, researchers are only just beginning to design and evaluate interventions that directly target social identification on health grounds. OBJECTIVE: This longitudinal study evaluated a whole-of-community intervention at scale (Neighbour Day, 2019), in which Australian residents were encouraged to build social connections in their local community. Neighbour Day is a campaign that seeks to raise public awareness of the importance of connecting with neighbours and had a reach of approximately 300,000 people in 2019. METHODS: Participants were 437 hosts of neighbourhood events held across 276 diverse suburbs across Australia. Participants were surveyed at three-time points; before and after Neighbour Day, as well as at six-month follow up. RESULTS: Hosting a Neighbour Day event led to a significant increase in neighbourhood social identification, which was sustained six months later. This increase in social identification predicted increased social cohesion, reduced loneliness and improved wellbeing. CONCLUSIONS: This study provides evidence that neighbourhood identification is an effective target mechanism to curb loneliness and social fragmentation in the community. Implications are discussed with a focus on how social identity-building interventions can be effectively implemented in community settings to benefit public health.

Erenumab for headaches in idiopathic intracranial hypertension: A prospective open-label evaluation.

OBJECTIVE: To determine the effectiveness of erenumab in treating headaches in idiopathic intracranial hypertension (IIH) in whom papilledema had resolved. BACKGROUND: Disability in IIH is predominantly driven by debilitating headaches with no evidence for the use of preventative therapies. Headache therapy in IIH is an urgent unmet need. METHODS: A prospective, open-label study in the United Kingdom was conducted. Adult females with confirmed diagnosis of IIH now in ocular remission (papilledema resolved) with chronic headaches (≥15 days a month) and failure of ≥3 preventative medications received erenumab 4-weekly (assessments were 3-monthly). The primary end point was change in monthly moderate/severe headache days (MmsHD) from baseline (30-day pretreatment period) compared to 12 months. RESULTS: Fifty-five patients, mean (SD) age 35.3 (9) years and mean duration of headaches 10.4 (8.4) years with 3.7 (0.9) preventative treatment failures, were enrolled. Mean baseline MmsHD was 16.1 (4.7) and total monthly headache days (MHD) was (29) 2.3. MmsHD reduced substantially at 12 months by mean (SD) [95% CI] 10.8 (4.0) [9.5, 11.9], p < 0.001 and MHD reduced by 13.0 (9.5) [10.2, 15.7], p < 0.001. Crystal clear days (days without any head pain) increased by 13.1 (9.5) [9.6, 15.3], p < 0.001, headache severity (scale 0-10) fell by 1.3 (1.7) [0.9, 1.9], p < 0.001, and monthly analgesic days reduced by 4.3 (9.2) [1.6, 6.9], p = 0.002. All these measures had improved significantly by 3 months, with a consistent significant response to 12 months. Headache impact test-6 score and quality of life Short Form-36 Health Survey significantly improved at 12 months. Sensitivity analysis revealed similar results for patients with and without a prior migraine diagnosis (28/55 (52%) patients) or those with or without medication overuse (27/55 (48%) patients). CONCLUSIONS: This study provides evidence for the effectiveness of erenumab to treat headaches in IIH patients with resolution of papilledema. It provides mechanistic insights suggesting that calcitonin gene-related peptide is likely a modulator driving headache and a useful therapeutic target.

Calcitonin gene related peptide monoclonal antibody treats headache in patients with active idiopathic intracranial hypertension.

BACKGROUND: Headache is the dominant factor for quality of life related disability in idiopathic intracranial hypertension (IIH) and typically has migraine-like characteristics. There are currently no evidence-based therapeutics for headache in IIH, and consequently this is an important unmet clinical need. CASE SERIES: We report a series of seven patients in whom headaches were the presenting feature of IIH and the headaches had migraine-like characteristics, as is typical in many IIH patients. Papilloedema settled (ocular remission) but headaches continued. These headaches responded markedly to erenumab, a monoclonal antibody targeted against the calcitonin gene related peptide (CGRP) receptor. Of note, there was a recurrence of raised ICP, as evidenced by a return of the papilloedema, however the headaches did not recur whilst treated with erenumab. CONCLUSIONS: Those with prior IIH who have their headaches successfully treated with CGRP therapy, should remain under close ocular surveillance (particularly when weight gain is evident) as papilloedema can re-occur in the absence of headache. These cases may suggest that CGRP could be a mechanistic driver for headache in patients with active IIH.

Fe-S cluster biogenesis by the bacterial Suf pathway.

Biogenesis of iron-sulfur (FeS) clusters in an essential process in living organisms due to the critical role of FeS cluster proteins in myriad cell functions. During biogenesis of FeS clusters, multi-protein complexes are used to drive the mobilization and protection of reactive sulfur and iron intermediates, regulate assembly of various FeS clusters on an ATPase-dependent, multi-protein scaffold, and target nascent clusters to their downstream protein targets. The evolutionarily ancient sulfur formation (Suf) pathway for FeS cluster assembly is found in bacteria and archaea. In Escherichia coli, the Suf pathway functions as an emergency pathway under conditions of iron limitation or oxidative stress. In other pathogenic bacteria, such as Mycobacterium tuberculosis and Enterococcus faecalis, the Suf pathway is the sole source for FeS clusters and therefore is a potential target for the development of novel antibacterial compounds. Here we summarize the considerable progress that has been made in characterizing the first step of mobilization and protection of reactive sulfur carried out by the SufS-SufE or SufS-SufU complex, FeS cluster assembly on SufBC2D scaffold complexes, and the downstream trafficking of nascent FeS clusters to A-type carrier (ATC) proteins. Cell Biology of Metals III edited by Roland Lill and Mick Petris.

No compelling evidence that more physically attractive young adult women have higher estradiol or progesterone.

Putative associations between sex hormones and attractive physical characteristics in women are central to many theories of human physical attractiveness and mate choice. Although such theories have become very influential, evidence that physically attractive and unattractive women have different hormonal profiles is equivocal. Consequently, we investigated hypothesized relationships between salivary estradiol and progesterone and two aspects of women's physical attractiveness that are commonly assumed to be correlated with levels of these hormones: facial attractiveness (N = 249) and waist-to-hip ratio (N = 247). Our analyses revealed no compelling evidence that women with more attractive faces or lower (i.e., more attractive) waist-to-hip ratios had higher levels of estradiol or progesterone. One analysis did suggest that women with more attractive waist-to-hip ratios had significantly higher progesterone, but the relationship was weak and the relationship not significant in other analyses. These results do not support the influential hypothesis that between-women differences in physical attractiveness are related to estradiol and/or progesterone.

No Compelling Evidence that Preferences for Facial Masculinity Track Changes in Women's Hormonal Status.

Although widely cited as strong evidence that sexual selection has shaped human facial-attractiveness judgments, findings suggesting that women's preferences for masculine characteristics in men's faces are related to women's hormonal status are equivocal and controversial. Consequently, we conducted the largest-ever longitudinal study of the hormonal correlates of women's preferences for facial masculinity ( N = 584). Analyses showed no compelling evidence that preferences for facial masculinity were related to changes in women's salivary steroid hormone levels. Furthermore, both within-subjects and between-subjects comparisons showed no evidence that oral contraceptive use decreased masculinity preferences. However, women generally preferred masculinized over feminized versions of men's faces, particularly when assessing men's attractiveness for short-term, rather than long-term, relationships. Our results do not support the hypothesized link between women's preferences for facial masculinity and their hormonal status.

General sexual desire, but not desire for uncommitted sexual relationships, tracks changes in women's hormonal status.

Several recent longitudinal studies have investigated the hormonal correlates of both young adult women's general sexual desire and, more specifically, their desire for uncommitted sexual relationships. Findings across these studies have been mixed, potentially because each study tested only small samples of women (Ns = 43, 33, and 14). Here we report results from a much larger (N = 375) longitudinal study of hormonal correlates of young adult women's general sexual desire and their desire for uncommitted sexual relationships. Our analyses suggest that within-woman changes in general sexual desire are negatively related to progesterone, but are not related to testosterone or cortisol. We observed some positive relationships for estradiol, but these were generally only significant for solitary sexual desire. By contrast with our results for general sexual desire, analyses showed no evidence that changes in women's desire for uncommitted sexual relationships are related to their hormonal status. Together, these results suggest that changes in hormonal status contribute to changes in women's general sexual desire, but do not influence women's desire for uncommitted sexual relationships.

Interrelationships Among Men's Threat Potential, Facial Dominance, and Vocal Dominance.

The benefits of minimizing the costs of engaging in violent conflict are thought to have shaped adaptations for the rapid assessment of others' capacity to inflict physical harm. Although studies have suggested that men's faces and voices both contain information about their threat potential, one recent study suggested that men's faces are a more valid cue of their threat potential than their voices are. Consequently, the current study investigated the interrelationships among a composite measure of men's actual threat potential (derived from the measures of their upper-body strength, height, and weight) and composite measures of these men's perceived facial and vocal threat potential (derived from dominance, strength, and weight ratings of their faces and voices, respectively). Although men's perceived facial and vocal threat potential were positively correlated, men's actual threat potential was related to their perceived facial, but not vocal, threat potential. These results present new evidence that men's faces may be a more valid cue of these aspects of threat potential than their voices are.

Does the Interaction Between Cortisol and Testosterone Predict Men's Facial Attractiveness?

Although some researchers have suggested that the interaction between cortisol and testosterone predicts ratings of men's facial attractiveness, evidence for this pattern of results is equivocal. Consequently, the current study tested for a correlation between men's facial attractiveness and the interaction between their cortisol and testosterone levels. We also tested for corresponding relationships between the interaction between cortisol and testosterone and ratings of men's facial health and dominance (perceived traits that are correlated with facial attractiveness in men). We found no evidence that ratings of either facial attractiveness or health were correlated with the interaction between cortisol and testosterone. Some analyses suggested that the interaction between cortisol and testosterone levels may predict ratings of men's facial dominance, however, with testosterone being more closely related to facial dominance ratings among men with higher cortisol. Our results suggest that the relationship between men's facial attractiveness and the interaction between cortisol and testosterone is not robust.

Are physiological and behavioral immune responses negatively correlated? Evidence from hormone-linked differences in men's face preferences.

Behaviors that minimize exposure to sources of pathogens can carry opportunity costs. Consequently, how individuals resolve the tradeoff between the benefits and costs of behavioral immune responses should be sensitive to the extent to which they are vulnerable to infectious diseases. However, although it is a strong prediction of this functional flexibility principle, there is little compelling evidence that individuals with stronger physiological immune responses show weaker behavioral immune responses. Here we show that men with the combination of high testosterone and low cortisol levels, a hormonal profile recently found to be associated with particularly strong physiological immune responses, show weaker preferences for color cues associated with carotenoid pigmentation. Since carotenoid cues are thought to index vulnerability to infectious illnesses, our results are consistent with the functional flexibility principle's prediction that individuals with stronger physiological immune responses show weaker behavioral immune responses.

Are Men's Perceptions of Sexually Dimorphic Vocal Characteristics Related to Their Testosterone Levels?

Feminine physical characteristics in women are positively correlated with markers of their mate quality. Previous research on men's judgments of women's facial attractiveness suggests that men show stronger preferences for feminine characteristics in women's faces when their own testosterone levels are relatively high. Such results could reflect stronger preferences for high quality mates when mating motivation is strong and/or following success in male-male competition. Given these findings, the current study investigated whether a similar effect of testosterone occurs for men's preferences for feminine characteristics in women's voices. Men's preferences for feminized versus masculinized versions of women's and men's voices were assessed in five weekly test sessions and saliva samples were collected in each test session. Analyses showed no relationship between men's voice preferences and their testosterone levels. Men's tendency to perceive masculinized men's and women's voices as more dominant was also unrelated to their testosterone levels. Together, the results of the current study suggest that testosterone-linked changes in responses to sexually dimorphic characteristics previously reported for men's perceptions of faces do not occur for men's perceptions of voices.

Women's facial attractiveness is related to their body mass index but not their salivary cortisol.

OBJECTIVES: Although many theories of human facial attractiveness propose positive correlations between facial attractiveness and measures of actual health, evidence for such correlations is somewhat mixed. Here we sought to replicate a recent study reporting that women's facial attractiveness is independently related to both their adiposity and cortisol. METHODS: Ninety-six women provided saliva samples, which were analyzed for cortisol level, and their height and weight, which were used to calculate their body mass index (BMI). A digital face image of each woman was also taken under standardized photographic conditions and rated for attractiveness. RESULTS: There was a significant negative correlation between women's facial attractiveness and BMI. By contrast, salivary cortisol and facial attractiveness were not significantly correlated. CONCLUSIONS: Our results suggest that the types of health information reflected in women's faces include qualities that are indexed by BMI but do not necessarily include qualities that are indexed by cortisol. Am. J. Hum. Biol. 28:352-355, 2016. © 2015 Wiley Periodicals, Inc.

A longitudinal analysis of women's salivary testosterone and intrasexual competitiveness.

Research on within-subject changes in women's intrasexual competitiveness has generally focused on possible relationships between women's intrasexual competitiveness and estimates of their fertility. While this approach is useful for testing hypotheses about the adaptive function of changes in women's intrasexual competitiveness, it offers little insight into the proximate mechanisms through which such changes might occur. To investigate this issue, we carried out a longitudinal study of the hormonal correlates of changes in intrasexual competitiveness in a large sample of heterosexual women (N=136). Each woman provided saliva samples and completed an intrasexual competitiveness questionnaire in five weekly test sessions. Multilevel modeling of these data revealed a significant, positive within-subject effect of testosterone on intrasexual competitiveness, indicating that women reported greater intrasexual competitiveness when testosterone was high. By contrast, there were no significant effects of estradiol, progesterone, estradiol-to-progesterone ratio, or cortisol and no significant effects of any hormones on reported relationship jealousy. This is the first study to demonstrate correlated changes in measured testosterone levels and women's reported intrasexual competitiveness, implicating testosterone in the regulation of women's intrasexual competitiveness.

Sex-Specificity in the Reward Value of Facial Attractiveness.

Studies of the sex-specificity of sexual arousal in adults (i.e., the tendency to respond more strongly to preferred-sex individuals than non-preferred sex individuals) have suggested that heterosexual men, homosexual men, and homosexual women show stronger sex-specific responses than do heterosexual women. Evidence for a similar pattern of results in studies investigating the reward value of faces is equivocal. Consequently, we investigated the effects of (1) sexual orientation (homosexual vs. heterosexual), (2) sex (male vs. female), (3) image sex (preferred-sex vs. non-preferred-sex), and (4) the physical attractiveness of the individual shown in the image on the reward value of faces. Participants were 130 heterosexual men, 130 homosexual men, 130 heterosexual women, and 130 homosexual women. The reward value of faces was assessed using a standard key-press task. Multilevel modeling of responses indicated that images of preferred-sex individuals were more rewarding than images of non-preferred-sex individuals and that this preferred-sex bias was particularly pronounced when more physically attractive faces were presented. These effects were not qualified by interactions involving either the sexual orientation or the sex of our participants, however, suggesting that the preferred-sex bias in the reward value of faces is similar in heterosexual men, homosexual men, heterosexual women, and homosexual women.

Women's Preference for Attractive Makeup Tracks Changes in Their Salivary Testosterone.

Previous research suggests that women's motivation to appear attractive is increased around the time of ovulation. However, the specific hormonal correlates of within-woman changes in motivation to appear attractive have not been investigated. To address this issue, we used a longitudinal design and a data-driven visual preference task. We found that women's preference for attractive makeup increases when their salivary testosterone levels are high. The relationship between testosterone level and preference for attractive makeup was independent of estradiol level, progesterone level, and estradiol-to-progesterone ratio. These results suggest that testosterone may contribute to changes in women's motivation to wear attractive makeup and, potentially, their motivation to appear attractive in general. Our results are also consistent with recent models of the role of testosterone in social behavior, according to which testosterone increases the probability of behaviors that could function to support the acquisition of mates and competition for resources.

Testing the Utility of a Data-Driven Approach for Assessing BMI from Face Images.

Several lines of evidence suggest that facial cues of adiposity may be important for human social interaction. However, tests for quantifiable cues of body mass index (BMI) in the face have examined only a small number of facial proportions and these proportions were found to have relatively low predictive power. Here we employed a data-driven approach in which statistical models were built using principal components (PCs) derived from objectively defined shape and color characteristics in face images. The predictive power of these models was then compared with models based on previously studied facial proportions (perimeter-to-area ratio, width-to-height ratio, and cheek-to-jaw width). Models based on 2D shape-only PCs, color-only PCs, and 2D shape and color PCs combined each performed significantly and substantially better than models based on one or more of the previously studied facial proportions. A non-linear PC model considering both 2D shape and color PCs was the best predictor of BMI. These results highlight the utility of a "bottom-up", data-driven approach for assessing BMI from face images.