Revealing the Specificity of a Range of Antimicrobial Peptides in Lipid Nanodiscs by Native Mass Spectrometry.

Antimicrobial peptides (AMPs) interact directly with lipid membranes of pathogens and may have the potential to combat antibiotic resistance. Although many AMPs are thought to form toxic oligomeric pores, their interactions within lipid membranes are not well understood. Here, we used native mass spectrometry to measure the incorporation of a range of different AMPs in lipoprotein nanodiscs. We found that the truncation of human LL37 increases the lipid specificity but decreases the specificity of complex formation. We also saw that the reduction of disulfide bonds can have a dramatic effect on the ability of AMPs to interact with lipid bilayers. Finally, by examining a wider range of peptides we discovered that AMPs tend to interact specifically with anionic lipids but form nonspecific complexes with wide oligomeric state distributions. Overall, these data reveal that each AMP has unique behaviors but some common trends apply to many AMPs.

Active molecular iodine photochemistry in the Arctic.

During springtime, the Arctic atmospheric boundary layer undergoes frequent rapid depletions in ozone and gaseous elemental mercury due to reactions with halogen atoms, influencing atmospheric composition and pollutant fate. Although bromine chemistry has been shown to initiate ozone depletion events, and it has long been hypothesized that iodine chemistry may contribute, no previous measurements of molecular iodine (I2) have been reported in the Arctic. Iodine chemistry also contributes to atmospheric new particle formation and therefore cloud properties and radiative forcing. Here we present Arctic atmospheric I2 and snowpack iodide (I-) measurements, which were conducted near Utqiagvik, AK, in February 2014. Using chemical ionization mass spectrometry, I2 was observed in the atmosphere at mole ratios of 0.3-1.0 ppt, and in the snowpack interstitial air at mole ratios up to 22 ppt under natural sunlit conditions and up to 35 ppt when the snowpack surface was artificially irradiated, suggesting a photochemical production mechanism. Further, snow meltwater I- measurements showed enrichments of up to ∼1,900 times above the seawater ratio of I-/Na+, consistent with iodine activation and recycling. Modeling shows that observed I2 levels are able to significantly increase ozone depletion rates, while also producing iodine monoxide (IO) at levels recently observed in the Arctic. These results emphasize the significance of iodine chemistry and the role of snowpack photochemistry in Arctic atmospheric composition, and imply that I2 is likely a dominant source of iodine atoms in the Arctic.

Native Mass Spectrometry of Antimicrobial Peptides in Lipid Nanodiscs Elucidates Complex Assembly.

Antimicrobial peptides (AMPs) are generally cationic and amphipathic peptides that show potential applications to combat the growing threat of antibiotic resistant infections. AMPs are known to interact with bacterial membranes, but their mechanisms of toxicity and selectivity are poorly understood, in part because it is challenging to characterize AMP oligomeric complexes within lipid bilayers. Here, we used native mass spectrometry to measure the stoichiometry of AMPs inserted into lipoprotein nanodiscs with different lipid components. Titrations of increasing peptide concentration and collisional activation experiments reveal that AMPs can exhibit a range of behaviors from nonspecific incorporation into the nanodisc to formation of specific complexes. This new approach to characterizing formation of AMP complexes within lipid membranes will provide unique insights into AMP mechanisms.

Zn(II) stimulation of Fe(II)-activated repression in the iron-dependent repressor from Mycobacterium tuberculosis.

Thermodynamic measurements of Fe(II) binding and activation of repressor function in the iron-dependent repressor from Mycobacterium tuberculosis (IdeR) are reported. IdeR, a member of the diphtheria toxin repressor family of proteins, regulates iron homeostasis and contributes to the virulence response in M. tuberculosis. Although iron is the physiological ligand, this is the first detailed analysis of iron binding and activation in this protein. The results showed that IdeR binds 2 equiv of Fe(II) with dissociation constants that differ by a factor of 25. The high- and low-affinity iron binding sites were assigned to physical binding sites I and II, respectively, using metal binding site mutants. IdeR was also found to contain a high-affinity Zn(II) binding site that was assigned to physical metal binding site II through the use of binding site mutants and metal competition assays. Fe(II) binding was modestly weaker in the presence of Zn(II), but the coupled metal binding-DNA binding affinity was significantly stronger, requiring 30-fold less Fe(II) to activate DNA binding compared to Fe(II) alone. Together, these results suggest that IdeR is a mixed-metal repressor, where Zn(II) acts as a structural metal and Fe(II) acts to trigger the physiologically relevant promoter binding. This new model for IdeR activation provides a better understanding of IdeR and the biology of iron homeostasis in M. tuberculosis.

What do we know when we know a person across contexts? Examining self-concept differentiation at the three levels of personality.

OBJECTIVE: Previous research examining self-concept differentiation (SCD) has been characterized by (a) a focus on behavioral traits and (b) the conflation of mean-level and inter-contextual differentiation. In two studies, we considered non-conflated measures of SCD at the three levels of personality description in relation to adjustment. METHOD: In Study 1, participants completed measures of adjustment, rated their behavioral tendencies (dispositional traits), produced a list of goals (characteristic adaptations), and recalled a self-defining memory (life narratives), from within professional and personal domains. In Study 2, the procedure was modified: Participants reporting either low or high levels of adjustment subsequently rated their behavioral traits, provided a list of goals, or produced a self-defining memory, from five contexts. RESULTS: In Study 1, adjustment related positively to SCD at the level of characteristic adaptations but negatively to SCD at the level of life narratives. In Study 2, well-adjusted participants exhibited a greater degree of SCD at the level of characteristic adaptations but a greater degree of thematic consistency at the level of life narratives, relative to those low in adjustment. CONCLUSIONS: These results highlight the dynamic nature of SCD across levels of personality and align with the notion that differentiation represents virtue and vice.

Exemplars' moral behavior is self-regarding.

What fundamentally motivates moral behavior? What is the nature and source of moral motivation? The argument developed in this chapter is that moral action is not merely other-regarding; it also can, and should be, self-regarding. When there is something significant for the self in the moral enterprise, it can legitimately be self-enhancing and, thus, powerfully motivating. The empirical warrant for this argument is found in the study of the psychological functioning of moral exemplars. The research reviewed here indicates that moral exemplars do synergistically integrate their self-promoting agentic motivation in service to their other-promoting communal values. Therein is the powerful motivational impetus for doing good and living rightly.

Our Experience of Deep Sclerectomy at a Tertiary Center in the United Kingdom Over 14 Years.

Background Deep sclerectomy (DS) is a non-penetrating surgical procedure for glaucoma, reducing the resistance to aqueous outflow and lowering intraocular pressure while maintaining a physiological barrier between the anterior chamber and the sub-scleral space. This offers a lower complication profile than penetrating procedures, though with less intraocular pressure (IOP) reduction. Methods We retrospectively reviewed the electronic record for all DS undertaken at our hospital (a tertiary care center) over 14 years, collecting data on demographics, diagnosis, IOP, visual acuity, complications, medications, and further procedures required. Results Eighty eyes of 69 patients underwent DS, with a mean follow-up period of 53.5 months. The mean pre-operative IOP was 23.55 mmHg (range 11-52, standard deviation 8.46); the mean final IOP was 13.61 mmHg (range 5-35, SD 4.73), with a mean reduction of 42.21%. The mean change in glaucoma medications was -1.64. 78.40% experienced a reduction in glaucoma treatment. Post-operatively, 43.80% had no complications; this improved to 85.0% when numerical hypotony and raised IOP without visual sequelae were excluded. Further procedures required included Nd:YAG goniopuncture (10%), bleb needling (13.75%) or revision (7.5%), iridectomy (3.75%), goniosynechiolysis (1.25%), and autologous blood injection (1.25%). Two eyes were converted to trabeculectomy peri-operatively, with seven overall (8.75%) requiring trabeculectomy over the course of follow-up. 3.75% underwent glaucoma drainage device implantation, and 3.75% underwent cyclodiode laser. Conclusion We have found DS to be a safe, effective procedure for selected patients where trabeculectomy has a high likelihood of failure or where a higher IOP can be tolerated.

Hierarchical integration of agency and communion: a study of influential moral figures.

The purpose of this research is to (a) identify which of recent history's influential figures did and which did not personify moral excellence, and (b) to examine the motives that drove these individuals along such divergent paths. In Study 1, 102 social scientists evaluated the moral qualities of influential figures from Time Magazine's lists. In Study 2, we selected the 15 top ranking of these figures to comprise a moral exemplar group and the bottom 15 to comprise a comparison group of similarly influential people. We measured the motivational aspects of their personality (agency and communion) by content-analyzing extant speeches and interviews. Moral exemplars exhibited the hierarchical integration of agency and communion by treating agentic motives as a means to an end of communal motives. Comparison subjects, by contrast, personified unmitigated agency by treating motives of agency as both a means to an end and an end unto itself. These results imply that both the strength and structure of a person's motives account for moral behavior.

Lipid tails modulate antimicrobial peptide membrane incorporation and activity.

Membrane disrupting antimicrobial peptides (AMPs) are often amphipathic peptides that interact directly with lipid bilayers. AMPs are generally thought to interact mostly with lipid head groups, but it is less clear how the lipid alkyl chain length and saturation modulate interactions with membranes. Here, we used native mass spectrometry to measure the stoichiometry of three different AMPs-LL-37, indolicidin, and magainin-2-in lipid nanodiscs. We also measured the activity of these AMPs in unilamellar vesicle leakage assays. We found that LL-37 formed specific hexamer complexes but with different intermediates and affinities that depended on the bilayer thickness. LL-37 was also most active in lipid bilayers containing longer, unsaturated lipids. In contrast, indolicidin incorporated to a higher degree into more fluid lipid bilayers but was more active with bilayers with thinner, less fluid lipids. Finally, magainin-2 incorporated to a higher degree into bilayers with longer, unsaturated alkyl chains and showed more activity in these same conditions. Together, these data show that higher amounts of peptide incorporation generally led to higher activity and that AMPs tend to incorporate more into longer unsaturated lipid bilayers. However, the activity of AMPs was not always directly related to amount of peptide incorporated.

Varieties of moral personality: beyond the banality of heroism.

Four perspectives dominate thinking about moral heroism: One contends that moral action is primarily instigated by situational pressures, another holds that moral excellence entails the full complement of virtues, the third asserts a single superintending principle, and the fourth posits different varieties of moral personality. This research addresses these competing perspectives by examining the personalities of moral heroes. Participants were 50 national awardees for moral action and 50 comparison individuals. They responded to personality inventories and a life-review interview that provided a broadband assessment of personality. Cluster analysis of the moral exemplars yielded three types: a "communal" cluster was strongly relational and generative, a "deliberative" cluster had sophisticated epistemic and moral reasoning as well as heightened self-development motivation, and an "ordinary" cluster had a more commonplace personality. These contrasting profiles imply that exemplary moral functioning can take multifarious forms and arises from different sources, reflecting divergent person x situation interactions.

Moral personality of brave and caring exemplars.

Two contrasting types of moral exemplars were examined so as to identify personality variables associated with moral action. The sample comprised 50 Canadian awardees for either exceptional bravery or caring, as well as 50 comparison participants. Participants responded to a set of personality questionnaires and a life-review interview. Personality variables were found to substantially augment moral cognition in the prediction of exemplary action. In support of the notion that there is a personological core to the moral domain, it was found that moral exemplars were distinguished from the comparison groups by themes embodied in their life narratives. Specifically, moral exemplars had stronger motivational themes of both agency and communion, were more likely to construe critical life events redemptively, more frequently identified helpers in early life, and reported more secure attachments. Furthermore, the personality of caring exemplars was more nurturant, generative, and optimistic than that of brave exemplars; these somewhat divergent personality profiles imply multiple ideals of moral maturity.

Unambiguous identification and discovery of bacterial siderophores by direct injection 21 Tesla Fourier transform ion cyclotron resonance mass spectrometry.

Under iron-limiting conditions, bacteria produce low molecular mass Fe(iii) binding molecules known as siderophores to sequester the Fe(iii), along with other elements, increasing their bioavailability. Siderophores are thought to influence iron cycling and biogeochemistry in both marine and terrestrial ecosystems and hence the need for rapid, confident characterization of these compounds has increased. In this study, the type of siderophores produced by two marine bacterial species, Synechococcus sp. PCC 7002 and Vibrio cyclitrophicus 1F53, were characterized by use of a newly developed 21 T Fourier Transform Ion Cyclotron Resonance Mass Spectrometer (FTICR MS) with direct injection electrospray ionization. This technique allowed for the rapid detection of synechobactins from Synechococcus sp. PCC 7002 as well as amphibactins from Vibrio cyclitrophicus 1F53 based on high mass accuracy and resolution allowing for observation of specific Fe isotopes and isotopic fine structure enabling highly confident identification of these siderophores. When combined with molecular network analysis two new amphibactins were discovered and verified by tandem MS. These results show that high-field FTICR MS is a powerful technique that will greatly improve the ability to rapidly identify and discover metal binding species in the environment.

Differing conceptions of moral exemplarity: just, brave, and caring.

People's conceptions of different types of moral exemplarity were examined in an attempt to augment the current emphasis on moral rationality with a fuller understanding of moral personality. In Study 1 (with 805 adults), a free-listing procedure was used to generate the attributes of 3 types of moral exemplars (just, brave, and caring). In Study 2 (with 401 undergraduates), prototypicality- and personality-rating procedures were used to generate a personality profile for each type of moral exemplar and to examine the relations among them. In Study 3 (with 240 undergraduates), a similarity-sorting procedure was used to identify the typologies implicit in people's understanding of these different types of moral exemplarity. The findings indicate that moral excellence can be exemplified in rather divergent ways and that understanding of moral functioning would be enhanced by attention to this wider range of moral virtues.

Plant succession as an integrator of contrasting ecological time scales.

Ecologists have studied plant succession for over a hundred years, yet our understanding of the nature of this process is incomplete, particularly in relation to its response to new human perturbations and the need to manipulate it during ecological restoration. We demonstrate how plant succession can be understood better when it is placed in the broadest possible temporal context. We further show how plant succession can be central to the development of a framework that integrates a spectrum of ecological processes, which occur over time scales ranging from seconds to millions of years. This novel framework helps us understand the impacts of human perturbations on successional trajectories, ecosystem recovery, and global environmental change.

The nature of professional and relational self-aspects at the goal and narrative levels of personality.

The self-concept is constituted by a series of context-specific self-aspects. Researchers have considered the manner in which personality traits vary across these self-aspects. Here, we examined self-aspects corresponding to professional and relational contexts at the goal and narrative levels of personality. In each of two studies, participants provided lists of goals and recounted self-defining narratives, corresponding to the aforementioned contexts. Goals and narratives were coded for themes of agency and communion. At both descriptive levels, agency more characterized the professional self-aspect and communion, the relational self-aspect. A consideration of context-specific goals and narratives informs understanding regarding the nature of the self in its multifaceted form.

Moral identity as moral ideal self: links to adolescent outcomes.

The purposes of this study were to conceptualize moral identity as moral ideal self, to develop a measure of this construct, to test for age and gender differences, to examine links between moral ideal self and adolescent outcomes, and to assess purpose and social responsibility as mediators of the relations between moral ideal self and outcomes. Data came from a local school sample (Data Set 1: N = 510 adolescents; 10-18 years of age) and a national online sample (Data Set 2: N = 383 adolescents; 15-18 years of age) of adolescents and their parents. All outcome measures were parent-report (Data Set 1: altruism, moral personality, aggression, and cheating; Data Set 2: environmentalism, school engagement, internalizing, and externalizing), whereas other variables were adolescent-report. The 20-item Moral Ideal Self Scale showed good reliability, factor structure, and validity. Structural equation models demonstrated that, even after accounting for moral identity internalization, in Data Set 1 moral ideal self positively predicted altruism and moral personality and negatively predicted aggression, whereas in Data Set 2 moral ideal self positively predicted environmentalism and negatively predicted internalizing and externalizing symptoms. Further, purpose and social responsibility mediated most relations between moral ideal self and the outcomes in Data Set 2. Moral ideal self was unrelated to age but differentially predicted some outcomes across age. Girls had higher levels of moral ideal self than boys, although moral identity did not differentially predict outcomes between genders. Thus, moral ideal self is a salient element of moral identity and may play a role in morally relevant adolescent outcomes.

Liberals and conservatives rely on common moral foundations when making moral judgments about influential people.

Do liberals and conservatives have qualitatively different moral points of view? Specifically, do liberals and conservatives rely on the same or different sets of moral foundations-care, fairness, loyalty, authority, and purity (Haidt, 2012)-when making moral judgments about influential people? In Study 1, 100 experts evaluated the impact that 40 influential figures had on each moral foundation, yielding stimulus materials for the remaining studies. In Study 2, 177 American liberal and conservative professors rated the moral character of the same figures. Liberals and conservatives relied on the same 3 moral foundations: For both groups, promoting care, fairness, and purity-but not authority or loyalty-predicted moral judgments of the targets. For liberals, promoting authority negatively predicted moral judgments. Political ideology moderated the purity-moral and especially authority-moral relationships, implying that purity and authority are grounds for political disagreement. Study 3 replicated these results with 222 folk raters. Folk liberals and conservatives disagreed even less about the moral standing of the targets than did experts. Together, these findings imply that moral foundation theory may have exaggerated differences between liberals and conservatives. The moral codes of liberals and conservatives do differ systematically; however, their similarities outweigh their differences. Liberals and conservatives alike rely on care, fairness, and purity when making moral judgments about influential people.

Four opportunities for studies of ecological succession.

Lessons learned from the study of ecological succession have much to offer contemporary environmental problem solving but these lessons are being underutilized. As anthropogenic disturbances increase, succession is more relevant than ever. In this review, we suggest that succession is particularly suitable to address concerns about biodiversity loss, climate change, invasive species, and ecological restoration. By incorporating modern experimental techniques and linking results across environmental gradients with meta-analyses, studies of succession can substantially improve our understanding of other ecological phenomena. Succession can help predict changes in biodiversity and ecosystem services impacted by invasive species and climate change and guide manipulative responses to these disruptions by informing restoration efforts. Succession is still a critical, integrative concept that is central to ecology.

The integration of agency and communion in moral personality: Evidence of enlightened self-interest.

Agency and communion are fundamental human motives, often conceptualized as being in tension. This study examines the notion that moral exemplars overcome this tension and adaptively integrate these 2 motives within their personality. Participants were 25 moral exemplars-recipients of a national award for extraordinary volunteerism-and 25 demographically matched comparison participants. Each participant responded to a life review interview and provided a list of personal strivings, which were coded for themes of agency and communion; interviews were also coded for the relationship between agency and communion. Results consistently indicated that exemplars not only had both more agency and communion than did comparison participants but were also more likely to integrate these themes within their personality. Consistent with our claim that enlightened self-interest is driving this phenomenon, this effect was evident only when agency and communion were conceptualized in terms of promoting interests (of the self and others, respectively) and not in terms of psychological distance (from others) and only when the interaction was observed with a person approach and not with the traditional variable approach. After providing a conceptual replication of these results using different measures elicited in different contexts and relying on different coding procedures, we addressed and dismissed various alternative explanations, including chance co-occurrence and generalized complexity. These results provide the first reliable evidence of the integration of motives of agency and communion in moral personality.