The Study That Made Rats Jump for Joy, and Then Killed Them: The Gap between Knowledge and Practice Widens When Scientists Fail to Engage with the Ethical Implications of Their Own Work.

Much contemporary behavioral science stops short of considering the ethical implications of its own findings. This generates a contradiction between methods and discoveries, and hinders translation between updated scientific evidence for animal sentience and corresponding political and legal changes. A recent and particularly illustrative example in rodents is described here.

Females undergo selection too.

Extending Campbell's (1999) staying alive theory (SAT) beyond aggression, we reviewed evidence that females are more self-protective than males. Many commentators provided additional supporting data. Sex differences in life-history adaptations, in the optimal relation between survival and reproduction, and in the mechanisms underlying trade-offs involved with self-protection remain important topics with numerous opportunities for improved understanding.

Self-protection as an adaptive female strategy.

Many male traits are well explained by sexual selection theory as adaptations to mating competition and mate choice, whereas no unifying theory explains traits expressed more in females. Anne Campbell's "staying alive" theory proposed that human females produce stronger self-protective reactions than males to aggressive threats because self-protection tends to have higher fitness value for females than males. We examined whether Campbell's theory has more general applicability by considering whether human females respond with greater self-protectiveness than males to other threats beyond aggression. We searched the literature for physiological, behavioral, and emotional responses to major physical and social threats, and found consistent support for females' responding with greater self-protectiveness than males. Females mount stronger immune responses to many pathogens; experience a lower threshold to detect, and lesser tolerance of, pain; awaken more frequently at night; express greater concern about physically dangerous stimuli; exert more effort to avoid social conflicts; exhibit a personality style more focused on life's dangers; react to threats with greater fear, disgust, and sadness; and develop more threat-based clinical conditions than males. Our findings suggest that in relation to threat, human females have relatively heightened protective reactions compared to males. The pervasiveness of this result across multiple domains suggests that general mechanisms might exist underlying females' unique adaptations. An understanding of such processes would enhance knowledge of female health and well-being.

The expression of empathy in human's closest relatives, bonobos and chimpanzees: current and future directions.

Empathy is a complex, multi-dimensional capacity that facilitates the sharing and understanding of others' emotions. As our closest living relatives, bonobos (Pan paniscus) and chimpanzees (P. troglodytes) provide an opportunity to explore the origins of hominin social cognition, including empathy. Despite certain assumptions that bonobos and chimpanzees may differ empathically, these species appear to overlap considerably in certain socio-emotional responses related to empathy. However, few studies have systematically tested for species variation in Pan empathic or socio-emotional tendencies. To address this, we synthesise the growing literature on Pan empathy to inform our understanding of the selection pressures that may underlie the evolution of hominin empathy, and its expression in our last common ancestor. As bonobos and chimpanzees show overlaps in their expression of complex socio-emotional phenomena such as empathy, we propose that group comparisons may be as or more meaningful than species comparisons when it comes to understanding the evolutionary pressures for such behaviour. Furthermore, key differences, such as how humans and Pan communicate, appear to distinguish how we experience empathy compared to our closest living relatives.

An inversion effect modified by expertise in capuchin monkeys.

The face inversion effect may be defined as the general impairment in recognition that occurs when faces are rotated 180°. This phenomenon seems particularly strong for faces as opposed to other objects and is often used as a marker of a specialized face-processing mechanism. Four brown capuchin monkeys (Cebus apella) were tested on their ability to discriminate several classes of facial and non-facial stimuli presented in both their upright and inverted orientations in an oddity task. Results revealed significantly better performance on upright than inverted presentations of capuchin and human face stimuli, but not on chimpanzee faces or automobiles. These data support previous studies in humans and other primates suggesting that the inversion effect occurs for stimuli for which subjects have developed an expertise.

CCR2 receptor antagonists: optimization of biaryl sulfonamides to increase activity in whole blood.

A series of biarylsulfonamides was identified as hCCR2 receptor antagonist but suffered from high plasma protein binding resulting in a >100 fold shift in activity in a functional GTPγS assay run in tandem in the presence and absence of human serum albumin. Introduction of an aryl amide with ethylenediamine linker led to compounds with reduced shifts and improved activity in whole blood.

Jealous Behavior in Chimpanzees Elicited by Social Intruders.

Despite increasing interest in animal emotions, jealousy has rarely been directly addressed in comparative research, except for studies of human-pet interactions. Jealous behavior emerges when a valuable social bond is threatened by a third-party, prompting aggression or intervention attempts to direct the partner's attention away from the rival. Emotional reactions that protect relationships are expected in species in which social relationships are important for fitness, including primates. Previous primate studies have alluded to this ultimate function, but never explicitly tested predictions corresponding to a proximate jealousy mechanism. We demonstrate jealous behavior in a long-established colony of chimpanzees (N = 17) during a socially disruptive period due to group introductions, which provided an ideal experimental opportunity to test predictions of a jealousy hypothesis. Specifically, we found that negative reactions (agonism and intervention attempts) towards social closeness between two groupmates were generally more common when the aggressor/intervener had a valuable relationship to one (as compared with both or neither) of the dyad's members, indicating that the other partner represented a potential social rival. In line with this suggestion, we found that negative reactions most often targeted dyads containing newly introduced individuals, especially when the social conditions for jealousy were met, and in particular during the socially unstable introduction period. Results underscore the potential adaptive role of jealousy in protecting fitness-enhancing relationships from social interlopers, by extension indicating that this emotion likely evolved in diverse animal societies.

Do chimpanzees (Pan troglodytes) console a bereaved mother?

Comparative thanatology encompasses the study of death-related responses in non-human animals and aspires to elucidate the evolutionary origins of human behavior in the context of death. Many reports have revealed that humans are not the only species affected by the death of group members. Non-human primates in particular show behaviors such as congregating around the deceased, carrying the corpse for prolonged periods of time (predominantly mothers carrying dead infants), and inspecting the corpse for signs of life. Here, we extend the focus on death-related responses in non-human animals by exploring whether chimpanzees are inclined to console the bereaved: the individual(s) most closely associated with the deceased. We report a case in which a chimpanzee (Pan troglodytes) mother experienced the loss of her fully developed infant (presumed stillborn). Using observational data to compare the group members' behavior before and after the death, we found that a substantial number of group members selectively increased their affiliative expressions toward the bereaved mother. Moreover, on the day of the death, we observed heightened expressions of species-typical reassurance behaviors toward the bereaved mother. After ruling out several alternative explanations, we propose that many of the chimpanzees consoled the bereaved mother by means of affiliative and selective empathetic expressions.

Synthesis and SAR of potent LXR agonists containing an indole pharmacophore.

A novel series of 1H-indol-1-yl tertiary amine LXR agonists has been designed. Compounds from this series were potent agonists with good rat pharmacokinetic parameters. In addition, the crystal structure of an LXR agonist bound to LXRalpha will be disclosed.

The discovery of tertiary-amine LXR agonists with potent cholesterol efflux activity in macrophages.

The liver X receptors (LXR) play a key role in cholesterol homeostasis and lipid metabolism. SAR studies around tertiary-amine lead molecule 2, an LXR full agonist, revealed that steric and conformational changes to the acetic acid and propanolamine groups produce dramatic effects on agonist efficacy and potency. The new analogs possess good functional activity, demonstrating the ability to upregulate LXR target genes, as well as promote cholesterol efflux in macrophages.

Informed consent to healthcare interventions in people with learning disabilities--an integrative review.

AIM: This paper is a report of an integrative review of informed consent to healthcare interventions in people with learning disabilities. BACKGROUND: Consent to treatment lies at the heart of the relationship between patient and healthcare professional. In order for people with learning disabilities to have equity of access to health care, they need to be able to give informed consent to health interventions--or be assessed as incompetent to give consent. DATA SOURCES: The British Nursing Index (BNI), CINAHL, MEDLINE, Social Care Online, ERIC and ASSIA and PsycINFO databases were searched using the search terms: Consent or informed choice or capacity or consent to treat* or consent to examin* AND Learning disab* or intellectual* disab* or mental* retard* or learning difficult* or mental* handicap*. The search was limited to papers published in English from January 1990 to March 2007. REVIEW METHODS: An integrative review was conducted and the data analysed thematically. RESULTS: Twenty-two studies were reviewed. The main themes identified were: life experience, interaction between healthcare professionals and participants, ability to consent, and psychometric variables. A consensus seemed to emerge that capacity to consent is greater in people with higher cognitive ability and verbal skills, but that the attitudes and behaviour of healthcare professionals was also a crucial factor. CONCLUSION: The findings support use of the functional approach to assessing mental capacity for the purpose of obtaining informed consent. Future research into informed consent in people with learning disabilities is needed using real life situations rather than hypothetical vignettes.

Professional identity as a resource for talk: exploring the mentor-student relationship.

This paper discusses a study examining how mentors in nurse education make professional judgments about the clinical competence of their pre-registration nursing students. Interviews were undertaken with nine UK students and 15 mentors, using critical incidents in practice settings as a focus. The study was undertaken for the English National Practice-Based Professional Learning Centre for Excellence in Teaching and Learning. This paper reports on the conversation analytic thread of the work. The mentor role with pre-registration nursing students is not only supportive but involves formal assessment. Central to the relationship is communication. In professional education, communication is seen as a skill to be applied and assessed in practice settings but is also the medium mentors and mentees use to talk about the relationship. Analysis of excerpts of conversation in the interviews shows that episodes of communication are used as topics of conversation to establish professional identity. It also reveals that judgments about the extent of professional capacity of both students and mentors are grounded in everyday behaviours (for example, enthusiasm, indifference and confidence) as well as professional competence. In addition to focusing on clinical issues, mentors can and do use mundane communication as a resource for judgments about competence.

Judgements about mentoring relationships in nurse education.

Much has been written about the use of portfolios and mentoring in the clinical assessment of nursing students in the United Kingdom. Research reports have focused on difficulties in using portfolios, mentoring relationships and mentor preparation. The aim of this study was to deepen understanding of how mentors actually make judgements about students' clinical competence. Qualitative data were gathered in 2006 using a critical incident technique in interviews with a convenience sample of students and mentors from two different geographical regions in the UK. Thematic analysis generally confirmed previous findings regarding the qualities of a good student and resource issues in mentoring. 'Good mentoring' depended on students building a relationship with their mentors, and undertaking a great deal of 'emotional labour' to convince mentors that they were 'good students' in terms of attitudes as well as clinical competence. It seems clear that much of the burden of creating effective mentoring relationships falls on students. At the same time, many issues identified in previous research do not appear to have been tackled, including appropriate mentor preparation and support, the format of portfolios and competency statements, and ensuring that enough time is available for mentoring and student supervision.

Stepping forward together: Could walking facilitate interpersonal conflict resolution?

Walking has myriad benefits for the mind, most of which have traditionally been explored and explained at the individual level of analysis. Much less empirical work has examined how walking with a partner might benefit social processes. One such process is conflict resolution-a field of psychology in which movement is inherent not only in recent theory and research, but also in colloquial language (e.g., "moving on"). In this article, we unify work from various fields pointing to the idea that walking together can facilitate both the intra- and interpersonal pathways to conflict resolution. Intrapersonally, walking supports various psychological mechanisms for reconciliation, including creativity, locomotion motivation, and embodied notions of forward progress. Both alone and in combination with its effects on mood and stress, walking can encourage individual mindsets conducive to resolving conflict (e.g., divergent thinking). Interpersonally, walking can allow partners to reap the cognitive, affective, and behavioral advantages of synchronous movement, such as increased positive rapport, empathy, and prosociality. Walking partners naturally adopt cooperative (as opposed to competitive) postural stances, experience shared attention, and can benefit from discussions in novel environments. Overall, despite its prevalence in conflict resolution theory, little is known about how movement influences conflict resolution practice. Such knowledge has direct implications for a range of psychological questions and approaches within negotiation and alternative mediation techniques, clinical settings, and the study of close relationships. (PsycINFO Database Record

Long-term consistency in chimpanzee consolation behaviour reflects empathetic personalities.

In contrast to a wealth of human studies, little is known about the ontogeny and consistency of empathy-related capacities in other species. Consolation-post-conflict affiliation from uninvolved bystanders to distressed others-is a suggested marker of empathetic concern in non-human animals. Using longitudinal data comprising nearly a decade of observations on over 3000 conflict interactions in 44 chimpanzees (Pan troglodytes), we provide evidence for relatively stable individual differences in consolation behaviour. Across development, individuals consistently differ from one another in this trait, with higher consolatory tendencies predicting better social integration, a sign of social competence. Further, similar to recent results in other ape species, but in contrast to many human self-reported findings, older chimpanzees are less likely to console than are younger individuals. Overall, given the link between consolation and empathy, these findings help elucidate the development of individual socio-cognitive and -emotional abilities in one of our closest relatives.Non-human animals are known to exhibit behaviours suggestive of empathy, but the development and maintenance of these traits is unexplored. Here, Webb and colleagues quantify individual consolation tendencies over 10 years across two chimpanzee groups and show evidence of consistent 'empathetic personalities'.

Moving on or digging deeper: Regulatory mode and interpersonal conflict resolution.

Conflict resolution, in its most basic sense, requires movement and change between opposing motivational states. Although scholars and practitioners have long acknowledged this point, research has yet to investigate whether individual differences in the motivation for movement from state-to-state influence conflict resolution processes. Regulatory Mode Theory (RMT) describes this fundamental motivation as locomotion. RMT simultaneously describes an orthogonal motivational emphasis on assessment, a tendency for critical evaluation and comparison. We argue that this tendency, in the absence of a stronger motivation for locomotion, can obstruct peoples' propensity to reconcile. Five studies, using diverse measures and methods, found that the predominance of an individual's locomotion over assessment facilitates interpersonal conflict resolution. The first two studies present participants with hypothetical conflict scenarios to examine how chronic (Study 1) and experimentally induced (Study 2) individual differences in locomotion predominance influence the motivation to reconcile. The next two studies investigate this relation by way of participants' own conflict experiences, both through essay recall of previous conflict events (Study 3) and verbal narratives of ongoing conflict issues (Study 4). We then explore this association in the context of real-world conflict discussions between roommates (Study 5). Lastly, we examine results across these studies meta-analytically (Study 6). Overall, locomotion and assessment can inform lay theories of individual variation in the motivation to "move on" or "dig deeper" in conflict situations. We conclude by emphasizing the importance of using RMT to go beyond instrumental approaches to conflict resolution to understand fundamental individual motivations underlying its occurrence. (PsycINFO Database Record

Poloxamer 407 (P-407)-mediated reduction in the gene expression of ATP-binding-cassette transporter A1 may contribute to increased cholesterol in peripheral tissues of P-407-treated rats.

The purpose of this study was to determine whether poloxamer 407, a chemical known to increase plasma lipid levels in rodents following parenteral administration, decreased the gene expression of ATP-binding-cassette transporter A1. Using human macrophages cultured with poloxamer 407, there was a significant reduction in the gene expression of ATP-binding-cassette transporter A1; however, there was no effect on the gene expression of either fatty acid synthase or sterol regulatory element binding protein-1. Reduction of ATP-binding-cassette transporter A1 mRNA levels was also observed in both liver and intestine of poloxamer 407-treated rats. When macrophages were cultured with poloxamer 407, the percent of cholesterol effluxed decreased in a concentration-dependent fashion, both in the absence and presence of a synthetic liver X receptor agonist. Lastly, total and unesterified (free) cholesterol concentrations were determined in the liver and 9 peripheral tissues of poloxamer 407- and saline-injected (control) rats. In every tissue, the concentration of total cholesterol for poloxamer 407-treated rats was significantly greater than the corresponding value for controls. Our findings would seem to suggest that the poloxamer 407-mediated reduction in both ATP-binding-cassette transporter A1 gene expression and cellular cholesterol efflux may potentially be one factor that contributes to the accumulation of cholesterol and cholesteryl esters in the liver and 9 peripheral tissues of poloxamer 407-treated rats. Furthermore, the surprising specificity by poloxamer 407 for inhibition of ATP-binding-cassette transporter A1 gene expression over fatty acid synthase and sterol regulatory element binding protein-1 may potentially be due to either disruption of a transcriptional cofactor required for ATP-binding-cassette transporter A1 gene expression, or enhanced turnover of ATP-binding-cassette transporter A1 mRNA.

Discovery of substituted maleimides as liver X receptor agonists and determination of a ligand-bound crystal structure.

Substituted 3-(phenylamino)-1H-pyrrole-2,5-diones were identified from a high throughput screen as inducers of human ATP binding cassette transporter A1 expression. Mechanism of action studies led to the identification of GSK3987 as an LXR ligand. GSK3987 recruits the steroid receptor coactivator-1 to human LXRalpha and LXRbeta with EC(50)s of 40 nM, profiles as an LXR agonist in functional assays, and activates LXR though a mechanism that is similar to first generation LXR agonists.