γ-glutamyl-propenyl-cysteine sulfoxide (GPCS), a gamma-glutamyl peptide from onion (Allium cepa L.). phytochemistry and pharmacology

Gamma-glutamyl peptides are widely found in plants. γ-Glutamyl-propenyl-cysteine sulfoxide (GPCS), a glutamyl peptide present in onion (Allium cepa L.), was identified by a bioassayguided fractionation in vitro to be the compound responsible for the inhibition of bone resorption by onion in rats. Therefore, GPCS was selected for an extended investigation in our studies. The aim of the first part of this work was to examine the presence of GPCS in various plants, which were previously shown to inhibit bone resorption in rats. A fast and reliable method to determine GPCS in plant material was developed and validated. GPCS was found in onion at various concentrations, but no GPCS was detected in the material from other plants. In the second part of the present work, the aim was to provide GPCS for further in vitro and in vivo studies. Small quantities (milligram-amounts) were obtained by isolation of GPCS from onion. As large-scale isolation (gram amounts) is not feasible under non-industrial conditions, and GPCS is not commercially available, an approach for synthesis was performed. The intermediate products S-(1-propenyl)-L-cysteine sulfoxide and Boc-Lglutamyl-α-t-butyl-N-oxo-succinimide ester were synthesised, but unfortunately, coupling of these two compounds failed and the final product could not be obtained. The aim of the third part of this work was to examine pharmacodynamic and pharmacokinetic parameters of GPCS. In vitro experiments on the effects of GPCS on the activity, activation and recruitment of osteoclasts (OCs) were performed. The effect of GPCS on the activity of OCs was tested in the pit assay. GPCS, at 8 mM, significantly reduced the number of pits per OCs. The effect of GPCS on the activation of OCs was examined by determination of the OCs with actin ring(s). After incubation of the cells with 2 and 8 mM of GPCS, the percentage of OCs with actin rings did not change. The formation of OCs was inhibited at GPCS concentrations of 1 mM and higher in our experiments with CSF-1/RANKL primed bone marrow cells. A structure-function relationship was assessed by testing GPCS structurally related compounds in the same assay, namely γ-glutamyl-cysteine-ethylester, glycylcysteine, allyl-cysteine, cysteine, glutamyl-glycine and glycyl-valine. All test substances which contained a cysteine moiety inhibited osteoclastogenesis while the others did not show an effect. The pharmacokinetic properties of GPCS were studied in vitro and in vivo. Within 24 hours no change in the concentration of GPCS was observed when GPCS was incubated with simulated gastric acid. 24-hour incubation of GPCS with simulated intestinal fluid caused a 90 % decrease of the GPCS concentration, while GPCS concentration in onion incubated with simulated intestinal fluid decreased only by 30 %. In a pilot study with rats on the kinetics of GPCS in vivo, the bioavailability of orally administered GPCS was determined to be about 1 %. Finally, onion without GPCS and onion containing GPCS, as well as GPCS-structure related compounds were tested in a rat model in vivo to analyse their effect on bone resorption. Allyl-cysteine and γ-glutamyl-cysteine-ethylester did not inhibit bone resorption while 3 g of onion without GPCS and 3 g of onion containing GPCS significantly inhibited bone resorption. The in vitro results indicate that the effects of GPCS might be mediated by the cysteine moiety of the molecule. An in vivo oral application of pure GPCS in an aqueous solution is not suitable due to the low bioavailability of GPCS, however, application of GPCS embedded in onion might prevent cleavage of the compound and therefore increase the bioavailability. Because both onion without GPCS and onion containing GPCS inhibited bone resorption in vivo, we can postulate that the inhibition of bone resorption by onion is not exclusively mediated by GPCS. Future experiments using natural GPCS-free onions spiked with synthetic GPCS should clarify, to which extent GPCS contributes to the inhibition of bone resorption

Mothers make a difference: Mothers develop weaker bonds with immature sons than daughters

Among mammals, individuals form strong social bonds preferentially with their kin. Differences in these relationships are linked to differential kin availability due to sex-specific dispersal patterns, but there is some indication that differential bonding among sexes already occurs prior to maturation. However, little is known about how these patterns arise during individual development. Here we investigated sex differences in the development of mother-offspring bonds in rhesus macaques (Macaca mulatta). Our results revealed that mothers showed sex-biased bonding toward their offspring. Sons had a distinctly higher probability of receiving aggression from their mothers than did daughters in the first year of life, while no differences were found with respect to affiliative interactions. After the first year, probabilities of all affiliative and aggressive behaviours investigated were higher for daughters than for sons, although generally declining. Furthermore, sons spending less time with their mother and receiving more maternal aggression tended to disperse earlier. The results of our study suggest that mothers influence their bonding strength with offspring by interacting less affiliative with sons than daughters

Langos responds to Spyrou: changing group norms may foster positive responses to victimisation

Colette Lango

Responding to cyberbullying: the case for family conferencing

Cyberbullying is a form of anti-social conduct which is best understood as an online social relationship problem. Because of our growing understanding of the phenomenon, we can now see that any socio-legal response should envisage, therefore, a relationship solution. This article considers how one diversionary criminal justice process is particularly well suited to responding to incidents of cyberbullying where juveniles are involved yet which are deemed to be sufficiently serious to attract a potential criminal penalty. It explores, specifically, the option of family conferences (facilitated by youth justice co-ordinators) within the South Australian youth court framework. It concludes that both young cyberbullies and young victims of cyberbullying may benefit from alternatives to a retributive justice process, given that the primary focus of family conferencing is the repair of harm and the restoration of relationships.Colette Langos, Rick Sarr

Examining the Psychosocial and Behavioral Factors Associated with Adolescent Engagement in Multiple Types of Cyberdeviance: Results from an Australian Study

OnlinePublResearch has shown that psychosocial and behavioral factors are associated with engagement in a range of deviant behaviors across offline settings. To date, however, very little research has explored the impact of these factors in online contexts. This article addresses this gap by examining the psychosocial and behavioral factors associated with common types of adolescent cyberdeviance. This is accomplished through an empirical study of 327 adolescents enrolled in a high school located in a large Australian city. The study assesses various aspects of psychosocial and behavioral functioning using the Strengths and Difficulties Questionnaire (total difficulties, internalizing problems, externalizing problems, prosocial behavior), as well as numerous types of cyberdeviance relevant to young people, including cyberfraud, cyberhate, cyberviolence, sexting, digital piracy, hacking, and cyberbullying. A series of multivariate logistic regression analyses were conducted to demonstrate the association between psychosocial and behavioral difficulties and various types of cyberdeviance, independent of gender, school grade, socioeconomic status, and engagement in offline delinquency. Results indicate that total difficulties, internalizing problems, and externalizing problems were significantly associated with greater likelihood of engagement in most types of cyberdeviance examined in this study, whereas prosocial behavior was associated with a lower likelihood of engagement in digital piracy only. A discussion of the findings highlights the importance of understanding these factors in a digital context, as well as demonstrating the need to account for them when designing targeted interventions.Russell Brewer, Tyson Whitten, Katie Logos, Morgan Sayer, Colette Langos, Thomas J. Holt, Jesse Cale, Andrew Goldsmit

Awareness, Policy, Privacy, and More: Post-Secondary Students Voice Their Solutions to Cyberbullying

This paper discusses solutions to cyberbullying posed by post-secondary students from four Canadian universities. The qualitative data used in this analysis were drawn from one open-ended question on an online student survey completed by 1458 undergraduate students, as well as 10 focus group transcripts involving a total of 36 students. Seven key themes emerged: awareness and education; policy; protecting one’s privacy; technology-based solutions; empowering better choices and responses; university culture; and disciplinary measures. The findings show that post-secondary institutions need to make preventing and curtailing cyberbullying more of a priority within their campus communities, including engaging in responsive consultation with key stakeholder groups, such as students, to develop meaningful solutions

Social and ecological factors influencing offspring survival in wild macaques.

Premature loss of offspring decreases direct fitness of parents. In gregarious mammals, both ecological and social variables impact offspring survival and may interact with each other in this regard. Although a number of studies have investigated factors influencing offspring loss in mammals, we still know very little on how different factors interact with one another. We therefore investigated fetal and infant mortality in 3 large groups of wild crested macaques (Macaca nigra) over a period of up to 5 years by including potential social causes such as maternal dominance rank, male immigration, between group encounters, and ecological conditions such as rainfall in a multivariate survival analysis using Cox proportional hazards model. Infant but not fetal survival was most impaired after a recent takeover of the alpha-male position by an immigrant male. Furthermore, infant survival probability increased when there was an increase in number of group adult females and rainfall. Fetal survival probability also increased with an increase of these 2 factors, but more in high-ranking than low-ranking females. Fetal survival, unlike that of infants, was also improved by an increase of intergroup encounter rates. Our study thus stresses the importance of survival analyses using a multivariate approach and encompassing more than a single offspring stage to investigate the determinants of female direct fitness. We further provide evidence for fitness costs and benefits of group living, possibly deriving from high pressures of both within- and between-group competition, in a wild primate population

Mother-male bond, but not paternity, influences male-infant affiliation in wild crested macaques

In promiscuous primates, interactions between adult males and infants have rarely been investigated. However, recent evidence suggests that male affiliation towards infants has an influence on several aspects of the infants’ life. Furthermore, affiliations may be associated with male reproductive strategy. In this study, we examined which social factors influenced male-infant affiliation initiated by either male or infant, in wild crested macaques (Macaca nigra). We combined behavioral data and genetic paternity analysis from 30 infants living in three wild groups in Tangkoko Reserve, Indonesia. Our results indicate that adult males and infants do not interact at random, but rather form preferential associations. The social factors with the highest influence on infant-initiated interactions were male rank and male association with the infant’s mother. While infants initiated affiliations with males more often in the absence of their mothers, adult males initiated more affiliations with infants when their mothers were present. Furthermore, males initiated affiliations more often when they were in the same group at the time the infant was conceived, when they held a high dominance rank or when they had a close relationship with the mother. Interestingly, paternity did not affect male-infant affiliation despite being highly skewed in this species. Overall, our results suggest that adult males potentially associate with an infant to secure future mating with the mother. Infants are more likely to associate with a male to receive better support, suggesting a strategy to increase the chance of infant survival in a primate society with high infant mortality