Predictors of dominance rank and agonistic interactions in captive Livingstone’s fruit bats

Male dominance hierarchies have been studied in many animals but rarely in bats (Chiroptera). The dominance rank of social animals may dictate access to resources and mates; therefore, it has important implications for an individual’s fitness and is crucial for successful captive management. Between January and December 2018, at both Bristol Zoo Gardens (Bristol, UK) and Jersey Zoo (Jersey, British Isles), we observed 19 male Livingstone’s fruit bats Pteropus livingstonii using focal follows for 345 h overall, noting the outcome of all agonistic interactions. We recorded instigators of interactions, along with winners and losers, and analyzed these data using the R-package “EloRating” to create Elo-rating temporal plots of dominance ranks. We used generalized linear mixed models and multiple linear regression to analyze interaction data and test hypotheses regarding predictors of dominance rank, frequency of agonistic interaction, and choice of interaction partner. Age was positively correlated with dominance rank up to around year 9, when an asymptote was attained. Highly ranked bats instigated the most agonistic interactions, and largely directed these interactions at bats with much lower rankings than themselves. Hierarchies were extremely stable throughout the data collection period at both sites. We conclude that Livingstone’s fruit bats have a stable linear dominance hierarchy, with high-ranking, typically older males instigating the most interactions with lowest ranking males to secure dominance rank. This study adds to the limited discourse on Pteropus social behaviors, indicating that some bat species may have social systems similar in complexity to some nonhuman primates.<br/

Xrn1/Pacman affects apoptosis and regulates expression of hid and reaper

Programmed cell death, or apoptosis, is a highly conserved cellular process that is crucial for tissue homeostasis under normal development as well as environmental stress. Misregulation of apoptosis is linked to many developmental defects and diseases such as tumour formation, autoimmune diseases and neurological disorders. In this paper, we show a novel role for the exoribonuclease Pacman/Xrn1 in regulating apoptosis. Using Drosophila wing imaginal discs as a model system, we demonstrate that a null mutation in pacman results in small imaginal discs as well as lethality during pupation. Mutant wing discs show an increase in the number of cells undergoing apoptosis, especially in the wing pouch area. Compensatory proliferation also occurs in these mutant discs, but this is insufficient to compensate for the concurrent increase in apoptosis. The phenotypic effects of the pacman null mutation are rescued by a deletion that removes one copy of each of the pro-apoptotic genes reaper, hid and grim, demonstrating that pacman acts through this pathway. The null pacman mutation also results in a significant increase in the expression of the pro-apoptotic mRNAs, hid and reaper, with this increase mostly occurring at the post-transcriptional level, suggesting that Pacman normally targets these mRNAs for degradation. Our results uncover a novel function for the conserved exoribonuclease Pacman and suggest that this exoribonuclease is important in the regulation of apoptosis in other organisms

Rank-related contrasts in longevity arise from extra-group excursions not delayed senescence in a cooperative mammal

In many cooperatively breeding animal societies, breeders outlive non-breeding subordinates, despite investing heavily in reproduction [1-3]. In eusocial insects, the extended lifespans of breeders arise from specialized slowed aging profiles [1], prompting suggestions that reproduction and dominance similarly defer aging in cooperatively breeding vertebrates, too [4-6]. Although lacking the permanent castes of eusocial insects, breeders of vertebrate societies could delay aging via phenotypic plasticity (similar rank-related changes occur in growth, neuroendocrinology, and behavior [7-10]), and such plastic deferment of aging may reveal novel targets for preventing aging-related diseases [11]. Here, we investigate whether breeding dominants exhibit extended longevity and delayed age-related physiological declines in wild cooperatively breeding meerkats. We show that dominants outlive subordinates but exhibit faster telomere attrition (a marker of cellular senescence and hallmark of aging [12]) and that in dominants (but not subordinates), rapid telomere attrition is associated with mortality. Our findings further suggest that, rather than resulting from specialized aging profiles, differences in longevity between dominants and subordinates are driven by subordinate dispersal forays, which become exponentially more frequent with age and increase subordinate mortality. These results highlight the need to critically examine the causes of rank-related longevity contrasts in other cooperatively breeding vertebrates, including social mole-rats, where they are currently attributed to specialized aging profiles in dominants [4]

Reproductive conflict resolution in cooperative breeders

Female infanticide is common in animal societies where groups comprise multiple co-breeding females. To reduce the risk that their offspring are killed, mothers can synchronize breeding and pool offspring, making it hard for females to avoid killing their own young. However, female reproductive conflict does not invariably result in reproductive synchrony, and we lack a general hypothesis explaining the variation in conflict resolution strategies seen across species. Here, we investigate the fitness consequences of birth timing relative to other females and the prevalence of birth synchrony in cooperatively breeding Kalahari meerkats (Suricata suricatta). We show that, although there would be substantial benefits to females in synchronizing births and reducing their risk of infanticide, birth synchrony is rare. Since precise breeding synchrony has evolved in a related species with similar infanticidal female reproductive conflict, its absence in meerkats requires an evolutionary explanation. We therefore explore the costs and benefits of synchronizing breeding in two theoretical models, each of which contrasts synchrony with an alternative reproductive strategy: (i) breeding opportunistically and accepting fitness losses to infanticide or (ii) suppressing the reproduction of others to prevent infanticide. Our models show that the costs of synchrony constrain its development if subordinates breed infrequently, and that selection instead favors the suppression of subordinate reproduction by the dominant and opportunistic reproduction by subordinates. Together, our results suggest that the resolution of reproductive conflict in animal societies is shaped by differential breeding propensities among female group members, leading to divergent conflict resolution strategies even in closely related species.A European Research Council grant to T.C.-B. (#294494). A. J. was supported by a Henslow Fellowship jointly provided by the Cambridge Philosophical Society and Hughes Hall, Cambridge. The Kalahari Meerkat Project is supported by the Universities of Cambridge, Zurich and Pretoria.https://academic.oup.com/beheco2020-08-29hj2020Mammal Research InstituteZoology and Entomolog

Reproductive conflict resolution in cooperative breeders

Female infanticide is common in animal societies where groups comprise multiple co-breeding females. To reduce the risk that their offspring are killed, mothers can synchronize breeding and pool offspring, making it hard for females to avoid killing their own young. However, female reproductive conflict does not invariably result in reproductive synchrony, and we lack a general hypothesis explaining the variation in conflict resolution strategies seen across species. Here, we investigate the fitness consequences of birth timing relative to other females and the prevalence of birth synchrony in cooperatively breeding Kalahari meerkats (Suricata suricatta). We show that, although there would be substantial benefits to females in synchronizing births and reducing their risk of infanticide, birth synchrony is rare. Since precise breeding synchrony has evolved in a related species with similar infanticidal female reproductive conflict, its absence in meerkats requires an evolutionary explanation. We therefore explore the costs and benefits of synchronizing breeding in two theoretical models, each of which contrasts synchrony with an alternative reproductive strategy: (i) breeding opportunistically and accepting fitness losses to infanticide or (ii) suppressing the reproduction of others to prevent infanticide. Our models show that the costs of synchrony constrain its development if subordinates breed infrequently, and that selection instead favors the suppression of subordinate reproduction by the dominant and opportunistic reproduction by subordinates. Together, our results suggest that the resolution of reproductive conflict in animal societies is shaped by differential breeding propensities among female group members, leading to divergent conflict resolution strategies even in closely related species.A European Research Council grant to T.C.-B. (#294494). A. J. was supported by a Henslow Fellowship jointly provided by the Cambridge Philosophical Society and Hughes Hall, Cambridge. The Kalahari Meerkat Project is supported by the Universities of Cambridge, Zurich and Pretoria.https://academic.oup.com/beheco2020-08-29hj2020Mammal Research InstituteZoology and Entomolog

KDM4B is a master regulator of the estrogen receptor signalling cascade

The importance of the estrogen receptor (ER) in breast cancer (BCa) development makes it a prominent target for therapy. Current treatments, however, have limited effectiveness, and hence the definition of new therapeutic targets is vital. The ER is a member of the nuclear hormone receptor superfamily of transcription factors that requires co-regulator proteins for complete regulation. Emerging evidence has implicated a small number of histone methyltransferase (HMT) and histone demethylase (HDM) enzymes as regulators of ER signalling, including the histone H3 lysine 9 tri-/di-methyl HDM enzyme KDM4B. Two recent independent reports have demonstrated that KDM4B is required for ER-mediated transcription and depletion of the enzyme attenuates BCa growth in vitro and in vivo. Here we show that KDM4B has an overarching regulatory role in the ER signalling cascade by controlling expression of the ER and FOXA1 genes, two critical components for maintenance of the estrogen-dependent phenotype. KDM4B interacts with the transcription factor GATA-3 in BCa cell lines and directly co-activates GATA-3 activity in reporter-based experiments. Moreover, we reveal that KDM4B recruitment and demethylation of repressive H3K9me3 marks within upstream regulatory regions of the ER gene permits binding of GATA-3 to drive receptor expression. Ultimately, our findings confirm the importance of KDM4B within the ER signalling cascade and as a potential therapeutic target for BCa treatment

The effect of high dose antibiotic impregnated cement on rate of surgical site infection after hip hemiarthroplasty for fractured neck of femur : a protocol for a double-blind quasi randomised controlled trial

Background: Mortality following hip hemiarthroplasty is in the range of 10-40% in the first year, with much attributed to post-operative complications. One such complication is surgical site infection (SSI), which at the start of this trial affected 4.68% of patients in the UK having this operation. Compared to SSI rates of elective hip surgery, at less than 1%, this figure is elevated. The aim of this quasi randomised controlled trial (RCT) is to determine if high dose antibiotic impregnated cement can reduce the SSI in patients at 12-months after hemiarthroplasty for intracapsular fractured neck of femur. Methods: 848 patients with an intracapsular fractured neck of femur requiring a hip hemiarthroplasty are been recruited into this two-centre double-blind quasi RCT. Participants were recruited before surgery and quasi randomised to standard care or intervention group. Participants, statistician and outcome assessors were blind to treatment allocation throughout the study. The intervention consisted of high dose antibiotic impregnated cement consisting of 1 gram Clindamycin and 1 gram of Gentamicin. The primary outcome is Health Protection Agency (HPA) defined deep surgical site infection at 12 months. Secondary outcomes include HPA defined superficial surgical site infection at 30 days, 30 and 90-day mortality, length of hospital stay, critical care stay, and complications. Discussion: Large randomised controlled trials assessing the effectiveness of a surgical intervention are uncommon, particularly in the speciality of orthopaedics. The results from this trial will inform evidence-based recommendations for antibiotic impregnated cement in the management of patients with a fractured neck of femur undergoing a hip hemiarthroplasty. If high dose antibiotic impregnated cement is found to be an effective intervention, implementation into clinical practice could improve long-term outcomes for patients undergoing hip hemiarthroplasty

Suicide inhibition of alpha-oxamine synthases:structures of the covalent adducts of 8-amino-7-oxononanoate synthase with trifluoroalanine

The suicide inhibition of the α-oxamine synthases by the substrate analog, L-trifluoroalanine was investigated. The inhibition resulted in the formation of a complex with loss of all three fluorine atoms. Decarboxylation and loss of fluoride occurred immediately after aldimine formation. The inherent flexibility could allow the difluorinated intermediate complex to adopt a suitable conformation. Decarboxylation in the normal mechanism occurs after formation of the ketoacid intermediate.link_to_subscribed_fulltex

Gender-based violence-supportive cognitions in adolescent girls and boys: The function of violence exposure and victimisation

Violence against women and girls is widespread in the Caribbean, which may be due to heightened acceptance of such acts in this specific social context. In spite of this, studies investigating attitudes towards violence and their correlates among participants drawn from the region are missing. In order to address this void in the literature, we examined associations between violence exposure and victimisation and two gender-based violence-related cognitions (attitudes towards male physical domestic violence and social norms regarding physical violence against girls) as well as general beliefs about violence, using structural equation modelling. Participants were a sample of adolescent girls (n = 661; M age = 13.15) and boys (n = 639; M age = 13.22) from two Eastern Caribbean countries, Barbados and Grenada, recruited from 10 primary schools, nine secondary schools, and two youth offender centres. In considering that girls and boys were previously demonstrated to differ in their experiences as well as tolerance of violence, structural models were specified and tested separately for the two sexes. Results indicated that violence victimisation was positively strongly associated with attitudes towards male physical domestic violence and social norms regarding physical violence against girls among boys. Increased violence victimisation among girls, in turn, correlated with increased acceptance of social norms regarding physical violence against girls, but this relationship was weak. Violence exposure did not have any significant associations with any of the attitudinal variables included in the study. We discuss the importance of these findings for the development of appropriate gender-based violence prevention strategies for youths from the Eastern Caribbean

A model for determining cardiac mitochondrial substrate utilisation using stable 13 C-labelled metabolites

Abstract: Introduction: Relative oxidation of different metabolic substrates in the heart varies both physiologically and pathologically, in order to meet metabolic demands under different circumstances. 13C labelled substrates have become a key tool for studying substrate use—yet an accurate model is required to analyse the complex data produced as these substrates become incorporated into the Krebs cycle. Objectives: We aimed to generate a network model for the quantitative analysis of Krebs cycle intermediate isotopologue distributions measured by mass spectrometry, to determine the 13C labelled proportion of acetyl-CoA entering the Krebs cycle. Methods: A model was generated, and validated ex vivo using isotopic distributions measured from isolated hearts perfused with buffer containing 11 mM glucose in total, with varying fractions of universally labelled with 13C. The model was then employed to determine the relative oxidation of glucose and triacylglycerol by hearts perfused with 11 mM glucose and 0.4 mM equivalent Intralipid (a triacylglycerol mixture). Results: The contribution of glucose to Krebs cycle oxidation was measured to be 79.1 ± 0.9%, independent of the fraction of buffer glucose which was U-13C labelled, or of which Krebs cycle intermediate was assessed. In the presence of Intralipid, glucose and triglyceride were determined to contribute 58 ± 3.6% and 35.6 ± 0.8% of acetyl-CoA entering the Krebs cycle, respectively. Conclusion: These results demonstrate the accuracy of a functional model of Krebs cycle metabolism, which can allow quantitative determination of the effects of therapeutics and pathology on cardiac substrate metabolism