Promiscuous tendencies in the round-eared sengi: a male’s perspective

Although monogamy is interpreted as risk-adverse strategy by reducing intra-sexual conflicts, most pair-living males increase their reproductive success by engaging in extra-pair copulations. However, little is known about costs involved in such extra-pair attempts from the male’s perspective. We investigated promiscuous tendencies of paired Macroscelides proboscideus (round-eared elephant-shrew or round-eared sengi), a pair-living small mammal occurring in southern Africa. In particular, we measured potential costs of extra-pair attempts for the males. For this, we conducted laboratory experiments, involving interactions between neighbouring male–female pairs. Data collection included direct behavioural observations and establishing the morphological and physiological characteristics of males. Both sexes intruded into the neighbouring area, and initiated sexual behaviour with neighbours of the opposite sex. Males which displayed a higher marking frequency in the neighbouring area received more sexually motivated behaviour from neighbouring females. Resident males attacked intruding males. Aggression experienced by and marking behaviour of intruding males was positively correlated with body mass losses. Furthermore, glucocorticoid levels, determined from analyses of faeces and urine samples, correlated positively with body mass losses and marking behaviour of intruding males, indicating costs of intruding. We conclude that male as well as female round-eared sengis have promiscuous tendencies. Although interactions with neighbouring females may offer potential benefits for males in terms of enhanced reproductive success, males also seem to pay substantial costs, as indicated by body mass losses and elevated stress hormone levels.     

Induction of enhanced immunity to intestinal nematodes using IL-9-producing dendritic cells

Dendritic cells can be considered natural adjuvants and are able to act as cellular vaccines to protect against disease. Adoptive transfer of Ag-pulsed bone marrow-derived dendritic cells (BMDCs) enhanced expulsion of the intestinal nematode, Trichinella spiralis, from the small intestine. IL 9 is a critical cytokine in protective immunity to intestinal nematode infection and is believed to enhance Th2 immune responses. Deriving dendritic cells from an IL-9 transgenic (IL-9t) mouse has enabled a detailed investigation of the importance of IL-9 during Ag presentation. Indeed, IL-9t dendritic cells significantly enhanced T cell proliferation and Th2 responses and, after adoptive transfer, enhanced parasite-specific IgG1 and intestinal mastocytosis in vivo, leading to accelerated expulsion of adult worms from the intestine. Overall, this paper demonstrates that dendritic cell vaccination can be used to successfully protect the host against intestinal nematode infection and suggests that IL-9 can act as a potent type 2 adjuvant during Ag presentation and the early stages of Th2 activation.     

In situ phosphorylation of immobilized receptors on biosensor surfaces: application to E-cadherin/beta-catenin interactions

Phosphorylation is a key posttranslational modification for modulating biological interactions. Biosensor technology is ideally suited for examining in real time the role of phosphorylation on protein-protein interactions in signaling pathways. We have developed processes for on-chip phosphorylation of immobilized receptors on biosensor surfaces. These processes have been used to analyze E-cadherin/beta-catenin interactions. Phosphorylation of the intracellular domain (ICD) of E-cadherin modulates its affinity to beta-catenin and consequently the strength of cell-cell adhesion. We have phosphorylated immobilized E-cadherin ICD in situ using casein kinase 1 (CK1), casein kinase 2 (CK2), and src. On-chip phosphorylation of E-cadherin was confirmed using anti-phosphoserine and anti-phosphotyrosine antibodies. The binding of beta-catenin to E-cadherin was analyzed quantitatively. CK1 phosphorylation of E-cadherin increased the binding affinity to beta-catenin from approximately 230 to 4 nM. A similar increase in affinity, from 260 to 4 nM, was obtained with CK2 phosphorylation of E-cadherin. However, phosphorylation by src kinase decreased the affinity constant from approximately 260 nM to 4 microM. Interestingly, phosphorylation of E-cadherin by CK1 or CK2 prevented the inhibition of beta-catenin binding by src phosphorylation.     

RGS2 determines short-term synaptic plasticity in hippocampal neurons by regulating Gi/o-mediated inhibition of presynaptic Ca2+ channels

RGS2, one of the small members of the regulator of G protein signaling (RGS) family, is highly expressed in brain and regulates G(i/o) as well as G(q)-coupled receptor pathways. RGS2 modulates anxiety, aggression, and blood pressure in mice, suggesting that RGS2 regulates synaptic circuits underlying animal physiology and behavior. How RGS2 in brain influences synaptic activity is unknown. We therefore analyzed the synaptic function of RGS2 in hippocampal neurons by comparing electrophysiological recordings from RGS2 knockout and wild-type mice. Our study provides a general mechanism of the action of the RGS family containing RGS2 by demonstrating that RGS2 increases synaptic vesicle release by downregulating the G(i/o)-mediated presynaptic Ca(2+) channel inhibition and therefore provides an explanation of how regulation of RGS2 expression can modulate the function of neuronal circuits underlying behavior.     

Vertical jumping performance of bonobo (Pan paniscus) suggests superior muscle properties

Vertical jumping was used to assess muscle mechanical output in bonobos and comparisons were drawn to human jumping. Jump height, defined as the vertical displacement of the body centre of mass during the airborne phase, was determined for three bonobos of varying age and sex. All bonobos reached jump heights above 0.7 m, which greatly exceeds typical human maximal performance (0.3-0.4m). Jumps by one male bonobo (34 kg) and one human male (61.5 kg) were analysed using an inverse dynamics approach. Despite the difference in size, the mechanical output delivered by the bonobo and the human jumper during the push-off was similar: about 450 J, with a peak power output close to 3000 W. In the bonobo, most of the mechanical output was generated at the hips. To account for the mechanical output, the muscles actuating the bonobo's hips (directly and indirectly) must deliver muscle-mass-specific power and work output of 615 Wkg-1 and 92 Jkg-1, respectively. This was twice the output expected on the basis of muscle mass specific work and power in other jumping animals but seems physiologically possible. We suggest that the difference is due to a higher specific force (force per unit of cross-sectional area) in the bonobo.     

Fatty acid amide hydrolase inhibitors. Surprising selectivity of chiral azetidine ureas

We report the discovery of a novel, chiral azetidine urea inhibitor of Fatty Acid Amide Hydrolase (FAAH,) and describe the surprising species selectivity of VER-156084 versus rat and human FAAH and also hCB1.     

Discovery of novel aminothiadiazole amides as selective EP3 receptor antagonists

This Letter discloses a series of 2-aminothiadiazole amides as selective EP₃ receptor antagonists. SAR optimization resulted in compounds with excellent functional activity in vitro. In addition, efforts to optimize DMPK properties in the rat are discussed. These efforts have resulted in the identification of potent, selective EP₃ receptor antagonists with excellent DMPK properties suitable for in vivo studies.