Animal societies provide perfect conditions for the spread of infections and are therefore expected to employ mechanisms that reduce the probability of transmitting pathogens to group members [1-4]. Death in nature rarely results from old age but commonly results from diseases. Leaving one's group to die in seclusion might be an efficient way of minimizing the risk of infecting kin. Anecdotal observations of moribund individuals deserting from their groups exist for several species, including humans (e.g., [5]), but have rarely been substantiated by quantitative analysis. Furthermore, to confirm that dying in solitude has evolved because of its altruistic benefits requires refuting the alternative explanation of pathogen manipulation of host behavior. Here we show that workers of the ant Temnothorax unifasciatus dying from fungal infection, uninfected workers whose life expectancy was reduced by exposure to 95% CO(2)[6, 7], and workers dying spontaneously in observation colonies exhibited the same suite of behavior of isolating themselves from their nestmates days or hours before death. Actively leaving the nest and breaking off all social interactions thus occurred regardless of whether individuals were infected or not. Social withdrawal might be a commonly overlooked altruistic trait serving the inclusive fitness interests of dying individuals in social animals.

Oncogenic wingless-related mouse mammary tumour virus (Wnt) signalling, caused by epigenetic inactivation of specific pathway regulators like the putative tumour suppressor secreted frizzled-related protein 1 (SFRP1), may be causally involved in the carcinogenesis of many human solid tumours including breast, colon and kidney cancer. To evaluate the incidence of SFRP1 deficiency in human tumours, we performed a large-scale SFRP1 expression analysis using immunohistochemistry on a comprehensive tissue microarray (TMA) comprising 3448 tumours from 36 organs. This TMA contained 132 different tumour subtypes as well as 26 different normal tissues. Although tumour precursor stages of, for example kidney, colon, endometrium or adrenal gland still exhibited moderate to abundant SFRP1 expression, this expression was frequently lost in the corresponding genuine tumours. We defined nine novel tumour entities with apparent loss of SFRP1 expression, i.e., cancers of the kidney, stomach, small intestine, pancreas, parathyroid, adrenal gland, gall bladder, endometrium and testis. Renal cell carcinoma (RCC) exhibited the highest frequency of SFRP1 loss (89% on mRNA level; 75% on protein level) and was selected for further analysis to investigate the cause of SFRP1 loss in human tumours. We performed expression, mutation and methylation analysis in RCC and their matching normal kidney tissues. SFRP1 promoter methylation was frequently found in RCC (68%, n=38) and was correlated with loss of SFRP1 mRNA expression (p<0.05). Although loss of heterozygosity was found in 16% of RCC, structural mutations in the coding or promoter region of the SFRP1 gene were not observed. Our results indicate that loss of SFRP1 expression is a very common event in human cancer, arguing for a fundamental role of aberrant Wnt signalling in the development of solid tumours. In RCC, promoter hypermethylation seems to be the predominant mechanism of SFRP1 gene silencing and may contribute to initiation and progression of this disease.

Promyelocytic leukemia (PML) bodies are nuclear organelles implicated in intrinsic and innate antiviral defense. The eponymous PML proteins, central to the self-organization of PML bodies, and other restriction factors found in these organelles are common targets of viral antagonism. The 72-kDa immediate-early protein 1 (IE1) is the principal antagonist of PML bodies encoded by the human cytomegalovirus (hCMV). IE1 is believed to disrupt PML bodies by inhibiting PML SUMOylation, while PML was proposed to act as an E3 ligase for IE1 SUMOylation. PML targeting by IE1 is considered to be crucial for hCMV replication at low multiplicities of infection, in part via counteracting antiviral gene induction linked to the cellular interferon (IFN) response. However, current concepts of IE1-PML interaction are largely derived from mutant IE1 proteins known or predicted to be metabolically unstable and globally misfolded. We performed systematic clustered charge-to-alanine scanning mutagenesis and identified a stable IE1 mutant protein (IE1cc172-176) with wild-type characteristics except for neither interacting with PML proteins nor inhibiting PML SUMOylation. Consequently, IE1cc172-176 does not associate with PML bodies and is selectively impaired for disrupting these organelles. Surprisingly, functional analysis of IE1cc172-176 revealed that the protein is hypermodified by mixed SUMO chains and that IE1 SUMOylation depends on nucleosome rather than PML binding. Furthermore, a mutant hCMV expressing IE1cc172-176 was only slightly attenuated compared to an IE1-null virus even at low multiplicities of infection. Finally, hCMV-induced expression of cytokine and IFN-stimulated genes turned out to be reduced rather than increased in the presence of IE1cc172-176 relative to wild-type IE1. Our findings challenge present views on the relationship of IE1 with PML and the role of PML in hCMV replication. This study also provides initial evidence for

The importance of artificial nest boxes for North Island saddlebacks (Philesturnus carunculatus rufusater) on Tiritiri Matangi Island has increased significantly, suggesting that "natural" nesting cavities are now a limited resource for this growing population. The design and position of artificial nest boxes directly affects the likelihood of saddleback use for nesting: small boxes (0.005 and 0.0lm3 ) with large (140-160 mm high) north facing openings had the highest probability of being used. One of the disadvantages of using artificial nest boxes in conservation management is the potential for parasite build-up. Two species of mesostigmatid mites were found in the artificial nest boxes used by saddlebacks on Tiritiri Matangi Island. One was an undescribed species of Dermanyssid mite the other was Ornithonyssus bursa, the fowl mite. The numbers of mites detected increased over the saddleback nesting cycle from September to December. However, our results strongly suggest that, for saddlebacks, no negative correlations exist between mite abundance and chick weight, fledging date, or the number of fledglings produced. Mite abundance was extremely variable and did not correlate with nest box temperature or relative humidity.

Cohesion of social groups requires the suppression of individual selfishness. Indeed, worker egg laying in insect societies is usually suppressed or punished through aggression and egg removal. The effectiveness of such "policing" is expected to increase with decreasing relatedness, as inclusive fitness of group members is more strongly affected by selfish worker reproduction when group members are less closely related to each other. As inclusive fitness is also influenced by the costs and benefits of helping, the effectiveness of policing should decrease with increasing colony size, because the costs for the whole colony from selfish worker reproduction are proportionally reduced in large groups. Here, we show that policing effectiveness in colonies of the ant Temnothorax unifasciatus is low in large groups and high in small groups when relatedness is high. When we experimentally decreased the relatedness in groups, the policing effectiveness reached the same high level as in small, highly related groups, irrespective of group size. Therefore, our results indicate that policing effectiveness is simultaneously shaped by relatedness and group size, that is, an ecological factor. This may have major implications for testing policing across species of animals.