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Biomedical subjects

T Slagsvold

Publications and source records attributed to T Slagsvold.

9 recordsLinked to original sources

Parasites and supernormal manipulation.

Social parasites may exploit their hosts by mimicking other organisms that the hosts normally benefit from investing in or responding to in some other way. Some parasites exaggerate key characters of the organisms they mimic, possibly in order to increase the response from the hosts. The huge gape and extreme begging intensity of the parasitic common cuckoo chick (Cuculus canorus) may be an example. In this paper, the evolutionary stability of manipulating hosts through exaggerated signals is analysed using game theory. Our model indicates that a parasite's signal intensity must be below a certain threshold in order to ensure acceptance and that this threshold depends directly on the rate of parasitism. The only evolutionarily stable strategy (ESS) combination is when hosts accept all signallers and parasites signal at their optimal signal intensity, which must be below the threshold. Supernormal manipulation by parasites is only evolutionarily stable under sufficiently low rates of parasitism. If the conditions for the ESS combination are not satisfied, rejector hosts can invade using signal intensity as a cue for identifying parasites. These qualitative predictions are discussed with respect to empirical evidence from parasitic mimicry systems that have been suggested to involve supernormal signalling, including evicting avian brood parasites and insect-mimicking Ophrys orchids.

Adaptation, Physiological↗

DNA binding-independent transcriptional activation by the androgen receptor through triggering of coactivators.

Androgens have critical roles in the development and maintenance of the male reproductive system and are important for progression of prostate cancer. The effects of androgens are mediated by the androgen receptor (AR), which is a ligand-modulated transcription factor that belongs to the nuclear receptor superfamily. In the presence of androgens, AR binds to androgen response elements in the vicinity of androgen receptor target genes and activates transcription. In addition, liganded AR can interfere with the activity of other transcription factors, such as activator protein-1 and nuclear factor kappaB, for which DNA binding by AR is not necessary. In this study, we describe a novel ligand-dependent transactivation function for AR that is independent of its DNA binding ability. AR dramatically increased the intrinsic transcriptional activity of the nuclear receptor coactivators glucocorticoid receptor-interacting protein-1 (GRIP1), cAMP response element-binding protein-binding protein, and p300 that are tethered to DNA. This "triggering" phenomenon required both similar and distinctly different regions of AR compared with those needed for ligand-dependent transactivation from androgen-responsive elements. Furthermore, the domains of GRIP1 required for triggering by AR are different from those required when GRIP1 serves as a coactivator for AR at androgen-responsive promoters. These data suggest that triggering may constitute an important part of the mechanism by which AR regulates transcription.

DNA↗

Mutational analysis of the androgen receptor AF-2 (activation function 2) core domain reveals functional and mechanistic differences of conserved residues compared with other nuclear receptors.

A short C-terminal sequence that forms the core of the activation function-2 (AF-2) domain is conserved in members of the nuclear receptor superfamily and is required for their normal biological function. Despite a high degree of sequence similarity, there are differences in the context and structure of AF-2 in different nuclear receptors. To gain deeper insight into these differences, we carried out an extensive mutational analysis of the AF-2 core in the androgen receptor (AR) and compared the changes in transcriptional activity with similar mutations that have previously been generated in other nuclear receptors. Mutagenesis of Met894 to Asp resulted in substantial decreases in both DNA and ligand binding activities and, consequently, a significant drop in ligand-dependent transcriptional activation. In contrast, substitution of Met894 with Ala did not affect DNA or hormone binding, and the transactivation potential was comparable to that of wild-type AR. Mutagenesis of Glu897 either with Val or Ala significantly impaired ligand-dependent activation that was not due to changes in DNA or ligand binding. There are both similarities and distinct differences between these findings compared with previous mutagenesis studies of the corresponding residues in other nuclear receptors. All mutants efficiently interfered with AP-1 activity, indicating that ligand-dependent activation of transcription and interference with AP-1 activity are separable functions in AR. For the Glu897 substitutions, the decrease in ligand-dependent transactivation could partially be reversed by overexpression of GRIP1 (GR-interacting protein 1) or CBP, putative coactivators for AR. However, there was no correlation between ligand-dependent in vitro or in vivo association with coactivators and the ability of the mutants to support ligand-dependent transactivation. This is in contrast to similar mutations in other nuclear receptors that lose interactions with putative coactivators concomitant with their loss of transcriptional activity. However, the Glu897 mutations disrupted the intramolecular interaction between the N-terminal domain and the ligand-binding domain of AR that was recently suggested to be required for normal AR function. We conclude that residues in the AF-2 core domain of AR make distinctly different contributions to its transcriptional activities compared with those of other nuclear receptors studied to date.

Animals↗

Mate choice copying versus preference for actively displaying males by female pied flycatchers.

Should a female copy the mate choice of other females? A female may rank a mated male higher in quality than an unmated male because the former has demonstrated that he is able to attract a female. However, a prospecting female may also avoid a mated male because of the risk that she has to compete with the male's initial mate over access to copulations, breeding resources and male parental care. We studied the mate choice of female pied flycatchers Ficedula hypoleuca, in aviaries divided into three compartments, two for males, and one for a female. A female was allowed to choose (build a nest in a nestbox) between two males after a period when she had been kept in a cage behind a one-way mirror and had presumably seen that one of the males was in the company of another female for 5 h. There was no evidence that females copied the mate choice of conspecific females, or that they avoided males that had recently been in the company of another female. Instead, females apparently chose a mate independently of others, choosing the male showing most courtship display. The latter result explains the consistency in mate choice observed when different females chose between the same pair of males in repeat trials. The ability of females to pick out the same male independently may also explain why a few males obtain most copulations in lekking species. Copyright 1999 The Association for the Study of Animal Behaviour.

Journal Article↗

CREB binding protein is a coactivator for the androgen receptor and mediates cross-talk with AP-1.

Androgens are critical in the development and maintenance of the male reproductive system and important in the progression of prostate cancer. The effects of androgens are mediated through the androgen receptor (AR), which is a ligand-modulated transcription factor that belongs to the nuclear receptor superfamily. In addition to its ability to activate transcription from androgen response elements, AR can inhibit activator protein-1 (AP-1) activity, composed of Jun and Fos oncoproteins, in a ligand-dependent manner. Conversely, when activated, AP-1 can block AR activity. We found that CREB (cAMP response element-binding protein) binding protein (CBP) had a direct role in both of these activities of AR. CBP significantly increased the ability of endogenous AR in LNCaP cells to activate transcription from an AR-dependent reporter construct. On the other hand, repression of AR activity by treatment of LNCaP cells with an activator of AP-1 was largely relieved when CBP was ectopically expressed. AR and CBP can physically interact in vitro as was shown in glutathione S-transferase pulldown assays. Whereas both the N terminus and ligand-binding domain of AR can interact with CBP, a short region in the N terminus of CBP is required for these interactions. As opposed to the interaction of CBP with other nuclear receptors studied so far, CBP-AR interactions were not affected by ligand binding to AR in vitro. These data suggest that CBP is a coactivator for AR in vivo and that the transcriptional interference between AR and AP-1 is the result of competition for limiting amounts of CBP in the cell.

Cyclic AMP Response Element-Binding Protein↗

Experimentally reduced paternity affects paternal effort and reproductive success in pied flycatchers

The question of whether, and how, male birds should change their parental effort in response to reduced paternity is a controversial issue among behavioural ecologists. We report a study on pied flycatchers, Ficedula hypoleuca, in which paternity was manipulated through experimentally induced mate switching during the female's fertile period. The paternity of care-giving males ranged from 0 to 100% of the brood. The number of parental males per nest varied between zero and two, and the amount of male assistance in nestling provisioning had a marked effect on female reproductive success. For 17 monogamous males, provisioning effort and the body mass of nestlings on day 12 were reduced at low levels of paternity. However, the shape of the effort function was not unambiguously determined. Male provisioning effort showed a curvilinear decline, whereas nestling body mass showed a linear decline. Two important assumptions of the theory of optimal parental effort seem to be fulfilled in this case: that males had reliable cues to their paternity, and that paternity is likely to be increased in future (normal) breeding attempts. The fact that males reduced their effort at the expense of the welfare of the offspring suggests that there are significant costs of parental care in this species. Whether a similar response to cuckoldry occurs in unmanipulated breeding situations remains to be studied.Copyright 1998 The Association for the Study of Animal Behaviour.

Journal Article↗

Experimental mate switching in pied flycatchers: male copulatory access and fertilization success

By making female birds pair successively with different males, and analysing the paternity of the eggs laid, it is possible to examine how a male's success in obtaining fertilizations is determined by the timing of his copulatory access to the female. Such an experiment is reported here with pied flycatchers, Ficedula hypoleucaMate switching was induced at different stages within the female's fertile period by removing the resident male. The paternity of the clutch was analysed by microsatellite DNA typing. Removed males had full paternity in the clutch if they were removed as late as after the second egg was laid (day 1), and they lost all paternity if they were removed more than 1 day before the first egg was fertilized (less than day -2). Male switching during the period day -2 to day 1 always resulted in mixed paternity in the clutch. Males that were paired to the female for only a few (1-3) days during this period achieved on average more than one fertilization per access day, with a peak on day -1. Thus, assuming that the timing of observed pair bonds reflects the timing of each male's copulatory access to the female, the first eggs in the laying sequence were fertilized by inseminations occurring shortly before the time of fertilization, whereas the last eggs were fertilized by inseminations taking place several days prior to their fertilization. Our documentation of the most important period for copulatory access has some important implications for understanding sexual behaviour in this species.

Journal Article↗

Brood division in birds in relation to offspring size: sibling rivalry and parental control

In some altricial birds with biparental care, it is the female, and in others the male, that provides more food to the smallest offspring within the brood. Many hypotheses have been proposed to account for such puzzling patterns of parental care. A parsimonious explanation is that no difference exists between the parents in priority of care but that differences arise simply from sibling rivalry, with dominant chicks trying to position themselves closest to the parent that provides most care (the sibling rivalry hypothesis). A refinement of the idea is that parents use the way they approach the chicks to counter selfish offspring and in this way control allocation of care (the parental approaching hypothesis). A comparison across species suggested that female care of the smallest chick within a brood is the ancestral and most common pattern. However, strong variation exists within single populations. In one species, the American robin, Turdus migratorius the sibling rivalry hypothesis and the parental approaching hypothesis were both supported because in broods where males provided more care than females, the largest chick was predominantly fed by the male whereas the smallest chick was predominantly fed by the female. When the male provided less care than the female, an opposite result was found. The same patterns of allocation of care also seemed to exist when chicks were quite immobile just after having left the nest and when their positions were experimentally controlled, suggesting parental control.Copyright 1997 The Association for the Study of Animal BehaviourCopyright 1997The Association for the Study of Animal Behaviour.

Journal Article↗