Review: unchained maladie - a reassessment of the role of Ubb(+1) -capped polyubiquitin chains in Alzheimer's disease.

Molecular misreading allows the formation of mutant proteins in the absence of gene mutations. A mechanism has been proposed by which a frameshift mutant of the ubiquitin protein, Ubb(+1) , which accumulates in an age-dependent manner as a result of molecular misreading, contributes to neuropathology in Alzheimer's disease (Lam et al. 2000). Specifically, in the Ubb(+1) -mediated proteasome inhibition hypothesis Ubb(+1) 'caps' unanchored (that is, nonsubstrate linked) polyubiquitin chains, which then act as dominant inhibitors of the 26S proteasome. A review of subsequent literature indicates that this original hypothesis is broadly supported, and offers new insights into the mechanisms accounting for the age-dependent accumulation of Ubb(+1) , and how Ubb(+1) -mediated proteasome inhibition may contribute to Alzheimer's disease. Further, recent studies have highlighted a physiological role for free endogenous unanchored polyubiquitin chains in the direct activation of certain protein kinases. This raises the possibility that Ubb(+1) -capped unanchored polyubiquitin chains could also exert harmful effects through the aberrant activation of tau or other ubiquitin-dependent kinases, neuronal NF-κB activity or NF-κB-mediated neuroinflammatory processes.

Fat reserves and perceived predation risk in the great tit, Parus major.

The fat reserves of small birds are built up daily as insurance against starvation. They are believed to reflect a trade-off between the risks of starvation and predation such that in situations of high predation risk birds are expected either to reduce their fat reserves in response to mass-dependent predation risk or to increase them in response to foraging interruptions. We assessed the effect on fat reserves of experimentally altering the perceived (but not the actual) risk of predation of wild great tits at a winter feeding site. The perceived predation risk was alternated between 'safe' and 'risky'. Increasing the perceived risk of predation involved 'swooping' a model sparrowhawk over the feeder at four unpredictable times each day using a remote mechanism We produce evidence that the experiment was suceessfull in altering the perceived risk of predation. As predicted from the hypothesis of mass-dependent predation risk, great tits (Parus major) carried significantly reduced fat reserves during the 'risky' treatment. Furthermore, dominant individuals were able to reduce their reserves more than subordinates. As birds returned to feeders within seconds after a predator 'attack', the reduction in fat reserves cannot be attributed to an interruption in feeding.

Conditioning pigeons to discriminate naturally lit insect specimens.

Pigeons (Columba livia) were trained on a visual discrimination task using a novel apparatus which enabled pinned specimens of insects, illuminated by natural daylight, to be presented under a pecking key transparent to ultraviolet light. Three birds showed evidence of learning to discriminate between sets of wasp and fly specimens. This response transferred to specimens of four hoverfly species, the strength of the response varying between the different hoverfly species. This conditioning technique offers a promising means of analysing mechanisms of visual processing in birds that are relevant to theories of the evolution of camouflage and mimicry.

Bioactive and immunoreactive FSH concentrations in ewe and ram lambs over the first year of life.

Several studies suggest that the concentration of immunoreactive (I) FSH measured in peripheral plasma by radioimmunoassay does not always reflect the level of bioactive (B) hormone capable of eliciting a biological response (e.g. oestradiol synthesis by Sertoli cells in vitro). The aim of this study was to measure both B-FSH and I-FSH concentrations in male and female sheep during the first year of life, and to relate this to pubertal development. The hypothesis being tested was that B-FSH is present in both male and female sheep during the prepubertal period and that discrete changes in B-FSH are associated with the onset of puberty. Eight ewe lambs and eight rams lambs were blood sampled fortnightly form 2 to 52 weeks of age. All samples were assayed for B-FSH content. Pubertal development was monitored in ewe lambs from behavioural oestrus and from plasma progesterone concentrations, and in ram lambs from penile and testicular development and from plasma testosterone concentrations. Mean I-FSH concentrations varied significantly with time after birth, in both females and males (P < 0.01). In contrast, B-FSH was found to vary with time in females only (P < 0.01). Around the expected time of puberty in ram lambs (i.e. at 30-40 weeks of age), and thereafter, I-FSH concentrations were undetectable (< 0.2 ng ml-1), whereas the B-FSH concentrations were measurable at concentrations up to twice the assay detection limit (0.8 ng ml-1) until 38 weeks of age. In ewe lambs, but not ram lambs, there was a significant linear relationship between B-FSH and I-FSH values (R = 0.595; P < 0.005). When standardised about the time of puberty, B-FSH (P < 0.05) but not I-FSH was significantly higher in ewe lambs that failed to reach puberty. No differences for either B-FSH or I-FSH between pubertal and non-pubertal ram lambs were noted. In summary, B-FSH was soften measurable in plasma throughout prepubertal development in sheep and the concentrations often differed from those of I-FSH, especially in ram lambs. However, there appeared to be no discrete change in B-FSH that could be directly related to specific pubertal events. It is concluded that although FSH may be a prerequisite for prepubertal testicular development and/or ovarian follicular growth, it is not a critical factor in determining whether puberty is attained during the first year of life in this seasonally breeding species.

Bioactive follicle-stimulating hormone concentrations in plasma during the estrous cycle of the ewe.

Bioactive FSH (B-FSH) concentrations in plasma were determined during the ovine estrous cycle by means of an in vitro bioassay. The concentrations of B-FSH were elevated during and after the preovulatory LH surge and were significantly (p < 0.05) lower during the late-luteal to mid-follicular phases compared with the mid-luteal phase. A significant (p < 0.05) increase in B-FSH was found about 36 h before the LH surge, at a time when the immunoreactive FSH (I-FSH) concentrations were low and unchanged. The plasma B/I ratio for FSH was relatively constant during the luteal phase; it then increased significantly (p < 0.05) before the LH surge and decreased again at the time of the LH surge itself. Pulsar analysis showed that there were 4 peaks of B-FSH throughout the estrous cycle with 2 during the luteal phase, 1 after the LH surge, and the other either during the follicular phase or associated with the LH surge. For I-FSH there were approximately 8 peaks throughout the cycle with 4 during the luteal phase, 2 after the LH surge, and 1 each during the follicular phase and the preovulatory LH surge. There was a weak negative correlation between I-FSH and immunoreactive inhibin (I-inhibin) during most of the estrous cycle, but B-FSH and the B/I ratio were only correlated (negatively) with I-inhibin in the 24 h before the preovulatory LH surge. These findings suggest that there are significant changes in the circulating isoforms of FSH during the ovine estrous cycle that may affect the growth of antral follicles developing towards ovulation.