Prostate cancer: Re-focusing on androgen receptor signaling

Prostate cancer is the most common, non-dermatologic cancer in men. Since prostate cancer is highly associated with increased age, the incidence of this disease is expected to increase as the population ages. In its initial stages prostate cancer depends upon the actions of androgen, and androgen deprivation therapy induces tumor regression. Currently, androgen deprivation is achieved by either surgical or chemical androgen blockade. Unfortunately, nearly all prostate cancer patients develop tumors that grow despite androgen blockade and ultimately relapse. Many alterations in prostate cancer cells contribute to this state. Although chemotherapy induces short remissions in some patients, there are no curative therapies for metastatic disease. This review summarizes our current understanding in androgen signaling and the mechanisms that allow tumor cells to bypass androgen manipulation therapy. The identification of novel survival pathways and effector molecules that drive androgen independent growth is necessary to develop effective therapies for advanced prostate cancers.     

Inactivation of MOXD2 and S100A15A by exon deletion during human evolution

We devised a bioinformatics method for systematic identification of putative human-specific exon-deletion mutations that occurred after the divergence of human and chimpanzee and experimentally verified 2 of the predicted mutations in MOXD2 and S100A15A genes. MOXD2 gene encodes a monooxygenase that is highly conserved in mammals and is mostly expressed in the olfactory epithelium in mouse. The presence of a deletion of the last 2 exons and a polymorphic nonsense mutation in exon 6 suggests that MOXD2 gene is inactive in humans. S100A15A is a member of the S100 family of calcium-binding proteins, the mouse ortholog of which is expressed during epidermal maturation. Human S100A15A gene is likely to be inactive because the start codon-bearing exon is deleted in human. We propose that modification or inactivation of MOXD2 and S100A15A genes have contributed to the loss of certain smell sense in humans and to the development of human skin.     

Significance of the 19-kDa hemolymph protein HP19 for the development of the rice moth Corcyra cephalonica: morphological and biochemical effects caused by antibody application

The hemolymph protein HP19 of the rice moth, Corcyra cephalonica, mediates the 20-hydroxyecdysone (20E)-dependent acid phosphatase (ACP) activity at a nongenomic level. Affinity-purified polyclonal antibody against HP19 (alphaHP19-IgG) was used in the present study to understand the role of HP19 during the postembryonic development of Corcyra. In the in vitro studies, HP19 action was blocked either by immuno-precipitation using alphaHP19-IgG, prior to its addition to the fat body culture or by the addition of the antibody directly to the culture, along with 20E and hemolymph containing HP19. The alphaHP19-IgG blocked the HP19-mediated 20E-dependent ACP activation. In the in vivo studies, the alphaHP19-IgG was injected into the fully developed last (final/Vth) instar larvae of Corcyra, to complex the HP19 in vivo, in order to block the action of HP19. The injection of alphaHP19-IgG resulted in defective development of larvae, which grew either into non-viable larvae or larval-pupal/pupal-adult intermediates relative to the effect of pre-immune IgG injected controls. The present study shows that HP19 plays an important role in controlling the metamorphosis of Corcyra by regulating the 20E-dependent ACP activity. Coupled with the earlier findings, the ecdysteroid hormone regulates this action at a nongenomic level.     

Indirect benefits for choosy female grasshoppers (Chorthippus biguttulus)?

Since direct benefits are likely to be absent in the grasshopper Chorthippus biguttulus, indirect genetic benefits are a potential explanation for costly female preference. Choosy females may improve their fitness in terms of enhanced attractiveness of sons alone or additionally by improved viability of offspring. We tested the predictions of these two hypotheses by comparing attractiveness-related song traits and viability in offspring of attractive and unattractive grasshopper males. The experiment was conducted with larvae reared under semi natural lab conditions in one year and under natural conditions in the field in the following year. If reared under natural conditions no significant differences in viability and song traits between offspring of attractive and unattractive males could be found. Offspring reared in the lab produced calling songs with a significantly more exact song rhythm when sired by attractive males than offspring of unattractive males. Offspring of attractive males should thus have a theoretical advantage in mate choice, which, however, did not translate into higher attractiveness values in acoustic female choice experiments. Therefore our experiments could not resolve whether female choice in C. biguttulus evolved according to the sexy son hypothesis. Since viability in offspring of attractive males did not differ from offspring of unattractive males, “good genes” seems unlikely to be the underlying mechanism of female choice.     

Clostridium taeniosporum spore ribbon-like appendage structure, composition and genes

Clostridium taeniosporum spores have about 12 large, flat, ribbon-like appendages attached through a common trunk at one spore pole to a previously unknown surface layer outside the coat that is proposed to be called the 'encasement'. Appendages are about 4.5 microm long, 0.5 microm wide and 30 nm thick and taper at the attachment end into a semicircle that is twisted relative to the flat ribbon. Individual fibrils, about 45 nm in length with spherical heads and long thin tails, form a hair-like nap, visible along the appendage edge. Four appendage proteins have been detected: a paralogous pair of 29 kDa (designated P29a and P29b), a glycoprotein of about 37 kDa (designated GP85) and an orthologue of the Bacillus spore morphogenetic protein SpoVM. The P29 proteins consist of duplicated regions and each region includes a domain of unknown function 11. The GP85 glycoprotein contains a collagen-like region. The genes for P29a and b, GP85 and possibly related proteins are closely linked on two small chromosome fragments. Putative sigma(K)-dependent promoters upstream of the P29a and b genes indicate that they likely are expressed late in the mother cell, consistent with their deposition into the layer external to the coat.     

Mosaic cycles in agricultural landscapes of Northwest Europe

Mosaic cycles were originally understood as cyclical regeneration phases in forests. In this review, we shall examine how far the concept can be extended towards cyclical mosaics of habitat quality in patterned landscapes as a special case of ‘dynamic landscapes’. We will concentrate on habitats and plants in European temperate agricultural landscapes and grasslands in particular. Mosaic cycles of habitat quality are characterised by spatiotemporal shifts between disturbance and secondary succession. We found evidence for mosaic cycles in traditional agricultural systems, modern crop farming, and in recent conservation management. The relevant disturbance parameters to describe land-use drivers of mosaic cycles are spatial extent, frequency, and magnitude (biomass loss). Land-use-related drivers are usually regular and deterministic in space and time, with the exception of year-round grazing by free-ranging large herbivores. Fluctuating soil resources such as water and nutrients in interaction with climate variability add a stochastic component to these (land-use-related) drivers. The proportion of deterministic and stochastic components and their autocorrelation in time and space divides purely deterministic mosaic cycles from purely stochastic dynamic landscapes. In a second part, we briefly review plant life-history traits that may facilitate survival of plants in mosaic cycles of habitat quality. Theoretical studies emphasise (i) dispersal functions for extinction and recolonisation processes of metapopulations, (ii) storage effects as a component of buffered population growth in response to temporal fluctuations of habitat quality, and (iii) competitive ability in metacommunities. We propose a simple scheme relating these functions to the temporal and spatial correlation of patterned landscapes. There are only a very limited number of field studies available that give some support for the proposed scheme. We provide perspectives for further research in this field.