Female‐biased sex allocation and lack of inbreeding avoidance in Cubitermes termites

Sexually reproducing organisms face a strong selective pressure to find a mate and ensure reproduction. An important criterion during mate‐selection is to avoid closely related individuals and subsequent potential fitness costs of resulting inbred offspring. Inbreeding avoidance can be active through kin recognition during mate choice, or passive through differential male and female‐biased sex ratios, which effectively prevents sib‐mating. In addition, sex allocation, or the resources allotted to male and female offspring, can impact mating and reproductive success. Here, we investigate mate choice, sex ratios, and sex allocation in dispersing reproductives (alates) from colonies of the termite Cubitermes tenuiceps. Termites have a short time to select a mate for life, which should intensify any fitness consequences of inbreeding. However, alates did not actively avoid inbreeding through mate choice via kin recognition based on genetic or environmental cues. Furthermore, the majority of colonies exhibited a female‐biased sex ratio, and none exhibited a male‐bias, indicating that differential bias does not reduce inbreeding. Sex allocation was generally female‐biased, as females also were heavier, but the potential fitness effect of this costly strategy remains unclear. The bacterium Wolbachia, known in other insects to parasitically distort sex allocation toward females, was present within all alates. While Wolbachia is commonly associated with termites, parasitism has yet to be demonstrated, warranting further study of the nature of the symbiosis. Both the apparent lack of inbreeding avoidance and potential maladaptive sex allocation implies possible negative effects on mating and fitness.     

Investigations of the transfructosylation reaction by fructosyltransferase from B. subtilis NCIMB 11871 for the synthesis of the sucrose analogue galactosyl-fructoside

The exo-fructosyltransferase produced from B. subtilis NCIMB 11871 strain transfers the fructose moiety from donor alpha12 linked saccharides such as sucrose, raffinose and stachyose to the acceptor d-galactose, leading to the sucrose analogue, galactosyl-fructoside. Here, we report detailed kinetic studies. The enzyme showed a remarkably high optimal temperature at 50 degrees C and was effectively immobilised on Eupergit C 250 L and Trisopor-Amino. This is also the first report about the equilibrium of the transfructosylation reaction, its activation energy determination, the structure of the product and its preparative scale isolation.     

5-Heteroatom substituted pyrazoles as canine COX-2 inhibitors. Part III: molecular modeling studies on binding contribution of 1-(5-methylsulfonyl)pyrid-2-yl and 4-nitrile

The structure-activity relationship toward canine COX-1 and COX-2 in vitro whole blood activity of 4-hydrogen versus 4-cyano substituted 5-aryl or 5-heteroatom substituted N-phenyl versus N-2-pyridyl sulfone pyrazoles is discussed. The differences between the pairs of compounds with the 4-nitrile pyrazole derivatives having substantially improved in vitro activity are highlighted for both COX-2 and COX-1. This difference in activity may be due to the contribution of the hydrogen bond of the 4-cyano group with Ser 530 as shown by our molecular modeling studies. In addition, our model suggests a potential contribution from hydrogen bonding of the pyridyl nitrogen to Tyr 355 for the increased activity over the phenyl sulfone analogs.     

Microwave-assisted glycosylation for the synthesis of glycopeptides

An efficient one-step synthesis of O-linked glycosylamino acids is described. This methodology converts commercially available peracetylated mono- and disaccharides activated by cheap and environmentally safe FeCl(3) under microwave irradiation with Fmoc-Ser-OBn to the corresponding beta-glycosides in short reaction times and moderate yields.     

Perinatal testosterone surge is required for normal adult bone size but not for normal bone remodeling

Although testosterone (T) has striking effects on mature skeletal size and structure, it is not clear whether this depends exclusively on adult circulating levels of T or whether additional early-life factors also play a role. We have compared the androgen-deficient hypogonadal (hpg) mutant mouse with intact, orchidectomized, and T-treated non-hpg mice to determine relative contributions of adult and perinatal T to bone growth and development. At 3 wk of age, although trabecular and cortical bone structure was normal, bone turnover was significantly altered in hpg male mice; osteoid volume (OV/BV) and osteoblast surface (ObS/BS) were significantly lower and osteoclast surface (OcS/BS) significantly higher in hpg mice compared with age-matched non-hpg mice, pointing to a role for the perinatal T surge in determining bone turnover levels before sexual maturity. At 9 wk of age, the hpg bone phenotype mimicked closely that of age-matched non-hpg mice that had been orchidectomized at 3 wk of age, including low trabecular bone mass and high bone turnover. These bone phenotypes of hpg and orchidectomized non-hpg mice were all prevented by replacement doses of T or dihydrotestosterone (DHT), suggesting that these are determined by adult sex steroid hormones. In contrast, a short bone phenotype that could not be prevented by T or DHT treatment was observed in 9-wk-old hpg mice yet not in intact or castrated non-hpg mice. These data suggest a role for the perinatal T surge in determining adult bone length and confirms that adult circulating T determines adult bone density.     

Inhibitory effects of the HDAC inhibitor valproic acid on prostate cancer growth are enhanced by simultaneous application of the mTOR inhibitor RAD001

AimsTo analyze the combined impact of the histone deacetylase (HDAC) inhibitor valproic acid (VPA) and the mammalian target of rapamycin (mTOR) inhibitor RAD001 on prostate cancer cell growth.Main methodsPC-3, DU-145 and LNCaP cells were treated with RAD001, VPA or with an RAD001–VPA combination for 3 or 5 days. Tumor cell growth, cell cycle progression and cell cycle regulating proteins were then investigated by MTT assay, flow cytometry and Western blotting, respectively. Effects of drug treatment on cell signaling pathways were determined.Key findingsSeparate application of RAD001 or VPA distinctly reduced tumor cell growth and impaired cell cycle progression. Significant additive effects were evoked when both drugs were used in concert. Particularly, the cell cycle regulating proteins cdk1, cdk2, cdk4 and cyclin B were reduced, whereas p21 and p27 were enhanced by the RAD001–VPA combination. Signaling analysis revealed deactivation of EGFr, ERK1/2 and p70S6k. Phosphorylation of Akt was diminished in DU-145 but elevated in PC-3 and LNCaP cells.SignificanceThe RAD001–VPA combination exerted profound antitumor properties on a panel of prostate cancer cell lines. Therefore, simultaneous blockage of HDAC and mTOR related pathways should be considered when designing novel therapeutic strategies for treating prostate carcinoma.