Gonadal control of male scent in the tarmarin Saguinus fuscicollis (Callitrichidae, Primates)

Spontaneous responses to the scent marks of male Saguinus fuscicolliswere tested in experiments where the subjects received a choicebetween scent of intact males and castrated males. Male tamarinsdiscriminated between the odors of intact and castrated males,both on the basis of fresh individual scent marks and on thebasis of marks from several donors pooled in methanol. Theirdiscriminatory response to pooled odors was more pronouncedthan that to individual odors. Females discriminated betweenintact and castrated male scents only on the basis of pooledsamples. This result shows that castration causes changes inthe odor of males. The difference in the response of the tamarinsto individual scent marks as compared to pooled samples is discussedin terms of quantitative changes caused by extraction and ofindividual recognition.     

Synthesis and evaluation of arylaminoethyl amides as noncovalent inhibitors of cathepsin S. Part 3: heterocyclic P3

A series of N(alpha)-2-benzoxazolyl-alpha-amino acid-(arylaminoethyl)amides were identified as potent, selective, and noncovalent inhibitors of cathepsin S. Structure-activity relationships including strategies for modulating the selectivities among cathepsins S, K, and L, and in vivo pharmacokinetics are discussed. A X-ray structure of compound 3 bound to the active site of cathepsin S is also reported.     

Social influences on first reproductive success and related behaviors in the saddle-back tamarin (Saguinus fuscicollis,callitrichidae)

Some aspects of sociosexual behavior and the age at which maturing females experienced their first evident pregnancy and at which maturing males caused their first evident pregnancy were recorded in Saguinus fuscicolliscohabiting from 6 months of age with either an adult or a maturing sex partner. The following pair combinations and trios were studied: young male -young female, young male-adult female, adult male-young female, and adult male-young male-young female. The most frequent type of social interaction between young animals was rough and tumble play, while huddling was the most frequent interaction between young animals and their adult partners. Grooming and sexual interactions were very infrequent and there were no differences in the frequencies of these interactions among subject groups. Maturing females cohabiting with an adult male conceived significantly earlier than maturing females cohabiting with a male of their own age. Maturing males cohabiting with adult females sired offspring at a significantly earlier age than males cohabiting with a female of their own age. Some possible behavioral and physiological processes involved in the causation of early reproductive success in young tamarins cohabiting with adults are discussed. Saguinus fuscicollis fuscicollis andSaguinus fuscicollis illigeri.     

Escherichia coli alpha-haemolysin induces focal leaks in colonic epithelium: a novel mechanism of bacterial translocation

Extraintestinal pathogenic Escherichia coli (ExPEC) are usually harmless colonizer of the intestinal microflora. However, they are capable to translocate and cause life-threatening disease. Translocation of ExPEC isolates was quantified in colonic monolayers. Transepithelial resistance (R(t)) was monitored and local changes in conductivity analysed with conductance scanning. Confocal microscopy visualized the translocation route. Corroboratory experiments were performed on native rat colon. One translocating strain E. coli O4 was identified. This translocation process was associated with an R(t) decrease (36 +/- 1% of initial resistance) beginning only 2 h after inoculation. The sites of translocation were small defects in epithelial integrity (focal leaks) exhibiting highly increased local ion permeability. Translocation was enhanced by preincubation of monolayers with tumour necrosis factor-alpha or interleukin-13. Mutant strains lacking alpha-haemolysin lost the ability to induce focal leaks, while this effect could be restored by re-introducing the haemolysin determinant. Filtrate of a laboratory strain carrying the alpha-haemolysin operon was sufficient for focal leak induction. In native rat colon, E. coli O4 decreased R(t) and immunohistology demonstrated focal leaks resembling those in cell monolayers. E. coli alpha-haemolysin is able to induce focal leaks in colonic cell cultures as well as in native colon. This process represents a novel route of bacterial translocation facilitated by pro-inflammatory cytokines.     

3,4,5-Trisubstituted isoxazoles as novel PPARdelta agonists: Part 1

We report the identification of a novel series of trisubstituted isoxazoles as PPAR activators from a high-throughput screen. A series of structural optimizations led to improved efficacy and excellent functional receptor selectivity for PPARdelta. The isoxazoles represent a series of agonists which display a scaffold that lies outside the typical PPAR agonist motif.