The ligand binding profiles of estrogen receptors alpha and beta are species dependent

Estrogens and selective estrogen receptor modulators are used for the treatment and prevention of conditions resulting from menopause. Since estrogens exert their activity by binding to nuclear receptors, there is intense interest in developing new ligands for the two known estrogen receptor subtypes, ER-alpha and ER-beta. Characterization assays used to profile new estrogen receptor ligands often utilize receptors from different species, with the assumption that they behave identically. To test this belief, we have profiled a number of estrogens, other steroids, phytoestrogens and selective estrogen receptor modulators in a solid phase radioligand binding assay using recombinant protein for human, rat, and mouse ER-alpha and ER-beta. Certain compounds show species dependent binding preferences for ER-alpha or ER-beta, leading to differences in receptor subtype selectivity. The amino acids identified by crystallography as lining the ligand binding cavity are the same among the three species, suggesting that as yet unidentified amino acids contribute to the structure of the binding site. We conclude from this analysis that the ability of a compound to selectively bind to a particular ER subtype can be species dependent.     

Elution of cell-bound anti-prostatic epithelial antibodies after multiple cryotherapy of carcinoma of the prostate

Antibodies reactive with the cytoplasmic membrane or intercellular areas of autologous human and monkey prostatic secretory epithelial cells have been demonstrated by immunofluorescence in an eluate prepared from prostatic tissue obtained from a patient with metastatic adenocarcinoma of the prostate (CaP) after multiple cryotherapy of his primary prostatic tumour. While limited to the study of one patient, elution of anti-prostatic antibodies offers further documentation to previous studies pointing toward the participation of immunologic processes in CaP.     

Habitat differentiation among three Nigeria–Cameroon chimpanzee (Pan troglodytes ellioti) populations

Ecological niche models (ENMs) are often used to predict species distribution patterns from datasets that describe abiotic and biotic factors at coarse spatial scales. Ground‐truthing ENMs provide important information about how these factors relate to species‐specific requirements at a scale that is biologically relevant for the species. Chimpanzees are territorial and have a predominantly frugivorous diet. The spatial and temporal variation in fruit availability for different chimpanzee populations is thus crucial, but rarely depicted in ENMs. The genetic and geographic distinction within Nigeria–Cameroon chimpanzee (Pan troglodytes ellioti) populations represents a unique opportunity to understand fine scale species‐relevant ecological variation in relation to ENMs. In Cameroon, P. t. ellioti is composed of two genetically distinct populations that occupy different niches: rainforests in western Cameroon and forest–woodland–savanna mosaic (ecotone) in central Cameroon. We investigated habitat variation at three representative sites using chimpanzee‐relevant environmental variables, including fruit availability, to assess how these variables distinguish these niches from one another. Contrary to the assumption of most ENM studies that intact forest is essential for the survival of chimpanzees, we hypothesized that the ecotone and human‐modified habitats in Cameroon have sufficient resources to sustain large chimpanzee populations. Rainfall, and the diversity, density, and size of trees were higher at the rainforest. The ecotone had a higher density of terrestrial herbs and lianas. Fruit availability was higher at Ganga (ecotone) than at Bekob and Njuma. Seasonal variation in fruit availability was highest at Ganga, and periods of fruit scarcity were longer than at the rainforest sites. Introduced and secondary forest species linked with anthropogenic modification were common at Bekob, which reduced seasonality in fruit availability. Our findings highlight the value of incorporating fine scale species‐relevant ecological data to create more realistic models, which have implications for local conservation planning efforts.     

Gene flow in wild chimpanzee populations: what genetic data tell us about chimpanzee movement over space and time

The isolation of phylogenetically distinct primate immunodeficiency viruses from at least seven wild-born, captive chimpanzees indicates that viruses closely related to HIV-1 may be endemic in some wild chimpanzee populations. The search for the chimpanzee population or populations harbouring these viruses is therefore on. This paper attempts to answer the question of whether or not such populations of chimpanzees are likely to exist at all, and, if so, where they are likely to be found. We summarize what is known about gene flow in wild populations of chimpanzees, both between major phylogeographical subdivisions of the species, and within these subdivisions. Our analysis indicates that hitherto undocumented reproductively isolated chimpanzee populations may in fact exist. This conclusion is based on the observation that, despite limited geographical sampling and limited numbers of genetic loci, conventional notions of the nature and extent of chimpanzee gene flow have recently been substantially revised. Molecular genetic studies using mitochondrial DNA sequences and hypervariable nuclear microsatellite markers have indicated the existence of heretofore undocumented barriers to chimpanzee gene flow. These studies have identified at least one population of chimpanzees genetically distinct enough to be classified into a new subspecies (Pan troglodytes vellerosus). At the same time, they have called into question the long-accepted genetic distinction between eastern chimpanzees (Pan troglodytes schweinfurthii) and western equatorial chimpanzees (Pan troglodytes troglodytes). The same studies have further indicated that gene flow between local populations is more extensive than was previously thought, and follows patterns sometimes inconsistent with those documented through direct behavioural observation. Given the apparently incomplete nature of the current understanding of chimpanzee gene flow in equatorial Africa, it seems reasonable to speculate that a chimpanzee population or populations may exist which both harbour the putative HIV-1 ancestor, and which have remained reproductively isolated from other chimpanzee populations over the time-scale relevant to the evolution of the SIVcpz-HIV-1 complex of viruses. Continued extensive sampling of wild chimpanzee populations, both for their genes and their viruses, should be performed quickly considering the high probability of extinction that many wild chimpanzee populations face today. The history of human-chimpanzee contacts is discussed.     

Bacterial Cyanuric Acid Hydrolase for Water Treatment

Di- and trichloroisocyanuric acids are widely used as water disinfection agents, but cyanuric acid accumulates with repeated additions and must be removed to maintain free hypochlorite for disinfection. This study describes the development of methods for using a cyanuric acid-degrading enzyme contained within nonliving cells that were encapsulated within a porous silica matrix. Initially, three different bacterial cyanuric acid hydrolases were compared: TrzD from Acidovorax citrulli strain 12227, AtzD from Pseudomonas sp. strain ADP, and CAH from Moorella thermoacetica ATCC 39073. Each enzyme was expressed recombinantly in Escherichia coli and tested for cyanuric acid hydrolase activity using freely suspended or encapsulated cell formats. Cyanuric acid hydrolase activities differed by only a 2-fold range when comparing across the different enzymes with a given format. A practical water filtration system is most likely to be used with nonviable cells, and all cells were rendered nonviable by heat treatment at 70°C for 1 h. Only the CAH enzyme from the thermophile M. thermoacetica retained significant activity under those conditions, and so it was tested in a flowthrough system simulating a bioreactive pool filter. Starting with a cyanuric acid concentration of 10,000 μM, more than 70% of the cyanuric acid was degraded in 24 h, it was completely removed in 72 h, and a respike of 10,000 μM cyanuric acid a week later showed identical biodegradation kinetics. An experiment conducted with water obtained from municipal swimming pools showed the efficacy of the process, although cyanuric acid degradation rates decreased by 50% in the presence of 4.5 ppm hypochlorite. In total, these experiments demonstrated significant robustness of cyanuric acid hydrolase and the silica bead materials in remediation.