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Sonja Schmidt Birthe Gericke Giulio Fracasso Dunia Ramarli Marco Colombatti Hassan Y. Naim 《PloS one》2013,8(6)
Prostate-specific membrane antigen (PSMA) is a type-II membrane glycoprotein that was initially identified in LNCaP cells. It is expressed at elevated levels in prostate cancer. In view of the correlation between the expression levels of PSMA and disease grade and stage, PSMA is considered to be one of the most promising biomarkers in the diagnosis and treatment of prostate cancer. In LNCaP cells PSMA undergoes internalization via clathrin-coated pits followed by accumulation in the endosomes. PSMA associates with different types of detergent-resistant membranes (DRMs) along the secretory pathway. Its mature form is mainly insoluble in Lubrol WX, but does not associate with Triton X-100-DRMs. To understand the mechanism of PSMA internalization we investigated its association during internalization with DRMs. For this purpose, internalization was induced by antibody cross-linking. We demonstrate at the biochemical and cell biological levels that: [i] exclusively homodimers of PSMA are associated with Lubrol WX-DRMs, [ii] antibody-induced cross-linking of PSMA molecules results in a time-dependent partitioning into another DRMs type, namely Triton X-100-DRMs, and [iii] concomitant with its association with Triton-X-100-DRMs internalization of PSMA occurs along tubulin filaments. In a previous work (Colombatti et al. (2009) PLoS One 4: e4608) we demonstrated that the small GTPases RAS and RAC1 and the MAPKs p38 and ERK1/2 are activated during antibody cross-linking. As downstream effects of this activation we observed a strong induction of NF-kB associated with an increased expression of IL-6 and CCL5 genes and that IL-6 and CCL5 enhanced the proliferative potential of LNCaP cells synergistically. These observations together with findings reported here hypothesize a fundamental role of DRMs during activation of PSMA as platforms for trafficking, endocytosis and signalling. Understanding these mechanisms constitutes an essential prerequisite for utilization of PSMA as a therapeutically suitable target in prostate cancer. 相似文献
3.
M D Kock R K Clark C E Franti D A Jessup J D Wehausen 《Journal of wildlife diseases》1987,23(4):652-662
Blood samples and physiological data were collected from 634 bighorn sheep (Ovis canadensis) captured by four different methods between 1980 and 1986 in the western United States. These parameters were evaluated for selected physiological, biochemical and hematological values. Postcapture biological parameters were compared among bighorn sheep according to four different outcomes; normal, stressed or compromised, capture myopathy (CM) mortality, and accidental mortality. Significant differences (P less than 0.05) were noted between outcome groups relative to certain parameters: temperature, respiration, creatinine phosphokinase (CPK), lactic dehydrogenase (LDH), serum glutamic oxaloacetic transaminase (SGOT), blood urea nitrogen (BUN), glucose, white blood cell count (WBC) and plasma pH. Such differences between groups may help in evaluating the clinical status of bighorn sheep at capture, enabling one to predict those animals that might develop CM at a later date, indicate candidates for preventive medical treatment prior to release, and/or which should be followed closely to determine long-term survival. Evaluation of follow-up data (n = 77) related to outcome status and long-term survival of bighorn sheep indicated that less than 4% (3 of 77) were dead within 1 mo of capture (one of these had been classified as normal and two as stressed or compromised at capture); less than 3% (3 of 77) were dead greater than 1 mo, and less than 6 mo after capture two were classified in the stressed outcome and one as diseased. Eighty-eight percent (68 of 77) were alive from 1 mo to 5 yr after capture (53 were classified as normal, 12 as stressed or compromised and 3 as diseased), and 2% (1 of 77) had chronic CM but was still alive (this animal had been classified as normal). Of 77 sheep in the follow-up group, less than 3% (2 of 77) were not observed following capture (one was classified as normal and one as stressed and diseased). Of the fatalities, less than 3% (2 of 40) had been captured by the net-gun and less than 4% (1 of 27) by drive-net. Those two unobserved in the follow-up group also had been caught with the net-gun, 5% (2 of 40). The single surviving CM case had been captured by the net-gun. Although the net-gun appears to be one of the safest methods of capturing individual bighorn sheep, based on evaluation of capture data and biological parameters, it may not be associated with the best long-term survival in some bighorn sheep.(ABSTRACT TRUNCATED AT 400 WORDS) 相似文献
4.
Kristensen Birte Thomsen Preben Dybdahl Palludan Birthe Wegger Inger 《Acta veterinaria Scandinavica》1986,27(4):486-496
Recently an inherited vitamin G deficiency in the pigs presumably based on an autosomal recessive gene was decribed* Homozygotes are in contrast to heterozygotes and normal pigs unable to synthesize ascorbic acid. In an experiment comprising 3 littermate pigs, 2 homozygous and 1 heterozygous for the vitamin C deficiency gene, the influence of ascorbic acid depletion, and repletion on mitogen stimulation of peripheral blood lymphocytes was studied. Ascorbic acid depletion of the vitamin C dependent pigs resulted in a rapid decline in plasma ascorbic acid. Response of lymphocytes to stimular tion with Concanavalin A (Con A) and phytohemagglutinin M (PHA) decreased more slowly reaching a minimum, which coincidedi with the occurrence of the first clinical symptoms of scurvy. Following resupplementation with vitamin C the plasma content of ascorbic acid rapidly returned to normal, while the lymphocyte response to Con A and PHA stimulation only gradually approached the initial values. The repletion with ascorbic acid caused a transitory increase in the response to pokeweed mitogen (PWM) stimulation. The significance of these findings in relation to the cellular immune system in normal pigs is discussed. 相似文献
5.
We studied variation at 25 to 31 allozymic loci in African and Asian rhinoceroses. Four taxa in three genera were examined: African Ceratotherium simum simum (northern white rhinoceros), C. s. cottoni (southern white rhinoceros), Diceros bicornis (black rhinoceros), and Rhinoceros unicornis (Indian rhinoceros). Extremely small amounts of intraspecific variation were observed in sample sizes of 2 to 10 presumably unrelated individuals per taxon: P = .00-.10, H = 0.00-0.02. We examined demographic bottlenecks and sampling errors as possible reasons for the low levels of detectable variation. The very small intraspecific genetic distance (D = 0.005) between the two living white rhinoceros subspecies is far less than the distance that has been reported for other mammal subspecies. The mean D value of 0.32 +/- 0.11 between the two African genera was also less than expected given the divergence time of greater than 7 million years suggested by the fossil record. Rhinoceroses may be evolving more slowly at the structural gene loci than are some other mammal groups. The estimate of D = 1.05 +/- 0.24 for the African-Indian split supports this idea, as the lineage diverged at least 26 million years ago. Our results contribute to the currently available scientific information on which management decisions aimed toward saving endangered rhinoceroses should be based. 相似文献
6.
Using radioimmunoassay, blood platelet aggregation studies and GC-MS the existence of prostaglandins in the endomycetalean yeastDipodascopsis uninucleata was confirmed by our group. These findings triggered the search for similar eicosanoids in the rest of the Endomycetales. We commenced by scanning for the easily detectable precursors of eicosanoids, linoleic- and linolenic acid. We selected two families (i.e. Lipomycetaceae and Dipodascaceae), both producing these precursors, for further investigation.Representative strains of the two families were tested for their ability to grow in the presence of 1mM aspirin, a specific inhibitor of prostaglandin biosynthesis. In contrast to the lipomycetaceous species the dipodascaceous species were insensitive to this drug. These results were verified when representative strains of both families were investigated for their ability to produce eicosanoids from externally fed radio-labeled arachidonic acid along an aspirin sensitive pathway. Thin layer chromatography of culture extracts, followed by autoradiography, showed that while none of the Dipodascaceae produced aspirin sensitive arachidonic acid metabolites, the members of the Lipomycetaceae tested positive for these metabolites. These findings supported the separation of the lipomycetaceous yeastDipodascopsis from the Dipodascaceae. The findings also correlate with the delimitation of these yeasts in two families (i.e. Dipodascaceae and Lipomycetaceae).Further investigation indicated that prostaglandin production by the genusDipodascopsis is mainly associated with ascosporogenesis. Thin layer chromatography of cell extracts fromDipodascopsis tóthii, followed by scintillation counting, indicated the presence of PGF2 and PGE2 during ascosporogenesis. 相似文献
7.
The taxonomic importance of fatty acid composition at genus and sub-genus level was evaluated by analysing the fatty acid
composition of fourteen different Microcystis isolates and seven additional members of the order Chroococcales. Fatty acid composition proved to be consistent within isolates.
Isolates were clustered into two major groups, namely A and B. Group B contained all the Microcystis isolates and was further divided into subgroups of varying similarity indicating the existence of different taxa. The Microcystis isolates were characterised by a high content of polyunsaturated fatty acids (27–44%) and a low content of palmitoleate.
The test organisms were arranged in a scheme indicating their possible phylogenetic relationship based on fatty acid composition
and other phenotypic characteristics. According to our data the toxic strains, represented by different isolates, of Microcystis appear as a distinct group. Furthermore two dubious species namely Microcystis incerta and a Synechocystis sp. could clearly be reasigned to different genera. The results demonstrated that fatty acid composition is an effective
taxonomic tool in clarifying taxonomical problems of Microcystis isolates.
Department of Microbiology, University of the Orange Free State 相似文献
8.
J. C. du Preez M. Immelman J. L. F. Kock S. G. Kilian 《World journal of microbiology & biotechnology》1997,13(1):81-87
The effect of different initial acetic acid concentrations on the growth of and lipid and gamma-linolenic acid (GLA) production
byMucor circinelloides CBS 203.28 was determined in a 14 litre stirred tank reactor operated in a fedbatch, pH-stat mode with acetic acid as carbon
source and pH titrant. Increased acetic acid concentrations in the culture resulted in a significant increase in the crude
oil content of the biomass. By contrast, all the other parameters such as the biomass concentration, GLA and oil yield on
acetic acid, the GLA content of the biomass and oil, the growth rate and volumetric rate of GLA production decreased with
an increase in acetic acid concentration. The best results were obtained with acetic acid at 2 g/1, which gave 39.8 mg GLA/g
biomass and 15.6% GLA in the neutral lipid fraction, amounting to 340 mg GLA/1 culture. A decrease in the glyco- and phospho-lipid
fractions during the cultivation coincided with an increase in the neutral lipid fraction. The GLA content of the biomass
remained within rather narrow limits of 3.5% to 4% of the biomass, irrespective of the oil content of the biomass. The fatty
acid profile was not greatly affected by the acetic acid concentration. The hyphae of the fungus were characterized by the
accumulation of large intracellular oil droplets and some septa delimited the hyphae. 相似文献
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10.
Robert K Logan Kock 《Environmental Biology of Fishes》1982,7(2):121-136
Synopsis Development of the fish community on a submerged 16 m barge and variation in fish abundance on nearby transects were surveyed twice monthly for twenty months. A steady increase in abundance was observed for certain fishes on the barge, whereas a few species exhibited distinct seasonal variation on both the barge and transects. Most of the seasonal species settled between March and May.Some seasonal species appeared to be site selective in their settlement and consequently settled juveniles were clumped in their distribution. An abundance of preferred topographical features may be why settlement was relatively high at the study site and indirectly why predators became significantly (r3 = 7.67***, N = 37) more abundant at the study area during the months of maximum prey settlement. Concurrent settlement of several species during the same few months may be important because juveniles become an abundant food source to predators during those few months only. Periodic swamping of predators by abundant juvenile prey may improve the chances for individuals of rarer prey species to be overlooked and therefore be succesfully recruited. 相似文献