Anti-plasmodial and anti-trypanosomal activity of synthetic naphtho[2,3-b]thiophen-4,9-quinones

Naphtho[2,3-b]thiophen-4,9-quinone and five derivatives were prepared using the Friedel-Crafts reaction and tandem-lithiation of aromatic diethylamides. These quinones were evaluated for their trypanocidal and anti-plasmodial activities by their effects on: (1) growth of epimastigote forms of Trypanosoma cruzi in vitro, (2) lysis of trypomastigote forms of T. cruzi in murine blood, (3) growth of Plasmodium falciparum in vitro, and (4) inhibition of the recombinant enzyme trypanothione reductase. The parent compound, naphtho[2,3-b]thiophen-4,9-quinone (3a), was among the most active quinone tested in vitro against P. falciparum at 0.2 μM. However, it was inactive against P. berghei-infected mice treated with 2.3 mmol/kg daily for 5 days. Most of the quinones prepared were active against T. cruzi epimastigotes in culture but exhibited weak activity at 4 °C against trypomastigotes in murine blood as well against the enzyme trypanothione reductase. Further structural modifications will be necessary to improve the in vivo activity of the naphthothiophenquinones.     

Glucocorticoid-mediated alteration in growth factor binding and action: Analysis of the binding change

The addition of the glucocorticoid analog dexamethasone (DX) to serum-free cultures of human fibroblasts caused a twofold enhancement of the mitogenic response to epidermal growth factor (EGF), although DX by itself was not mitogenic. A basis for this effect was suggested by studies showing that DX also increased the cellular binding of ¹²⁵I-EGF. DX increased the ability of the cells to bind ¹²⁵I-EGF only at low physiological concentrations of this polypeptide. Thus, data from ¹²⁵I-EGF binding to cells incubated without DX produced a linear Scatchard plot, whereas the data from ¹²⁵I-EGF binding to DX-treated cells led to an upwardly curvilinear Scatchard plot. Measurements of ¹²⁵I-EGF association with the cell surface and cytoplasm indicated that this binding change involved an alteration of cell surface EGF receptors. The binding change appeared not to involve negatively cooperative interactions between EGF receptors, nor a change in the number of receptors. The binding alteration could be explained by a model in which DX converted 25–30% of the cell surface EGF receptors to a form having a fourfold increased affinity.     

The morphometric relationship of Upper Cave 101 and 103 to modern Homo sapiens

Since the discovery of the Homo sapiens crania from the Upper Cave of Zhoukoudian in northern China (UC 101, UC 102, and UC 103), no clear consensus has arisen regarding their affinities with modern populations. We use linear craniofacial measurements to compare UC 101 and UC 103 to a worldwide sample of H. sapiens that includes Paleoamericans and Archaic Indians, and employ Mahalanobis distance analysis and associated unweighted, unrestricted canonical variate analysis for the comparisons. Analyses indicate that UC 101 has consistent affinities with Easter Island and European populations, whereas UC 103 has more tenuous similarities with Australo-Melanesian groups. Both fossils exhibit some similarities to certain Paleoamerican and Archaic Indian individuals, but rarely cluster together. Upper Cave 103 is more of an outlier to modern populations than is UC 101. The fossils are not representative of any group to which they have been compared, but may be part of the generalized population that was ancestral to Paleoamericans.     

Predator-prey interactions between Isochrysis galbana and Oxyrrhis marina. III. Mathematical modelling of predation and nutrient regeneration

A mathematical model was derived to simulate ingestion, growthand nitrogen (N) regeneration for the phagotrophic dinoflagellateOxyrrhis marina. Two types of experimental study were undertaken:prey-deplete O.marina were supplied with lsochrysis galbanain continuous darkness (thus preventing growth of the prey),and predator-prey interactions were also followed in culturesmaintained in a light-dark cycle (allowing growth of the prey).During light-dark cycles, Oxyrrhis volume increased more inthe light phase than in the dark. Digestion of isochrysis lasted{small tilde}0.3 days. with an average maximum ingestion rateof 55 prey predator–1 day–1 During active predation,30% of Oxyrrhis-carbon (C) was lost from the particulate phase:per day, with this loss falling to 10%: per day at the cessationof herbivory when cannibalism became noticeable. Ingestion wasmodelled as a function of prey density, C-loss and divisionas functions of cellular predator C. with cannibalism by Oxyrrhisalso included. Two N-regeneration expressions were investigated:one proposed by D.A.Caron and J.C.Goldman (Journal of Protozoology.35, 247–249, 1988) and an alternative function which relatedN regeneration to intracellular carbon and N based on the conceptof an optimal Oxyrrhis C:N ratio. The latter was more successfulin simulating batch culture data and did not require a priorcalculation of Oxyrrhis gross growth efficiency. The model ofOxyrrhis numbers, C and N contained only nine parameters whosevalues were fully obtainable from batch culture experiments.By using this model, we were able to use a single parameterset to simulate the transient dynamics of Oxyrrhis ingestingN-replete and N-stressed prey. Further experiments in whichOxyrrhis grew on Isochrysis in light-dark cycles were simulatedby combining the Oxyrrhis model with the nutrient-processingmodel for Isochrysis of K.Davidson et al. (Journal of PlanktonResearch, 15, 351–359, 1993). The dynamics of the fullpredator-prey model were found to be sensitive to the levelof sophistication of the prey model; the Quota model was foundto be less successful than the nutrient-processing prey model.Theoretical model runs indicated the importance of being ableto simulate changes in both prey numbers and biomass, and alsoin including realistic equations for nutrient regeneration frompredators in microbial predator-prey models.     

Production of citric and oxalic acids and solubilization of calcium phosphate by Penicillium bilaii.

An isolate of Penicillium bilaii previously reported to solubilize mineral phosphates and enhance plant uptake of phosphate was studied. Using agar media with calcium phosphate and the pH indicator alizarin red S, the influence of the medium composition on phosphate solubility and medium acidification was recorded. The major acidic metabolites produced by P. bilaii in a sucrose nitrate liquid medium were found to be oxalic acid and citric acid. Citric acid production was promoted under nitrogen-limited conditions, while oxalic acid production was promoted under carbon-limited conditions. Citric acid was produced in both growth and stationary phases, but oxalic acid production occurred only in stationary phase. When submerged cultures which normally produce acid were induced to sporulate, the culture medium shifted toward alkaline rather than acid reaction with growth.     

Uptake Hydrogenase Activity Determined by Plasmid pRL6JI in Rhizobium leguminosarum Does Not Increase Symbiotic Nitrogen Fixation

We examined three groups of wild baboons (Papio cynocephalus) in Amboseli National Park, Kenya, to determine the prevalence of aerobic antibiotic-resistant fecal bacteria in nonhuman primates with and without contact with human refuse. Using standard isolation and replica plating techniques, we found only low numbers of antibiotic-resistant gram-negative enteric bacteria in two groups of baboons leading an undisturbed existence in their natural habitat and having limited or no contact with humans. However, resistance was significantly higher among enteric bacteria from the third group of baboons living in close proximity to a tourist lodge and having daily contact with unprocessed human refuse. Conjugation studies and analysis of the cell DNA by gel electrophoresis showed that in many cases resistance was plasmid-borne and transferable. These data suggest that wild nonhuman primates in frequent contact with human debris have a higher proportion of antibiotic-resistant enteric bacteria than do conspecifics without this contact. The findings further suggest that such groups of wild animals may constitute a heretofore overlooked source of antibiotic resistance in the natural environment.     

Aldehyde oxidase distribution in haltere discs of homoeotic bithorax mutants in Drosophila melanogaster.

Summary Distribution of the enzyme aldehyde oxidase in transformed haltere discs from the homoeotic bithorax series of mutants was investigated by histochemical means. The bithorax (bx) mutant, which transforms the anterior part of the haltere into an alterior with blade, possesses in the haltere disc an aldehyde oxidase staining pattern similar to that of the anterior side of the wing disc. The postbithorax (pbx) mutant, which transforms the posterior haltere into a structure resembling the posterior wing blade, reveals an aldehyde oxidase staining pattern in the haltere disc characteristic of the posterior side of the wing disc pouch. When both (bx ³ (pbx) mutants are present the haltere develops into a metathoracic wing. It is shown here that the transformed haltere disc closely resembles the previously established pattern in the wing disc with respect to aldehyde oxidase distribution. Change in the pattern of aldehyde oxidase in bithorax mutants signals alteration in gene expression which at least for this particular enzyme correlates well with the morphological transformation from haltere to wing. A possible correlation between pattern of enzyme activity and developmental compartmentalization has been discussed.     

Feline immunodeficiency virus in puma: Estimation of force of infection reveals insights into transmission

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