Comparative field cage tests of the population suppressing efficiency of three genetic control systems for Aedes Aegypti.

Cycling populations of Aedes aegypti were set up in cages and managed in such a way that the populations had a maximum of threefold recovery potential in response to control measures. Into three such populations daily releases were made of males which had been chemosterilised, or were double translocation heterozygotes (T1T3) or T1T3 with sex ration distortion (DT1T3). Eradication of the populations was achieved with all cases, but the rate of suppression was markedly slower with T1T3 than the other two systems, with which the rates were similar. T1T3 and DT1T3 releases introduced considerable inherited genetic loads into the target populations. The results were in general agreement with computer predictions.     

Self-rotation of red blood cells in optical tweezers: prospects for high throughput malaria diagnosis

A simple and sensitive approach for detection of malarial parasite in blood samples is demonstrated. The approach exploits our finding that, in hypertonic buffer, a normal red blood cell (RBC) rotates by itself when trapped by an optical tweezers. The rotational speed increases linearly at lower trap-beam powers and more rapidly at higher powers. In contrast, under the same experimental conditions, RBC having a malarial parasite does not rotate. The rotational speeds of other RBCs from malaria-infected sample are of an order of magnitude less than that for normal RBC and also increase much more slowly with an increase in trap beam power than that for normal RBC. The difference in rotational speeds could be exploited for the diagnosis of malaria.     

The effects of a single dose of 5-fluorouracil on keloid scars: a clinical trial of timed wound irrigation after extralesional excision

The possibility of altering the pathophysiology of keloid scars was investigated in 11 patients, using a single application of 5-fluorouracil solution for 5 minutes after extralesional excision was performed. Similar excisional wounds treated with phosphate-buffered saline for 5 minutes served as synchronous controls. An objective scoring system and subjective assessment were made to assay the change in the quality of the wound-healing and scar tissue produced by this treatment. A keloid scar score was used at regular time intervals after treatment to assess the quality of scar produced, thereby enabling the treated and control scars to be clinically compared.Biopsies were taken of the control and treated scars 1 month after treatment; the biopsy specimens were then subjected to immunohistochemical analysis as well as a functional assessment of cultured keloid fibroblasts. The immunohistochemical antigens assayed were Ki-67 (also called MIB-1; a marker of cell proliferation); vascular cell adhesion molecule-1 (a marker of inflammation); transforming growth factor beta-1 (a factor involved in scarring) and CD-68 (a macrophage-specific marker). Fibroblast-populated collagen lattices provided a functional assessment of fibroblast contraction.All treated and control wounds healed without any dehiscence or infection. The keloid scar score revealed that there was a perceived improvement in condition for those treated with 5-fluorouracil, compared with the control specimens, during the 6-month follow-up period in the five patients who attended all their clinic appointments; data on later recurrence are not complete as yet. The wounds treated with 5-fluorouracil produced scars that had a significant (p < 0.01) reduction in all the markers assayed, apart from CD-68. Functionally, the keloid fibroblasts from three of five of the treated patients showed reduced contractile capacity.This pilot study demonstrates that a "single-touch" technique with 5-fluorouracil can produce a change in the characteristics of the healing keloid wound after extralesional excision. Long-term studies are required to elucidate the correct dosage and time of exposure to improve the efficacy of this potential treatment.     

Terpenoids from Zingiber officinale (Ginger) Induce Apoptosis in Endometrial Cancer Cells through the Activation of p53

Novel strategies are necessary to improve chemotherapy response in advanced and recurrent endometrial cancer. Here, we demonstrate that terpenoids present in the Steam Distilled Extract of Ginger (SDGE) are potent inhibitors of proliferation of endometrial cancer cells. SDGE, isolated from six different batches of ginger rhizomes, consistently inhibited proliferation of the endometrial cancer cell lines Ishikawa and ECC-1 at IC₅₀ of 1.25 µg/ml. SDGE also enhanced the anti-proliferative effect of radiation and cisplatin. Decreased proliferation of Ishikawa and ECC-1 cells was a direct result of SDGE-induced apoptosis as demonstrated by FITC-Annexin V staining and expression of cleaved caspase 3. GC/MS analysis identified a total of 22 different terpenoid compounds in SDGE, with the isomers neral and geranial constituting 30–40%. Citral, a mixture of neral and geranial inhibited the proliferation of Ishikawa and ECC-1 cells at an IC₅₀ 10 µM (2.3 µg/ml). Phenolic compounds such as gingerol and shogaol were not detected in SDGE and 6-gingerol was a weaker inhibitor of the proliferation of the endometrial cancer cells. SDGE was more effective in inducing cancer cell death than citral, suggesting that other terpenes present in SDGE were also contributing to endometrial cancer cell death. SDGE treatment resulted in a rapid and strong increase in intracellular calcium and a 20–40% decrease in the mitochondrial membrane potential. Ser-15 of p53 was phosphorylated after 15 min treatment of the cancer cells with SDGE. This increase in p53 was associated with 90% decrease in Bcl2 whereas no effect was observed on Bax. Inhibitor of p53, pifithrin-α, attenuated the anti-cancer effects of SDGE and apoptosis was also not observed in the p53^neg SKOV-3 cells. Our studies demonstrate that terpenoids from SDGE mediate apoptosis by activating p53 and should be therefore be investigated as agents for the treatment of endometrial cancer.     

Evolution of specialized microbial cooperation in dynamic fluids

Here, we study the evolution of specialization using realistic computer simulations of bacteria that secrete two public goods in a dynamic fluid. Through this first‐principles approach, we find physical factors such as diffusion, flow patterns and decay rates are as influential as fitness economics in governing the evolution of community structure, to the extent that when mechanical factors are taken into account, (a) generalist communities can resist becoming specialists despite the invasion fitness of specialization; (b) generalist and specialists can both resist cheaters despite the invasion fitness of free‐riding; and (c) multiple community structures can coexist despite the opposing force of competitive exclusion. Our results emphasize the role of spatial assortment and physical forces on niche partitioning and the evolution of diverse community structures.     

Relation between blood pressure,weight, and plasma sugar and serum insulin levels in schoolchildren aged 9-12 years in Westland,Holland.

In 2388 schoolchildren aged 9-12 years who took part in a study of cardiovascular risk factors in Westland, Holland, plasma sugar concentrations were found to be positively correlated with systolic and diastolic blood pressure, independently of weight. Serum cholesterol levels were also related to systolic blood pressure in boys, but much less strongly than plasma sugar levels. The relation between serum insulin and blood pressure, independent of plasma sugar, was weak. The relation between plasma sugar and systolic pressure existed for both sexes and regardless of whether measurements were made in the morning or afternoon; its association with diastolic pressure was weaker, and was not so consistent over all groups. These findings suggest that the relations between risk factors for coronary heart disease that exist in adults are already evident in childhood.     

Ligand migration and hexacoordination in type 1 non-symbiotic rice hemoglobin

Type 1 non-symbiotic rice hemoglobin (rHb1) shows bis-histidyl heme hexacoordination and is capable of binding diatomic ligands reversibly. The biological function is as yet unclear, but the high oxygen affinity makes it unlikely to be involved in oxygen transport. In order to gain insight into possible physiological roles, we have studied CO rebinding kinetics after laser flash photolysis of rHb1 in solution and encapsulated in silica gel. CO rebinding to wt rHb1 in solution occurs through a fast geminate phase with no sign of rebinding from internal docking sites. Encapsulation in silica gel enhances migration to internal cavities. Site-directed mutagenesis of FB10, a residue known to have a key role in the regulation of hexacoordination and ligand affinity, resulted in substantial effects on the rebinding kinetics, partly inhibiting ligand exit to the solvent, enhancing geminate rebinding and enabling ligand migration within the internal cavities. The mutation of HE7, one of the histidyl residues involved in the hexacoordination, prevents hexacoordination, as expected, but also exposes ligand migration through a complex system of cavities. This article is part of a Special Issue entitled: Protein Dynamics: Experimental and Computational Approaches.