Permeability of housefly mitochondria towards dicarboxylate ions

Studies with labelled substrates show that housefly mitochondria are permeable towards dicarboxylate anions, provided the phosphate concentration is low. Dicarboxylate anions compete with each other for entry. Phosphate also competes with the dicarboxylate anions for translocation and this effect is prevented by the sulphydryl reagent mersalyl.     

New 1-aryl-4-(biarylmethylene)piperazines as potential atypical antipsychotics sharing dopamine D(2)-receptor and serotonin 5-HT(1A)-receptor affinities

This paper describes the syntheses of several 1-aryl-4-(biarylmethylene)piperazines and the results of the determination of their affinity for D(2) and 5-HT(1A) receptors. A selection of these compounds was evaluated in vivo, resulting in the identification of a drug candidate which is being clinically evaluated as a potential atypical antipsychotic with reduced extrapyrimidal side effects.     

High levels of fluctuating asymmetry in isolated stickleback populations

ABSTRACT: BACKGROUND: Fluctuating asymmetry (FA), defined as small random deviations from the ideal bilateral symmetry, has been hypothesized to increase in response to both genetic and environmental stress experienced by a population. We compared levels of FA in 12 bilateral meristic traits (viz. lateral-line system neuromasts and lateral plates), and heterozygosity in 23 microsatellite loci, among four marine (high piscine predation risk) and four pond (zero piscine predation risk) populations of nine-spined sticklebacks (Pungitius pungitius). RESULTS: Pond sticklebacks had on average three times higher levels of FA than marine fish and this difference was highly significant. Heterozygosity in microsatellite markers was on average two times lower in pond (HE [almost equal to] 0.3) than in marine (HE [almost equal to] 0.6) populations, and levels of FA and heterozygosity were negatively correlated across populations. However, after controlling for habitat effect on heterozygosity, levels of FA and heterozygosity were uncorrelated. CONCLUSIONS: The fact that levels of FA in traits likely to be important in the context of predator evasion were elevated in ponds compared to marine populations suggests that relaxed selection for homeostasis in ponds lacking predatory fish may be responsible for the observed habitat difference in levels of FA. This inference also aligns with the observation that the levels of genetic variability across the populations did not explain population differences in levels of FA after correcting for habitat effect. Hence, while differences in strength of selection, rather than in the degree of genetic stress could be argued to explain habitat differences in levels of FA, the hypothesis that increased FA in ponds is caused by genetic stress cannot be rejected.     

Bleomycin resistance: a new dominant selectable marker for plant cell transformation

Summary Plant cells are sensitive to the antibiotic bleomycin, a DNA damaging glycopeptide. A bleomycin resistance determinant, located on transposon Tn5 and functional in bacteria, has been cloned in a plant expression vector and introduced into Nicotiana plumbaginifolia using Agrobacterium tumefaciens. The expression of this determinant in plant cells confers resistance to bleomycin and allows selection of transformed plant cells.     

Solution structure of RING finger-like domain of retinoblastoma-binding protein-6 (RBBP6) suggests it functions as a U-box

Retinoblastoma-binding protein-6 (RBBP6) plays a facilitating role, through its RING finger-like domain, in the ubiquitination of p53 by Hdm2 that is suggestive of E4-like activity. Although the presence of eight conserved cysteine residues makes it highly probable that the RING finger-like domain coordinates two zinc ions, analysis of the primary sequence suggests an alternative classification as a member of the U-box family, the members of which do not bind zinc ions. We show here that despite binding two zinc ions, the domain adopts a homodimeric structure highly similar to those of a number of U-boxes. Zinc ions could be replaced by cadmium ions without significantly disrupting the structure or the stability of the domain, although the rate of substitution was an order of magnitude slower than any previous measurement, suggesting that the structure is particularly stable, a conclusion supported by the high thermal stability of the domain. A hallmark of U-box-containing proteins is their association with chaperones, with which they cooperate in eliminating irretrievably unfolded proteins by tagging them for degradation by the proteasome. Using a yeast two-hybrid screen, we show that RBBP6 interacts with chaperones Hsp70 and Hsp40 through its N-terminal ubiquitin-like domain. Taken together with the structural similarities to U-box-containing proteins, our data suggest that RBBP6 plays a role in chaperone-mediated ubiquitination and possibly in protein quality control.     

Separation of human metaphase chromosomes at neutral pH by velocity sedimentation at 20 times gravity

A method for the separation of large quantities of human metaphase chromosomes at neutral pH is described. The separation was performed in a specially designed sedimentation chamber which was placed in a bucket of a speed-controlled centrifuge. Flow deflectors in the chamber allowed both the undisturbed introduction of gradient and chromosomes, as well as the undisturbed fractionation of the content of the chamber. The centrifuge was run at 20 g for 1 h taking care of slow acceleration and deceleration. The slow morphological changes of the chromosomes due to ageing at neutral pH do not affect the resolving power of the sedimentation technique within this hour. This in contrast to separation of chromosomes at neutral pH by velocity sedimentation at unit gravity during 20 h, as described before. The main advantage of chromosome sorting at neutral pH is that the fractionated chromosomes are more suitable for gene transfer and gene mapping experiments.     

Bed Net Durability Assessments: Exploring a Composite Measure of Net Damage

Background

The durability of Long Lasting Insecticidal Nets (LLINs) in field conditions is of great importance for malaria prevention and control efforts; however, the physical integrity of the net fabric is not well understood making it challenging to determine overall effectiveness of nets as they age. The 2011 World Health Organization Pesticide Evaluation Scheme (WHOPES) guidelines provide a simple, standardized method using a proportional hole index (PHI) for assessing net damage with the intent to provide national malaria control programs with guidelines to assess the useful life of LLINS and estimate the rate of replacement.

Methods

We evaluated the utility of the PHI measure using 409 LLINs collected over three years in Nampula Province, Mozambique following a mass distribution campaign in 2008. For each LLIN the diameter and distance from the bottom of the net were recorded for every hole. Holes were classified into four size categories and a PHI was calculated following WHOPES guidelines. We investigate how the size, shape, and location of holes influence the PHI. The areas of the WHOPES defined categories were compared to circular and elliptical areas based on approximate shape and actual measured axes of each hole and the PHI was compared to cumulative damaged surface area of the LLIN.

Results

The damaged area of small, medium, large, and extra-large holes was overestimated using the WHOPES categories compared to elliptical areas using the actual measured axes. Similar results were found when comparing to circular areas except for extra-large holes which were underestimated. (Wilcoxon signed rank test of differences p< 0.0001 for all sizes). Approximating holes as circular overestimated hole surface area by 1.5 to 2 times or more. There was a significant difference in the mean number of holes < 0.5 cm by brand and there were more holes of all sizes on the bottom of nets than the top. For a range of hypothetical PHI thresholds used to designate a “failed LLIN”, roughly 75 to 80% of failed LLINs were detected by considering large and extra-large holes alone, but sensitivity varied by brand.

Conclusions

Future studies may refine the PHI to better approximate overall damaged surface area. Furthermore, research is needed to identify whether or not appropriate PHI thresholds can be used to deem a net no longer protective. Once a cutoff is selected, simpler methods of determining the effective lifespan of LLINs can help guide replacement strategies for malaria control programs.     

Honey--a novel antidiabetic agent

Diabetes mellitus remains a burden worldwide in spite of the availability of numerous antidiabetic drugs. Honey is a natural substance produced by bees from nectar. Several evidence-based health benefits have been ascribed to honey in the recent years. In this review article, we highlight findings which demonstrate the beneficial or potential effects of honey in the gastrointestinal tract (GIT), on the gut microbiota, in the liver, in the pancreas and how these effects could improve glycemic control and metabolic derangements. In healthy subjects or patients with impaired glucose tolerance or diabetes mellitus, various studies revealed that honey reduced blood glucose or was more tolerable than most common sugars or sweeteners. Pre-clinical studies provided more convincing evidence in support of honey as a potential antidiabetic agent than clinical studies did. The not-too-impressive clinical data could mainly be attributed to poor study designs or due to the fact that the clinical studies were preliminary. Based on the key constituents of honey, the possible mechanisms of action of antidiabetic effect of honey are proposed. The paper also highlights the potential impacts and future perspectives on the use of honey as an antidiabetic agent. It makes recommendations for further clinical studies on the potential antidiabetic effect of honey. This review provides insight on the potential use of honey, especially as a complementary agent, in the management of diabetes mellitus. Hence, it is very important to have well-designed, randomized controlled clinical trials that investigate the reproducibility (or otherwise) of these experimental data in diabetic human subjects.     

Effects of melatonin on behavioral dopaminergic supersensitivity

This study examines the effects of melatonin on dopaminergic supersensitivity induced by long-term treatment with haloperidol in rats. Enhancements of spontaneous general activity in an open-field and of stereotyped behavior induced by apomorphine after abrupt withdrawal from long-term treatment with haloperidol were used as experimental parameters for dopaminergic supersensitivity. Experiment 1 was conducted to investigate the effects of melatonin on the development of dopaminergic supersensitivity, and experiment 2 was conducted to investigate the effects of melatonin on the development as well as on expression of dopaminergic supersensitivity. Rats of both experiments were long-term treated with saline or haloperidol concomitant to saline or melatonin. In experiment 1 behavioral observations were performed after abrupt withdrawal from long-term treatment. In experiment 2 behavioral observations were performed 1 hour after an acute injection of saline or melatonin, administered after the abrupt withdrawal from long-term treatment. Both behavioral parameters used showed the development of central dopaminergic supersensitivity in rats treated with haloperidol since 24 hours after abrupt withdrawal. Concomitant treatment with melatonin intensified haloperidol-induced dopaminergic supersensitivity, observed 72 hours after withdrawal. Melatonin treatment per se also induced behavioral supersensitivity evaluated by both open-field and stereotyped behaviors, although it was more fugacious than that presented by haloperidol. Acute treatment with melatonin reverted the enhancement of the haloperidol-induced dopaminergic supersensitivity produced by concomitant long-term treatment with melatonin, as well as melatonin-induced dopaminergic supersensitivity per se. Our results support previous evidence of antidopaminergic effects of melatonin and demonstrate that repeated administration of this hormone modifies the plasticity of behaviors mediated by central dopaminergic systems.