Superoxide Radical-Mediated Alteration of Synaptosome Membrane Structure and High-Affinity γ-[14C]Aminobutyric Acid Uptake

Mouse cortical synaptosomal structure and function are altered when exposed to hypoxanthine/xanthine oxidase (HPX/XOD)-generated active oxygen/free radical species. The structure of both the synaptic vesicle and plasma membrane systems are altered by HPX/XOD treatment. The alteration of synaptic vesicle structure is exhibited by a significant increase in the cumulative length of nonsynaptic vesicle membrane per nerve terminal. With respect to the nerve terminal plasma membrane, the length of the perimeter of the synaptosome is increased as the membrane pulls away from portions of the terminal in blebs. The functional lesion generated by HPX/XOD treatment results in a reduction in selective high-affinity gamma-[14C]aminobutyric acid (GABA) uptake. Kinetic analysis of the reduction in high-affinity uptake reveals that the Vmax is significantly altered whereas the Km is not. Preincubation with specific active oxygen/free radical scavengers indicates that the super-oxide radical is directly involved. This radical, most probably in the protonated perhydroxyl form, initiates lipid peroxidative damage of the synaptosomal membrane systems. Low-affinity [14C]GABA transport is unaltered by the HPX/XOD treatment. The apparent ineffectiveness of free radical exposure on low-affinity [14C]GABA transport coupled with its effectiveness in reducing high-affinity transport supports the idea that two separate and different amino acid uptake systems exist in CNS tissue, with the high-affinity being more sensitive (lipid-dependent) and/or more energy-dependent (Na+,K+-ATPase) than the low-affinity system.     

Y-chromosomal insights into the genetic impact of the caste system in India

The caste system has persisted in Indian Hindu society for around 3,500 years. Like the Y chromosome, caste is defined at birth, and males cannot change their caste. In order to investigate the genetic consequences of this system, we have analysed male-lineage variation in a sample of 227 Indian men of known caste, 141 from the Jaunpur district of Uttar Pradesh and 86 from the rest of India. We typed 131 Y-chromosomal binary markers and 16 microsatellites. We find striking evidence for male substructure: in particular, Brahmins and Kshatriyas (but not other castes) from Jaunpur each show low diversity and the predominance of a single distinct cluster of haplotypes. These findings confirm the genetic isolation and drift within the Jaunpur upper castes, which are likely to result from founder effects and social factors. In the other castes, there may be either larger effective population sizes, or less strict isolation, or both. Electronic supplementary material Supplementary material is available in the online version of this article at and is accessible for authorized users. Tatiana Zerjal and Arpita Pandya contributed equally to this work.     

How reinforcer type affects choice in economic games

Behavioral economists stress that experiments on judgment and decision-making using economic games should be played with real money if the results are to have generality. Behavior analysts have sometimes disputed this contention and have reported results in which hypothetical rewards and real money have produced comparable outcomes. We review studies that have compared hypothetical and real money and discuss the results of two relevant experiments. In the first, using the Sharing Game developed in our laboratory, subjects' choices differed markedly depending on whether the rewards were real or hypothetical. In the second, using the Ultimatum and Dictator Games, we again found sharp differences between real and hypothetical rewards. However, this study also showed that time off from a tedious task could serve as a reinforcer every bit as potent as money. In addition to their empirical and theoretical contributions, these studies make the methodological point that meaningful studies may be conducted with economic games without spending money: time off from a tedious task can serve as a powerful reward.     

Evaluation of Populus and Salix continuously irrigated with landfill leachate I. Genotype-specific elemental phytoremediation

There is a need for the identification and selection of specific tree genotypes that can sequester elements from contaminated soils, with elevated rates of uptake. We irrigated Populus (DN17, DN182, DN34, NM2, NM6) and Salix (94003, 94012, S287, S566, SX61) genotypes planted in large soil-filled containers with landfill leachate or municipal water and tested for differences in inorganic element concentrations (P, K, Ca, Mg, S, Zn, B, Mn, Fe, Cu, Al, Na, and Cl) in the leaves, stems, and roots. Trees were irrigated with leachate or water during the final 12 wk of the 18-wk study. Genotype-specific uptake existed. For genera, tissue concentrations exhibited four responses. First, Populus had the greatest uptake of P, K, S, Cu, and Cl. Second, Salix exhibited the greatest uptake of Zn, B, Fe, and Al. Third, Salix had greater concentrations of Ca and Mg in leaves, while Populus had greater concentrations in stems and roots. Fourth, Populus had greater concentrations of Mn and Na in leaves and stems, while Salix had greater concentrations in roots. Populus deltoides x P. nigra clones exhibited better overall phytoremediation than the P. nigra x P. maximowiczii genotypes tested. Phytoremediation for S. purpurea clones 94003 and 94012 was generally less than for other Salix genotypes. Overall, concentrations of elements in the leaves, stems, and roots corroborated those in the plant-sciences literature. Uptake was dependent upon the specific genotype for most elements. Our results corroborated the need for further testing and selecting of specific clones for various phytoremediation needs, while providing a baseline for future researchers developing additional studies and resource managers conducting on-site remediation.     

Are We Losing the Best Parts of Our Protected Areas in Tropical Mountains?

Protected areas (PAs) on tropical mountains undergo greater forest destruction in their lower altitudes. We compared the extent of forested, nonforested, and fragmented areas between lowland (<1000 m asl) and montane zones of the Blue Mountains inside the Blue and John Crow Mountains National Park established in Jamaica in 1993. We found that in 2008, inside the montane zone, only 4 percent of forest was cleared, and forest fragmentation was minimal. In the lowland zone, however, the percentage of forest cleared was seven times as high, and the density of fragments was 11-fold higher. We established twenty-five 0.04 ha lowland plots; ordination of tree species composition in these plots reflected a rainfall gradient, showing that plots on the wetter northern side of the Blue Mountains were floristically different from those on the drier southern side. The conservation value of the remaining lowland forest is high because of its high endemism (18% of species in our plots) and beta diversity. In addition, IUCN Red List data show that about 71 percent of threatened tree species in the Blue Mountains grow in the lowland region, 92 percent of which are endemic. From these findings, we identify a ‘protected area hotspot zone’, which lies between the PA boundary and the core high-altitude zone, and which should be instituted in IUCN categories I and II PAs.     

Pralidoxime in Acute Organophosphorus Insecticide Poisoning—A Randomised Controlled Trial

Background

Poisoning with organophosphorus (OP) insecticides is a major global public health problem, causing an estimated 200,000 deaths each year. Although the World Health Organization recommends use of pralidoxime, this antidote''s effectiveness remains unclear. We aimed to determine whether the addition of pralidoxime chloride to atropine and supportive care offers benefit.

Methods and Findings

We performed a double-blind randomised placebo-controlled trial of pralidoxime chloride (2 g loading dose over 20 min, followed by a constant infusion of 0.5 g/h for up to 7 d) versus saline in patients with organophosphorus insecticide self-poisoning. Mortality was the primary outcome; secondary outcomes included intubation, duration of intubation, and time to death. We measured baseline markers of exposure and pharmacodynamic markers of response to aid interpretation of clinical outcomes. Two hundred thirty-five patients were randomised to receive pralidoxime (121) or saline placebo (114). Pralidoxime produced substantial and moderate red cell acetylcholinesterase reactivation in patients poisoned by diethyl and dimethyl compounds, respectively. Mortality was nonsignificantly higher in patients receiving pralidoxime: 30/121 (24.8%) receiving pralidoxime died, compared with 18/114 (15.8%) receiving placebo (adjusted hazard ratio [HR] 1.69, 95% confidence interval [CI] 0.88–3.26, p = 0.12). Incorporating the baseline amount of acetylcholinesterase already aged and plasma OP concentration into the analysis increased the HR for patients receiving pralidoxime compared to placebo, further decreasing the likelihood that pralidoxime is beneficial. The need for intubation was similar in both groups (pralidoxime 26/121 [21.5%], placebo 24/114 [21.1%], adjusted HR 1.27 [95% CI 0.71–2.29]). To reduce confounding due to ingestion of different insecticides, we further analysed patients with confirmed chlorpyrifos or dimethoate poisoning alone, finding no evidence of benefit.

Conclusions

Despite clear reactivation of red cell acetylcholinesterase in diethyl organophosphorus pesticide poisoned patients, we found no evidence that this regimen improves survival or reduces need for intubation in patients with organophosphorus insecticide poisoning. The reason for this failure to benefit patients was not apparent. Further studies of different dose regimens or different oximes are required.

Trial Registration

Controlled-trials.com ISRCTN55264358 Please see later in the article for Editors'' Summary     

The Superoxide Dismutase-Mimic Copper-Putrescine-Pyridine Suppresses Lipid Peroxidation in CHO Cells. Implications for its Prooxidative and Antioxidative Mechanisms of Action

Copper-Putrescine-Pyridine (Cu-PuPy) is a membrane-permeable complex which efficiently dismutates superoxide. In excess of 0.1 mM it is highly cytotoxic and oxidizes cellular GSH with concomitant production of H₂O₂. Here we show that treatment of CHO cells with 0.2 mM Cu-PuPy (0-200 min) leads to an accumulation of H₂O₂. Organic hydroperoxides which are also formed at low levels in the presence of Cu-PuPy, increase significantly after removal of the copper complex. We conclude that Cu-PuPy acts as an oxidant until cellular GSH is depleted. However, by interfering with radical chain propagation reactions, it suppresses lipid peroxidation and thus substitutes for consumed physiological antioxidants in a later stage of treatment. This consistently explains our previous, seemingly paradox, finding that longer Cu-PuPy treatments may be significantly less toxic than shorter ones.     

Ontogenetic Shift in Efficacy of Antipredator Mechanisms in a Top Aquatic Predator,Anax junius (Odonata: Aeshnidae)

The ability of prey to escape predation often lies in the occurrence and efficacy of their predator avoidance and antipredator behaviors, which are often coupled with specialized morphology. How the use and efficacy of these behaviors change throughout ontogeny may be indicative of the vulnerability and ecological roles these animals experience throughout their lives. We examined the antipredator behavior of a large dragonfly nymph, Anax junius, from a historically fishless pond where these animals have traditionally been classified as top predators. These dragonfly nymphs displayed a series of distinct aggressive antipredator behaviors when grasped that involved stabbing with lateral and posterior spines and seizing with labial hooks. Larger (older) nymphs displayed these aggressive behaviors significantly more than smaller (younger) animals in simulated predation trials. During encounters with live larval salamander predators (Ambystoma tigrinum), all large nymphs, but only 12.5% of small nymphs successfully escaped predation attempts by the amphibians through the use of antipredator behavior. Large nymphs were also significantly more active than smaller nymphs in the presence of salamander larvae. Despite often being considered top predators in fishless ponds, our study demonstrates that their true role is more complex, depending on ontogeny and body size, and that effective antipredator behavior is likely necessary for survival in these systems.     

Possible consequences of genes of major effect: transient changes in the G-matrix

Understanding the process of evolutionary divergence requires knowledge of the strength, form, and targets of selection, as well as the genetic architecture of the divergent traits. Quantitative genetic approaches to understanding multivariate selection and genetic response to selection have proven to be powerful tools in this endeavor, particularly with respect to short-term evolution. However, the application of quantitative genetic theory over periods of substantial phenotypic change is controversial because it requires that the requisite genetic parameters remain constant over the period of time in question. We show herein how attempts to determine the stability of key genetic parameters may be misled by the many genes of small effect type of genetic architecture generally assumed in quantitative genetics. The presence of genes of major effect (GOMEs) can alter the genetic variance-covariance matrix dramatically for brief periods of time, significantly alter the rate and trajectory of multivariate evolution, and thereby mislead attempts to reconstruct or predict long term evolution.     

Information encoding in the inferior temporal visual cortex: contributions of the firing rates and the correlations between the firing of neurons

The encoding of information by populations of neurons in the macaque inferior temporal cortex was analyzed using quantitative information-theoretic approaches. It was shown that almost all the information about which of 20 stimuli had been shown in a visual fixation task was present in the number of spikes emitted by each neuron, with stimulus-dependent cross-correlation effects adding for most sets of simultaneously recorded neurons almost no additional information. It was also found that the redundancy between the simultaneously recorded neurons was low, approximately 4% to 10%. Consistent with this, a decoding procedure applied to a population of neurons showed that the information increases approximately linearly with the number of cells in the population. AcknowledgementsThis research was supported by the Medical Research Council, grant PG9826105, by the Human Frontier Science Program, by the MRC Interdisciplinary Research Centre for Cognitive Neuroscience, and by the Wellcome Trust.