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The adenine nucleotide translocation in mitochondria has previously been established as an exchange between exogenous and endogenous adenine nucleotides across the inner membrane. The specificity and the control of the exchange are examined with the following major results: The adenine nucleotide translocation is relatively specific for exogenous ADP and ATP, AMP being nearly inactive. Among other nucleotides tested, only dADP and dATP exchange with a noticeable activity. In the controlled state ADP exchanges 2–4 times faster than ATP. If simultaneously added, ADP and ATP compete for the exchange, with ADP being about tenfold more active than ATP. The specificity of the exit of adenine nucleotides in the exchange is similar to the specificity of the entrance with the difference that ADP and ATP are released with equal activity in proportion to their intramitochondrial content. AMP is released only after a slow conversion to ADP. Therefore the short time exchange is limited by the endogenous content of ADP plus ATP. The exchange is influenced by the metabolic state of the mitochondria. The ATP exchange is more variable than the ADP exchange. Two effects are elucidated: (a) the influence of the metabolic state on the relative content of AMP which inhibits both the ADP and ATP exchange (b) the coupling of the energy transfer system which inhibits only the ATP exchange. An example for case (a) is the inhibition of the ADP and ATP exchange by arsenate and an example for case (b) is the strong increase of the ATP exchange on uncoupling. The following effects are relevant to the mechanism of the control of the exchange by ATP. The stimulation of the ATP exchange by uncoupler has the same concentration dependence as the uncoupling of oxidative phosphorylation (Km [CCP] = 0.08 μM, where CCP = carbonyl‐cyanide‐phenylhydrazone). Oligomycin does not abolish the uncoupler effect on the ATP exchange. “Endogenous uncoupling” on aging of mitochondria also stimulates the ATP exchange. Valinomycin plus K+ only slightly stimulate the ATP exchange. Anaerobiosis stimulates the ATP exchange to a smaller extent than uncoupling.In competition with ADP the effects of energy transfer on ATP exchange are more strongly revealed. On uncoupling the more than tenfold preference for ADP is fully abolished. It is concluded that basically the exchange for ADP and ATP has equal specificity in forward and reverse reaction. In the controlled state a superimposed force makes the specificity asymmetric and inhibits the entrance of ATP. This control of the ATP exchange is concluded to be based on the anionic character of the adenine nucleotides. Thus the ATP4‐ex–ADP3‐in exchange is inhibited unless the charge difference is compensated for by an uncoupler stimulated H+ movement across the membrane. Furthermore an electric potential gradient appears to be effective in the controlled state which is abolished on uncoupling.

Abstract Background Malaria remains one of the most devastating diseases globally, and the control of mosquitoes as the vector is mainly dependent on chemical insecticides. Elevated temperatures associated with future warmer climates could affect mosquitoes' metabolic enzyme expression and increase insecticide resistance, making vector control difficult. Understanding how mosquito rearing temperatures influence their susceptibility to insecticide and expression of metabolic enzymes could aid in the development of novel tools and strategies to control mosquitoes in a future warmer climate. This study evaluated the effects of temperature on the susceptibility of Anopheles gambiae sensu lato (s.l.) mosquitoes to pyrethroids and their expression of metabolic enzymes. Methods Anopheles gambiae s.l. eggs obtained from laboratory-established colonies were reared under eight temperature regimes (25, 28, 30, 32, 34, 36, 38, and 40 °C). Upon adult emergence, 3- to 5-day-old female non-blood-fed mosquitoes were used for susceptibility tests following the World Health Organization (WHO) bioassay protocol. Batches of 20–25 mosquitoes from each temperature regime (25–34 °C) were exposed to two pyrethroid insecticides (0.75% permethrin and 0.05% deltamethrin). In addition, the levels of four metabolic enzymes (α-esterase, β-esterase, glutathione S-transferase [GST], and mixed-function oxidase [MFO]) were examined in mosquitoes that were not exposed and those that were exposed to pyrethroids. Results Mortality in An. gambiae s.l. mosquitoes exposed to deltamethrin and permethrin decreased at temperatures above 28 °C. In addition, mosquitoes reared at higher temperatures were more resistant and had more elevated enzyme levels than those raised at low temperatures. Overall, mosquitoes that survived after being exposed to pyrethroids had higher levels of metabolic enzymes than those that were not exposed to pyrethroids. Conclusions This study provides evidence that elevated temperatures decreased An. gambiae s.l. mosquitoes' susceptibility to pyrethroids and increased the expression of metabolic enzymes. This evidence suggests that elevated temperatures projected in a future warmer climate could increase mosquitoes' resistance to insecticides and complicate malaria vector control measures. This study therefore provides vital information, and suggests useful areas of future research, on the effects of temperature variability on mosquitoes that could guide vector control measures in a future warmer climate. Graphical Abstract

The latest information from Hiroshima and Nagasaki on radiation-induced cancer in man includes new DS86 dose assignments and extension of the Life-Span Study Sample cohort through 1985. The implications of these new doses and updated data for the assessment of cancer risk at low to moderate doses have been evaluated. Results from the fitting of three dose-response models (linear, quadratic, linear-quadratic) to the data at doses less than 1.5 Gy are reported. Based on statistical analyses of the authors' results, comments are made concerning the possible shapes of dose-response curves for human cancer.

White sweet clover found voluntarily growing on a deep bed of soft coal fly ash was found to contain high concentrations of a number of elements including selenium, bromine, and molybdenum, rubidium, strontium, and others. The clover was harvested and fed as 23.5% of a dry pelleted ration to lambs and pregnant goats for up to 173 days. High concentrations of selenium were found in 11 tissues, blood, goats' milk, and excreta of lambs, goats, and newborn kids. Molybdenum in liver, strontium in bone, and bromine and rubidium in animal tissues were also elevated over those in the corresponding tissues of animals fed an identical ration containing control clover grown on soil. No gross or histologic lesions were present in any of the animals.

Consumer interest in food products, including fresh vegetables, with health promoting properties is rising. In fresh vegetables, these properties include vitamins, minerals, dietary fiber, and secondary compounds, which collectively impart a large portion of the dietary, nutritional or health value associated with vegetable intake. Many, including farmers, aim to increase the health-promoting properties of fresh vegetables on the whole but they face at least three obstacles. First, describing crop composition in terms of its nutrition-based impact on human health is complex and there are few, if any, accepted processes and associated metrics for assessing and managing vegetable composition on-farm, at the origin of supply. Second, data suggest that primary and secondary metabolism can be 'in conflict' when establishing the abundance versus composition of a crop. Third, fresh vegetable farmers are rarely compensated for the phytochemical composition of their product. The development and implementation of a fresh vegetable 'nutritional yield' index could be instrumental in overcoming these obstacles. Nutritional yield is a function of crop biomass and tissue levels of health-related metabolites, including bioavailable antioxidant potential. Data from a multi-factor study of leaf lettuce primary and secondary metabolism and the literature suggest that antioxidant yield is sensitive to genetic and environmental production factors, and that changes in crop production and valuation will be required for fresh vegetable production systems to become more focused and purposeful instruments of public health.

In biomedical scientific investigations, expositions of findings are conceptually simplest when they comprise comparisons of discrete groups of individuals or involve discrete features or characteristics of individuals. But the descriptive benefits of categorization become outweighed by their limitations in studies involving dose-response relationships, as in many teratogenic and environmental exposure studies. This article addresses a pair of categorization issues concerning the effects of prenatal alcohol exposure that have important public health consequences: the labeling of individuals as fetal alcohol syndrome (FAS) versus fetal alcohol effects (FAE) or alcohol-related neurodevelopmental disorder (ARND), and the categorization of prenatal exposure dose by thresholds. We present data showing that patients with FAS and others with FAE do not have meaningfully different behavioral performance, standardized scores of IQ, arithmetic and adaptive behavior, or secondary disabilities. Similarly overlapping distributions on measures of executive functioning offer a basis for identifying alcohol-affected individuals in a manner that does not simply reflect IQ deficits. At the other end of the teratological continuum, we turn to the reporting of threshold effects in dose-response relationships. Here we illustrate the importance of multivariate analyses using data from the Seattle, Washington, longitudinal prospective study on alcohol and pregnancy. Relationships between many neurobehavioral outcomes and measures of prenatal alcohol exposure are monotone without threshold down to the lowest nonzero levels of exposure, a finding consistent with reports from animal studies. In sum, alcohol effects on the developing human brain appear to be a continuum without threshold when dose and behavioral effects are quantified appropriately.

Forty-nine schools (N = 5,680 fifth and sixth grade students) were assigned to pre test/treatment, pretest/no treatment, no pretest/treatment, and no pretest/no treat ment conditions in the context of an alcohol misuse prevention study. At the first posttest, five months after the pretest and two months after the intervention, the effects of the pretest and of the intervention were examined. The analyses showed that failure to correct for the design effect due to clustering within schools resulted in the overestimation of the significance of treatment and pretest effects. After correction for the design effect, a significant treatment effect in the hypothesized direction was found with respect to students' awareness of the content of the curriculum. As hypo thesized, significant treatment effects on the alcohol use and misuse measures had not yet developed but are expected to occur at subsequent posttest occasions. Significant pretest effects were found for indices measuring trouble with peers resulting from students' alcohol use, students' internal health locus of control, and their perceptions of adults as a locus of control for their health. Two of the three pretest effects were in the direction that would be hypothesized if the pretest were providing the same impe tus as the intervention. Implications of these findings for school-based substance abuse prevention programs are discussed.

This article presents a model of development, civil war and climate change. There are multiple interactions. Economic growth reduces the probability of civil war and the vulnerability to climate change. Climate change increases the probability of civil war. The impacts of climate change, civil war and civil war in the neighbouring countries reduce economic growth. The model has two potential poverty traps – one is climate-change-induced and one is civil-war-induced – and the two poverty traps may reinforce one another. The model is calibrated to sub-Saharan Africa and a double Monte Carlo analysis is conducted in order to account for both parameter uncertainty and stochasticity. Although the IPCC Special Report on Emission Scenarios (SRES) is used as the baseline, thus assuming rapid economic growth in Africa and convergence of African living standards to the rest of the world, the impacts of civil war and climate change (ignored in SRES) are sufficiently strong to keep a number of countries in Africa in deep poverty with a high probability.