Is ligation the only solution to the pyrophosphate problem?

Pyrophosphate linkages are easily formed during the nonenzymatic oligomerization of activated nucleotides. They often form caps which terminate an oligonucleotide with a 5-5 pyrophosphate. Owing to their structural resemblance to the intermediates in enzymatic ligation reactions, it has been suggested that pyrophosphate caps might have been capable of acting as activating groups in chain elongation processes. We argue that an alternative possibility would have been the specific hydrolysis of pyrophosphates.     

How do children with and without ADHD talk about frustration?: Use of a novel emotion narrative recall task

Children with attention-deficit/hyperactivity disorder (ADHD) experience difficulties related to emotional reactivity and regulation. The current study examines differences in the emotional reactivity and regulation of children with and without ADHD in the context of their real-life experiences of negative emotion using a novel ecologically valid methodology. Eighty-three 8–12-year-old children (46 ADHD, 38 non-ADHD) participated in the study. Children completed the negative emotion narrative recall task, a novel task whereby children provided a narrative recall of a real-life event where they experienced negative emotion. ANCOVA indicated children with ADHD recalled significantly more overall frustration and intense frustration than children without ADHD. Children with ADHD exhibiting more negative emotional reactivity while recalling negative emotions than children without ADHD. The current study suggests that children with ADHD are uniquely impacted by negative emotional experiences and represents an important step in understanding the emotional reactivity and regulation of children with ADHD.     

Is the treatment with psychostimulants in children and adolescents with attention deficit hyperactivity disorder harmful for the dopaminergic system?

A major concern regarding psychostimulant medication (amphetamine and methylphenidate) in the treatment of children and adolescents with attention deficit/hyperactivity disorder (ADHD) are the potential adverse effects to the developing brain, particularly in regard to dopaminergic brain function. The present review focuses on the pharmacology of these psychostimulants, their mode of action in the human brain and their potential neurotoxic effects to the developing brain in animals, particularly concerning DA brain function. The potential clinical significance of these findings for the treatment of ADHD in children and adolescents is discussed. Studies on sensitization to psychostimulants’ rewarding effects, which is a process expected to increase the risk of substance abuse in humans, are not included. The available findings in non-human primates support the notion that the administration of amphetamine and methylphenidate with procedures simulating clinical treatment conditions does not lead to long-term adverse effects in regard to development, neurobiology or behaviour as related to the central dopaminergic system.     

Is the relationship between fertility of parents and children really weak?

The relationship between fertility of parents and children has been designated as "weak" by most investigators. This paper reviews the evidence over the past century and argues that, even allowing for problems with available data sources, the relationship was probably close to zero for pre-transitional populations. However, over time, the relationship has tended to become more substantial and is now of a similar order of magnitude in developed countries as other widely used explanatory variables. Possible mechanisms for the observed relationship are discussed, especially the roles of socialization and inherited factors. The types of data used are compared to the scientific questions posed, and the limitations of the common comparison of married-mother/married-daughter pairs are considered. Finally, some evidence from recent large-scale surveys in Britain and the United States is presented to show changes over recent periods and the relative effects of sibship size of fathers and mothers.     

Is the host or the parasitoid in control?: effects of host age and temperature on pseudoparasitization by Microplitis rufiventris in Spodoptera littoralis

We compared the production of pseudoparasitization by Microplitis rufiventris females in most (third) and less (fourth) preferred instars of Spodoptera littoralis larvae at 20+/-1 and 27+/-1 degrees C. The parasitized hosts were classified into hosts producing parasitoids (type A hosts) and hosts producing no parasitoids, i.e., pseudoparasitized hosts (type B hosts). The latter were further classified into: (a) pseudoparasitized hosts with "well" arrested development (type B1 hosts); (b) pseudoparasitized hosts with partially arrested development (type B2 hosts); and (c) pseudoparasitized hosts that successfully pupated to apparently normal host pupae (type B3 hosts). The present series of experiments showed that parasitization by M. rufiventris was clearly affected by host instar, age within an instar and rearing temperature. Production of type B hosts was less when third instar S. littoralis larvae were exposed to the wasp females than when the host larvae were in fourth instar. The production of type A hosts was much greater when early or mid ages of an instar was stung by the wasp females comparing with stung late age of the same instar. Production of type B hosts may be due to one or overall of the following: (a) dosage dilution of M. rufiventris female's factors in the different age classes of the instar; (b) endocrine system (physiological state) at parasitization time, i.e., early vs late age of the instar; (c) growth rate of host larvae. The lowest production of type B hosts was at highest growth rate; and (d) temperature, larger proportions of type B hosts were produced at 27+/-1 than at 20+/-1degrees C. The three types host development (B1, B2 and B3) are possibly representing three levels of host resistance (host control) resulting in partial or complete failure of parasitoid control. Type A hosts represent complete success of parasitoid control. The results suggest that the impact of parasitoid factor(s) on developmental arrest is affected by host age at the time of parasitism and/or by temperature.     

Tolerability and effects of OROS® MPH (Concerta®) on functioning, severity of disease and quality of life in children and adolescents with ADHD: results from a prospective, non-interventional trial

Attention-deficit/hyperactivity disorder may have substantial impact on family life, peer interactions, and quality of life. Stimulants are recommended as first-line pharmacotherapy for ADHD. OROS(?) MPH (Concerta(?)) is a long-acting preparation with duration of effect for up to 12 h. In this 8-week, prospective, open-label, non-interventional trial the impact of therapy with OROS(?) MPH on functioning in four different areas of life (school, recreation, family life, and peer interaction), severity of disease, and quality of life (QoL) as well as tolerability were investigated under daily routine care. 306 patients, aged 10.2±2.3 years, were either transitioned to OROS(?) MPH from short-acting, immediate-release MPH (-IR) preparations (n=231; 75%), or treatment was initiated with OROS(?) MPH in MPH-na?ve patients (n =75; 25%). In both groups, therapy with OROS(?) MPH was associated with significant improvements in daily functioning, severity of disease, and QoL. Adverse events (AE) were documented in 160 patients (52.3%). In 95 patients (31.0%) a causal relationship was assessed as at least possible. Four serious AEs were reported in 2 patients and rated as doubtfully related to study medication. Most frequent AEs (≥5% of patients) were insomnia, anorexia, ineffectiveness of medication, and headache. In 12.1% of patients AE led to discontinuation of study participation. Considering the limitations of this non-interventional study, the results refer to the importance of a therapy that covers not only school-time, but also takes other areas of life into account. Initiating treatment with long-acting preparations, such as OROS(?) MPH in MPH-na?ve patients might be a feasible option.     

The effects of pathogen challenges on the performance of naïve and immune animals: the problem of prediction

Predictive frameworks for performance under both physical and social stressors are available, but no general framework yet exists for predicting the performance of animals exposed to pathogens. The aim of this paper was to identify the key problems that would need to be solved to achieve this. Challenges of a range of hosts by a range of pathogens were reviewed to consider reductions in growth beyond those associated with reductions in voluntary food intake (VFI). Pair-feeding and marginal response studies identified the extent and mechanisms of how further reductions in growth occur beyond those caused by reduced VFI. Further reductions in growth depended on the pathogen, the host and the dose and were time dependent. In some instances the reduction in VFI fully explained the reduction in growth. Marginal response experiments showed increased maintenance requirements during exposure to pathogens, but these were different for specific amino acids. There were no clear effects on marginal efficiency. Innate immune functions, repair of damaged tissue and expression of acquired immunity caused significant but variable increases in protein (amino acid) requirements. More resistant genotypes had greater requirements for mounting immune responses. The partitioning of protein (amino acids) was found to be different during pathogen challenges. Prediction of the requirements and partitioning of amino acids between growth and immune functions appears to be a crucial problem to solve in order to predict performance during pathogen challenges of different kinds and doses. The problems of accounting for reductions in performance during pathogen challenges that are described here provide a useful starting point for future modelling and experimental solutions.     

Central effects of TNFα on thermogenesis and fever in the rat

Intracerebroventricular (icv) injection of purified recombinant human tumour necrosis factor (TNF , 4–8g) in conscious rats, produced increases in colonic temperature (1.0°C) and resting oxygen consumption (VO₂, 14%) which were maximal after 80–90 minutes. Pretreatment with propranolol (10mg/kg s.c) significantly inhibited the rise in VO₂, and prevented the increase in body temperature. Icv injection of an antagonist to corticotropin releasing factor (-helical CRF 9-41, 25 g), which prevents the pyrogenic and thermogenic actions of interleukin-1, did not influence the effects of TNF on temperature or VO₂. Injection of a fragment of TNF (113–130 amino acid sequence) did not affect body temperature or VO₂. TNF injection (icv) significantly increased brown adipose tissue (BAT)in vitro mitochondrial GDP binding, and this effect was slightly inhibited, but not prevented, by surgical denervation of the tissue, and was unaffected by pretreatment with -helical CRF 9-41. These data indicate that TNF can stimulate thermogenesis by a direct central action. The effects are largely, but not totally, dependent on the sympathetic nervous system but, unlike the thermogenic actions of interleukin they do not require release of CRF.     

Is the self always better than a friend? Self-face recognition in Christians and atheists

Early behavioral studies found that human adults responded faster to their own faces than faces of familiar others or strangers, a finding referred to as self-face advantage. Recent research suggests that the self-face advantage is mediated by implicit positive association with the self and is influenced by sociocultural experience. The current study investigated whether and how Christian belief and practice affect the processing of self-face in a Chinese population. Christian and Atheist participants were recruited for an implicit association test (IAT) in Experiment 1 and a face-owner identification task in Experiment 2. Experiment 1 found that atheists responded faster to self-face when it shared the same response key with positive compared to negative trait adjectives. This IAT effect, however, was significantly reduced in Christians. Experiment 2 found that atheists responded faster to self-face compared to a friend's face, but this self-face advantage was significantly reduced in Christians. Hierarchical regression analyses further showed that the IAT effect positively predicted self-face advantage in atheists but not in Christians. Our findings suggest that Christian belief and practice may weaken implicit positive association with the self and thus decrease the advantage of the self over a friend during face recognition in the believers.     

Is extinction the hallmark of operant discrimination?: Reinforcement and S effects

Using a successive discrimination procedure with rats, three experiments investigated the contribution of reinforcement rate and amount of S(Delta) exposure on the acquisition of an operant discrimination. S(D) components and were always 2 min in length, while S(Delta) (extinction) components were either 1 min or 4 min in length; responses in S(D) were reinforced on one of four schedules. In Experiment 1, each of eight groups were exposed to one possible combination of rate of reinforcement and S(Delta) component length. At every level of reinforcement, the 4 min S(Delta) groups acquired the discrimination more quickly. However, within each level of reinforcement, the proportions of responding in S(D) as a function cumulative S(Delta) exposure were equivalent, regardless of the number of reinforcers earned in S(D), suggesting that extinction is the "hallmark" of discrimination. Experiment 2 sought to replicate these results in a within-subjects design, and although the 4 min S(Delta) conditions always produced superior discriminations, the lack of discriminated responding in some conditions suggested that stimulus disparity was reduced. Experiment 3 clarified those results and extended the finding that the acquisition of operant discrimination closely parallels extinction of responding in S(Delta). In sum, it appears that higher reinforcement rates and longer S(Delta) exposure facilitate the acquisition of discriminated operant responding.     

The effects of acute treatment with Δ9-THC on exploratory behaviour and memory in the rat

The aim of the present study was to evaluate the effects of delta9-tetrahydrocannabinol (delta9-THC) on exploratory behaviour and memory, independent of its locomotor suppressive effects. Dopamine (DA) and noradrenaline (NA) contents were determined in the areas of the brain directly related to such behaviours (hippocampus, striatum and amygdala). An acute dose of delta9-THC led to a decrease in exploratory parameters and motor activity during the holeboard test. The radial arm maze was used to evaluate the effects of this cannabinoid substance on memory. Animals treated with delta9-THC committed more errors in the maze test compared to control, particularly when the retention process was put to test. Furthermore, treatment with delta9-THC led to reduced NA contents in the hippocampus and increased DA contents in the amygdala, without changes in the striatum.