Motivation and timing: clues for modeling the reward system

There is growing evidence that a change in reward magnitude or value alters interval timing, indicating that motivation and timing are not independent processes as was previously believed. The present paper reviews several recent studies, as well as presenting some new evidence with further manipulations of reward value during training vs. testing on a peak procedure. The combined results cannot be accounted for by any of the current psychological timing theories. However, in examining the neural circuitry of the reward system, it is not surprising that motivation has an impact on timing because the motivation/valuation system directly interfaces with the timing system. A new approach is proposed for the development of the next generation of timing models, which utilizes knowledge of the neuroanatomy and neurophysiology of the reward system to guide the development of a neurocomputational model of the reward system. The initial foundation along with heuristics for proceeding with developing such a model is unveiled in an attempt to stimulate new theoretical approaches in the field.     

The nuclear experience of CPEB: Implications for RNA processing and translational control

CPEB is a sequence-specific RNA binding protein that promotes polyadenylation-induced translation in early development, during cell cycle progression and cellular senescence, and following neuronal synapse stimulation. It controls polyadenylation and translation through other interacting molecules, most notably the poly(A) polymerase Gld2, the deadenylating enzyme PARN, and the eIF4E-binding protein Maskin. Here, we report that CPEB shuttles between the nucleus and cytoplasm and that its export occurs via the CRM1-dependent pathway. In the nucleus of Xenopus oocytes, CPEB associates with lampbrush chromosomes and several proteins involved in nuclear RNA processing. CPEB also interacts with Maskin in the nucleus as well as with CPE-containing mRNAs. Although the CPE does not regulate mRNA export, it influences the degree to which mRNAs are translationally repressed in the cytoplasm. Moreover, CPEB directly or indirectly mediates the alternative splicing of at least one pre-mRNA in mouse embryo fibroblasts as well as certain mouse tissues. We propose that CPEB, together with Maskin, binds mRNA in the nucleus to ensure tight translational repression upon export to the cytoplasm. In addition, we propose that nuclear CPEB regulates specific pre-mRNA alternative splicing.     

Substrate use during and following moderate- and low-intensity exercise: Implications for weight control

Substrate utilization during and after low- and moderate-intensity exercise of similar caloric expenditure was compared. Ten active males [age: 26.9 (4.8) years; height: 181.1 (4.8) cm; Mass: 75.7 (8.8) kg; maximum O₂ consumption (V˙O_{2 max} ): 51.2 (4.8) ml · kg⁻¹ · min⁻¹] cycled at 33% and 66% V˙O_{2 max} on separate days for 90 and 45 min, respectively. After exercise, subjects rested in a recumbent position for 6 h. Two h post-exercise, subjects ate a standard meal of 66% carbohydrate (CHO), 11% protein, and 23% fat. Near-continuous indirect calorimetry and measurement of urinary nitrogen excretion were used to determine substrate utilization. Total caloric expenditure was similar for the two trials; however, significantly (P<0.05) more fat [42.4 (3.6) g versus 24.0 (12.2) g] and less CHO [142.5 (28.5) g versus 188.8 (45.2) g] was utilized as a substrate during the low-intensity compared to the moderate-intensity trial. Protein utilization was similar for the two trials. The difference in substrate use can be attributed to the exercise period because over twice as much fat was utilized during low-intensity [30.0 (11.0) g] compared to moderate-intensity exercise [13.6 (6.6) g]. Significantly more (P<0.05) CHO was utilized during the moderate-intensity [106.0 (27.8) g] compared to the low-intensity exercise [68.7 (20.0) g]. Substrate use during the recovery period was not significantly different. We conclude that low-intensity, long-duration exercise results in a greater total fat oxidation than does moderate intensity exercise of similar caloric expenditure. Dietary-induced thermogenesis was not different for the two trials. Accepted: 3 November 1997     

Drug-induced Alterations in the Extracellular Signal-regulated Kinase (ERK) Signalling Pathway: Implications for Reinforcement and Reinstatement

Drug addiction, characterized by high rates of relapse, is recognized as a kind of neuroadaptive disorder. Since the extracellular signal-regulated kinase (ERK) pathway is critical to neuroplasticity in the adult brain, understanding the role this pathway plays is important for understanding the molecular mechanism underlying drug addiction and relapse. Here, we review previous literatures that focus on the effects of exposure to cocaine, amphetamine, Δ⁹-tetrahydrocannabinol (THC), nicotine, morphine, and alcohol on ERK signaling in the mesocorticolimbic dopamine system; these alterations of ERK signaling have been thought to contribute to the drug’s rewarding effects and to the long-term maladaptation induced by drug abuse. We then discuss the possible upstreams of the ERK signaling pathway activated by exposure of drugs of abuse and the environmental cues previously paired with drugs. Finally, we argue that since ERK activation is a key molecular process in reinstatement of conditioned place preference and drug self-administration, the pharmacological manipulation of the ERK pathway is a potential treatment strategy for drug addiction. Haifeng Zhai and Yanqin Li contributed equally to this paper.     

Indirect nontarget effects of host-specific biological control agents: Implications for biological control

Classical biological control of weeds currently operates under the assumption that biological control agents are safe (i.e., low risk) if they do not directly attack nontarget species. However, recent studies indicate that even highly host-specific biological control agents can impact nontarget species through indirect effects. This finding has profound implications for biological control. To better understand the causes of these interactions and their implications, we evaluate recent case studies of indirect nontarget effects of biological control agents in the context of theoretical work in community ecology. We find that although particular indirect nontarget effects are extremely difficult to predict, all indirect nontarget effects of host specific biological control agents derive from the nature and strength of the interaction between the biological control agent and the pest. Additionally, recent theoretical work suggests that the degree of impact of a biological control agent on nontarget species is proportional to the agent’s abundance, which will be highest for moderately successful control agents. Therefore, the key to safeguarding against indirect nontarget effects of host-specific biological control agents is to ensure the biological control agents are not only host specific, but also efficacious. Biological control agents that greatly reduce their target species while remaining host-specific will reduce their own populations through density-dependent feedbacks that minimize risks to nontarget species.     

Physical and ant-mediated refuges from parasitism: Implications for non-target effects in biological control

A promising natural enemy for release against the Asian soybean aphid, Aphis glycines Matsumura, in North America is the aphidiine braconid wasp Binodoxys communis (Gahan). The aphid Aphis monardae Oestlund, a native of North America’s tall-grass prairies, is a non-target species that may be at risk from releases of B. communis. This paper describes ecological facets of A. monardae populations in their native habitat that could protect them from attack by this exotic biological control agent. In prairie habitats, A. monardae populations aggregate in flower heads of their host plant, Monarda fistulosa L. On this host plant, aphids are also commonly tended by four ant species, and ant-tended colonies are larger than un-attended colonies. Laboratory studies showed that parasitism rates of A. monardae by B. communis are significantly higher on vegetative M. fistulosa than on M. fistulosa flower heads. In addition, attendance of A. monardae by the ant Lasius neoniger Emery significantly decreased parasitism by B. communis. Ants attacked and killed host-seeking adult parasitoids, and preyed upon B. communis mummies. No evidence was found that B. communis reared from A. monardae are less susceptible to attack by ants than parasitoids reared from A. glycines. M. fistulosa flower heads and attendance by L. neoniger may act as refuges for A. monardae against B. communis. Our work describes spatial refuges as ecological filters that separate non-target organisms from exotic natural enemies. Implications for classical biological control of A. glycines are discussed.     

Tannins and self-medication: Implications for sustainable parasite control in herbivores

Animals adapt to the variability of the external environment and to their changing internal needs not only by generating homeostatic physiological responses, but also by operating in the external environment. In this study, we determined whether sheep with a gastrointestinal parasite infection increased intake of a low-quality food containing a natural antiparasitic agent (tannins) relative to non-parasitized sheep. Four groups of lambs (n = 8 lambs/group) were assigned to a 2 × 2 factorial design with parasitic burden (P = parasites; NP = no parasites) and the offer of a supplement containing tannins (yes, no) as the main factors. Parasitized lambs ate more of the tannin-containing food than non-parasitized lambs for the first 12 days of the study, when parasite burdens were high, but differences became smaller and disappeared toward the end of the study when parasite burdens decreased. This result suggests the lambs detected the presence of internal parasites or associated symptoms and modified their ingestion of an antiparasitic agent as a function of need.     

Flavonoids and cognitive function: a review of human randomized controlled trial studies and recommendations for future studies

Evidence in support of the neuroprotective effects of flavonoids has increased significantly in recent years, although to date much of this evidence has emerged from animal rather than human studies. Nonetheless, with a view to making recommendations for future good practice, we review 15 existing human dietary intervention studies that have examined the effects of particular types of flavonoid on cognitive performance. The studies employed a total of 55 different cognitive tests covering a broad range of cognitive domains. Most studies incorporated at least one measure of executive function/working memory, with nine reporting significant improvements in performance as a function of flavonoid supplementation compared to a control group. However, some domains were overlooked completely (e.g. implicit memory, prospective memory), and for the most part there was little consistency in terms of the particular cognitive tests used making across study comparisons difficult. Furthermore, there was some confusion concerning what aspects of cognitive function particular tests were actually measuring. Overall, while initial results are encouraging, future studies need to pay careful attention when selecting cognitive measures, especially in terms of ensuring that tasks are actually sensitive enough to detect treatment effects.     

A randomized, placebo-controlled, double-blind trial of supplemental docosahexaenoic acid on cognitive processing speed and executive function in females of reproductive age with phenylketonuria: A pilot study

Low blood docosahexaenoic acid (DHA) is reported in patients with phenylketonuria (PKU); however, the functional implications in adolescents and adults are unknown. This pilot study investigated the effect of supplemental DHA on cognitive performance in 33 females with PKU ages 12–47 years. Participants were randomly assigned to receive DHA (10 mg/kg/day) or placebo for 4.5 months. Performance on cognitive processing speed and executive functioning tasks was evaluated at baseline and follow up. Intention-to-treat and per protocol analyses were performed. At follow up, biomarkers of DHA status were significantly higher in the DHA-supplemented group. Performance on the cognitive tasks and reported treatment-related adverse events did not differ. While no evidence of cognitive effect was seen, a larger sample size is needed to be conclusive, which may not be feasible in this population. Supplementation was a safe and effective way to increase biomarkers of DHA status (www.clinicaltrials.gov; Identifier: NCT00892554).     

Skewed reproductive success among male white-spotted charr land-locked by an erosion control dam: Implications for effective population size

In 1996 and 1997, the spawning behavior of fluvial white-spotted charr Salvelinus leucomaenis, was observed in the upstream area of an erosion control dam. A small number of males with relatively large body size mated successfully with females as a pair, while almost all satellite males did not sneak successfully, resulting in a non-random mating system. The low sneaking success of subordinate males, in addition to the monopolization of spawning opportunities by a few dominant males, is one of the most important causes of skewed reproductive success among males. The total number of adult fishes in the study area (N: approximately half of the whole tributary above a dam) was estimated as 148 and 102 in 1996 and 1997, respectively. Based on these findings and some further assumptions, the estimated effective population size (N_e) was low in both years. The N_e/N ratio ranged from 0.33 to 0.36 in both years. In addition to reduced population size by construction of an impassable dam, the above-dam population suffered low N_e due to skewed reproductive success among males. The low N_e may be one cause of extinction in above-dam populations of fluvial charr, especially just after the construction of impassable barriers.     

Review. Genetics of addictions: strategies for addressing heterogeneity and polygenicity of substance use disorders

Addictions are common psychiatric disorders that exert high cost to the individual and to society. Addictions are a result of the interplay of multiple genetic and environmental factors. They are characterized by phenotypic and genetic heterogeneity as well as polygenicity, implying a contribution of different neurobiological mechanisms to the clinical diagnosis. Therefore, treatments for most substance use disorders are often only partially effective, with a substantial proportion of patients failing to respond. To address heterogeneity and polygenicity, strategies have been developed to identify more homogeneous subgroups of patients and to characterize genes contributing to their phenotype. These include genetic linkage and association studies as well as functional genetic analysis using endophenotypes and animal behavioural experimentation. Applying these strategies in a translational context aims at improving therapeutic response by the identification of subgroups of addiction patients for individualized, targeted treatment strategies. This article aims to discuss strategies addressing heterogeneity and polygenicity of substance use disorders by presenting results of recent research on genetic and environmental components of addiction. It will also introduce the European IMAGEN study that aims to integrate methodical approaches discussed in order to identify the genetic and neurobiological basis of behavioural traits relevant to the development of addictions.     

Advanced model‐based control strategies for the intensification of upstream and downstream processing in mAb production

Current industrial trends encourage the development of sustainable, environmentally friendly processes with minimal energy and material consumption. In particular, the increasing market demand in biopharmaceutical industry and the tight regulations in product quality necessitate efficient operating procedures that guarantee products of high purity. In this direction, process intensification via continuous operation paves the way for the development of novel, eco‐friendly processes, characterized by higher productivity and lower production costs. This work focuses on the development of advanced control strategies for (i) a cell culture system in a bioreactor and (ii) a semicontinuous purification process. More specifically, we consider a fed‐batch culture of GS‐NS0 cells and the semicontinuous Multicolumn Countercurrent Solvent Gradient Purification (MCSGP) for the purification process. The controllers are designed following the PAROC framework/software platform and their capabilities are assessed in silico, against the process models. It is demonstrated that the proposed controllers efficiently manage to increase the system productivity, returning strategies that can lead to continuous, stable process operation. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:966–988, 2017     

Short-distance dispersal behavior and establishment of the parasitoid Gonatocerus ashmeadi (Hymenoptera: Mymaridae) in Tahiti: Implications for its use as a biological control agent against Homalodisca vitripennis (Hemiptera: Cicadellidae)

The egg parasitoid Gonatocerus ashmeadi Girault (Hymenoptera: Mymaridae), was introduced into French Polynesia as a biological control agent to control the invasive plant feeding pest Homalodisca vitripennis (Germar) (Hemiptera: Cicadellidae). The short-distance dispersal of G. ashmeadi was monitored as part of the biological control program. G. ashmeadi showed exponential dispersal capacity with 47 m/day being a minimum estimate of its natural rate of spread at high host densities (>150 nymphs per minute of sweep net sampling) in urbanized areas at sea level, which were characterized by a high diversity of exotic ornamental plants. This rate of spread contrasted starkly with almost nonexistent establishment and dispersal where host densities were very low (<2 nymphs per minute of sweep net sampling) at high elevation (800 m) with relatively undisturbed native vegetation. Survey results across different altitudes revealed an effect of vegetative diversity and host density on the measurable mobility and establishment of G. ashmeadi. In contrast, no significant influence of wind direction was found on G. ashmeadi dispersal rate or direction. Survey results for G. ashmeadi from French Polynesia suggest that the best release establishment strategies for classical biological control of H. vitripennis are: (1) many small releases where host density is high, or (2) larger and fewer releases where host densities are low.     

Parasitoids, predators and PCR: the use of diagnostic molecular markers in biological control of Arthropods

Abstract:  The polymerase chain reaction (PCR) revolutionized the field of diagnostics, and today it has routine applications in medical, veterinary, forensic and botanical sciences. The fields of biological control and insect pest management have generally been slow to adopt PCR-based diagnostics in comparison with other fields of science. However, there has been increasing interest in the use of molecular diagnostic tools in arthropod biological control. In applied entomology, molecular techniques have generally been used for insect identification and systematics; however, PCR-based techniques are increasingly becoming recognized as valuable tools in ecological studies. Here, we review research that has used PCR-based techniques for parasitoid and predator/prey identification and detection, and place these studies in the context of their contributions to biological control of arthropods. The status and future directions of diagnostic molecular markers in applied entomology and insect pest management are also discussed.