ANALYSIS OF SEROTONERGIC MODULATION OF NEURONS INVOLVED IN TWO DEFENSIVE BEHAVIORS IN APLYSIA CALIFORNICA (CYCLIC-AMP, AROUSAL, CALCIUM, POTASSIUM)

Sensitization is a simple form of learning which refers to an enhancement of a behavioral response resulting from an exposure to a novel stimulus. While sensitization is found throughout the animal world, little is known regarding the underlying neural mechanisms. By taking advantage of the simple nervous system of the marine mollusc Aplysia, I have begun to examine the cellular and molecular mechanisms underlying this simple form of learning. In an attempt to determine the generality of the mechanisms of neuromodulation underlying sensitization, I have investigated and compared the modulation of neurons involved in two defensive behaviors in Aplysia, the defensive inking response and defensive tail withdrawal.^ The motor neurons that produce the defensive release of ink receive a slow decreased conductance excitatory postsynaptic potential (EPSP) in response to sensitizing stimuli. Using electrophysiological techniques, it was found that serotonin (5-HT) mimicked the physiologically produced slow EPSP. 5-HT produced its response through a reduction in a voltage-independent conductance to K('+). The 5-HT sensitive K('+) conductance of the ink motor neurons was separate from the fast K('+), delayed K('+), and Ca('2+)-activated K('+) conductances found in these and other molluscan neurons. 5-HT was shown to produce a decrease in K('+) conductance in the ink motor neurons through an elevation of cellular cAMP.^ The mechanosensory neurons that participate in the defensive tail withdrawal response are also modulated by sensitizing stimuli through the action of 5-HT. Using electrophysiological techniques, it was found that 5-HT modulated the tail sensory neurons through a reduction in a voltage-dependent conductance to K('+). The serotonin-sensitive K('+) conductance was found to be largely a Ca('2+)-activated K('+) conductance. Much like the ink motor neurons, 5-HT produced its modulation through an elevation of cellular cAMP. While the actual K('+) conductance modulated by 5-HT in these two classes of neurons differs, the following generalizations can be made: (1) the effects of sensitizing stimuli are mimicked by 5-HT, (2) 5-HT produces its effect through an elevation of cellular cAMP, and (3) the conductance to K('+) is modulated by 5-HT. ^

Radical chain reactions involving 9-alkyl-9-borafluorenes

The preparation of 9-alkyl-9-borafluorenes and their use as radical precursors in chain reactions were investigated. These organoboranes were found to be excellent precursors of primary and secondary alkyl radicals. Reactions were readily initiated by traces of oxygen and efficient processes involving sulfonyl-based radical traps were discovered. Due to the very high reactivity of the intermediate 9-H and 9-alkyl-9-borafluorenes, problems of reproducibility were identified.

Patient information leaflets: informing or frightening? A focus group study exploring patients' emotional reactions and subsequent behavior towards package leaflets of commonly prescribed medications in family practices.

BACKGROUND The purpose of patient information leaflets (PILs) is to inform patients about the administration, precautions and potential side effects of their prescribed medication. Despite European Commission guidelines aiming at increasing readability and comprehension of PILs little is known about the potential risk information has on patients. This article explores patients' reactions and subsequent behavior towards risk information conveyed in PILs of commonly prescribed drugs by general practitioners (GPs) for the treatment of Type 2 diabetes, hypertension or hypercholesterolemia; the most frequent cause for consultations in family practices in Germany. METHODS We conducted six focus groups comprising 35 patients which were recruited in GP practices. Transcripts were read and coded for themes; categories were created by abstracting data and further refined into a coding framework. RESULTS Three interrelated categories are presented: (i) The vast amount of side effects and drug interactions commonly described in PILs provoke various emotional reactions in patients which (ii) lead to specific patient behavior of which (iii) consulting the GP for assistance is among the most common. Findings show that current description of potential risk information caused feelings of fear and anxiety in the reader resulting in undesirable behavioral reactions. CONCLUSIONS Future PILs need to convey potential risk information in a language that is less frightening while retaining the information content required to make informed decisions about the prescribed medication. Thus, during the production process greater emphasis needs to be placed on testing the degree of emotional arousal provoked in patients when reading risk information to allow them to undertake a benefit-risk-assessment of their medication that is based on rational rather than emotional (fearful) reactions.

Defensive weapons and defense signals in plants: Some metabolites serve both roles

The defense of plants against herbivores and pathogens involves the participation of an enormous range of different metabolites, some of which act directly as defensive weapons against enemies (toxins or deterrents) and some of which act as components of the complex internal signaling network that insures that defense is timed to enemy attack. Recent work reveals a surprising trend: The same compounds may act as both weapons and signals of defense. For example, two groups of well-studied defensive weapons, glucosinolates and benzoxazinoids, trigger the accumulation of the protective polysaccharide callose as a barrier against aphids and pathogens. In the other direction, several hormones acting in defense signaling (and their precursors and products) exhibit activity as weapons against pathogens. Knowing which compounds are defensive weapons, which are defensive signals and which are both is vital for understanding the functioning of plant defense systems.

Recommendations for HLA-B*15:02 and HLA-A*31:01 genetic testing to reduce the risk of carbamazepine-induced hypersensitivity reactions.

OBJECTIVE To systematically review evidence on genetic risk factors for carbamazepine (CBZ)-induced hypersensitivity reactions (HSRs) and provide practice recommendations addressing the key questions: (1) Should genetic testing for HLA-B*15:02 and HLA-A*31:01 be performed in patients with an indication for CBZ therapy to reduce the occurrence of CBZ-induced HSRs? (2) Are there subgroups of patients who may benefit more from genetic testing for HLA-B*15:02 or HLA-A*31:01 compared to others? (3) How should patients with an indication for CBZ therapy be managed based on their genetic test results? METHODS A systematic literature search was performed for HLA-B*15:02 and HLA-A*31:01 and their association with CBZ-induced HSRs. Evidence was critically appraised and clinical practice recommendations were developed based on expert group consensus. RESULTS Patients carrying HLA-B*15:02 are at strongly increased risk for CBZ-induced Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) in populations where HLA-B*15:02 is common, but not CBZ-induced hypersensitivity syndrome (HSS) or maculopapular exanthema (MPE). HLA-B*15:02-positive patients with CBZ-SJS/TEN have been reported from Asian countries only, including China, Thailand, Malaysia, and India. HLA-B*15:02 is rare among Caucasians or Japanese; no HLA-B*15:02-positive patients with CBZ-SJS/TEN have been reported so far in these groups. HLA-A*31:01-positive patients are at increased risk for CBZ-induced HSS and MPE, and possibly SJS/TEN and acute generalized exanthematous pustulosis (AGEP). This association has been shown in Caucasian, Japanese, Korean, Chinese, and patients of mixed origin; however, HLA-A*31:01 is common in most ethnic groups. Not all patients carrying either risk variant develop an HSR, resulting in a relatively low positive predictive value of the genetic tests. SIGNIFICANCE This review provides the latest update on genetic markers for CBZ HSRs, clinical practice recommendations as a basis for informed decision making regarding the use of HLA-B*15:02 and HLA-A*31:01 genetic testing in patients with an indication for CBZ therapy, and identifies knowledge gaps to guide future research. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.

Role of phytohormones in insect-specific plant reactions

The capacity to perceive and respond is integral to biological immune systems, but to what extent can plants specifically recognize and respond to insects? Recent findings suggest that plants possess surveillance systems that are able to detect general patterns of cellular damage as well as highly specific herbivore-associated cues. The jasmonate (JA) pathway has emerged as the major signaling cassette that integrates information perceived at the plant–insect interface into broad-spectrum defense responses. Specificity can be achieved via JA-independent processes and spatio-temporal changes of JA-modulating hormones, including ethylene (ET), salicylic acid (SA), abscisic acid (ABA), auxin, cytokinins (CK), brassinosteroids (BR) and gibberellins (GB). The identification of receptors and ligands and an integrative view of hormone-mediated response systems are crucial to understand specificity in plant immunity to herbivores.

A specialist root herbivore exploits defensive metabolites to locate nutritious tissues

he most valuable organs of plants are often particularly rich in essential elements, but also very well defended. This creates a dilemma for herbivores that need to maximise energy intake while minimising intoxication. We investigated how the specialist root herbivore Diabrotica virgifera solves this conundrum when feeding on wild and cultivated maize plants. We found that crown roots of maize seedlings were vital for plant development and, in accordance, were rich in nutritious primary metabolites and contained higher amounts of the insecticidal 2,4-dihydroxy-7-methoxy-1,4-benzoxazin-3-one (DIMBOA) and the phenolic compound chlorogenic acid. The generalist herbivores Diabrotica balteata and Spodoptera littoralis were deterred from feeding on crown roots, whereas the specialist D. virgifera preferred and grew best on these tissues. Using a 1,4-benzoxazin-3-one-deficient maize mutant, we found that D. virgifera is resistant to DIMBOA and other 1,4-benzoxazin-3-ones and that it even hijacks these compounds to optimally forage for nutritious roots

Signal signature of aboveground-induced resistance upon belowground herbivory in maize

Plants activate local and systemic defence mechanisms upon exposure to stress. This innate immune response is partially regulated by plant hormones, and involves the accumulation of defensive metabolites. Although local defence reactions to herbivores are well studied, less is known about the impact of root herbivory on shoot defence. Here, we examined the effects of belowground infestation by the western corn rootworm Diabrotica virgifera virgifera on aboveground resistance in maize. Belowground herbivory by D. v. virgifera induced aboveground resistance against the generalist herbivore Spodoptera littoralis, and the necrotrophic pathogen Setosphaeria turcica. Furthermore, D. v. virgifera increased shoot levels of 2,4-dihydroxy-7-methoxy-1,4-benzoxazin-3-one (DIMBOA), and primed the induction of chlorogenic acid upon subsequent infestation by S. littoralis. To gain insight into the signalling network behind this below- and aboveground defence interaction, we compiled a set of 32 defence-related genes, which can be used as transcriptional marker systems to detect activities of different hormone-response pathways. Belowground attack by D. v. virgifera triggered an ABA-inducible transcription pattern in the shoot. The quantification of defence hormones showed a local increase in the production of oxylipins after root and shoot infestation by D. v. virgifera and S. littoralis, respectively. On the other hand, ABA accumulated locally and systemically upon belowground attack by D. v. virgifera. Furthermore, D. v. virgifera reduced the aboveground water content, whereas the removal of similar quantities of root biomass had no effect. Our study shows that root herbivory by D. v. virgifera specifically alters the aboveground defence status of a maize, and suggests that ABA plays a role in the signalling network mediating this interaction.

Punitive reactions to completed crimes versus accidentally uncompleted crimes

Previous studies have shown that the harm caused by crime affects punitive reactions even if differences in the degree of harm are merely accidental. However, it remains unclear whether the effect is direct or whether it is mediated by attributed responsibility or blame. Participants were 303 university students who listened to 4 case vignettes (between-subjects design). Half received information about a completed crime and half about an accidentally uncompleted crime. Crime type was either fraud or rape. The results suggest that individuals consider the actual harm to a significantly greater extent than attribution theory would predict. Moreover, the link between harm and punishment was virtually not mediated by attributed blame and not moderated by individual differences in morality. Future studies should investigate whether the harm-punishment link is a result of an automatic act of retaliation or a desire to compensate for the harm done to the victim (restorative justice).

Restoring balance within cognitive unit or deservingness evaluation? The role of attitudes and deservingness in shaping emotional reactions to others’ outcomes

Based on Heider’s theory I persumed that personal attitudes are stronger predictors of emotional responses to others’ outcomes than deservingness evaluation. I manipulated outcome, attitude and deservingness experimentally, and measured specific emotions. It appeared deservingness to play a secondary role in eliciting joy and sorrow when interpersonal attitudes were involved.