Dopamine Receptor Stimulation Does Not Affect Phosphoinositide Hydrolysis in Slices of Rat Striatum

The effect of dopamine receptor stimulation on the accumulation of labelled inositol phosphates in rat striatal slices under basal and stimulated conditions was examined following preincubation with [3H]inositol. Incubation of striatal slices with the selective D-1 agonist SKF 38393 or the selective D-2 agonist LY 171555 for 5 or 30 min did not affect the basal accumulation of labelled inositol mono-, bis-, tris-, and tetrakisphosphate. Resolution by HPLC of inositol trisphosphate into inositol-1,3,4-tris-phosphate and inositol-1,4,5-trisphosphate isomers revealed that under basal conditions dopamine did not influence the accumulation of inositol-1,4,5-trisphosphate. Depolarisation evoked by KCl, or addition of the muscarinic receptor agonist carbachol, produced a marked increase in the accumulation of labelled inositol phosphates in both the presence and absence of lithium. Addition of dopamine did not reduce the ability of KCl or carbachol to increase inositol phospholipid hydrolysis. In the presence of lithium, dopamine (100 microM) enhanced KCl-stimulated inositol phospholipid hydrolysis, but this effect appears to be mediated by alpha 1 adrenoceptors because it was blocked by prazosin. SKF 38393 (10 microM) or LY 171555 (10 microM) also did not affect carbachol-stimulated inositol phospholipid hydrolysis. These data, in contrast to recent reports, suggest that striatal dopamine receptors do not appear to be linked to inositol phospholipid hydrolysis.     

Calmodulin-stimulated protein kinase activity from rat pancreas

Previous work from our laboratory has demonstrated that neurohumoral stimulation of the exocrine pancreas is associated with the phosphorylation of the Mr 29,000 ribosomal protein S6. In a cell-free system using pancreatic postmicrosomal supernatant as the kinase donor, we found that the following co-factors stimulate the phosphorylation of the Mr 29,000 ribosomal protein: calcium with calmodulin, calcium with phosphatidyl serine, and cAMP. These findings suggest that the pancreas contains a calcium-calmodulin-dependent protein kinase (CaM-PK) that can phosphorylate the Mr 29,000 ribosomal protein. A CaM-PK activity was partially purified sequentially by ion exchange, gel filtration, and calmodulin-affinity chromatography. Phosphorylation of the Mr 29,000 ribosomal protein by the partially purified CaM-PK was dependent on the presence of both calcium and calmodulin and not on the other co- factors. The CaM-PK fraction contained a phosphoprotein of Mr 51,000 whose phosphorylation was also dependent on calcium and calmodulin. When 125I-calmodulin-binding proteins from the CaM-PK fraction were identified using electrophoretic transfers of SDS-polyacrylamide gels, a single Mr 51,000 protein was labeled. The preparation enriched in CaM- PK activity contained an Mr 51,000 protein that underwent phosphorylation in a calcium-calmodulin-dependent manner and an Mr 51,000 calmodulin-binding protein. It is therefore possible that the CaM-PK may comprise a calmodulin-binding phosphoprotein component of Mr 51,000.     

Preoperative diagnosis of bilateral renal oncocytoma by needle aspiration cytology. A case report

The cytohistologic and ultrastructural findings in a case of bilateral renal oncocytoma diagnosed by needle aspiration cytology are presented. This case appears to be the first reported example in which the preoperative needle aspiration cytologic diagnosis of bilateral renal oncocytoma was made due to the presence of characteristic tumor cells that were seen singly or in small clusters with rounded polygonal shapes and abundant eosinophilic granular cytoplasm. The preoperative diagnosis of bilateral oncocytoma permitted a timely decision as to the appropriate management in this case.     

Fast to Forgive,Slow to Retaliate: Intuitive Responses in the Ultimatum Game Depend on the Degree of Unfairness

Evolutionary accounts have difficulty explaining why people cooperate with anonymous strangers they will never meet. Recently models, focusing on emotional processing, have been proposed as a potential explanation, with attention focusing on a dual systems approach based on system 1 (fast, intuitive, automatic, effortless, and emotional) and system 2 (slow, reflective, effortful, proactive and unemotional). Evidence shows that when cooperation is salient, people are fast (system 1) to cooperate, but with longer delays (system 2) they show greed. This is interpreted within the framework of the social heuristic hypothesis (SHH), whereby people overgeneralize potentially advantageous intuitively learnt and internalization social norms to ‘atypical’ situations. We extend this to explore intuitive reactions to unfairness by integrating the SHH with the ‘fast to forgive, slow to anger’ (FFSA) heuristic. This suggests that it is advantageous to be prosocial when facing uncertainty. We propose that whether or not someone intuitively shows prosociality (cooperation) or retaliation is moderated by the degree (certainty) of unfairness. People should intuitively cooperate when facing mild levels of unfairness (fast to forgive) but when given longer to decide about another''s mild level of unfairness should retaliate (slow to anger). However, when facing severe levels of unfairness, the intuitive response is always retaliation. We test this using a series of one-shot ultimatum games and manipulate level of offer unfairness (50:50 60:40, 70:30, 80:20, 90:10) and enforced time delays prior to responding (1s, 2s, 8s, 15s). We also measure decision times to make responses after the time delays. The results show that when facing mildly unfair offers (60:40) people are fast (intuitive) to cooperate but with longer delays reject these mildly unfair offers: ‘fast to forgive, and slow to retaliate’. However, for severely unfair offers (90:10) the intuitive and fast response is to always reject.     

A model for gain of function in superoxide dismutase

Studies have found that mutant, misfolded superoxide dismutase [Cu–Zn] (SOD1) can convert wild type SOD1 (wtSOD1) in a prion-like fashion, and that misfolded wtSOD1 can be propagated by release and uptake of protein aggregates. In developing a prion-like mechanism for this propagation of SOD1 misfolding we have previously shown how enervation of the SOD1 electrostatic loop (ESL), caused by the formation of transient non-obligate SOD1 oligomers, can lead to an experimentally observed gain of interaction (GOI) that results in the formation of SOD1 amyloid-like filaments. It has also been shown that freedom of ESL motion is essential to catalytic function. This work investigates the possibility that restricting ESL mobility might not only compromise superoxide catalytic activity but also serve to promote the peroxidase activity of SOD1, thus implicating the formation of SOD1 oligomers in both protein misfolding and in protein oxidation.     

Kinematic and electromyographic analysis of the Nordic Hamstring Exercise

The Nordic Hamstring Exercise (NHE) has been introduced as a training tool to improve the efficiency of eccentric hamstring muscle contraction. The aim of this study was to perform a biomechanical analysis of the NHE. Eighteen participants (20.4 ± 1.9 years) performed two sets of five repetitions each of the NHE and maximal eccentric voluntary contraction (MEVC) of the knee flexors on an isokinetic dynamometer whilst knee angular displacement and electrical activity (EMG) of biceps femoris were measured. EMG was on average higher during the NHE (134.3% of the MEVC). During the forward fall of the NHE, the angle at which a sharp increase in downward velocity occurred varied between 47.9 and 80.5 deg, while the peak knee angular velocity (pVelocity) varied between 47.7 and 132.8 deg s^?1. A significant negative correlation was found between pVelocity and peak EMG (r = ?0.62, p < 0.01) and EMG at 45 deg (r = ?0.75, p < 0.01) expressed as a percentage of peak MEVC EMG. Some of the variables analyzed exhibited good to excellent levels of intra- and inter-session reliability. This type of analysis could be used to indirectly monitor the level of eccentric strength of the hamstring muscles while performing the NHE and potentially any training- or injury-related changes.     

Von Hippel-Lindau disease

Germline mutations in the VHL tumour suppressor gene may cause a variety of phenotypes including von Hippel-Lindau (VHL) disease, familial phaeochromocytoma and inherited polycythaemia. VHL disease is a multisystem familial cancer syndrome and is the commonest cause of familial renal cell carcinoma (RCC). VHL disease provides a paradigm for illustrating how studies of a rare familial cancer syndrome can produce advances in clinical medicin and important insights into basic biological processes. Thus the identification of the VHL gene has improved the diagnosis and clinical management of VHL disease and provided insights into the pathogenesis of sporadic clear cell RCC. Functional investigations of the VHL gene product have provided novel information on how cells sense oxygen and the role of hypoxia-response pathways in human tumourigenesis. Such information offers prospects of novel therapeutic interventions for VHL disease and common cancers including RCC.