Characterization of a mutated KCNJ5 gene, G387R, in unilateral primary aldosteronism

Somatic mutation in the KCNJ5 gene is a common driver of autonomous aldosterone overproduction in aldosterone-producing adenomas (APA). KCNJ5 mutations contribute to a loss of potassium selectivity, and an inward Na+ current could be detected in cells transfected with mutated KCNJ5. Among 223 unilateral primary aldosteronism (uPA) individuals with a KCNJ5 mutation, we identified 6 adenomas with a KCNJ5 p.Gly387Arg (G387R) mutation, previously unreported in uPA patients. The six uPA patients harboring mutant KCNJ5-G387R were older, had a longer hypertensive history, and had milder elevated preoperative plasma aldosterone levels than those APA patients with more frequently detected KCNJ5 mutations. CYP11B2 immunohistochemical staining was only positive in three adenomas, while the other three had co-existing multiple aldosterone-producing micronodules. The bioinformatics analysis predicted that function of the KCNJ5-G387R mutant channel could be pathological. However, the electrophysiological experiment demonstrated that transfected G387R mutant cells did not have an aberrantly stimulated ion current, with lower CYP11B2 synthesis and aldosterone production, when compared to that of the more frequently detected mutant KCNJ5-L168R transfected cells. In conclusion, mutant KCNJ5-G387R is not a functional KCNJ5 mutation in unilateral PA. Compared with other KCNJ5 mutations, the observed mildly elevated aldosterone expression actually hindered the clinical identification of clinical unilateral PA. The KCNJ5-G387R mutation needs to be distinguished from functional KCNJ5 mutations during genomic analysis in APA evaluation because of its functional silence.

Old Story, New Results and Analyses

An eye-tracking and an electrophysiological experiment using a sentence/picture matching task were carried out in order to assess whether there would be significant differences between semantic restrictiveness properties of Prepositional Phrases (PPs) vis-à-vis those of Relative Clauses (RCs), attached as modifiers respectively to a local PP or to a non-local DP (e.g. the horse with the parrot with brown spots/the horse with the parrot that has brown spots). Two hypotheses were entertained, namely, (i) an operator construction such as an RC would be construed non-locally, that is, would attach high as a default, even if there is semantic bias attracting it to a low attachment; (ii) a light constituent (PP) has no prosodic autonomy and will be more available to local attachment and therefore would tend to attach locally as a default, even if there is semantic bias attracting it to a high attachment. Results in both experiments were in favor of the hypotheses and we speculate whether they could be more deeply grounded into the representational alternatives projected by linguistic theory itself.

Neurophysiology of grapheme decoding

This study zooms in on the specialization of visual processing that underlies grapheme and word form processing, and presents an electrophysiological experiment performed with 8th graders in a public state elementary school. The methodology of Event Related Brain Potential (EEG-ERP) was used to collect and analyze the N170 component, a neurophysiological signature sensitive to grapheme and word form processing. The test results indicated that, in this group, higher performance in grapheme recognition was not associated to a reduced difference between ERP wave amplitudes in response to word and false font stimuli, but instead to a clear left lateralization of print sensitive N170 responses. Differently from most ERP studies that uses the grand-averaging of all participants’ ERP responses, the current analysis also investigated individual performance of participants. In this modality, the varying levels of intensity and lateralization of the neurophysiological response indicate that a large portion of the participants remain in the process of obtaining reading fluency long after having started to learn how to read. The qualitative correlation between performance and the degree of lateralization is, thus, a novel and promising measurement involving the N170 component as a descriptive and predictive tool in the monitoring of reading acquisition stages.

Automatic System for Identification and Analysis of Burst

Although there are complex patterns of discharges exist in neurons, which are often clustered in bursts, the pattern of the burst discharge can substantially change with the alternation of the living environment of the neurons. Furthermore, there is a big difference in the physiological and pharmacological characteristics of various types of burst discharges. So it is necessary to analyze the information contained in various types of burst discharges. Here, an automatic system for identification and analysis of the neuron discharge based on plotting histograms of the logarithm of the interspike interval was designed. The system consists of neuron discharge collecting unit, neuron discharge processing unit, battery monitoring, real-time charging unit and bursts processing software. The system can identify the burst discharge from the neuron discharge without any omission and make statistical analysis. By using this device, the electrophysiological experiment that the spontaneous and evoked discharges of wide dynamic range neurons in spinal dorsal horn of rats were recorded was smoothly completed. The result of statistical analysis indicated that the device can give the corresponding interspike interval aimed at various types of burst discharges and respectively identify the burst discharges in the different amplitude spikes, which provide a tool for further research on the biosensor and the neural communication.

Dietary selection Behaviour in Spodoptera Littoralis: The Effects of conditioning Diet and conditioning period on Neural Responsiveness and selection Behaviour

1. This paper forms part of our study of the behavioural and neural mechanisms involved in dietary selection behaviour of larvae of the polyphagous noctuid Spodoptera littoralis (Boisduval). 2. Larvae were conditioned on one of four chemically defined artificial diets for 4, 8 or 12 h. Diets differed in their proportions of protein and digestible carbohydrate: the PC diet contained 20% protein and 10% carbohydrate; the P diet contained 20 % protein but the 10 % carbohydrate was replaced by indigestible cellulose; the C diet contained 10% digestible carbohydrate and the protein was replaced by cellulose, and the 0 diet lacked both protein and carbohydrate. After conditioning, the larvae were exposed to either behavioural or electrophysiological experiments. 3. In the behavioural choice experiment, larvae were provided with both P and C diets for 9 h. The conditioning diets P and 0 influenced which of the two choice diets was first contacted; significantly higher proportions of the larvae conditioned on the P diet initially contacted the C choice diet and significantly higher proportions of larvae conditioned on the 0 diet initially contacted the P choice diet. Larvae fed on the diet they first contacted and the probability of stopping the first meal was greater when that diet was P, regardless of the conditioning diet. The duration of the first meal on the C choice diet was significantly longer for larvae conditioned on diets lacking digestible carbohydrate (P and 0) than for those conditioned on either PC or C diets. 4. Larvae were observed to compensate for a deficiency in protein by increasing the frequency of feeding contacts with the P choice diet but not the duration of these contacts. To compensate for a deficiency in digestible carbohydrate, the larvae increased the duration of their feeding contacts with the C choice diet. 5. In the electrophysiological experiment, the maxillary styloconic sensilla were stimulated with an amino acid mixture and sucrose. Neural responses were recorded from two groups of larvae, one after they had been conditioned on one of the four diets for 4, 8 or 12 h and the other after they had subsequently been exposed to the choice diets for 9h. Larvae in the first group that had been conditioned on diets lacking sucrose (P and 0) were more responsive to sucrose than larvae conditioned on diets containing sucrose (PC and C). The reverse occurred with the response to the amino acid mixture, with larvae conditioned on diets containing protein (PC and P) being less responsive to the amino acid mixture than those conditioned on diets lacking protein (C and 0). After the 9h choice period, the responsiveness of sensilla was no longer related to the conditioning diet.