Correction: Ankyrin-G regulates forebrain connectivity and network synchronization via interaction with GABARAP.

In the original version of this article, affiliation 3 was given as: "Division of Life Sciences, State Key Laboratory of Molecular Neuroscience, Hong Kong, University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China". This has now been corrected to: "Division of Life Sciences, State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China".Additionally in the 'Data availability' section an incorrect accession code was given. The accession code has now been changed from 'PDB A9X (AnkG:GABARAPL)' to 'PDB 6A9X (AnkG:GABARAP)'.These errors have been corrected in both the PDF and HTML versions of the Article.

Ankyrin-G regulates forebrain connectivity and network synchronization via interaction with GABARAP.

GABAergic circuits are critical for the synchronization and higher order function of brain networks. Defects in this circuitry are linked to neuropsychiatric diseases, including bipolar disorder, schizophrenia, and autism. Work in cultured neurons has shown that ankyrin-G plays a key role in the regulation of GABAergic synapses on the axon initial segment and somatodendritic domain of pyramidal neurons, where it interacts directly with the GABAA receptor-associated protein (GABARAP) to stabilize cell surface GABAA receptors. Here, we generated a knock-in mouse model expressing a mutation that abolishes the ankyrin-G/GABARAP interaction (Ank3 W1989R) to understand how ankyrin-G and GABARAP regulate GABAergic circuitry in vivo. We found that Ank3 W1989R mice exhibit a striking reduction in forebrain GABAergic synapses resulting in pyramidal cell hyperexcitability and disruptions in network synchronization. In addition, we identified changes in pyramidal cell dendritic spines and axon initial segments consistent with compensation for hyperexcitability. Finally, we identified the ANK3 W1989R variant in a family with bipolar disorder, suggesting a potential role of this variant in disease. Our results highlight the importance of ankyrin-G in regulating forebrain circuitry and provide novel insights into how ANK3 loss-of-function variants may contribute to human disease.

Chromosomal loci that influence oral nicotine consumption in C57BL/6J x C3H/HeJ F2 intercross mice.

Several studies have demonstrated that there are genetic influences on free-choice oral nicotine consumption in mice. In order to establish the genetic architecture that underlies individual differences in free-choice nicotine consumption, quantitative trait loci (QTL) mapping was used to identify chromosomal regions that influence free-choice nicotine consumption in male and female F(2) mice derived from a cross between C57BL/6J and C3H/HeJ mice. These two mouse strains were chosen not only because they differ significantly for oral nicotine consumption, but also because they are at or near phenotypic extremes for all measures of nicotine sensitivity that have been reported. A four-bottle choice paradigm was used to assess nicotine consumption over an 8-day period. The four bottles contained water or water supplemented with 25, 50 or 100 microg/ml of nicotine base. Using micrograms of nicotine consumed per milliliter of total fluid consumed per day as the nicotine consumption phenotype, four significant QTL were identified. The QTL with the largest LOD score was located on distal chromosome 1 (peak LOD score = 15.7). Other chromosomes with significant QTL include central chromosome 4 (peak LOD score = 4.1), proximal chromosome 7 (peak LOD score = 6.1) and distal chromosome 15 (peak LOD score = 4.8). These four QTL appear to be responsible for up to 62% of the phenotypic variance in oral nicotine consumption.

The effect of social class and dental features on referrals for orthodontic advice and treatment.

Patients referred to the Orthodontic Department of Glasgow Dental Hospital over a 5-year period were divided into social class. The analysis of some dental features revealed that the upper social classes presented with proportionally more minor malocclusions than the lower social classes.

The effect of social factors on referrals for orthodontic advice and treatment.

All patients with information related to social class who were referred to the Orthodontic Department of Glasgow Dental Hospital over a 5-year period were investigated in this study. This referred population is different from the general population with proportionally fewer of the lower social classes. Social class did not affect the distance travelled to receive advice or treatment. However, proportionally more patients from social Classes I and V received complicated therapy.

The effects of immunisation upon the natural history of pertussis. A family study in the Cardiff area.

During an outbreak of pertussis in the Cardiff area in 1974, 229 children with the disease were studied to assess the effect of immunisation upon its natural history and severity. The typical clinical features of pertussis, such as paroxysmal cough, whooping, vomiting, cyanosis, and irregular breathing, were less prevalent in both the immunised and the older children. Immunisation is the main factor in protecting against complications such as fits; and, together with older age, it protects against hospitalisation. Nevertheless, pertussis today can be just as severe as it was 40 years ago, and the vaccine remains the major factor ameliorating its natural history. The immunisation programme needs more active support by all child health workers.

The electrophysiological evaluation of intravenous acebutolol, a beta-blocking drug.

The electrophysiological effects of acebutolol were studied in 12 patients. Heart rate and systemic arterial pressure were monitored. Plasma acebutolol levels were estimated. The first 6 patients (group A) received 0.3 mg/kg body weight I.V. The subsequent 6 patients (group B) received 0.5 mg/kg body weight I.V. Acebutolol delayed both antegrade and retrograde conduction through the AV node. The effect was greater in group B patients. Effective and functional refractory periods of the AV node were also increased after acebutolol. Intraatrial and intraventricular conduction and the effective refractory periods of the atrium and ventricle were not affected. Acebutolol did not alter significantly the sinus node recovery time or the QTc interval. Heart rate fell, especially where initial rates were fast. Systolic arterial pressure was lowered in group B patients. Peak mean levels of acebutolol were reached 5 min after injection of the drug. In the doses used, acebutolol, although well tolerated, failed to demonstrate electrophysiological evidence of a membrane-stabilizing effect and is therefore unlikely to add to the areas of success achieved by other beta-blocking drugs in the management of arrhythmias.

Chemical modification of crude timothy grass pollen extract. II. Class and specificity of antibodies induced by chemically modified timothy grass pollen extract.

The effects have been studied of three different chemical modifications of timothy grass pollen extract on various immunological properties. The ability to induce IgG antibody with specificity for native antigen was least affected by glutaraldehyde treatment; IgE antibody production was reduced to a similar extent by all three modifications; there was no increase in IgM production; delayed reactions were reduced. New antigenic determinants were introduced by all the modifications, but the effect was minimal following glutaraldehyde treatment. The significance of these results and the potential application of modified allergen in hyposensitisation therapy are discussed.

On the possibility of excitation heating of ions to high temperature.

Cyclic or chainlike inelastic collision processes are invoked as an hypothesis to explain the grossly nonthermodynamic properties of energetic carbon and gas-fed carbon arcs confined by magnetic fields. Elastic collisions between the fast electrons (upsilon_ > upsilon(+) but E_ << E(+)) and the hot ions appear to be only about one-tenth as efficient a process for heating the ions as the proposed multiple inelastic collision process, which we call excitation-heating. In addition, a revised treatment of the rate of energy transfer from hot carbon ions to the very cold electrons (upsilon_ < upsilon(+)) reduces the conventional ion cooling rate by a factor of about 6.